Table of Content

21 February 2022, Volume 43 Issue 1

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Awards Introduction

Research and application of a new technical system of hypoxic and ischemic conditioning for prevention and treatment of ischemic stroke——The Second Prize of 2020 National Science and Technology Progress

Zhao Wenbo, Ren Changhong, Li Sijie, Ma Hongrui, Ji Xunming

2022, 43(1):  1-5.  doi:10.3969/j.issn.1006-7795.2022.01.001

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Stroke is the first cause of death and disability in China, with high morbidity, recurrence, disability, mortality, and economic burden. Professor Ji Xunming et al. devoted themselves to exploring the prevention and treatment for stroke that would be suitable for Chinese population. They proposed theory of “hypoxic tissue conditioning” and verified the brain protection effect of hypoxic conditioning and elucidated the mechanism of its anti-ischemia and hypoxic injury. A new method of “limb remote ischemic adaptation” has been established to improve the efficacy of the prevention and treatment for ischemic stroke. The international guidelines and Chinese expert consensus on remote ischemic conditioning for the prevention and treatment of cerebrovascular diseases have been formulated and achieved.

Establishment and application of key technologies and systems for improving health care quality of cerebrovascular diseases——The Second Prize of 2020 National Science and Technology Progress

Li Zixiao, Zhao Xingquan, Wang Yongjun

2022, 43(1):  6-12.  doi:10.3969/j.issn.1006-7795.2022.01.002

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Cerebrovascular disease is the first cause of adult disability and death at present in our country. The team led by Professor Wang Yongjun has developed a set of cerebrovascular disease treatment technology based on image feature, biological markers, and new gene indicators to reduce the recurrence rates, morbidity and mortality during 18 years, which has reduced the recurrence rate of cerebrovascular disease by 37%-73% relatively. Furthermore, the team has established an improvement and transformation technology system for medical quality, with the standardized application of precision treatment technology as the core. The one-year recurrence rate of cerebrovascular disease was reduced by 28%, and the disability rate by 26%. It means that they have explored an effective way of medical transformational technology into clinical practice. In addition, the team has integrated organizational management mode, hierarchical quality control framework and information data platform, real-time monitoring, and feedback of medical service quality into a medical quality improvement system of cerebrovascular disease, which covers 2 497 hospitals across the country. It effectively promotes the transformation and application of appropriate diagnosis and treatment technologies into clinical practice. The standardized implementation rate of cerebrovascular disease medical quality index in China was increased by 21%. The accumulative conversion funds were 105 million Yuan.

The innovation and application of key technologies in the otological radiology——The Second Prize of 2020 National Science and Technology Progress

Lyu Han, Zhao Pengfei, Yin Hongxia, Wang Zhenchang

2022, 43(1):  13-16.  doi:10.3969/j.issn.1006-7795.2022.01.003

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The otologic diseases features in deep and occult anatomy. The problems of traditional oto-radiology with invisibility, imprecision, and incomprehensibility leads to diagnostic inefficacy. Professor Wang Zhenchang's team developed a canonical oto-radiological examination protocol and systemic evaluation model to improve the visibility of pathophysiological features of otology disease. They illuminated the whole chain mechanism of pulsatile tinnitus, established the radiological examination and evaluation system of oto-radiology, invented micron-level computed tomography specific to clinical otology. By applying this program, they could precisely detect the disease with low-dose as well as high-quality radiological examination. The diagnostic efficacy was improved significantly.

Basic and Clinical Research of Gastroenteroloy

Incidence and influence factors of endoscopic non-curative resection of early gastric cancer

Ma Zonghui, Zhang Qian, Xing Jie, Zhu Shengtao, Li Peng, Zhang Shutian, Sun Xiujing

2022, 43(1):  17-21.  doi:10.3969/j.issn.1006-7795.2022.01.004

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Objective To explore the incidence and influence factors of non-curative resection after endoscopic resection of early gastric cancer. Methods We retrospectively collected the relevant data of patients with early gastric cancer who were hospitalized in the Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University from January 2014 to August 2020, and then we evaluated the resection's curability, calculated the incidence of non-curative resection, and analyzed its influence factors. Results A total of 347 lesions of early gastric cancer were included, of which 66 were non-curative resection lesions, thus the non-curative resection rate was 19.02% (66/347). Multivariate Logistic analysis showed that the lesions with diameter ≥20 mm (OR=3.248, 95%CI: 1.451-7.272, P=0.004), infiltration into submucosa (OR=26.549, 95%CI:10.087-69.875, P<0.001) and the pathological type of undifferentiated early gastric cancer (OR=18.021, 95%CI: 6.664-48.736, P<0.001) were influence independent factors for non-curative resection. Conclusion The endoscopic resection should be applied carefully after full evaluation for early gastric cancer with diameter ≥20 mm and infiltration into submucosa and/or undifferentiated pathological type as suggested by preoperative pathology.

