BACKGROUND: Diabetes mellitus with nonalcoholic fatty liver disease (DM-NAFLD) represents a complex metabolic syndrome with significant clinical challenges. This study explores the therapeutic potential and underlying mechanisms of umbilical cord-derived mesenchymal stem cells (UCMSCs)-derived extracellular vesicles (EVs) in DM-NAFLD. METHODS: UCMSCs-EVs were isolated and characterized. DM-NAFLD mouse model was developed through highenergy diet and streptozotocin injection. Additionally, primary mouse hepatocytes were exposed to high glucose to simulate cellular conditions. Hepatic tissue damage, body weight changes, lipid levels, glucose and insulin homeostasis, and hepatic lipid accumulation were evaluated. The interaction between UCMSCs-EVs and hepatocytes was assessed, focusing on the localization and function of circ-Tulp4. The study also investigated the expression of circularRNA TUBlike protein 4 (circ-Tulp4), heterogeneous nuclear ribonucleoprotein C (HNRNPC), abhydrolase domain containing 6 (ABHD6), cleaved Caspase-1, NLR family pyrin domain containing 3 (NLRP3) and cleaved N-terminal gasdermin D (GSDMD-N). The binding of circ-Tulp4 to lysine demethylase 6B (KDM6B) and the subsequent epigenetic regulation of ABHD6 by H3K27me3 were analyzed. RESULTS: Circ-Tulp4 was reduced, while HNRNPC and ABHD6 were elevated in DM-NAFLD models. UCMSCs-EVs attenuated hepatic steatosis and inhibited the NLRP3/cleaved Caspase-1/GSDMD-N pathway. EVs delivered circ-Tulp4 into hepatocytes, thereby restoring circ-Tulp4 expression. Elevated circ-Tulp4 enhanced the recruitment of H3K27me3 to the HNRNPC promoter through interaction with KDM6B, thus suppressing HNRNPC and ABHD6. Overexpression of HNRNPC or ABHD6 counteracted the protective effects of UCMSCs-EVs, exacerbating pyroptosis and hepatic steatosis in DM-NAFLD. CONCLUSION UCMSCs-EVs deliver circ-Tulp4 into hepatocytes, where circ-Tulp4 inhibits the HNRNPC/ABHD6 axis, thereby reducing pyroptosis and alleviating DM-NAFLD. These findings provide a novel therapeutic avenue for targeting DM-NAFLD through modulation of cell pyroptosis.

BACKGROUND: Diabetes mellitus with nonalcoholic fatty liver disease (DM-NAFLD) represents a complex metabolic syndrome with significant clinical challenges. This study explores the therapeutic potential and underlying mechanisms of umbilical cord-derived mesenchymal stem cells (UCMSCs)-derived extracellular vesicles (EVs) in DM-NAFLD. METHODS: UCMSCs-EVs were isolated and characterized. DM-NAFLD mouse model was developed through highenergy diet and streptozotocin injection. Additionally, primary mouse hepatocytes were exposed to high glucose to simulate cellular conditions. Hepatic tissue damage, body weight changes, lipid levels, glucose and insulin homeostasis, and hepatic lipid accumulation were evaluated. The interaction between UCMSCs-EVs and hepatocytes was assessed, focusing on the localization and function of circ-Tulp4. The study also investigated the expression of circularRNA TUBlike protein 4 (circ-Tulp4), heterogeneous nuclear ribonucleoprotein C (HNRNPC), abhydrolase domain containing 6 (ABHD6), cleaved Caspase-1, NLR family pyrin domain containing 3 (NLRP3) and cleaved N-terminal gasdermin D (GSDMD-N). The binding of circ-Tulp4 to lysine demethylase 6B (KDM6B) and the subsequent epigenetic regulation of ABHD6 by H3K27me3 were analyzed. RESULTS: Circ-Tulp4 was reduced, while HNRNPC and ABHD6 were elevated in DM-NAFLD models. UCMSCs-EVs attenuated hepatic steatosis and inhibited the NLRP3/cleaved Caspase-1/GSDMD-N pathway. EVs delivered circ-Tulp4 into hepatocytes, thereby restoring circ-Tulp4 expression. Elevated circ-Tulp4 enhanced the recruitment of H3K27me3 to the HNRNPC promoter through interaction with KDM6B, thus suppressing HNRNPC and ABHD6. Overexpression of HNRNPC or ABHD6 counteracted the protective effects of UCMSCs-EVs, exacerbating pyroptosis and hepatic steatosis in DM-NAFLD. CONCLUSION UCMSCs-EVs deliver circ-Tulp4 into hepatocytes, where circ-Tulp4 inhibits the HNRNPC/ABHD6 axis, thereby reducing pyroptosis and alleviating DM-NAFLD. These findings provide a novel therapeutic avenue for targeting DM-NAFLD through modulation of cell pyroptosis.

