Table of Content

21 December 2023, Volume 44 Issue 6

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Molecular medicine, surfing the deeper blue——with discussion about discipline and curriculum development in basic medical sciences

Zhang Chenguang, Ding Wei

2023, 44(6):  907-911.  doi:10.3969/j.issn.1006-7795.2023.06.001

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The establishment and rapid development of molecular biology paved the solid foundation for modern genetics and substantially reshaped related medical research. The human understanding of various diseases in aspect of etiology and genetic profiles has reached in-depth levels given the concept of molecular disease. As a novel discipline gradually established effective research strategy of principle features, including the theme of most consensus and accommodation for basic medical sciences, molecular medicine has made itself become a driving force to advance modern medicine. In this article, we introduced in brief the history of molecular medicine, explored retrospectively the literature contributed by molecular medicine focusing affiliations along medicine, and provided several consideration that might be helpful to the current discipline and curriculum development of basic medicine education, especially for domestic institution in medical universities. In addition, we also discussed in brief the adaptation to the impact or challenge from upcoming trend of artificial intelligence.

Composite piezoelectric nanoparticles based on P(VDF-TrFE) for precise imaging and targeted therapy of glioma

Chen Zhiguang, Zhang Wei, He Wen

2023, 44(6):  912-920.  doi:10.3969/j.issn.1006-7795.2023.06.002

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Objective  To explore the efficacy of composite piezoelectric nanoparticles constructed based on poly（vinylidene fluoride)-trifluoroethylene ［P(VDF-TrFE)］ in the treatment and imaging of glioma. Methods P(VDF-TrFE) piezoelectric materials were reshaped in crystal form and improved in hydrophilicity, and Arg-Gly-Asp (RGD) targeted peptides were connected to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-maleimide (DSPE-PEG-Mal) by click chemistry reaction. In addition, DSPE-PEG- tetranitroheterocyclic ligand (DSPE-PEG-DOTA) was mixed with a certain amount of gadolinium acetate solution was added to obtain DSPE-PEG-DOTA-Gd through chelation. And then the P(VDF-TrFE), DAPE-PEG-Mal RGD, and DSPE-PEG-DOTA-Gd in proportion were mixed to obtain composite piezoelectric nanoparticles P(VDF-TrFE)@DOTA-Gd@RGD. The obtained nanoparticles were characterized and assesed. Results  P(VDF-TrFE)@DOTA-Gd@RGD composite piezoelectric nanoparticles have excellent stability, especially in Dulbecco's modified eagle medium (DMEM) solutions where their particle size remained around 160 nm over time. After crystal reshaping, the piezoelectric performance of P(VDF-TrFE)@DOTA-Gd@RGD is significantly improved, with a surface potential of approximately 4.2 mV. The nanoparticles could be used as a magnetic resonance imaging (MRI) agent. Under ultrasound excitation, P(VDF-TrFE)@DOTA-Gd@RGD composite piezoelectric nanoparticles generated a large amount of reactive oxygen species, inhibited the proliferation, invasion, and migration ability of glioma cells, and promoted their apoptosis. Conclusion  P(VDF-TrFE)@DOTA-Gd@RGD composite piezoelectric nanoparticles could be used as an MRI agent for the localization of brain gliomas and as a sound sensitive agent for sonodynamic therapy of glioma.

The value of combined superb microvascular imaging and color Doppler flow imaging in breast BI-RADS class 4 micronodules

Yu Tengfei, Yin Lu, Tian Daoran, Song Haiman, Yin Ziyi, Zhang Wei, He Wen

2023, 44(6):  921-927.  doi:10.3969/j.issn.1006-7795.2023.06.003

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Objective  To investigate the role of superb microvascular imaging (SMI) and color Doppler flow imaging (CDFI) in the diagnosis of breast imaging reporting and data system (BI-RADS) type 4 micro nodules, and to compare it with contrast-enhanced ultrasound (CEUS). Methods  A total of 165 patients was enrolled, with 165 breast micro nodules rated as BI-RADS class 4, with the maximum diameter ≤1 cm and confirmed by postoperative pathology. It included 125 benign lesions and 40 malignant lesions, and each lesion was examined by CDFI, SMI and CEUS, and the sonogram data were analyzed. Adler semi-quantitative method was used to evaluate blood flow grading, and CDFI and SMI showed the difference in blood flow in micro nodules. The diagnostic criteria for predicting the nature of nodules by CDFI, combined CDFI and SMI were developed, and the diagnostic value of CDFI, combined CDFI, SMI and CEUS in the nature of micro nodules in the breast was analyzed. Results  Patients with malignant breast micro nodules were older than benign patients, and CDFI and SMI had different ability to detect breast micro nodules, and the CDFI blood flow rate was 47.3% (78/165) and SMI was 83.6% (138/165). Taking pathological results as the gold standard, the sensitivity of CDFI, combined CDFI, SMI and CEUS for the diagnosis of breast micro nodules is 72.5%, 87.5%, 72.5%, respectively, and the specificity is 60.8%, 59.2% and 82.4%, respectively. The accuracy was 63.6%, 66.1% and 80.0%, respectively, and the area under the curve(AUC)was 0.665, 0.771 and 0.772, respectively. The difference in the diagnosis of small nodules was statistically significant, so the combined application was better than CDFI alone. Conclusion  For micro nodules of the breast diagnosed with BI-RADS class 4, the combined application of SMI techniques can help improve the sensitivity to determine the nature of nodules and reduce the use of ultrasonography for invasive examinations.

