Objective:To investigate the efficacy of laparoscopic versus open hepatectomy for intrahepatic bile duct stones based on propensity score matching. Methods:This study used a case-control design to retrospectively analyze 163 patients with intrahepatic bile duct stones who were treated at The Second Hospital of Anhui Medical University between February 2014 and February 2024. Based on the surgical approach, the patients were divided into two groups: the laparoscopic hepatectomy group ( n = 72) and the open hepatectomy group ( n = 91). Using 1:1 PSM, two groups with similar baseline clinical characteristics were created to compare perioperative outcomes, stone residual rates, and recurrence rates. Results:After PSM, a total of 52 matched pairs were successfully obtained. Compared with the laparoscopic hepatectomy group, the open hepatectomy group demonstrated a significantly shorter operative time [233.00 (180.00, 315.00) minutes vs. 313.00 (222.25, 405.75) minutes, Z = 3.41, P = 0.01]. However, no statistically significant differences were observed between the open hepatectomy and laparoscopic hepatectomy groups in terms of pre- to postoperative hemoglobin change [(22.69 ± 14.27) g/L vs. (20.63 ± 14.36) g/L, t = 0.73, P = 0.465], postoperative bile leakage [5.77% (3/52) vs. 11.54% (6/52), χ2 = 1.10, P = 0.25], hypoalbuminemia [82.69% (43/52) vs. 84.62% (44/52), χ2 = 0.07, P = 0.791], pulmonary infection [28.85% (15/52) vs. 40.38% (21/52), χ2 = 1.53, P = 0.216], surgical site infection [5.77% (3/52) vs. 1.92% (1/52), χ2 = 1.04, P = 0.308], intra-abdominal infection [1.92% (1/52) vs. 5.77% (3/52), χ2 = 1.04, P = 0.308], postoperative drainage tube removal time [8.00 (6.00, 11.75) days vs. 8.00 (6.25, 10.00) days, t = 0.05, P = 0.958], postoperative hospital stay [8.00 (9.00, 15.00) days vs. 9.00 (7.00, 12.50) days, t = -1.22, P = 0.222], residual stone rate [11.54% (6/52) vs. 9.62% (5/52), χ2 = 0.10, P = 0.750], and stone recurrence rate [13.46% (7/52) vs. 3.85% (2/52), χ2 = 3.04, P = 0.081]. All differences were statistically significant (all P > 0.05). Conclusions:Laparoscopic hepatectomy and open hepatectomy have comparable efficacy in the treatment of intrahepatic bile duct stones.

Acute lung injury(ALI)is a common critical illness caused by intrapulmonary or extra-pulmonary factors,which is accompanied by ex-tremely high morbidity and mortality.Its pathogen-esis is extremely complex and difficult to treat.Src homology 2 domain-containing protein tyrosine phosphatase(Shp2),a key cellular signal transduc-tion molecule,plays a pivotal role in the pathophys-iological processes of diverse diseases.Notably,in the context of pathogen infection,Shp2 regulates the functionality of cellular immunity,lung epitheli-al cells,and vascular endothelial cells.This review article highlights the significant role of Shp2 in the onset and progression of ALI,emphasizing its regu-lation of inflammatory response,apoptosis,and ox-idative stress.Shp2 could emerge as a novel thera-peutic target for ALI,offering valuable insights for the development of innovative drug candidates to treat this debilitating condition.