BACKGROUND: Diabetes mellitus with nonalcoholic fatty liver disease (DM-NAFLD) represents a complex metabolic syndrome with significant clinical challenges. This study explores the therapeutic potential and underlying mechanisms of umbilical cord-derived mesenchymal stem cells (UCMSCs)-derived extracellular vesicles (EVs) in DM-NAFLD. METHODS: UCMSCs-EVs were isolated and characterized. DM-NAFLD mouse model was developed through highenergy diet and streptozotocin injection. Additionally, primary mouse hepatocytes were exposed to high glucose to simulate cellular conditions. Hepatic tissue damage, body weight changes, lipid levels, glucose and insulin homeostasis, and hepatic lipid accumulation were evaluated. The interaction between UCMSCs-EVs and hepatocytes was assessed, focusing on the localization and function of circ-Tulp4. The study also investigated the expression of circularRNA TUBlike protein 4 (circ-Tulp4), heterogeneous nuclear ribonucleoprotein C (HNRNPC), abhydrolase domain containing 6 (ABHD6), cleaved Caspase-1, NLR family pyrin domain containing 3 (NLRP3) and cleaved N-terminal gasdermin D (GSDMD-N). The binding of circ-Tulp4 to lysine demethylase 6B (KDM6B) and the subsequent epigenetic regulation of ABHD6 by H3K27me3 were analyzed. RESULTS: Circ-Tulp4 was reduced, while HNRNPC and ABHD6 were elevated in DM-NAFLD models. UCMSCs-EVs attenuated hepatic steatosis and inhibited the NLRP3/cleaved Caspase-1/GSDMD-N pathway. EVs delivered circ-Tulp4 into hepatocytes, thereby restoring circ-Tulp4 expression. Elevated circ-Tulp4 enhanced the recruitment of H3K27me3 to the HNRNPC promoter through interaction with KDM6B, thus suppressing HNRNPC and ABHD6. Overexpression of HNRNPC or ABHD6 counteracted the protective effects of UCMSCs-EVs, exacerbating pyroptosis and hepatic steatosis in DM-NAFLD. CONCLUSION UCMSCs-EVs deliver circ-Tulp4 into hepatocytes, where circ-Tulp4 inhibits the HNRNPC/ABHD6 axis, thereby reducing pyroptosis and alleviating DM-NAFLD. These findings provide a novel therapeutic avenue for targeting DM-NAFLD through modulation of cell pyroptosis.

