Both type 2 diabetes mellitus (T2DM) and metabolic associated fatty liver disease (MAFLD) fall within the spectrum of metabolic diseases, and they exhibit a bi-directional causal relationship and robust reciprocal association. Their shared pathological cornerstone is insulin resistance (IR), which involves the interplay of mitochondrial dysfunction and chronic inflammation, forming a cascading pathological process of “IR-mitochondrial dysfunction-inflammation”. This largely explains the notable upward trend in T2DM-MAFLD co-occurrence observed over recent years. Exercise intervention, as a safe and effective non-pharmacological approach, can improve the pathological progression of these patients at multiple levels. Following the logical framework of “pathogenesis-efficacy comparison-molecular mechanisms-clinical translation”, this article systematically compares the efficacy and molecular mechanisms of moderate-intensity continuous training (MICT), resistance exercise, high-intensity interval training (HIIT), and combined training. MICT reduces intrahepatic triglycerides by promoting lipolysis and improving cardiorespiratory fitness; resistance exercise increases muscle mass and basal metabolic rate, offering unique advantages in preserving muscle while reducing fat and improving insulin sensitivity; HIIT is a time-efficient exercise modality that enhances patients’ cardiorespiratory fitness and insulin sensitivity by alternating brief periods of vigorous exertion with recovery periods, with a prominent short-term triglyceride-lowering effect; combined training produces synergistic effects, comprehensively improving glucolipid metabolism and showing the best long-term adherence. Mechanistically, exercise exerts its beneficial effects through three common pathways: (1) AMPK-mediated lipid oxidation and mitochondrial biogenesis; (2) IRS/PI3K/Akt-mediated insulin signaling sensitization; and (3) Nrf2/ARE anti-oxidation and TGF-β/Smads anti-fibrosis regulation. Different exercise modalities activate these pathways with distinct emphases: MICT most directly and persistently activates the AMPK pathway; resistance exercise uniquely improves IRS/PI3K/Akt signaling through muscle mass gain; HIIT induces the highest AMPK activation intensity and triggers unique lactate-mediated signaling regulation; combined training integrates the above multiple mechanistic advantages. For clinical translation, multidisciplinary team collaboration is essential to ensure safety and adherence. Individualized prescriptions should be formulated according to the FITT-VP principle and patient phenotypes—frequency of 3-5 sessions/week of aerobic exercise combined with 2-3 sessions/week of resistance exercise; intensity of moderate-intensity (40%-60% heart rate reserve (HRR))aerobic exercise and 60%-80% of one-repetition maximum (1-RM) for resistance exercise; time of at least 150 min/week of moderate-intensity aerobic exercise, 30-60 min per session; type of combined training as the preferred modality; total volume of≥500-1 000 MET-min/week; and progression adjusted every 4-6 weeks—with real-time adjustments supported by wearable devices, ultimately forming a closed-loop management system from initial assessment to long-term follow-up. Notably, current studies have limitations such as small sample sizes and short intervention periods. Future research should focus on long-term follow-up, multi-omics biomarkers, and combined exercise-drug strategies. In conclusion, the systematic integration of structured, individualized, and sustainable exercise interventions into the multidisciplinary management pathway for patients with T2DM complicated by MAFLD is an urgent need in current clinical practice.

Objective To establish a stable liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for detecting gamma-aminobutyric acid(GABA)in plasma,and to evaluate the value of GABA detection in the diagnosis of sleep disorders.Methods GABA was detected using a UPLC Xevo TQs system.The method was pre-validated and its performance was verified to establish a reference range for healthy individuals.The difference in plasma GABA levels between apparently healthy individuals and patients with sleep disorders was compared.Results We employed deuterated compounds as isotopic internal standards and utilized an Amide chromatographic column for separation.The mobile phase was 0.050%formic acid in water and 90%acetonitrile in water containing 0.175%formic acid and 5 mmol/L ammonium acetate with gradient elution in the column temperature of 35℃.The linear range for the detection of GABA by LC-MS/MS was 0.05-10.00 μmol/L,with a lower limit of quantification of 0.02 μmol/L,the inter-day CV<3.00%and intra assay CV<4.00%,respectively,and the recovery rate was 101.06%-109.02%.The reference ranges for plasma GABA were established by analyzing 300 healthy controls stratified by age:18-34 years(0.08-0.15 μmol/L),35-49 years(0.10-0.20 μmol/L),and≥50 years(0.12-0.23 μmol/L).Then plasma GABA was used as a biomarker for auxiliary diagnosis of sleep disorders in analyzing 221 patients and 300 healthy controls,which revealed that AUC values were 0.510(P=0.850),0.686(P=0.002),and 0.890(P<0.001)in the groups of 18-34 years,35-49 years,and≥50 years,respectively,with optimal cut-off values of 0.09,0.10 and 0.11 μmol/L.Conclusion A reliable LC-MS/MS method for detecting GABA has been established,which can detect plasma GABA levels sensitively and accurately and can be used in assisting the clinical diagnosis of sleep disorders.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Objective To establish a stable liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for detecting gamma-aminobutyric acid(GABA)in plasma,and to evaluate the value of GABA detection in the diagnosis of sleep disorders.Methods GABA was detected using a UPLC Xevo TQs system.The method was pre-validated and its performance was verified to establish a reference range for healthy individuals.The difference in plasma GABA levels between apparently healthy individuals and patients with sleep disorders was compared.Results We employed deuterated compounds as isotopic internal standards and utilized an Amide chromatographic column for separation.The mobile phase was 0.050%formic acid in water and 90%acetonitrile in water containing 0.175%formic acid and 5 mmol/L ammonium acetate with gradient elution in the column temperature of 35℃.The linear range for the detection of GABA by LC-MS/MS was 0.05-10.00 μmol/L,with a lower limit of quantification of 0.02 μmol/L,the inter-day CV<3.00%and intra assay CV<4.00%,respectively,and the recovery rate was 101.06%-109.02%.The reference ranges for plasma GABA were established by analyzing 300 healthy controls stratified by age:18-34 years(0.08-0.15 μmol/L),35-49 years(0.10-0.20 μmol/L),and≥50 years(0.12-0.23 μmol/L).Then plasma GABA was used as a biomarker for auxiliary diagnosis of sleep disorders in analyzing 221 patients and 300 healthy controls,which revealed that AUC values were 0.510(P=0.850),0.686(P=0.002),and 0.890(P<0.001)in the groups of 18-34 years,35-49 years,and≥50 years,respectively,with optimal cut-off values of 0.09,0.10 and 0.11 μmol/L.Conclusion A reliable LC-MS/MS method for detecting GABA has been established,which can detect plasma GABA levels sensitively and accurately and can be used in assisting the clinical diagnosis of sleep disorders.