Objective To investigate the influencing factors for the short-term prognosis of patients with alcohol-related liver diseases-acute-on-chronic liver failure(ALD-ACLF)comorbid with infection.Methods A total of 89 ALD-ACLF patients with infection who were admitted to the Fifth Medical Center of PLA General Hospital from January 2019 to December 2021 were enrolled as subjects,and related clinical data were collected at baseline(time of patient enrollment).According to the 28-day survival status of patients,they were divided into survival group with 53 patients and death group with 36 patients,and baseline clinical data were compared between the two groups.The t-test was used for comparison of normally distributed continuous data between groups,and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups.A non-conditional Logistic regression analysis was used to perform the multivariate analysis.The Z-test was used for comparison of the area under the ROC curve(AUC),and the diagnostic value of the model was assessed.Results Compared with the survival group,the death group had significantly higher hemoglobin(t=-2.397,P=0.019),alanine aminotransferase(Z=-3.437,P=0.001),gamma-glutamyl transpeptidase(Z=-2.617,P=0.009),creatinine(Z=-3.938,P<0.001),blood urea nitrogen(Z=-3.423,P=0.001),NH3(Z=-4.406,P<0.001),international normalized ratio(Z=-3.428,P=0.001),C-reactive protein(Z=-2.128,P=0.033),procalcitonin(Z=-2.441,P=0.015),Model for End-Stage Liver Disease(MELD)score(t=-4.817,P<0.001),incidence rate of acute kidney injury(χ2=21.602,P<0.001),incidence rate of pulmonary infection(χ2=4.866,P=0.027),and incidence rate of shock(χ2=16.285,P<0.001),as well as significantly lower albumin(Z=-2.473,P=0.013)and incidence rate of abdominal infection(χ2=5.897,P=0.015).The multivariate analysis showed that NH3(odds ratio[OR]=1.027,95%confidence interval[CI]:1.006-1.049,P=0.012),MELD score(OR=1.103,95%CI:1.011-1.203,P=0.027],and the incidence rate of shock(OR=6.326,95%CI:1.533-26.101,P=0.011)were independent risk factors for 28-day mortality in ALD-ACLF patients comorbid with infection.Based on these factors,a predictive model was established as Y=0.027×NH3+0.098×MELD score+1.845×shock-4.111.The ROC curve analysis showed that the new model had an AUC of 0.861,a sensitivity of 77.78%,and a specificity of 88.68%,while MELD score had an AUC of 0.776,a sensitivity of 77.78%,and a specificity of 67.92%,suggesting that the new model had a significantly higher diagnostic value than MELD score(Z=2.136,P=0.032 6).Conclusion ALD-ACLF patients with infection tend to have a poor short-term prognosis,and MELD score,NH3,and shock are influencing factors for the short-term prognosis of such patients.The combination of these three factors has a high value in predicting short-term prognosis.

AIM:To investigate the potential mechanisms by which cell division cycle protein 42(Cdc42)regulates endothelial-mesenchymal transition(EndMT)in pulmonary hypertension(PH).METHODS:The pulmonary hypertension(PH)model was established using Sugen-5416 combined with hypoxia.Twenty-four C57BL/6 mice were ran-domly divided into four groups:normoxia control(CON)group,normoxia+ML141(CON+ML141)group,Sugen-5416+hypoxia(SuHx)group,and SuHx+ML141 group,with 6 mice in each group.After 4 weeks,right ventricular systolic pressure(RVSP)and cardiac ultrasound parameters were measured,and lung tissues were collected for immunofluores-cence staining.Pulmonary microvascular endothelial cells(PMVECs)were isolated using magnetic bead sorting.Calcium imaging was performed to assess Ca2+signaling,and Western blot was used to detect EndMT-related proteins as well as stromal interaction molecule 1(STIM1)and Orai1 expression.RESULTS:In the SuHx group,mice exhibited signifi-cantly increased RVSP,Fulton index(right ventricle/left ventricle+septum),end-diastolic right ventricular free wall thick-ness(RVEDWT),and end-systolic right ventricular free wall thickness(RVESWT)(P<0.01).Conversely,pulmonary artery acceleration time/pulmonary artery ejection time(PAT/PET)and tricuspid annulus plane systolic excursion(TAPSE)were significantly reduced(P<0.01).The Cdc42 inhibitor ML141 ameliorated these changes.The SuHx group exhibited a significant decrease in CD31 fluorescence intensity in pulmonary vascular endothelial cells(P<0.01),a marked increase in α-smooth muscle actin(α-SMA)fluorescence intensity in smooth muscle cells(P<0.01),and the emergence of CD31/α-SMA co-localization.These alterations were reversed by ML141.Hypoxia induced EndMT in PM-VECs,characterized by decreased CD31 and vascular endothelial cadherin(VE-cadherin)along with increased α-SMA and vimentin(P<0.01),which was suppressed by ML141(P<0.01).Hypoxia activated store-operated calcium entry(SOCE),enhancing intracellular Ca2? release,extracellular Ca2? influx,and basal Ca2? levels(P<0.01),while upregulat-ing STIM1 and Orai1 expression(P<0.01).These changes were reversed by ML141.Furthermore,both ML141 and STIM1 knockdown inhibited the upregulation of EndMT-related transcription factors Snail and Twist(P<0.05).CON-CLUSION:Cdc42 may participate in EndMT in PH by regulating store-operated calcium channels in pulmonary microvas-cular endothelial cells.

