OBJECTIVES: To investigate the regulatory role of the NLRP3 signaling pathway in hepatocyte pyroptosis in nonalcoholic steatohepatitis (NASH) under hypoxia. METHODS: Twenty-four male C57BL/6 mice were randomized equally into hypoxic control (A), hypoxic NASH model (B), hypoxic NASH+NLRP3 inhibitor (C), and hypoxic NASH+caspase-1 inhibitor (D) groups. In groups B-D, the mice were fed a methionine choline-deficient (MCD) diet under hypoxic conditions (to simulate a 5000 m altitude) for 6 weeks; the mice in groups C and D received intraperitoneal injections of the respective inhibitors every other day. RESULTS: Compared with those in group A, the mice in group B showed significantly elevated serum levels of FBG, TC, TG, ALT and AST, increased liver lipid content, inflammatory cell infiltration and collagen fiber deposition, and enhanced hepatic expressions of NLRP3, caspase-1, IL-1β and GSDMD proteins, with obvious swelling, cristae breakage, vacuolization, and outer membrane disruption of the mitochondria, ribosome loss in the cytoplasm, destruction of the nuclear membrane, and pathological changes of the rough endoplasmic reticulum. Treatment with NLRP3 inhibitor and caspase-1 inhibitor both significantly lowered serum levels of TC, TG, ALT and AST (but without significantly affecting FBG) in the mouse models, and reduced liver lipid content, inflammatory cell infiltration, collagen deposition, and expression levels of NLRP3, caspase-1, GSDMD and IL-1β. The treatments also significantly improved pathological changes in the mitochondria, ribosomes and endoplasmic reticulum in liver tissues of the mice. CONCLUSIONS NLRP3 signaling pathway plays a key role in promoting hepatocyte pyroptosis in NASH mice under hypoxic condition, and inhibiting this pathway can effectively reduce liver inflammation, suggesting its potential as a therapeutic target for NASH treatment.
Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Mice, Inbred C57BL ; Male ; Hepatocytes/pathology* ; Signal Transduction ; Mice ; Hypoxia/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

Objective To investigate the factors influencing the development of extra-pulmonary tuberculosis(EPTB)in patients with viral hepatitis complicated by pulmonary tuberculosis(PTB).Methods A retrospective analysis was conducted on 427 patients with Hepatitis B Virus(HBV)and Hepatitis C Virus(HCV)infections complicated by PTB admitted to the tuberculosis department of Kunming Third People's Hospital from January 2015 to December 2020.Patients were divided into the EPTB complication group(n=72)and the non-EPTB complication group(n=355)based on the presence of EPTB.Clinical treatment data of patients were collected.Univariate and multivariate Logistic regression analyse were used to screen independent risk factors for EPTB as predictive factors.A nomogram prediction model was established for Extrapulmonary Tuberculosis(EPTB)complications in patients with viral hepatitis and Pulmonary Tuberculosis(PTB),evaluated using the Hosmer-Lemeshow test and ROC curve analysis.Results Among the 427 patients,292(68.3%)were male and 135(31.7%)were female,with 72 cases of EPTB,resulting in an incidence rate of 16.86%.In the EPTB group,there were 34 males(47.2%)and 38 females(52.8%).The types of EPTB included tuberculous pleuritis(21 cases,29%),tuberculous peritonitis(16 cases,22%),lymph node tuberculosis(13 cases,18%),tuberculous encephalitis(5 cases,6%),intestinal tuberculosis(6 cases,8%),bone tuberculosis(5 cases,6%),pelvic tuberculosis(3 cases,4%),and genitourinary tuberculosis(3 cases,4%).Multivariate logistic regression analysis showed that gender(OR=0.425,95%CI:0.250-0.722,P=0.02),low triglyceride(TG)levels(OR=0.837,95%CI:0.717-0.978,P=0.025),the tuberculosis-specific antigen A(ESAT-6)(OR=1.007,95%CI:1.003～1.011 were independent influencing factors for EPTB in patients with PTB complicated by HBV and HCV infections.The optimal cutoff value for the nomogram model is 0.192,with a sensitivity of 0.611,specificity of 0.710,Youden index of 0.741,positive likelihood ratio of 2.103,and negative likelihood ratio of 0.548.The Hosmer-Lemeshow test yielded χ2=2.631,P=0.955.ROC curve analysis showed an AUC of 0.693,95%CI:0.629 1～0.7574.Conclusion The prediction model based on gender,low TG levels and ESAT-6 can well predict the occurrence of EPTB to some extent,providing a reference for clinical treatment.