Intelligent grading diagnosis of liver fibrosis, inflammation, and steatosis in chronic liver disease based on multimodal ultrasound imaging data

Wei Xingyue, Wang Lianshuang, Wang Yuanyuan, Gao Mengze, He Qiong, Zhang Yao, Luo Jianwen

2023, 44(6):  928-935.  doi:10.3969/j.issn.1006-7795.2023.06.004

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Objective  To develop a non-invasive, accurate, convenient, and widely applicable intelligent diagnostic system to diagnose simultaneously liver fibrosis, inflammation, and steatosis of chronic liver disease (CLD). Methods  This study is based on multimodal ultrasound imaging data from CLD patients, including two-dimensional B-mode ultrasound images, two-dimensional shear wave elastography, transient elastography data, and the corresponding original radio-frequency data. Quantitative ultrasound methods were used to extract multimodal features from these multimodal data, and the results of ultrasound-guided liver biopsy were used as the gold standard. Support vector machine (SVM) was used to construct an intelligent grading diagnosis system for CLD in a binary-classification manner. Results  The proposed method achieves high the receiver operating characteristic (ROC) area under the curve (AUC) of 0.81, 0.80, 0.89, 0.87 for the classification of fibrosis grade ≥F1, ≥F2, ≥F3 ≥F4, and 0.80, 0.93, 0.93 for inflammation ≥A2, ≥A3, ≥A4, and 0.75, 0.92 for steatosis ≥S1, ≥S2. Conclusion  The results indicated that the proposed method showed potential expected to be promoted to clinical applications.

Evaluation of the mechanical properties of supraspinatus tendons in hemodialysis patients with high frame rate sound touch elastography

Zhuang Jiamian, Zeng Yuran, Chen Shaoqi

2023, 44(6):  936-940.  doi:10.3969/j.issn.1006-7795.2023.06.005

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Objective  To evaluate the mechanical properties of supraspinatus tendons in hemodialysis patients with high frame rate sound touch elastography （HiFR STE). Methods  Forty-six patients who routinely underwent hemodialysis at the First Affiliated Hospital of Shantou University Medical College, as well as twenty three fit volunteers, were selected for the study. Patients on hemodialysis were divided into two groups based on their median dialysis duration （74.5 months)： the shorter dialysis duration group and the prolonged dialysis duration group ［49.00（14.00, 69.00) vs 91.00（78.00, 122.00)］. Two-dimensional ultrasound and HiFR STE imaging were performed using a Mindray Resona R9 Pro ultrasound diagnostic instrument and an L15-3Wu line array probe. The supraspinatus tendon thickness and the mean of Young's modulus （Emean)were measured and compared between hemodialysis patients with varying durations of dialysis and healthy controls. Additionally, the sonographic characteristics of the shoulder joint were observed, including bone destruction, synovial hypertrophy, and joint effusion.  Results  The differences in supraspinatus tendon thickness and Emean values among healthy control group, shorter dialysis age group and longer dialysis age group were statistically significant（P<0.001), with the supraspinatus tendon thickness (5.73±0.70)mm, (6.57±0.93)mm and (6.80±0.84)mm, respectively. The result of two-by-two comparisons showed that the supraspinatus tendons thickness were thicker in both groups of hemodialysis patients with differing dialysis durations than in controls（P<0.05). HiFR STE results showed that their Emean values was (61.27±21.64)kPa、(42.56±25.30)kPa and (31.13±17.40)kPa, respectively. The result of two-by-two comparisons showed that the Emean value of supraspinatus tendons was significantly lower in dialysis patients than in controls, and the incidence of bone erosion and synovial thickening were statistically significant among the three groups（P<0.05). Conclusion  Supraspinatus tendons in hemodialysis patients thickened and showed decreased mechanical properties. Quantitative evaluation of supraspinatus tendon elasticity in hemodialysis patients based on the Emean measured by the HiFR STE can provide objective evidence for clinical screening of potential group of rotator cuff tears. 

nalysis of factors related to the absorption rate of papillary thyroid microcarcinoma after ultrasound-guided radiofrequency ablation

Jia Xiaoxia, Chang Ying, Hou Wenying, Fu Ying, Zhang Huidan, Yang Jingchun

2023, 44(6):  941-947.  doi:10.3969/j.issn.1006-7795.2023.06.006

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Objective  To explore the ultrasound and pathological factors related to the absorption rate of ultrasound-guided radiofrequency ablation(RFA) in the treatment of papillary thyroid microcarcinoma (PTMC).Methods  This study performed a retrospective analysis of patients with ultrasound-guided RFA for PTMC between December 2020 and March 2022. General information of patients was collected before RFA, and follow-up was performed at 1, 3, 6, 12 and 18 months after RFA to obtain changes in thyroid nodules volume. Taking the time when postoperative nodules reach 100%  volume reduction ratio (VRR) as the absorption rate evaluation index, univariate  χ2 test and Logistic regression were used to analyze the influencing factors of RFA treatment.Results  A total of 64 TNs in 56 patients reached 100% VRR 18 months after RFA, the mean VRR of nodules at 1, 3, 6, 12, and 18 months after RFA were 61.43%, 87.86%, 96.62%, 99.70% and 100%.Through the analysis of ultrasound features, it was found that the nodule volume greater than 0.08  mL and the RFA time longer than 130 s were associated with low absorption rate (100% VRR time greater than 12 months). PTMC patients with Bethesda grade Ⅲ have a lower rate of absorption than patients with Bethesda class Ⅴ/Ⅵ. In addition, PTMC patients with Hashimoto's thyroiditis are associated with low absorption rate. Logistic regression analysis showed that RFA was independent influencing factors affecting the rate of absorption after RFA in PTMC patients. Conclusion  Ultrasound features affecting the absorption rate of TNs by ultrasound-guided RFA include nodules volume,duration of RFA, Bethesda grade and Hashimoto's thyroiditis. RFA was independent factors of PTMC absorption rate after RFA.

