Non-alcoholic fatty liver disease （NAFLD） is one of the most prevalent forms of liver diseases globally. Its progression can lead to cirrhosis and end-stage liver disease， and there is currently a lack of effective pharmacological treatments. Adenosine monophosphate-activated protein kinase （AMPK）， as a regulatory hub for maintaining cellular energy homeostasis， can coordinate key cellular processes such as adipogenesis， glucose metabolism， and mitochondrial functions. Its activation exerts metabolic regulatory effects through pathways including inhibiting lipogenesis， enhancing mitochondrial β-oxidation， regulating inflammation and oxidative stress， and promoting autophagy. Accordingly， AMPK emerges as a potential target for the prevention and treatment of NAFLD. Traditional Chinese Medicine （TCM）， with low toxicity， high accessibility， and multi-component， multi-target synergistic effects， has demonstrated unique value in NAFLD treatment， particularly showing notable advantages in regulating the AMPK signaling pathway. Sichuan is known as the treasure house of TCM， and the active components of its authentic medicinal materials such as Coptidis Rhizoma not only reflect regional characteristics in AMPK signaling regulation but also form a multi-level metabolic regulatory network through crosstalk with pathways such as sirtuin 1 （SIRT1） and peroxisome proliferator-activated receptor α （PPARα）. They can achieve specific regulation by directly activating AMPK and modulating upstream and downstream targets， exerting prominent effects in ameliorating hepatic steatosis and inflammation. This study systematically reviews the research findings on TCM for the prevention and treatment of NAFLD over the past five years， elaborating the mechanisms by which TCM treats NAFLD through regulating the AMPK signaling pathway. It aims to provide new perspectives and references for clinical diagnosis and treatment， basic research， and drug development.

Objective To investigate the expression pattern of six-transmembrane epithelial antigen of prostate 1(STEAP1)in pulmonary hypertension(PH)rat model and explore its potential clinical value.Methods A hypoxia-induced pulmonary arte-rial smooth muscle cell(PASMC)model was established,and the expression levels of STEAP1 in the hypoxia cell model were detected using Western blot and immunofluorescence analysis.Nine patients diagnosed with PH through right heart catheteriza-tion during hospitalization in the Division of Cardiovascular Surgery at Tongji Hospital,Tongji Medical College,Huazhong Uni-versity of Science and Technology,were selected as the PH group.Four organ donors without pulmonary disease were selected as the control group.Western blot analysis was used to detect STEAP1 expression levels in lung tissue from both groups.A rat PH model was established by Sugen5416 couple with chronic hypoxia treatment(SuHx,and control rats were housed in an at-mospheric environment).Hematoxylin-eosin staining and immunohistochemistry staining were used to detect α-SMA expression in lung tissue,and the degree of pulmonary artery perivascular cluster lesions and vascular muscularization in model rats was as-sessed.Dual-color immunofluorescence staining was used to co-stain α-SMA and STEAP1 to detect the expression levels and tis-sue localization of STEAP1 in the lung tissue of model rats.Bioinformatics methods were employed to analyze the potential downstream regulatory mechanisms of STEAP1.Results STEAP1 expression level was significantly upregulated in the hypoxi-a-induced PASMCs.STEAP1 expression level was also upregulated in the lung tissue of PH patients.Compared with the control group,the pulmonary arteries of rats with PH showed significant remodeling,particularly with marked thickening of the pulmo-nary arterial smooth muscle layer;STEAP1 expression was significantly upregulated in the thickened pulmonary arterial smooth muscle layer of rats with PH(P＜0.01).Bioinformatic analysis suggested that the downstream regulatory mechanisms of STEAP1 were enriched in signaling pathways such as apoptosis.Conclusion STEAP1 expression level is upregulated in the thickened pulmonary arterial smooth muscle layer in PH,suggesting that it may be associated with the pathological mechanisms of pulmonary vascular remodeling and may participate in the development of PH through signaling pathways such as apopto-sis.Further exploration of STEAP1 may uncover new targets for basic research and clinical prevention and treatment.