Objective To compile nursing guidelines for diabetic patients undergoing ultrasound-guided islet transplantation through percutaneous portal vein puncture and catheterisation,providing valuable insights for the care of such patients during the surgical procedure.Methods Between December 2017 to September 2023,a total of 27 patients underwent 44 surgical procedures for ultrasound-guided islet transplantation via percutaneous portal vein puncture and catheterisation at our hospital.Nursing assistance was provided preoperatively,intraoperatively and postoperatively for all the procedures.Results All 27 patients who had undergone 44 surgical procedures successfully went through the ultrasound-guided islet transplantation via percutaneous portal vein puncture and catheterisation.Among the 44 surgical procedures,3(6.8%)resulted in upper abdominal and liver area pain,nausea and vomiting during surgery,8(18.2%)had transient increase of portal vein pressure during transplantation,and 6(13.6%)encountered active bleeding following the removal of the portal vein catheters.None of the patients developed delayed portal vein bleeding or complication such as portal vein thrombosis after the surgery.Conclusions Nursing interventions play a crucial role in ensuring the successful outcomes of ultrasound-guided islet transplantation.Following measures are the keys and they play an important roles in ensuring the smooth completion of ultrasound-guided islet transplantation:preoperatively,carefully assess the condition of recipients and provide them with psychological supports and patient education.Intraoperatively,closely monitor the vital signs,portal vein pressure and blood glucose as well as to prevent complications.Postoperatively,implement the nursing measures to prevent the recipients from postoperative bleeding of portal vein.

Objective:To explore the risk factors for duodenal papillary adenocarcinoma by comparing the differences in clinical and endoscopic features between patients with duodenal papillary adenomas and adenocarcinomas.Methods:This study retrospectively included patients diagnosed as having duodenal papillary adenocarcinoma and adenoma from January 1st 2018 to June 1st 2023 at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School. Demographic, clinical manifestations, laboratory tests, imaging, endoscopic and pathological characteristics of patients with adenomas and adenocarcinomas were collected and compared. Multivariable logistic regression analysis was employed to identify high-risk factors for duodenal papillary adenocarcinoma.Results:A total of 119 cases of adenocarcinoma and 171 cases of adenoma were included. There were statistically significant differences between the two groups in terms of patient age, body mass index (BMI), clinical symptoms, family history of malignant tumors, bile duct dilation, pancreatic duct dilation, lesion size, adenoma site classification, stage assessed by EUS, and involvement of the bile and pancreatic ducts ( P<0.05). Univariate logistic regression analysis revealed that non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, involvement of the bile and pancreatic ducts assessed by EUS, age ≥60 years, lesion size ≥1.5 cm, clinical symptoms, family history of malignant tumors, bile duct dilation, and pancreatic duct dilation were risk factors for duodenal papillary adenocarcinoma. Multivariate logistic regression analysis showed that non-ampullary lesions ( OR=7.00, 95% CI:1.44-34.15, P=0.016), involvement not limited to the major duodenal papilla assessed by EUS ( OR=13.77, 95% CI: 4.69-40.45, P<0.001), age ≥60 years ( OR=2.52, 95% CI: 1.23-5.18, P=0.011), bile duct dilation ( OR=2.58, 95% CI: 1.12-5.94, P=0.026), and lesion size ≥1.5 cm ( OR=2.76, 95% CI:1.36-5.59, P=0.005) were independent risk factors for duodenal papillary adenocarcinoma. Conclusion:This study shows the independent risk factors for duodenal papillary adenocarcinoma, which include non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, age ≥60 years, bile duct dilation, and lesion size ≥1.5 cm.