BACKGROUND: Diabetes mellitus with nonalcoholic fatty liver disease (DM-NAFLD) represents a complex metabolic syndrome with significant clinical challenges. This study explores the therapeutic potential and underlying mechanisms of umbilical cord-derived mesenchymal stem cells (UCMSCs)-derived extracellular vesicles (EVs) in DM-NAFLD. METHODS: UCMSCs-EVs were isolated and characterized. DM-NAFLD mouse model was developed through highenergy diet and streptozotocin injection. Additionally, primary mouse hepatocytes were exposed to high glucose to simulate cellular conditions. Hepatic tissue damage, body weight changes, lipid levels, glucose and insulin homeostasis, and hepatic lipid accumulation were evaluated. The interaction between UCMSCs-EVs and hepatocytes was assessed, focusing on the localization and function of circ-Tulp4. The study also investigated the expression of circularRNA TUBlike protein 4 (circ-Tulp4), heterogeneous nuclear ribonucleoprotein C (HNRNPC), abhydrolase domain containing 6 (ABHD6), cleaved Caspase-1, NLR family pyrin domain containing 3 (NLRP3) and cleaved N-terminal gasdermin D (GSDMD-N). The binding of circ-Tulp4 to lysine demethylase 6B (KDM6B) and the subsequent epigenetic regulation of ABHD6 by H3K27me3 were analyzed. RESULTS: Circ-Tulp4 was reduced, while HNRNPC and ABHD6 were elevated in DM-NAFLD models. UCMSCs-EVs attenuated hepatic steatosis and inhibited the NLRP3/cleaved Caspase-1/GSDMD-N pathway. EVs delivered circ-Tulp4 into hepatocytes, thereby restoring circ-Tulp4 expression. Elevated circ-Tulp4 enhanced the recruitment of H3K27me3 to the HNRNPC promoter through interaction with KDM6B, thus suppressing HNRNPC and ABHD6. Overexpression of HNRNPC or ABHD6 counteracted the protective effects of UCMSCs-EVs, exacerbating pyroptosis and hepatic steatosis in DM-NAFLD. CONCLUSION UCMSCs-EVs deliver circ-Tulp4 into hepatocytes, where circ-Tulp4 inhibits the HNRNPC/ABHD6 axis, thereby reducing pyroptosis and alleviating DM-NAFLD. These findings provide a novel therapeutic avenue for targeting DM-NAFLD through modulation of cell pyroptosis.

BACKGROUND: Diabetes mellitus with nonalcoholic fatty liver disease (DM-NAFLD) represents a complex metabolic syndrome with significant clinical challenges. This study explores the therapeutic potential and underlying mechanisms of umbilical cord-derived mesenchymal stem cells (UCMSCs)-derived extracellular vesicles (EVs) in DM-NAFLD. METHODS: UCMSCs-EVs were isolated and characterized. DM-NAFLD mouse model was developed through highenergy diet and streptozotocin injection. Additionally, primary mouse hepatocytes were exposed to high glucose to simulate cellular conditions. Hepatic tissue damage, body weight changes, lipid levels, glucose and insulin homeostasis, and hepatic lipid accumulation were evaluated. The interaction between UCMSCs-EVs and hepatocytes was assessed, focusing on the localization and function of circ-Tulp4. The study also investigated the expression of circularRNA TUBlike protein 4 (circ-Tulp4), heterogeneous nuclear ribonucleoprotein C (HNRNPC), abhydrolase domain containing 6 (ABHD6), cleaved Caspase-1, NLR family pyrin domain containing 3 (NLRP3) and cleaved N-terminal gasdermin D (GSDMD-N). The binding of circ-Tulp4 to lysine demethylase 6B (KDM6B) and the subsequent epigenetic regulation of ABHD6 by H3K27me3 were analyzed. RESULTS: Circ-Tulp4 was reduced, while HNRNPC and ABHD6 were elevated in DM-NAFLD models. UCMSCs-EVs attenuated hepatic steatosis and inhibited the NLRP3/cleaved Caspase-1/GSDMD-N pathway. EVs delivered circ-Tulp4 into hepatocytes, thereby restoring circ-Tulp4 expression. Elevated circ-Tulp4 enhanced the recruitment of H3K27me3 to the HNRNPC promoter through interaction with KDM6B, thus suppressing HNRNPC and ABHD6. Overexpression of HNRNPC or ABHD6 counteracted the protective effects of UCMSCs-EVs, exacerbating pyroptosis and hepatic steatosis in DM-NAFLD. CONCLUSION UCMSCs-EVs deliver circ-Tulp4 into hepatocytes, where circ-Tulp4 inhibits the HNRNPC/ABHD6 axis, thereby reducing pyroptosis and alleviating DM-NAFLD. These findings provide a novel therapeutic avenue for targeting DM-NAFLD through modulation of cell pyroptosis.

