Objective To explore the short-term and long-term efficacy of partial splenic artery embolization(PSE)in the treat-ment of cirrhosis with hypersplenism.Methods A retrospective analysis was conducted on 35 patients with cirrhosis and hyper-splenism who underwent PSE treatment.Data on white blood cell(WBC),red blood cell(RBC),platelet count(PLT),hemoglobin(HGB),total bilirubin(TBiL),albumin(ALB),prothrombin time(PT),and D-dimer were collected at the three time points:before surgery,1 week after surgery,and 1 year after surgery.The changes in these parameters across the three time points were observed and compared.One-way ANOVA was used for repeated measurements,and time pairwise comparisons were made between the three time points.According to the formation of portal thrombosis,patients were divided into thrombus group and no-thrombus group.The D-dimer values were compared before surgery and 1 week after surgery.Results WBC and PLT were significantly higher 1 week and 1 year after surgery than those before surgery,with the most significant increase 1 week after surgery,and there was also statistically sig-nificant difference between 1 week after surgery and 1 year after surgery(P1,P2,P3<0.05).There were no significant differences in RBC and HGB between 1 week after surgery and before surgery(RBC P1=0.835,HGB P1=0.446).However,RBC and HGB 1 year after surgery were significantly higher than those before surgery and 1 week after surgery(RBC P2=0.039,P3=0.015;HGB P2=0.001,P3=0.010).There were significant differences in TBiL,ALB,PT,and D-dimer 1 week after surgery compared with those before surgery(TBiL P1=0.006,ALB P1<0.001,PT P1=0.001,D-dimer P1<0.001),but there was no significant differ-ence between 1 year after surgery and before surgery(all P2>0.05).The D-dimer of the thrombus group was significantly higher than that of the no-thrombus group 1 week after surgery,with a statistical significance(P=0.024),however,there was no signifi-cant difference in D-dimer between the two groups before surgery.Conclusion PSE in the treatment of cirrhosis with hypersplenism shows positive short-term and long-term efficacy for WBC and PLT.The short-term increase of RBC and HGB is not obvious,however the long-term efficacy is significant.In the short-term after surgery,TBiL increase,ALB decrease,PT prolonge,and liver reserve function decrease,but there was no long-term effect.The increase of D-dimer after surgery can easily induce portal thrombosis,and anticoagulation therapy can be given in the short-term after surgery.

Objective To investigate the risk factors of overt hepatic encephalopathy(OHE)and death in cirrhotic portal hyperten-sion patients after transjugular intrahepatic portosystemic shunt(TIPS).Methods A retrospective selection was conducted on 40 patients with cirrhotic portal hypertension who underwent TIPS.The follow-up time was 3-41 months,median follow-up time was 20.36 months.The postoperative hepatic encephalopathy(HE)were divided into OHE group(20 cases)and non-OHE group(20 cases)and were further divided into death group(11 cases)and survival group(29 cases)according to their postoperative survival status.Gender,age,preoperative height,weight,total bilirubin,albumin,alanine aminotransferase,aspartate aminotransferase,creatinine,international normalized ratio(INR),prothrombin time,blood glucose,white blood cells,hemoglobin and platelet of all patients were recorded in detail,as well as whether they had diabetes and portal thrombosis before surgery.Child score and model for end-stage liver disease(MELD)score were also performed.The related risk factors of HE and death were obtained by statistical analysis of the two groups.Results The incidence rate of OHE after TIPS was 50%.The analysis revealed that age[hazard ratio(HR)1.115,95%confidence interval(CI)1.007-1.234,P=0.036]and albumin(HR 0.776,95%CI 0.627-0.960,P=0.020)were independent risk factors for OHE after TIPS.The receiver operating characteristic(ROC)curves were drawn with area under the curve(AUC)of 0.733 for age and AUC of 0.784 for albumin.The mortality rate after TIPS was 27.5%,and the analysis indicated that albumin(HR 0.660,95%CI 0.453-0.961,P=0.030),creatinine(HR 1.031,95%CI 1.001-1.062,P=0.044),and aspartate aminotransferase(HR 1.074,95%CI 1.013-1.139,P=0.018)were independent risk factors for death after TIPS.The ROC curves were drawn with AUC of 0.716 for albumin,AUC of 0.762 for creatinine,and AUC of 0.710 for aspartate aminotransferase.Conclusion Postoperative OHE is posi-tively correlated with age and negatively correlated with albumin.Furthermore,the risk of postoperative death is positively correlated with creatinine and aspartate aminotransferase and negatively correlated with albumin.