Objective To explore the characteristics and prognosis of follicular lymphoma(FL)with bulky disease under rituximab-based first-line treatment.Methods A retrospective analysis was conducted on 525 FL patients diagnosed between September 2009 and September 2021 who received rituximab as a first-line treat-ment[342 patients received rituximab combined with chemotherapy(R-chemo),183 patients received rituximab plus lenalidomide(R2)].The clinicopathologic characteristics,gene mutations,and prognosis of bulky FL patients were analyzed.Results Compared to non-bulky FL patients,bulky FL patients had a significantly higher proportion of lymph node≥5 sites,≥2 extranodal involvement,bone marrow involvement,elevated LDH,and a higher proportion in the high-risk group of FLIPI1 and FLIPI2.Gene sequencing revealed a significantly higher mutation rate of ZNF608 in bulky FL patients compared to non-bulky FL patients.In patients receiving R-chemo as the first-line treatment,there was no significant difference in progression-free survival(PFS)and overall survival(OS)between bulky and non-bulky FL patients.However,in patients treated with R2,the PFS and OS of bulky FL patients was significantly shorter.Conclusions Bulky FL patients compared to non-bulky FL patients have a significantly higher proportion of high-risk baseline characteristics.For bulky FL at diagnosis,chemo-free regimens require further exploration on the basis of R2.

Objective To comprehensively and systematically evaluate the clinical effect of Chuanzhi Tongluo capsule combined with western medical treatment in patients with cerebral infarction using meta-analysis.Methods Domestic databases were searched,including China Knowledge Network,Wanfang,and Wipu databases,and foreign databases were mainly PubMed.The qualified literature was screened according to the inclusion and exclusion criteria,and was evaluated using the software of RevMan5.3 and Stata14.0 after quality assessment.Results Eight randomized controlled trials(RCTs)on the combination of Chuanzhi Tongluo capsule and western medicine were included,with a total of 728 patients with cerebral infarction,among which 365 cases were in the group of Chuanzhi Tongluo capsule combined with western medicine and 363 cases were in the group of western medicine alone.The results were analyzed in terms of the total effective rate,neurological deficit score such as the National Institutes of Health Stroke Scale(NIHSS),daily living scores,such as the Barthel Index and Activities of Daily Living(ADL)scores and inflammation level(Inflammatory mediator IL-6,ultrasensitive C-reactive protein)as the outcome indexes.Meta-analysis results showed that the total effective rate[95%CI,1.18(1.12,1.25),P<0.00001],neurological function impairment score[95%CI,-1.37(-2.08,-0.67),P=0.0001],daily life score[95%,0.88(0.51,1.25),P<0.00001],and inflammation level[95%CI,-0.75(-0.96,-0.54),P<0.00001]were better than those of the control group and showed significant differences.The incidence of adverse events[95%CI,0.89(0.37,2.15),P=0.80],and the difference was not statistically significant with that of western medicine treatment alone.Conclusion Compared with the control group which only used western medicine,the treatment effect of Chuanzhi Tongluo capsule combined with western medicine in the treatment of cerebral infarction is more significant,and the combined treatment can improve the neurological function of the patients,enhance the quality of daily life,and reduce the level of inflammation more effectively.

Purpose To analyze the expression of SNAP23 in esophageal squamous cell carcinoma(ESCC)and its influence on invasion of ESCC cells.Methods A total of 41 cases of ESCC and paired normal adjacent tissue(NAT)were collected.The expression and localization of SNAP23 were detected by immunohistochemical EnVision method.The differences of SNAP23 expression levels between ESCC tissues and NAT tissues were compared to analyze the relationship between SNAP23 expression and clinicopathological characteristics.The expression level of SNAP23 in human immortalized esophageal epithelial cells SHEE and ESCC cell lines TE-1,TE-13 and KYSE150 were detected by Western blot.Lentiviral vector transfection technique was used to construct stable transfection cell lines with knock-down and overexpression of SNAP23 gene.The effect of SNAP23 on invasion of ESCC cell line TE-13 was evaluated by cell invasion experiment.Results The expression of SNAP23 in ESCC was significantly higher(53.7％,22/41)than that in the NAT group(19.5％,8/41),the difference was statistically significant(x2=10.303,P＜0.01).The expression level of SNAP23 in ESCC tissues was significantly correlated with maximum tumor diameter(x2=4.193,P＜0.05)and invasion depth(x2=7.264,P＜0.05),but was not correlated with patient gender,age,tumor site,tumor type,pathologic grade,vascular embolus,nerve invasion and lymph node metastasis(P＞0.05).Compared with human immortalized esophageal epithelial cells SHEE,SNAP23 was highly expressed in ESCC cell lines(P＜0.000 1).Compared with the sh-NT group,the invasion of ESCC cell line TE-13 was inhibited when SNAP23 expression was knocked down(P＜0.000 1);compared with the Vector group,the invasion of ESCC cell line TE-13 was enhanced after overexpression of SNAP23(P＜0.000 1).Conclusion SNAP23 is highly expressed in ESCC tis-sue and cell lines,and its expression level in ESCC tissues is positively correlated with tumor maximum diameter and invasion depth;SNAP23 promotes the invasion of ESCC cells.

