ObjectiveTo observe the pharmacodynamic efficacy of phlorizin in improving hepatic glycolipid metabolism disorders in type 2 diabetic mellitus （T2DM） rats and to explore its mechanism of action based on the insulin receptor substrate-1 （IRS-1）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsA high-fat diet and streptozotocin （STZ） were used to establish T2DM rat models. The rats were randomly assigned into six groups： the blank control group， model group， metformin group （300 mg·kg^-1）， and phlorizin high-dose （100 mg·kg^-1） and low-dose groups （25 mg·kg^-1）. The rats were given intragastric administration for 6 weeks. The changes in body weight and fasting blood glucose （FBG） were observed， and the oral glucose tolerance test （OGTT） was carried out. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， glycated serum protein （GSP）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in serum were detected by an automatic biochemical analyzer. The levels of fasting insulin （FINS）， interleukin （IL）-1β， IL-6， and tumour necrosis factor （TNF）-α were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were detected by the biochemical assays. The pancreas index， liver index， and insulin resistance index were calculated. Hematoxylin-eosin （HE） staining was used to evaluate the pathological changes in liver and pancreatic tissues. The immunofluorescence method was used to detect the changes in insulin and glucagon in pancreatic tissue. Western blot was used to detect the expression of related proteins in the IRS-1/PI3K/Akt pathway of liver tissue and its downstream glycogen synthase kinase-3β （GSK-3β） and forkhead box transcription factor O1 （FoxO1） proteins. ResultsCompared with the blank control group， the body weight of rats in the model group continued to decrease， while the FBG level increased significantly. The area under the OGTT blood glucose curve （AUC）， GSP， TC， TG， LDL-C， IL-1β， IL-6， TNF-α， MDA， pancreatic index and liver index increased significantly， while the levels of HDL-C， SOD， and FINS decreased significantly （P0.05， P0.01）. Histological results showed that the pancreatic islets of rats in the model group exhibited atrophy and severe structural abnormalities. The insulin-positive β-cells decreased significantly （P0.01）， while the glucagon-positive α-cells increased significantly （P0.01）. Inflammatory cell infiltration and partial necrosis were observed in the liver tissues of the model group rats. The expressions of p-IRS-1/IRS-1， p-GSK-3β/GSK-3β， and p-FoxO1/FoxO1 proteins in the liver of the model group increased significantly （P0.01）， while the expressions of p-PI3K/PI3K and p-Akt/Akt proteins decreased significantly （P0.01）. Compared with the model group， the diabetic symptoms of rats in all administration groups were improved. The changes in body weight and FBG were close to those of the blank control group. The levels of OGTT-AUC， GSP， TC， TG， LDL-C， MDA， IL-1β， IL-6， TNF-α and the pancreatic index， liver index were obviously reduced （P0.05， P0.01）， while the levels of HDL-C， SOD， and FINS obviously increased （P0.05， P0.01）. The pathological changes of the pancreas and liver in rats in all treatment groups were effectively improved. The insulin-positive β-cells in the pancreas increased significantly （P0.01）， while the glucagon-positive α-cells decreased significantly （P0.01）. The protein expressions of p-IRS-1/IRS-1， p-GSK-3β/GSK-3β， and p-FoxO1/FoxO1 in the liver were significantly reduced （P0.01）， while the protein expressions of p-PI3K/PI3K and p-Akt/Akt significantly increased （P0.01）. ConclusionPhlorizin reversed the weight loss and abnormal increase of FBG in T2DM rats， improved blood lipid profiles， oxidative stress， and inflammatory levels， alleviated insulin resistance， and had certain protective effects on the liver and pancreas. The hypoglycemic mechanism may involve regulating the IRS-1/PI3K/Akt signaling pathway to inhibit the activities of GSK-3β and FoxO1， thereby promoting liver glycogen synthesis and suppressing hepatic gluconeogenesis， ultimately improving glycolipid metabolism disorders.

