1.Investigation of the regulatory effect of overexpressed Ptpn2 on SiO2-mediated mouse alveolar macrophages based on iTRAQ technology
Yi WEI ; Yaqian LI ; Xinjie LI ; Mengfei FENG ; Fuyu JIN ; Hong XU ; Ying ZHU
Acta Universitatis Medicinalis Anhui 2026;61(2):183-191
ObjectiveTo investigate the regulatory effect of overexpressed protein tyrosine phosphatase non-receptor type 2 (Ptpn2) on the inflammatory response of mouse alveolar macrophages (MH-S) induced by SiO₂. MethodsCells with overexpressed Ptpn2 were constructed and induced by SiO₂. The experimental groups were divided into four groups: the negative control group with an empty vector (NC), the overexpressed Ptpn2 group (P), the negative control group with an empty vector + SiO₂ induction (NS), and the overexpressed Ptpn2 + SiO₂ induction group (PS). Isobaric tags for relative and absolute quantification (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to screen differential proteins, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses. Immunofluorescence staining was used to detect the expressions of Tumor necrosis factor (TNF) α, Gasdermin D (GSDMD), and Transforming growth factor (TGF)-β1. Western blot was used to detect the protein expression levels of PTPN2, Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), and proteins related to the TGF-β1 signaling pathway in the cells of each group. ResultsiTRAQ results identified 144 differential proteins among the four groups. GO analysis showed that in biological processes (BP), these differential proteins were mainly enriched in IκB kinase/nuclear factor-κB (NF-κB) signaling, cell activation and signal transduction involved in immune responses, and regulation of receptor signaling pathways by signal transducer and activator of transcription (STAT), etc. KEGG analysis revealed that the differential proteins were mainly enriched in Toll-like receptor signaling pathway, NF-κB signaling pathway, NOD-like receptor signaling pathway, TGF-β signaling pathway, and TNF signaling pathway. The results of immunofluorescence staining showed that compared with the NC group, the expressions of TNF α, GSDMD, and TGF-β1 in the cells of the NS group increased (P < 0.05); compared to the NS group, the expression of the aforementioned proteins in the PS group decreased in cellular proteins(P < 0.05). The results of Western blot showed that compared with the NC group, the protein expression levels of PTPN2, p-NF-κB,MyD88,TLR4,NLRP3,GSDMD,Caspase-1,IL-1β, TGF-βR1, TGF-βR,p-Smad2/3 in the NS group were significantly upregulated (P < 0.05); compared with the NS group, the expression levels of the aforementioned proteins in the PS group were significantly downregulated (P < 0.05). ConclusionOverexpression of Ptpn2 can inhibit the protein expressions of TLR4-TNF-α signaling, NLRP3 signaling, and TGF-β1 signaling closely related to inflammatory response in SiO₂-mediated MH-S macrophages.
2.A review on cell-based models of human pancreatic diseases in vitro
Wei-feng ZHU ; Li-jun PENG ; Jing LIU ; Shu-hong PENG
Chinese Pharmacological Bulletin 2025;41(1):23-29
Unhealthy diet,smoking and drinking can cause a variety of pancreatic diseases,including pancreatitis,diabetes and pancreatic cancer,which seriously threaten human health.The construction of cell models in vitro is of great significance in the study of the etiology and pathogenesis of pancreatic diseases and the development and screening of medicines.At present,domestic and foreign scholars have developed a variety of in vitro pancreatic disease models.In this paper,we summarize the cell models of common pancreatic diseases in vitro,and review the characteristics,culture methods,modeling methods,and evalu-ation indexes of the model cells,so as to provide references for researchers related to pancreatic diseases.
3.Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells
Rongrong CHEN ; Chunxiang JIN ; Kai LIU ; Mengyu ZHAO ; Tingting YANG ; Mingming ZHANG ; Pingnan XIAO ; Jingjing FENG ; Ruimin HONG ; Shan FU ; Jiazhen CUI ; Simao HUANG ; Guoqing WEI ; He HUANG ; Yongxian HU
Chinese Medical Journal 2025;138(19):2481-2490
Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.