Forty adult male C57BL/6 mice were randomly divided into four groups:the control group,Salmonella typhimurium(S.typhimurium)(ST)group,phlorizin(PHZ)+S.typhimuri-um(ST)group,and PHZ(80 mg/kg)group,with 10 mice in each group.Morphological observa-tion,HE staining,ELISA,immunofluorescence and Western blot were performed,the results showed that PHZ significantly increased the cecal index,decreased the spleen index of S.typhi-murium-induced mice(P＜0.05),and reduce the pathological damage of cecum in mice.Mean-while,PHZ treatment also significantly reduced colonization of S.typhimurium in the cecum,spleen,mesenteric lymph nodes and liver(P＜0.05).The results of ELISA showed that PHZ treatment also significantly inhibited the S.ty phimurium-induced increase in the expression of IL-1β,INF-γ,TNF-a and IL-6 in the cecum of mice(P＜0.05).Immunofluorescence and Western blot results showed that PHZ significantly increased the protein expression levels of Occludin,Claudin-3,and ZO-1 in the cecal barrier of mice induced by S.typhimurium(P＜0.05).These results con-firmed that phlorizin could improve cecal inflammation and intestinal barrier damage induced by S.typhimurium in mice.

Objective To investigate the expression pattern of six-transmembrane epithelial antigen of prostate 1(STEAP1)in pulmonary hypertension(PH)rat model and explore its potential clinical value.Methods A hypoxia-induced pulmonary arte-rial smooth muscle cell(PASMC)model was established,and the expression levels of STEAP1 in the hypoxia cell model were detected using Western blot and immunofluorescence analysis.Nine patients diagnosed with PH through right heart catheteriza-tion during hospitalization in the Division of Cardiovascular Surgery at Tongji Hospital,Tongji Medical College,Huazhong Uni-versity of Science and Technology,were selected as the PH group.Four organ donors without pulmonary disease were selected as the control group.Western blot analysis was used to detect STEAP1 expression levels in lung tissue from both groups.A rat PH model was established by Sugen5416 couple with chronic hypoxia treatment(SuHx,and control rats were housed in an at-mospheric environment).Hematoxylin-eosin staining and immunohistochemistry staining were used to detect α-SMA expression in lung tissue,and the degree of pulmonary artery perivascular cluster lesions and vascular muscularization in model rats was as-sessed.Dual-color immunofluorescence staining was used to co-stain α-SMA and STEAP1 to detect the expression levels and tis-sue localization of STEAP1 in the lung tissue of model rats.Bioinformatics methods were employed to analyze the potential downstream regulatory mechanisms of STEAP1.Results STEAP1 expression level was significantly upregulated in the hypoxi-a-induced PASMCs.STEAP1 expression level was also upregulated in the lung tissue of PH patients.Compared with the control group,the pulmonary arteries of rats with PH showed significant remodeling,particularly with marked thickening of the pulmo-nary arterial smooth muscle layer;STEAP1 expression was significantly upregulated in the thickened pulmonary arterial smooth muscle layer of rats with PH(P＜0.01).Bioinformatic analysis suggested that the downstream regulatory mechanisms of STEAP1 were enriched in signaling pathways such as apoptosis.Conclusion STEAP1 expression level is upregulated in the thickened pulmonary arterial smooth muscle layer in PH,suggesting that it may be associated with the pathological mechanisms of pulmonary vascular remodeling and may participate in the development of PH through signaling pathways such as apopto-sis.Further exploration of STEAP1 may uncover new targets for basic research and clinical prevention and treatment.