Objective To investigate the application value of systemic inflammatory response index(SIRI)in patients with acute-on-chronic liver failure(ACLF)and co-infection.Methods A retrospective analysis was performed for the clinical data of 579 ACLF patients with co-infection who were diagnosed and treated in The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to March 2016,including demographic features,laboratory markers,and complications,and SIRI,Model for End-Stage Liver Disease(MELD)score,MELD combined with serum sodium concentration(MELD-Na)score,and Child-Pugh score were calculated.According to the results of follow-up on day 90,the patients were divided into survival group with 210 patients and death group with 369 patients.The independent-samples t test was used for comparison of normally distributed continuous data between two groups;the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test were used for comparison of categorical data between two groups.The binary logistic regression analysis was used to investigate the independent risk factors for 90-day death.The receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to assess the performance of SIRI,MELD-Na score,and Child-Pugh score in predicting the prognosis of ACLF patients with co-infection.The Kaplan-Meier survival analysis was performed based on the optimal cut-off value of SIRI.Results Among the 597 ACLF patients with co-infection,384(66.32%)had HBV-related ACLF and 114(19.69%)had alcohol-related ACLF;as for the main infection sites,316(54.58%)had abdominal infection and 133(22.97%)had pulmonary infection;the 90-day mortality rate was 63.73%.The multivariate logistic regression analysis showed that SIRI(odds ratio[OR]=1.177,95%confidence interval[CI]:1.117-1.239,P<0.05),blood ammonia(OR=1.009,95%CI:1.001-1.018,P<0.05),MELD-Na score(OR=1.047,95%CI:1.016-1.080,P<0.05),Child-Pugh score(OR=1.351,95%CI:1.054-1.730,P<0.05),age(OR=1.045,95%CI:1.021-1.070,P<0.05),comorbidity with hepatic encephalopathy(OR=2.269,95%CI:1.305-3.946,P<0.05),and comorbidity with acute kidney injury(OR=1.730,95%CI:0.990-3.023,P<0.05)were independent risk factors for 90-day death in ACLF patients with co-infection.The Pearson correlation analysis showed that SIRI was positively correlated with MELD-Na score(r=0.282,P<0.001)and Child-Pugh score(r=0.168,P<0.001).SIRI,MELD-Na score,and Child-Pugh score had an AUC of 0.855,0.734,and 0.690,respectively,in predicting 90-day death,and SIRI had a higher predictive efficiency than MELD-Na score and Child-Pugh score(Z=4.922 and 6.289,both P<0.001),with a sensitivity of 76.7%and a specificity of 82.9%.In addition,SIRI combined with MELD-Na score or Child-Pugh score improved the predictive efficiency of MELD-Na score(0.854 vs 0.734,Z=6.899,P<0.001)and Child-Pugh score(0.858 vs 0.690,Z=8.725,P<0.001).The patients with high SIRI(≥4.08)had a 90-day survival rate of 11.29%(36/319),which was significantly lower than that in the patients with low SIRI(<4.08)(χ2=225.24,P<0.001).Conclusion SIRI is an independent risk factor for death in ACLF patients with co-infection and has a good clinical value in predicting prognosis,with the advantages of convenience and low costs.