Objective To explore the short-term and long-term efficacy of partial splenic artery embolization(PSE)in the treat-ment of cirrhosis with hypersplenism.Methods A retrospective analysis was conducted on 35 patients with cirrhosis and hyper-splenism who underwent PSE treatment.Data on white blood cell(WBC),red blood cell(RBC),platelet count(PLT),hemoglobin(HGB),total bilirubin(TBiL),albumin(ALB),prothrombin time(PT),and D-dimer were collected at the three time points:before surgery,1 week after surgery,and 1 year after surgery.The changes in these parameters across the three time points were observed and compared.One-way ANOVA was used for repeated measurements,and time pairwise comparisons were made between the three time points.According to the formation of portal thrombosis,patients were divided into thrombus group and no-thrombus group.The D-dimer values were compared before surgery and 1 week after surgery.Results WBC and PLT were significantly higher 1 week and 1 year after surgery than those before surgery,with the most significant increase 1 week after surgery,and there was also statistically sig-nificant difference between 1 week after surgery and 1 year after surgery(P1,P2,P3<0.05).There were no significant differences in RBC and HGB between 1 week after surgery and before surgery(RBC P1=0.835,HGB P1=0.446).However,RBC and HGB 1 year after surgery were significantly higher than those before surgery and 1 week after surgery(RBC P2=0.039,P3=0.015;HGB P2=0.001,P3=0.010).There were significant differences in TBiL,ALB,PT,and D-dimer 1 week after surgery compared with those before surgery(TBiL P1=0.006,ALB P1<0.001,PT P1=0.001,D-dimer P1<0.001),but there was no significant differ-ence between 1 year after surgery and before surgery(all P2>0.05).The D-dimer of the thrombus group was significantly higher than that of the no-thrombus group 1 week after surgery,with a statistical significance(P=0.024),however,there was no signifi-cant difference in D-dimer between the two groups before surgery.Conclusion PSE in the treatment of cirrhosis with hypersplenism shows positive short-term and long-term efficacy for WBC and PLT.The short-term increase of RBC and HGB is not obvious,however the long-term efficacy is significant.In the short-term after surgery,TBiL increase,ALB decrease,PT prolonge,and liver reserve function decrease,but there was no long-term effect.The increase of D-dimer after surgery can easily induce portal thrombosis,and anticoagulation therapy can be given in the short-term after surgery.

Objective To investigate the risk factors of overt hepatic encephalopathy(OHE)and death in cirrhotic portal hyperten-sion patients after transjugular intrahepatic portosystemic shunt(TIPS).Methods A retrospective selection was conducted on 40 patients with cirrhotic portal hypertension who underwent TIPS.The follow-up time was 3-41 months,median follow-up time was 20.36 months.The postoperative hepatic encephalopathy(HE)were divided into OHE group(20 cases)and non-OHE group(20 cases)and were further divided into death group(11 cases)and survival group(29 cases)according to their postoperative survival status.Gender,age,preoperative height,weight,total bilirubin,albumin,alanine aminotransferase,aspartate aminotransferase,creatinine,international normalized ratio(INR),prothrombin time,blood glucose,white blood cells,hemoglobin and platelet of all patients were recorded in detail,as well as whether they had diabetes and portal thrombosis before surgery.Child score and model for end-stage liver disease(MELD)score were also performed.The related risk factors of HE and death were obtained by statistical analysis of the two groups.Results The incidence rate of OHE after TIPS was 50%.The analysis revealed that age[hazard ratio(HR)1.115,95%confidence interval(CI)1.007-1.234,P=0.036]and albumin(HR 0.776,95%CI 0.627-0.960,P=0.020)were independent risk factors for OHE after TIPS.The receiver operating characteristic(ROC)curves were drawn with area under the curve(AUC)of 0.733 for age and AUC of 0.784 for albumin.The mortality rate after TIPS was 27.5%,and the analysis indicated that albumin(HR 0.660,95%CI 0.453-0.961,P=0.030),creatinine(HR 1.031,95%CI 1.001-1.062,P=0.044),and aspartate aminotransferase(HR 1.074,95%CI 1.013-1.139,P=0.018)were independent risk factors for death after TIPS.The ROC curves were drawn with AUC of 0.716 for albumin,AUC of 0.762 for creatinine,and AUC of 0.710 for aspartate aminotransferase.Conclusion Postoperative OHE is posi-tively correlated with age and negatively correlated with albumin.Furthermore,the risk of postoperative death is positively correlated with creatinine and aspartate aminotransferase and negatively correlated with albumin.

