ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P0.05）， and compared with the model group， both were significantly increased in the Sini San group （P0.05， P0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P0.05， P0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P<0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P<0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P<0.05）， and compared with the model group， both were significantly increased in the Sini San group （P<0.05， P<0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P<0.05， P<0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P<0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

Based on the theory of 'spleen governing the containment of blood' in The Classic of Difficult Issues （《难经》）， it is proposed that medication toxicity damaging the middle jiao （焦） and failure of the spleen to contain blood constitute the core pathogenesis of cancer therapy induced thrombocytopenia （CTIT）. It is believed that the anti-tumor drug toxicity directly hits middle jiao， leading to spleen qi depletion， impairment of transportation and transformation， and insufficiency of the source of blood production. Consequently， the vessels and collaterals are deprived of nourishment and become structurally damaged. Blood fails to be contained and stored within the vessels， resulting in extravasation beyond the vascular system. Persistent retention of drug toxicity may further cause stasis due to blood deviating from its normal pathway and gradually consume the essence. In view of this root deficiency with branch excess， it is proposed that the treatment should focus on fortifying spleen， boosting qi and containing blood， with the aim of restoring spleen and stomach transportation functions， repairing vascular damage， and recovering the spleen's blood-containing function. According to individual syndrome patterns， prescriptions may be supplemented with herbs that stabilize vessels and consolidate collaterals， remove stasis and promote regeneration， and replenish essence and nourish marrow， providing new perspectives for the prevention and treatment of CTIT with traditional Chinese medicine.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective:To explore differences in the clinical and pathological features and postoperative survival after radical resection of biliary tract cancer in different locations such as intrahepatic cholangiocarcinoma,perihilar cholangiocarcinoma,distal cholangiocarcinoma,and gallbladder cancer.Methods:This is a retrospective case series study. The clinical and pathological data of 4 852 patients with biliary tract cancer admitted to the Department of Hepatobiliary Surgery,the First Affiliated Hospital of Xi ′an Jiaotong University from January 2013 to December 2022 were retrospectively analyzed. Among them, 2 110(43.49%%) patients were male and 2 742(56.51%) patients were female,aged from 26 to 88 years with age of (61.3±10.8) years. Observation indicators: (1) The distribution,diagnosis and treatment of patients with biliary tract cancer; (2) Comparison of clinical and pathological features of patients with biliary tract cancer after curative-intent resection; (3) Survival analysis of patients with biliary tract cancer after curative-intent resection; (4) Analysis of effect on adjuvant therapy for patients with biliary tract cancer after curative-intent resection. One-way analysis of variance,Kruskal-Wallis H test and χ 2 test were used for among-group comparisons,respectively. Survival univariate analysis was performed using the Kaplan-Meier method and Log-rank test. Results:Among the 4 852 patients with biliary tract cancer,there were 2 303 cases (47.46%) of gallbladder cancer,952 cases (19.62%) of intrahepatic cholangiocarcinoma,892 cases (18.38%) of perihilar cholangiocarcinoma,and 705 cases(14.53%) of distal cholangiocarcinoma. From the perspective of the year of diagnosis and treatment,the overall number of patients diagnosed and treated for biliary tract cancer has shown an upward trend. From the perspective of diagnosis and treatment,the curative-intent resection rate was 33.37%(1 619/4 852),and the curative-intent resection rate of distal cholangiocarcinoma was higher than that of other biliary tract cancer ( χ2=23.897, P<0.01). Univariate analysis showed that there were statistical differences in gender,age,bile duct stones,total bilirubin at admission,carcinoembryonic antigen,CA19-9,CA125,the degree of pathological differentiation,vascular invasion,microvascular invasion,perineural invasion,surgical margins,pT staging,and pN staging among patients for biliary tract cancer in different locations (all P<0.05). Survival comparison analysis showed that recurrence-free survival and overall survival of patients with gallbladder cancer after curative-intent resection were significantly better than those of intrahepatic cholangiocarcinoma,perihilar cholangiocarcinoma,and distal cholangiocarcinoma ( χ 2=87.780,83.717,both P<0.01). Comparing the postoperative prognosis of patients with biliary tract cancer between the two periods of 2013 to 2017 and 2018 to 2022, the results showed that recurrence-free survival and overall survival of patients with biliary tract cancer from 2018 to 2022 were significantly better than those from 2013 to 2017 ( χ 2=31.202,25.615, both P<0.01),and the proportion of early recurrence and short-term death after curative-intent resection was significantly reduced ( χ 2=21.588,9.623, both P<0.01),with gallbladder cancer being the most significant ( P<0.01). Postoperative adjuvant therapy for patients with biliary tract cancer can effectively prolong recurrence-free survival and overall survival ( χ 2=5.033,11.273,both P<0.05). Conclusions:Gallbladder cancer remains the most common biliary tract cancer with a relatively favorable prognosis after radical resection. There are significant differences in the clinical and pathological features of biliary tract cancer in different locations,and patients with adjuvant therapy effectively improving prognosis.