Application of ovarian-adnexal ultrasound reporting and data system in the diagnosis of ovarian benign and malignant tumors

Song Haiman, He Wen, Kang Ruijun, Wang Lishu, Yu Tengfei, Zhang Wei

2023, 44(6):  948-952.  doi:10.3969/j.issn.1006-7795.2023.06.007

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Objective  To evaluate the diagnostic efficiency and clinical application of ovarian-adnexal reporting and data system (O-RADS) risk scoring system in the ovarian tumor diagnosis through comparison of the diagnostic performance of the sonographers with varying levels of expertise.Methods  The ultrasound images of 200 patients who were treated at Beijing Tiantan Hospital, Capital Medical University from January 2019 to June 2022 with ovarian tumors were retrospectively analyzed. The ovarian tumors were diagnosed by a senior doctor and a junior doctor separately, and then another two trained junior doctors -classified the diagnosed ovarian tumors referring to O-RADS. These two doctors came to a unanimous conclusion after discussion when they disagreed to each other. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and kappa value by senior doctor, junior doctor and O-RADS system were calculated and compared by using the pathological diagnosis as the gold standard. Results  A total of 222 ovarian tumors in 200 patients were enrolled, among which 147 were benign and 75 were malignant by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and kappa value for the senior doctor were 89.3%, 93.1%, 87.0%, 94.4%, 91.8%, 0.82, respectively, while that for the junior doctor were 73.3%, 80.9%, 66.2%, 85.6%, 78.4%, 0.53, respectively. Taken pathological diagnosis as the gold standard, the receiver operating characteristic   was drawn，and the area under the curve was 0.892. Taken O-RADS > 3 as the best cut-off value, the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and kappa value of the O-RADS were 93.3%, 81.6%, 72.1%, 96.0%, 85.5%, 0.70, respectively. Conclusion  O-RADS has good diagnostic efficacy in the diagnosis of ovarian tumors, and can be applied as a useful tool for junior doctor. When the application of O-RADS system meets with difficult classification, it is still necessary to refer to a senior doctor for consultation.

Influencing factors of the ultrasonic subharmonic-aided pressure estimation technology

Zhang Yanfen, Zheng Shuai, Chen Zhiguang, Cheng Linggang, Wang Hongbin, Li Rui, Zhang Yukang, Zhang Wei, He Wen

2023, 44(6):  953-958.  doi:10.3969/j.issn.1006-7795.2023.06.008

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Objective  To explore the factors influencing the ultrasonic subharmonic-aided pressure estimation （SHAPE)technology. Methods  An in vitro simulation of dynamic flow was constructed in a water tank. Three thousand and six hundred subharmonic amplitudes under different mechanical index (MI), sonazoid ultrasound contrast agent concentrations, and flow rates were obtained by SHAPE. The MI and subharmonic amplitude ranges during the pressure-related subharmonic rapid growth stage, the optimal ultrasound contrast agent concentration, and flow rate were quantified using a total fitting curve. Results  The MI and sub-harmonic amplitude ranges were 0.04－0.38 and －61.94-－12.82 dB, respectively. When the other parameters were constant, the maximum differences of the subharmonic amplitude under different concentrations, flow rates, and MIs were －10.0 dB,－12.84 dB, and 35.96 dB, respectively. The subharmonic amplitude and MI demonstrated the strongest correlation (r=0.973) when the contrast agent concentration and flow rate were 3.2 μL/100 mL and 8 μL/min, respectively. With MI difference of 0.04, the mean relative subharmonic amplitude was (3.18±1.55)dB (95% CI： 2.80－3.56). Under the same concentration and flow rate, the increase of MI caused a gradual decrease in the subharmonic amplitude from 9 dB to 0.31 dB. Conclusion  Identification and quantification of the influencing factors may improve the accuracy and effectiveness of SHAPE.

Clinical value of Lindegaard in the early diagnosis of sepsis-associated encephalopathy

Song Qian, Zhou Qian, Sun Hong, Li Shuo, Mei Xue, Guo Ruijun, Ge Huiyu

2023, 44(6):  959-965.  doi:10.3969/j.issn.1006-7795.2023.06.009

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Objective  To investigate the clinical value of Lindegaard index (LR) in early diagnosis of sepsis-associated encephalopathy (SAE). Methods  A retrospective analysis was performed on sepsis patients admitted to the Emergency Department of Beijing Chaoyang Hospital, Capital Medical University, from November 2021 to March 2022. Clinical data were collected during 24 h after admission. Within three days after the diagnosis of sepsis, the SAE was diagnosed with diagnostic gold standard: the positive confusion assessment method for the intensive care unit (CAM-ICU) evaluation or persistent Glasgow coma score (GCS) ≤ 14.Patients were divided into the SAE group and the non-SAE group. The differences in ultrasound parameters of the middle cerebral artery (MCA) including systolic velocity (Vs), diastolic velocity (Vd), mean velocity (Vm), pulsatility index (PI), resistant index (RI), LR on the first and third day of admission were analyzed between the two groups. Logistic regression was used to analyze the risk factors of early SAE in patients with sepsis. The receiver operating characteristic  (ROC) curve was plotted to assess the predictive value of each risk factor for SAE. Results  Thirty-seven patients with sepsis were included in this study, with 17 in the SAE group and 20 in the non-SAE group. The 28-day mortality and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, GCS, blood lactate, incidence of cerebral vasospasm within 24 h of admission were significantly higher in the SAE group than those in the non-SAE group (P<0.05). On the first day (D1), VsD1, VdD1, VmD1, and LRD1 in the SAE group were significantly higher than those in the non-SAE group (P<0.05). There were no significant differences in those ultrasound parameters between the SAE group and the non-SAE group on the third day. On the third day (D3), VsD3, VdD3, VmD3, and LRD3 in the SAE group were significantly lower compared to the first day (P<0.05). ΔLR (LRD1－LRD3) in the SAE group was significantly higher than that in the non-SAE group (P<0.05). Logistic regression analysis showed that the APACHE Ⅱ score within 24 h of admission, LRD1 and ΔLR were risk factors for SAE. ROC analysis showed that the area under the curve (AUC) of APACHE Ⅱ score within 24 h of admission, LRD1, ΔLR and APACHE Ⅱ score combined with ΔLR predicting SAE were 0.94, 0.86, 0.77 and 0.96 respectively, with P<0.05. The cut-off value of LRD1 for diagnosing SAE was 2.6, the sensitivity was 76.47%, and the specificity was 95.00%. The APACHE Ⅱ combined with ΔLR had the best diagnostic efficacy for SAE (AUC=0.96,95% CI： 0.85－0.99, P<0.05), with a sensitivity of 88.24% and a specificity of 95.00%. Conclusion  The APACHE Ⅱ score within 24 h of admission, LRD1, ΔLR are all valuable in predicting the occurrence of early SAE. The APACHE Ⅱ score combined with ΔLR demonstrates the best diagnostic significance of SAE. The bedside ultrasound can dynamically obtain LR in patients with sepsis, which has great predictive value of early SAE.