ObjectiveOur recent study has demonstrated that extracellular acidification promotes lipid accumulation in macrophages via the activation of acid sensing ion channel 1 (ASIC1), but the underlying mechanism remains unclear. This study aims to explore the effect of extracellular acidification on macrophage lipophagy and the underlying mechanism. MethodsRAW264.7 macrophages were incubated with 25 mg/Lox-LDL in a pH 6.5 culture medium for 24 h to build macrophage-derived foam cell models induced by extracellular acidification. Then, RAW264.7 macrophages were cultured in the acidic medium of pH 6.5 with or without PcTx-1 (ASIC1 specific blocker, 10 μg/L) or Nec-1 (RIP1 specific inhibitor, 20 μmol/L) for 24 h, intracellular lipid accumulation was observed by oil red O staining. The expressions of total ASIC1, plasma membrane ASIC1, RIP1, p-RIP1 Ser166, TFEB, p-TFEB Ser142, LC3 and p62 were measured by Western blot. The co-localization of lipids (indicated by Bodipy) with LC3II (autophagosomes) and LAMP1 (lysosomes) was analyzed by a confocal laser scanning microscopy, respectively. Morphological changes of lipophagy in the cells were observed by using transmission electron microscopy. ABCA1-mediated cholesterol efflux was determined by cholesterol fluorescence kits. ResultsCompared with pH 7.4+ox-LDL group, the intracellular lipid accumulation in the pH 6.5+ox-LDL group was significantly increased. Meanwhile, the expressions of plasma membrane ASIC1, p-RIP1 Ser166, p-TFEB Ser142, and p62 proteins were elevated significantly, while LC3II protein level and LC3II/LC3I ratio were decreased. Accordingly, compared with pH 7.4+ox-LDL group, the macrophage lipophagy of the pH 6.5+ox-LDL group was inhibited as indicated by the decreased localization of lipid droplets with LC3 and LAMP1, a decrease in the number of lipophagosomes as well as an increase in lipid droplets. Furthermore, ATP binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux from the macrophages of pH 6.5+ox-LDL group reduced dramatically. However, these above effects of extracellular acidification on RAW264.7 macrophages were abolished by PcTx-1 and Nec-1, respectively. ConclusionThese findings suggest extracellular acidification promotes the phosphorylation of TFEB at Ser142 via activating ASIC1/RIP1 pathway, thereby impeding lipophagy in RAW 264.7 macrophages, and that ASIC1 may be a new potential target for preventing aberrant lipid accumulation diseases including atherosclerosis.

