ObjectiveTo investigate the effect and mechanism of Zhenwutang on renal oxidative damage in the mouse model of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency via the nuclear factor erythroid 2-related factor-2 （Nrf2）/heme oxygenase-1 （HO-1）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodTwenty-five 7-week-old SPF-grade male db/m mice and 95 7-week-old SPF-grade male db/db mice were adaptively fed for a week. A blank group was set with the db/m mice without treatment， and the other mice were administrated with Rhei Radix et Rhizoma decoction and hydrocortisone for the modeling of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency. The modeled mice were randomized into the model， irbesartan （25 mg·kg^-1）， and high-， medium-， low-dose （33.8， 16.9， 8.45 g·kg^-1） Zhenwutang groups （n=15） and administrated with corresponding drugs for 8 weeks. The survival status of mice was observed， and the traditional Chinese medicine （TCM） syndrome score was recorded. The indicators related to spleen-kidney Yang deficiency， fasting blood glucose （FBG）， and renal function indicators were determined. Hematoxylin-eosin staining was employed to observe the histopathological changes of the renal tissue in each group. Biochemical kits were used to determine the oxidative stress-related indicators in the renal tissue. Real-time polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Nrf2， HO-1， glutamate-cysteine ligase catalytic subunit （GCLC）， and GPX4 in the renal tissue of mice in each group. ResultCompared with the blank group， the modeling increased the TCM syndrome score （P<0.05）， elevated the estradiol （E₂） and FBG levels （P<0.05）， lowered the testosterone （T）， triiodothyronine （T3）， and tetraiodothyronine （T4） levels （P<0.05）， and weakened the renal function （P<0.05）. In addition， the modeling led to glomerular hypertrophy and glomerular mesangial and basal thickening， decreased the catalase （CAT） activity， total antioxidant capacity （T-AOC）， and glutathione （GSH） content （P<0.05）， increased the malondialdehyde （MDA） content （P<0.05）， and down-regulated the mRNA and protein levels of Nrf2， HO-1， GCLC， and GPX4 in the renal tissue （P<0.05）. Compared with the model group， high and medium doses of Zhenwutang decreased the TCM syndrome score and E₂ content （P<0.05）， increased the T， T3， and T4 content （P<0.05）， improved the renal function （P<0.05）， alleviated the pathological changes in the renal tissue， increased CAT， T-AOC， and GSH （P<0.05）， reduced MDA （P<0.05）， and up-regulated the mRNA and protein levels of Nrf2， HO-1， GCLC， and GPX4 in the renal tissue （P<0.05）. ConclusionZhenwutang can improve the general state and renal function and reduce the oxidative damage and pathological changes in the renal tissue of db/db mice with spleen-kidney Yang deficiency by regulating the Nrf2/HO-1/GPX4 signaling pathway.

Diabetic nephropathy （DN）， a major cause of chronic kidney disease （CKD）， aggravates the prevalence of end-stage renal disease （ESRD） and threatens human health. The pathogenesis of DN is complex， in which inflammation is a key pathological link in the cascade injury. Therefore， the treatment targeting inflammation helps to delay the progression of DN. NOD-like receptor protein 3 （NLRP3）， a classical proteasome， acts as an inducer of innate immune responses. The activated NLRP3 inflammasomes produce and release inflammatory mediators to trigger pyroptosis and uncontrolled autophagy and mediate the stress signals promoting renal fibrosis， thus participating in the development and progression of DN. The NLRP3 inflammasome as a core site inducing inflammation is widely involved in DN progression and may be a novel target. The active components and compound prescriptions of Chinese medicines are increasingly applied in the prevention and treatment of DN. The latest studies have discovered that Chinese medicines can treat DN by regulating the activation of NLRP3 inflammasomes. Although studies have been conducted to explore the mechanism of Chinese medicines in the treatment of DN via NLRP3 inflammasome， the systematic review remains to be carried out. This paper reviews the relevant publications in recent years and introduces the research progress from the assembly and activation of NLRP3 inflammasomes， the mechanism of NLRP3 inflammasomes in the treatment of DN， and the regulation of NLRP3 inflammasomes by Chinese medicines for the prevention and treatment of DN， aiming to lay a foundation for the relevant studies and provide new targets and strategies for the prevention and treatment of DN.

