Table of Content

21 April 2025, Volume 46 Issue 2

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Statistical methods and application cases examples for multiplicity issues in multiple endpoints clinical trials

Bai Xiudan, Xu Qin, Wang Anxin

2025, 46(2):  184-190.  doi:10.3969/j.issn.1006-7795.2025.02.002

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Performing multiple tests without adjusting the test level results in a higher-than-intended overall familywise error rate (FWER). This phenomenon is known as the multiplicity problem. In this paper, we  first introduced the mechanism of multiplicity problem based on the classification and characterization of clinical endpoints. Then,  strategies and methods to solve the multiplicity problem were introduced, including the parallel strategy/single-step method, the sequential strategy/multistep method/stepwise method, and their combinations. The results of different analytic strategies may vary. The practical application of the above common strategies and statistical methods were introduced through the case studies of domestic and foreign investigator initiated clinical trial. Multiplicity adjustment for multiple endpoints in clinical trials can be achieved by a single strategy or a combination of strategies. Depending on the selected strategy or combination, the statistical  methods and significance level (denoted as α) for each test hypothesis are determined to effectively control the multiplicity problem.

Application of the win ratio method to clinical trials in cerebrovascular disease

Tian Ruobing, Xu Qin, Zhou Quan, Tian Xue, Li Xinya, Zheng Manqi, Wang Anxin

2025, 46(2):  191-196.  doi:10.3969/j.issn.1006-7795.2025.02.003

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Objective  To introduce the concepts and principles of the win ratio method and to analyze it in the context of a case study of a clinical trial in cerebrovascular disease. Methods  Based on the study of clopidogrel with aspirin in high risk patients with acute non disabling cerebrovascular events 2, and key prognostic factors, the outcome events were defined sequentially as ① time to death within 90 d, ② time to recurrence of ischemic stroke within 90 d, ③ time to moderate-to-severe hemorrhage within 90 d. Using clopidogrel combined with aspirin as the reference group, the winning ratio (R_w) of ticagrelor combined with aspirin was analyzed by the win ratio method, and the 95% confidence interval (CI) of R_w was estimated by the Bootstrap method and compared with the hazard ratio (HR) calculated by the competing risk model. Results  When only fatal events were considered, the win ratio method suggested that the ticagrelor group was significantly better than the clopidogrel group, R_w=2.00 (95%CI:1.52-2.47), and after stepwise inclusion of  ischemic stroke and moderate-to-severe hemorrhage recurrence, the win ratio method yielded a value of 1.29(95% CI:1.25-1.57), and the HR value from Fine and Gray competing risk regression was 0.78 (95% CI:0.65-0.95), both of which indicated that the efficacy of the ticagrelor group was superior to that of the clopidogrel group. Conclusion  The win ratio method can be used to analyze clinical trials with composite endpoints after prioritizing multiple outcome variables, showing the advantages of win ratio and its promising application in cerebrovascular disease research.

Transition of body mass index and metabolic syndrome in patients with major depressive disorder

Qi Han, Dong Chengcheng, Liu Rui, Zhu Xuequan, Lin Xuzhou, Qin Yanshu, Yu Zibo, Wang Haining, Li Lei, Feng Yuan, Zhang Ling, Yan Fang

2025, 46(2):  202-209.  doi:10.3969/j.issn.1006-7795.2025.02.005

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Objective  To evaluate the transition rules of   normal body mass index (BMI), overweight and metabolic syndrome (MetS) in patients with major depressive disorder (MDD). Methods  Patients with MDD who had multiple admission records between Jan 2016 and Nov 2021 in Beijing Anding Hospital, Capital Medical University were included. Based on the overweight and metabolic syndrome status assessed at each admission, the patients were categorized into three states: normal BMI, overweight and metabolic syndrome. A multi-state Markov model was used to analyze the transition intensity and transition frequency between three states and the influence of covariates on transitions. Results  A total of 892 records of 398 subjects were included, with a median age of 56 years old and 31.4% males. The median follow-up period was 40 months. The multi-state model showed that there were 494 transitions between the three states, of which 5.1% moved from normal BMI to overweight and 5.5% moved from overweight to MetS. The intensity of transition was the highest from overweight to MetS, 9.52 times greater than overweight to normal BMI. After 48.53 months, MDD patients with normal BMI began to transition to MetS. For overweight MDD patients, the transition to MetS started after 8.77 months. MDD patients with normal BMI or overweight had 31.4% and 50.4% probabilities of developing Mets after 36 months. For MDD patients comorbid with MetS, the probability of staying at MetS was 51.2% after 36 months. Multivariate analysis showed that being unmarried was a risk factor against developing overweight in normal BMI MDD patients, while  a higher level of education was a protective factor against developing MetS in overweight MDD patients. Conclusion  MDD patients exhibited a higher intensity and risk of developing MetS, and it is not easy to reverse MetS, suggesting that BMI management and MetS intervention should be strengthened in MDD patients.