Objective To comprehensively and systematically evaluate the clinical effect of Chuanzhi Tongluo capsule combined with western medical treatment in patients with cerebral infarction using meta-analysis.Methods Domestic databases were searched,including China Knowledge Network,Wanfang,and Wipu databases,and foreign databases were mainly PubMed.The qualified literature was screened according to the inclusion and exclusion criteria,and was evaluated using the software of RevMan5.3 and Stata14.0 after quality assessment.Results Eight randomized controlled trials(RCTs)on the combination of Chuanzhi Tongluo capsule and western medicine were included,with a total of 728 patients with cerebral infarction,among which 365 cases were in the group of Chuanzhi Tongluo capsule combined with western medicine and 363 cases were in the group of western medicine alone.The results were analyzed in terms of the total effective rate,neurological deficit score such as the National Institutes of Health Stroke Scale(NIHSS),daily living scores,such as the Barthel Index and Activities of Daily Living(ADL)scores and inflammation level(Inflammatory mediator IL-6,ultrasensitive C-reactive protein)as the outcome indexes.Meta-analysis results showed that the total effective rate[95%CI,1.18(1.12,1.25),P<0.00001],neurological function impairment score[95%CI,-1.37(-2.08,-0.67),P=0.0001],daily life score[95%,0.88(0.51,1.25),P<0.00001],and inflammation level[95%CI,-0.75(-0.96,-0.54),P<0.00001]were better than those of the control group and showed significant differences.The incidence of adverse events[95%CI,0.89(0.37,2.15),P=0.80],and the difference was not statistically significant with that of western medicine treatment alone.Conclusion Compared with the control group which only used western medicine,the treatment effect of Chuanzhi Tongluo capsule combined with western medicine in the treatment of cerebral infarction is more significant,and the combined treatment can improve the neurological function of the patients,enhance the quality of daily life,and reduce the level of inflammation more effectively.

Objective To explore the characteristics and prognosis of follicular lymphoma(FL)with bulky disease under rituximab-based first-line treatment.Methods A retrospective analysis was conducted on 525 FL patients diagnosed between September 2009 and September 2021 who received rituximab as a first-line treat-ment[342 patients received rituximab combined with chemotherapy(R-chemo),183 patients received rituximab plus lenalidomide(R2)].The clinicopathologic characteristics,gene mutations,and prognosis of bulky FL patients were analyzed.Results Compared to non-bulky FL patients,bulky FL patients had a significantly higher proportion of lymph node≥5 sites,≥2 extranodal involvement,bone marrow involvement,elevated LDH,and a higher proportion in the high-risk group of FLIPI1 and FLIPI2.Gene sequencing revealed a significantly higher mutation rate of ZNF608 in bulky FL patients compared to non-bulky FL patients.In patients receiving R-chemo as the first-line treatment,there was no significant difference in progression-free survival(PFS)and overall survival(OS)between bulky and non-bulky FL patients.However,in patients treated with R2,the PFS and OS of bulky FL patients was significantly shorter.Conclusions Bulky FL patients compared to non-bulky FL patients have a significantly higher proportion of high-risk baseline characteristics.For bulky FL at diagnosis,chemo-free regimens require further exploration on the basis of R2.

Lipoatrophic diabetes(LD) is a rare and distinct form of diabetes characterized by notable clinical heterogeneity. It is often considered one of the manifestations of lipodystrophy syndrome(LDS). In clinical practice, LD is frequently misdiagnosed as type 2 diabetes; however, its management protocols and prognostic outcomes differ significantly from those of other diabetes subtypes. Therefore, timely and accurate diagnosis is of great clinical importance. This paper presents two detailed case reports of female patients with LD. Through an in-depth analysis of their clinical features, it also provides an comprehensive review of the key clinical manifestations of LDS, potential pathogenic mechanisms, and current approaches to genetic diagnosis. The aim is to enhance clinicans′ awareness of LDS and improve corresponding diagnostic and therapeutic strategies.