Objective To evaluate the relationship between nutritional parameters and the risk of venous thromboembolicism(VTE)in patients with tuberculosis so as to identify the risk factors and predictors of thrombosis and assist in the early identification of high-risk factors for VTE in patients with the pulmonary tuberculosis.Methods A total of 323 patients diagnosed with the pulmonary tuberculosis and hospitalized in Kunming Third People's Hospital from August 2021 to August 2023 were collected.According to the VTE risk assessment of non-operative patients,they were divided into the high-risk group and the low-risk group respectively with 116 and 207 in each group.The nutritional indicators with statistically significant differences between the two groups were screened by Lasso regression.Multivariate Logistic regression was used to screen the independent risk factors for high VTE risk in pulmonary tuberculosis patients,and a nomogram prediction model was constructed.The prediction model was evaluated by receiver operating characteristic curve(ROC),calibration curve,decision curve,and influence curve.Results Patients in the high-risk group were significantly older than those in the low-risk group(59 vs.41,P<0.001),hypertension,gender,and Type 2 diabetes did not differ significantly(P values were 0.084,0.724 and 0.488,respectively).9 variables were selected from the inter-group comparison and Lasso regression,including ALB,HCT,NRS2002 scores,HBDH,RDW-SD,RDW-CV,TG,CONUT scores,and NEFA.Multivariate Logistic regression analysis showed that ALB,NRS2002 scores,RDW-SD,and CONUT scores were independent influencing factors for the high risk of VTE scores in patients with tuberculosis(P<0.005).Area under the ROC curve showed that the AUC(0.892)for high-risk VTE scores in patients with the pulmonary tuberculosis was greater than that of ALB(0.803),NRS2002 score(0.735),RDW-SD(0.685),and CONUT score(0.774).Fitting prediction model:Logit(P):Y=0.433×NRS-0.136×ALB+0.411×CONUT score+0.072×RDW-SD-1.770,P=1/(1+e-Y)(Y:prediction index,P:prediction probability).Calibration curve showed that the model prediction tended to be consistent with the actual results(U:>0.05),and the decision curve and influence curve showed that the model can bring clinical benefits.Conclusion ALB,NRS2002 scores,RDW-SD,and CONUT scores are independent influencing factors for the high risk of VTE scores in patients with tuberculosis.They can guide the clinical practice,improve these indicators as soon as possible,reduce VTE scores,and reduce the thrombosis risk.At the same time,the prediction model performs well in the verification cohort,with its discrimination ability,calibration accuracy and clinical utility(decision curve analysis)all reaching a satisfactory level.

Objective To investigate the clinical effect of acupotomology combined with Bushenzhuanggu prescription in the treatment of residual lumbar pain after percutaneous kyphoplasty(PKP)for osteoporotic vertebral compression fractures.Methods A total of 77 patients with PKP postoperative residual lumbar pain admitted to the Department of Orthopedics,Ningbo Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from January 2018 to December 2021 were randomly divided into control group and observation group.Patients in control group were treated with calcitriol soft capsules and calcium carbonate D3 tablets,and patients in observation group were treated with acupotomy combined with Bushenzhuanggu prescription.The pain degree,lumbar function and self-care ability of the two groups were compared.Results After treatment,the pain level,lumbar function,and self-care abilityof the two groups of patients improved compared to before treatment.Compared with control group,the visual analogue score(VAS)score and Oswestry disability index(ODI)index of observation group decreased more significantly,and the difference was statistically significant(P<0.05);The Barthel index of observation group increased more significantly in the early stage(3 days and 1 month after treatment),with a statistically significant difference(P<0.05).However,there was no statistically significant difference in Barthel index between the two groups at 3 months after treatment(P>0.05).Conclusion Acupotomy combined with Bushenzhuanggu prescription has satisfactory clinical efficacy in the treatment of residual lumbar pain after PKP operation of osteoporotic vertebral compression fracture.It can significantly reduce pain,improve lumbar function,shorten the improvement time of patients'self-care ability,improve patients'quality of life,and effectively promote patients'rapid recovery.