ObjectiveTo observe the pharmacodynamic efficacy of phlorizin in improving hepatic glycolipid metabolism disorders in type 2 diabetic mellitus （T2DM） rats and to explore its mechanism of action based on the insulin receptor substrate-1 （IRS-1）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsA high-fat diet and streptozotocin （STZ） were used to establish T2DM rat models. The rats were randomly assigned into six groups： the blank control group， model group， metformin group （300 mg·kg^-1）， and phlorizin high-dose （100 mg·kg^-1） and low-dose groups （25 mg·kg^-1）. The rats were given intragastric administration for 6 weeks. The changes in body weight and fasting blood glucose （FBG） were observed， and the oral glucose tolerance test （OGTT） was carried out. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， glycated serum protein （GSP）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in serum were detected by an automatic biochemical analyzer. The levels of fasting insulin （FINS）， interleukin （IL）-1β， IL-6， and tumour necrosis factor （TNF）-α were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were detected by the biochemical assays. The pancreas index， liver index， and insulin resistance index were calculated. Hematoxylin-eosin （HE） staining was used to evaluate the pathological changes in liver and pancreatic tissues. The immunofluorescence method was used to detect the changes in insulin and glucagon in pancreatic tissue. Western blot was used to detect the expression of related proteins in the IRS-1/PI3K/Akt pathway of liver tissue and its downstream glycogen synthase kinase-3β （GSK-3β） and forkhead box transcription factor O1 （FoxO1） proteins. ResultsCompared with the blank control group， the body weight of rats in the model group continued to decrease， while the FBG level increased significantly. The area under the OGTT blood glucose curve （AUC）， GSP， TC， TG， LDL-C， IL-1β， IL-6， TNF-α， MDA， pancreatic index and liver index increased significantly， while the levels of HDL-C， SOD， and FINS decreased significantly （P0.05， P0.01）. Histological results showed that the pancreatic islets of rats in the model group exhibited atrophy and severe structural abnormalities. The insulin-positive β-cells decreased significantly （P0.01）， while the glucagon-positive α-cells increased significantly （P0.01）. Inflammatory cell infiltration and partial necrosis were observed in the liver tissues of the model group rats. The expressions of p-IRS-1/IRS-1， p-GSK-3β/GSK-3β， and p-FoxO1/FoxO1 proteins in the liver of the model group increased significantly （P0.01）， while the expressions of p-PI3K/PI3K and p-Akt/Akt proteins decreased significantly （P0.01）. Compared with the model group， the diabetic symptoms of rats in all administration groups were improved. The changes in body weight and FBG were close to those of the blank control group. The levels of OGTT-AUC， GSP， TC， TG， LDL-C， MDA， IL-1β， IL-6， TNF-α and the pancreatic index， liver index were obviously reduced （P0.05， P0.01）， while the levels of HDL-C， SOD， and FINS obviously increased （P0.05， P0.01）. The pathological changes of the pancreas and liver in rats in all treatment groups were effectively improved. The insulin-positive β-cells in the pancreas increased significantly （P0.01）， while the glucagon-positive α-cells decreased significantly （P0.01）. The protein expressions of p-IRS-1/IRS-1， p-GSK-3β/GSK-3β， and p-FoxO1/FoxO1 in the liver were significantly reduced （P0.01）， while the protein expressions of p-PI3K/PI3K and p-Akt/Akt significantly increased （P0.01）. ConclusionPhlorizin reversed the weight loss and abnormal increase of FBG in T2DM rats， improved blood lipid profiles， oxidative stress， and inflammatory levels， alleviated insulin resistance， and had certain protective effects on the liver and pancreas. The hypoglycemic mechanism may involve regulating the IRS-1/PI3K/Akt signaling pathway to inhibit the activities of GSK-3β and FoxO1， thereby promoting liver glycogen synthesis and suppressing hepatic gluconeogenesis， ultimately improving glycolipid metabolism disorders.

"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

Microorganisms have high application value in the field of drug development such as antibacterial and anti-tumor. By using genetic engineering to modify microorganisms, intelligent engineering bacteria can be contained that can sense, transmit, compute, and feedback disease signals in real time. In this review, three crucial aspects in the construction of intelligent engineering bacteria were summarized, including the selection of chassis strains, the construction of a biosensor system, and the design of a controlled release mode of functional factors. The clinical applications of intelligent engineering bacteria in the adjunctive diagnosis and treatment of metabolic diseases, inflammatory diseases, tumors, and infectious diseases were further discussed. The challenges and prospects of the current research were also analyzed to provide reference for relevant personnel.

Objective To investigate the predictive value of B-type natriuretic peptide(BNP)for acute exacerbation of chronic obstructive pulmonary disease(AECOPD)complicated by right heart failure(RHF).Methods This study selected AECOPD patients admitted to Jiangyin Hospital Affiliated to Nantong University and Nanjing Chest Hospital from January 2022 to January 2024 as ob-jects.According to the inclusion and exclusion criteria,122 patients were ultimately enrolled.The patients were divided into observation group(AECOPD with RHF,n=72)and control group(AECOPD without RHF,n=50)based on whether they had RHF.Differences in various indicators between the two groups were compared,and the predictive value of BNP for AECOPD patients with RHF was assessed through Logistic regression analysis and receiver operating characteristic(ROC)curves.The cut-off value of BNP was determined using the ROC curve.Results Statistically signifi-cant differences were observed between the two groups in terms of gender,body temperature,albumin,blood glucose,chloride ions,pulmonary artery pressure(PAP),and BNP levels(P＜0.05).Logistic regression analysis showed that BNP was an independent predictor for AECOPD patients with RHF(OR=1.03;95％CI,1.01 to 1.04;P＜0.05).The ROC curve results indicated that when the BNP cut-off value was 83.5 pg/mL,the sensitivity was 0.820,the specificity was 0.972,and the Youden index was 0.792.The area under the curve for BNP was 0.875(95％CI,0.800 to 0.949,P＜0.001).When the BNP level in AECOPD patients exceeded 83.5 pg/mL,the incidence of RHF significantly increased.Conclusion Patients with AECOPD complicated by RHF have higher plasma BNP levels than those without RHF,and BNP has significant predictive value for determining whether AECOPD patients have RHF.