Effect of CD38 expression of tumor-infiltrating immune cells on the prognosis of esophageal squamous cell carcinoma with lymph node metastasis

Shi Feng, ZhaoYanjie, Gao Ying, Song Qingkun

2025, 46(2):  210-215.  doi:10.3969/j.issn.1006-7795.2025.02.006

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Objective  To investigate the prognostic effect of CD38 in patients with esophageal squamous cell carcinoma patients (ESCC). Methods  A retrospective cohort study with 142 ESCC patients was performed. The clinicopathological features and expression of CD38, CD4, CD8, Ki-67, programmed cell death ligand 1(PD-L1) and programmed cell death 1(PD-1) in tumor and immune cells were evaluated. Results  Among ESCC patients with lymph node metastasis, the expression of CD38 had a significant association with the overall survival (P=0.037). The median overall survival was 14 months and 38 months among patients with low and high expression of CD38, respectively. The crude and adjusted hazard ratio of high CD38 expression was 0.46 (95%CI： 0.21-0.98) and 0.32 (95%CI： 0.13-0.76) respectively. The expression of CD38 had a negative correlation with PD-L1 expressed in tumor cells. Conclusion  The high expression of CD38 was associated with a better survival for ESCC with lymph node metastasis. 

The correlation of serum hypoxia-inducible factor-1α level with cerebral microbleeds and cognitive impairment

Li Qing, Zhao Xiaowen, Ren Jing, Yu Miao, Cui Hanfang, Ding Fangyuan, Liu Hao, Li Qiong, Wang Fan, Li Qing, Chen Xiyan, Lu Chengbiao, Li Shaomin, Zhao Jianhua

2025, 46(2):  216-227.  doi:10.3969/j.issn.1006-7795.2025.02.007

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Objective  To explore the correlation between serum hypoxia-inducible factor-1α(HIF-1α) levels and cerebral microbleeds (CMBs) and cognitive impairment  and to assess the predictive value of HIF-1α for CSVD-related cognitive impairment. Methods  A total of 104 patients with CSVD who attended the Department of Neurology, First Affiliated Hospital of Xinxiang Medical University from June 2022 to November 2023 were enrolled. All enrolled patients were subjected to basic statistics, cranial nuclear magnetic resonance examination, cognitive function assessment, and serum HIF-1α test, and the number and location of CMBs were counted. Based on the above data the enrolled patients were grouped.The correlation between HIF-1α and cognitive function and CMBs was studied the influencing factors of CMBs and cognitive impairment were analyzed, and the predictive value of HIF-1α on the occurrence of cognitive impairment was evaluated. Results  There were statistically significant differences in HIF-1α levels and cognitive function among different CMBs groups. Serum HIF-1α levels were significantly negatively correlated with overall cognitive function, visuospatial and executive function, attention, and delayed recall, and serum HIF-1α was positively correlated with the number of  CMBs. HIF-1α may be a risk factor for CMBs and cognitive impairment associated with CSVD, and serum HIF-1α has potential in predict the cognitive impairment caused by CSVD. Conclusion  Serum levels of HIF-1α were associated with the number of CMB and CSVD-related cognitive impairment, and serum levels of HIF-1α may have a predictive value for CSVD-related cognitive impairment.

Effect of large artery atherosclerosis subtype on the efficacy of Ginkgo Diterpene Lactone Meglumine in acute ischemic stroke

Jing Jiao, Zhang Siyao, Liu Yanling, Wang Fen, Xiao Wei, Wang Zhenzhong

2025, 46(2):  228-233.  doi:10.3969/j.issn.1006-7795.2025.02.008

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Objective  To investigate the effect of large artery atherosclerosis (LAA) and non-LAA subtypes on the efficacy of Ginkgo Diterpene Lactone Meglumine (GDLM) in patients with acute ischemic stroke. Methods  This was a post-hoc analysis of multicenter, randomized, double-blind, placebo-controlled, and  parallel-group trial. A total of 3 448 patients who had acute ischemic stroke were randomly assigned in a 1∶1 ratio  to receive the injection of GDLM or the placebo once day within 48 h after symptoms and continued for 14 d. The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) of 0 or 1 on day 90 after randomization. Results  A total of 3 448 patients were enrolled, with 1 604 (46.52%) patients with non-LAA and 1 844 (53.48%) with LAA. Compared to the placebo treatment. GDLM  injection effectively improve the functional prognosis, with a higher proportion of mRS score of 0-1 in both non-LAA (OR=1.24, 95% CI: 1.02-1.51; P=0.03) and LAA (OR=1.37, 95% CI:1.14-1.65; P<0.001) group. There was no significant interaction between LAA subtypes with treatment (P=0.48 for interaction). Conclusion  Among patients with acute ischemic stroke  in this randomized clinical trial, GDLM might improve the  favorable clinical outcomes at 90 d compared with placebo, regardless of LAA subtypes. Nevertheless, it is necessary to confirm the findings  in the future.

Advances in the application of antiplatelet therapy in intravenous thrombolysis for acute ischemic stroke patients