Experience in endoscopic treatment of esophageal and gastric varices with upper gastrointestinal mass

Cheng Rui, Zhu Siying, Liu Simao, Zhou Yanhua, Zong Ye, Li Peng, Zhang Shutian

2022, 43(1):  22-27.  doi:10.3969/j.issn.1006-7795.2022.01.005

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Objective To investigate the effect of endoscopic treatment for liver cirrhosis complicated with esophageal and gastric varices accompanied by upper gastrointestinal(GI) mass. Methods Clinical data of 18 patients were retrospectively collected, who underwent menstrual endoscopic treatment for esophageal gastric varices with upper gastrointestinal neoplasm in Beijing Friendship Hospital, Capital Medical University, Department of Gastroenterology since January 2010 to July 2021. The pathological results after upper gastrointestinal neoplasm resection indicated 4 cases of early esophageal cancer, 6 cases of early gastric cancer, and 8 cases of gastric hyperplastic polyp. The varices were diagnosed with LDRf classification method. The esophageal varices were treated with ligation operation or hardening treatment. The gastric varices were treated with embolization. The upper gastrointestinal tract neoplasm was treated with endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). The clinical manifestations, laboratory examination, endoscopic performance, endoscopic treatment, pathological results, and follow-up were summarized and analyzed. Results A total of 18 patients (10 males and 8 females) were aged 37-81 years old, with an average age of (65.88±9.09) years old. According to Child-Pugh grading of liver function, there were 15 patients with grade A and 3 patients with grade B, 4 patients with platelet less than 50×10⁹/L, 3 patients with prothrombin time activity (PTA) less than 60%, and international normalized ratio (INR) of all the cases was less than 1.5. Among all the cases, 4 cases had the digestive tract neoplasm located at the end of the esophagus or stomach varicose vein on or close to, and 8 patients had a history of ruptured esophageal gastric varices bleeding and underwent the esophageal or gastric varices endoscopic treatment, five of which were treated with leading endoscopic esophageal or gastric varices endoscopic treatment. The patients underwent elective review gastroscope after treatment one to six months. The upper digestive tract masses were treated with EMR or ESD after the improvement of esophageal or gastric varices. Follow-up observation was made on the endoscopic treatment of esophageal and gastric varices, and no bleeding, perforation or other serious complications occurred during or after EMR or ESD. The lesions were completely removed, and the postoperative pathology showed that the incision margin was clean. None of the patients died at 12 months of follow-up after upper GI mass resection. Conclusion EMR and ESD are safe and effective for the treatment of esophageal and gastric varices with upper digestive tract early cancer and polyps and other masses in cirrhosis. Endoscopic intervention of esophageal and gastric varices at an appropriate time could reduce postoperative bleeding and other complications.

Safety evaluation of pancreatic duct stent placement through duodenal accessory papilla cannulation

Li Jielin, Liu Tianyu, Zhang Shutian, Wei Yongqiu, Ji Ming, Li Peng, Wang Yongjun, Wu Yongdong

2022, 43(1):  28-33.  doi:10.3969/j.issn.1006-7795.2022.01.006

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Objective To evaluate the safety of pancreatic duct stent placement through duodenal accessory papilla cannulation. Methods Data of 114 patients with pancreatic diseases who underwent duodenal papilla cannulation and pancreatic stent placement in Beijing Friendship Hospital from January 2016 to August 2021 were analyzed retrospectively. There were 88 patients underwent the main papilla cannulation,while 26 patients treated by accessory papilla cannulation.We compare the differences of the age, sex, previous history, history of endoscopic retrograde cholangiopancreatography (ERCP) operation, operator, preoperative blood coagulation function, endoscopic pancreatic sphincterotomy, difficult cannulation, number of pancreatic duct stents, post-ERCP complications, the length of hospital stay after ERCP between two groups.The independent risk factors for postoperative complications were analyzed by binary Logistic regression.Results There was no significant difference in the incidence of postoperative complications and length of hospital stay after ERCP between the two groups (P>0.05), and binary Logistic regression showed that duodenal accessory papilla cannulation was not a risk factor for post-ERCP complications(P>0.05). Conclusion According to the current limited data, the placement of pancreatic duct stent through duodenal accessory papilla cannulation will not increase the incidence of the incidence of post-ERCP complications and the length of hospital stay compared with main papilla cannulation.

Clinical research of endoscopic submucosal dissection in low rectal early cancer

Sun Can, Xing Jie, Zhang Xi, Sun Xiujing, Zhang Shutian

2022, 43(1):  34-37.  doi:10.3969/j.issn.1006-7795.2022.01.007

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Objective To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of low rectal early cancer. Methods The data of 449 patients (269 male,59.9%)with early colorectal cancer who underwent ESD treatment and were pathologically diagnosed from January 2016 to Decmeber 2020 in the Department of Gastroenterology of Beijing Friendship Hospital were retrospectively analyzed. The average age of the patients was (63.90±9.99) years, and the median size of the lesion was [20(14,27)]mm. The patients were divided into low rectum group (n=48) and control group(n=401), according to the different locations of lesions. The clinicopathological characteristics, operation time, en bloc resection rate, R0 resection rate, and complications were compared with each other between the two groups. Results There were no significant differences in gender ratio and age between the two groups. The median size of lesions was [20.5(15,34.5)]mm in the low rectum group and [19(13,27)]mm in the control group, with a significant difference. The median operation time was [60(33.25,88.75)]min in the low rectum group and [40(25,60.5)]min in the control group. The rate of invasion depth of submucosal in the low rectum group was 22.9%, which was significantly higher than that in the control group (10.7%). There were no significant differences in the en bloc resection rate, complete resection rate, and postoperative complication rate between the two groups. Conclusion ESDtreatment of low rectal early cancer took longer operation time than that of the other colorectal parts. The possibility of deep submucosal invasion was higher. On the premise of fully evaluating the indications, ESD was a safe and effective treatment for low rectal early cancer.

