BACKGROUND:In mammals,white adipose tissue stores energy,whereas brown adipose tissue dissipates energy.Conversion from White to brown/beige adipocytes is a potential therapeutic strategy to fight obesity,but the molecular mechanisms that drive this process is unclear.OBJECTIVE:To reveal the potential relationship between Hr mutation and adipocyte browning.METHODS:Ten 10-week-old male Yuyi hairless mice and 10 littermate wild-type controls were selected and changes in food intake,body mass and inguinal white adipose tissue mass were recorded.Serum levels of leptin and adiponectin were estimated by ELISA.Glucose tolerance test was used to assess glucose metabolic function and insulin tolerance test was performed to analyze insulin sensitivity.Hematoxylin-eosin staining was performed to observe pathological changes of inguinal white adipose tissue in mice.Real-time fluorescence quantitative PCR and immunofluorescent staining were performed to analyze the expression of genes and proteins associated with browning of white adipose tissue in the groin.RESULTS AND CONCLUSION:(1)Compared with wild-type mice,Yuyi hairless mice had increased brown fat content and ultimately increased glucose tolerance and insulin sensitivity.Hr mutation reduced body mass and inguinal adipose mass in mice,but food intake did not change significantly compared with wild-type mice,suggesting that there was a reduction in body mass and adipose mass but not in food intake.(2)Hematoxylin-eosin staining results showed browning of adipocytes in the inguinal white adipose tissue of Yuyi hairless mice,which became smaller,rounder and accompanied by the appearance of multilocular cells.(3)There was increased level of peroxisome proliferator-activated receptor γ coactivator 1α and activation of thyroid hormone receptor α,uncoupling protein 1,and the mitochondria-shaping genes(nuclear respiratory factor 1and mitochondrial transcription factor A),thereby promoting browning of adipocytes.Thus,Hr mutation activates the peroxisome proliferator-activated receptor γ coactivator 1α/thyroid hormone receptorα/uncoupling protein 1 signaling pathway and increases brown adipose content in mice,thereby promoting energy expenditure and thermogenesis and inhibiting obesity.

BACKGROUND:In mammals,white adipose tissue stores energy,whereas brown adipose tissue dissipates energy.Conversion from White to brown/beige adipocytes is a potential therapeutic strategy to fight obesity,but the molecular mechanisms that drive this process is unclear.OBJECTIVE:To reveal the potential relationship between Hr mutation and adipocyte browning.METHODS:Ten 10-week-old male Yuyi hairless mice and 10 littermate wild-type controls were selected and changes in food intake,body mass and inguinal white adipose tissue mass were recorded.Serum levels of leptin and adiponectin were estimated by ELISA.Glucose tolerance test was used to assess glucose metabolic function and insulin tolerance test was performed to analyze insulin sensitivity.Hematoxylin-eosin staining was performed to observe pathological changes of inguinal white adipose tissue in mice.Real-time fluorescence quantitative PCR and immunofluorescent staining were performed to analyze the expression of genes and proteins associated with browning of white adipose tissue in the groin.RESULTS AND CONCLUSION:(1)Compared with wild-type mice,Yuyi hairless mice had increased brown fat content and ultimately increased glucose tolerance and insulin sensitivity.Hr mutation reduced body mass and inguinal adipose mass in mice,but food intake did not change significantly compared with wild-type mice,suggesting that there was a reduction in body mass and adipose mass but not in food intake.(2)Hematoxylin-eosin staining results showed browning of adipocytes in the inguinal white adipose tissue of Yuyi hairless mice,which became smaller,rounder and accompanied by the appearance of multilocular cells.(3)There was increased level of peroxisome proliferator-activated receptor γ coactivator 1α and activation of thyroid hormone receptor α,uncoupling protein 1,and the mitochondria-shaping genes(nuclear respiratory factor 1and mitochondrial transcription factor A),thereby promoting browning of adipocytes.Thus,Hr mutation activates the peroxisome proliferator-activated receptor γ coactivator 1α/thyroid hormone receptorα/uncoupling protein 1 signaling pathway and increases brown adipose content in mice,thereby promoting energy expenditure and thermogenesis and inhibiting obesity.