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

Hepatic fibrosis （HF） is a widespread disease caused by various forms of chronic liver injury， significantly impacting human health. HF often has an insidious onset with inconspicuous symptoms， but in its advanced stages， it can progress to cirrhosis or even hepatocellular carcinoma. The pathogenic mechanisms of HF are highly complex， primarily characterized by excessive extracellular matrix （ECM） deposition. Autophagy is a lysosome-mediated degradation system employed by cells to recycle cellular contents， eliminate aggregated proteins， damaged organelles， and invading pathogens （such as viruses and bacteria） to maintain normal cellular function and dynamic balance. Autophagy can regulate various signaling pathways and factors， including mammalian target of rapamycin （mTOR）， adenosine monophosphate-activated protein kinase （AMPK）， and transforming growth factor-β （TGF-β）， to reduce the activation of hepatic stellate cells （HSCs） and hepatocyte necrosis and apoptosis， thereby mitigating ECM deposition and slowing the progression of HF. Numerous studies also suggest that traditional Chinese medicine （TCM） can effectively treat HF， and its mechanism of action may be related to autophagy. This article provides a review by summarizing recent literature in China and abroad on the mechanisms of autophagy， related signaling factors and pathways， as well as the role of TCM in regulating autophagy for the prevention and treatment of HF， aiming to offer insights and references for the development of TCM in the prevention and clinical rational medication in the treatment of HF.

Objective To study the mechanism of ferulic acid(FA)on hepatic fibrosis(HF)based on network pharmacology,and establish an in vitro model of rat hepatic stellate Cell-T6(HSC-T6)according to the results.Methods The potential targets of FA were screened through PubChem,swisstargetprediction and pharmmapper,and overlapped with the FA targets screened in disgenet,genecards and OMIM.Then,protein protein interaction(PPI)was analyzed by using string platform.Gene ontology(go)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out for key targets by using R64 4.0.3,and the"component target disease"network diagram was constructed by Cytoscape 3.7.2 software.Based on this,the proliferation of HSC-T6 was detected by cell counting kit-8(CCK-8)method,and the grouping was determined:blank group and low-dose group(100 μg·mL-1 FA),medium dose group(200 μg·mL-1 FA),high dose group(400 μg·mL-1 FA)and positive control group(200 μg·mL-1 colchicine),the migration ability of HSC-T6 was detected by scratch test,and the content of HSC-T6 was detected by enzyme linked immunosorbent assay(ELISA)α-Alpha smooth muscle actin,α-Flow cytometry was used to detect the changes of HSC-T6 cycle,quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the relative expression of JAK2 and STAT3 mRNA,and Western Blot was used to detect the molecular expression of JAK2 and STAT3 protein.Results 254 intersection targets of FA and HF were obtained.The core targets were signal transducer and activvator of Transcription(STAT3),albumin(ALB),protein kinase B(AKT1),tumor suppressor protein p53(TP53),epidermal growth factor receptor(EGFR)and caspase-3(CASP3).KEGG analysis showed that the action pathway of FA on HF mainly involved phosphatidylinositol 3 kinase protein kinase B(PI3K-Akt),vascular endothelial growth factor(VEGF),Janus kinase/signal transducer and activator of transcription(JAK/STAT)Tumor necrosis factor(TNF)and other pathways.The experimental results showed that in CCK-8 experiment,scratch experiment and ELISA experiment,compared with the blank group,the cell proliferation rate,migration ability and the expression of α-SMA protein decreased significantly(P<0.05).Compared with the blank group,the cycle arrest rate of low,medium and high dose groups and positive control group increased significantly(P<0.05).Compared with the blank group,the molecular weight and mRNA expression of JAK2 and STAT3 protein in low,medium and high dose groups and positive control group decreased gradually(P<0.05).Conclusion FA has the characteristics of multi-channel and multi-target.FA may inhibit the apoptosis of hepatic stellate cell(HSC)by down regulating JAK2 and STAT3 targets.