Objective:To prepare ((2-(2-chlorophenyl)-3-(4-((2- 18F-fluoroethyl)oxy)phenyl)-5, 6, 7, 8-tetrahydrooxepino[3, 2-c]pyrazol-8-yl)amino)methanoic acid methyl ester ( 18F-JR-1001) and evaluate its binding affinity to the cannabinoid type 1 receptor (CB1R). Methods:18F-JR-1001 was synthesized using an integrated automated synthesis module, and its radiochemical yield (RCY) and molar activity were determined. Cell-specific uptake, lipid-water partition coefficient (log P), competitive binding assays, and in vitro stability tests were performed. Rimonabant-fed rat models (blocking group) with pre-occupied CB1R were established. Radioautography and microPET/CT imaging were conducted on both the blocking group and normal Sprague-Dawley (SD) rats to evaluate the brain uptake of 18F-JR-1001 and its blood-brain barrier (BBB) penetration capability. Results:The RCY of the synthetic 18F-JR-1001 after decay correction was (32.5±9.2)% ( n=10), with the molar activity of (194.6±67.3)GBq/μmol. Cell experiments demonstrated that 18F-JR-1001 exhibited specificity for CB1R, with log P of 3.40±0.11 ( n=3) and half-maximal inhibitory concentration of 0.975nmol/L. Within 3h at 37℃, the radiochemical purity of 18F-JR-1001 in physiological saline and blood remained above 92%, with no significant radioactive by-product peaks observed. Radioautography showed that the whole brain uptake of 18F-JR-1001 in the blocking group was 65.6% of that in normal SD rats. MicroPET/CT imaging showed that the mean whole brain uptake of 18F-JR-1001 in the blocking group was 0.4706, which was lower than that in normal SD rats (1.0561). Additionally, continuous scanning for 60min demonstrated that 18F-JR-1001 exhibited good BBB penetration capability. Conclusion:The synthesized 18F-JR-1001 meets the requirements of production and application, and is proved the potential as a CB1R-targeted tracer in the in vitro experiments, microPET/CT imaging and radioautography.

