In recent years, the rising prevalence of obesity and its associated metabolic syndromes has emerged as a critical global public health concern. Sustained weight loss exceeding 10% of total body weight has been shown to ameliorate obesity-related comorbidities, including type 2 diabetes mellitus, hypertension, and hepatic steatosis. Recently, the potential of brown adipose tissue (BAT) to improve metabolism has garnered significant attention. However, evidence regarding weight loss therapies that promote BAT activation remains limited in preclinical models and is even scarcer in clinical studies, partly due to the paucity of appropriate BAT assessment techniques. This review aims to explore the potential impact of various weight loss therapies on BAT, with the goal of providing novel insights and strategies for the treatment of obesity.

Objective To explore the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in patients with locally advanced resectable non-small cell lung cancer (NSCLC). Methods The clinical data of patients with stage ⅡA-ⅢB NSCLC who underwent surgical treatment after receiving neoadjuvant immunotherapy combined with chemotherapy or chemotherapy alone at the First People’s Hospital of Jining between April 2021 and January 2024 were retrospectively analyzed. According to the preoperative neoadjuvant regimens, the patients were divided into a combined group and a chemotherapy group, and the clinical data of the two groups were compared. Results A total of 66 patients were included, including 61 males and 5 females. There were 53 patients in the combined group with a mean age of (63.40±6.80) years, and 13 patients in the chemotherapy group with a mean age of (58.62±8.30) years. There was a statistical difference in age between the two groups (P＜0.001), while no statistical difference was observed in other baseline data (P>0.05). The major pathological response rates in the combined group and the chemotherapy group were 54.7% and 23.1%, respectively (P=0.041), and the pathological complete response rates were 39.6% and 0.0%, respectively (P=0.006). The operative time in the combined group was shorter (P=0.039). There were no statistical differences between the two groups in intraoperative blood loss, duration of postoperative tube carrying, incidence of postoperative complications, overall survival, or event-free survival (P>0.05). Conclusion Surgical treatment following neoadjuvant immunotherapy combined with chemotherapy is safe and feasible, and its long-term efficacy requires further follow-up for confirmation.

Objective To observe the efficacy and safety of neoadjuvant sintilimab combined with chemotherapy in the treatment of patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Methods Clinical data were collected from patients with locally advanced resectable ESCC who received neoadjuvant immunotherapy combined with chemotherapy followed by surgical treatment at the Department of Thoracic Surgery of Jining No.1 People's Hospital from April 2020 to April 2022. The endpoints included major pathological response (MPR), pathological complete response (pCR), R0 resection rate, safety, and postoperative survival. Results A total of 43 patients with ESCC who received at least one cycle of neoadjuvant immunotherapy before surgery were included. Among them, there were 31 males and 12 females with a median age of 65 years (interquartile range: 58-69). All patients successfully completed the surgery without any surgical delays. The pCR rate was 14.0% (6/43), the MPR rate was 58.1% (25/43), and the R0 resection rate was 97.7% (42/43). Patients exhibited reliable safety during neoadjuvant therapy and postoperatively. The 2-year overall survival and disease-free survival rates were 90.7% and 81.4%, respectively. Kaplan-Meier survival analysis and log-rank test revealed lower recurrence rates and better survival in the MPR patients compared to the non-MPR patients. Conclusion The combination of neoadjuvant sintilimab and chemotherapy in the treatment of patients with locally advanced resectable ESCC has demonstrated significant clinical efficacy, while also being safe and reliable.

The incidence rate of hepatic fibrosis remains at a high level， and there is still a lack of specific therapeutic drugs， posing a serious threat to human health. As a type of natural active components widely present in plants， flavonoids have multiple physiological functions such as antioxidant， anti-inflammatory， and anti-fibrotic activities， and a large number of studies have confirmed the anti-hepatic fibrosis effect of flavonoids. As for the mechanism of action， flavonoids can target the functions of hepatic stellate cells by inhibiting their proliferation and differentiation， promoting their apoptosis， regulating the level of autophagy， reducing the formation of extracellular matrix， and regulating iron metabolism in hepatic stellate cells， and meanwhile， they can inhibit chronic liver inflammatory response， improve oxidative stress status， regulate intestinal flora balance， and block epithelial-mesenchymal transition， thereby blocking the progression of fibrosis through multiple dimensions. At the level of signaling pathways， flavonoids mainly exert an anti-fibrotic effect by regulating the abnormal activation of the signaling pathways such as transforming growth factor-β1/Smad， Janus kinase/signal transducer and activator of transcription， nuclear factor erythroid 2-related factor 2， nuclear factor-kappa B， phosphatidylinositol 3-kinase/protein kinase B， mitogen-activated protein kinase， Wnt/β-catenin， and adenosine 5'-monophosphate-activated protein kinase. This article summarizes the research advances in the anti-fibrotic effect of flavonoids， in order to provide a theoretical basis for further exploring their medicinal potential.

