ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

ObjectiveTo evaluate the therapeutic effects of modified Buwangsan on cognitive dysfunction in the rat model of type 2 diabetes mellitus with mild cognitive impairment （T2DM-MCI） and explore the underlying mechanism. MethodsThirty-six 5-week-old SPF-grade SD rats were randomly assigned into 6 groups： Normal （Con， fed with a normal diet）， model （DM， fed with a high-sugar and high-fat diet）， low-dose modified Buwangsan （L-BWS， 1.86 g·kg^-1）， medium-dose modified Buwangsan （M-BWS， 3.72 g·kg^-1）， high-dose modified Buwangsan （H-BWS，7.44 g·kg^-1）， and huperzine A （SSJJ， 0.018 mg·kg^-1）. The rats were treated by gavage once a day for 12 weeks. The body weight and blood glucose level were monitored dynamically. Morris water maze was employed to test the cognitive function of rats. Hematoxylin-eosin and Nissl staining were employed to observe the pathological changes of the hippocampus. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the serum and hippocampus were assessed by enzyme-linked immunosorbent assay. Western blotting was employed to determine the expression levels of key autophagy-related proteins including microtubule-associated protein 1 light chain 3 （LC3）， type Ⅲ phosphatidylinositol 3-kinase complex regulatory subunit （Beclin1）， and phosphorylated UNC-51-like kinase （p-ULK） 1/2 in the hippocampus. Immunofluorescence staining was employed to observe the regulation of p-PI3K/PI3K， p-mTOR/mTOR， and p-Akt/Akt ratios. ResultsCompared with the DM group， the L-BWS， M-BWS， H-BWS， and SSJJ groups showed increases in body weight at the end of the experiment （P<0.05）， and the M-BWS， H-BWS and SSJJ groups showed declines in fasting blood glucose level （P<0.05）. In the water maze test， compared with the DM group， the M-BWS， H-BWS， and SSJJ groups presented shortened escape latency （P<0.001）. The L-BWS， M-BWS， H-BWS， and SSJJ group showcased regularly arranged cells in the hippocampus and cortex， markedly increased number of neurons， and significantly recovered Nissl bodies. Compared with the DM group， the L-BWS， M-BWS， H-BWS， and SSJJ groups had reductions in the levels of IL-1β and IL-6 in the serum and hippocampus （P<0.05）， increases in the LC3-II/LC3-I ratio and expression level of beclin1 in the hippocampus （P<0.05） and the p-ULK level （P<0.05）. The p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR ratios in the hippocampus decreased in the M-BWS， H-BWS， and SSJJ groups （P<0.01）. ConclusionModified Buwangsan significantly ameliorates cognitive dysfunction and neurological damage in the rat model of T2DM through multiple mechanisms. It regulates metabolic disorders， lowers the blood glucose level， improves lipid metabolism， and alleviates oxidative stress. It promotes the protection and repair of neurons by inhibiting inflammatory responses and activating the autophagy pathway in the hippocampus. At the same time， modified Buwangsan relieves autophagy inhibition by regulating the PI3K/Akt/mTOR signaling pathway to alleviate the brain tissue injury.

ObjectiveTo evaluate the therapeutic effects of modified Buwangsan on cognitive dysfunction in the rat model of type 2 diabetes mellitus with mild cognitive impairment （T2DM-MCI） and explore the underlying mechanism. MethodsThirty-six 5-week-old SPF-grade SD rats were randomly assigned into 6 groups： Normal （Con， fed with a normal diet）， model （DM， fed with a high-sugar and high-fat diet）， low-dose modified Buwangsan （L-BWS， 1.86 g·kg^-1）， medium-dose modified Buwangsan （M-BWS， 3.72 g·kg^-1）， high-dose modified Buwangsan （H-BWS，7.44 g·kg^-1）， and huperzine A （SSJJ， 0.018 mg·kg^-1）. The rats were treated by gavage once a day for 12 weeks. The body weight and blood glucose level were monitored dynamically. Morris water maze was employed to test the cognitive function of rats. Hematoxylin-eosin and Nissl staining were employed to observe the pathological changes of the hippocampus. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the serum and hippocampus were assessed by enzyme-linked immunosorbent assay. Western blotting was employed to determine the expression levels of key autophagy-related proteins including microtubule-associated protein 1 light chain 3 （LC3）， type Ⅲ phosphatidylinositol 3-kinase complex regulatory subunit （Beclin1）， and phosphorylated UNC-51-like kinase （p-ULK） 1/2 in the hippocampus. Immunofluorescence staining was employed to observe the regulation of p-PI3K/PI3K， p-mTOR/mTOR， and p-Akt/Akt ratios. ResultsCompared with the DM group， the L-BWS， M-BWS， H-BWS， and SSJJ groups showed increases in body weight at the end of the experiment （P<0.05）， and the M-BWS， H-BWS and SSJJ groups showed declines in fasting blood glucose level （P<0.05）. In the water maze test， compared with the DM group， the M-BWS， H-BWS， and SSJJ groups presented shortened escape latency （P<0.001）. The L-BWS， M-BWS， H-BWS， and SSJJ group showcased regularly arranged cells in the hippocampus and cortex， markedly increased number of neurons， and significantly recovered Nissl bodies. Compared with the DM group， the L-BWS， M-BWS， H-BWS， and SSJJ groups had reductions in the levels of IL-1β and IL-6 in the serum and hippocampus （P<0.05）， increases in the LC3-II/LC3-I ratio and expression level of beclin1 in the hippocampus （P<0.05） and the p-ULK level （P<0.05）. The p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR ratios in the hippocampus decreased in the M-BWS， H-BWS， and SSJJ groups （P<0.01）. ConclusionModified Buwangsan significantly ameliorates cognitive dysfunction and neurological damage in the rat model of T2DM through multiple mechanisms. It regulates metabolic disorders， lowers the blood glucose level， improves lipid metabolism， and alleviates oxidative stress. It promotes the protection and repair of neurons by inhibiting inflammatory responses and activating the autophagy pathway in the hippocampus. At the same time， modified Buwangsan relieves autophagy inhibition by regulating the PI3K/Akt/mTOR signaling pathway to alleviate the brain tissue injury.