Application status and prospects of pleural ultrasound in respiratory diseases

Sun Zhe, Ma Jiaojiao, Zhang Bo

2023, 44(6):  966-972.  doi:10.3969/j.issn.1006-7795.2023.06.010

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As a part of lung ultrasound, pleural ultrasound is a simple, efficient, important, and effective tool in the assessment and monitoring of respiratory diseases. Routine techniques include static and dynamic assessment of the pleura, such as pleural morphology, thickness, motion, subpleural changes, and pleural effusion, which are closely related to the pathophysiology of various respiratory diseases. Therefore, different respiratory diseases show different pleural changes, which can help us to quickly differentiate between diseases such as pulmonary edema, chronic obstructive pulmonary disease, pneumonia, pulmonary embolism, and interstitial fibrosis. Pleural ultrasound demonstrates unique advantages in the qualitative and quantitative assessment of pleural effusion and peripheral lung occupations. New ultrasound technologies such as speckle tracking technology, ultrasonography, elastography, and the application of deep learning algorithms have brought pleural ultrasound into a new phase. With the advancement of technology, pleural ultrasound demonstrates great potential for application, especially artificial intelligence (AI) recognition of dynamic signs, 3D models calculation of pleural effusion volume, AI recognition of peripheral lung nodules, and qualitative diagnosis, which may provide clinical information and change the diagnostic and treatment modes more efficiently. In this review, the status and future development of pleural ultrasound application in respiratory diseases are discussed.

The effect assessment of 8-like ring assisted endoscopic submucosal dissection for colorectal lesions

He Zhen, Qin Da, Li Peng, Zhu Shengtao, Ji Ming, Zhang Shutian

2023, 44(6):  973-977.  doi:10.3969/j.issn.1006-7795.2023.06.011

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Objective  To assess the clinical outcomes of 8-like ring-assisted endoscopic submucosal dissection (ESD) for challenging colorectal cases. Methods  In this study, we conducted a retrospective data collection of 42 patients with colorectal adenomas or early-stage cancer who underwent 8-like ring-assisted ESD at Beijing Friendship Hospital from November 2018 to September 2021. The baseline data, including age, gender, lesion morphology, and lesion size, were collected. Safety and efficacy were evaluated by analyzing operative time, enbloc resection rate, complete resection rate, and complications. Results  The mean procedure time of ESD was （60.26±37.77） min, en bloc resection rate was 98% (41/42) and complete resection rate was 93% (39/42). Histopathologic examinations showed that there were 11 low-grade intraepithelial neoplasia cases, 23 high-grade intraepithelial neoplasia cases, and 8 submucosal （SM)adenocarcinoma cases. For the complication, perforation occurred in 3 cases and delayed bleeding occurred in 0 cases. All complications were successfully resolved under endoscopy management. No recurrences, anal stenosis and defecation difficulties events were observed during the follow-up period in all patients. Conclusion  The 8-like ring assisted ESD is safe and feasible as a minimal invasive way for treatment. 

Risk factors associated with recurrence of achalasia after peroral endoscopic myotomy

Liu Juan, Wang Wenjing, Zhao Guiping, Wang Yongjun, Li Peng, Wu Yongdong, Zhang Shutian

2023, 44(6):  978-981.  doi:10.3969/j.issn.1006-7795.2023.06.012

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Objective  To analyze the risk factors associated with recurrence of achalasia (AC) treated with peroral endoscopic myotomy (POEM). Methods  The data of 81 patients diagnosed with AC and underwent POEM at Beijing Friendship Hospital from 2014 to 2019 were collected retrospectively, and multivariate Logistic regression analysis was conducted to analyze the risk factors of recurrence after POEM. Results  Postoperative recurrence occurred in 6 patients, recurrence rate was 7.41% and the medium recurrence duration was 3 years. Gender （P =0.04)and smoking （P=0.02) were related to the recurrence of AC after POEM. There was no significant difference between the groups in age, disease duration, drinking, integrated relaxation pressure (IRP), esophageal diameter and muscularis propria layer thickness. Further COX regression analysis showed that the smoking was an independent risk factor for recurrence of AC after POEM （HR=10.84，P =0.04). Conclusion  Smoking was an independent risk factor for recurrence of AC after POEM.

Preliminary study on risk factors of short-term adverse events after endoscopic papillectomy

Qiao Xinwei, Qiu Yuting, Li Peng, Wu Jing, Zhang Shutian

2023, 44(6):  982-989.  doi:10.3969/j.issn.1006-7795.2023.06.013

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Objective  To explore the risk factors related to short-term adverse events after endoscopic papillectomy (EP). Methods  Patients with duodenal papilla neoplasms (DPNs) undergoing EP were included in this study, and their general information, laboratory examination indicators, operation related conditions and pathological conditions were collected. The above indicators were preliminarily statistically analyzed by independent sample t test, Mann Whitney U test and chi square test, and the clinical factors related to postoperative adverse events were screened. Results  Among 78 patients with DPNs who received EP, 43 patients had the above four adverse events, including 14 cases (17.9%) of postoperative acute pancreatis (AP), 7 cases (9.0%) of postoperative bleeding, 14 cases (17.9%) of hyperamylasemia, and 10 cases (12.8%) of nonspecific abdominal pain. The history of diabetes and height of patients may be the related factors of postoperative adverse events. The elevation of preoperative ALT level and immediate postoperative inflammatory indicators is helpful to early identify the occurrence of postoperative AP and bleeding. Endoscopic mucosal resection (EMR) is helpful to reduce the incidence of postoperative AP, while en bloc resection of the lesion is conducive to the prevention of postoperative bleeding. The size of the lesion and the degree of malignancy also affect the occurrence of postoperative adverse events. Conclusion  Prophylactic stent placement and submucosal injection during EP can not improve the postoperative situation, while indicators such as endoscopic resection method and en bloc resection have an impact on the occurrence of adverse events after EP.