Objective:To evaluate the clinical efficacy, safety and treatment persistence of upadacitinib in Crohn's disease (CD) patients.Methods:The single-center retrospective cohort study was conducted. The patients with moderate-to-severe active CD initiating upadacitinib therapy from November 2023 to November 2024 in Nanjing Drum Tower Hospital were collected through searching the electronic medical records and paper-based patient databases. The primary outcome was the clinical remission rate at week 12. Secondary outcomes included the clinical response rate at week 12; clinical response and remission rates at weeks 4, 24 and 48; biomarker (fecal calprotectin or C-reactive protein) remission rates at all time points; as well as endoscopic remission and response rates, treatment persistence and safety evaluation.Results:A total of 44 CD patients were included, comprising 24 males (54.5%) and 20 females (45.5%). The median age was 33 (25, 40) years. The baseline Crohn's disease activity index (CDAI) score was 260.5 (225.9, 550.0) points. Patients had previously received a median of 2 (1, 2) biologic treatments. All 44 patients completed the 12-week induction therapy. With a median follow-up of 30.00 (16.25, 46.25) weeks, the clinical remission rate was 50.0% (22/44) at week 12. The clinical remission rate, clinical response rate, and biomarker remission rate were 52.3% (23/44), 88.6% (39/44) and 72.7% (32/44) respectively at week 4, and the clinical response rate and biomarker remission rate were 88.6% (39/44) and 77.2% (34/44) respectively at week 12. The clinical remission rates, clinical response rates and biomarker remission rates evolved to 43.3% (13/30), 86.7% (26/30) and 80.0% (24/30) at week 24, and further to 44.4% (4/9), 77.8% (7/9) and 77.8% (7/9) at week 48. During the follow-up period, 13 CD patients completing endoscopic evaluation, endoscopic remission and response rates were 30.8% and 23.1% respectively. CD-related surgery rate was 4.5% (2/44). Safety analysis demonstrated that the overall adverse events rate was 56.8% (25/44) including 7 patients with serious adverse events. A total of 8 patients discontinued treatment, among which 3 were due to primary loss of response, 1 due to secondary loss of response, 2 due to drug-related adverse events alone, and 2 due to concurrent primary loss of response and adverse events. The Kaplan-Meier curve for treatment persistence showed that among 39 CD patients who achieved clinical response at week 12, the continued treatment rates were 90.3% at week 12 and 85.3% at week 24 of follow-up. Two patients (5.6%) received dose escalation of upadacitinib, both of whom achieved clinical remission.Conclusion:Real-world research data demonstrate that upadacitinib exhibits significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe active CD patients with prior biologic exposure, and no new unexpected adverse events are identified.