The effect assessment of endoscopic submucosal dissection for rectal lesion extending to the dentate line

He Zhen, Liu Juan, Ji Ming, Li Peng, Zhang Shutian

2022, 43(1):  38-41.  doi:10.3969/j.issn.1006-7795.2022.01.008

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Objective To investigate the feasibility of endoscopic submucosal dissection(ESD) in rectal lesions extending to the dentate line. Methods The clinical data of 30 patients who underwent ESD in Beijing Friendship Hospital from October 2015 to February 2021 because of the rectal lesions extending to the dentate line were collected retrospectively in this study. Clinical characteristics including age, gender, lesion morphology, and lesion size were collected to illustrate the base lines of patients. The safety and effectiveness of ESD were accessed by analyzing procedure time, En bloc resection rate, complete resection rate, adverse events and recurrences rate of these patients. Results The mean procedure time of ESD was (89.83±49.55)min, En bloc resection rate was 93.0% (28/30), and complete resection rate was 90% (27/30). Histopathologic examinations of the resection samples showed that 23 cases of adenoma (7 cases of low-grade intraepithelial neoplasia and 16 cases of high-grade intraepithelial neoplasia), 6 cases of intramucosal adenocarcinoma, and 1 case of submucosal adenocarcinoma (SM2) were included in these patients. About the complication of ESD, perforation occurred in 3 cases and delayed bleeding occurred in 4 cases. All complications were successfully resolved under endoscopy management. The average follow-up time was (3.33±1.44) years. No recurrences, anal stenosis and defecation difficulties events were observed during the follow-up period in all patients. Conclusion As a minimal invasive way for curable treatment, ESD is safe and feasible for rectal lesions extending to the dentate line.

Pilot study on the mechanism of B cell chemotaxis of macrophage in ulcerative colitis

Zhang Xinghua, Xing jie, Sun Can, Zhang Xi, Wang Yongjun

2022, 43(1):  42-46.  doi:10.3969/j.issn.1006-7795.2022.01.009

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Objective To study the infiltration ratio of B cell and macrophage in the colon tissue during the progression of ulcerative colitis and explore the mechanism of chemotaxis between the two cells. Methods With the classic AOM/DSS mouse ulcerative colitis carcinogenesis model as the research object, the peripheral blood and colon tissues of mice at different disease stages were obtained. The proportion of immune cells was detected by flow cytometry, and the real-time PCR method and immunofluorescence method were used to detect chemokine monocyte chemoattractant protein-1 (MCP1/CCL2).Results The proportion of B cell and macrophage infiltration in colorectal tissues increased with the progress of ulcerative colitis-related colon cancer in mice. The infiltration of macrophages was significantly reduced if there was a lack of B cells. Further research found that B cell was one of the important sources of the chemokine CCL2 of macrophages. Conclusion During the progression of ulcerative colitis, B cells could chemoattract macrophages to colorectal tissues by up-regulating the expression of CCL2.

Advanced endoscopic imaging in diagnosis of early gastrointestinal cancer

Yang Yi, Li Xue, Cheng Rui, Chen Wei, Chen Chuyan, Zhang Shutian

2022, 43(1):  47-52.  doi:10.3969/j.issn.1006-7795.2022.01.010

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It is vital to detect and intervene early gastrointestinal cancer before its progression to advanced carcinoma, which is highly dependent on digestive endoscopy screening. There are certain limitations in conventional white-light inspection. It becomes possible to accurately screen early gastrointestinal cancer with advanced endoscopic imaging techniques.

Medical Imaging and Clinical Research of Cerebrovascular Disease

To explore the influence of lenticulostriate artery on quantitative perfusion of basal ganglia brain tissue and predict the prognosis of patients

Huang Lixiang, Wang Shaozhou, Cao Chen, Xia Shuang

2022, 43(1):  53-60.  doi:10.3969/j.issn.1006-7795.2022.01.011

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Objective Vessel wall imaging (VWI) and self-calibrated echo planar perfusion weighted imaging(SCALE-PWI) were used to explore the effects of imaging characteristics of lenticulostriate artery(LSA)on lacunar infarction (LIs) and cerebral tissue perfusion in the basal ganglia region, and its correlation with the severity and prognosis of stroke.Methods A retrospective analysis was performed on 46 patients with ischemic stroke or transient ischemic attack who underwent VWI and scale-PWI examinations in Tianjin First Central Hospital from January 2018 to January 2021.According to National Institute of Health Stroke Scale(NIHSS) score at discharge, the patients were divided into good prognosis group (≤6) and poor prognosis group (＞6). The LSA parameters (number, total length and curvature of LSA) in VWI images were measured;the differences of clinical baseline data between the good prognosis group and the bad prognosis group were compared, the differences of symptom side LSA parameters, cerebral blood flow (CBF),cerebral blood volume (CBV) and infarction volume were compared between the two groups. The correlation between imaging parameters and admission NIHSS score, and the indicators affecting poor prognosis of patients were evaluated. Finally, the diagnostic efficacy of significant indexes between poor prognosis group and good prognosis group was evaluated. Results There were significant differences in the number of LSA (P=0.015), total length of LSA (P=0.032), CBF (P=0.001) and CBV (P<0.001) of basal ganglia between the good prognosis group and the bad prognosis group. Multiple linear regression analysis showed that infarct volume could predict stroke severity (F=7.408, P=0.002) indicating that the regression model was statistically significant. After adjusting for age, gender, hypertension and diabetes, the CBV of the affected side was still an important indicator of improvement, with an area under the ROC curve of 0.922 (95% CI: 0.904-0.981). Conclusion LSA features from VWI can reflect the perfusion status of basal ganglia, and quantitative cerebral perfusion parameters of basal ganglia are influential factors for poor prognosis of LIs patients.