Autism spectrum disorder (ASD) is one of the common neurodevelopmental disorders in children. Its etiology and pathogenesis are poorly understood. Previous studies have suggested potential changes in the complement and coagulation pathways in individuals with ASD. In this study, using multiple reactions monitoring proteomic technology, 16 of the 33 proteins involved in this pathway were identified as differentially-expressed proteins in plasma between children with ASD and controls. Among them, CFHR3, C4BPB, C4BPA, CFH, C9, SERPIND1, C8A, F9, and F11 were found to be altered in the plasma of children with ASD for the first time. SERPIND1 expression was positively correlated with the CARS score. Using the machine learning method, we obtained a panel composed of 12 differentially-expressed proteins with diagnostic potential for ASD. We also reviewed the proteins changed in this pathway in the brain and blood of patients with ASD. The complement and coagulation pathways may be activated in the peripheral blood of children with ASD and play a key role in the pathogenesis of ASD.
Child ; Humans ; Autism Spectrum Disorder/metabolism* ; Proteomics ; Brain/metabolism*

Objective:To investigate the effect of Yiqi Dihuang Decoction assisting conventional western medicine therapy in the treatment of early diabetic nephropathy (DN) with deficiency of qi and yin.Methods:A total of 117 patients with early DN who met the inclusion criteria from June 2018 to December 2020 in Beijing Hospital of Traditional Chinese Medicine Shunyi Branch were divided into a control group of 58 patients and a treatment group of 59 patients according to the random number table method. The control group was treated with conventional western medicine therapy, and the treatment group was additionally treated with Yiqi Dihuang Decoction on the basis of the control group. Both groups were treated for 1 month. Serum levels of IL-1, macrophage scavenger receptor A (SR-A), TNF-α, C-C motif chemokine 2 (CCL2), GSH-Px and SOD were detected by ELISA before and after treatment. Cystatin C (Cys C) and SCr levels were detected by automatic biochemical analyzer. The urinary albumin was determined by radioimmunoassay, urinary creatinine determined by rate method, and urinary albumin/creatinine ratio (UACR) and glomerular filtration rate (eGFR) were calculated. The adverse events during treatment and clinical efficacy were evaluated.Results:The total effective rate was 94.92% (56/59) in the treatment group and 81.03% (47/58) in the control group, and the difference between the two groups was statistically significant ( χ2=5.35, P=0.021). After treatment, UACR [(92.28±15.42) mg/g vs. (108.42±20.76)mg/g, t=4.78], eGFR [(91.42±13.18) m·min -1·1.73m -2vs. (95.30±15.94) m·min -1·1.73m -2, t=2.02], SCr [(65.30±9.54) μmol/L vs. (70.18±12.53) μmol/L, t=5.42], Cys C [(0.65±0.12)mg/L vs. (1.07±0.26)mg/L, t=11.25] in the treatment group were significantly lower than those in the control group ( P<0.05). Serum SR-A [(37.18±6.10) μg/L vs. (51.51±7.12) μg/L, t=11.70], CCL2 [(13.12±1.63) μg/L vs. (19.68±2.90) μg/L, t=15.12], TNF-α [(20.57±3.50) ng/L vs. (29.68±4.17) ng/L, t=12.81], IL-1 [(8.47±0.97) ng/L vs. (13.12±1.57) ng/L, t=19.31] levels in the treatment group were significantly lower than those in the control group ( P<0.01); serum SOD [(24.09±3.12) mg/L vs. (18.72±2.76) mg/L, t=9.85] activity and GSH-Px [(231.57±25.38) mg/L vs. (174.58±22.96) mg/L, t=12.73] in the treatment group were significantly higher than those in the control group ( P<0.01). During the treatment period, the incidence of adverse events was 10.34% (6/58) in the control group and 6.78% (4/59) in the treatment group, and there was no significant difference between the two groups ( χ2=0.48, P=0.490). Conclusion:Yiqi Dihuang Decoction assisted with conventional western medicine can effectively improve the renal function of patients with early DN syndrome of qi and yin deficiency, inhibit the body's inflammatory response and oxidative stress response, and improve clinical efficacy.