Objective To investigate the efficacy and safety of programmed cell death protein-1 (PD-1) monoclonal antibody on the treatment of malignant tumor after solid organ transplantation (SOT). Methods The relevant literatures in 7 databases were searched. The data on 54 cases of recipients with malignant tumors treated with PD-1 monoclonal antibody after SOT were collected, and the clinical effects and rejection of SOT recipients treated with PD-1 monoclonal antibody were analyzed. Results Total 32 acceptable articles including 54 SOT recipients were incorporated, including 43 males and 11 females aged 14-79 years old. There are 29 renal transplant recipients, 19 liver transplant recipients and 6 heart transplant recipients. The types of PD-1 monoclonal antibody agent used by SOT recipients included pembrolizumab for 28 patients and nivolumab for 26 patients. The overall remission rate, disease progression rate and fatality rate of PD-1 monoclonal antibody for postoperative malignant tumors of SOT recipients were 32% (17/54), 44% (24/54) and 36% (19/54), respectively. After treatment with PD-1 monoclonal antibody for postoperative malignant tumors of SOT recipients, the incidence of rejection was 39% (21/54), indicating no significant correlation between rejection and type of PD-1 monoclonal antibody (P > 0.05). Conclusions PD-1 monoclonal antibody can effectively treat postoperative malignant tumors of SOT recipients, and may induce rejection during the treatment. But rejection is not the most common cause for death of recipients.

Objective To evaluate the effect of donor risk index (DRI) on the early prognosis of liver transplantation for acute-on-chronic liver failure (ACLF). Methods Clinical data of 159 ACLF recipients undergoing liver transplantation were retrospectively analyzed. According to the calculation formula of DRI, all recipients were divided into DRI < 1.65 group (n=96) and DRI≥1.65 group (n=63). Based on the Chronic Liver Failure Consortium acute-on-chronic liver failure score (CLIF-C ACLFs), all recipients were divided into CLIF-C ACLFs < 48 group (n=78) and CLIF-C ACLFs≥48 group (n=81). The early prognosis indexes including the length of intensive care unit (ICU) stay and the length of postoperative hospital stay of the recipients in each group were observed after liver transplantation. The 90 dsurvival rate of the recipients after liver transplantation was analyzed by Kaplan-Meier survival curve. The risk factors affecting the early prognosis of ACLF recipients after liver transplantation were analyzed by Cox's hazards regression model. Results The length of ICU stay and the length of postoperative hospital stay did not significantly differ between the DRI < 1.65 group and DRI≥1.65 group (both P > 0.05). The length of postoperative hospital stay did not significantly differ between the CLIF-C ACLFs < 48 group and CLIF-C ACLFs≥48 group (P > 0.05). The length of ICU stay in the CLIF-C ACLFs < 48 group was 4 (3-14) d, significantly shorter than 7 (1-33) d in the CLIF-C ACLFs≥48 group (P < 0.05). The CLIF-C ACLFs was a risk factor of the early prognosis of ACLF recipients after liver transplantation (P < 0.05). The postoperative 90 d survival rate did not significantly differ between the DRI < 1.65 group and DRI≥1.65 group (P > 0.05). The postoperative 90 d survival rate in the CLIF-C ACLFs < 48 group was 94%, significantly higher than 79% in the CLIF-C ACLFs≥48 group (P < 0.05). Conclusions The early prognosis of ACLF recipients after liver transplantation is correlated with the severity of the disease rather than the DRI. Liver transplantation should be performed early and promptly.

Objective To evaluate the outcome of 1iver transplantation for acute-on-chronic liver failure (ACLF) patients .Methods We included 453 consecutive patients with previously cirrhosis who underwent liver transplantation between January 2013 and December 2017 .Patients were categorized as no ACLF (n=294) and ACLF(n=159) according to EASL-CLIF consortium criteria .Furthermore ,we used ACLF grades to categorize the ACLF patients .Their clinical data were reviewed and their 90-days survival outcomes were compared .Results Compared with the no ACLF group ,the length of stay in the ICU was significantly prolonged for all patients with ACLF ,and the 90-days survival rate after transplantation was significantly reduced in ACLF group .The length of stay in the ICU was shorter in Grade 1 and Grade 2 group when compared to Grade 3 group .The 90-days survival rate of no ACLF ,Grade 1 ,Grade 2 and Grade 3 group were 93 .20％ ,92 .59％ ,93 .33％ and 73 .68％ ,respectively .There were no statistically significant differences in 90-days survival rate among the no ACLF ,Grade 1 and Grade 2 group .However , the 90-days survive rate of Grade 3 group was lower than that of other groups .Conclusions Liver transplantation has been shown to be safe and effective with good outcome in patients with ACLF and should be offered in early course of ACLF before onset of multi-organ failure .