Association between A1 segment dysplasia, bifurcation angles of anterior cerebral artery and the formation of anterior communicating aneurysms

Wang Li, Shi Zhao, Kong Xiang, Yang Liu, Liu Ya, Luo Song, Zhang Longjiang

2022, 43(1):  61-66.  doi:10.3969/j.issn.1006-7795.2022.01.012

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Objective To investigate the relationship between the dysplasia and bifurcation angles of A1 segment of the anterior cerebral artery (ACA) and the formation of the anterior communicating aneurysms (ACoA). Methods Totally 272 patients with anterior communicating artery (Acom) bifurcation aneurysms who underwent CT angiography (CTA) and digital subtraction angiography (DSA) or clipping surgery (aneurysm group) and 272 age and sex matched subjects (control group) were retrospectively collected in Jinling Hospital, Nanjing, China between Jan. 2010 and Mar. 2017. A1 segment of ACA was assessed by an experienced radiologist in the aneurysm group and normal group as symmetric, hypoplasia, and absence, as well as ACA bifurcation angles. The angles between the A1 or A2 segment and Acom (A1/Acom, A2/Acom) and between the A1 and A2 segments (A1/A2) were measured. Results The mean age of all patients was (54±11) years and 55.15% subjects were female. In the aneurysm group, 70.96% of aneurysms were in the left Acom bifurcation, and 29.04% in the right. The median size was 4.54 (3.64, 6.01) mm. 229 cases (84.19%) had A1 segment hypoplasia or absence in aneurysm group, of which 223 cases (81.99%) were contralateral, 6 cases (2.21%) were ipsilateral. In the control group, 126 cases (46.32%) had A1 segment hypoplasia or absence. A1 segment hypoplasia or absence in the aneurysm group (84.19%) was higher than that in the control group (46.32%) (P<0.001). The A2/Acom angle [125.01 (108.89,144.55)°] in the aneurysm group was higher than that in the control group [101.44 (91.30,115.17)°], and the A1/A2 angle (110.01±20.72)° was lower than that in the control group (130.28±18.30)° (P<0.001), and the A1/Acom angle [107.86 (93.47,128.18)°] was lower than that in the control group [111.99 (100.18,126.66)°](P=0.05). Conclusions The presence of ACoA is associated with hyposplasia or absence of A1 segment (especially contralateral), larger A2/Acom and smaller A1/A2 and A1/Acom angles of the ACA bifurcation,and A1 segment hypoplasia or absence and the A2/Acom bifurcation angle were independent risk factors for AcoA formation.

Diagnostic value of magnetic resonance imaging for cerebral venous sinus thrombosis

Zhang Huibo, Yang Xiaoxu, Liu Xinyuan, Gu Hua, Wang Shuangkun, Yang Qi

2022, 43(1):  67-73.  doi:10.3969/j.issn.1006-7795.2022.01.013

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Objective To investigate the diagnostic value of magnetic resonance imaging (MRI) multi-contrast weighted sequences (T1WI, T2WI, FLAIR, DWI and TOF-MRV) based on the signal characteristics of thrombosis and secondary venous parenchymal changes. Methods Patients suspected with cerebral venous thrombosis (CVT) were included in our study. Two experienced radiologists reviewed the abnormal signal of thrombus on MRI multi-contrast weighted sequences (T1WI, T2WI, FLAIR, DWI and TOF-MRV), respectively with double-blind evaluation of seven venous segments (superior sagittal sinus, straight sinus, right transverse sinus, right sigmoid sinus, left transverse sinus, left sigmoid sinus, and intracranial cortical vein). Then, the sensitivity and specificity of each MRI sequence on patient' level and segment' level were analyzed. The characteristics of abnormal cerebral parenchymal changes and the treatment of CVT patients were recorded. And the correlation between abnormal brain parenchymal changes and thrombosed segments and the endovascular interventions were analyzed.Results Fifteen of 22 patients were finally diagnosed with CVT and a total of 56 thrombosed segments were involved. (1) On patient' level, the sensitivity of T1WI, T2WI, FLAIR, DWI and TOF-MRV were 66.7%, 86.7%, 100.0%, 46.7% and 100.0%, respectively; On segment' level, the sensitivity of T1WI, T2WI, FLAIR, DWI and TOF-MRV were 32.1%, 57.1%, 78.6%, 19.6% and 91.1%, respectively. (2) In 15 CVT patients, 6 patients (40%) were with abnormal parenchyma change, which mainly located in cerebral cortex and subcortex of venous drainage area. Of these, 4 lesions (50%) were hemorrhagic (hemorrhagic infarction and hematoma). There was no difference in ADC values between lesion side and contralateral side (P=0.583). (3) Of the six patients with CVT received endovascular treatment, four patients (66.7%) had brain parenchymal abnormalities and the other two patients (44.4%) were normal in cerebral parenchymal. Conclusion TOF-MRV has the highest diagnostic sensitivity for CVT among conventional MRI sequences, followed by FLAIR and T2WI sequences. In addition, secondary venous brain parenchymal changes have certain spatial distribution characteristics on MRI images. Identification of these characteristics may help in the clinical diagnosis of CVT and the selection of treatment decisions.

