1.PXMP4 activates the ERK1/2 signaling pathway to promote proliferation,migra-tion,and invasion of cervical cancer cells
Zhidan WAN ; Zishan XU ; Wei LI ; Na LIU ; Jianqiang WANG ; Guoyang HE
Chinese Journal of Clinical and Experimental Pathology 2025;41(11):1436-1445
Purpose This study aims to explore the effect of peroxisomal membrane protein 4(PXMP4)on the migration and invasion of cervical cancer(CC)cells,as well as the epithelial-mesenchymal transition(EMT)process.Methods Bioinformatics and immunohistochemical analysis were employed to examine the expression of PXMP4 in CC tissues and its correlation with clinical pathological characteristics.Western blot and RT-qPCR were used to detect the expression of PXMP4 in CC cells.CCK-8 assay,scratch healing assay,and Transwell invasion assay were utilized to assess the proliferation,migration,and invasion capabilities of CC cells.Western blot was conducted to measure the expression of N-cadherin,E-cadherin,vimentin,phosphorylated ERK(p-ERK),and total ERK proteins in cervical CC.Results The TCGA database showed that the mRNA expression level of PXMP4 was significantly elevated in non-paired CC tissues(P=0.000 29),while the GEO database showed that the mRNA expression level of PXMP4 was sig-nificantly elevated in paired CC tissues(P=0.02).Immunohistochemical analysis showed that PXMP4 was primarily localized in the cytoplasm and cell membrane,with a positive rate of 70.31%(45/64)in CC tissues,significantly higher than 29.69%(19/64)in adjacent tissues.Clinical pathological analysis found that PXMP4 expression was as-sociated with maximum tumor differentiation(P=0.000 328)and lymph node metastasis(P=0.000 226),but not with age(P=0.637)or tumor diameter(P=0.304).CCK-8 assay,wound healing assay,and Transwell invasion as-say demonstrated that interference with PXMP4 inhibited the proliferation,invasion,and migration of CC cells,while overexpression of PXMP4 promoted these processes.Western blot results indicated that interference with PXMP4 signif-icantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expression(P<0.05).Conversely,overexpression of PXMP4 led to a significant decrease in E-cadherin and an increase in N-cadherin,vim-entin,and p-ERK expression(P<0.05).Additionally,stimulation of CC cells with different concentrations of the U0126 inhibitor significantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expres-sion(P<0.05).Conclusion PXMP4 is highly expressed in CC tissues and is closely related to tumor differentiation and lymph node metastasis.PXMP4 promotes the EMT process of CC cells through the phosphorylated ERK1/2 signa-ling pathway.
2.Professor TONG Xiaolin's Experience in Treating Prediabetes with Overweight and Obesity Using the Method of Relieving Depression and Reducing Turbidity
Sicheng WANG ; Yangyang LIU ; Yan YAN ; Zishan JIN ; Boxun ZHANG ; Qingwei LI ; Xiaoxuan XU ; Linhua ZHAO ;
Journal of Traditional Chinese Medicine 2025;66(14):1424-1427
To summarise the clinical experience of Professor TONG Xiaolin in treating prediabetes combined with overweight or obesity using the method of relieving depression and reducing turbidity. It is believed that prediabetes belongs to the category of "spleen-heat syndrome" in traditional Chinese medicine, and its core pathogenesis is center fullness with internal heat, while obesity is the initiating factor for exacerbating center fullness and internal heat, therefore, it is of great significance to reduce the risk of diabetes by interrupting the transformation between overweight, obesity and glucose metabolism abnormality. It is proposed that the main pathogenesis of prediabetes combined with overweight or obesity is qi depression and turbidity obstruction in middle jiao, with qi depression as the root and turbidity obstruction as the cause, forming a treatment idea with the method of relieving depression and reducing turbidity as the core. In clinic, Dahuang Huanglian Xiexin Decoction (大黄黄连泻心汤) is used as the basic prescription, with a primary focus on directing the turbid downward, supplemented by regulating qi, which embodies the concept of "promoting movement through descent, then figuring out the root of spleen-heat syndrome. Furthermore, the treatment is flexibly modified based on the patient's deficiency-excess syndrome to ensure individualized therapy.
