1.Efficacy and safety analysis of reduced-field postoperative radiotherapy of upper tract urothelial carcinoma
Xiaoying LI ; Xianshu GAO ; Hongzhen LI ; Shangbin QIN ; Xin QI ; Mingwei MA ; Yun BAI ; Tian CHENG ; Zheng ZHANG ; Qi TANG ; Zihao TAO ; Chunru XU ; Xuesong LI
Chinese Journal of Radiation Oncology 2025;34(12):1215-1222
Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.
2.Hypoxia characteristics and prognostic significance of glioblastoma MES-like subpopulation through multi-transcriptomics sequencing
Tao CHEN ; Fan YANG ; Shuai WANG ; Min LUO ; Zexuan YAN ; Caidie TANG ; Yun NING ; Sisi YANG ; Ruofei CAO ; Zhengbo LI ; Xuanyu FANG ; Xiaohong YAO
Journal of Army Medical University 2025;47(16):1904-1912
Objective To analyze the composition characteristics and biological functions of tumor cell subpopulations in glioblastoma(GBM)through multi-transcriptomics sequencing technology,and explore the hypoxia characteristics and spatial localization features of the mesenchymal-like(MES-like)tumor cell subpopulation in GBM and the influence on malignant biological behaviors.Methods Multi-transcriptomics sequencing data,including single-cell RNA sequencing(scRNA-seq)data(18 patients),bulk RNA sequencing(bulk RNA-seq)and spatial transcriptomics(ST)data of GBM,were employed to define cell subpopulations in GBM,and Gene Ontology(GO)and Gene Set Enrichment Analysis(GSEA)were utilized to analyze their functions.The proportions and locations of cell subpopulations in bulk RNA-seq data were evaluated with BayesPrism deconvolution.Immunofluorescence assay was conducted for verification on 12 paraffin samples of GBM from patients who visited the neurosurgical department of our hospital from 2015 to 2023 and met the pathological diagnostic criteria for GBM(10 males and 2 females,at an average age of 53.50 years and a median age of 54.50 years).pySCENIC was applied to predict specific transcription factors of tumor cell subpopulations.Results Tumor cells in GBM were highly heterogeneous,and could be mainly divided into 4 subpopulations:astrocyte-like(AC-like),neural progenitor-like(NPC-like),oligodendrocyte progenitor-like(OPC-like)and MES-like.Differential gene analysis found that the MES-like tumor cells highly expressed vascular endothelial growth factor A(VEGFA),adrenomedullin(ADM),N-myc downstream regulated 1(NDRG1),insulin like growth factor binding protein 5(IGFBP5),and A-kinase anchoring protein 12(AKAP12)(P<0.001).pySCENIC transcription factor prediction found that the high-active transcription factors of the MES-like tumor cells were AT-rich interaction domain 3A(ARID3A),FOS like 2,AP-1 transcription factor subunit(FOSL2),endothelial PAS domain protein 1(EPAS1),CCAAT enhancer binding protein delta(CEBPD),and CCAAT enhancer binding protein beta(CEBPB)(P<0.05).GO and GSEA enrichment analyses found that the MES-like tumor cells were enriched in hypoxia-related pathways,especially the pathway of cell responses to hypoxia levels(NES=2.437,P<0.001).BayesPrism deconvolution showed that the MES-like tumor cells mainly existed in PAN(Pseudopalisading cells around necrosis)and perinecrotic zone.Immunofluorescence assay confirmed CD44+(CD44 antigen)MES-like tumor cells were mainly located in hypoxia areas with highly expression of hypoxia inducible factor 1 subunit alpha(HIF1α)(P<0.01).Multivariate Cox regression analysis indicated that the MES-like tumor cells were significantly correlated with the adverse prognosis of GBM patients(HR=1.71,95%CI:1.38~2.11,P<0.001).Conclusion Tumor cells in GBM are of highly heterogeneity.They could be mainly divided into 4 subpopulations:AC-like,NPC-like,OPC-like and MES-like.MES-like tumor cells,mainly locating in PAN and perinecrotic zone,are characterized by hypoxia,which can promote the malignant progression of GBM.
