1.Identification and mechanistic analysis of core genes associated with morphine tolerance in dorsal root ganglion:an integrative transcriptomics approach using WGCNA and machine learning algorithms
Zhiyuan YU ; Haiping DONG ; Nan GAO ; Ke MA
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(10):1308-1319
Objective·To develop a multi-algorithm collaborative computational biology strategy for constructing a predictive model of the peripheral morphine tolerance network and for screening high-confidence candidate targets.Methods·A murine model of morphine tolerance was established across multiple treatment time points.Bulk RNA sequencing was performed on harvested dorsal root ganglion(DRG)tissues.Using the expression matrix as a basis,a weighted gene co-expression network was constructed to identify co-expressed gene modules.Candidate genes were subsequently screened through the integration of differentially expressed genes(DEGs)with key weighted gene co-expression network modules.These candidates underwent functional annotation via Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.A protein-protein interaction(PPI)network was established,and hub genes were systematically identified using the cytoHubba algorithm.Three distinct machine learning approaches,least absolute shrinkage and selection operator(LASSO)regression,support vector machine recursive feature elimination(SVM-RFE)model,and random forest(RF)model,were strategically integrated to screen characteristic signature genes.Finally,gene set enrichment analysis(GSEA)was implemented to functionally validate both the hub and signature genes.Results·Weighted gene co-expression network analysis(WGCNA)identified 8 297 key module genes,of which 177 candidate genes overlapped with DEGs.These genes were significantly enriched in biological processes including ion channel regulation and vascular smooth muscle contraction.A combination of PPI network analysis and machine learning revealed four signature genes[actin γ2,smooth muscle(Actg2),centriolar coiled-coil protein 110(Ccp110),neural cell adhesion molecule 2(Ncam2),and selenium binding protein 1(Selenbp1)]and six hub genes[actin α2,smooth muscle(Acta2),von Willebrand factor(Vwf),cellular communication network factor 2(Ccn2),integrin β4(Itgb4),integrin α11(Itga11),and TEK receptor tyrosine kinase(Tek)]closely associated with morphine tolerance.Conclusion·In this study,we successfully constructed a multi-algorithm collaborative peripheral nerve regulation network prediction model for morphine tolerance,and screened out 10 core genes with high confidence.
2.Identification and mechanistic analysis of core genes associated with morphine tolerance in dorsal root ganglion:an integrative transcriptomics approach using WGCNA and machine learning algorithms
Zhiyuan YU ; Haiping DONG ; Nan GAO ; Ke MA
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(10):1308-1319
Objective·To develop a multi-algorithm collaborative computational biology strategy for constructing a predictive model of the peripheral morphine tolerance network and for screening high-confidence candidate targets.Methods·A murine model of morphine tolerance was established across multiple treatment time points.Bulk RNA sequencing was performed on harvested dorsal root ganglion(DRG)tissues.Using the expression matrix as a basis,a weighted gene co-expression network was constructed to identify co-expressed gene modules.Candidate genes were subsequently screened through the integration of differentially expressed genes(DEGs)with key weighted gene co-expression network modules.These candidates underwent functional annotation via Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.A protein-protein interaction(PPI)network was established,and hub genes were systematically identified using the cytoHubba algorithm.Three distinct machine learning approaches,least absolute shrinkage and selection operator(LASSO)regression,support vector machine recursive feature elimination(SVM-RFE)model,and random forest(RF)model,were strategically integrated to screen characteristic signature genes.Finally,gene set enrichment analysis(GSEA)was implemented to functionally validate both the hub and signature genes.Results·Weighted gene co-expression network analysis(WGCNA)identified 8 297 key module genes,of which 177 candidate genes overlapped with DEGs.These genes were significantly enriched in biological processes including ion channel regulation and vascular smooth muscle contraction.A combination of PPI network analysis and machine learning revealed four signature genes[actin γ2,smooth muscle(Actg2),centriolar coiled-coil protein 110(Ccp110),neural cell adhesion molecule 2(Ncam2),and selenium binding protein 1(Selenbp1)]and six hub genes[actin α2,smooth muscle(Acta2),von Willebrand factor(Vwf),cellular communication network factor 2(Ccn2),integrin β4(Itgb4),integrin α11(Itga11),and TEK receptor tyrosine kinase(Tek)]closely associated with morphine tolerance.Conclusion·In this study,we successfully constructed a multi-algorithm collaborative peripheral nerve regulation network prediction model for morphine tolerance,and screened out 10 core genes with high confidence.