Zi Xiaohui, Xia Xue, Li jing, Zhang Xiaoli, Zhou Quan, Wang Anxin, Wang Yilong

2025, 46(2):  234-242.  doi:10.3969/j.issn.1006-7795.2025.02.009

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Acute ischemic stroke (AIS) is associated with high mortality and disability rates, presenting a substantial challenge to global public health challenge. Intravenous thrombolysis (IVT) is recognized as a cornerstone of early AIS treatment and is recommended as the standard therapeutic approach by both national and international guidelines. However, the clinical efficacy of IVT remains suboptimal due to several limitations, including a narrow therapeutic time window and the inevitable activation of the coagulation system and platelet aggregagation during thrombolysis. These factors may contribute to adverse outcomes such as early neurological deterioration (END) and vascular re-occlusion. Antiplatelet therapy (APT), which inhibits platelet aggregations, reduces microthrombus formation, and stabilizes the vascular endothelium with multifaceted mechanisms, has emerged as a promising adjunctive strategy to IVT, offering potential synergistic effects. This review summarized the latest evidence from both domestic and international studies, focusing on the mechanisms of APT, recent clinical advancements in IVT combined with APT, and the safety and efficacy of APT administration at different time windows relative to IVT. Emphasis is placed on the influence of various antiplatelet agents, dosing regimens, and initiation timing on therapeutic outcomes, alongside a comprehensive evaluation in the context of current guideline recommendations and clinical practice. Current guidelines recommend initiating APT 24 h after IVT, following imaging confirmation to exclude the risk of intracranial hemorrhage. However, the efficacy and safety of earlier APT initiation remain inconclusive. Individualized treatment strategies, such as early administration of low-dose, short-acting APT or combination therapy in specific patient subgroups, may effectively balance therapeutic benefits and risks. The adjunctive use of APT in IVT holds promise for enhancing efficacy and improving clinical outcomes, but precise stratification of safety and efficacy is essential. Future research should focus on optimizing combination IVT and APT strategies through individualized patient profiling, appropriate drug selection, and dynamic imaging monitoring to achieve precision management in AIS treatment.

Prediction model for extraprostatic extension of prostate based on MRI and clinical indicators

Fan Yunpeng, Xiong Tianyu, Yang Kun, Liu Zhanliang, Jin Song, Xie Ping, Niu Yinong

2025, 46(2):  243-251.  doi:10.3969/j.issn.1006-7795.2025.02.010

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Objective  To develop a Nomogram clinical prediction model for the pathological occurrence of extraprostatic extension (EPE) after radical prostatectomy in prostate cancer patients, using simplified site-specific magnetic resonance imaging (MRI) indicators and other clinical parameters. Methods  A total of 181 prostate cancer patients ［mean age (69.0±7.3) years］ who underwent radical prostatectomy were included. These patients had received 3-Tesla multi-parametric magnetic resonance imaging (3-T mpMRI) within 6 months prior to surgery. Based on mpMRI measurements ［capsular contact length (CCL)　> 15 mm, capsular bulging/irregularities, diameter of index lesion(dIL), and evident extraprostatic extension (eEPE)］, the dIL*sEPE grading system was derived. The optimal cut-off value of dIL (denoted as dIL) was determined using the Youden J index, and categorized it into a binary variable. A Logistic regression model was established based on the dIL*sEPE grading and clinical scores. The predictive performance of clinical indicators, MRI indicators, and combined clinical and MRI indicators were compared. Finally, a clinical prediction model integrating both clinical and MRI data was developed. Results  Pathological EPE was found in 46 out of 181 cases (25.4%). A Nomogram prediction model for EPE was established with a combination of the dIL*sEPE grading and clinical indicators. Conclusion  The combination of dIL*sEPE grading with clinical indicators accurately predicts extracapsular extension in prostate cancer. The Nomogram model that established, based on MRI imaging characteristics and clinical indicators has good performance and is easy to use. It is beneficial to stratifying management for prostate cancer patients, and it provides valuable guidance for patients suitable for nerve-sparing surgery.

Relationship between chronic diseases and benign prostatic hyperplasia in middle-aged and older Chinese adults: A cross-sectional study based on CHARLS database

Ming Jie, Jin Song, Liu Zhanliang, Wang Zongwei, Niu Yinong

2025, 46(2):  252-262.  doi:10.3969/j.issn.1006-7795.2025.02.011

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Objective  To explore the correlation between chronic diseases and the risk of benign prostatic hyperplasia (BPH) in middle-aged and older Chinese man.Methods  Data from the 2013 China Health and Retirement Longitudinal Study (CHARLS) were used, including 4 509 male participants aged 45 years and older. Chronic diseases and BPH diagnoses were obtained through a questionnaire survey. Logistic regression analysis was performed to identify independent risk factors for BPH. Restricted cubic splines (RCS) were used to explore the nonlinear relationship between variables and BPH prevalence, while stratified analyses were conducted to assess the differential impact of chronic diseases on BPH prevalence in different subgroups.Results  Compared to patients without BPH, those with BPH had a significantly higher prevalence of comorbid chronic diseases, including hypertension, diabetes, chronic respiratory diseases, chronic heart disease, stroke, chronic kidney disease, chronic digestive diseases, arthritis or rheumatism, depression, and memory-related disorders. Multivariable Logistic regression analysis indicated that factors such as the 10-item Center for Epidemiological Studies Depression Scale (CESD-10) scores (OR = 1.043, 95% CI: 1.022－1.063, P < 0.001), chronic respiratory disease (OR = 1.518, 95% CI: 1.143－1.998, P = 0.003), chronic heart disease (OR = 1.515, 95% CI: 1.143－1.998, P = 0.003),  chronic kidney disease (OR = 2.384, 95% CI: 1.799－3.137, P < 0.001), and chronic digestive disease (OR=1.427， 95%CI：1.129-1.796,P=0.003) were independently associated with the occurrence of BPH. RCS analysis demonstrated no non-linear association between age, BMI, and CESD-10 scores and BPH. Stratified analysis revealed that the influence of these chronic conditions on BPH remained constantly stable across different subgroups.Conclusion  BPH is commonly comorbid with various chronic diseases. Future treatment strategies for BPH should consider the shared pathological mechanisms between BPH and these chronic conditions, with a focus on integrated interventions targeting common pathways.