4.Clinical effect of sofosbuvir-velpatasvir on treatment of patients with genotype 3 chronic hepatic C and liver cirrhosis
MAIMAITIJIANG·WUBULIAISHAN ; Hong YU ; AMINAI·AIBI ; Zhuanguo WANG ; Jing DOU ; Wei SUN ; Zhonghui NING ; Xiaobo WANG ; Qiang XU ; Xiaozhong WANG ; Hongyan ZHANG ; Feng GUO
Chinese Journal of Nosocomiology 2025;35(9):1322-1326
OBJECTIVE To explore the efficacy and safety of sofosbuvir-velpatasvir(SOF/VEL)combined with or without ribavirin(RBV)in treatment of the patients with genotype 3(GT3)chronic hepatitis C(CHC)and liver cirrhosis.METHODS Totally 230 patients with CT3 CHC and liver cirrhosis who were treated in Traditional Chi-nese Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Hetian Specialized Hospital of Infectious Diseases and Xinjiang Manasi County People's Hospital from Jun.2018 to Mar.2023 were recruited as the research sub-jects.The clinical curative effects were observed after the subjects were treated with single SOF-VEL or the com-bination with RBV for 12 to 24 weeks.The indexes including high-sensitivity hepatitis C RNA(HCV RNA),blood routine indexes,liver function indexes and noninvasive diagnosis indexes for liver fibrosis were observed,and the sustained virological response 12 weeks after the treatment(SVR12)was analyzed.RESULTS The mean age of the enrolled patients was(42.31±11.18)years old,the male patients accounted for 66.52%,and there were 137 cases of GT3a and 93 cases of GT3b 93,there were 183 cases of CHC,44 cases of compensated cirrhosis(CC)and 3 cases of decompensated cirrhosis(DCC).There were 189 cases of single HCV infection,33 cases of mixed infections of HCV and HIV,6 cases of mixed infections of HBV/HCV and 2 cases of triple infections of HBV/HCV/HIV.The overall SVR12 of the 230 patients was 99.57%,the SVR12 of the GT3a type patients was 100.00%,the GT3b type patients 98.92%.The SVR12 of the patients with CHC,CC and DCC were 99.45%,100.00%and 100.00%,respectively.The SVR12 of the patients with single HCV infection,HCV/HIV infec-tion,HBV/HCV infection and HBV/HCV/HIV were 99.47%,100.00%,100.00%and 100.00%,respective-ly.No patient quit the direct-acting antivirals(DAAs)treatment due to the drug-induced adverse reactions.1 pa-tient had relapse due to irregular administration of DAAs.CONCLUSION The virological response rate is high a-mong the patients with GT3 CHC and liver cirrhosis who are treated with single SOF/VEL or the combination with RBV,with the safety favorable.
5.Poly gala fallax Hemsl.improves diabetic kidney disease in rats via Nrf2/SLC7A11/GPX4 signaling pathway
Si-chao WANG ; Qiu-hong LIU ; Shi-wei ZHAO ; Yu-qiong LEI ; Min-chao FENG
Chinese Pharmacological Bulletin 2025;41(6):1186-1193
Aim To observe the interventional effects of Polygala fallax Hemsl.(PFH)on diabetic kidney disease(DKD)rats and the regulatory mechanism of ferroptosis.Methods Thirty-six SD rats were ran-domly divided into the control group,DKD group,fer-rostatin-1(Fer-1)group,PFH-L group,PFH-M group,and PFH-H group,with six rats in each group.Model-ing was induced by a one-time intraperitoneal injection of 35 mg·kg-1 streptozocin(STZ)in combination with high-sugar and high-fat feed.Ferrostatin-1(25μmol·kg-1)was injected intraperitoneally in Fer-1 group.The PFH-L,PFH-M,and PFH-H groups were gavaged with 50,100 and 200 mg·kg-1 of alcoholic extracts of PFH respectively,and the control and DKD groups were gavaged with an equal volume of distilled water once a day for eight weeks.At the end of drug administration,blood glucose,24h-UP,BUN and Scr levels were measured in each group of rats.HE stai-ning and Masson staining were used to observe renal histopathological changes.ELISA was employed to de-termine the levels of total iron,MDA and GSH activity.IHC was used to observe the expression of Nrf2,SLC7A11,and GPX4 in renal tissues.Western blot was used to detect the protein expression of COL1A1,α-SMA,TGF-,FTH-1,TFR-1,Nrf2,SLC7A1 