Prediction on neurological deterioration based on imaging features in patients with stroke-associated pneumonia

Sun Penghui, Li Yingying, Liu Xin, Jia Xuejia, Jia Xiuqin, Yang Qi

2022, 43(1):  74-81.  doi:10.3969/j.issn.1006-7795.2022.01.014

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Objective To investigate the risk factors for the occurrence of neurological deterioration (ND) in patients with stroke-associated pneumonia (SAP) and to establish a predictive model using imaging features. Methods We retrospectively recruited SAP patients admitted to emergency or neurology departments during January to December 2020, and SAP patients were divided into ND and non-ND groups according to whether the National Institutes of Health Stroke Scale (NIHSS) score increased by ≥ 4 (total) during hospitalization. The clinical characteristics, laboratory tests, brain and lung imaging features of the two groups were compared. Variables with a P value<0.05 by univariate analysis were included in Logistic regression analysis. Results We retrospectively recruited 73 SAP patients. ND was diagnosed in 15 patients (20.54%). The chest computed tomography (CT) score, large infarction, thalamic infarction and occipital lobe infarction were significantly different between the two groups (P<0. 05). In particular, chest CT score (OR=1.218,95%CI:1.010-1.469), thalamic infarction (P<0.05, OR=10.016, 95%CI:1.523-65.862) and large cerebral infarction (P<0.05, OR=9.033, 95%CI:1.746-46.742) were independent risk factors for the occurrence of ND. For prediction of ND, the area under curve (AUC) of the logistic model was 0.849 (95% CI:0.752-0.947); the AUC of chest CT score was 0.744 (95% CI:0.611-0.878) with sensitivity 80.00%, specificity 63.80%, predictive positive value (PPV) 36.36%,predictive negative value (PNV) 92.50%, accuracy 67.12%; the AUC of thalamic infarction was 0.624 (95% CI :0.450-0.797), with sensitivity 33.33%, specificity 91.38%, PPV 50.00%, PNV 84.13%, accuracy 79.45%; and the AUC of combined large infarction and chest CT score was 0.799 (95%CI:0.690-0.909) with sensitivity 100.00%, specificity 48.28%, PPV 33.33%, PNV 100.00%, accuracy 58.9%. Conclusion Our study indicated that chest CT score, thalamic infarction and large cerebral infarction may be independently associated with ND in SAP. The chest CT score may predict ND in SAP patients with higher sensitivity and accuracy, what's more, the higher the chest CT score (>4.5), the more likely to develop ND in SAP patients. Thalamic infarction may predict ND in SAP patients with higher specificity and accuracy. The combined analysis of chest CT score and lesion size of infarction can help clinicians to stratify the SAP patients with higher risk to develop ND.

Basic Research

CD200R1 deletion promotes LPS-induced endocytosis of microglia

Du Tianshu, Gong Xiaoli, Aizier Ainiwaer, Zhang Zhen, Liu Yang, Wang Xiaomin, Zhang Ting

2022, 43(1):  82-90.  doi:10.3969/j.issn.1006-7795.2022.01.015

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Objective To study the effect of CD200R1 on the endocytosis of microglia induced by bacterial lipopolysaccharide (LPS). Methods The changes of microglia endocytosis level was observed with fluorescentmicrobeads endocytosis experiment, and the expression of CD200R1mRNA was detected with RT-qPCR, and also it was observed in the BV2-SH-SY5Y co-culture model. Moreover, the primary microglia was extracted from CD200R1 knockout mice to observe the changes of the endocytic function induced by LPS. Results LPS activated microglia and promoted the increase of endocytosis and the decrease of CD200R1 expression in microglia. In the BV2-SH-SY5Y co-culture model, the neuronal cells contacted microglia to repress the increase of LPS-induced microglia endocytosis. The level of endocytosis increased more significantly in the CD200R1 knockout microglia treated with LPS. Conclusion CD200R1 knockout microglia showed more significant increase in endocytosis after LPS stimulation.

Role of microglial histone deacetylases 3 in hypobaric hypoxia-induced oxidative stress

Li Jun, Li Shuoshuo, Peng Zhixin, Liao Yajin, Cheng Jinbo, Yuan Zengqiang

2022, 43(1):  91-98.  doi:10.3969/j.issn.1006-7795.2022.01.016

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Objective To investigate the effect of hypobaric hypoxiaon the brain tissue oxidative stress level and whether microglial HDAC3 is involved in this process. Methods First, wild type mice were treated in a hypobaric chamber at a simulated altitude of 6 000 meters for 7 days.The mRNA levels of hypoxia inducible factors-1α (HIF-1α), inducible nitric oxide synthase(iNOS), superoxidase dismutase(SOD) and histone deacetylases 3 (HDAC3) in the hippocampus were analyzed by real-time quantitative polymerase chain reaction (real-time PCR). Then, BV2 cells were treated in atmosphere with 0.1% O₂ in a hypoxia incubator and the mRNA and protein levels of iNOS, SOD, HDAC3 and HIF-1α were determined by Western blotting and real-time PCR.The levels of reactive oxygen species (ROS) were analyzed by flow cytometry.Furthermore, HDAC3-silenced and wild type BV2 cells were cultured in 0.1% O₂ atmosphere and the levels of ROS, iNOS and SOD were analyzed as above. Last, microglial HDAC3 conditional knockout mice and wild type mice were treated in hypoxia atmosphere, and the mRNA level of iNOS were analyzed by real-time PCR. Results The mRNA levels of iNOS, SOD and HDAC3 were upregulated in the hippocampus from mice underwent hypobaric hypoxia.The in vitro experiments indicated that the protein levels of iNOS, HDAC3 and HIF-1α were increased in BV2 cells treated 0.1% O₂, and the mRNA levels of iNOS and SOD were increased as well. By flow cytometry, we found the level of ROS was increased when BV2 cells were cultured in hypoxia atmosphere. Inhibition of HDAC3 significantly reduced the production of hypoxia-induced ROS, as well as decreased expression of SOD and iNOS. In addition, knockout of HDAC3 in microglia inhibited the hypoxia-induced upregulation iNOS. Conclusion The hypoxia treatment resulted in increased oxidative stress in the hippocampus and microglia, and inhibition of microglial HDAC3 ameliorated hypoxia-induced oxidative stress.