Effect of the “five-step” method holmium laser enucleation for benign prostatic hyperplasia with  large volume on urinary control and sexual protection

Wen Zhu, , Zhang Chao, Zhang Xiansheng

2025, 46(2):  263-268.  doi:10.3969/j.issn.1006-7795.2025.02.012

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Objective  To analyze the effects of “five-step” Holmium laser enucleation  on  urinary continence and sexual function  of the patients with the large volume prostate. Methods  Data of 105 patients with massive prostatic hyperplasia admitted to the First People's Hospital of Hefei from June 2021 to May 2024 were retrospectively analyzed. Among them,52 patients were treated with the five-step Holmium laser enucleation of prostate (HoLEP),and the others were treated with transurethral plasma kinetic enucleation of the prostate(TUKEP). The perioperative data were collected, and the incidence of urinary incontinence and the changes of sexual function　［incidence of retrograde ejaculation and international index of erectile function-5 (IIEF-5) score］ were observed in the two groups.The changes of maximum urine flow rate (Qmax), international prostate symptom score (IPSS), quality of life (QOL) score, prostate specific antigen (PSA) were compared between the two groups before and 6 months after surgery.Results  There were no significant differences in  indwelling catheterization time and weight of resected glands(P>0.05).The postoperative hemoglobin decline, the average operation time in the HoLEP group was significantly reduced  than that in the TUKEP group(P<0.05). The index of C-reactive protein after surgery in the two groups was higher than before surgery (P< 0.05), but HoLEP group was better than that of TUKEP group (P< 0.05). After 6 months, there were no significant differences in PSA, Qmax, IPSS, QOL and IIEF-5 between the two groups (P> 0.05).The incidence of transient urinary incontinence and retrograde ejaculation in the HoLEP group was significantly better than that in the TUKEP group (P< 0.05).Conclusion  The “five-step” HoLEP method is effective in the treatment for large benign prostatic hyperplasia with large volume. Compared with TUKEP group, HoLEP showed the same treatment efficacy, the less impact on urinary control and retrograde ejaculation, and the more improved postoperative QOL.The “five-step” HoLEP is feasible and safe with promising clinical application prospects.

Advances in research on the interaction mechanisms between androgen receptor and PI3K/AKT pathways in prostate cancer

Xiong Tianyu, Zhao Youquan, Xie Ping, Niu Yinong

2025, 46(2):  269-282.  doi:10.3969/j.issn.1006-7795.2025.02.013

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Both the androgen receptor pathway and PI3K/AKT pathway play pivotal roles in the progression of prostate cancer. There are intricate interactions between these two pathways, showing a negative regulatory relationship of mutual restriction between them. In view of the above, a combined inhibition strategy targeting these two pathways is expected to become a significant therapeutic approach for prostate cancer. This article aims to comprehensively review the molecular mechanisms underlying the interactions between the androgen receptor and PI3K/AKT pathways,  to provide new perspectives and insights for research in the fields.

Regulation of unilateral stimulating striatal D1-MSN with different frequencies on movement in mice

Cheng Fangyuan, Chen Dongkun, Liu Huijin, Jia Jun, Wang Ke

2025, 46(2):  283-288.  doi:10.3969/j.issn.1006-7795.2025.02.014

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Objective  To clarify the effect of unilateral activation of the dopamine type I receptor medium-sized multi-spiny neurons (D1-MSN) in the dorsal striatum of mice on speed.   Methods  The transgenic animals were combined with optogenetic experiments to specifically activate the D1-MSN in the dorsal striatum of mice at different frequencies and to analyze the rotational behavior and speed of mice when stimulating the D1-MSN.   Results  Unilateral activation of D1-MSN induces contralateral rotational behavior in mice and either increases or decreases speed. The mechanisms by which different frequencies affect the speed of mice differently. As the frequency of stimulus increased, the contralateral rotational behavior of the mice increased. Unilateral stimulus of D1-MSN increased speed and induced contralateral rotational behavior, and the rotational behavior increased with increasing stimulus frequency. In the experiment where D1-MSN stimulus did not induce rotational behavior, it was found that 5 Hz stimulus still induced an increase in speed, but 15 Hz and 25 Hz stimulus did not induce an increase in speed. Further analysis of the pre-stimulus locomotor state of the mice showed that 5 Hz, 15 Hz and 25 Hz stimulus increased speed when the average speed before stimulus was less than 5 cm/s. However, 15 Hz stimulus decreased the speed when the average speed before stimulus was greater than 5 cm/s.   Conclusion  Unilateral activation of D1-MSN in the dorsal striatum modulates speed and induces contralateral rotational behavior in mice, and is related to the frequency of stimulus and the locomotor state of the mice before stimulus.

