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 investigate the associations of screen time (ST) and dietary behavior with sleep quality among first-year junior high school students, and further analyze the joint exposure effect of weekend ST and dietary usage, so as to provide scientific evidence for improving adolescent sleep quality and developing related health intervention measures. Methods: From September 19 to October 18, 2023, a combination of cluster sampling and convenience sampling method was used to select 733 first-year junior high school students from 4 public junior high schools in Jinshan District, Shanghai. ST on weekdays and weekends of students was investigated. The Chinese Diet Quality Questionnaire and the Pittsburgh Sleep Quality Index were applied to assess dietary behaviors and sleep quality. Binary Logistic regression was used to analyze the associations of ST and dietary behavior with sleep quality during weekdays and weekends. Results: The proportion of students with high level ST was 31.8% on weekdays and 65.3% on weekends. Students with poor dietary quality accounted for 45.3%, and the detection rate of poor sleep quality was 14.6 %. Binary Logistic regression analysis showed that, compared with students with low level ST on weekend and good dietary quality, those with high level ST on weekend and those with poor dietary quality had increased risks of poor sleep quality [ OR (95% CI )=1.89(1.10-3.26), 2.30(1.47-3.58), both P <0.05]. Combined exposure showed that compared to students with good diet quality and low level ST on weekend, students with good dietary quality and high level ST on weekend, those with poor dietary quality and low level ST on weekend, and those with poor dietary quality and high level ST on weekend also had increased risks of poor sleep quality [ OR (95% CI )=3.00(1.25-7.25), 4.07(1.60-10.33), 5.72(2.37-13.81), all P <0.05]. Conclusion Excessive weekend ST and poor dietary quality are associated with poor sleep quality among first-year junior high school students, and their co-occurrence further increases the risk.

Objective To establish an expert consensus on the management of mini-midline catheters(hereinafter referred to as the'consensus')to guide nurses in standardizing the insertion and maintenance of mini-midline catheters.Methods Evidence was systematically retrieved,scientifically evaluated,and synthesized using evidence-based methods to draft the initial version of the consensus.From December 2023 to July 2024,totally 2 rounds of expert correspondence and 2 rounds of expert panel discussions were conducted to revise the content,resulting in the final version.Results There were 17 experts from tertiary A general hospitals in Beijing,Shanghai,Hunan,Hubei,Sichuan,Jiangsu,Hainan,Guangxi Zhuang Autonomous Region,and Shandong participating in the consultation,with a 100％response rate.In the 2 rounds of expert correspondence,the authority coefficients were 0.947 and 0.962,respectively.The mean importance scores of all items exceeded 4.00 points.The coefficients of variation(CV)were 0-0.32(first round)and 0-0.15(second round).Kendall's concordance coefficients were 0.097 and 0.101(both P＜0.001).The consensus covers 11 sections,including definition,indications,contraindications,qualification training,pre-insertion preparation,catheter insertion,catheter use,catheter maintenance,catheter removal,prevention and management of common complications,and health education.Conclusion The Consensus demonstrates scientific rigor and comprehensively addresses key procedures before,during,and after the insertion of mini-midline catheters,providing actionable guidance for nurses in catheter insertion and maintenance.

Objective:To explore the impact of Epstein-Barr Virus(EBV) infection on treatment response and survival in newly diagnosed multiple myeloma(MM).Methods:The clinical data of 196 patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from June 1st, 2019 to February 25th,2021 were analyzed retrospectively and divided into EBV-positive group (106 cases) and negative group (90 cases) according to the primary EBV DNA results in peripheral blood mononuclear cells.To analyse the distribution of EBV positive rates in each type and in each stage of the Revised International Staging System (R-ISS), and to compare EBV DNA loads in EBV-positive patients among R-ISS stages.Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis between the two groups.The clinical prognosis of EBV-positive patients was summarized through survival analysis and Cox regression.Results:The EBV positive rate in patients with newly diagnosed MM was 54% (106/196), with the highest rate in patients with κ light chain type (9/12).Patients with R-ISS stage Ⅲ had a significantly higher positive rate than with stage Ⅰ ( χ2=4.68, P=0.031) and stage Ⅱ ( χ2=6.04, P=0.014), but there was no significant difference in EBV DNA loads between EBV-positive MM patients by stage ( Z=3.27, P=0.195).Serum creatinine (Scr) and β 2-microglobulin (β 2-MG) levels were higher in the EBV-positive group than in the EBV-negative group ( Z=1.98, P=0.048 and Z=2.08, P=0.038), and the occurrence of t(4;14) was also higher in the EBV-positive group ( χ2=3.93, P=0.047).The proportion of complete response (CR)/stringent complete response(sCR) and very good partial response(VGPR) after completion of the fourth chemotherapy were significantly lower in the EBV-positive group than in the EBV-negative group ( χ2=12.82, P=0.001 and χ2=8.30, P=0.004), and a higher rate of progressive disease (PD) occurred in the EBV-positive group ( χ2=4.48, P=0.046).The 2-year progression-free survival (PFS) of MM patients was shorter in the EBV-positive group compared to that in the EBV-negative group ( Z=-4.50, P0.01).Cox regression analysis showed that R-ISS stage Ⅲ ( HR=5.38, 95% CI 1.28-22.56, P=0.021), failure to achieve VGPR after the fourth chemotherapy ( HR=3.02, 95% CI 1.42-6.46, P=0.004), EBV-positive ( HR=1.98, 95% CI 1.02-3.87, P=0.045), with 1q21 amplification ( HR=2.35, 95% CI 1.16-4.75, P=0.017) and 13q14 deletion ( HR=1.93, 95% CI 1.01-3.67, P=0.046) were independent risk factors for PFS in newly diagnosed MM. Conclusions:EBV infection is an independent risk factor for poor prognosis, which has important clinical implications for the outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

