Objective To analyze the change in levels of high mobility group box 1 protein (HMGB1), interleukin-32 (IL-32), matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in peripheral blood of patients with lupus nephritis (LN) and their values in predicting prognosis. Methods A total of 86 patients with LN from October 2021 to June 2023 were selected and treated with induction therapy for 6 months. Based on remission status of the disease, patients were divided into remission group (n=66) and non-responder group (n=20). Baseline data, change in levels and reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1, and the partial correlation of reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels in peripheral blood with treatment response as well as their predictive values for treatment response were compared between the two groups. Disease progression was compared between patients with different reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1. Results HMGB1, IL-32 and MMP-9/TIMP-1 levels in the remission group decreased significantly at 1 and 3 months after treatment compared to before treatment (P < 0.05); the levels of HMGB1, IL-32 and MMP-9/TIMP-1 in the remission group were significantly lower than those in the non-responder group at 1 and 3 months after treatment (P < 0.05); the reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels in the remission group were significantly higher than those in the non-responder group at 1 and 3 months after treatment (P < 0.05). Partial correlation analysis showed that the reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels were independently significantly correlated with treatment response (P < 0.05). One and three months after treatment, the values of the area under the curve (AUC) for the combined prediction of remission by the reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels were 0.910 and 0.932 respectively, with the AUC being the largest at 3 months after treatment (P < 0.05). Patients were divided into high and low reduction rate subgroups based on theoptimal cut-off value from the ROC curve analysis at 3 months after treatment, and the disease progression rate was significantly lower in the high reduction rate subgroup than in the low reduction rate subgroup for HMGB1, IL-32 and MMP-9/TIMP-1 (P < 0.05). Conclusion The great change in levels of HMGB1, IL-32 and MMP-9/TIMP-1 in peripheral blood of LN patients is significantly correlated with treatment response and disease progression, and the combined detections of HMGB1, IL-32 and MMP-9/TIMP-1 levels at 1 and 3 months after treatment have high value in predicting the treatment response of LN patients.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder and its clinical manifestation including haemangioblastomas of the central nervous system, renal cell carcinoma, haeochromocytomas, and pancreatic cyst. The deletion, mutation and promoter methylation of VHL gene can cause VHL disease. Swine is considered as an ideal model for human disease because of its physiological and anatomical similarity to human. We cloned pig VHL gene that is 2 725 bp in length. VHL highly expressed in adrenal gland, liver, pancreas, heart and testis. We designed 5 shRNAs and screened the most effective interference RNA fragment with a knockdown efficiency of 72%. Porcine embryonic fibroblasts stably transfected with pGenesil-shRNA vector were used as donor cells for nuclear transfer and there was no significant difference of embryo development compared with the control group. Moreover, VHL was efficiently knocked-down with efficiency of 71% in porcine cloned blastocyst, these results lay a solid foundation for constructing the VHL knock-down model of pig.
Animals ; Cloning, Molecular ; Disease Models, Animal ; Embryo, Mammalian ; Gene Knockdown Techniques ; Swine ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

Objective The aims of this study were to analyze the clinical characteristics and laboratory test results of stageⅣ lung cancer patients with Pulmonary thromboembolism(PTE),and to find out the risk factors for pulmonary thromboembolism. Methods A total of 70 patients with stage IV lung cancer were selected from the First Affiliated Hospital of Nan Chang University from January 2011 to October 2017. Blood routine,blood biochemistry,coagulation function,tumor markers(CEA,CA199,CA125, NSE,Cyfra211)and multi-slice spiral CT pulmonary angiography(CTPA)were collected in these patients. Univariate analysis was applied to compare the clinical features and laboratory tests between PTE and non-PTE groups. Multivariate logistic regression analy-sis was applied to explore significant risk factors of PTE. Results Univariate analysis showed that serum albumin,blood leukocyte, neutrophil percentage,increased Cyfra211 and abnormal tumor markers were risk factors for PTE in patients with stage IV lung canc-er. Multivariate logistic regression analysis showed that the number of abnormal tumor markers ≥4(OR=7. 016,95% CI:1. 916 ~25. 686)was an independent risk factor for PTE in stage IV lung cancer. Conclusion The number of abnormal tumor markers is an independent risk factor for pulmonary thromboembolism in stageⅣlung cancer. When the number of abnormal tumor markers is≥4, it is necessary to highly alert the possibility of stage IV lung cancer with pulmonary thromboembolism.

