Background and Aims:Approximately 20％-25％of individuals experience insufficient weight loss(IWL)or weight regain(WR)after bariatric surgery.However,there is limited research on using semaglutide in this patient population,and its efficacy and safety remain to be confirmed.Therefore,this study was conducted to evaluate the effectiveness and safety of semaglutide in patients with IWL or WR after bariatric surgery through a systematic review to provide evidence to support clinical decision-making.Methods:A comprehensive search was conducted across multiple domestic and international databases for studies using semaglutide in patients with IWL or WR after bariatric surgery.The search period was from the database's inception to July 1,2024.Relevant studies were screened according to inclusion and exclusion criteria,and data were analyzed using Stata 14.0 software.Results:A total of 5 retrospective studies were included,encompassing 289 patients who received semaglutide treatment after bariatric surgery.The analysis showed that,compared to baseline,semaglutide use resulted in an average total weight reduction of 10.66％(MD=10.66％,95％CI=6.47％-14.89％);body mass index decreased by 3.57 kg/m2(MD=3.57 kg/m2,95％CI=2.46-4.67 kg/m2);the type of surgery did not significantly affect the degree of weight loss(P＞0.05).The proportion of patients who experienced＞5％weight loss was 80％(OR=0.80,95％CI=0.76-0.85);＞10％weight loss was observed in 45％of patients(OR=0.45,95％CI=0.41-0.50);and＞15％weight loss occurred in 18％of patients(OR=0.18,95％CI=0.08-0.27).Most patients had undergone sleeve gastrectomy(69.8％).There was no significant difference in HbA1c levels before and after treatment(P＞0.05).The incidence of adverse events was 14％(OR=0.14,95％CI=0.01-0.28),primarily gastrointestinal side effects.Conclusion:Semaglutide can significantly reduce body weight in patients with IWL or WR after bariatric surgery,with a relatively low incidence of adverse effects.It may be considered for patients who experience suboptimal weight loss following bariatric surgery.However,further prospective and large-scale clinical studies are needed to confirm these findings.

Background and Aims:Approximately 20％-25％of individuals experience insufficient weight loss(IWL)or weight regain(WR)after bariatric surgery.However,there is limited research on using semaglutide in this patient population,and its efficacy and safety remain to be confirmed.Therefore,this study was conducted to evaluate the effectiveness and safety of semaglutide in patients with IWL or WR after bariatric surgery through a systematic review to provide evidence to support clinical decision-making.Methods:A comprehensive search was conducted across multiple domestic and international databases for studies using semaglutide in patients with IWL or WR after bariatric surgery.The search period was from the database's inception to July 1,2024.Relevant studies were screened according to inclusion and exclusion criteria,and data were analyzed using Stata 14.0 software.Results:A total of 5 retrospective studies were included,encompassing 289 patients who received semaglutide treatment after bariatric surgery.The analysis showed that,compared to baseline,semaglutide use resulted in an average total weight reduction of 10.66％(MD=10.66％,95％CI=6.47％-14.89％);body mass index decreased by 3.57 kg/m2(MD=3.57 kg/m2,95％CI=2.46-4.67 kg/m2);the type of surgery did not significantly affect the degree of weight loss(P＞0.05).The proportion of patients who experienced＞5％weight loss was 80％(OR=0.80,95％CI=0.76-0.85);＞10％weight loss was observed in 45％of patients(OR=0.45,95％CI=0.41-0.50);and＞15％weight loss occurred in 18％of patients(OR=0.18,95％CI=0.08-0.27).Most patients had undergone sleeve gastrectomy(69.8％).There was no significant difference in HbA1c levels before and after treatment(P＞0.05).The incidence of adverse events was 14％(OR=0.14,95％CI=0.01-0.28),primarily gastrointestinal side effects.Conclusion:Semaglutide can significantly reduce body weight in patients with IWL or WR after bariatric surgery,with a relatively low incidence of adverse effects.It may be considered for patients who experience suboptimal weight loss following bariatric surgery.However,further prospective and large-scale clinical studies are needed to confirm these findings.