1,GPX4,in renal tissues.RT-qPCR was used to detect the ex-pression levels of Nrf2,SLC7A11,GPX4 mRNA in re-nal tissues.Results Compared with the control group,blood glucose,24h-UP,BUN,Scr increased(P<0.05);glomerular volume increased,tubular dilata-tion and collagen fiber deposition were obvious;total i-ron,MDA content increased and GSH activity de-creased(P<0.05);there was increased protein ex-pression of COL1A1,α-SMA,TGF-β,TFR-1 and de-creased protein expression of FTH-1(P<0.01);there was decreased mRNA and protein expression of Nrf2,SLC7A11,GPX4 in DKD group rats(P<0.01).Compared with the DKD group,blood glucose,24h-UP,BUN and Scr decreased(P<0.05);renal tissue le-sions were significantly reduced;total iron and MDA content decreased,and GSH activity increased(P<0.05);COL1A1,α-SMA,TGF-β,and TFR-1 protein expression decreased and FTH-1 protein expression in-creased(P<0.05,P<0.01);Nrf2,SLC7A11,GPX4 mRNA and protein expression increased in Fer-1 and PFH dose groups(P<0.05,P<0.01).Conclusions PFH attenuates renal histopathological injury in DKD rats,and the mechanism may be related to the regula-tion of the Nrf2/SLC7A11/GPX4 signaling pathway.
6.Troubleshooting of Philips Ingenia Series MRI scanners:Three case reports
Hong-wei LI ; Peng-kai BAI ; Xiao-yang CHU ; Xi-ming FENG
Chinese Medical Equipment Journal 2025;46(6):116-120
The principle and composition of Philips Ingenia Series MRI scanners were introduced.Three common faults of Philips Ingenia Series MRI scanners were analyzed in terms of the phenomenon,cause and elimination measure.References were provided for clinical engineers to treat similar faults.[Chinese Medical Equipment Journal,2025,46(6):116-120]
7.Distribution and resistance profiles of bacterial strains isolated from cerebrospinal fluid in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Juan MA ; Lixia ZHANG ; Yang YANG ; Fupin HU ; Demei ZHU ; Han SHEN ; Wanqing ZHOU ; Wenen LIU ; Yanming LI ; Yi XIE ; Mei KANG ; Dawen GUO ; Jinying ZHAO ; Zhidong HU ; Jin LI ; Shanmei WANG ; Yafei CHU ; Yunsong YU ; Jie LIN ; Yingchun XU ; Xiaojiang ZHANG ; Jihong LI ; Bin SHAN ; Yan DU ; Ping JI ; Fengbo ZHANG ; Chao ZHUO ; Danhong SU ; Lianhua WEI ; Fengmei ZOU ; Xiaobo MA ; Yanping ZHENG ; Yuanhong XU ; Ying HUANG ; Yunzhuo CHU ; Sufei TIAN ; Hua YU ; Xiangning HUANG ; Sufang GUO ; Xuesong XU ; Chao YAN ; Fangfang HU ; Yan JIN ; Chunhong SHAO ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Fang DONG ; Zhiyong LÜ ; Lei ZHU ; Jinhua MENG ; Shuping ZHOU ; Yan ZHOU ; Chuanqing WANG ; Pan FU ; Yunjian HU ; Xiaoman AI ; Ziyong SUN ; Zhongju CHEN ; Hong ZHANG ; Chun WANG ; Yuxing NI ; Jingyong SUN ; Kaizhen WEN ; Yirong ZHANG ; Ruyi GUO ; Yan ZHU ; Jinju DUAN ; Jianbang KANG ; Xuefei HU ; Shifu WANG ; Yunsheng CHEN ; Qing MENG ; Yong ZHAO ; Ping GONG ; Ruizhong WANG ; Hua FANG ; Jilu SHEN ; Jiangshan LIU ; Hongqin GU ; Jiao FENG ; Shunhong XUE ; Bixia YU ; Wen HE ; Lin JIANG ; Longfeng LIAO ; Chunlei YUE ; Wenhui HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(3):279-289
Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3%)and from outpatient and emergency care patients(4.7%).Overall,19.6%of the isolates were from children and 80.4%were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0%and 32.0%,respectively.Coagulase negative Staphylococcus accounted for 73.0%of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2%in children and 45.6%in adults.The prevalence of MRCNS was 67.6%in adults and 69.5%in children.A small number of vancomycin-resistant Enterococcus faecium(2.2%)and linezolid-resistant Enterococcus faecalis(3.1%)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2%and 76.4%in children,70.5%and 63.5%in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3%and 47.7%in children,6.4%and 47.9%in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0%and 37.1%in children,81.7%and 39.9%in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.