Objective:To explore differences in the clinical and pathological features and postoperative survival after radical resection of biliary tract cancer in different locations such as intrahepatic cholangiocarcinoma,perihilar cholangiocarcinoma,distal cholangiocarcinoma,and gallbladder cancer.Methods:This is a retrospective case series study. The clinical and pathological data of 4 852 patients with biliary tract cancer admitted to the Department of Hepatobiliary Surgery,the First Affiliated Hospital of Xi ′an Jiaotong University from January 2013 to December 2022 were retrospectively analyzed. Among them, 2 110(43.49%%) patients were male and 2 742(56.51%) patients were female,aged from 26 to 88 years with age of (61.3±10.8) years. Observation indicators: (1) The distribution,diagnosis and treatment of patients with biliary tract cancer; (2) Comparison of clinical and pathological features of patients with biliary tract cancer after curative-intent resection; (3) Survival analysis of patients with biliary tract cancer after curative-intent resection; (4) Analysis of effect on adjuvant therapy for patients with biliary tract cancer after curative-intent resection. One-way analysis of variance,Kruskal-Wallis H test and χ 2 test were used for among-group comparisons,respectively. Survival univariate analysis was performed using the Kaplan-Meier method and Log-rank test. Results:Among the 4 852 patients with biliary tract cancer,there were 2 303 cases (47.46%) of gallbladder cancer,952 cases (19.62%) of intrahepatic cholangiocarcinoma,892 cases (18.38%) of perihilar cholangiocarcinoma,and 705 cases(14.53%) of distal cholangiocarcinoma. From the perspective of the year of diagnosis and treatment,the overall number of patients diagnosed and treated for biliary tract cancer has shown an upward trend. From the perspective of diagnosis and treatment,the curative-intent resection rate was 33.37%(1 619/4 852),and the curative-intent resection rate of distal cholangiocarcinoma was higher than that of other biliary tract cancer ( χ2=23.897, P<0.01). Univariate analysis showed that there were statistical differences in gender,age,bile duct stones,total bilirubin at admission,carcinoembryonic antigen,CA19-9,CA125,the degree of pathological differentiation,vascular invasion,microvascular invasion,perineural invasion,surgical margins,pT staging,and pN staging among patients for biliary tract cancer in different locations (all P<0.05). Survival comparison analysis showed that recurrence-free survival and overall survival of patients with gallbladder cancer after curative-intent resection were significantly better than those of intrahepatic cholangiocarcinoma,perihilar cholangiocarcinoma,and distal cholangiocarcinoma ( χ 2=87.780,83.717,both P<0.01). Comparing the postoperative prognosis of patients with biliary tract cancer between the two periods of 2013 to 2017 and 2018 to 2022, the results showed that recurrence-free survival and overall survival of patients with biliary tract cancer from 2018 to 2022 were significantly better than those from 2013 to 2017 ( χ 2=31.202,25.615, both P<0.01),and the proportion of early recurrence and short-term death after curative-intent resection was significantly reduced ( χ 2=21.588,9.623, both P<0.01),with gallbladder cancer being the most significant ( P<0.01). Postoperative adjuvant therapy for patients with biliary tract cancer can effectively prolong recurrence-free survival and overall survival ( χ 2=5.033,11.273,both P<0.05). Conclusions:Gallbladder cancer remains the most common biliary tract cancer with a relatively favorable prognosis after radical resection. There are significant differences in the clinical and pathological features of biliary tract cancer in different locations,and patients with adjuvant therapy effectively improving prognosis.