Objective:To investigate the efficacy and safety of prednisone combined with standard quadruple antituberculosis therapy (HRZE) in the treatment of tuberculous pleurisy.Methods:A prospective study was conducted involving 120 patients with tuberculous pleurisy who were admitted to the Shaanxi Provincial Tuberculosis Prevention and Control Hospital from February 2021 to February 2023. The patients were randomly assigned to a study group and a control group, with 60 patients in each group, using a computer-generated randomization method. The control group received HRZE alone, while the study group received prednisone therapy and HRZE. The efficacy, clinical indicators, adverse reactions, and serum inflammatory factor levels were compared between the two groups.Results:The total response rate in the study group was significantly higher than that in the control group [93.33% (56/60) vs. 78.33% (47/60), χ2 = 5.55, P < 0.05). In the study group, the time for clinical symptom improvement was (10.34 ± 1.65) days, the time for pleural effusion absorption was (21.37 ± 4.16) days, the pleural thickness measured (2.15 ± 0.35) mm, and the duration of hospitalization was (23.19 ± 4.56) days. They were significantly shorter or smaller than those in the control group [(13.27 ± 2.30) days, (27.25 ± 4.95) days, (2.62 ± 0.40) mm, (28.42 ± 5.60) days, t = 8.02, 7.04, 6.85, 5.61, all P < 0.05]. There was no significant difference in the incidence of adverse reactions between the two groups (χ2 = 2.91, P > 0.05). After 8 weeks of treatment, all serum inflammatory factors improved in both groups compared with baseline levels. In the study group, levels of interleukin-6 [(90.37 ± 12.05) ng/L] and interleukin-18 [(270.94 ± 14.58) ng/L] were significantly lower than those in the control group [(110.59 ± 16.90) ng/L, (296.10 ± 25.29) ng/L, t = 7.55, 6.68, both P < 0.05]. Levels of interleukin-10 [(78.91 ± 8.25) ng/L] and soluble interleukin-2 receptor [(1875.82 ± 359.23) pg/L] in the study group were significantly higher than those in the control group [(70.40 ± 7.16) ng/L, (1566.87 ± 311.02) pg/L, t = -6.03, -5.04, both P < 0.05]. Conclusion:The combination of prednisone and HRZE demonstrates good efficacy and safety, and it is beneficial for improving inflammatory factors.

Objective To detect the serum levels of CC chemokine receptor 2(CCR2)and C-reactive pro-tein(CRP)in stroke patients,and analyze their relationship with the severity of stroke associated pneumonia and their clinical significance.Methods A total of 78 patients with stroke associated pneumonia who were di-agnosed and treated in the hospital from October 2022 to February 2023 were collected as the study group,ac-cording to the severity of pneumonia,the study group was divided into mild group(31 cases),moderate group(29 cases),and severe group(18 cases),78 stroke patients who did not develop pneumonia were included into control group.Pearson method was applied to analyze the correlation between serum CCR2 and CRP levels in stroke associated pneumonia patients.Multivariate Logistic regression was applied to analyze the factors influ-encing the occurrence of stroke associated pneumonia.Receiver operating characteristic(ROC)curve was ap-plied to analyze the diagnostic value of serum CCR2 and CRP for stroke associated pneumonia.Results The National Institute of Health stroke scale(NIHSS)score,serum CCR2,and CRP levels in the study group were obviously higher than those in the control group(P<0.05).The levels of serum CCR2 and CRP increased with the aggravation of pneumonia(P<0.05).The levels of serum CCR2 and CRP in the study group were positively correlated(r=0.799,P<0.05).NIHSS score,CCR2,and CRP levels were risk factors for stroke associated pneumonia in stroke patients(P<0.05).The area under the curve(AUC)for the diagnosis of stroke associated pneumonia using serum CCR2 and CRP alone was 0.873 and 0.888,respectively,and the AUC for the combined detection of the two was 0.936,the combined detection of the two was superior to the individual detection of serum CCR2 and CRP(Zcombination-CCR2=1.987,Zcombination-CRP=1.832,P=0.041,0.047).Conclusion Serum CCR2 and CRP are closely related to the severity of stroke associated pneumonia,and their combined detection has high diagnostic value for stroke associated pneumonia.