Establishment and characterization of a method for inducing differentiation of mouse monocyte into Kupffer cells in vitro

Li Weiyang, Li Liying, Yang Lin

2025, 46(2):  289-295.  doi:10.3969/j.issn.1006-7795.2025.02.015

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Objective To establish a method for inducing mouse bone marrow monocytes differentiating into Kupffer cells in vitro, for the study of Kupffer cells. Methods  Monocytes were separated from mouse bone marrow and induced by transforming growth factor 1 (TGF-β1), macrophage colony-stimulating factor (M-CSF) and delta-like protein 4 (DLL4). Induced monocyte-derived Kupffer cells (iMoKCs) were identified by real-time fluorescent quantitative polymerase chain reaction(qPCR), immunofluorescence staining and flow cytometry. Immunofluorescence staining and flow cytometry were used to evaluate the phagocytic capacity of iMoKCs. Cell counting kit-8(CCK-8) was used to evaluate the proliferation capacity. Results  Bone marrow monocytes were isolated, after 24 h combined induction, iMoKCs express C-type lectin domain family 4, member f（CLEC4F）,C-type lectin domain family 1, member b（CLEC1B） and V-set and immunoglobulin domain containing 4（VSIG4）at mRNA level, and protein CLEC4F. Phagocytic function of iMoKCs were detected by flow cytometry, and nearly 80% of total iMoKCs show bioparticle acceptance. The number of iMoKCs were detected by CCK-8, the counts were 1.4, 2.0 and 2.9 times of the initial number (0 h) at 24, 48 and 72 h.  Conclusion  These cells display the immunophenotype of Kupffer cells and show the ability of phagocytosis and proliferation induction through M-CSF, TGF-β1 and DLL4, which could replace primary Kupffer cells for in vitro research.

Effect of the ribosome biogenesis factor BMS1 on proliferation of neuroblastoma cells

Guo Jinxin, Jia Anna, Zhan Shijia, Zhang Yao, Zhang Xuan, Guo Yongli, Chang Yan

2025, 46(2):  296-305.  doi:10.3969/j.issn.1006-7795.2025.02.016

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Objective  To elucidate the functional role and underlying mechanisms of the ribosome biogenesis factor BMS1 in neuroblastoma (NB) cellular proliferation. Methods  We utilized the R2 genomics analysis and visualization platform to analyze the correlation between BMS1 expression levels and clinical characteristics of NB children. The BMS1 mRNA level in three human neuroblastoma cells SK-N-BE(2), BE(2)-C, IMR-32 and two normal cells hTERT RPE-1, IMR-90 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Two distinct small interfering RNA (siRNA) sequences were used to target BMS1 mRNA in NB cells SK-N-BE(2) and BE(2)-C, with normal cells hTERT RPE-1 serving as controls. We used RT-qPCR to quantify the mRNA levels of BMS1 and two key neuroblastoma-associated molecules (MYCN and p53). After transfection with siRNA, cellular proliferation was detected by various experimental approaches: crystal violet staining, real-time cell analysis (RTCA), colony-forming unit assay and immunofluorescence. Results  By analyzing two independent neuroblastoma clinical cohorts (GSE85047/NRC-283 and Westermann-144 datasets), it was found that the BMS1 mRNA level in MYCN-amplified NB was significantly higher than that in MYCN-non-amplified NB (P<0.05). Furthermore, the overall survival rate of NB children in the BMS1 high-expression group was decreased (P<0.05). Consistent with these clinical observations, the BMS1 mRNA level in NB cells SK-N-BE(2), BE(2)-C and IMR-32 was significantly higher than that in normal cells hTERT RPE-1, IMR-90 (P<0.05).  The targeted transient knockdown of BMS1 in NB cell lines SK-N-BE(2) and BE(2)-C resulted in decreased intracellular MYCN mRNA expression levels (P<0.05), significantly reduced cell proliferation capacity and colony-forming ability (P<0.05). Immunofluorescence revealed that the expression of Ki-67, a proliferation marker, was decreased (P<0.05). At the molecular level, RT-qPCR showed that  the p53 mRNA level was significantly elevated in the BMS1-knockdown groups (siBMS1-1# and siBMS1-2#) compared with the control group (P<0.05). However, transient knockdown of BMS1 had no significant impact on the proliferative capacity of normal cells hTERT RPE-1. Conclusion  BMS1 expression was up-regulated in MYCN-amplified NB and negatively correlated with the prognosis of the NB children. Mechanistically, interfering with BMS1 expression may transcriptionally activate p53 in NB cells, thereby inhibiting their proliferative ability, while having minimal impact on normal cells growth kinetics. These findings suggest that BMS1 serves as an important proliferation driver in NB and is expected to be a promising therapeutic target for NB children, particularly MYCN-amplified pediatric patients.

Analysis of infiltration of neutrophils and macrophages in tissues of eosinophilic gastroenteritis mice

Xu Longwei, Wang Yadan, Zhou Minsi, Wu Jing

2025, 46(2):  306-313.  doi:10.3969/j.issn.1006-7795.2025.02.017

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Objective  To study the infiltration of neutrophils and macrophages in the tissues of eosinophilic gastroenteritis mice. Methods  Thirty female C57BL/6 mice aged 6-8 weeks were selected to induce the model of eosinophilic gastroenteritis in wild-type mice. They were sensitized by intraperitoneal injection of  ovalbumin （OVA） protein and they were gastric stimulated with OVA. The successful modeling of eosinophilic gastroenteritis was verified by measuring the weight change of mice, detecting OVA specific immunoglobulin E (IgE) and Immunoglobulin G (IgG) levels in peripheral blood of mice by enzyme-linked immunosorbent assay （ELISA）, and detecting intestinal eosinophils count by flow cytometry. The proportion of neutrophils and monocytes in peripheral blood and the proportion of neutrophils and macrophages in spleen, mesenteric lymph nodes, small intestine and colon tissues were detected by flow cytometry. Results  The mice model of eosinophilic gastroenteritis was successfully induced by OVA abdominal sensitization and gavage stimulation. In mice with eosinophilic gastroenteritis, the infiltration of monocytes in peripheral blood, macrophages infiltration of spleen, mesenteric lymph nodes, small intestine and colon tissues were increased. And the neutrophil were increased infiltrated in peripheral blood, small intestine and colon tissues. Conclusion  Macrophage and neutrophil were increased infiltrated in peripheral blood, intestinal tissue of mice with eosinophilic gastroenteritis. Furthermore, the infiltration of macrophage was increased in lymphoid tissues, such as spleen and mesenteric lymph nodes of mice with eosinophilic gastroenteritis.