3.Correlation between the expression of serum miR-1298-5p,miR-625-5p and miR-155 and the degree of Helicobacter pylori infection in elderly gastric cancer patients
Chunli TANG ; Shujuan FAN ; Sheng TAO ; Jianning LIU ; Feng SU ; Caiyun YUAN ; Meiling ZHU ; Ruimei ZHONG ; JiaoJiao CAO ; Yun WANG
International Journal of Laboratory Medicine 2025;46(2):151-156
Objective To explore the correlation between the expression of serum microRNA(miR)-1298-5p,miR-625-5p,and miR-155 with the degree of Helicobacter pylori(Hp)infection in elderly gastric cancer patients.Methods From January 2021 to November 2023,120 elderly patients with gastric cancer admitted to the hospital from January 2021 to November 2023 were selected as the gastric cancer group,and 130 non-gas-tric cancer patients who underwent gastroscopy were selected as the control group.The expression levels of miR-1298-5p,miR-625-5p and miR-155 in serum were detected by fluorescence quantitative PCR(qPCR).Car-bon 13 urea breath test was used to detect the positive rate of Hp infection in two groups,and the degree of Hp infection in elderly patients with gastric cancer were evaluated.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum miR-1298-5p,miR-625-5p,and miR-155 expression levels for Hp infection in elderly gastric cancer patients.Pearson method was applied to analyze the correlation between serum miR-1298-5p,miR-625-5p,miR-155 expression and positive rate of Hp infection in elderly gas-tric cancer patients.Results Compared with the control group,the expression levels of miR-1298-5p and miR-625-5p in serum of gastric cancer group decreased(P<0.05),while the positive rate of Hp infection and the expression level of serum miR-155 increased(P<0.05).The expression levels of serum miR-1298-5p and miR-625-5p in elderly gastric cancer patients with Hp grade Ⅰ,Ⅱ,and Ⅲ infection were lower than those without Hp infection,while the expression level of miR-155 was higher(P<0.05).Patients with poor differ-entiation,lymph node metastasis,and TNM stage Ⅲ-Ⅳ had lower expressions of serum miR-1298-5p and miR-625-5p(P<0.05),and higher expression of miR-155(P<0.05)than those with moderate-high differen-tiation,no lymph node metastasis,and TNM stage Ⅰ-Ⅱ.The expression levels of serum miR-1298-5p and miR-625-5p were negatively correlated with the positive rate of Hp infection in elderly patients with gastric cancer(r=-0.443,-0.386,both P<0.001),and the expression levels of serum miR-155 were positively correlated with the positive rate of Hp infection(r=0.525,P<0.001).The area under the curve(AUC)of serum miR-1298-5p,miR-625-5p and miR-155 combined diagnosis of Hp infection in elderly gastric cancer pa-tients was higher than that of single diagnosis(P<0.05).Conclusion The expression levels of miR-1298-5p and miR-625-5p in serum of elderly gastric cancer patients with Hp infection decrease,while the expression level of miR-155 increases.These three factors are related to the degree of Hp infection and have good diag-nostic value for the occurrence of Hp infection.
4.Evidence-based guideline for diagnosis and early fixation of severe open tibiofibular fractures (version 2025)
Yongjun RUI ; Yongqing XU ; Qingtang ZHU ; Xin WANG ; Zhao XIE ; Shanlin CHEN ; Jingyi MI ; Xianyou ZHENG ; Juyu TANG ; Xiaoheng DING ; Aixi YU ; Tao SONG ; Jianxi HOU ; Jian QI ; Xinyu FAN ; Jun FEI ; Lin GUO ; Xingwen HAN ; Weixu LI ; Aiguo WANG ; Yun XIE ; Tao XING ; Meng LI ; Baoqing YU ; Yan ZHUANG ; Xiaoqing HE ; Tao SUN ; Pengcheng LI ; Jihui JU ; Hongxiang ZHOU ; Haidong REN ; Guangyue ZHAO ; Gang ZHAO ; Yongwei WU ; Jun LIU ; Yunhong MA ; Yapeng WANG
Chinese Journal of Trauma 2025;41(11):1021-1034
Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.