Phloretin inhibits oxidative stress response in LPS-stimulated BV2 microglia

Li Chenchen, Xu Junmei, He Qianqian, Li Jiaying, Li Zhiheng, Xu Zhiqing, Yang Yutao

2022, 43(1):  99-105.  doi:10.3969/j.issn.1006-7795.2022.01.017

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Objective To explore the inhibition effect of phloretin (PHL) on oxidative stress response in lipopolysaccharide (LPS)-stimulated BV2 microglia and its related molecular mechanism. Methods LPS was used to establish BV2 microglia oxidative stress damage cell model, and the cell model was pretreated with different concentrations of PHL. MTS assay was used to examine the cell survival rate of BV2 microglia. ELISA kits were used to detect oxidative stress related products such as nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activity. Luciferase reporter gene system was used to determine the transcriptional activity of antioxidant reaction element luciferase reporter plasmid (ARE-LUC). Western blotting was used to detect the level of phosphorylated nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein. Results LPS treatment significantly decreased the viability of BV2 microglia, the level of GSH and the activity of SOD, but increased the level of NO, MDA. However, the pretreatment of PHL remarkably increased the viability of BV2 microglia and the level of GSH and SOD, but decreased the level of NO and MDA. Meanwhile, the pretreatment of PHL further increased the level of phosphorylated Nrf2, the activity of ARE-LUC reporter gene and the level of HO-1. Conclusion PHL can significantly inhibit the oxidative stress response of BV2 microglia induced by LPS, and the inhibition effect might be mediated activating the Nrf2/ARE pathway.

Similarities and differences of cerebral β-amyloid protein characteristics between 5xFAD transgenic mice and alzheimer's disease patients

Meng Xia, Li Meng, Wang Jingjing, Zhang Jing, Chen Baian, Lu Jing

2022, 43(1):  106-112.  doi:10.3969/j.issn.1006-7795.2022.01.018

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Objective To explore the relationship between 5xfad transgenic mice and Alzheimer's disease similarities and differences amyloid β-protein (Aβ) plaque characteristics. Methods Immunofluorescence staining was used to detect Aβ plaques in the brain of 5xFAD transgenic mice and Alzheimer's disease (AD) patients by monoclonal antibody (4G8). The qualitative and quantitative analysis of Aβ plaques in the brain of 5xFAD transgenic mice and AD patients was conducted by CaseViewer software, and the similarities and differences in the morphology, quantity and type of Aβ plaques in the brain of 5xFAD transgenic mice and AD patients were compared Results The main similarities between the characteristics of Aβ plaques in the brain of 5xFAD transgenic mice and AD patients were as follows: obvious Aβ plaques were found in the cerebral cortex and hippocampus of both mice and AD patients; Diffused Aβ plaques and dense Aβ plaques were observed in both of them. The proportion of Aβ plaques with A diameter of <15 μm was the highest in both brain regions. The number of Aβ plaques at [45,60)μm and ≥60 μm in the same brain area was similar between the two groups. Both have obvious cerebral amyloid angiopathy (CAA) in their brains. The main differences in the characteristics of Aβ plaques in the brains of 5xFAD transgenic mice and AD patients were as follows: Aβ plaques with A diameter of <15 μm in the brains of 5xFAD transgenic mice were significantly less than Aβ plaques of the same area in the brains of AD patients (P<0.001); Aβ plaques with diameters of [15,30)μm and [30,45)μm were significantly higher than those with the same area in AD patients (P=0.001, P=0.020); In addition, Aβ plaques with typical coronal structure were observed in the dense Aβ plaques in AD patients, but not in 5xFAD transgenic mice. Conclusion The location, main morphology of Aβ plaques, number of Aβ plaques with diameter of [45,60) μm and ≥60 μm in the same area and characteristics of CAA are highly similar to the AD patient; however, the number of Aβ plaques with a diameter of <15 μm, [15,30)μm and[30,45)μm in the same area of the brain, and the characteristics of Aβ plaque with or without typical coronal structure are different from those of AD patients.

Identification of protein-coding genes regulated by differential DNA methylation enhancer regions in glioblastoma

Zhao Xiaoxiao, Yu Qiuhong, Ji Jianghuai, Wang Shijia, Wang Rendong, Li Dongguo

2022, 43(1):  113-119.  doi:10.3969/j.issn.1006-7795.2022.01.019

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Objective By integrating and analyzing DNA methylation data and expression data in glioblastoma (GBM), we identified protein-coding genes (PCGs) that might be regulated by differential DNA methylation enhancer regions (DMERs) in GBM, predicted the biological functions of PCGs regulated by DMERs in GBM, and explored the potential biomarkers related to the GBM prognosis. Methods Based on methylation data and expression data in public disease databases, we used a computational strategy to construct genome-wide enhancer regions and screened for DMERS in GBM. We identified PCGs whose expression might be regulated by DMERs and performed enrichment analysis on these PCGs. Based on the patient's clinical information and the expression data of the corresponding samples, we performed Kaplan-Meier prognostic analysis on the identified PCGs. Results We screened 16 287 DMERs and identified 795 pairs of DMER-PCGs in this study, including 593 hypomethylated enhancers, 82 hypermethylated enhancers and 642 PCGs. We excavated 45 PCGs that were significantly related to the overall survival of GBM. Conclusion This study has further deepened the understanding of the regulatory pattern of enhancer methylation in GBM, and provided assistance for the development of novel biomarkers and targets for diagnosis and treatment of GBM.