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide, with above 80% of cases be non-small cell lung cancer (NSCLC), among which lung squamous cell carcinoma (LUSC) occupies a significant proportion. Although comprehensive cancer therapies have considerably improved the overall survival of patients, patients with advanced LUSC have a poorer prognosis. Therefore, there is a need for a biomarker to predict the progress of advanced LUSC in order to improve prognosis through early diagnosis. Previous studies have shown that miRNAs are differentially expressed in lung cancer tissues and play roles as potential oncogenes or tumor suppressors. The aim of this study is to identify differentially expressed miRNAs between early-stage and advanced-stage LUSC, and to establish a set of miRNAs that can predict the progress of advanced LUSC. METHODS: Clinical data and miRNA-related data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatic methods were applied to analyze the data. Receiver operating characteristic (ROC) curves were plotted, and various online tools were used to predict target genes, with subsequent analysis of the potential biological mechanisms of these genes. RESULTS: A total of 58 differentially expressed miRNAs were identified between the experiment group and the control group. Seven miRNAs were selected for potential construction of a miRNA biomarker through LASSO regression, and based on the area under the curve (AUC) values of each miRNA, four of these miRNAs (miR-377-3p, miR-4779, miR-6803-5p, miR-3960) were ultimately chosen as biomarkers for predicting advanced LUSC. The AUC under the ROC curve for the combined four miRNAs was 0.865. Enrichment analysis showed that these target genes were involved in several pathways, including cancer-related pathways, mitogen-activated protein kinase (MAPK) signaling pathway, serine/threonine kinase, and tyrosine kinase signaling pathways. CONCLUSIONS The combined use of miR-377-3p, miR-4779, miR-6803-5p and miR-3960 provides a good predictive ability for the progress of advanced LUSC patients, with an AUC of 0.865.
Humans ; MicroRNAs/metabolism* ; Lung Neoplasms/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Prognosis ; ROC Curve ; Middle Aged

Objective To analyze the influencing factors and action paths of frailty in elderly patients with col-orectal cancer,so as to provide a theoretical clinical intervention.Methods A convenience sampling method was adopted.A total of 254 elderly patients with colorectal cancer who were scheduled for elective surgery in a tertiary A hospital in Shanxi Province from March 2023 to September 2024 were selected as the research subjects.General information questionnaires,Fried frailty phenotype,Perceived Ageism Scale,Multidimensional Assessment Scale of In-teroceptive Awareness Version 2-Chinese,Cancer Patient Self-Management Assessment Scale,and Anderson Symptom Inventory were used for the investigation,and a structural equation model was constructed.Results The incidence of frailty in elderly colorectal cancer patients before surgery is 38.98％.Anderson Symptom Assessment and Per-ceived Ageism were positively correlated with frailty(r=0.534,0.568,P＜0.01),while interoceptive sensitivity and the self-management level were negatively correlated with frailty(r=-0.444,-0.659,P＜0.01).Self-management behavior had only a direct effect on patients' frailty(β=-0.349,P＜0.001),while Anderson Symptom Assessment,perceived age discrimination and interoceptive sensitivity had both direct and indirect effects on patients' frailty(direct effects β=0.235,0.287,-0.220;indirect effects β=0.147,0.090,-0.113;all P＜0.001).Conclusion The incidence of frailty in elderly patients with colorectal cancer before surgery is high.Attention should be paid to patients who are elderly,female and have a low level of education.Medical staff can take targeted measures to enhance patients' interocep-tive concentration and stability,so that patients can better monitor and regulate their bodies and emotions,and im-prove their health-promoting decisions and behaviors.At the same time,attention should also be paid to the prob-lem of age discrimination to create a good medical environment for patients.