3.Application of artificial intelligence in biomedical research
Jianyi LYU ; Chunxi WANG ; Sicheng LIU ; Yilin YE ; Congrui ZHANG ; Feiyang LI ; Zishan ZHANG ; Xiaoyan DU
Chinese Journal of Comparative Medicine 2025;35(7):169-176
Rapid developments in biotechnology have led researchers to seek new method to improve the efficiency and accuracy of biomedical research and drug development,promoting interdisciplinary integration.Recent advancements in artificial intelligence(AI)technologies have brought unprecedented opportunities to this field.The integration of various AI models allows researchers to better utilize multi-omics data,identify disease phenotypes,interpret animal behavior,assess treatment effects,improve experimental designs,reduce the use of experimental animals,enhance animal facility management,and improve animal welfare.This article reviews the advancements in AI biomedical research over the past decade and discusses its contributions to disease phenotype identification,the selection and design of experimental animal models,animal behavior analysis,and animal facility management.It also points out the challenges related to data standardization,AI model selection and interpretability,the extrapolation process from AI models to animal experiments and clinical practice,as well as ethical considerations in using AI in sensitive areas involving human genetics and personalized medicine.This review aims to help researchers and practitioners in relevant fields understand the current state and opportunities of AI development,thus providing support for its broader application.
4.Application of artificial intelligence in biomedical research
Jianyi LYU ; Chunxi WANG ; Sicheng LIU ; Yilin YE ; Congrui ZHANG ; Feiyang LI ; Zishan ZHANG ; Xiaoyan DU
Chinese Journal of Comparative Medicine 2025;35(7):169-176
Rapid developments in biotechnology have led researchers to seek new method to improve the efficiency and accuracy of biomedical research and drug development,promoting interdisciplinary integration.Recent advancements in artificial intelligence(AI)technologies have brought unprecedented opportunities to this field.The integration of various AI models allows researchers to better utilize multi-omics data,identify disease phenotypes,interpret animal behavior,assess treatment effects,improve experimental designs,reduce the use of experimental animals,enhance animal facility management,and improve animal welfare.This article reviews the advancements in AI biomedical research over the past decade and discusses its contributions to disease phenotype identification,the selection and design of experimental animal models,animal behavior analysis,and animal facility management.It also points out the challenges related to data standardization,AI model selection and interpretability,the extrapolation process from AI models to animal experiments and clinical practice,as well as ethical considerations in using AI in sensitive areas involving human genetics and personalized medicine.This review aims to help researchers and practitioners in relevant fields understand the current state and opportunities of AI development,thus providing support for its broader application.
5.PXMP4 activates the ERK1/2 signaling pathway to promote proliferation,migra-tion,and invasion of cervical cancer cells
Zhidan WAN ; Zishan XU ; Wei LI ; Na LIU ; Jianqiang WANG ; Guoyang HE
Chinese Journal of Clinical and Experimental Pathology 2025;41(11):1436-1445
Purpose This study aims to explore the effect of peroxisomal membrane protein 4(PXMP4)on the migration and invasion of cervical cancer(CC)cells,as well as the epithelial-mesenchymal transition(EMT)process.Methods Bioinformatics and immunohistochemical analysis were employed to examine the expression of PXMP4 in CC tissues and its correlation with clinical pathological characteristics.Western blot and RT-qPCR were used to detect the expression of PXMP4 in CC cells.CCK-8 assay,scratch healing assay,and Transwell invasion assay were utilized to assess the proliferation,migration,and invasion capabilities of CC cells.Western blot was conducted to measure the expression of N-cadherin,E-cadherin,vimentin,phosphorylated ERK(p-ERK),and total ERK proteins in cervical CC.Results The TCGA database showed that the mRNA expression level of PXMP4 was significantly elevated in non-paired CC tissues(P=0.000 29),while the GEO database showed that the mRNA expression level of PXMP4 was sig-nificantly elevated in paired CC tissues(P=0.02).Immunohistochemical analysis showed that PXMP4 was primarily localized in the cytoplasm and cell membrane,with a positive rate of 70.31%(45/64)in CC tissues,significantly higher than 29.69%(19/64)in adjacent tissues.Clinical pathological analysis found that PXMP4 expression was as-sociated with maximum tumor differentiation(P=0.000 328)and lymph node metastasis(P=0.000 226),but not with age(P=0.637)or tumor diameter(P=0.304).CCK-8 assay,wound healing assay,and Transwell invasion as-say demonstrated that interference with PXMP4 inhibited the proliferation,invasion,and migration of CC cells,while overexpression of PXMP4 promoted these processes.Western blot results indicated that interference with PXMP4 signif-icantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expression(P<0.05).Conversely,overexpression of PXMP4 led to a significant decrease in E-cadherin and an increase in N-cadherin,vim-entin,and p-ERK expression(P<0.05).Additionally,stimulation of CC cells with different concentrations of the U0126 inhibitor significantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expres-sion(P<0.05).Conclusion PXMP4 is highly expressed in CC tissues and is closely related to tumor differentiation and lymph node metastasis.PXMP4 promotes the EMT process of CC cells through the phosphorylated ERK1/2 signa-ling pathway.