Clinical Research

Differential diagnosis of early osteoarthritis based on in-line phase contrast imaging and support vector machine

Li Jun, Cheng Cheng, Dong Linan, Wu Mingshu, Zhang Lu

2022, 43(1):  120-126.  doi:10.3969/j.issn.1006-7795.2022.01.020

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Objective To establish the classification model for normal and early osteoarthritis (OA) of cartilage tissue by in-line phase contrast imaging (IL-PCI) technique and support vector machine (SVM) algorithm. Methods The study samples were in vitro knee cartilage samples from patients undergoing arthroplasty. The research subjects were divided into normal group and early OA group, 18 cases in each group. Computed tomography (CT) images of cartilage tissues were obtained by in-line phase contrast imaging (IL-PCI) technology. Totally 26 texture parameters were extracted from the two groups of CT images by using three analysis methods of stroke length matrix, fractal dimension and discrete wavelet transform. Dimensionality of texture parameters was reduced by principal component analysis. A SVM classification model was established based on texture parameters to classify normal cartilage and early OA cartilage automatically. Results The changes of microstructure in normal and early OA cartilage could be clearly observed by IL-PCI technique. The cartilage texture parameters of the two groups were compared, and the results showed that most of the texture parameters were significantly different. The classification accuracy of the two groups can reach 86.1% by support vector machine algorithm. Conclusion The support vector machine algorithm and IL-PCI method can provide an effective auxiliary method for the diagnosis of early osteoarthritis.

Correlation between the expression of cytokeratin in colorectal cancer and clinicopathological features

Si Hai, Liu Ran, Xiong Zhongyuan, Cao Bangwei

2022, 43(1):  127-131.  doi:10.3969/j.issn.1006-7795.2022.01.021

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Objective To explore the expression of cytokeratin in colorectal cancer and its relationship with clinicopathological features. Methods A total of 200 specimens with colorectal carcinoma confirmed by surgery and postoperative pathology were selected, and corresponding adjacent normal tissues were selected as controls. The expression of CK7,8,18-20 in colorectal cancer tissues and in adjacent normal tissues were detected by immunohistochemistry. Their correlation with pathological characteristics and general information was compared. Results CK7 was not expressed in cancer tissues and adjacent normal tissues. The positive expression rates of CK8 and 18-20 in tumor tissues were significantly higher than those in the corresponding adjacent normal tissue (all P<0.05). The expression of CK8 in cancer tissue was positively correlated with the depth of tumor invasion. The expression of CK19 was positively correlated with lymph node metastasis. The expression of CK20 was negatively correlated with the degree of tumor differentiation. Conclusion The expression levels of CK8, 19 and 20 are closely related to tumor invasion, lymph node metastasis and differentiation. The expression levels of CK8, 19 and 20 are significant in judging the malignant degree of colorectal cancer.

Analysis of risk factors in patients with reflux esophagitis with extra-esophageal
symptoms

Wang Rongxin, Wang Jing, Hu Shuiqing

2022, 43(1):  132-137.  doi:10.3969/j.issn.1006-7795.2022.01.022

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Objective To determine the risk factors of the reflux esophagitis (RE) with extra-esophageal(EE)symptoms by comparing general demographic information, lifestyle, eating habits, comorbidities, current medications, anxiety, depression of RE patients with and without EE symptoms. Methods The subjects of the study were seen in the Department of Gastroenterology, Xuanwu Hospital, Capital Medical University from September 2016 to August 2017 and were clearly diagnosed as RE under gastroscopy. There were 361 cases in total. They were divided into group with EE symptoms and group without EE symptoms. The patients were surveyed on General demographic information, lifestyle, eating habits, comorbidities, current medications, Patient Health Questionnaire-9(PHQ-9) Depression Scale, General Anxiety Disorder-7(GAD-7) Anxiety Scale, Gastroesophageal Reflux Disease Questionnaire(GerdQ)and Reflux Symptom Index(RSI). Results Among the 361 patients with RE, there were 218 patients with EE symptoms. Sensation of foreign body within the throat, recurrent sore throat and chronic cough were more common, accounting for 52.75%, 46.79% and 26.15% respectively. Univariate analysis showed that there were significant differences in low education level, smoking, constipation, high body mass index (BMI), anxiety, and depression (P<0.05) between two groups. Multivariate Logistic regression analysis identified that low education level (OR:1.646, 95%CI:1.049-2.572,P<0.05), smoking (OR:2.488,95%CI: 2.047-3.281, P<0.01), high BMI (OR:1.067, 95%CI: 1.004-1.135, P<0.05), depression (OR: 1.062, 95%CI: 1.002-1.133, P<0.05), anxiety(OR: 1.061, 95%CI: 1.001-1.131, P<0.05) were the risk factors of onset of EE symptoms in RE patients. Conclusion The main extra-esophageal symptoms of RE were sensation of foreign body within the throat and recurrent sore throat, chronic cough. Low education level, high BMI, smoking, depression and anxiety were risk factors of RE with extra-esophageal symptoms.