5.Discussion on curative effect of electronic bronchoscope in treating tracheobronchial tuberculosis at clinical activity stage
Shenglin MO ; Yun HUANG ; Xiaohong HUANG ; Gui TANG ; Yanping SUN ; Jinyu QIN ; Tao CHEN ; Jiaguang HU ; Peng ZHANG ; Jinliang KONG ; Zhongsheng JIANG
China Medical Equipment 2025;22(6):76-80
Objective:To evaluate the clinically curative effect of intervention treatment of electronic bronchoscope in treating tracheobronchial tuberculosis at clinical activity stage.Methods:Sixty patients with tracheobronchial tuberculosis at clinical activity stage(type I,II,III and VI)who admitted to Liuzhou People's Hospital from September 2020 to September 2023 were selected,and they were divided into drug group(anti-tuberculosis drug treatment)and combination group(anti-tuberculosis drug treatment+interventional treatment with electronic bronchoscope)by the random number table method,with 30 cases in each group.The curative effects of the two groups were observed,and the negative conversion rate of sputum bacteria,clinical symptom scores(cough symptom,expectoration symptom)before and after treatment,Modified British Medical Research Council Dyspnea Scale(mMRC)score between two groups were compared,and the differences in indicators of pulmonary function such as forced expiratory volume in the first second(FEV1),forced vital capacity(FVC)and maximum voluntary ventilation(MVV)between the two groups also were compared.And then,the incidence of complications was calculated.Results:During the 1,2 and 3 months of follow-up,there were respectively 21 cases,27 cases and 30 cases occurred negative conversion of sputum bacteria in 30 patients of the combination group,and there were respectively 15 cases,18 cases and 23 cases occurred negative conversion of sputum bacteria in 30 patients of the drug group.At the 1st month of follow-up,the negative conversion rate of sputum bacteria in combination group was higher than that in drug group,while there was no statistically significant difference between the two groups(P>0.05).At the 2nd and 3rd month of follow-up,the negative conversion rate of sputum bacteria in the combination group was higher than that in the drug group,and the differences were statistically significant(x2=7.200,7.925,P<0.05).The effective rate of treatment of the combination group was 100%,which was higher than 80%of the drug group,and the difference of that between two groups was significant(x2=6.667,P<0.05).After 2 months of treatment,the mMRC score,cough symptom score and expectoration symptom score of the combination group were all lower than those of the drug group,and the differences were statistically significant(t=3.504,3.950,3.530,P<0.05).The improvement effects of FEV1,FVC and MVV of the combination group were all better than those of the drug group,and the differences were statistically significant(t=6.626,4.966,4.097,P<0.05).There was no significant difference in the incidence of complications between the two groups(P>0.05).Conclusion:Anti-tuberculosis drug therapy combined with electronic bronchoscopy intervention has a good therapeutic effect in clinically active tracheobronchial tuberculosis.
6.Discussion on curative effect of electronic bronchoscope in treating tracheobronchial tuberculosis at clinical activity stage
Shenglin MO ; Yun HUANG ; Xiaohong HUANG ; Gui TANG ; Yanping SUN ; Jinyu QIN ; Tao CHEN ; Jiaguang HU ; Peng ZHANG ; Jinliang KONG ; Zhongsheng JIANG
China Medical Equipment 2025;22(6):76-80
Objective:To evaluate the clinically curative effect of intervention treatment of electronic bronchoscope in treating tracheobronchial tuberculosis at clinical activity stage.Methods:Sixty patients with tracheobronchial tuberculosis at clinical activity stage(type I,II,III and VI)who admitted to Liuzhou People's Hospital from September 2020 to September 2023 were selected,and they were divided into drug group(anti-tuberculosis drug treatment)and combination group(anti-tuberculosis drug treatment+interventional treatment with electronic bronchoscope)by the random number table method,with 30 cases in each group.The curative effects of the two groups were observed,and the negative conversion rate of sputum bacteria,clinical symptom scores(cough symptom,expectoration symptom)before and after treatment,Modified British Medical Research Council Dyspnea Scale(mMRC)score between two groups were compared,and the differences in indicators of pulmonary function such as forced expiratory volume in the first second(FEV1),forced vital capacity(FVC)and maximum voluntary ventilation(MVV)between the two groups also were compared.And then,the incidence of complications was calculated.Results:During the 1,2 and 3 months of follow-up,there were respectively 21 cases,27 cases and 30 cases occurred negative conversion of sputum bacteria in 30 patients of the combination group,and there were respectively 15 cases,18 cases and 23 cases occurred negative conversion of sputum bacteria in 30 patients of the drug group.At the 1st month of follow-up,the negative conversion rate of sputum bacteria in combination group was higher than that in drug group,while there was no statistically significant difference between the two groups(P>0.05).At the 2nd and 3rd month of follow-up,the negative conversion rate of sputum bacteria in the combination group was higher than that in the drug group,and the differences were statistically significant(x2=7.200,7.925,P<0.05).The effective rate of treatment of the combination group was 100%,which was higher than 80%of the drug group,and the difference of that between two groups was significant(x2=6.667,P<0.05).After 2 months of treatment,the mMRC score,cough symptom score and expectoration symptom score of the combination group were all lower than those of the drug group,and the differences were statistically significant(t=3.504,3.950,3.530,P<0.05).The improvement effects of FEV1,FVC and MVV of the combination group were all better than those of the drug group,and the differences were statistically significant(t=6.626,4.966,4.097,P<0.05).There was no significant difference in the incidence of complications between the two groups(P>0.05).Conclusion:Anti-tuberculosis drug therapy combined with electronic bronchoscopy intervention has a good therapeutic effect in clinically active tracheobronchial tuberculosis.