Objective To investigate the therapeutic effect and potential mechanisms of allogeneic renal subcapsular transplantation of CD24+renal epithelial cells for the treatment of acute kidney injury(AKI)induced by ischemia-reperfusion(I/R).Methods CD24+renal epithelial cells were isolated from mouse kidneys using flow cytometric sorting and expanded by passaging.C57BL/6N mice were randomly divided into three groups:the normal control group(n=8,sham surgery only),the model control group(n=8,unilateral kidney I/R plus contralateral nephrectomy),and the CD24+cell treatment group(n=8,AKI model followed by renal subcapsular transplantation of CD24+cells).Mice were euthanized at 24 h after modeling and serum was collected to measure biochemical markers[serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)].Renal tissues were subjected to pathological evaluation and macrophage staining.An M1-polarized macrophage model was established using mouse bone marrow-derived macrophages co-cultured with CD24+renal epithelial cells.The polarization state of macrophages was assessed by quantitative real-time polymerase chain reaction(qPCR)and flow cytometry.Results CD24+renal epithelial cells were successfully isolated and passaged stably.Compared with the normal control group,the model control group exhibited significantly elevated Scr and BUN levels and renal pathological damage.In contrast,the CD24+cell treatment group showed significant reduction in serum biochemical markers and pathological injury compared with the model control group,along with reduction in M1 macrophage infiltration in the kidneys(P<0.05,P<0.01).In vitro co-culture experiments demonstrated that in the CD24+co-culture group,the expression of M1 polarization-related markers in macrophages was significantly lower than that in the non-co-culture group,and the proportion of CD80+M1 macrophages in the co-culture group decreased(P<0.05,P<0.01).Conclusion Allogeneic renal subcapsular transplantation of CD24+renal epithelial cells can alleviate I/R-induced AKI by inhibiting M1 macrophage polarization through paracrine mechanisms.

Objective To investigate the therapeutic effect and potential mechanisms of allogeneic renal subcapsular transplantation of CD24+renal epithelial cells for the treatment of acute kidney injury(AKI)induced by ischemia-reperfusion(I/R).Methods CD24+renal epithelial cells were isolated from mouse kidneys using flow cytometric sorting and expanded by passaging.C57BL/6N mice were randomly divided into three groups:the normal control group(n=8,sham surgery only),the model control group(n=8,unilateral kidney I/R plus contralateral nephrectomy),and the CD24+cell treatment group(n=8,AKI model followed by renal subcapsular transplantation of CD24+cells).Mice were euthanized at 24 h after modeling and serum was collected to measure biochemical markers[serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)].Renal tissues were subjected to pathological evaluation and macrophage staining.An M1-polarized macrophage model was established using mouse bone marrow-derived macrophages co-cultured with CD24+renal epithelial cells.The polarization state of macrophages was assessed by quantitative real-time polymerase chain reaction(qPCR)and flow cytometry.Results CD24+renal epithelial cells were successfully isolated and passaged stably.Compared with the normal control group,the model control group exhibited significantly elevated Scr and BUN levels and renal pathological damage.In contrast,the CD24+cell treatment group showed significant reduction in serum biochemical markers and pathological injury compared with the model control group,along with reduction in M1 macrophage infiltration in the kidneys(P<0.05,P<0.01).In vitro co-culture experiments demonstrated that in the CD24+co-culture group,the expression of M1 polarization-related markers in macrophages was significantly lower than that in the non-co-culture group,and the proportion of CD80+M1 macrophages in the co-culture group decreased(P<0.05,P<0.01).Conclusion Allogeneic renal subcapsular transplantation of CD24+renal epithelial cells can alleviate I/R-induced AKI by inhibiting M1 macrophage polarization through paracrine mechanisms.

Viruses,with high adaptability and immune evasion capabilities,are responsible for a wide spectrum of diseases from lo-calized infections to global pandemics,continuously posing threats to global public health.In recent years,traditional Chinese medi-cine(TCM)has demonstrated significant potential in antiviral therapy.With its multi-component,multi-target synergistic mechanism,TCM offers unique advantages in the intervention of viral diseases.However,progress in elucidating the active antiviral constituents of TCM and identifying their precise molecular targets remains limited,primarily due to the lack of humanized models that can faithfully recapitulate the natural course of viral infection.The emergence of organoid technology has introduced new opportunities for antiviral research in TCM.Human organoids,which recapitulate the three-dimensional architecture and physiological functions of human tis-sues,provide an advanced platform for modeling host-virus interactions in a human-relevant context.This article highlights the latest advances in applications of human tissue organoids,including lung,liver,and brain organoids,in the study of respiratory viruses(SARS-CoV-2,influenza virus,respiratory syncytial virus),hepatitis viruses(HBV,HCV,HEV),and neurotropic viruses(ZIKV,pri-ons,HCMV);illustrates how organoid models have been leveraged to evaluate both the efficacy and safety of TCM-based antiviral inter-ventions.Although human tissue organoids still face technical challenges in insufficient vascularization and incomplete immune micro-environment,they represent a powerful tool for dissecting the mechanism of TCM antiviral action and for guiding the development of personalized antiviral strategies.Looking ahead,human tissue organoid technology is expected to become key enabling platform for pro-moting the clinical transformation of TCM in the field of antiviral medicine.