3.Investigation and management of a clustered incident of incision infection after microtia plastic surgery
Jian SUN ; Zhiyuan CHEN ; Hua XU ; Limei MA ; Weiguang LI
Chinese Journal of Nosocomiology 2025;35(16):2432-2436
OBJECTIVE To summarize the process of investigation,disposal and prevention of a cluster incident of post-operative incision infection following microtia plastic surgery in the otorhinolaryngology department of a terti-ary care hospital,in order to provide a basis for hospital-aquired infection prevention and control.METHODS An epidemiological survey was conducted on seven patients who underwent otorhinolaryngoplasty for microtia in the ENT department of a tertiary care hospital from 27 Jul.to 7 Sep.2023,and interventions were implemented.RESULTS The incidence rate of infection was 71.43%among post-otorhinolaryngoplasty patients.In 5 patients,area for electrocoagulation of haemostatic increased by approximately 50%compared to the previous period,and drainage tubes were left in the surgical area for 11 to 13 days.Patients changed dressings in a shared dressing room.Pseudomonas aeruginosa was detected in three of the infected patients,and their antibiotic sensitivity pat-terns were similar to that of a lower respiratory tract infection patient(case 0)in the same department.CONCLUSION Inadequate aseptic practice by medical staff,longer retention of drainage tubes,incomplete disin-fection of the environment of the dressing room,and changes in surgical procedures may be the primary factors contributing to the occurrence of this cluster of infections.
4.Clinical applications of molecular biomarkers in precision diagnosis and management of classical philadelphia chromosome-negative myeloproliferative neoplasms
Xiaotong MA ; Ming GUAN ; Zhiyuan WU
Chinese Journal of Laboratory Medicine 2025;48(12):1608-1615
Classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) comprise a group of clonal disorders originating from hematopoietic stem cells, commonly characterized by thrombotic events, extramedullary hematopoiesis, and a propensity for malignant progression to myelofibrosis or acute leukemia. With the inclusion in the core diagnostic criteria, molecular biomarkers has exhibited applicational valus in multiple levels in the aspects of personalized therapy to subtype MPN, interpret phenotypic heterogeneity, and predict clinical outcomes. Molecular biomarkers are currently being applied in disease diagnosis, progression prediction, therapeutic strategy refinement, precision monitoring, familial MPN screening, and the development of emerging detection technologies, advancing the shift from fundamental MPN research to individualized clinical management.
5.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
6.High glucose induces hippocampal neuron impairment through the SKP1/COX7C pathway: A potential mechanism for perimenopausal depression.
Ziqi WANG ; Zhiyuan LIU ; Sijia FENG ; Xintong SONG ; Dequan LIU ; Ning MA ; Xinyue ZHANG ; Weiwei LIU ; Dan Ohtan WANG ; Xiaoling LIU ; Takashi IKEJIMA
Acta Pharmaceutica Sinica B 2025;15(11):5832-5853
Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCDSS) and the VCD depression resilient group (VCDRES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.
7.Investigation and management of a clustered incident of incision infection after microtia plastic surgery
Jian SUN ; Zhiyuan CHEN ; Hua XU ; Limei MA ; Weiguang LI
Chinese Journal of Nosocomiology 2025;35(16):2432-2436
OBJECTIVE To summarize the process of investigation,disposal and prevention of a cluster incident of post-operative incision infection following microtia plastic surgery in the otorhinolaryngology department of a terti-ary care hospital,in order to provide a basis for hospital-aquired infection prevention and control.METHODS An epidemiological survey was conducted on seven patients who underwent otorhinolaryngoplasty for microtia in the ENT department of a tertiary care hospital from 27 Jul.to 7 Sep.2023,and interventions were implemented.RESULTS The incidence rate of infection was 71.43%among post-otorhinolaryngoplasty patients.In 5 patients,area for electrocoagulation of haemostatic increased by approximately 50%compared to the previous period,and drainage tubes were left in the surgical area for 11 to 13 days.Patients changed dressings in a shared dressing room.Pseudomonas aeruginosa was detected in three of the infected patients,and their antibiotic sensitivity pat-terns were similar to that of a lower respiratory tract infection patient(case 0)in the same department.CONCLUSION Inadequate aseptic practice by medical staff,longer retention of drainage tubes,incomplete disin-fection of the environment of the dressing room,and changes in surgical procedures may be the primary factors contributing to the occurrence of this cluster of infections.