8.Changing antibiotic resistance profiles of the bacterial strains isolated from geriatric patients in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Xiaoman AI ; Yunjian HU ; Chunyue GE ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Hui LI ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(3):290-302
Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3%of the total number of clinical isolates from all patients.Overall,21.8%of the 514 715 strains were gram-positive bacteria,and 78.2%were gram-negative bacteria.Majority(90.9%)of the strains were isolated from inpatients.About 42.9%of the strains were isolated from respiratory specimens,and 22.9%were isolated from urine.More than half(60.7%)of the strains were isolated from male patients,and 39.3%isolated from females.About 51.1%of the strains were isolated from patients aged 65-<75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8%in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2%,1.5%)and linezolid-resistant strains(3.4%,0.3%)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3%,4.0%,and 1.7%in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2%)to imipenem and meropenem were 20.9%and 22.3%,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7%-7.8%of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6%)to imipenem and meropenem were 68.4%and 70.6%respectively,while 28.5%and 24.3%of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-<75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.
9.Clinical characteristics and prognosis of perioperative myocardial injury after non-cardiac surgery in intensive care unit patients
Shi-hong XIA ; Xue-li MA ; Guo-feng SHEN ; Li-jing JIANG ; Kang-yi LIU ; Wei-yi TANG ; Jin-di NI ; Xiang LI
Fudan University Journal of Medical Sciences 2025;52(3):424-428,445
Objective To retrospectively analyze the clinical risk factors and prognosis of perioperative myocardial injury(MINS)in non-cardiac surgery patients admitted to the intensive care unit(ICU).Methods A total of 478 postoperative patients admitted to the Department of Intensive Medicine,Minhang Hospital,Fudan University from Jan 2020 to Dec 2023 were selected.They were divided into MINS group(n=302)and normal group(n=176)based on whether myocardial injury occurred within 7 days after surgery.The differences in clinical characteristics between the two groups were compared,and risk factors for perioperative myocardial injury were identified.Risk factors for mortality in the MINS group were analyzed with 30-day mortality as the clinical endpoint.Results The prevalence of acute physiology and chronic health evaluation Ⅱ(Apache Ⅱ)score,coronary artery disease,and chronic kidney disease were all higher in the MINS group than those in the normal group,with statistically significant differences(P<0.05).The proportion of emergency surgeries,co-infection,and perioperative hypotension were significantly different between the MINS group and the normal group(P<0.05).Multivariate logistic regression analysis revealed that chronic kidney disease,emergency surgery,co-infection,and intraoperative and postoperative hypotension were risk factors for MINS occurrence.Prognostic analysis indicated that perioperative hypotension was a risk factor for 30-day mortality in MINS patients.Conclusion MINS is closely associated with patients'underlying conditions,timing of surgery,and perioperative hypotension status,and especially perioperative hypotension affects the final outcomes.
10.Effects of various types of rodent Plasmodium parasites on the mouse immune response
Xiao-feng LIANG ; Yu-hong ZHANG ; Yan-wei QI
Chinese Journal of Zoonoses 2025;41(1):75-84
Malaria,an ancient disease caused by Plasmodium pathogens,poses a serious threat to human health.The body resists and suppresses Plasmodium invasion through two types of immune response:innate immunity and adaptive immunity.Innate immune cells and the cytokines that they produce constitute the first line of defense against foreign pathogens,whereas adaptive immunity has antimalarial effects primarily through humoral and cellular immunity.Rodent models of Plasmodium in-fection are suitable for studying the mechanism of malaria pathogenesis;therefore,exploring the effects of various rodent para-site types on the immune response in mice can advance understanding of malaria and provide research directions for the develop-ment of new treatment targets.This review summarizes various types of rodent Plasmodium parasites;immune cells and their cytokines acting during the immune response;and new targets for malaria treatment,in hopes of enhancing understanding of the immune response to malaria and exploring new directions in malaria treatment.

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