Objective To investigate the mechanism by which Erastin affects ferroptosis in lung fibroblasts.Meth-ods Mouse lung fibroblasts (C57/B6-L) were treated with varying concentrations of the iron death inducer Eras-tin.Cell viability was assessed using the cell counting Kit-8 (CCK-8) assay.Oxidative stress levels were visualized using a fluorescence microscope, and the expression of proteins related to the mitogen-activated protein kinase (MAPK) signaling pathway was analyzed using Western blot.Additionally, the p38 and extracellular regulated protein kinase (ERK) inhibitors SB203580 and U0126 were employed to further elucidate the mechanism by which Erastin induces iron death in lung fibroblasts.Results At a concentration of 100 μmol/L, Erastin effectively in-duced ferroptosis in lung fibroblasts, leading to an upregulation of oxidative stress.Furthermore, the phosphoryla-tion levels of p38 and ERK proteins in the MAPK pathway were elevated (P<0.05) .The addition of SB203580 and U0126 inhibitors resulted in a significant reduction in oxidative stress levels and a notable increased in cell ac-tivity in lung fibroblasts (P<0.05).Conclusion It can be concluded that Erastin induces ferroptosis in lung fi-broblasts, potentially through the mediation of oxidative stress via the MAPK signaling pathway.

Objective To investigate the molecular mechanism underlying Porphyromonas gingivalis(Pg)-induced autophagy in esophageal squamous cell carcinoma(ESCC).Methods After Pg infected KYSE70 cells and KYSE140 cells pretreated with siAtg7 or Chloroquin(CQ),Western blot was used to measure protein levels of Atg7,LC3-Ⅱ/LC3-Ⅰ,and p62;Immunofluorescent confocal imaging analysis was used to detect autophagosome and autolysosome;CCK-8 assay was used to test cell viability;Transwell assay was used for ESCC cell migration and invasion potentials.Likewise,miR-21-5p inhibitor,RASA1 overexpression plasmid,or U0126 were used to block miR-21-5p/RASA1/ERK signaling pathway prior to Pg infection,followed by the aforementioned methods.In addition,immunohistochemistry was used to examine Pg abundance and LC3 protein levels,and RT-PCR was used to evaluate miR-21-5p expression in ESCC and adjacent tissue samples,followed by correlation analyses be-tween Pg and LC3,and Pg and miR-21-5p.Results Pg infected KYSE70 cells and KYSE140 cells showed upreg-ulation Atg7 protein and LC3-Ⅱ/LC3-Ⅰ protein but downregulation of RASA1 protein and p62 protein,enhanced cell proliferation,migration,and invasion as well as immunofluorescent spots of red,green,and yellow in mRFP-GFP-LC3-labeled ESCC cells.Pretreatment with CQ or siAtg7 abolished the above alterations induced by Pg.Con-sistently,pretreatment with miR-21-5p inhibitor,U0126,or RASA1 overexpression plasmid also blocked Pg-stimu-lated autophagy.In ESCC samples,Pg abundance was correlated with upregulation of miR-21-5p and LC3.Con-clusion Pg promotes autophagy in esophageal squamous cell carcinoma via miR-21-5p/RASA1/ERK signaling pathway.

Pancreatobiliary maljunction(PBM)represents a congenital anatomical abnormality of the pancreaticobiliary ductal system,frequently predisposing individuals to recurrent cholangitis and pancreatitis.Accumulating evidence indicates that PBM is a precancerous lesion,and PBM plays an important role in the development and progression of gallbladder cancer(GBC).GBC arising from PBM is designated as PBM-associated GBC.Consequently,early diagnosis and treatment of PBM is paramount in mitigating the risk of GBC.This review outlined the epidemiology and advancements in the diagnosis and management of PBM,along with the clinical features,underlying mechanisms,and therapeutic progressions pertaining to PBM-associated GBC,in order to underscore the clinical significance of early intervention in PBM,so as to reduce the incidence of PBM-associated GBC.