AIM To investigate the ameliorative effects of Schisandrol A(Sol A)in Suhuang antitussive capsule on post-infectious cough(PIC).METHODS The in vivo mouse PIC model was established by intratracheal instillation of lipopolysaccharide(LPS)combined with cigarette smoke exposure.The mice were randomly divided into the control group,the model group,the Suhuang antitussive capsule group(14 g/kg),the montelukast sodium positive control group(3 mg/kg),and low and high dose Sol A groups(10,30 mg/kg).The in vitro PIC model was established by stimulating human bronchial epithelial cells(BEAS-2B)with LPS.The cells were divided into the control group,the model group,the Suhuang antitussive capsule group(10 μg/mL)and low and high dose Sol A groups(3,10 μmol/L).HE and Masson staining were used to detect the pathological changes of the lung and bronchial tissues.ELISA was used to detect the levels of IL-1β,IL-6,TNF-α,ROS,MDA,SOD and GSH in the lung tissues.RT-qPCR was used to detect the IL-1β,IL-6 and TNF-α mRNA expressions in BEAS-2B cells.And Western blot was applied to detect the protein expressions of p-PI3K,p-Akt,NOX4,SIRT1,p-ERK,Fibronectin,E-cadherin,Vimentin and α-SMA in mouse lung tissue and BEAS-2B cells.RESULTS Compared with the model group,the groups intervened with Sol A or Suhuang antitussive capsule displayed prolonged cough latency(P＜0.01);reduced cough frequency(P＜0.01);relieved pulmonary inflammatory cell infiltration and collagen deposition in PIC mice;decreased pulmonary levels of IL-1β,IL-6,TNF-α,ROS,MDA and protein expressions of Fibronectin,Vimentin,α-SMA,p-ERK,p-PI3K,p-Akt,and NOX4(P＜0.05,P＜0.01);increased pulmonary levels of SOD and GSH and protein expressions of E-cadherin and SIRT1(P＜0.05,P＜0.01);decreased ROS level,IL-1β,IL-6,TNF-α mRNA expressions and p-ERK,p-PI3K,p-Akt,NOX4 protein expressions in vitro(P＜0.05,P＜0.01);and increased SIRT1 protein expression in vitro as well(P＜0.01).CONCLUSION Being the main antitussive component of Suhuang antitussive capsule upon the PIC model,Sol A inhibits the inflammation via SIRT1/ERK signaling pathway and relieve the oxidative stress via PI3K/Akt/NOX4 signaling pathway.

AIM To explore the effects of praeruptorin A from Suhuang antitussive capsules on cough variant asthma(CVA).METHODS The rats were randomly divided into the normal group,the model group,the dexamethasone group(0.5 mg/kg),the Suhuang antitussive capsules group(7 g/kg)and the low,medium and high dose praeruptorin A groups(15,30 and 60 mg/kg).The rat model of CVA was established by intraperitoneal injection of sensitizer(1 mg/mL ovalbumin and 10 mg/mL aluminum hydroxide)and aerosol inhalation of 1%ovalbumin followed by the corresponding dosing of drugs by gavage initiated on the 14th day.Another 14 days later,the rats had their pathological pulmonary changes observed by HE,Masson and PAS stainings;their number of inflammatory cells in bronchoalveolar lavage fluid(BALF)detected by hematology analyzer;and their levels of IL-4,IL-5,IL-13 and MUC5AC in BALF detected by ELISA.The RAW264.7 cell inflammatory model induced by lipopolysaccharide(LPS)was treated with 4,8,16 μmol/L praeruptorin A or 0.25 mg/mL Suhuang antitussive capsules,respectively.And the cells had their NO level detected by Griess method,and their ROS expression observed using fluorescence microscopy.The detections of the pulmonary and cellular mRNA expressions of IL-6,IL-1β,COX-2,iNOS and PPAR-γ by RT-qPCR;and the protein expressions of p-P65,P65,p-IκBα,IκBα,NLRP3,caspase-1(p20)and IL-1β by Western blot were conducted in both the cells and the rats.RESULTS The in vivo result showed that praeruptorin A reduced the cough frequency(P＜0.01);prolonged the cough latency(P＜0.05,P＜0.01);reduced the number of eosinophils and neutrophils in BALF(P＜0.05,P＜0.01);decreased the levels of IL-4,IL-5,IL-13 and MUC5AC in BALF and the pulmonary mRNA expressions of IL-6,IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);and decreased the phosphorylation of P65 and IκBα protein and NLRP3,caspase-1(p20)and IL-1β protein expressions(P＜0.05,P＜0.01)as well.The in vitro result showed that praeruptorin A inhibited the release of LPS-induced NO and reduce the ROS level(P＜0.01);decreased the mRNA expressions of IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);increased PPAR-γ mRNA expression(P＜0.05),and decreased the phosphorylation of P65 and IκBα protein and the expression of NLRP3 protein(P＜0.05,P＜0.01).CONCLUSION Praeruptorin A,one of the main antitussive components of Suhuang antitussive capsules,may improve CVA because of its anti-inflammatory and antitussive role by inhibiting the activation of NF-κB signaling pathway and reducing the expression of NLRP3 inflammatory corpuscles.