BACKGROUND:Previous studies have confirmed that the new compound cottonrose hibiscus leaf gel plaster has a good effect in the treatment of acute soft tissue swelling. OBJECTIVE:To observe the clinical efficacy of compound cottonrose hibiscus leaf gel plaster in the treatment of synovitis of the knee joint. METHODS:Seventy-two patients with knee synovitis were selected from Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2019 to May 2021.These patients were randomly divided into a trial group and a control group,with 36 cases in each group.The trial group was treated with compound cottonrose hibiscus leaf gel plaster,once a day,12 hours each time,while the control group was treated with Diclofenac Diethylamine Emulgel,twice a day.After 28 days of treatment,visual analog scale score,WOMAC Osteoarthritis Index score,quality of life score(SF-36),thickness of knee synovium and comprehensive curative effect were compared between the two groups. RESULTS AND CONCLUSION:(1)Visual analog scale scores after treatment were lower than those before treatment(P<0.05).Visual analog scale scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).The WOMAC Osteoarthritis Index scores of the two groups after treatment were lower than those before treatment(P<0.05),and the WOMAC Osteoarthritis Index scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).(3)The SF-36 quality of life score in the two groups after 28 days of treatment was higher than that before treatment(P<0.05).SF-36 quality of life score in the trial group after 28 days of treatment was higher than that in the control group(P<0.05).(4)After 28 days of treatment,the thickness of knee synovium in the trial group was less than that in the control group(P<0.05),and the effective rate in the trial group was higher than that in the control group(P<0.05).(5)These findings indicate that compared with Diclofenac Diethylamine Emulgel,the compound cottonrose hibiscus leaf gel plaster can better relieve knee pain,enhance knee joint function,reduce synovial hyperplasia,and elevate the overall quality of life of patients.

Objective To investigate the diagnostic value of serum soluble fms-like tyrosine kinase 1(sFlt-1)and soluble differentiation cluster 14(sCD14)in stroke-associated pneumonia(SAP).Methods A total of 67 SAP patients admitted to the hospital from March 2022 to January 2023 were selected as the study group,and 50 stroke patients without pneumonia during the same period were selected as the control group.Enzyme-linked immunosorbent assay was used to measure serum sFlt-1 and sCD14 levels.Pearson correlation analysis was used to analyze the correlation between serum sFlt-1,sCD14 levels and clinical data.Multivariate Logistic regression was used to analyze the influencing factors of SAP in patients with stroke.Receiver operating char-acteristic(ROC)curve was used to analyze the diagnostic value of serum sFlt-1 and sCD14 levels in predicting SAP in patients with stroke.Results The serum levels of sFlt-1 and sCD14 in SAP patients were higher than those in stroke patients without pneumonia and stroke patients with pneumonia alone(P＜0.05).SAP in stroke patients was associated with age,atrial fibrillation,heart failure,aspiration,dysphagia,brain stem stroke,proton pump inhibitor use,fever,cough,dyspnea,low-density lipoprotein cholesterol,procalcitonin(PCT),C-reactive protein,white blood cell count,national institutes of health stroke scale(NIHSS)score,clinical pulmonary infection(CPIS)score(P＜0.05).Correlation analysis showed that serum sFlt-1 level was positively correlated with sCD14(r=0.439,P＜0.001),and serum sFlt-1 and sCD14 levels were positively correlated with NIHSS score and CPIS score(P＜0.05).Multivariate Logistic regression analysis showed that sFlt-1,sCD14,proton pump inhibitor use,PCT,dysphagia,and age were the influencing factors of SAP in stroke patients(P＜0.05).ROC curve results showed that the area under the curve of serum sFlt-1 and sCD14 combined to evaluate SAP in stroke patients was higher than that of single detection(ZsFlt-1-combined=2.194,P=0.028,ZscD14-combined=2.310,P=0.002).Conclusion The serum levels of sFlt-1 and sCD14 are in-creased in SAP patients,and the combination of the two has a good diagnostic value for predicting the occur-rence of SAP.