Objective To investigate the role of luteolin(Lut)in regulating reactive oxygen species(ROS)levels through nuclear factor erythroid 2-related factor 2(NFE2L2)/cystine glutamate antitransporter(x-CT)/glutathione peroxidase 4(GPX4)signaling axis to inhibit the viability of glioblastoma and promote apoptosis.Methods U87 MG and U251 cells were cultured in vitro.The CCK-8 assay was used to detect cell survival rates after 48 hours of treatment with different concentrations(0,6.25,12.5,25,50 and 100 μmol/L)of Lut.According to whether cells were treated with Lut,cells were divided into the U87 control group,the U87 Lut group,the U251 control group and the U251 Lut group.The half-maximal inhibitory concentration(IC50)at 48 hours was used as the unified treatment concentration for subsequent experiments.The apoptosis level of cells was detected by flow cytometry double staining method.Changes of reactive oxygen species(ROS)levels in cells were detected by the DCFH-DA method.Molecular docking was conducted using AutoDock software to verify the proteins related to the Lut and oxidative stress pathway.Real-time fluorescence quantitative reverse transcription(RT-qPCR)was used to detect the mRNA levels of NFE2L2 and GPX4.The expression levels of NFE2L2,x-CT and GPX4 proteins were detected by Western blot assay.Results After U87 MG and U251 cells were treated with Lut for 48 hours,the cell viability was significantly inhibited,and with the increase of Lut concentration,the cell viability decreased(P＜0.05).Compared with the U87 control group and the U251 control group respectively,the apoptosis rate of cells increased in the U87 Lut group and the U251 Lut group,the green fluorescence intensity was enhanced,and the intracellular ROS level was upregulated(P＜0.05).Results of molecular docking showed that Lut was tightly bound to NFE2L2,x-CT and GPX4.The results of RT-qPCR and Western blot assay showed that compared with the U87 control group and the U251 control group respectively,the protein and mRNA levels of NFE2L2 and GPX4 in cells of the U87 Lut group and the U251 Lut group,as well as the expression level of x-CT protein,decreased(P＜0.05).Conclusion Lut regulates ROS levels through the NFE2L2/x-CT/GPX4 signaling axis to inhibit the viability of glioblastoma and promote cell apoptosis.

Objective: This study aimed to elucidate the mechanisms underlying the impaired bone healing capacity in type 1 diabetes (T1DM) by investigating the role of the Hedgehog (Hh) signaling pathway in the impaired healing of cranial defects caused by T1DM. Methods: This study was approved by the experimental animal ethics committee of our hospital. A cranial defect model was established using Akita transgenic mice with spontaneous type I diabetes. The impact of T1DM on osteogenic differentiation and the Hh signaling pathway during cranial defect healing was explored by MicroCT scanning and immunohistochemical (IHC) analysis of osteocalcin (Ocn), Indian Hedgehog (Ihh), Patched1 (Ptch1), and zinc finger protein GLI1 (Gli1). Subsequently, the Hh signaling pathway was activated using smoothened agonist (SAG) (10 mg/kg, gavage), and its potential to improve cranial defect healing in T1DM was assessed by MicroCT and IHC staining. Finally, the ability of SAG (1 000 nmol/L) to counteract the inhibitory effects of a high-glucose environment (25 mol/L) on osteogenic differentiation of mouse bone marrow mesenchymal stem cells (BMSCs) was investigated through in vitro experiments. Detection methods included Alkaline Phosphatase and Alizarin Red staining, as well as quantitative real-time PCR (qPCR) analysis of the osteogenesis-related genes Alp, Spp1, Bglap, and Sp7. Results: Akita mice exhibited early, stable, and significant spontaneous T1DM characteristics. On postoperative day 21, the newly formed bone in the cranial defect area of Akita mice showed significant decreases in the bone volume-to-tissue volume ratio, volumetric bone mineral density, and Ocn expression (P < 0.05), with significant downregulation of Ihh, Ptch1, and Gli1 (P < 0.05). Activation of the Hh signaling pathway by SAG significantly mitigated the negative impact of T1DM on cranial defect healing in Akita mice (P < 0.05). Moreover, after SAG treatment, the inhibitory effects of the high-glucose environment on the alkaline phosphatase activity and in vitro mineralization capacity of BMSCs were significantly alleviated (P < 0.05), and the expression levels of osteogenic differentiation-related genes were significantly upregulated (P < 0.05). Conclusion T1DM inhibits cranial defect healing in Akita mice by suppressing the expression of the Hh signaling pathway, whereas activation of the Hh signaling pathway promotes osteogenesis and ameliorates the inhibitory effects of T1DM on bone healing.

Focal therapy has emerged as an alternative to surgical treatment for selected renal tumors.The core principle of this approach lies in the local destruction of tumor tissue through physical or chemical means to achieve tumor control.Focal therapy is particularly applicable to patients with tumors ≤4 cm in diameter who are unfit for surgery or anesthesia due to advanced age,comorbidities,solitary kidney,or renal insufficiency,as well as those with recurrent tumors after prior partial nephrectomy.This review summarizes the mechanisms,advantages,limitations,and clinical efficacy of six focal therapy modalities for renal tumors,including radiofrequency ablation,cryoablation,microwave ablation,irreversible electroporation,high-intensity focused ultrasound,and stereotactic ablative radiotherapy.The aim is to provide reference for achieving individualized and precise clinical management.