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.

Approximately 10% of the global adult population has diabetes, with accumulating evidence linking suboptimal vitamin D levels to an increased risk of type 2 diabetes and its complications. Current clinical studies suggest that vitamin D supplementation may enhance insulin sensitivity and improve glycemic control, prompting significant interest in its potential as a therapeutic intervention. However, further high-quality, large-scale randomized controlled trials are required to validate its efficacy in glucose metabolism regulation and clarify the underlying molecular mechanisms. These investigations will provide critical evidence to inform precision medicine approaches for diabetes prevention and management.

Background and Aims:Currently,the treatment of hepatocellular carcinoma(HCC)faces significant challenges due to recurrence and metastasis,with tumor immune evasion being one of the key mechanisms underlying these issues.Signal transducer and activator of transcription 3(STAT3),an important transcription factor,is overactivated in many malignancies and is involved in both tumorigenesis and progression,closely associated with immune evasion.Programmed cell death ligand 1(PD-L1),a key immune checkpoint,helps tumor cells evade immune surveillance when its expression is upregulated,thereby suppressing anti-tumor immunity.Studies have shown that STAT3 may activate the MYC signaling pathway through interaction with DNA-activated protein kinase(PRKDC),thereby promoting PD-L1 expression and inducing immune evasion.However,the specific mechanism of the STAT3/PRKDC/MYC axis in HCC remains unclear.This study aims to elucidate the molecular mechanism by which STAT3 regulates PD-L1 expression through the PRKDC/MYC signaling pathway,potentially inducing immune evasion in HCC,with the goal of providing potential targets for HCC immunotherapy.Methods:The expressions of STAT3 in human normal liver cells(HL-7702)and human HCC cells(HuH-7,HepG2)were detected by qRT-PCR and Western blot.Plasmids with STAT3 knockdown(si-STAT3)and PRKDC overexpression(oe-PRKDC),along with their respective negative controls(si-NC,oe-NC),were constructed and transfected into HCC cells(HuH-7)according to the experimental design,with untreated HuH-7 cells as the blank control.Western blot was used to analyze the expression of STAT3,PRKDC,PD-L1,and MYC pathway-related proteins.Cell proliferation,invasion,migration,and apoptosis of HCC cells were assessed by CCK-8,Transwell,wound healing assay,and flow cytometry.After co-culturing HuH-7 cells with human peripheral blood mononuclear cells(hPBMCs),ELISA was used to detect the secretion of the immune regulatory factor interferon γ(IFN-γ).Co-immunoprecipitation and immunofluorescence co-localization were performed to verify the interaction between STAT3 and PRKDC proteins.Results:Results of qRT-PCR and Western blot showed that the mRNA and protein levels of STAT3 were significantly elevated in HCC cells(both P＜0.05).Functional experiments demonstrated that in the si-STAT3 group,HCC cell proliferation,migration,and invasion were significantly weakened,and cell apoptosis was notably increased;the expression of PD-L1 and MYC pathway-related proteins was significantly downregulated;the secretion of IFN-γ was significantly increased after co-culturing with hPBMCs(all P＜0.05).After co-culturing with oe-PRKDC plasmids,the effects of STAT3 knockdown on HCC cells were significantly reversed(all P＜0.05).Scansite 4.0 database analysis revealed that STAT3 and PRKDC have binding sites,and co-immunoprecipitation and immunofluorescence co-localization experiments confirmed the interaction between STAT3 and PRKDC proteins.Conclusion:STAT3 is highly expressed in HCC cells and can promote HCC cell proliferation,migration,invasion,and immune evasion through interaction with PRKDC,suppress cell apoptosis,activate the MYC pathway,and increase PD-L1 expression.The STAT3/PRKDC/MYC axis may serve as a potential target for HCC immunotherapy.