Study on the role and mechanism of AMP-activated protein kinase in regulating mitochondrial function and modulating cardiomyocyte injury in sepsis

Huang Kang, Dai Yao, Wu Songbai, Lü Jianlei, Feng Jie

2025, 46(2):  314-323.  doi:10.3969/j.issn.1006-7795.2025.02.018

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Objective  To investigate the role and mechanism of AMP-activated protein kinase (AMPK) in regulating mitochondrial function and cardiomyocyte injury in sepsis.  Methods  Forty Balb/c mice were randomly divided into four groups: Sham group (n=10), Sham+ 5-aminoimidazole-4-carboxamide ribonucleotide(AICAR) group (n=10), CLP group (n=10), and CLP+AICAR group (n=10). A sepsis mouse model was established through cecal ligation and puncture (CLP). Echocardiography and histological analysis were used to assess sepsis-induced cardiac injury. Neonatal rat cardiomyocytes (NRCMs) were incubated with lipopolysaccharide (LPS) (10 μg/mL) for 24 h to induce an in vitro sepsis model, and treated with AICAR. Mitochondrial function and dynamics were assessed  by using Western blotting, enzyme-linked immunosorbent assay （ELISA）, and immunofluorescence assays. Results  Compared with the Sham group, AMPK expression in the myocardial tissue of CLP mice was significantly reduced (P < 0.05). Compared with the CLP group, AMPK expression in the CLP+AICAR group was significantly increased (P < 0.05). Survival analysis showed that CLP led to a high mortality rate (~60%), while AICAR treatment significantly improved the survival rate of CLP mice (P < 0.05). Compared with the Sham group, cardiac output (CO), stroke volume (SV), and left ventricular end-diastolic volume (LVEDV) were significantly decreased in the CLP group (P < 0.05), while  left ventricular posterior wall systolic (LVPWs) and left ventricular posterior wall thickness (LVPWd) were significantly increased (P < 0.05). AICAR treatment alleviated the cardiac dysfunction induced by CLP. Compared with the CLP group, mitochondrial size and the number of mitochondrial cristae in the myocardial tissue of CLP+AICAR group mice were significantly increased (P < 0.05), while DHE fluorescence intensity and the number of TUNEL-positive cells were significantly reduced (P < 0.05). Compared with the LPS group, ATP production, mitochondrial respiration rate, and complex I, II, and III activities in NRCMs of the LPS+AICAR group were significantly increased (P < 0.05), while mitochondrial and cytoplasmic ROS levels were significantly reduced (P < 0.05). Compared with the control group, mitochondrial size in NRCMs of the LPS group was significantly reduced (P < 0.05), while Bax and Caspase-3 expression, as well as mitochondrial fission index, were significantly increased (P < 0.05), and these changes were mitigated by AICAR (P < 0.05).  Conclusion  AMPK plays a crucial role in maintaining cardiac function and mitigating septic myocardial injury by regulating mitochondrial structure and function, energy metabolism, oxidative stress, and apoptosis.

Establishment and evaluation of Pseudomonas aeruginosa-induced sepsis model in mice

Liu Wei, Wang Jingyi, Zheng Xi, Han Yue, Li Wenxiong, Zhang Jin

2025, 46(2):  324-332.  doi:10.3969/j.issn.1006-7795.2025.02.019

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Objective  To establish a reliable Pseudomonas aeruginosa (PA)-induced sepsis model, providing an effective experimental method for investigating the pathogenicity, antibiotic resistance mechanism and infection-related inflammatory pathways of PA. Methods  PA ATCC 27853 was selected as experimental strain. Different concentrations of bacterial suspension were applied to the surface of erector spinae muscle in mice. Echocardiography was performed 24 h after infection to examine cardiac function. Heart, lung, kidney tissue  and blood samples were collected. Serum creatinine (Cr), blood urea nitrogen (BUN), inflammatory factors, and cardiac troponin Ⅰ (CTNI) were detected. The pathological changes in the heart, lung, and kidney tissues were observed. Results  The survival rates of the 10⁷ CFU/mL group, 10⁸ CFU/mL, 10⁹ CFU/mL, and 10¹⁰ CFU/mL groups were 100%, 93.3%, 73.3%, and 26.7%, respectively. The concentration of interleukin-6 (IL-6) in the PA-infected group was significantly higher than that in the non-infected group. The concentration of tumor necrosis factor-α (TNF-α) in 10⁸ CFU/mL group and 10⁹ CFU/mL group were significantly higher than that in the non-infected group. The left ventricular ejection fraction (LVEF) of 10⁸ CFU/mL and 10⁹ CFU/mL groups decreased significantly compared to the non-infected group, and the CTNI level increased significantly in infected group compared to the non-infected group. Compared with the non-infected group, only the 10⁹ CFU/mL group showed significant statistical differences in Cr and BUN levels, while no significant differences were observed in the other PA-infected groups. The results of histopathology showed that the heart, lung, and kidney tissues of mice in the 10⁹ CFU/mL group were significantly infiltrated by inflammatory cells, with obvious edema of tissue cells, disordered structural arrangement, thickening of alveolar septa, and renal interstitial stenosis. Conclusion  The experiment successfully established a sepsis model induced by PA with a bacterial concentration of 10⁹ CFU/mL, which is stable and reliable, and can provide a model basis for exploring sepsis and PA infection diseases.