Objective To explore the application value of intravoxel incoherent motion(IVIM)imaging parameters in the differential diagnosis of benign and malignant breast nodules and their correlation with the expression of Ki-67 receptor in breast cancer.Methods The data of 41 female patients who completed 3.0 T breast magnetic resonance imaging(MRI)with complete surgical pathology results in the Second Hospital of Jiaxing City from October 2022 to January 2025 were analysed and evaluated.Conventional images and diffusion-weighted images with 11 b values were collected.The IVIM imaging parameters of real diffusion coefficient(D),perfusion related diffusion coefficient(D*)and perfusion fraction(f)were measured and calculated in the region of interest of each lesion.The receiver operating characteristic curve were plotted to quantify the differential diagnostic efficacy of each parameter of IVIM imaging in benign and malignant breast nodules.The differences of parameters between benign and malignant breast nodules and between the groups with different expression levels of Ki-67 receptor in breast cancer were analysed,and the correlation between each parameter and the expression level of Ki-67 in breast cancer was counted.Results The D value of benign breast nodules group(benign groups)was significantly higher than that of malignant breast nodules group(malignant groups),and the D*value was significantly lower than that of malignant group,and the differences between benign group and malignant group were statistically significant(t=-4.773,t=2.063,P＜0.05);Thefvalue of benign group was slightly lower than that of malignant group,and the differences between two groups were not statistically significant(t=0.035,P＞0.05).Among the parameters of IVIM imaging,D value had the best differential diagnostic efficacy for benign and malignant breast nodules,with area under the curve(AUC)of 0.870(95％CI:0.755-0.985)and a specificity of 75.0％;D*value had the second best differential diagnostic efficacy after D value,with an AUC of 0.789(95％CI:0.658-0.920),but it had the highest sensitivity of 88.2％;And the differential diagnosis efficiency off value was the worst,much less than D and D*values.The D value in the high Ki-67 expression group of breast cancer was lower than that in the low expression group,while the D* and f values in the high expression group were higher than that in the low expression group,and the differences of each imaging parameter of IVIM were not statistically significant between two groups(t=-2.617,t=2.169,t=0.647,P＞0.05).There was a significant negative correlation between the expression of the Ki-67 receptor and the D value(r=-0.615,P＜0.05),and no significant correlation was seen with either D *or f value(r=0.223,r-0.031,P＞0.05).Conclusion The D and D*values of IVIM imaging parameters have great clinical value in the differential diagnosis of benign and malignant breast nodules.

Objective To observe the effects of Yifei Jianpi Prescription on airway mucus hypersecretion and protein expressions of EGFR/PKC/NF-κB pathway in lipopolysaccharide(LPS)-induced acute lung injury(ALI)model rats;To explore its mechanism in the treatment of ALI.Methods Ten of 60 SPF SD rats were randomly selected as blank group,and the other rats were intratracheal instilled with LPS to establish ALI model.The model rats were randomly divided into model group,dexamethasone group and Yifei Jianpi Prescription high-,medium-and low-dosage groups,with 8 rats in each group.Each treatment group was given corresponding drug solution by gavage,and the blank group and model group were given equal volume of normal saline by gavage,once a day for 14 days.The pulmonary functions of rats were measured[peak expiratory flow(PEF),tidal volume(TV),expiratory volume(EV),50%expiratory flow rate(EF50)],HE staining was used to observe the morphology of lung tissue,AB-PAS staining was used to evaluate the proliferation and mucus secretion of goblet cells,the expressions of epidermal growth factor receptor(EGFR),protein kinase C(PKC),nuclear factor-κB(NF-κB)p65 and MUC5AC in lung tissue were detected by immunofluorescence staining,the mRNA expressions of EGFR and MUC5AC in lung tissue were detected by fluorescent quantitative PCR,and the content of MUC5AC in lung tissue was detected by ELISA.Results Compared with the blank group,PEF,TV,EV and EF50 of the model group rats significantly decreased(P<0.01);the bronchial wall was significantly thickened,the lumen narrowed,pulmonary interstitial edema and hyperemia,the thickness of alveolar wall increased,accompanied by a large number of inflammatory cells infiltration,and the lung tissue injury score increased significantly(P<0.01);goblet cells proliferated significantly,mucus secretion increased significantly(P<0.01);the protein expressions of EGFR,PKC,NF-κB p65,MUC5AC and mRNA expressions of EGFR and MUC5AC in lung tissue increased significantly(P<0.01),and the content of MUC5AC in lung tissue increased significantly(P<0.01).Compared with the model group,PEF,TV,EV and EF50 in dexamethasone group and Yifei Jianpi Prescription each dosage groups increased in varying degrees;the pathological injury of lung tissue was alleviated to varying degrees,the score of lung tissue injury was reduced;the proliferation of goblet cells was reduced,and the secretion of mucus was reduced,the expressions of EGFR,PKC,NF-κB p65,MUC5AC protein and EGFR,MUC5AC mRNA in lung tissue decreased,and the content of MUC5AC in lung tissue decreased.There was statistical significance in dexamethasone group and Yifei Jianpi Prescription high-and medium-dosage groups(P<0.01).Conclusion Yifei Jianpi Prescription can inhibit the hypersecretion of airway mucus and the high expression of EGFR/PKC/NF-κB pathway protein in rats with ALI induced by LPS.