Background and Aims:Currently,the treatment of hepatocellular carcinoma(HCC)faces significant challenges due to recurrence and metastasis,with tumor immune evasion being one of the key mechanisms underlying these issues.Signal transducer and activator of transcription 3(STAT3),an important transcription factor,is overactivated in many malignancies and is involved in both tumorigenesis and progression,closely associated with immune evasion.Programmed cell death ligand 1(PD-L1),a key immune checkpoint,helps tumor cells evade immune surveillance when its expression is upregulated,thereby suppressing anti-tumor immunity.Studies have shown that STAT3 may activate the MYC signaling pathway through interaction with DNA-activated protein kinase(PRKDC),thereby promoting PD-L1 expression and inducing immune evasion.However,the specific mechanism of the STAT3/PRKDC/MYC axis in HCC remains unclear.This study aims to elucidate the molecular mechanism by which STAT3 regulates PD-L1 expression through the PRKDC/MYC signaling pathway,potentially inducing immune evasion in HCC,with the goal of providing potential targets for HCC immunotherapy.Methods:The expressions of STAT3 in human normal liver cells(HL-7702)and human HCC cells(HuH-7,HepG2)were detected by qRT-PCR and Western blot.Plasmids with STAT3 knockdown(si-STAT3)and PRKDC overexpression(oe-PRKDC),along with their respective negative controls(si-NC,oe-NC),were constructed and transfected into HCC cells(HuH-7)according to the experimental design,with untreated HuH-7 cells as the blank control.Western blot was used to analyze the expression of STAT3,PRKDC,PD-L1,and MYC pathway-related proteins.Cell proliferation,invasion,migration,and apoptosis of HCC cells were assessed by CCK-8,Transwell,wound healing assay,and flow cytometry.After co-culturing HuH-7 cells with human peripheral blood mononuclear cells(hPBMCs),ELISA was used to detect the secretion of the immune regulatory factor interferon γ(IFN-γ).Co-immunoprecipitation and immunofluorescence co-localization were performed to verify the interaction between STAT3 and PRKDC proteins.Results:Results of qRT-PCR and Western blot showed that the mRNA and protein levels of STAT3 were significantly elevated in HCC cells(both P＜0.05).Functional experiments demonstrated that in the si-STAT3 group,HCC cell proliferation,migration,and invasion were significantly weakened,and cell apoptosis was notably increased;the expression of PD-L1 and MYC pathway-related proteins was significantly downregulated;the secretion of IFN-γ was significantly increased after co-culturing with hPBMCs(all P＜0.05).After co-culturing with oe-PRKDC plasmids,the effects of STAT3 knockdown on HCC cells were significantly reversed(all P＜0.05).Scansite 4.0 database analysis revealed that STAT3 and PRKDC have binding sites,and co-immunoprecipitation and immunofluorescence co-localization experiments confirmed the interaction between STAT3 and PRKDC proteins.Conclusion:STAT3 is highly expressed in HCC cells and can promote HCC cell proliferation,migration,invasion,and immune evasion through interaction with PRKDC,suppress cell apoptosis,activate the MYC pathway,and increase PD-L1 expression.The STAT3/PRKDC/MYC axis may serve as a potential target for HCC immunotherapy.

Background Lipid metabolism in liver shows circadian-dependent profiles. The hepatotoxicity of environmental chemicals is dependent on circadian time. Objective To observe the effects of bisphenol A (BPA) exposure at different zeitgeber time (ZT) on hepatic and blood lipid metabolism and decipher the underlying mechanisms related to circadian rhythm in mice. Methods Thirty-five female C57BL/6J mice were sacrificed every 4 h in a light-dark cycle (12 h/12 h). The liver tissues were collected to describe the circadian profiles of hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels within 24 h. Thirty female mice were divided into 6 groups by the timing (ZT3 represents the 3 h after light on, ZT15 represents the 3 h after light off) and dose (50 or 500 μg·kg⁻¹·d⁻¹) of BPA exposure to observe hepatotoxicity. Mice were gavaged with designed doses of BPA once per day for 4 weeks. Mice were maintained with ad libitum access to food and water and measured body weight weekly. After the experiment, mice were euthanatized and liver tissues were separated to determine the biochemical indicators of lipid metabolism and lipid metabolism- and circadian-related gene mRNA expressions. Results Hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels were rhythmic during a 24 h period in mice. At ZT3 and ZT15, BPA did not alter body weight, plasma glucose, plasma total cholesterol, plasma low density lipoprotein cholesterol, and plasma triglycerides (P>0.05). The plasma high density lipoprotein cholesterol decreased in the 50 μg·kg⁻¹·d⁻¹ BPA group at ZT3 by 14.56% compared with the control group (P<0.05). The liver triglycerides increased in the 50 μg·kg⁻¹·d⁻¹ BPA group at ZT15 by 115.20% compared with the control group (P<0.05). BPA decreased Srebp1c mRNA expression level when dosing at ZT3 and increased Chrebp, Srebp1c, and Acc1 mRNA expression levels when dosing at ZT15 compared with the control group (P<0.05). BPA increased Bmal1 mRNA expression level and decreased Rev-erbα mRNA expression level at ZT3 exposure and decreased Bmal1 and increased Rev-erbα mRNA expression level at ZT15 exposure (P<0.05). Conclusion BPA exposure at light or dark period has different effects on hepatic lipid metabolism in mice. Hepatic lipid deposit appears when BPA is dosed at dark period. Rev-erbα-Bmal1 regulation circuits and the subsequent upregulation of Srebp1c and Chrebp and the target gene Acc1 may be involved.