Analysis of clinical characteristics of patients with duodenal papilla neoplasms and the diagnostic value for advanced carcinoma

Qiao Xinwei, Qiu Yuting, Li Peng, Wu Jing, Zhang Shutian

2023, 44(6):  990-998.  doi:10.3969/j.issn.1006-7795.2023.06.014

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Objective  To explore valuable indicators for the differential diagnosis of early and advanced duodenal papilla neoplasms (DPNs).Methods  Data of general conditions, laboratory tests and imaging examinations including digestive endoscopy were collected from patients with DPNs. LASSO (least absolute shrinkage and selection operator) regression was used to screen predictive factors. Univariate and multivariate Logistic analysis were used to determine the independent risk factors for advanced DPNs. ResultsA total of 95 DPNs patients were included in this study. Symptoms, carbohydrate antigen 125 （CA125）, CA50, γ-glutamyltransferase （GGT),  total bilirubin （TBIL） and  hemoglobin （Hb) were screened out by LASSO regression for Logistic regression analysis. Finally, clinical symptoms, elevated GGT and CA50 were validated to be independent predictors of progressive DPNs (P<0.05). Conclusion  The clinical symptoms such as jaundice, significantly increased GGT and CA50 are independent risk factors, and it may be more valuable than imaging examination in the judgment of DPNs as advanced carcinoma.

Application of circulating tumor DNA in digestive system neoplasms

Yu Mingxin, Yang Aiming

2023, 44(6):  999-1005.  doi:10.3969/j.issn.1006-7795.2023.06.015

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Circulating tumor DNA (ctDNA) is a type of circulating free DNA (cfDNA), which is released into the blood by apoptotic or necrotic tumor cells, or directly secreted by tumors. ctDNA carries tumor-specific genetic and epigenetic characteristics, including gene mutations, chromosome rearrangements, copy number variations, and methylation changes. ctDNA liquid biopsy technique has the advantages of easy operation, high repeatability and minimal invasion. ctDNA can be used to screen and diagnose early stage of digestive system tumor, guide treatment, monitor therapeutic effect, analyze postoperative residual lesions and prevent disease recurrence. This article discusses the biological characteristics, detection methods, and application of ctDNA in digestive system neoplasms.

Effects of Lsd1 on the development and activation of regulatory T cells in mice

Xia Miaoran, Zhou Hang, Wang Dayi, Chen Ping

2023, 44(6):  1006-1013.  doi:10.3969/j.issn.1006-7795.2023.06.016

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Objective  To investigate the effects of lysine-specific demethylase 1 (Lsd1) in the development and activation of regulatory T cells (Treg). Methods  Thymi, spleens, and lymph nodes were isolated from control and T cell-specific Lsd1 conditional knockout (Lsd1^fl/flLck-Cre) mice. The numbers and proportions of Tregs and the ratio changes of eTreg/cTreg were measured by flow cytometry. Results  Compared with the control mice, the thymus indices and numbers of thymic CD4⁺ T cells decreased in the Lsd1 knockout mice, but the numbers and proportions of thymic Treg increased. In the spleen and lymph nodes, the proportions of Treg increased, so did the eTreg/cTreg ratio. Conclusion  Conditional knockout of Lsd1 in T cells promotes the development of Tregs in the thymus and the activation of Tregs in the spleen and lymph nodes.

mpact of prenatal stress on evoked expression of c-Fos in emotion-related brain areas

Li Zhiheng, Yu Xin, Yuan Ying, Xu Zhiqing

2023, 44(6):  1014-1021.  doi:10.3969/j.issn.1006-7795.2023.06.017

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Objective  To elucidate the impact of prenatal stress (PS) on evoked expression of c-Fos in select emotion-related brain areas. Methods An experimental model of maternal exposure to chronic restraint stress in rats was employed as PS model. Subsequently, we assessed c-Fos and NeuN staining by immunofluorescence staining method in various brain regions of PS offspring rats, including the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), ventral hippocampus (VH), and ventrolateral periaqueductal gray (vlPAG).  Results Our findings revealed a significant decrease in the density and proportion of c-Fos positive neurons in the mPFC and BLA regions of PS-exposed offspring compared to control offspring. The density of c-Fos positive neurons in the VH region reduced in PS-exposed offspring, while no change was observed in the vlPAG region. Conclusion Our results indicated that PS induced  a decreased density of stress-sensitive neurons in mPFC,BLA and VH brain regions, suggesting a potential underlying mechanism for the observed behavioral changes.

Identification the monoclonal antibodies recognizing the α-synuclein N-terminal domain and their application in immunotherapy

Jia Huanzhen, Jiao Jie, Gao Ge, Yang Hui

2023, 44(6):  1022-1028.  doi:10.3969/j.issn.1006-7795.2023.06.018

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Objective  To analyze the specificity of five monoclonal antibodies 1C16, 2B8, 2P21, 3O18 and 1J6 that recognize α-synuclein (α-syn) N-terminal domains, to provide antibody support for early diagnosis and immunotherapy of Parkinson's disease (PD). Methods  We generated human α-syn(h-α-syn), mouse α-syn (m-α-syn), β-syn, N-terminus human α-syn (α-syn/N) and delete N-terminus human α-syn (α-syn/ΔN) protein using recombinant protein purification technology in vitro. The specific recognition domains of the five monoclonal antibodies were detected by dot blotting. Using Western blotting to detect the denatured α-syn from purified protein and mice brain. Results  Antibody 1C16 recognized h-α-syn proteins in native form and h-α-syn protein in the mice brain in denatured form rather than m-α-syn and β-syn. Antibody 1J6 could recognize h-α-syn and α-syn/N protein in native form rather than full-length α-syn protein and h-α-syn protein in the mouse brain in denatured form. Conclusion  The two selected antibodies are specific to human α-syn, which provide the basis for the detection of biomarkers by enzyme linked immunosorbent assay and can be used for immunotherapy in PD. 