6.Research Advances in Mongolian Gerbil Models of Cerebral Ischemia and Auditory Impairment
Zishan ZHANG ; Ying WU ; Feiyang LI ; Xiaoyan DU
Laboratory Animal and Comparative Medicine 2024;44(4):419-427
The Mongolian gerbil currently used as laboratory animals worldwide all originates from China.As early as the 1930s,wild Mongolian gerbils were domesticated and introduced into medical research.Today,they have become recognized multifunctional laboratory animals and are extensively used in various fields such as brain nerve studies,parasitology and microbiology,and oncology,etc.Mongolian gerbils possess unique anatomical characteristics in the basal cerebral arteries,such as a congenital absence of the Willis'circle,making it possible to construct cerebral ischemia or cerebral ischemia-reperfusion injury models with simple procedures of unilateral common carotid artery ligation,while also enabling intra-individual control.These anatomical features also increase their sensitivity to cerebral ischemia and make them more prone to cochlear ischemia,therefore playing a crucial role in the preparation of auditory impairment models.The disease progression and pathological manifestations in Mongolian gerbils show many similarities to those observed in human patients.Researchers have successfully used Mongolian gerbils to develop models of cerebral ischemia,cerebral ischemia-reperfusion,cochlear ischemia,cochlear implantation,and sensorineural hearing loss,achieving significant results.This article focuses on the current methods and assessment indicators for constructing Mongolian gerbils models of cerebral ischemia and auditory impairment.It discusses the advantages and disadvantages of various modelling techniques,and explores their application progress,aiming to provide a theoretical basis and reference for the application of Mongolian gerbils in these two important research areas.
7.Reliability and validity of assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Peri-operative Period
Boyang YU ; Yanyan YANG ; Ao MA ; Tao LI ; Xiaoxie LIU ; Zhengyang LI ; Yajing DUAN ; Jiaqi LIU ; Yuxiao XIE ; Cui WANG ; Zhen HUANG ; Lining ZHANG ; Xinyi LIU ; Zishan JIA ; Mouwang ZHOU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(9):1053-1059
Objective To investigate the reliability and validity of the assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Perioperative Period(ICSAKOPP). Methods From May,2022 to April,2023,320 patients undergoing knee arthroplasty were selected in Peking University Third Hospital,China-Japan Friendship Hospital,Peking University First Hospital and Chinese PLA General Hospital.Trained assessors used Brief ICSAKOPP to evaluate all enrolled patients before arthroplasty,three days(±one day)after arthroplasty,three weeks(±one week)after arthroplasty,and three months(±one month)after ar-throplasty.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores were recorded at the same time.Five professionals were asked to score all the items of Brief ICSAKOPP,and the content validity index(CVI)was caculated. Results A total of 64 cases were dropped down.CVI of all the items of the Brief ICSAKOPP were above 0.8,with a av-erage CVI of the scale of 0.938.The Cronbach's α coefficient of the Brief ICSAKOPP was 0.813.There was a moderate correlation(r=0.681,P<0.001)between the overall Brief ICSAKOPP and WOMAC scores,as well as body functional dimension score(r=0.668,P<0.001)and activities and participation dimension score(r=0.657,P<0.001). Conclusion Brief ICSAKOPP is good in content validity,internal consistency reliability and criterion validity.
8.Application of endoscopic ultrasound-guided enteroenterostomy in treatment of malignant bowel obstruction
Zishan LI ; Hua YANG ; Lei WANG ; Yufang TENG ; Qin ZHAO ; Muhan NI
China Journal of Endoscopy 2024;30(9):47-55
Objective To assess the efficacy of endoscopic ultrasound-guided enteroenterostomy(EUS-EE)in the management of malignant bowel obstruction(MBO).Methods Retrospective analysis was conducted on clinical data from 14 patients who underwent EUS-EE for MBO from June 2022 to December 2023.A modified intestinal preparation protocol was employed prior to the procedure,and the resolution of symptoms,improvement in nutritional status,and occurrence of complications were statistically analyzed post-EUS-EE.Results EUS-EE was successfully performed in all 14 cases.The Colorectal obstruction scoring system(CrOSS)was used to evaluate preoperative and postoperative symptom relief and alleviation of bowel obstruction.One week after the procedure,CrOSS scores increased from 1 to 2 before surgery to 2~4.The patient-generated subjective global assessment(PG-SGA)score for malignancy patients demonstrated a mean score of(9.64±3.13)one week after surgery among the study cohort of 14 patients.This score showed a significant decrease compared to their preoperative PG-SGA score(12.36±3.22),with a statistical difference(t=2.26,P=0.032).Postoperatively,five patients experienced elevated body temperature,three had pneumoperitoneum,and two developed short bowel syndrome;However,these complications were effectively managed through symptomatic treatment resulting in recovery or relief thereof.At one-year follow-up,the median survival time was recorded as 81(41,500)d with a one-year survival rate at 64.29%.Conclusion EUS-EE offers advantages such as high remission rates for symptoms,minimal trauma,and low reintervention rates.For patients with poor baseline conditions or limited life expectancy,EUS-EE can alleviate physical discomfort symptoms,improve quality of life,and prolong survival period.