Objective:To explore the application effect of case-based learning (CBL) in teaching magnetic resonance imaging (MRI) for non-imaging clinical professional postgraduates.Methods:Eighty non-imaging clinical professional postgraduates who had standardized residency training from 2017 to 2019 were selected as the participants and were randomly divided into two groups, experimental group and control group. The experimental group adopted CBL, and the control group adopted traditional teaching mode. After the standardized training in the radiology department, the differences in image reading scores, theoretical scores and course evaluation were compared between the two groups. SPSS 25.0 statistical software was used for analysis. Independent t test was used for the measurement data of normal distribution, Mann-Whitney U test was used for the measurement data of skewed distribution, and categorical variables were compared by chi-square test. Results:In the reading scores of MRI, the scores of the experimental group and the control group were (82.53 ± 5.72) points and (77.38 ± 6.14) points respectively, and the number of students in the experimental group whose reading scores were between 80-100 segment was 63.6% higher than that in the control group, with significant differences between the two groups ( P < 0.001), but without significant differences in theoretical average scores between the two groups ( P > 0.05). In addition, in the course evaluation, except for the index of learning burden, there were significant differences in other indexes between the experimental group and the control group ( P < 0.05). Conclusion:In the teaching of MRI, the application of the CBL helps non-imaging clinical professional postgraduates improve their MRI diagnostic thinking and independent reading ability.

Objective    To summarize the experience of minimally invasive anterior mediastinal tumor resection in our center, and compare the Da Vinci robotic and video-assisted thoracoscopic approaches in the treatment of mediastinal tumor. Methods    A retrospective cohort study was conducted to continuously enroll 102 patients who underwent minimally invasive mediastinal tumor resection between September 2014 and November 2019 by the single medical group in our department. They were divided into two groups: a robotic group (n=47, 23 males and 24 females, average age of 52 years) and a thoracoscopic group (n=55, 29 males and 26 females, average age of 53 years). The operation time, intraoperative blood loss, postoperative thoracic drainage volume, postoperative thoracic drainage time, postoperative hospital stay, hospitalization expense and other clinical data of two groups were compared and analyzed. Results    All the patients successfully completed the surgery and recovered from hospital, with no perioperative death. Myasthenia gravis occurred in 4 patients of the robotic group and 5 of the thoracoscopic group. The tumor size was 2.5 (0.8-8.7) cm in the robotic group and 3.0 (0.8-7.7) cm in the thoracoscopic group. Operation time was 62 (30-132) min in the robotic group and 60 (29-118) min in the thoracoscopic group. Intraoperative bleeding volume was 20 (2-50) mL in the robotic group and 20 (5-100) mL in the thoracoscopic group. The postoperative drainage volume was 240 (20-14 130) mL in the robotic group and 295 (20-1 070) mL in the thoracoscopic group. The postoperative drainage time was 2 (1-15) days in the robotic group and 2 (1-5) days in the thoracoscopic group. There was no significant difference between the two groups in the above parameters and postoperative complications (P>0.05). The postoperative hospital stay were 3 (2-18) days in the robotic group and 4 (2-14) in the thoracoscopic group (P=0.014). The hospitalization cost was 67 489 (26 486-89 570) yuan in the robotic group and 27 917 (16 817-67 603) yuan in the thoracoscopic group (P=0.000). Conclusion    Compared with the video-assisted thoracoscopic surgery, Da Vinci robot-assisted surgery owns the same efficacy and safety in the treatment of mediastinal tumor, with shorter postoperative hospital stay, but higher cost.