Objective: To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies. Methods: A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE). Results: There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years. Conclusions The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.

ObjectiveTo investigate and analyze an outbreak of rotavirus infectious diarrhea in a prison in Chongqing Municipality, to provide a basis for adult rotavirus surveillance and prevention, and to explore the public health problems in special settings. MethodsA retrospective survey was conducted to collect and analyze data on individual cases with diarrheal disease on-site. The clinical characteristics, as well as the temporal, spatial and geographical distribution patterns of the epidemic were described. Multi-pathogen detection tests were conducted both on diarrhea cases and environmental samples, with viral genotyping performed on positive samples. A case-control analysis was performed to identify the causes of the outbreak, and an SEIR model was adopted to predict the outbreak trend and evaluate the effectiveness of interventions. ResultsA total of 65 cases were found among the inmates, with an attack rate of 2.03%. The predominant clinical manifestations included diarrhea (89.23%), watery stool (73.85%), and dehydration (18.46%). The epidemic curve indicated a “human-to-human” transmission pattern, with an average incubation period of 5‒6 days. The attack rates among chefs in the main canteen (80.00%, 8/10) and caterers (28.33%, 17/60) were significantly higher than those of other inmates （P<0.05）. Multi-pathogen polymerase chain reaction (PCR) testing detected positive for group A rotavirus, with the viral genotyping identified as G9P [8] strain. Factors such as unprotected "bare-handed" food distribution among cases with diarrhea (OR=9.512, 95%CI: 4.261‒21.234) and close contact with diarrhea cases (OR=3.656, 95%CI: 1.719‒7.778) were the possible cause of the outbreak. The SEIR model (r₀=5, α=0.3, β₁=0.08, β₂=0.04) was constructed using prison inmates as susceptible population, aiming at fitting the initial transmission trend of the outbreak, and the epidemic rate declined rapidly after intervention measures were implemented (r_t≈0). ConclusionThis rare rotavirus infection diarrhea outbreak among adults in confined settings suggests that the construction of public health prevention and control systems in prison may be overlooked. Cross infection during meal processing and distribution in the canteens of such settings is likely to be the cause of the outbreak. Given the potential neglect of public heath system construction in special settings, it is imperative to enhance the surveillance and monitoring of rotavirus and other intestinal multi-pathogens among adults, as well as the construction of public health prevention and control systems in these special settings.

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

Alzheimer's disease is a common central neurodegenerative disease， mainly manifested by cognitive impairment and non-cognitive neuropsychiatric symptoms that severely affect patients' daily life and behavioral functioning. The pathogenesis of Alzheimer's disease is still unclear， and the western medicine currently used to treat Alzheimer's disease is only symptomatic， with a single pathway， limited efficacy， and many side effects. In recent years， with the deepening of research on Alzheimer's disease， the study and application of traditional Chinese medicine （TCM） in the treatment of Alzheimer's disease have gradually increased. Several studies have shown that TCM and its effective components can exert anti-Alzheimer's disease effects by regulating molecular mechanisms such as pathological protein production and aggregation， oxidative stress， neuroinflammation， ferroptosis， mitochondrial dysfunction， neurogenesis and neurotransmission， and brain-gut axis. This paper summarized the research progress of TCM in the treatment of Alzheimer's disease in recent years， so as to provide a reference for further study of the specific mechanism of TCM in the prevention and treatment of Alzheimer's disease and the discovery of effective components of TCM.

The concept of"one qi peripheral flow"originates from the ancient Chinese philosophy of"qi monism"and the theory of yin and yang chi chemistry in the Yellow Emperor's Classic of Internal Medicine,and was formally proposed in Huang Yuanyu's The Origin of the Four Sacred Hearts,which elaborates on the theory of one qi circumference in which the earth pivots on four signs and the left rises and the right descends.Based on this theory,this paper discusses the diagnosis and treatment of thyroid nodules,believes that the development of thyroid nodules is closely related to the deficiency of the earth and qi,and the disorder of the liver and lungs,and combines the evidence of modern research to argue that the deficiency of the earth and qi,and the disorder of the liver and lungs are the important pathomechanisms of the thyroid nodules,proposes to refer to the results of ultrasound elasticity imaging of the thyroid gland for staging and typing treatment of thyroid nodules.It also summarizes the clinical use of medicines in different stages and types,aiming at estoring the"one qi peripheral flow"in the body,and provides a new diagnostic and therapeutic idea for the clinical diagnosis and treatment of thyroid nodules.

ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.