8.Clinical applications of molecular biomarkers in precision diagnosis and management of classical philadelphia chromosome-negative myeloproliferative neoplasms
Xiaotong MA ; Ming GUAN ; Zhiyuan WU
Chinese Journal of Laboratory Medicine 2025;48(12):1608-1615
Classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) comprise a group of clonal disorders originating from hematopoietic stem cells, commonly characterized by thrombotic events, extramedullary hematopoiesis, and a propensity for malignant progression to myelofibrosis or acute leukemia. With the inclusion in the core diagnostic criteria, molecular biomarkers has exhibited applicational valus in multiple levels in the aspects of personalized therapy to subtype MPN, interpret phenotypic heterogeneity, and predict clinical outcomes. Molecular biomarkers are currently being applied in disease diagnosis, progression prediction, therapeutic strategy refinement, precision monitoring, familial MPN screening, and the development of emerging detection technologies, advancing the shift from fundamental MPN research to individualized clinical management.
9.Comparison on efficacy of MRI-transrectal ultrasound software fusion-guided biopsy and cognitive fusion-guided biopsy for detecting prostate cancer
Jing YANG ; Hao FENG ; Han XIA ; Yanhui MA ; Xiao XIAO ; Zhiyuan WANG ; Wenjuan XU ; Zheng WANG ; Qibing FAN ; Yuyong SHEN ; Jing DING ; Tingyue QI
Chinese Journal of Interventional Imaging and Therapy 2024;21(7):403-407
Objective To compare the efficacy of MRI-transrectal ultrasound(TRUS)software fusion-guided biopsy and cognitive fusion-guided biopsy for detecting prostate cancer(PC).Methods Data of 120 patients with suspected PC(127 lesions)who underwent transperineal prostate biopsy with 2-3 times of target biopsy(TB)and 10 times of system biopsy were retrospectively analyzed.According to TB guidance methods,73 cases(78 lesions)received MRI-TRUS software fusion-guided biopsy were classified into group A,and 47 cases(49 lesions)received cognitive fusion-guided biopsy were classified into group B.The positive rate of PC,clinic significant PC(csPC)and PC in different sized lesions by TB were compared between groups,and the positive rate of PC between 2 or 3 times TB was also compared within each group.Results The positive rate of PC and csPC detected by TB was 55.13%(43/78)and 39.74%(31/78)in group A,53.06%(26/49)and 34.69%(17/49)in group B,respectively,no significant difference was found(all P>0.05).The positive rate of PC in lesions with the maximum diameter≤10 mm detected by TB in group A was higher than that in group B(P<0.05),but no significant difference of lesions with the maximum diameter>10 mm and<15 mm nor≥15 mm was found between groups(all P>0.05).No significant difference of positive rate of PC was found between 2 and 3 times TB in group A(P>0.05),while positive rate of PC of 3 times TB was significantly higher than that of 2 times TB in group B(P<0.05).Conclusion MRI-TRUS software fusion-guided biopsy had positive rate of PC and csPC similar to that of cognitive fusion-guided biopsy,but was helpful for reducing times of TB and increasing detecting rate for lesions with the maximum diameter≤10 mm.
10.Three-station OSCE skill assessment for standardized training of radiation oncology residents
Jishi LI ; Lingyu MA ; Qiongya LAN ; Tingyue LUO ; Ying HAN ; Zhiyuan XU ; Lee Wing Mui Anne
Chinese Journal of Radiation Oncology 2024;33(11):1064-1069
Objective:To conduct simulated graduation skill assessment and annual skill assessment by self-designed objective structured clinical examination (OSCE) for standardized training of radiation oncology residents.Methods:The structured examination, standardized questions and standardized tasks of each disease were designed by teaching team of radiation oncology in the University of Hong Kong-Shenzhen Hospital. The implementation effect of the annual assessment and simulated completion assessment of standardized training for residents in radiation oncology from Class 2019 to 2021 was prospectively observed. The difference between scores by two independent examiners was analyzed by the paired t-test. The overall feedback of residents and examiners for the implementation were collected after the completion of OSCE. Results:A total of 18 residents participated in 67 sessions of 3-station skill assessments of different diseases, including 2 make-up tests. There was no difference in the score pairing and grade pairing tests between two examiners at 3 stations ( t=0.85, -0.68, -1.16; P=0.401, 0.499, 0.255). A total of 91.3% of the residents reported that the assessment well reflected their actual clinical competency. Conclusions:The current program of OSCE assessment for radiation oncology meets objectification, standardization and high efficiency, and achieves the goal of making trainers familiar with the graduation skill assessment and assessing comprehensive clinical competence. It is a reproducible and flexible structured assessment model.

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