Objective To investigate the mechanism of Shugan Zhixie Prescription in treating irritable bowel syndrome with diarrhea(IBS-D)using network pharmacology;To validate the findings through in vivo experiments.Methods Active components and potential targets of Shugan Zhixie Prescription were identified via the TCMSP database.Disease targets for IBS-D were retrieved from GeneCards,DisGeNET and OMIM databases.The intersection of drugs and disease targets was taken,and the protein interaction network was constructed by using STRING database.GO and KEGG pathways were enriched to identify the key signaling pathways of Shugan Zhixie Prescription in the treatment of IBS-D.The rat model of liver depression and spleen deficiency type IBS-D was established by the method of abnormal hunger and satiety,restraint pinch stress and intestinal perfusion of acetic acid.The rats were intervened with low-,medium-and high-dosage of Shugan Zhixie Prescription respectively for 14 days.Serum contents of diamine oxidase(DAO),interleukin(IL)-8,and IL-18 were measured by ELISA.Protein expressions and mRNA expressions of relevant targets in colonic tissue were detected using Western blot and RT-qPCR.Results A total of 26 active components and 553 targets of Shugan Zhixie Prescription were obtained,and 1 930 targets of IBS-D disease were obtained,with 184 drug-disease intersection targets.The possible mechanism was related to NF-κB,AGE-RAGE,Th17 cell differentiation and other signaling pathways.Animal experiments demonstrated that Shugan Zhixie Prescription could significantly reduce defecation frequency,fecal water content,and inflammatory cytokine levels in model rats.It markedly decreased TLR4 and NF-κB protein expressions(P<0.01),while increased AQP3,AQP8 and Occludin protein expressions in colonic tissue(P<0.01,P<0.05).Conclusion Shugan Zhixie Prescription exerts therapeutic effects on IBS-D through multiple pathways and targets,and the mechanism may be related to inhibiting TLR4/NF-κB signaling pathway and promoting intestinal barrier repair.

Objective:To investigate the clinical characteristics, treatment and prognostic factors in patients with primary central nervous system lymphoma (PCNSL) .Methods:This retrospective study included 52 patients with PCNSL treated in Peking University Third Hospital between January 2013 and December 2023. An analysis was conducted on the clinical characteristics, treatment and prognostic factors of the patients. Univariate and multivariate Cox proportional hazards models were used to determine factors associated with progression-free survival and overall survival (OS) .Results:In the overall cohort, the median age at diagnosis was 57 (range, 23-87) years, with a male/female ratio of 1.08:1. Neurological dysfunction (71.2%) and intracranial hypertension (57.7%) were common clinical manifestations. The tumors involved the deep brain tissue and presented as multifocal lesions. Treatment efficacy was evaluable in 49 patients, with a median follow-up of 23 (95% CI: 8.6-37.4) months. The 2- and 5-year PFS rates were 56.4% (95% CI: 42.2%-68.3%) and 36.3% (95% CI: 17.3%-53.4%), respectively, whereas the OS rates were 75.5% (95% CI: 61.7%-87.2%) and 66.0% (95% CI: 43.9%-78.3%), respectively. By univariate Cox regression analysis, age >60 years ( HR=3.436, 95% CI: 1.008-11.710, P=0.049) and Memorial Sloan-Kettering Cancer Center grade 3 tumor ( HR=22.10, 95% CI: 4.736 - 103.400, P< 0.001) were prognostic factors for worse OS, whereas auto-hematopoietic stem cell transplantation (HSCT) as consolidation therapy was significantly associated with longer OS ( HR=0.223, 95% CI: 0.077-0.643, P=0.006). By multivariate Cox regression analysis, high-dose methotrexate chemotherapy ( HR=0.082, 95% CI: 0.008-0.873, P=0.038) and auto-HSCT ( HR=0.151, 95% CI: 0.030-0.747, P= 0.020) were independent predictors of prolonged OS. Conclusion:The prognosis was poor in patients with PCNSL who are elderly and those at high risk according to risk stratification. Adopting treatment regimens containing high-dose methotrexate and performing auto-HSCT can improve survival in patients with PCNSL.