7.Evidence-based guideline for diagnosis and early fixation of severe open tibiofibular fractures (version 2025)
Yongjun RUI ; Yongqing XU ; Qingtang ZHU ; Xin WANG ; Zhao XIE ; Shanlin CHEN ; Jingyi MI ; Xianyou ZHENG ; Juyu TANG ; Xiaoheng DING ; Aixi YU ; Tao SONG ; Jianxi HOU ; Jian QI ; Xinyu FAN ; Jun FEI ; Lin GUO ; Xingwen HAN ; Weixu LI ; Aiguo WANG ; Yun XIE ; Tao XING ; Meng LI ; Baoqing YU ; Yan ZHUANG ; Xiaoqing HE ; Tao SUN ; Pengcheng LI ; Jihui JU ; Hongxiang ZHOU ; Haidong REN ; Guangyue ZHAO ; Gang ZHAO ; Yongwei WU ; Jun LIU ; Yunhong MA ; Yapeng WANG
Chinese Journal of Trauma 2025;41(11):1021-1034
Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.
8.Efficacy and safety analysis of reduced-field postoperative radiotherapy of upper tract urothelial carcinoma
Xiaoying LI ; Xianshu GAO ; Hongzhen LI ; Shangbin QIN ; Xin QI ; Mingwei MA ; Yun BAI ; Tian CHENG ; Zheng ZHANG ; Qi TANG ; Zihao TAO ; Chunru XU ; Xuesong LI
Chinese Journal of Radiation Oncology 2025;34(12):1215-1222
Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.
9.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.
10.Diazepam alleviates pulmonary fibrosis in mice by inhibiting LPS-induced pyroptosis and inflammation via the let-7a-5p/MYD88 axis
Duanyi SONG ; Yun LI ; Xuefang TANG ; Hua LI ; Kang TAO
Journal of Southern Medical University 2024;44(11):2092-2101
Objective To explore the mechanism by which diazepam alleviates lipopolysaccharide(LPS)-induced pyroptosis and inflammation to delay the progression of pulmonary fibrosis.Methods MRC-5 cells challenged with LPS were treated with diazepam and transfected with a let-7a-5p mimic alone or co-transfected with pc-DNA-MYD88.The changes in cellular expressions of inflammatory factors were analyzed with ELISA,and the expressions of fibrosis-and pyroptosis-related proteins were detected using Western blotting.In the animal experiment,C57BL/6 mice were randomized for treatment with LPS,LPS+diazepam,LPS+diazepam+let-7a-5p mimic,LPS+diazepam+ST2825(a MYD88 inhibitor),or LPS+diazepam+let-7a-5p mimic+pc-DNA-MYD88,and pulmonary fibrosis and pulmonary expression of α-SMA were examined using Masson staining and immunofluorescence staining,respectively.Results LPS exposure of MRC-5 cells significantly downregulated let-7a-5p expression,up-regulated MYD88 expression,increased the levels of IL-4,IL-6,TGF-β and TNF-α,and enhanced the expressions of fibrosis-related proteins(Col-I,Col-III,and α-SMA)and pyroptosis-related proteins(NLRP3,caspase-1,ASC,and GSDMD-N).Diazepam treatment of LPS-stimulated cells effectively inhibited the expressions of inflammation-related factors and the fibrosis-and pyroptosis-related proteins.In C57BL/6 mice,diazepam treatment obviously alleviated LPS-induced pulmonary fibrosis and reduced and pulmonary expression of α-SMA,and these effects were further enhanced by treatment with let-7a-5p mimic or ST2825,but the effect of let-7a-5p mimic was significantly attenuated by MYD88 over-expression.Conclusion Diazepam can negatively regulate MYD88 by upregulating the expression of let-7a-5p to inhibit LPS-induced pyroptosis and inflammatory response,thereby alleviating lung fibrosis in mice.

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