Effects of high fat diet with low dose TCDD on hepatic lipid metabolism in female obesity-prone SD rats

Liu Yue, Zhu Dan, Hong Yujing, Sun Wenxing, Xu Guangfei

2023, 44(6):  1029-1035.  doi:10.3969/j.issn.1006-7795.2023.06.019

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Objective  To study the effect of combination of high fat diet (HFD) induced obesity and low dose persistent organic pollutants 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD) on liver lipid metabolism. Methods  By 2×2 factorial design, the effects of combination of HFD and low dose TCDD (10 ng·kg^－1·d^－1) on liver lipid metabolism in obesity-prone (OP) 10-week-old female rats were studied. The four groups of experimental animals were: the group treated with no TCDD in chow diet (Cont+TCDD 0), the group treated with low dose TCDD in chow diet (Cont+TCDD 10), and the group high fat diet without TCDD (HFD+TCDD 0) and high fat diet group treated with low dose TCDD (HFD+TCDD 10). Lipid deposition in liver was observed by oil red O staining. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver were determined by enzyme method. mRNA expression of genes related to lipid metabolism in liver was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Results  The body weight of rats in Cont+TCDD 0 group, Cont+TCDD 10 group, HFD+TCDD 0 group and HFD+TCDD 10 group were (301.29±18.47) g, (312.16±20.45) g, (358.20±27.11) g and (373.83±26.50) g, respectively (F=7.43, P<0.01), liver oil red O positive area ratios were （1.26±0.16)%,（1.66±0.50)%，（9.06±1.54)%,（32.56±2.66)% (F=11.32, P<0.01), liver SOD activity were (1.54±0.06) U/mg, (1.41±0.15) U/mg, (1.25±0.08) U/mg and (0.76±0.11) U/mg (F=4.31, P<0.05), respectively. Liver GSH-PX activity were Liver GSH-PX activity were (1 511.00±69.30) U/mg, (1 409.00±60.81) U/mg, (1 232.00±65.05) U/mg and (965.00±83.44) U/mg (F=3.91, P<0.05). The interaction analysis of the above indexes suggested that the combination of high fat diet and low dose TCDD resulted in synergistic increases in the body weight (F=6.33, P<0.05) and liver fat accumulation (F=12.51, P<0.01) of obese-prone female SD rats, and the activities of antioxidant enzymes such as SOD in liver (F=4.15, P<0.05) and GSH-PX enzyme activity (F=3.97, P<0.05) were decreased synergistically. Analysis on mRNA expression levels of 12 genes related to lipid metabolism in liver showed that high fat diet combined with low dose TCDD increased adipose lipase (Atgl) (F=3.69, P<0.05), mRNA expression of cluster of differentiation 36 (CD36) (F=5.58, P<0.01), inhibited the mRNA expression of hormone sensitive lipase (Hsl) (F=4.01, P<0.05), and there was no significant difference in the expression of other 9 genes (P>0.05). Conclusion  The combination of high fat diet and low dose TCDD can synergistically increase the abnormal liver lipid metabolism in female obesity-prone female SD rats.

Comparative study of effect of different components of Edwardsiella tarda on pulmonary inflammation

Li Qin, Hu Yue, Qin Xiaofeng, Feng Zhihong, Wang Wei, Sun Ying

2023, 44(6):  1036-1043.  doi:10.3969/j.issn.1006-7795.2023.06.020

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Objective  To explore the effects of different components of Edwardsiella tarda on pulmonary inflammatory responses and to clarify the potential role of Edwardsiella tarda in progression of chronic obstructive pulmonary disease(COPD), which might provide a novel theoretical basis for the pathogenesis of COPD.  Methods  In vivo, mice were given different components derived from Edwardsiella tarda (inactivated bodies, bacterial lysates and supernatant of cultured bacteria) intranasally to establish mice models of acute lung injury. Inflammatory cells in bronchoalveolar lavage fluid (BALF) were analyzed by cell differential counting on stained smears; enzyme-linked immunosorbent assay (ELISA)was used to measure the concentrations of proinflammatory cytokines in BALF; Histochemical and immunohistochemical staining were individually employed to detect eosinophils and IL-33+ cells in lung tissue. In vitro, different components derived from Edwardsiella tarda were used to stimulate pulmonary epithelial cells and macrophages, and concentrations of proinflammatory cytokines in the cell culture supernatant were also measured by ELISA. Results  The bacterial lysates and metabolites of Edwardsiella tarda significantly increased the number of neutrophils and macrophages and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and tumor necrosis factor α (TNF-α) in BALF; inactivated bacteria induced more eosinophils and IL-33⁺ cells infiltration in lung tissue. The different components of Edwardsiella tarda also stimulated production of proinflammatory cytokines by human and murine pulmonary epithelial cells and macrophages. Conclusion  Edwardsiella tarda can cause pulmonary inflammatory response, possibly through inducing inflammatory cytokines by epithelial cells and macrophages.

A nonsynonymous single nucleotide variant of the tumor-related gene ADAM15 in colon cancer and its impact on cell adhesion phenotype