Expression and detection significance of CARDS toxin in bronchoalveolar lavage fluid in children with severe Mycoplasma pneumoniae pneumonia

Zheng Baoying, Fu Hanyu, Xue Guanhua, Cao Ling

2025, 46(2):  333-339.  doi:10.3969/j.issn.1006-7795.2025.02.020

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Objective  To analyze the expression and detection significance of community acquired respiratory distress syndrome (CARDS) toxin in bronchoalveolar lavage fluid (BALF) in children with severe Mycoplasma pneumoniae pneumonia (SMPP).  Methods  The BALF samples of children diagnosed with Mycoplasma pneumoniae pneumonia (MPP) were collected from the Department of  Pulmonology，  Children's Hospital Affiliated to   Capital Institute of Pediatrics from August 2021 to April 2022, the relative expression of CARDS toxins was determined by  quantitative realtime polymerase chain reaction (qPCR). The patients were divided into SMPP group and non-SMPP group (control group). The relative expression of CARDS toxin and other clinical indicators were compared between the two groups. The risk factors of SMPP were analyzed. The predictive value of the indicators was analyzed using receiver operating characteristic (ROC) curves.  Results  ①The relative expression level of CARDS toxin (Z=－6.151), D-dimer (Z=－5.102) and lactate dehydrogenase (LDH) (Z=－6.337) in SMPP group were significantly higher than those in control group (P<0.001). The white blood cell  (Z=－2.155), neutrophil ratio (t=2.988) and C-reactive protein (CRP) (Z=－3.360) were higher than those in control group (P<0.05). ②The relative expression of CARDS toxin was positively correlated with serum LDH (r=0.258, P<0.05). ③Binary Logistic regression analysis showed that  fever time (OR=1.271, 95%CI:1.079-1.497), LDH (OR=1.011, 95%CI:1.005-1.017) and CARDS toxin (OR=6.210, 95%CI: 2.646-14.577) were risk factors for SMPP.  Conclusion  CARDS toxin was closely related to MPP disease, and was significantly increased in SMPP group. CARDS toxin was one of the independent risk factors for SMPP and positively correlated with serum LDH level. It can be used as a good indicator to evaluate the condition，combined with fever time and LDH has clinical significance.

The relationship between the serum uric acid to high density lipoprotein-cholesterol ratio and female infertility

Jian Huanling , Dai Zi, Cen Xiaoli, Chen Huiling, Liu Zhiwen, Zhao Ying

2025, 46(2):  348-355.  doi:10.3969/j.issn.1006-7795.2025.02.022

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Objective  To conduct a cross-sectional study on the relationship between the serum uric acid (sUA) to high density lipoprotein-cholesterol (HDL-C) ratio (UHR) and female infertility. Methods  We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2013—2018 cycle, examining 2,963 women aged 18 to 45 years.A multivariable Logistic regression model was used to assess the association between UHR and infertility, adjusting for various confounding factors. The study also explored interactions and dose-response relationships through subgroup analyses and restricted cubic spline (RCS) models, and evaluated the predictive value of UHR for infertility by using receiver operating characteristic (ROC) curve analysis. Results  The results showed that the prevalence of infertility was significantly higher among women with elevated UHR. Baseline characteristics revealed that the mean UHR in women with infertility (9.68±4.23) was significantly higher than in those without infertility (8.7±3.81, P<0.001). Multivariable Logistic regression analysis indicated that women in the highest quartile (Q4) of UHR had a significantly increased likelihood of infertility compared to those in the lowest quartile (Q1), with adjusted odds ratios (ORs) ranging from 1.61 (95% CI: 1.14－2.28) to 1.98 (95% CI: 1.42－2.78) across different models (P for trend<0.001). Subgroup analyses demonstrated that these associations were consistent across different age groups, body mass index (BMI) categories, and racial groups. The RCS model showed a significant linear dose-response relationship between UHR and infertility risk (nonlinear P=0.03, overall association P<0.001). Additionally, ROC analysis indicated that UHR had a moderate ability to discriminate infertility status, with an area under the curve (AUC) of 0.570. Conclusion  A higher UHR is significantly associated with an increased risk of female infertility，and UHR has the potential to serve as a predictive biomarker for the risk of female infertility.