Objective:To understand the current status of the use of aspirin in perioperative period of thoracic surgery in China and the awareness of thoracic surgeons on the prevention and treatment of arterial thromboembolic diseases during the perioperative period.Methods:A survey was conducted among thoracic surgeons nationwide using an electronic questionnaire through a software platform from January 20, 2024 to February 29, 2024. The questionnaire mainly included three parts: basic information, aspirin use, and awareness of arterial thromboembolic diseases, with a total of 27 questions.Results:A total of 1318 valid questionnaires were collected, covering all 33 provincial administrative regions except Taiwan. 69.7%(919/1 318) of thoracic surgeons stopped using aspirin for all patients before surgery; differences could be found in the timing of aspirin withdrawal before surgery and resumption after surgery. 65.1%(858/1 318) of surgeons made perioperative medication decisions based on domestic guidelines or consensus, while 20.9%(276/1 318) of surgeons based their decisions on departmental or personal experience. 87.9%(1 159/1 318) of surgeons believed that it is necessary to develop guidelines for the prevention of arterial thromboembolic diseases in the perioperative period of thoracic surgery.Conclusion:The current use strategy of aspirin in the perioperative period of thoracic surgery in China shows a high degree of inconsistency, and there are also significant differences in the awareness of arterial thromboembolic diseases. It is necessary to establish guidelines for the prevention and treatment of arterial thromboembolic diseases in the perioperative period.

Objective:To investigate the predictive value of pregnancy-associated plasma protein A(PAPP-A),fasting blood glucose(FPG),body mass index(BMI)and age in gestational diabetes mellitus(GDM)during the first trimester.Methods:A retrospective analysis was performed on 792 pregnant women who underwent pre-natal examination and delivered in Sichuan Provincial Maternal and Child Health Care Hospital from December 2021 to June 2022.They were divided into GDM group(232 cases)and control group(560 cases)according to whether they had GDM.The clinical data,serum PAPP-A median multiple(PAPP-A MoM)in early pregnancy and FPG levels were compared between the two groups.The indicators with statistical significance in univariate analy-sis were included in multivariate Logistic regression analysis to analyze the related factors affecting the occurrence of GDM.The receiver operating curve(ROC)and area under the curve(AUC)of different indexes were plotted to compare the efficacy of GDM prediction.Results:①The age,pre pregnancy BMI,early pregnancy FPG and the proportion of assisted reproductive technology in GDM group were higher than those in control group,and the differences were statistically significant(P＜0.05).The early pregnancy PAPP-A MoM level in GDM group was lower than that in control group,and the difference was statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that older age,lager pre-pregnancy BMI and lager FPG in the first trimester were in-dependent risk factors for GDM occurrence(OR＞1,P＜0.05),while an increase of PAPP-A MoM in the first tri-mester was a protective factor(OR＜1,P＜0.05).③ROC showed that the combination of PAPP-A MoM in early pregnancy,FPG in early pregnancy,BMI in pre-pregnancy and age had the highest AUC(0.752)when predicting GDM,with a sensitivity of 55.6％and a specificity of 84.3％.Conclusions:The combined screening of serologi-cal(PAPP-A +FPG)and clinical data(pre-pregnancy BMI +age)in early pregnancy has a high clinical application prospect and can be popularized.

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.