Objective:To investigate the efficacy of liver wedge resection and liver Ⅳb and Ⅴ segmentectomy for T2 gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 168 patients who underwent radical resection of T2 GBC in The First Affiliated Hospital of Xi′an Jiaotong University from January 2011 to December 2021 were collected. There were 59 males and 109 females, aged (65±10)years. Of 168 patients, there were 112 cases in T2a stage and 56 cases in T2b stage. Of 112 patients in T2a stage, 73 cases underwent liver wedge resection and 39 cases underwent liver Ⅳb and Ⅴ segmentectomy. Of 56 patients in T2b stage, 27 cases underwent liver wedge resection and 29 cases underwent liver Ⅳb and Ⅴ segmen-tectomy. Measurement data with normal distribution were represented as Mean± SD, and measure-ment data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX proportional risk model was used for univariate and multivariate analyses. Results:(1) Clinical data analysis of patients undergoing different extent of hepatic resection for T2 GBC. There was no significant difference in gender, age, cholecystoli-thiasis, preoperative total bilirubin, carcinoembryonic antigen, CA19-9, CA125, incidental GBC, perineural invasion, microvascular invasion, pathological differentiation, histopathological subtypes, N staging, TNM staging between patients with T2a and T2b GBC who underwent different extent of hepatic resection ( P>0.05). (2) Prognostic analysis of T2 GBC patients undergoing different extent of hepatic resection. The 1-, 3- and 5-year cumulative disease-free survival rates of T2 GBC patients undergoing liver wedge resection were 78.0%, 60.1% and 51.4%, respectively, versus 86.8%, 80.0% and 68.0% of T2 GBC patients undergoing liver Ⅳb and Ⅴ segmentectomy, showing a significant difference between them ( χ2 =5.205, P<0.05). The 1-, 3-, and 5-year cumulative overall survival rates of T2 GBC patients undergoing liver wedge resection were 85.0%, 62.5%, and 55.1%, respectively, versus 92.6%, 81.6%, and 68.8% for T2 GBC patients undergoing liver Ⅳb and Ⅴ segmentectomy, showing a significant difference in cumulative overall survival rate between them ( χ2=4.351, P<0.05). The 1-, 3-, and 5-year cumulative disease-free survival rates of T2b GBC patients undergoing liver wedge resection were 70.4%, 45.9% and 39.2%, respectively, versus 89.7%, 71.3% and 54.0% of T2b GBC patients undergoing liver Ⅳb and Ⅴ segmentectomy, showing a significant difference between them ( χ2=5.047, P<0.05). The 1-, 3-, and 5-year cumulative overall survival rates of T2b GBC patients undergoing liver wedge resection were 81.5%, 53.2%, and 41.0%, respectively, versus 89.7%, 77.0%, and 60.7% of T2b GBC patients undergoing liver Ⅳb and Ⅴ segmentectomy, showing no significant difference in cumulative overall survival rate between them ( χ2=4.014, P<0.05). (3) Analysis of factors influencing prognosis of patients undergoing radical resection for T2 GBC. Results of multivariate analysis showed that CA19-9>39.0 U/mL, perineural invasion, N1 and N2 stage were independent risk factors influencing disease-free survival time of patients undergoing radical resection for T2 GBC ( hazard ratio=2.736, 3.496, 2.638, 17.440, 95% confidence interval as 1.195-6.266, 1.213-10.073, 1.429-4.869, 8.362-36.374, P<0.05). Liver Ⅳb and Ⅴ segmentectomy was an independent protective factor influencing disease-free survival time of patients undergoing radical resection for T2 GBC ( hazard ratio=0.418, 95% confidence interval as 0.230-0.759, P<0.05). CA19-9 >39.0 U/mL, perineural invasion, ⅡB stage, ⅢB stage and ⅣB stage of TNM staging were independent risk factors influencing overall survival time of patients undergoing radical resection for T2 GBC ( hazard ratio=2.740, 3.210, 2.037, 3.439, 24.466, 95% confidence interval as 1.127-6.664, 1.049-9.819, 1.004-4.125, 1.730-6.846, 10.733-55.842, P<0.05). Liver Ⅳb and Ⅴ segmentectomy was an independent protective factor influencing overall survival time of patients undergoing radical resec-tion for T2 GBC ( hazard ratio=0.476, 95% confidence interval as 0.261-0.867, P<0.05). (4) Analysis of postoperative complications in patients undergoing different extent of hepatic resection for T2 GBC. There was no significant difference in postoperative complications of patients with T2a and T2b GBC undergoing liver wedge resection or liver Ⅳb and Ⅴ segmentectomy ( P>0.05). Conclusions:Compared to liver wedge resection, liver Ⅳb and Ⅴ segmentectomy can effectively prolong the disease-free survival overall survival time of T2b GBC patients. There is no significant difference in the major complications. Liver Ⅳb and Ⅴ segmentectomy is an independent protective factor for prognosis of patients undergoing radical resection for T2 GBC.