Objective:To develop and validate a novel PET tracer, N-cyclohexyl-4-((2, 4-dichlorophenyl)(4-(fluoro- 18F)phenyl)methyl)piperazine-1-carboxamide ( 18F-SQKJ-2), targeting cannabinoid type 1 (CB1) receptors for diagnosing psychiatric disorders associated with fear memory. Methods:18F-SQKJ-2 was prepared using a nucleophilic substitution radiochemical synthesis method. For the CB1 receptor blocking experiment, 7 ICR mice were divided into blocking group ( n=4; rimonabant for blocking treatment) and control group 1 ( n=3; no rimonabant blocking treatment). The affinity and specificity of 18F-SQKJ-2 for CB1 receptors were analyzed based on the differences in 18F-SQKJ-2 uptake (percentage injected dose per gram of tissue, %ID/g) by various organs between two groups. The metabolic stability of 18F-SQKJ-2 in vitro was studied using animal tissue homogenates. Ten C57 mice were used to establish fear memory mouse models (fear group, n=6; control group 2, n=4), and the percentage of freezing time was compared between 2 groups. MicroPET scans were used to detect the intracranial distribution of 18F-SQKJ-2, and the relative uptake in each brain region compared to total brain uptake was calculated. Statistical analysis was conducted to compare the differences in CB1 receptor relative total brain uptake in fear-related brain regions between 2 groups. Independent-sample t test and Mann-Whitney U test were used to analyze the data. Results:18F-SQKJ-2 was successfully synthesized with a radiochemical purity ≥98.0% and a corrected radioactive yield of (12.3±6.0)%( n=4). In vitro metabolic stability experiments showed that 18F-SQKJ-2 was basically stable in the liver, blood, and brain within 60min. The CB1 receptor blocking experiment demonstrated that the uptake of 18F-SQKJ-2 in the brains of mice in blocking group was significantly lower than that in control group 1 ((0.95±0.28) vs (3.44±1.16) %ID/g; t=-3.57, P=0.023). The percentage of freezing time in fear group was significantly higher than that in control group 2 (43.28%(39.46%, 52.93%) vs 2.74%(1.52%, 4.85%); Z=-2.45, P=0.010). 18F-SQKJ-2 microPET imaging showed that the uptake of 18F-SQKJ-2 in the cerebral cortex of mice in fear group was significantly increased compared with that in control group 2 ((5.83±0.47)% vs (5.00±0.52)%; t=2.42, P=0.046). Conclusion:18F-SQKJ-2 is successfully prepared with acceptable radiochemical purity and metabolic stability, demonstrating potential for visualizing and quantifying fear memory.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective To compare the effect of transcranial direct current stimulation(tDCS)combined with seated Taijiquan Yun-shou in different sequences on brain functional activation in healthy youths.Methods From September to December,2024,14 healthy young medical interns or probationers were recruited from the Fifth Hospital of Xiamen.They randomly completed three interventions in a crossover design:Yunshou training followed immediately by tDCS(Y-S group),tDCS intervention followed immediately by Yunshou training(S-Y group),and simultaneous implementation of tDCS intervention and Yunshou training(Sim group).Yunshou was practiced in a seated position.For tDCS,the anode was placed over the left primary motor cortex(M1),and the cathode over the right M1.Changes in oxyhemoglobin(HbO2)concentration in the regions of interest were mea-sured using functional near-infrared spectroscopy.Results Three cases dropped down.The brain regions with significant differences before and after intervention included:CH3,CH7 and CH23 of right prefrontal cortex(PFC)in Y-S group;CH12 of left PFC in S-Y group;and CH9,CH10 and CH25 of the left PFC,CH13 and CH14 of the left sensorimotor cortex(SMC),CH15 of the right pre-motor and supplementary motor cortex(PMC),and CH16 of the right SMC in Sim group(P<0.05).After inter-vention,HbO2 concentration was the highest in the bilateral PFC,bilateral PMC and left SMC in the Y-S group(P<0.05);and it was almost the same between Sim group and S-Y group(P>0.05),except that of the right PFC decreased in Sim group.Conclusion The sequential combination of brain-limb integrated regulation is a key factor influencing the immediate cor-tical activation pattern.

Objective:To explore the clinical characteristics and prognosis of malignant melanoma (MM) in the Xinjiang Uygur Autonomous Region.Methods:We collected the clinical and follow-up data of 503 MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University between 2010 and 2022. The Kaplan-Meier method was employed for survival analysis, with Log rank test used for comparing the survival rates between groups. Cox regression analysis was conducted to identify the influencing factors of patient prognosis.Results:From 2010 to 2022, the number of MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University demonstrated an upward trend. Among the 503 MM patients, the primary tumor sites were located in the extremities in 264 cases, the skin in 155 cases, the mucosal in 49 cases, and the ocular uvea in 22 cases, and in 13 cases the primary lesion was unknown. The median follow-up duration was 44 months, with a median overall survival time of 44.0 months. The overall survival rates at 1, 3, and 5 years were 85.2%, 54.3%, and 42.1%, respectively. Univariate analysis revealed that age, Breslow thickness, Clark grading, presence of ulcers, lactate dehydrogenase (LDH) levels, clinical stage at initial treatment, tumor recurrence, distant metastasis (lung, liver, bone, or brain), and postoperative adjuvant therapy were all associated with overall survival in MM patients (all P<0.05). Multivariate Cox regression analysis revealed that age ( HR=1.022, 95% CI: 1.013-1.032), LDH level ( HR=1.696, 95% CI: 1.223-2.353), clinical stage at initial treatment (TxN0M0 vs stage Ⅱ: HR=0.255, 95% CI: 0.096-0.679; TxN0M0 vs stage Ⅲ: HR=0.293, 95% CI: 0.190-0.452; TxN0M0 vs stage Ⅳ: HR=0.414, 95% CI: 0.284-0.603), bone metastasis ( HR=2.032, 95% CI: 1.252-3.298), and postoperative adjuvant therapy ( HR=0.551, 95% CI: 0.426-0.713) are independent factors influencing the overall survival of MM patients. Stratified analysis by different subtype indicated that age, clinical stage at initial treatment, gene mutations, and postoperative adjuvant therapy usage are independent factors affecting the overall survival of patients with limb MM, while age and clinical stage at initial treatment are independent factors influencing the overall survival of patients with skin and mucosal MM. Conclusions:The number of MM patients in Xinjiang Uygur Autonomous Region may be on the rise. Age, LDH level, clinical stage at initial treatment, presence of bone metastasis, and postoperative adjuvant therapy are independent risk factors for the prognosis of MM patients. Among these, age and clinical stage at initial treatment are common independent risk factors that affect the prognosis of different subtypes of MM patients.