Wang Jing, He Libing, Zhang Guoyan, Liu Xiaohan, Cheng Shan

2023, 44(6):  1044-1052.  doi:10.3969/j.issn.1006-7795.2023.06.021

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Objective  To elucidated the specific functional roles of the a disintegrin and metalloproteinase 15 (ADAM15) gene single nucleotide variant (SNV) in the cellular processes associated with the development of colon cancer through combination of high throughput sequencing and suitable cellular models.Methods  We initially performed whole exome sequencing on cancerous tissues and adjacent tissues from colon cancer patients exhibiting invasive phenotypes. Subsequently, functional experiments were conducted using wild-type/mutant ADAM15 colon cancer HCT-8 cell lines. This was followed by transcriptome sequencing analysis of the wild-type/mutant ADAM15 cell lines.Results  The whole exome sequencing study identified a highly recurrent SNV, rs6427128, located at the ADAM15 gene, which demonstrated a significant association with adverse prognosis in patients, suggesting its potential influence on the progression of colon cancer. The functional assays utilizing cells overexpressing the variant gene, indicated that the expression product of this variant gene lost the effect of upregulating cell invasion capabilities while increased cell adhesion by approximately 26% compared to wild-type ADAM15 cells. To comprehensively investigate the mechanisms underlying the impact of rs6427128 variation on colon cancer cell phenotypes, we performed transcriptome sequencing analysis on HCT-8 cells transfected with the overexpressed variant protein. The results revealed differential expression genes were enriched in various cellular biological processes, including cell adhesion junction pathways, DNA replication and transcription, as well as inflammatory responses, in comparison to wild-type samples. Conclusion  This study indicated that the rs6427128 variant may alter the tumor microenvironment by affecting tumor cell adhesion and contributed to extensive transcriptional changes in tumor cells, ultimately promoted the malignant phenotype of colon cancer. Although individual gene mutations in malignant tumors often do not act as primary causative factors, high-frequency recurrent variants detected in clinical samples can provide valuable molecular candidates for unraveling the structural-functional relationships of tumor-related genes. Using rs6427128 as an example, in combination with appropriate cell models and refined analytical methods, some potential functional variants can yield informative laboratory data regarding their specific roles in cellular processes related to the development of colon cancer, such as proliferation, adhesion, invasion, and metastasis.

Effects of new bone allograft on physiological and biochemical indices of animals

hu Liming, Jiao Kun, Liu Wei, Li Shengli

2023, 44(6):  1053-1059.  doi:10.3969/j.issn.1006-7795.2023.06.022

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Objective  To study the effects of new bone allogeneic repair on physiological and biochemical indexes of the tested animals. Methods  Male New Zealand rabbits were used to construct the animal model of bone injury, and 60 rabbits were randomly divided into experimental group, control group and blank control group. At the outer edge of proximal femur, the bone defect with a depth of about 1 mm was prepared by precision grinding mechanism with a diameter of 4 mm ball head.  In the experimental group and control group, the left femoral defect was filled with cortical bone particles, and the right femoral defect was filled with cancellous bone fragments. Animals in the blank group underwent the same operation as described above without any material filling. Blood samples were collected at 1, 4, 8 and 12 weeks after operation, and blood routine and blood biochemical examination were performed. Results  One week after surgery, the weight of animals in both groups decreased slightly, and one week later, most of the experimental animals showed an increasing trend. However, there was no significant difference in body weight change among all groups in each experimental period (P>0.05). The results of blood routine test showed that the implant had no adverse effect on the blood system and hematopoietic function of the animals. The results of biochemical examination suggest that the implantation of the test product may have some effects on the biochemical reaction and metabolism of the recipient animal, but this is still a adaptive reaction of the body and does not cause pathological effects. Conclusion  This type of allograft bone has no adverse effects on the body weight, blood routine and biochemical indexes of the tested animals, and is a safe implant repair material.

Correlation between serum vitamin A and vitamin E and cognitive function in aging subjects with type 2 diabetes mellitus

Gao Yanyan, Ren Xiuwen, Wang Xixiang, Xu Jingjing, Ma Xiaojun, Liu Lu, Liu Yu, Yuan Linhong

2023, 44(6):  1060-1066.  doi:10.3969/j.issn.1006-7795.2023.06.023

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Objective  To investigate the correlation between serum vitamin A and vitamin E levels and cognitive function in aging subjects in older adults with type 2 diabetes mellitus (T2DM). Methods  A total of 500 T2DM patients were recruited from Communities. And 500 age, gender and education level matched non-diabetic healthy adults were recruited as normal control subjects. A self-designed questionnaire was used to investigate socio-demography, lifestyle, disease history and other factors. Montreal Cognitive Assessment (MoCA) scale was used to assess the cognitive function. Fasting venous blood was collected for biochemical parameters including fasting blood glucose (FBG), total blood cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) levels. The serum levels of vitamin A (VA) and vitamin E (VE) were detected by high performance liquid chromatography (HPLC). SPSS 20.0 was used to statistically analyze the data. ResultsAmong the T2DM group, the serum VA level of those with normal cognitive function (0.59 μg/mL) was higher than that of those with mild cognitive impairment (MCI) (0.50 μg/mL), and the difference was statistically significant (P<0.01). The serum VE level of those with normal cognitive function (12.22 μg/mL) were higher than those with MCI (11.40 μg/mL), but the difference was no statistically significance (P>0.05). Serum VA levels in T2DM group were positively correlated with the total MoCA score and all scores (except the orienting function); and higher concentrations of serum VA levels were associated with a reduced risk of developing diabetes compared with lower levels (OR<1, P<0.05). Conclusion  In this study, we found that higher serum VA levels were associated with better cognitive function. Thus, higher serum VA levels may act as a protective factor for cognitive function in elderly with T2DM. However, there is no association between serum VE level and cognitive function in the elderly. 

Clinical analysis of lymphoma with lymphedema as the first manifestation

Hao Kun, Sun Yuguang, Li Bin, Xin Jianfeng, Zhang Li, Yu Chunkai, Wang Rengui, Shen Wenbin

2023, 44(6):  1067-1073.  doi:10.3969/j.issn.1006-7795.2023.06.024

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Objective  To investigate the clinical features of lymphoma patients with the first symptom of lymphedema. Methods  From August 2010 to February 2022, 12 patients with lymphoma who presentied with lymphedema as the first manifestation were selected as the observation group, and 20 patients with secondary lymphedema of the lower limbs after gynecological tumor surgery were selected as the control group. We collected the clinical characteristics of two groups of patients and analyze the clinical characteristics of lymphoma patients with lymphedema as the first manifestation. Results  There were 12 cases with lymphoedema caused or aggravated by lymphoma, including 1 case with upper limb edema, 10 cases with lower limb edema, and 1 case with systemic edema. These patients are often accompanied by clinical symptoms such as weakness, emaciation, pain, lumps, and enlarged lymph nodes. The proportion of patients with abnormal tumor markers is 6/8, and the prevalence of anemia is  6/12. The positive rates of ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) are  8/8, 8/8, and  3/3, respectively. The patients are diagnosed by pathological diagnosis and immunohistochemistry. There were significant differences between the two groups in course of disease, main and concomitant symptoms, past history, tumor markers, anemia, and imaging examinations(P<0.01). Conclusion  Lymphoma associated malignant lymphedema is rare and the incidence is insidious. In order to avoid misdiagnosis and delayed treatment of lymphoma, we should actively identify cause of lymphedema during follow-up.