Objective:To investigate gut microbiota differences between individuals with and without colorectal adenoma(CRA)and to identify gut microbes associated with CRA.Methods:This cross-sectional study analyzed the gut microbiota of 100 patients with CRA and 68 individuals without CRA(aged 40-75 years)who underwent colonoscopies between March 2021 and March 2022 at Tianjin Nankai Hospital.Fecal samples were sequenced for the V3-V4 region of the bacterial 16S rRNA gene using the Illumina NovaSeq platform.Results:Compared to the non-CRA group,the CRA group exhibited reduced relative abundances of identified and unidentified Lachnospiraceae,with increased Faecalibacterium and Streptococcus.In the non-CRA group,the relative abundances of Coprococcus,unidentified Clostridiaceae,and Clostridium were higher.LEfSe analysis revealed significant enrichment of Gammaproteobacteria,Proteobacteria,Enterobacteriales,and Faecalibacterium in the CRA group,while the non-CRA group was enriched for Moraxellaceae,Acinetobacter,and Anaerostipes.Conclusions:These findings suggest a discernible disparity in the gut microbiota structure between CRA patients and individuals without adenoma.The enrichment of potential pathogenic taxa,such as Faecalibacterium and Streptococcus,in the CRA group suggests a possible association with adenoma development.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective:To investigate the impact and mechanism of polydatin(PD)on lipopolysaccharide(LPS)induced in-flammatory damage in pancreatic acinar cells.Methods:Rat pancreatic exocrine cells AR42J were cultured in vitro,LPS treated cells were used to construct a cell inflammatory injury model,and co-cultured with 0,12.5,25,50,100 and 200 μg/L PD,CCK-8 method was applied to detect cell proliferation activity;AR42J cells were grouped into blank group(CT group),inflammatory injury model group(M group),PD group(100 μg/L),and PD+WZ811 group[stromal cell derived factor 1(SDF-1)/CXC chemokine receptor 4(CXCR4)pathway inhibitor](100 μg/L PD+1 μmol/L WZ811),dinitrophenylhydrazine method was applied to detect the leakage rate of lactate dehydrogenase(LDH)in each group of cells,flow cytometry was applied to detect cell apoptosis rate,ELISA kit was ap-plied to determine the levels of IL-1β and TNF-α in cell supernatant,thiobarbituric acid method were applied to determine the content of malondialdehyde(MDA),Xanthine oxidation method was applied to measure superoxide dismutase(SOD)activity,immunofluo-rescence staining was applied to detect the expressions of SDF-1 and CXCR4 proteins.Results:Compared with 0 μg/L group,100 μg/L and 200 μg/L PD obviously increased cell proliferation activity;compared with the CT group,the leakage rate of LDH,apoptosis rate,and the contents of IL-1β,TNF-α and MDA of cells in the M group increased,the SOD activity and expressions of SDF-1 and CXCR4 proteins decreased(P<0.05);compared with the M group,the leakage rate of LDH,apoptosis rate,and the contents of IL-1β,TNF-α and MDA of cells in the PD group decreased,the SOD activity and expressions of SDF-1 and CXCR4 proteins increased(P<0.05);compared with the PD group,the leakage rate of LDH,apoptosis rate,and the contents of IL-1β,TNF-α,and MDA of cells in the PD+WZ811 group increased,the SOD activity and expression of SDF-1 and CXCR4 proteins decreased(P<0.05).Conclusion:The protective effect of PD on LPS-induced inflammatory damage in AR42J cells may be related to the activation of the SDF-1/CXCR4 signaling pathway.

Objective To investigate the changes of 22 bile acid sub components and 17 traditional bio-chemical indicators in serum of patients with non-alcoholic fatty liver disease(NAFLD),and the diagnostic value of detecting the above indicators alone or in combination for NAFLD.Methods A total of 168 NAFLD patients(NAFLD group)and 216 non-NAFLD apparently healthy individuals(non-NAFLD group)were se-lected,bile acid sub components were determined by liquid chromatography tandem mass spectrometry,and traditional biochemical indicators were detected by automatic biochemical analyzer.Results There were sta-tistically significant differences in the levels of 12 bile acid sub components and 12 traditional biochemical indi-cators between NAFLD group and non-NAFLD group(P<0.05).Compared to traditional biochemical indica-tors,bile acid sub components were less affected by body mass index(BMI).The area under the curve for di-agnosing NAFLD by combining three bile acid sub components[taurocholic acid(TCA),sodium taurodeoxy-cholate(TDCA),and tauroursodeoxycholic acid(UDCA)]with three traditional biochemical indicators[ala-nine aminotransferase(ALT),5'Nucleotidase(5'-NT),and small and dense low-density lipoprotein cholester-ol(sd-LDL-C)]was the largest,which was 0.810.Conclusion Twelve kinds of bile acid sub components in the blood of NAFLD patients have changed,and the combined detection of bile acid sub components and tradi-tional biochemical indicators could improve the diagnostic efficacy of NAFLD to a certain extent.

Abstract In order to understand and analyze the current standards and application of school desks and chairs for primary and secondary schools, and to promote the healthy growth of primary and secondary school students. The article conducts a comprehensive review of the functional and dimensional standards for school furniture both domestically and internationally, and objectively analyzes the current utilization and existing issues concerning desks and chairs in schools. It further explores the multifaceted factors that influence the allocation of desks and chairs, and proposes effective countermeasures, so as to provide a reference for the risk factors of common diseases related to desks and chairs, such as myopia and abnormal spinal curvature.