AIM:To investigate the potential mechanisms by which cell division cycle protein 42(Cdc42)regulates endothelial-mesenchymal transition(EndMT)in pulmonary hypertension(PH).METHODS:The pulmonary hypertension(PH)model was established using Sugen-5416 combined with hypoxia.Twenty-four C57BL/6 mice were ran-domly divided into four groups:normoxia control(CON)group,normoxia+ML141(CON+ML141)group,Sugen-5416+hypoxia(SuHx)group,and SuHx+ML141 group,with 6 mice in each group.After 4 weeks,right ventricular systolic pressure(RVSP)and cardiac ultrasound parameters were measured,and lung tissues were collected for immunofluores-cence staining.Pulmonary microvascular endothelial cells(PMVECs)were isolated using magnetic bead sorting.Calcium imaging was performed to assess Ca2+signaling,and Western blot was used to detect EndMT-related proteins as well as stromal interaction molecule 1(STIM1)and Orai1 expression.RESULTS:In the SuHx group,mice exhibited signifi-cantly increased RVSP,Fulton index(right ventricle/left ventricle+septum),end-diastolic right ventricular free wall thick-ness(RVEDWT),and end-systolic right ventricular free wall thickness(RVESWT)(P<0.01).Conversely,pulmonary artery acceleration time/pulmonary artery ejection time(PAT/PET)and tricuspid annulus plane systolic excursion(TAPSE)were significantly reduced(P<0.01).The Cdc42 inhibitor ML141 ameliorated these changes.The SuHx group exhibited a significant decrease in CD31 fluorescence intensity in pulmonary vascular endothelial cells(P<0.01),a marked increase in α-smooth muscle actin(α-SMA)fluorescence intensity in smooth muscle cells(P<0.01),and the emergence of CD31/α-SMA co-localization.These alterations were reversed by ML141.Hypoxia induced EndMT in PM-VECs,characterized by decreased CD31 and vascular endothelial cadherin(VE-cadherin)along with increased α-SMA and vimentin(P<0.01),which was suppressed by ML141(P<0.01).Hypoxia activated store-operated calcium entry(SOCE),enhancing intracellular Ca2? release,extracellular Ca2? influx,and basal Ca2? levels(P<0.01),while upregulat-ing STIM1 and Orai1 expression(P<0.01).These changes were reversed by ML141.Furthermore,both ML141 and STIM1 knockdown inhibited the upregulation of EndMT-related transcription factors Snail and Twist(P<0.05).CON-CLUSION:Cdc42 may participate in EndMT in PH by regulating store-operated calcium channels in pulmonary microvas-cular endothelial cells.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.

Objective:To investigate the impact of the size of the liver tumor diameter on the prognosis of patients with hepatitis B-related hepatocellular carcinoma (HCC)-inducing acute-on-chronic liver failure (HBV-HCC/ACLF).Method:A retrospective cohort study was conducted. Clinical data of patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) diagnosed according to the Asia-Pacific Association for the Study of the Liver (APASLT) guidelines who were admitted to the Fifth Medical Center of PLA General Hospital between January 2016 and January 2021 were collected. The patients were enrolled in the HBV-HCC/ACLF group (116 cases) and the HBV-ACLF group (348 cases). General information, medical history, biochemical parameters, complications, and liver cancer status were collected. Clinical data and prognoses at 28 days and 12 months of follow-up were compared between the two groups. Factors influencing mortality in the HBV-HCC/ACLF group were analyzed to determine the prognostic significance of tumor diameter. The t test, χ 2 test, and multivariate logistic regression analysis were used to analyze factors influencing mortality. Receiver operating characteristic (ROC) curves were used to assess the sensitivity and specificity of tumor diameter for 28-day prognosis, and Kaplan-Meier curves were used for survival analysis. Result:There were statistically significant differences in the 28-day mortality rate [(55.17%, 64/116) vs. (38.51%, 134/348)] and 12-month mortality rate [(78.45%, 91/116) vs. (55.75%, 194/348)] between the HBV-HCC/ACLF group and the HBV-ACLF group ( P<0.05). The area under the ROC curve analysis for HBV-HCC/ACLF patients indicated that the tumor diameter was 0.707 (95% CI: 0.615-0.788). The survival group (52 cases) and the mortality group (64 cases) were divided into the HBV-HCC/ACLF group based on 28-day mortality. Univariate analysis showed that the levels of aspartate aminotransferase (AST), alkaline phosphatase, creatinine, alpha-fetoprotein, white blood cell count, international normalized ratio, model for end-stage liver disease score, acute kidney injury (AKI), the occurrence of infections and complications, and others were all significantly higher in the mortality group compared to the survival group ( P<0.05).The mortality group had a larger tumor diameter than the survival group ( P<0.01). The incidence of portal vein tumor thrombosis and distant liver cancer metastasis was also higher in the survival group ( P<0.01). The mortality group had a higher rate of HCC-related minimally invasive treatment within three months before ACLF diagnosis than the survival group ( P<0.01). AST levels, infection, size of tumor diameter, and minimally invasive treatment within three months before onset were independent risk factors for 28-day mortality in the HBV-HCC/ACLF group. The optimal significant value for tumor diameter affecting prognosis was 3.3 cm, with a sensitivity of 67.19% and a specificity of 73.08%. Patients with liver tumor diameters >3.3 cm had significantly lower 28-day survival rates than those with a tumor diameter ≤3.3 cm [(24.56%, 14/57) vs. (64.41%, 38/59)]. Eighty case analyses had the same findings in patients who had not previously received any therapy. Conclusion:Patients with HBV-HCC/ACLF had a high 28-day mortality rate, and the size of the tumor diameter is important in determining the 28-day prognosis.