Objective:To explore the causal relationship between gut microbiota and lung function (FEV1/FVC) using two-sample Mendelian randomization method; To explore its application in the TCM field.Methods:This was a Mendelian randomization study. The GWAS data of gut microbiota from the MiBioGen consortium study and the GWAS data of lung function (FEV1/FVC) published by IEU OpenGWAS in the public database were used, and instrumental variables were extracted according to prespecified thresholds. The inverse variance weighted method (IVW) was mainly used for analysis. The results were evaluated according to the effect indicator β value and 95% CI. When the IVW method was statistically significant, further sensitivity analysis was performed. Leave-one-out test, heterogeneity test, horizontal gene pleiotropy test and MR-Egger regression intercept analysis were used to verify the stability and reliability of the results. Results:A total of 10 causal relationships between gut microbiota and lung function (FEV1/FVC) were determined using the IVW method: family. BacteroidalesS24.7group ( β=-0.029, P=0.015), family. ClostridialesvadinBB60group ( β=-0.028, P=0.040), family. Streptococcaceae ( β=-0.056, P=0.042), genus. LachnospiraceaeFCS020group ( β=0.025, P=0.029), genus. Lactococcus ( β=-0.024, P=0.038), genus. Peptococcus ( β=0.025, P=0.049), genus. RuminococcaceaeUCG011 ( β=-0.030, P=0.038), genus. Ruminococcus2 ( β=0.028, P=0.033), genus. Terrisporobacter ( β=-0.030, P=0.018), phylum. Cyanobacteria ( β=0.027, P=0.039). Leave-one-out analysis showed that the results were stable, and the effects of heterogeneity and horizontal gene pleiotropy on causal effect estimation could be removed. Conclusion:The gut microbiota may play a role in the changes of lung function, which to a certain extent confirms the TCM theory of "exterior-interior relationship between the lung and large intestine", and can provide certain reference for the research direction of TCM.

Objective:To investigate the expression and significance of Nek2B and β-catenin expression in triple negative breast cancer (TNBC) at molecule levels.Methods:By using the methods of bioinformatics [GEO2R online tool, gene ontology (GO) function analysis, KEGG biological pathway enrichment analysis], the differentially expressed genes were screened from TNBC microarray data.Expression levels of Nek2B and β-catenin TNBC cell lines were detected by Western blot and qRT-PCR.From January 1, 2007 to December 31, 2012, eighty cases of TNBC were collected from the Second Hospital of Shanxi Medical University. The expression of Nek2B in TNBC tumor tissue was detected by immunohistochemistry and tissue microarray, and the relationship between Nek2B and clinical pathological characteristics of TNBC was analyzed.Results:Through bioinformatics analysis of the cDNA chip sets of 2 TNBC tumors(GSE38959,GSE27447), 998 differentially expressed genes were obtained in the initial screening, and 13 differentially expressed genes were revealed after intersection. The results of biological pathway analysis showed that the common differential expression genes were closely related to Wnt/β-catenin pathway, among which Nek2 expression showed the greatest difference and was associated with poor prognosis. Expression intensity of Nek2B and repeated β-catenin in the same TNBC cell line was consistent.The results of immunohistochemistry showed that the high expression of Nek2B was related to the high histological stage (G3;84.3% vs.37.9%, P<0.001), lymph node metastasis group (76.7% vs.54.1%, P=0.032), high Ki-67 positive index group (78.6% vs.52.6%, P=0.007) and β-catenin positive expression group (72.5% vs.27.3%, P=0.018). Conclusions:The high level of Nek2B expression is related to a poor prognosis in TNBC patients. In TNBC tissues and cells, the expression of Nek2B is correlated with β-catenin, suggesting that Nek2B may affect the occurrence and development of TNBC by regulating the Wnt/β-catenin patients signaling pathway.