Observation of clinical effect of remote ischemic conditioning in patients with spontaneous intracerebral hemorrhage

Wu Lin, Sun Junzhao, Han Chengchen, Nie Xingxing, Tian Yuhong, Pi Hongying

2025, 46(2):  356-362.  doi:10.3969/j.issn.1006-7795.2025.02.023

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Objective  To evaluate clinical effect of remote ischemic conditioning (RIC) in patients with spontaneous intracerebral hemorrhage (sICH). Methods  Sixty-four patients with sICH who were diagnosed and admitted to the Department of Neurosurgery, the Sixth Medical Center of PLA General Hospital from January 2023 to May 2024 were selected as research subjects. Following the principle of matching baseline characteristics between groups, a computerized random grouping program was used to divide them into an observation group of 32 cases and a control group of 32 cases. Patients in the control group received standard basic medication according to the ‘Chinese Clinical Management Guidelines for Cerebrovascular Diseases’，while the observation group received RIC treatment in addition to the control group's treatment, with a course of 14 d. The changes in National Institutes of Health Stroke Scale (NIHSS) scores and Barthel index (BI, daily living ability score table) on the day of admission and after 14 d of treatment, the changes in hematoma volume on computed tomography (CT) imaging, and the incidence of adverse events were compared between the two groups. Results  At admission, the difference is not statistically significant in NIHSS scores, BI, and CT imaging hematoma volume between the two groups (P>0.05). After 14 d of treatment, the NIHSS scores of both groups were reduced compared to before treatment, and the scores of the observation group were lower than those of the control group (P<0.05); the BI of both groups was increased compared to before, and the scores of the observation group were higher than those of the control group (P<0.05); there were no significant differences in CT imaging hematoma volume and the incidence of adverse events between the two groups (P>0.05). Conclusion  Continuous RIC treatment for 14 d is safe and well-tolerated in patients with spontaneous intracerebral hemorrhage and can effectively improve the neurological function of patients.

Analysis of the epidemic characteristics of notifiable infectious diseases in Xindu district, Chengdu  from 2008 to 2022

Liu Xianghuan, Wang Min, Liu Hua, Gao Min

2025, 46(2):  363-373.  doi:10.3969/j.issn.1006-7795.2025.02.024

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Objective  To analyze the epidemic trend and characteristics of notifiable infectious diseases in Xindu District of Chengdu, and to explore the changes of disease spectrum, so as to provide scientific basis for formulating prevention and control strategies. Methods  The epidemic data of notifiable infectious diseases in Xindu District of Chengdu from 2008 to 2022 were collected and analyzed by descriptive epidemiological method. Results  From 2008 to 2022, a total of 66 302 cases of 28 kinds of notifiable infectious diseases were reported in Xindu District of Chengdu, with an average annual reported incidence of 516.94 /100 000. A total of 266 deaths were reported, with an average annual mortality rate of 2.07 /100 000 and a case fatality rate of 0.40 %. No Class A infectious diseases were reported, and Class B infectious diseases had no obvious seasonality. Class C infectious diseases had two incidence peaks from June to August and from October to December. The sex ratio of male to female was 1.41∶1, and the age of onset was mostly 0-4 years old. The reported cases were mainly scattered children, preschool children, students, farmers, housework and unemployed people. According to the main mode of transmission, the annual average reported incidence rate from high to low was intestinal infectious diseases, respiratory infectious diseases, blood and sexually transmitted infectious diseases, insect-borne and natural focal infectious diseases, and other infectious diseases. The mode of transmission gradually transitioned from intestinal infectious diseases to respiratory infectious diseases. From 2020 to 2022, except for COVID-19 and influenza cases, the reported incidence of infectious diseases in other transmission routes decreased. The reported diseases were mainly concentrated in tuberculosis, hepatitis B, syphilis, mumps, hand-foot-mouth disease, influenza and other infectious diarrhea, and the annual reported incidence order changed slightly. Conclusion  From 2008 to 2022, the reported incidence of Class B infectious diseases in Xindu District of Chengdu  showed a steady decline, while the reported incidence of Class C infectious diseases showed a fluctuating upward trend. The prevention and control measures of the new coronavirus epidemic are conducive to reducing the incidence of notifiable infectious diseases. It is necessary to focus on the prevention and control of high-risk infectious diseases such as hand-foot-mouth disease, influenza, other infectious diarrhea, tuberculosis, hepatitis B, and acquired immune deficiency syndrome, with highly reported mortality. Targeted health interventions should be carried out for key populations, key seasons, and key areas. At the same time, the monitoring of new and rare infectious diseases should be strengthened.

Analysis of core competence of editors of scientific journals and improvement strategies

Chen Ruifang, Bai Liyuan

2025, 46(2):  379-389.  doi:10.3969/j.issn.1006-7795.2025.02.026

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Objective  This paper aims to summarize the core competencies that editors of scientific journals should possess and propose improvement strategies to promote the cultivation of editors of scientific journals to meet the needs of construction and cultivation of world-class scientific journals in China. Methods  The role, responsibilities, and qualifications of editors of top international academic journals were surveyed. Questionnaire surveys were conducted among researchers with academic publication experience, and interviews were held with experts in medicine, journalism, and publishing industry. The core competencies that editors of scientific journals should possess were analyzed. Results  The findings indicate that editors of scientific journals need to possess professional academic abilities, including keen academic insight and disciplinary expertise; editorial skills, including proficiency in norms and standards of academic journal and publishing processes, and the ability to learn promptly new knowledge related to publishing to meet the needs of modern academic publishing; and publishing service capabilities, including academic organizational capabilities and communication skills, as well as interpersonal communication skills. The ability to establish，maintain, and develop a network of interpersonal relationships is also crucial. Improvement strategies mainly include building an industry environment for talent growth, where the editor determines the goals and directions through their own efforts. Conclusion  The core competencies of editors of scientific journals can be enhanced through building an industry environment for talent growth and the efforts of editors themselves, making editors of scientific journals interdisciplinary talents and promoting the rapid and high-quality development of domestic scientific journals.