Association of OSA and asthma with the incidence rate of coronary heart disease

Xia Ning, Nie Xiuhong, Wang Hao, Fan Xiaojun

2022, 43(1):  138-142.  doi:10.3969/j.issn.1006-7795.2022.01.023

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Objective The aim of this study was to investigate the influence of obstructive sleep apnea (OSA) with bronchial asthma (asthma) on the prevalence of coronary heart disease (CHD). Methods A total of 3 152 patients who received sleep monitoring in the Sleep Medical Center of Xuanwu Hospital, Capital Medical University from October 2002 to September 2020 were retrospectively analyzed. All patients were divided into four groups: simple snoring group (n=1 335), bronchial asthma group (n=72), OSA group (n=1676) and OSA with asthma group (n=69). The independent risk factors of coronary heart disease were analyzed by multivariate Logistic model. Results The incidence rate of CHD in asthma with OSA group was significantly higher than that in simple snoring group, simple OSA group and simple asthma group (OR=13.389, 95%CI:7.930-22.607, P<0.01; OR=11.850, 95%CI: 7.116-19.733, P<0.01; OR=3.925, 95%CI: 1.827-8.431, P<0.01). After adjusting for age, gender, BMI and abdominal circumference, there was still statistical significance (OR=7.224, 95% CI: 3.989 - 13.083, P<0.01; OR=6.783, 95%CI: 3.811-12.073, P<0.01; OR=2.920, 95%CI: 1.240-6.878, P<0.01).There was an independent correlation betweenasthma with OSA and CHD (OR=5.464, 95% CI: 2.997-9.959, P<0.01) in patients with age ≥ 55 years and abdominal circumference ≥ 90 cm(OR=4.630, 95%CI: 2.667-8.026, P<0.01). Conclusion There is a significant correlation between asthma with OSA and CHD, especially in the elderly and central obesity patients.

Risk factors and predictive value of Framingham Risk Score of young men with coronary artery disease

Su Yunjuan, Wang Jingjing, Han Xiaotao, Liu Haiyan, Chen Yongfu, Yang Liu, Wu Qiming

2022, 43(1):  143-148.  doi:10.3969/j.issn.1006-7795.2022.01.024

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Objective To investigate the risk factors and predictive value of Framingham Risk Score of young men with coronary artery disease (CAD).Methods A total of 201 young male patients (30≤age<45 years old) who underwent coronary angiography in Beijing Ditan Hospital, Capital Medical University from July 2016 to July 2019 were selected as the research subjects. According to the results of coronary angiography, they were divided into two groups: CAD group (n=139) and non-CAD group (n=62). Framingham Risk Score was calculated for all patients, and patients in both groups were divided into two subgroups according to Framingham Risk Score: low risk group and high risk group/moderate risk group. The severity of coronary artery disease in patients with CAD was assessed by Gensini score, and the medical history and relevant clinical and laboratory indicators of all subjects were collected. Results The proportions of smoking, hypertension and family history of CAD in CAD group were higher than those in non-CAD group (P<0.05).There were significant differences in high density lipoprotein-cholesterol (HDL-C), ApoB/ApoA and non-HDL-C in CAD group (P<0.05). There was no statistical difference in the mean Framingham Risk Score between CAD group and non-CAD group as well as the proportion of patients in the low-risk Framingham Risk Score and the medium/high risk Framingham Risk Score. Further analysis of the correlation between the Framingham Risk Score and Ginsini Score in the CAD group showed no linear correlation (P=0.749).The area under the receiver operating characteristic (ROC) curve of the Framingham Risk Score was 0.544 (95%CI: 0.458-0.629, P =0.324).Binary linear multivariate Logistic regression analysis showed that hypertension, family history of premature coronary atery disease and homocysteine (HCY) were independent risk factors for coronary heart disease in young men,while HDL-C is a protective factor in these samples. Conclusion A single-center cross-sectional study shows that Framingham Risk Score cannot adequately assess coronary artery severity in young male patients with CAD. The importance of non-traditional CAD risk factors should be considered in young male patients with early onset CAD, and future prospective studies with more samples are needed to verify this.

Risk factors associated with loss of lordosis after multilevel anterior cervical surgery

Wang Yu, Li Xiangyu, Liu Chengxin, Kong Chao, Lu Shibao

2022, 43(1):  149-155.  doi:10.3969/j.issn.1006-7795.2021.06.025

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Objective To evaluate risk factors associated with the loss of lordosis after multilevel anterior cervical surgery. Methods We retrospectively reviewed 105 patients with cervical myelopathy who received anterior cervical surgery. Preoperative deep paraspinal muscles cross-sectional area (CSA) was evaluated. Cervical alignment assessment included cervical lordosis (CL), T1 slope(T1S), and cervical sagittal vertical axis (cSVA). The recovery rate of the Japanese Orthopedic Association (JOA) score was used to evaluate the effect of cervical spine surgery. The alignment change (^△CL) was used to assign groups for patients: lordosis loss group, lordosis kept group, and lordosis gain group. Results Pearson correlation analysis suggested the alignment changes negatively correlated with preoperative CL and preoperative T1S, and positively with deep flexor CSA. Comparisons among three alignment change groups suggested that a larger T1S, smaller extensor CSA, and smaller flexor CSA were related with lordosis loss. A smaller CL and larger cSVA were related with lordosis gain. The result of multivariate stepwise logistic regression showed that a larger preoperative T1S and a smaller deep flexor CSA were significant risk factors of lordosis loss. Conclusion The results of the present study demonstrated that a larger T1 slope and a smaller deep flexor CSA highly predicted the loss of lordosis for patients with multilevel anterior cervical surgery.