9.Mechanism of Gualou Xiebai Baijiu Decoction for regulating the intestinal microflora and its metabolites to improve atherosclerosis in mice
Zhifan CHEN ; Yulin CHEN ; Sha NIE ; Wenhao SUN ; Chang LI ; Zishan MA ; Kai HU ; Yingying HE ; Ying LIU ; Yaoping TANG
Chinese Journal of Comparative Medicine 2024;34(7):10-19
Objective To explore the mechanism of Gualou Xiebai Baijiu Decoction(GXB)in improving atherosclerosis(AS)in mice by regulating the gut microbiota(GM)and its metabolites.Methods Thirty-two male ApoE-/-mice were divided randomly into a Blank group,Model group,atorvastatin(Ato)group,and GXB group(n=8 mice per group).AS was established in all mice,except the Blank group,and the respective treatments were administered by gavage.Aortic plaques were detected by Oil red O staining and pathological changes in aortic tissue were detected by hematoxylin and eosin staining.The GM was analyzed using 16S rRNA gene sequencing technology,and mouse GM metabolites,including trimethylamine oxide(TMAO),short-chain fatty acids(SCFA),and serum levels of triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and nitric oxide(NO)were determined.Results Compared with the Blank group,mice in the Model and Ato groups showed an increase in AS plaque area(P<0.05).Serum levels of TG,TC,and LDL-C were increased(P<0.001)while levels of HDL-C and NO were decreased(P<0.01,P<0.001)in the Model group compared with the Blank group.The plaque area was decreased(P<0.05),serum levels of TG,TC,and LDL-C were decreased(P<0.001),and NO levels were increased(P<0.01)in the Ato and GXB groups,while HDL-C levels were increased in the GXB group(P<0.05)compared with the Model group.Plaque area was decreased(P<0.05)and the NO level was increased(P<0.01)in the GXB group compared with the Ato group.A total of 6345 characteristic sequences were obtained from 16S rRNA analysis.α-Diversity analysis indicated that GXB reduced the richness of the GM in AS mice(P<0.001)and improved its uniformity(P<0.05).β-Diversity analysis suggested that the microbial community structure in the GXB group was similar to that in the Blank group.The abundance of microbial communities differed among the groups at the phylum and genus levels.At the phylum level,the abundance of Proteobacteria was increased(P<0.01)in AS mice,while GXB intervention reduced the abundance of Proteobacteria(P<0.01)and increased the abundance of Verrucomimicrobiota(P<0.05).At the genus level,GXB effectively increased the abundance of Akkermansia(P<0.05).SCFAs were significantly increased(P<0.01)and TMAO levels were significantly decreased(P<0.01)in the GXB group compared with the Model group.Conclusions GXB can regulate the intestinal flora and intestinal flora metabolites SCFA and TMAO to improve AS.Akkermansia may be a key bacterial genus of the gut microbiota through which GXB may improve AS.
10.Clinical and genetic features of autosomal recessive spinocerebellar ataxia type 1:A case report
Li YANG ; Zishan MA ; Bonian MA
Journal of Apoplexy and Nervous Diseases 2024;41(8):753-756
This study analyzes the clinical phenotype and genetic testing results of a patient with autosomal recessive spinocerebellar ataxia type 1(SCAR1)caused by SETX gene mutations.Through medical history collection,neurological examination,radiological examination,neural electrophysiological examination,and genetic analysis,compound heterozy-gous mutations were found in the SETX gene on chromosome 9,i.e.,c.5812C>T(p.Q1938X)and c.501_508del,and these mutation sites were located in exon 14 and exon 6,respectively,and had not been reported in the literature.This study discovers for the first time that these two mutations can cause SCAR1,providing new insights into the pathogenic mechanism of the SETX gene in SCAR1 and a reference for the diagnosis and treatment of similar cases in the future.

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