Humans ; Asthma/drug therapy* ; Biological Therapy

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

Objective: To examine the prevalence and trend of tobacco and e-cigarettes uses and identify the influencing factors for smoking behavior in junior middle school students in Shanghai, and provide data support and scientific basis for the development of tobacco control intervention strategy in adolescents. Methods: Multi-stage stratified random sampling method was used to select junior middle school students in 8 districts and 10 districts in Shanghai in 2013 and in 2019 respectively. Information about tobacco and e-cigarettes uses in the students were collected by using self-administrated questionnaire. The prevalence of tobacco and e-cigarettes uses were calculated, the difference between two years was compared with χ² test. The influencing factors were identified by multivariate logistic regression analysis. Results: In 2019, the current smoking rate was 0.6% in junior middle school students in Shanghai, and the smoking attempt rate was 2.9%, both were lower than the levels in 2013 (0.7% and 6.9%). The current use rate of e-cigarettes was 0.6% in 2019,with no significant change compared with 2013 (0.6%). The proportion of the students who had heard of e-cigarettes in 2019 (78.4%) was higher than that in 2013 (47.2%). In 2019, the second-hand smoke (SHS) exposure rate at home, in both indoor and outdoor public places and on public transportations was 72.5%, which was slightly lower than the level in 2013 (73.0%), the differences were all significant (P<0.05). In 2019, the students seeing close friend smoking (OR=27.381, 95%CI: 12.037-62.287), seeing someone smoking in school (OR=2.477, 95%CI: 1.155-5.312), believing that SHS may not be harmful (OR=8.471, 95%CI: 1.464-49.005) had higher possibility of smoking. Being aged ≥15 years (compared with being aged ≤12 years, OR=8.688, 95%CI: 1.922-39.266), exposure to SHS in outdoor public place (OR=8.608, 95%CI: 1.048-70.692), close friend smoking (OR=8.115, 95%CI: 1.754-37.545) were positively associated with e-cigarettes use, and believing that smoking results in uncomfortable social contact [compared with believing that smoking results in comfortable social contact (OR=0.105,95%CI: 0.018-0.615)] were negatively associated with e-cigarettes use, the difference was significant (P<0.05). Conclusion: The prevalence of tobacco and e-cigarette uses in junior middle school students in Shanghai remained at a low level in recent years. The SHS exposure rate in junior middle school students is high. Smoking behavior of junior middle school students is closely related to personal attitude and awareness of tobacco, exposure to SHS, peer smoking and the situation of tobacco control in schools. Prevention and intervention should be carried out from multi-dimensions to effectively protect teenagers from tobacco hazards.
Adolescent ; China/epidemiology* ; Electronic Nicotine Delivery Systems ; Humans ; Prevalence ; Students ; Tobacco ; Tobacco Smoke Pollution

OBJECTIVE: To observe the effect of thumb-tack needles based on "Biaoben acupoint compatibility" on sequela symptoms, mental state and pulmonary ventilation function in patients with coronavirus disease 2019 (COVID-19) during recovery period. METHODS: Fifty cases of COVID-19 during recovery period were randomly divided into an observation group and a control group, 25 cases in each group. The patients in the observation group were treated with thumb-tack needles at Guanyuan (CV 4), Zusanli (ST 36) and Taiyuan (LU 9). The patients in the control group were treated with sham thumb-tack needles at identical acupoints as the observation group. The treatment in the two groups was given once a day, 7-day treatment was taken as a course of treatment, and totally two courses of treatment were given. The TCM symptom score, Hamilton anxiety scale (HAMA) score, Hamilton depression scale (HAMD) score, pulmonary function (forced vital capacity [FVC], forced expiratory volume in the first second [FEV1], peak expiratory flow [PEF]), the severity of pulmonary ventilation dysfunction and pulmonary imaging changes in the two groups were compared before and after treatment. RESULTS: Compared before treatment, the total scores and each item scores of TCM symptom scale, HAMA scores and HAMD scores in the two groups were reduced after treatment (P<0.05). Except for the symptom scores of dry throat and dry stool, the total score and each item score of TCM symptom scale, HAMA score and HAMD score in the observation group were lower than those in the control group (P<0.05). Compared before treatment, FVC, FEV1 and PEF in the two groups were increased after treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The severity of pulmonary ventilation dysfunction in the two groups was reduced after treatment (P<0.05), and the severity in the observation group was better than that in the control group (P<0.05). After treatment, the lung shadow area in the two groups was decreased (P<0.05), and that in the observation group was smaller than the control group (P<0.05). The improvement of imaging change in the observation group was better than that in the control group (P<0.05). CONCLUSION The thumb-tack needles based on "Biaoben acupoint compatibility" could significantly reduce the sequela symptoms, anxiety and depression in patients with COVID-19 during recovery stage, and improve the pulmonary ventilation function.
Acupuncture Points ; Anxiety/etiology* ; COVID-19/therapy* ; Depression/etiology* ; Humans ; Needles ; Respiratory Function Tests ; Thumb