Clinicopathology analysis of 21 cases in primary cardiac tumors in children

Song Yanting, Chen Dong, Shang Jianfeng, Fang Wei, Gong Shanshan, Lian Guoliang, Zhang Zhe

2023, 44(6):  1074-1080.  doi:10.3969/j.issn.1006-7795.2023.06.025

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Objective  To investigate the clinicopathological characteristics of primary cardiac tumor in children, diagnosis and differential diagnosis, treatment and prognosis．Methods  Totally 21 cases of primary cardiac tumor in children of pathological features of were made and the clinical data and combined with literature were analyzed.Results  According to the morphological characteristics, the results of immunohistochemistry, and the clinical data analysis, 21 children with primary cardiac tumors were all benign tumors, including 6 cases of cardiac rhabdomyoma, 6 cases of cardiac myxoma, 5 cases of cardiac fibroma, 1 cases of cardiac leiomyoma, 1 case of cardiac angioma and 2 cases of mesenchymal cardiac hamartoma.Conclusion  Primary cardiac tumors in children are rare and mostly benign. Although clinical manifestations are common, tumors with typical pathological features. Immunohistochemical staining is helpful for diagnosis and differentiation.

High risk factors and prediction model construction of cardiopulmonary complications in patients with abnormal lung function after pulmonary resection

Guo Junhao, Jin Gang, Zhao Zhi, Nan Fangyuan, Hu Yunsheng, Hu Qu

2023, 44(6):  1081-1086.  doi:10.3969/j.issn.1006-7795.2023.06.026

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Objective  To investigate the high risk factors and construct prediction model of cardiopulmonary complications in patients with abnormal lung function after pulmonary resection to provide more reference for follow-up clinical diagnosis and treatment. Methods  A total of 375 patients with abnormal pulmonary function who underwent pneumonectomy in our hospital from January 2015 to June 2022 were retrospectively enrolled. They were divided into complication group (70 cases) and non complication group (305 cases) according to whether cardiopulmonary complications occurred after surgery. The baseline clinical characteristics of the two groups were compared, and the independent risk factors of cardiopulmonary complications after pneumonectomy were evaluated by Logistic regression model. The predictive model for cardiopulmonary complications after pneumonectomy was developed and predictive efficacy was analyzed. Results  Cardiopulmonary complications occurred in 70 of the 375 patients (18.67%). There were significant differences in  the the first second forced expiratory volume as a percentage of the predicted value (FEV1%pred), diffusing capacity of the lungs for carbon monoxide as a percentage of the predicted value(DLCO%pred), landing height, heart rate difference before and after stair climb test (SCT), and arterial oxygen saturation difference before and after SCT between the two groups (P<0.05). The results of multi-factor analysis showed that the height of boarding, the difference of heart rate before and after SCT, and the difference of arterial oxygen saturation before and after SCT were independent risk factors for the occurrence of cardiopulmonary complications after pulmonary resection (P<0.05). The Logistic prediction probability was used to predict the occurrence of cardiopulmonary complications after pneumonectomy. The optimal cut-off value was 70.07% and the Jorden index was 54.15%. Conclusion  The incidence of cardiopulmonary complications in patients with pulmonary dysfunction after pulmonary resection was closely related to the height of boarding, the difference of heart rate before and after SCT, and the difference of arterial oxygen saturation before and after SCT. The model based on the above factors can accurately predict the risk of postoperative cardiopulmonary complications. 

ood practices in Mendelian randomization： common designs, key challenges, and optimization in Mendelian randomization analysis

Wang Jing, Zhang Guoyan, Cheng Shan

2023, 44(6):  1087-1094.  doi:10.3969/j.issn.1006-7795.2023.06.027

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Mendelian randomization (MR) is a causal inference method that utilizes genetic variations as instrumental variables to investigate the causal relationships between exposures (various factors) and outcomes (diseases or phenotypes). This article discusses the fundamental assumptions of MR methods in biomedical research, common designs, key challenges, optimizations and the future prospects of MR. The article introduces the core assumptions of MR methods and how to select common MR design types in biomedical research. Furthermore, the article discusses the key challenges currently faced by MR studies and their solutions, such as how to select instrumental variables that meet the core assumptions, how to choose causal estimation methods in MR, and how to interpret MR results biologically. In addition, the article suggests some directions for future research. As a powerful tool, MR contributes to exploring causal relationships, selecting therapeutic intervention targets, and conducting long-term population-based intervention studies. While MR cannot fully replace randomized controlled trials, it has a wide  application in biomedical research and clinical practice, helping us to deeply understand the complex relationships between health and disease.

Application and research progress of artificial intelligence combined with spectral diagnosis technology in the identification of lung cancer tissues

Luo Yi, Qin Qi, Wang Peihao, Guo Kangshun, Zhang Xinping, Cui Yong

2023, 44(6):  1095-1102.  doi:10.3969/j.issn.1006-7795.2023.06.028

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To systematically review the current research on spectral technology in the identification of lung cancer tissues and the application of artificial intelligence, to clarify the clinical application value and development direction of artificial intelligence combined with spectral diagnosis technology. Pubmed and CNKI databases were searched via using a specific strategy, and the better performing spectral techniques in the field of pathological diagnosis were summarized and briefly compared. The current mainstream spectral techniques include hyperspectral imaging, diffuse reflectance spectroscopy, Raman spectroscopy, fluorescence spectroscopy, and multispectral techniques.Artificial intelligence can further enhance the diagnostic performance of spectral techniques. Artificial intelligence combined with spectral diagnosis has the potential to realize the instant differentiation of lung cancer invasion degree, but most of the current research is still at the stage of differentiating benign and malignant tumors and determining the tumor boundary.