Purpose To develop and validate a radiomics-clinical model that could accurately predict the recurrence of hepatocellular carcinoma(HCC)after undergoing tumor resection.Materials and Methods A total of 311 HCC patients underwent tumor resection in the Affiliated Hospital of North Sichuan Medical College from January 2015 to June 2022 were retrospectively collected,and they were randomly divided into a training cohort(n=217)and a validation cohort(n=94)in the ratio of 7∶3.Tumor and peritumoral 5 mm regions of interest were outlined on arterial and portal venous phase images and radiomics features were extracted to establish an arterio-portal radiomics model.Independent clinical risk factors associated with postoperative recurrence were explored by univariate and multivariate Cox analysis,then clinical model was established.A combined radiomics-clinical model was established by combining clinical independent risk factors and radiomics features.The area under the curve,specificity,sensitivity,net reclassification improvement and integrated discrimination improvement were used to assess the discrimination of all models.The calibration curve assessed the calibration of the model and decision curve analysis assessed the clinical utility of the model.Validation was performed by validation cohort data.Results The Rad-A5V5-clinical model had the best predictive performance for postoperative recurrence of HCC,the area under the curve,specificity and sensitivity of the validation cohort were 0.743(95%CI 0.640-0.846),0.647 and 0.717,respectively.The results of net reclassification improvement and integrated discrimination improvement showed that compared with clinical model and radiomics model,the prediction ability of Rad-A5V5-clinical model was improved the best one.The calibration curves showed that the predicted values of the Rad-A5V5-clinical model conformed the most favorably to the true values.The results of the decision curve analysis curve analyses showed that,among all models,the Rad-A5V5-clinical model would obtain the largest net benefit within a certain threshold range.Conclusion The predictive efficacy for post-tumor resection recurrence in HCC is significantly improved by incorporating tumor-peritumor radiomics features along with clinically independent risk factors.This finding offers a crucial reference point for identifying at-risk patients and tailoring individualized treatment plans.

Objective:To investigate the effects of blocking MAPK signaling pathway on biological characteristics of residual cancer cells after radiofrequency ablation of hepatocellular carcinoma (HCC).Methods:HepG2 cell line was selected and residual liver cancer cells (HepG2-H cells) after radiofrequency ablation were prepared by stimulating radiofrequency ablation in vitro. The morphology of the 2 cells was observed after 48 h culture. The gene expression difference of HepG2 and HepG2-H cells was detected by using RNA sequencing, and the differential genes were analyzed by using Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. HepG2-H cells were treated with different concentrations (10, 20, 30 μmol /L) of MAPK signaling pathway specific blocker U0126, and cells without adding U0126 were treated as the control group. The proliferative ability of the cells in each group was detected by using methyl thiazolyl tetrazolium (MTT) method. The migration ability of cells in each group was detected by using cell scratch test. The invasion ability of cells in each group was detected by using cell invasion assay.Results:After 48 h culture of HepG2-H cells and HepG2 cells, adherent cells with epithelioid growth were closely arranged at the bottom of the petri dish. The confluence of HepG2-H cells reached about 80%, and the confluence of HepG2 cells reached about 70%. A total of 16 255 genes were determined in RNA sequencing. Compared with HepG2 cells, 85 up-regulated genes and 312 down-regulated genes were detected in HepG2-H cells. KEGG pathway enrichment analysis showed that MAPK signaling pathway was most significantly affected by differential genes. The absorbance values of the control group and HepG2-H cells treated with 10, 20 and 30 μmol /L U0126 for 72 h were 1.12±0.08, 0.69±0.08, 0.51±0.06 and 0.45±0.08, respectively, and the difference was statistically significant ( F = 5.12, P = 0.013). The migration areas of HepG2-H cells for 24 h were (6 054±269) μm 2, (5 640±285) μm 2, (5 082±238) μm 2, (4 822±246) μm 2, respectively, and the difference was statistically significant ( F = 3.37, P = 0.043). The number of invasive cells for 24 h was 227±17, 164±19, 138±18, 129±19, respectively, and the difference was statistically significant ( F = 4.04, P = 0.032). Conclusions:Blocking MAPK signaling pathway can inhibit the proliferation, migration and invasion ability of residual cancer cells after radiofrequency ablation of HCC.