Objective To investigate the effect of field angle on the results of in vivo dose validation of electronic portal imaging device(EPID)in patients.Methods Design the mold test and analyze the influence of different mold thicknesses and different frame angles on the 2D γ pass rate.Twenty-three patients who un-derwent radiotherapy in the Department of Radiotherapy of Jinhua Municipal Central Hospital from January to June 2023 were selected as the research object.In vivo dose verification was carried out during treatment to obtain 2D γ pass rate using same-day sector beam CT(FBCT)of planned CT and executive image guided(IG-RT)as reference images,and the influence of field angle on pass rate was analyzed.Results When the frame angle was unchanged,the area of the shooting field was larger than 17 cm×17 cm,and the 2D γ passing rate decreased with the increase of the thickness.The frame angle had no effect on the 2D γ pass rate when the mold thickness was constant.In clinical treatment data,the passage rate of 2D γ near 0°/180° was higher than that near 90°/270°(P＜0.05),and the passage rate near 90°/270° in the FBCT group was higher than that in the IGRT group(P＜0.05).The median passing rate of 3 mm 2D γ was 97.97％in 3％of the 23 patients.The non-IGRT group was 96.81％,the IGRT group was 97.89％,the FBCT group was 98.94％.There was a statistically significant difference in 2D γ passing rate between the non-IGRT group and the IGRT group(Z=-5.083,P＜0.05),and there was a statistically significant difference in 2D γ passing rate between the IGRT group and the FBCT group(Z=-10.657,P＜0.05).Conclusion Clinically,the difference of pass rate in vi-vo dose verification at different rack angles is mainly due to the difference of images within and between ses-sions.Using same-day FBCT as the reference image for in-vivo dose verification can improve the accuracy of pass rate and eliminate the influence of image difference between sessions.

Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO₂ and glucose oxidase (GOx) (LipoCaO₂/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H₂O₂ and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO₂ to produce H₂O₂ and release Ca²⁺, disrupting Ca²⁺ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca²⁺ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8⁺ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.

Patients with severe periodontal disease often involve multidisciplinary therapy.This paper reports a case of adult patients with severe periodontitis who was treated by orthodontics,restoration,and periodontics.The space between upper central incisors was closed,aesthetics and periodontal conditions were significantly improved.

Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease closely related to metabolism， which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years， with the increasing prevalence of obesity and metabolic syndrome， NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied， involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism， oxidative stress， and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD， and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines， inducing oxidative stress， and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine （TCM） can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years， covering a wide range of TCM active ingredients （such as polysaccharides， terpenoids， alkaloids， flavonoids） and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders， reduce insulin resistance， regulate intestinal flora， and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways， thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target， we can provide theoretical support for the application of TCM in the treatment of NAFLD， as well as new perspectives and directions for future clinical research and new drug development， thereby promoting the innovation and development of therapeutic strategies for NAFLD.

Objective To investigate the therapeutic mechanism of Dingkun Dan(DKD)in polycystic ovary syndrome(PCOS)by examining the effects of microRNA-30d-5p on ovarian granulosa cells(GCs).Methods A PCOS rat model was established using dehydroepiandrosterone(DHEA).Normal rat GCs and PCOS rat GCs were cultured in vitro and divided into four groups:blank control group,model group,low-dose DKD group,and high-dose DKD group.After grouping,GCs viability was assessed using the methyl thiazolyl tetrazolium(MTT)assay,GCs apoptosis was analyzed by flow cytometry,and the gene expression of transforming growth factor β1(TGF-β1),Smad2,Smad3,and microRNA-30d-5p in GCs was measured by real-time polymerase chain reaction(RT-PCR),protein expression of TGF-β1,Smad2,and Smad3 in GCs was detected by Western Blot.Results Compared with the blank control group,the model group exhibited significantly decreased GCs viability,increased GCs apoptosis,upregulated mRNA and protein expression of TGF-β1,Smad2,and Smad3,and downregulated microRNA-30d-5p expression,the differences were statistically significant(P＜0.01).Compared with the model group,both low-and high-dose DKD groups showed increased GCs viability,reduced GCs apoptosis,downregulated mRNA and protein levels of TGF-β1 Smad2 and Smad3,elevated microRNA-30d-5p expression,and the differences were statistically significant(P＜0.05 or P＜0.01).Conclusion DKD promotes GCs proliferation by targeting Smad2 via microRNA-30d-5p,suggesting a potential therapeutic role in PCOS-related ovulatory dysfunction.