BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis (MASH), liver fibrosis, cirrhosis, and relevant complications. The liver mainly comprises hepatocytes, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), immune cells (T cells, B cells), and hepatic stellate cells (HSCs). Crosstalk among these different liver cells, endogenous aberrant glycolipid metabolism, and altered gut dysbiosis are involved in the pathophysiology of MASLD. This review systematically examines advances in understanding the molecular pathogenesis of MASLD, with a focus on emerging therapeutic targets and translational clinical trials. We first delineate the crucial regulatory mechanisms involving diverse liver cells and the gut-liver axis in MASLD development. These cell-specific pathogenic insights offer valuable perspectives for advancing precision medicine approaches in MASLD treatment. Furthermore, we evaluate potential therapeutic targets and summarize clinical trials currently underway. By comprehensively updating the MASLD pathophysiology and identifying promising strategies, this review aims to facilitate the development of novel pharmacotherapies for this increasingly prevalent condition.
Humans ; Fatty Liver/therapy* ; Animals ; Liver/pathology* ; Kupffer Cells/metabolism* ; Hepatocytes/metabolism* ; Hepatic Stellate Cells/metabolism*

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

By reconstructing the integrated Chinese and western medicine diagnostic and treatment system， the "Two Reconstructions" theoretical framework establishes a standardized pathway of "classification-staging-syndrome differentiation"， which improves the accuracy of disease identification and strengthens the capacity for full-course intervention； in addition， by reconstructing the modern materia medica system， it innovatively integrates the traditional properties and efficacy of Chinese herbal medicinals with modern pharmacological mechanisms， forming a "state-target co-regulation" precise medication model， and builds a dose-effect theoretical system for prescriptions and medicinals， thereby enhancing both the targeting accuracy and dosage precision of therapeutic interventions. The "Two Reconstructions" theorecitcal framework is a key strategy for enhancing clinical efficacy. It can precisely identify "states" and "targets" for directed intervention， shift the focus of prevention and treatment earlier to enable full-cycle management， establish standardized paradigms for reproducible and evaluable efficacy， and expand the scope of clinical practice to address conditions without typical syndromes and critical illnesses. As a systematic pathway for innovation in TCM， this theoretical framework provides valuable insights and references for promoting the high-quality development of integrative Chinese and western medicine.

Objective To investigate the difference between structured triglyceride(STG)and Non-structured triglyceride(NSTG)in nutritional support for perioperative patients.Methods A nationwide survey was conducted through online questionnaire.The questionnaire consisted of four modules:questionnaire information,patient information,prescription investigation and postoperative observation.SPSS 24.0 software was used for statistical analysis.Results Before and after parenteral nutrition(PN),the average levels of albumin(ALB)increased in both groups(P＜0.01),while the levels of C-reactive protein(CRP)and alanine aminotransferase(ALT)decreased(P＜0.01).The difference in serum triglyceride(TG)levels in the STG group was not statistically significant,while there was a decrease in the NSTG group(P＜0.05).Generalized linear equation analysis of repeated measurements showed that compared to the NSTG group,the increase in ALB levels in the STG group patients was more significant(P＜0.001),CRP and ALT decreases were more pronounced(P＜0.001),but the impact on TG was smaller.Conclusions For perioperative patients with parenteral nutrition,STG supplementation can bring significant clinical benefits.STG should be used according to the organ function and economic situation of patients.

Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.

Objective To compare the differences in gut microbiota between cirrhosis patients receiving transjugular intrahepatic portosystemic shunt(TIPS)and those not,and explore the relationship between TIPS surgery and gut microbiota in order to provide new ideas for improving the prognosis of cirrhosis patients after TIPS surgery based on gut microbiota.Methods Those who had received TIPS surgery previously were assigned into the operation group,and those without the surgery served as the control group.Their stool samples were collected for 16S rRNA sequencing,and the correlation between gut microbiota and clinical indicators was analyzed.Results There were no significant differences in gender,age,body mass index(BMI),etiology and other baseline data between the 2 groups(P＞0.05),but obvious differences were observed in clinical serological indicators between them,including INR,APTT,RBC and PT counts,and HGB,ALP,ALB,total bilirubin(TBIL),and URE levels(P＜0.05).No statistical difference in alpha diversity was observed between the operation group and the control group(P＞0.05),but beta diversity was obviously different(P＜0.01),among which Bacteroides was increased in the operation group(P＜0.01)and Bifidobacterium was increased in the control group(P＜0.05).The function prediction analysis of gut microbiota showed that the metabolism of D-glutamine and D-glutamate(P＜0.05)and biosynthesis with secondary bile acids(P＜0.05)were up-regulated in the operation group compared with the control group.Correlation analysis between clinical indicators and flora indicated that TBIL and direct bilirubin(DBIL)were significantly correlated with the metabolic pathways of Bacteroides and Secondary bile acids biosynthesis.Conclusion Characteristic changes in gut microbiota are found in cirrhosis patients with and without TIPS surgery.Bacteroides may be involved in the regulation of metabolism of bile acids and thus increase bilirubin level.

Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors. Materials and methods:This study analyzed human liver and serum samples from five patients under-going the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results:Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating thera-peutic potential. Conclusions:Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.