Hierarchical diagnosis and treatment system is an important measure to rationally allocate medical resources and promote the homogenization of basic medical services. The medical alliance is an important service mode and service system of hierarchical diagnosis and treatment, whose role is to perfect the up-down linkage and meet the patient′s medical needs. Informatization construction is an important starting point to promote the services of the medical alliance. In order to solve the problem of connectivity, the medical alliance needs to establish a regional referral platform and realize the integrated service of all medical institutions. Renji Hospital, Shanghai Jiaotong University School of Medicine, has built a blockchain based referral system for hierarchical diagnosis and treatment, incorporating the S2B2C mode concept, and using the traceability, tamper proof and distributed accounting features of blockchain technology, realized independent storage of data in hospitals, realized real-time information sharing and interconnection, and provided a feasible solution for medical alliance management.

Objective:To evaluate the predictive value of stair climbing test combined with arterial blood gas analysis on postoperative complications in lung cancer patients with limited pulmonary function.Methods:A total of 1 231 hospitalized lung cancer patients with limited pulmonary function dating from August 2012 to August 2020 were retrospectively reviewed. Included in the cohort were 766 of patients who underwent stair climbing test(SCT) preoperatively and completed data collection. Patients were grouped according to their general condition, past medical history, surgical approach, pulmonary function test(PFT) and SCT results. Comparison of the postoperative cardiopulmonary complication rates were made between different groups, and independent risk factors were identified.Results:A total of 182 cardiopulmonary-related complications occurred in 144 cases, accounting for 18.8% of the entire cohort. Perioperative mortality rate was 0.9%(7/766). The rate of postoperative cardiopulmonary complications was significantly different between the groups stratified by gender, age, smoking index, PFT index(FEV1%, DLCO%), SCT results(height achieved, speed, changes in heart rate and oxygen saturation of the arteries before and after the test), ASA score, surgical approach(VATS/Open), resection range(Lobectomy/Sublobectomy), anesthetic duration, blood loss volume, etc. Logistic regression analysis showed that only height achieved( P<0.001), changes in heart rate( P<0.001), changes in oxygen saturation of the arteries( P=0.001), resection range( P=0.006) and anesthetic duration( P=0.025) were independent risk factors for cardiopulmonary-related complications in lung cancer patients with limited pulmonary function. Conclusion:The stair climbing test combined with arterial blood gas analysis could be used as a preoperative screening method for lung cancer patients with limited lung function and may have a predictive value for postoperative cardiopulmonary-related complications.

Objective To investigate the role of miR-155 in the development and lung metastasis of osteosarcoma, and to explore its target proteins and related mechanisms. Methods We detected differential miR-155 expression in osteosarcoma and its lung metastasis process through relevant database analysis combined with qPCR detection of clinical tissue and cell samples. iTRAQ quantitative proteomics was used to screen the target protein of miR-155 in osteosarcoma and its lung metastasis. The selected miR-155 target protein was verified by Western blot in clinical tissue and cell samples. Results miR-155 expression was significantly higher in osteosarcoma tissue and lung metastatic tumor tissue than that in the control group. Compared with human normal osteoblasts, miR-155 expression in human osteosarcoma cell line was also significantly increased. A total of 3714 proteins were obtained by iTRAQ assay, and 253 differentially-expressed proteins were screened out, 144 of which were up-regulated and 109 were down-regulated. The prediction analysis and experiment verified that C/EBP β was a potential target protein of miR-155. Conclusion miR-155 expression is significantly increased in osteosarcoma and its lung metastasis process, and C/EBP β is a potential target of miR-155.