Objective To investigate the influencing factors for the short-term prognosis of patients with alcohol-related liver diseases-acute-on-chronic liver failure(ALD-ACLF)comorbid with infection.Methods A total of 89 ALD-ACLF patients with infection who were admitted to the Fifth Medical Center of PLA General Hospital from January 2019 to December 2021 were enrolled as subjects,and related clinical data were collected at baseline(time of patient enrollment).According to the 28-day survival status of patients,they were divided into survival group with 53 patients and death group with 36 patients,and baseline clinical data were compared between the two groups.The t-test was used for comparison of normally distributed continuous data between groups,and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups.A non-conditional Logistic regression analysis was used to perform the multivariate analysis.The Z-test was used for comparison of the area under the ROC curve(AUC),and the diagnostic value of the model was assessed.Results Compared with the survival group,the death group had significantly higher hemoglobin(t=-2.397,P=0.019),alanine aminotransferase(Z=-3.437,P=0.001),gamma-glutamyl transpeptidase(Z=-2.617,P=0.009),creatinine(Z=-3.938,P<0.001),blood urea nitrogen(Z=-3.423,P=0.001),NH3(Z=-4.406,P<0.001),international normalized ratio(Z=-3.428,P=0.001),C-reactive protein(Z=-2.128,P=0.033),procalcitonin(Z=-2.441,P=0.015),Model for End-Stage Liver Disease(MELD)score(t=-4.817,P<0.001),incidence rate of acute kidney injury(χ2=21.602,P<0.001),incidence rate of pulmonary infection(χ2=4.866,P=0.027),and incidence rate of shock(χ2=16.285,P<0.001),as well as significantly lower albumin(Z=-2.473,P=0.013)and incidence rate of abdominal infection(χ2=5.897,P=0.015).The multivariate analysis showed that NH3(odds ratio[OR]=1.027,95%confidence interval[CI]:1.006-1.049,P=0.012),MELD score(OR=1.103,95%CI:1.011-1.203,P=0.027],and the incidence rate of shock(OR=6.326,95%CI:1.533-26.101,P=0.011)were independent risk factors for 28-day mortality in ALD-ACLF patients comorbid with infection.Based on these factors,a predictive model was established as Y=0.027×NH3+0.098×MELD score+1.845×shock-4.111.The ROC curve analysis showed that the new model had an AUC of 0.861,a sensitivity of 77.78%,and a specificity of 88.68%,while MELD score had an AUC of 0.776,a sensitivity of 77.78%,and a specificity of 67.92%,suggesting that the new model had a significantly higher diagnostic value than MELD score(Z=2.136,P=0.032 6).Conclusion ALD-ACLF patients with infection tend to have a poor short-term prognosis,and MELD score,NH3,and shock are influencing factors for the short-term prognosis of such patients.The combination of these three factors has a high value in predicting short-term prognosis.

Chronic hepatitis B（CHB）is one of the major challenges in the global public health field. As of 2022，approximately 254 million people worldwide were infected with the hepatitis B virus（HBV）. CHB is one of the main causes of liver cirrhosis and hepatocellular carcinoma（HCC）. Nucleos（t）ide analogs（NAs）and interferon therapy can delay the progression of liver fibrosis by inhibiting viral replication，but they cannot completely avoid the problem of heterogeneous treatment responses. Some patients are in a state of low-level viremia（LLV）during treatment. The persistent LLV state can induce chronic inflammation and the progression of liver fibrosis，ultimately increase the risk of HCC. In patients with poor treatment responses，the continuous active viral replication can induce immune disorders，accelerate the evolution of fibrosis to the decompensated stage of liver cirrhosis，and increase the risk of patient death. This article aims to review the definition，mechanisms，and impact on treatment outcomes of LLV and suboptimal response based on the latest research，provide a basis for optimizing antiviral therapy for CHB.