Objective: The study aimed to analyze the association between different types of obesity and dyslipidemia among rural primary and middle school students in Zhejiang Province, so as to inform strategies for prevention and control of childhood obesity and hyperlipidemia. Methods: As part of Nutrition Improvement Programme for Rural Compulsory Education Students, 1 244 participants were selected by stratified cluster random sampling in 5 counties of Zhejiang Province during September to December 2021. Physical examination, detection of blood lipid and questionnaire survey were conducted. The Chi -square test and Logistic regression analyses were used to assess the association between different types of obesity and dyslipidemia. Results: The prevalence rates of overweight, obesity, abdominal obesity, and hyperlipidemia were 15.11%, 12.46%, 17.60%, and 21.78%. Obesity and abdominal obesity were correlated to high risk of high triglycerides ( OR =3.97, 95% CI =2.54-6.20; OR =4.45, 95% CI =2.95- 6.72 )( P <0.05). Compared with the non overweight and obese group with normal waist circumference,the overweight and obesity group were correlated to high risk of high cholesterol ( OR=2.53, 95%CI =1.45-4.42, P <0.05). Abdominal overweight or obese group had the highest risk for dyslipidemia and triglycerides ( OR =1.82, 95% CI =1.33-2.48; OR =3.64, 95% CI =2.45-5.43) ( P < 0.05). Conclusions The prevalence rates of overweight, obesity, abdominal obesity, and hyperlipidemia are relatively high in rural primary and middle school students of Nutrition Improvement Programme for Rural Compulsory Education Students in Zhejiang Province. Abdominal obesity is a more important risk factor for hyperlipidemia. Waist circumference should be the focus of considerable attention.

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL^-1) were used to induce fibrotic model, and high glucose (30 mmol·L^-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

【Objective】 To analyze the influence of plasma donation on human total protein level and the impact of different blood collection tubes on total protein level detection. 【Methods】 A total of 1 373 plasma donors from 11 apheresis plasma stations in 6 provinces/autonomous regions from March to April, 2021 were selected. Whole blood was collected by ordinary blood collection tube without anticoagulant, heparin anticoagulant tube and sodium citrate anticoagulant tube, and then respectively divided into serum group, heparin anticoagulant group, and sodium citrate anticoagulant group. After separating serum and plasma, the samples were subjected to total protein detection using the biuret method. Kruskal-Wallis test was used to compare the total protein levels among different tubes. The plasma donors were divided into male group (n=597) and female group (n=776), and the total protein levels between different genders were compared by t test. The plasma donors were divided into Sichuan group, Hubei group and Gansu group according to the region, and the Games-Howell test was used for comparison. 【Results】 The median serum total protein level of 1 373 donors was 73.1g/L, which was consistent with the reference range of 65-85 g/L. The median total protein levels of the serum group, heparin anticoagulant group and sodium citrate anticoagulant group were 73.1g/L, 73.3g/L and 63.8g/L, respectively, with statistically significant difference (P<0.05). There was statistical significance in total protein level between sodium citrate anticoagulant group and serum group, sodium citrate anticoagulant group and heparin anticoagulant group(P<0.05), but no statistical significance was noticed between serum group and heparin anticoagulant group (P> 0.05). The serum total protein levels of male group and female group were (72.41±5.40)g/L and (73.67±4.95)g/L, reseectively, and the difference was statistically significant (P<0.05). The serum total protein level in Sichuan group, Hubei group and Gansu group was (73.91±4.29)g/L, (74.17±5.11)g/L and (67.09±3.65)g/L, respectively (P<0.05).The difference between Gansu group and Hubei group, Gansu group and Sichuan group was statistically significant (P<0.05), but no significant difference was noticed between Sichuan group and Hubei group (P>0.05). 【Conclusion】 Plasma donors who meet the donation criteria will not experience abnormal total protein levels due to regular plasma donation. There were differences in total protein levels among different blood collection tubes, different genders and different regions. The total protein level of females was higher than that of males. The total protein level was the highest in Hubei province, followed by Sichuan and Gansu.Heparin anticoagulant group was the highest, followed by serum group and sodium citrate anticoagulant group.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.