Objective:To discuss the application and effectiveness of the flipped classroom based on Wechat platform in the teaching of neurology.Methods:clinical students of grade 2014 of binjiang college of Zhejiang Chinese Medical University were selected as teaching subject. The students were divided into experimental group which contained a total of 74 students in class one and class three and the control group which contained a total of 38 students in class two. Peripheral neuropathy and neuromuscular-junction disease were selected as teaching contents. The experimental group adopted flipped classroom as the teaching mode and Wechat platform for pre-class preparation, after-school review and interactive communication. The control group was taught by traditional teaching mode. Before and after class, students in the two groups had a small-scale test and were surveyed by questionnaire, respectively. Students in the two groups took the same final exam which included case analysis when the course was over. The scores of the final exam and the results of the case analysis of each group were recorded and analyzed. All data were processed with statistical software SPSS 20.0, and t-test or chi-square test was used. Results:Students in the experimental group had significantly higher test scores in the after-class small-scale test than those in the control group ( P=0.038). Their final exam scores were higher than those in the control group ( P=0.046), and their scores of case analysis in the final exam were higher than those in the control group ( P=0.026). The results of pre-class questionnaire survey showed that the proportion of students who chose "good" in the experimental group was higher than that in the control group on the understanding of the learning content and the preparation ( P<0.05). In the after-class questionnaire survey, the proportion of students who chose "excellent" and "good" in the evaluation of learning interest in the experimental group was higher than those in the control group ( P<0.05), the proportion of students in the experimental chose "good" in evaluating their self-learning ability was higher than that in the control group ( P<0.05), the proportion of "excellent" on clinical thinking ability and teaching satisfaction was higher in the experimental group than that in the control group ( P<0.05), and the overall proportion of students who chose "excellent" and "good" in all items in the experimental group were higher than that in the control group ( P<0.05). In the experimental group, the overall proportion of students who selected "excellent" and "good" in on the evaluation of their learning interest was significantly increased in the after-class questionnaire survey compared with the pre-class questionnaire survey ( P<0.01). Conclusions:The application of flipped classroom based on Wechat platform is feasible and effective in the teaching of neurology. It can make up for the deficiency of traditional teaching methods. It is helpful to improve students' learning interest and self-learning ability, and is also helpful to exercise their clinical thinking ability. Thus this method deserves further popularization.

The technical combination of artificial intelligence (AI) and thoracic surgery is increasingly close, especially in the field of image recognition and pathology diagnosis. Additionally, robotic surgery, as a representative of high-end technology in minimally invasive surgery is flourishing. What progress has been or will be made in robotic surgery in the era of AI? This article aims to summarize the application status of AI in thoracic surgery and progress in robotic surgery, and looks ahead the future.

Objective: To evaluate and compare the clinical value of early enteral nutrition (EEN) and total parenteral nutrition (TPN) af-ter esophageal cancer surgery. Methods: We retrospectively analyzed 237 patients who underwent esophageal cancer surgery at Bei-jing Shijitan Hospital from March 2011 to March 2019. They were assigned into two groups based on the postoperative nutritional sup-port used: EEN (136 cases) and TPN (101 cases). Nutritional status, liver function, recovery of gastrointestinal function, days of hospital-ization, and postoperative complications were compared between the two groups after propensity score matching. Results: Using 1 :1 nearest neighbor matching, we successfully matched 91 pairs of patients. The prealbumin (PA) level was significantly higher in the EEN group than in the TPN group 7 days after surgery (P<0.05); however, there was no significant difference in albumin (ALB) level before surgery, 3 or 7 days after surgery. Additionally, the levels of ALT and AST in the EEN group were significantly lower than those in the TPN group 3 and 7 days after surgery (P<0.05). The incidence of acid reflux, vomiting, and diarrhea in the EEN group was higher than that in the TPN group, while the incidence of pulmonary edema and pulmonary infection was lower in the EEN group than in the TPN group (P<0.05). Conclusions: Compared with TPN, EEN is associated with a high incidence of acid reflux, vomiting, and diarrhea after esophageal cancer surgery, but it has a lower impact on liver function. EEN can promote the recovery of intestinal function, improve nutritional indicators, and shorten hospitalization time.