OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

As a strategic emerging industry, biomanufacturing faces core challenges in achieving precise optimization and efficient scale-up of fermentation processes. This review focuses on two critical aspects of fermentation-real-time sensing and intelligent control-and systematically summarizes the advancements in online monitoring technologies, artificial intelligence (AI)-driven optimization strategies, and digital twin applications. First, online monitoring technologies, ranging from conventional parameters (e.g., temperature, pH, and dissolved oxygen) to advanced sensing systems (e.g., online viable cell sensors, spectroscopy, and exhaust gas analysis), provide a data foundation for real-time microbial metabolic state characterization. Second, conventional static control relying on expert experience is evolving toward AI-driven dynamic optimization. The integration of machine learning technologies (e.g., artificial neural networks and support vector machines) and genetic algorithms significantly enhances the regulation efficiency of feeding strategies and process parameters. Finally, digital twin technology, integrating real-time sensing data with multi-scale models (e.g., cellular metabolic kinetics and reactor hydrodynamics), offers a novel paradigm for lifecycle optimization and rational scale-up of fermentation. Future advancements in closed-loop control systems based on intelligent sensing and digital twin are expected to accelerate the industrialization of innovative achievements in synthetic biology and drive biomanufacturing toward higher efficiency, intelligence, and sustainability.
Artificial Intelligence ; Fermentation ; Bioreactors/microbiology* ; Neural Networks, Computer ; Algorithms ; Biotechnology/methods*

The chemical composition of Paeoniae Radix Alba(PRA) is complex, with primary secondary metabolites including monoterpenoids, tannins, triterpenoids, and flavonoids. In previous studies on the material basis of PRA, it was found that, in addition to the widely studied characteristic monoterpene glycosides, tannic acid components also play an important role in the efficacy of PRA. However, their pharmacological effects have not been thoroughly investigated. This paper reviews the tannic acid components in PRA, including pentagaloyl glucose(PGG), tetragaloyl glucose(TGG), trigaloyl glucose(TriGG), and gallic acid, along with their structures, properties, and characteristics to provide a detailed discussion of their pharmacological activities and related mechanisms, aiming to offer a theoretical basis for the material basis research and clinical application of PRA.
Paeonia/chemistry* ; Tannins/chemistry* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Plant Extracts

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

Objective To analyze the factors influencing the occupational health literacy (OHL) level among workers in key industries from the perspectives of both individual workers and enterprises. Methods A total of 32 336 front-line workers from 12 key industries in the secondary industry in Guangdong Province were selected as the research subjects by a stratified cluster random sampling method. Their OHL level was investigated using Occupational Health Literacy Questionnaire of National Key Populations, and the influencing factors were analyzed. Results The OHL level of the research subjects was 48.5%. The OHL level of the research subjects in four dimensions from high to low was basic knowledge of occupational health protection, occupational health practice and behavior, legal knowledge of occupational health, and basic skills of occupational health protection (80.7%, 61.2%, 48.3% and 29.5%, respectively). The multivariable logistic regression analysis showed that the OHL level of female workers was lower than that of males (P<0.05). Lower OHL was also associated with older age, lower education level, lower personal monthly income of workers (all P<0.01). The workers with length of service < 3 years and ≥ 20 years had lower OHL level than those with length of service 3-<10 years and 10-<20 years, respectively (all P<0.05). Workers in larger enterprises had higher OHL levels (all P<0.01). The OHL level of workers in the sixth category of industries with occupational injuries had higher occupational injury risks than those in the third and fourth categories (all P<0.05). The OHL levels of workers in state-owned enterprises, private enterprises, foreign-funded enterprises, and other enterprises were higher than that of workers in public institutions (all P<0.05). Conclusion The influencing factors of workers′ OHL in key industries of the secondary industry include individual factors (gender, age, education level, personal monthly income, length of service) and enterprise factors (enterprise size, enterprise nature and industry injury risk category). Female, older workers, those with lower education or income, and those with short length of service represent priority groups for OHL interventions, while small and micro enterprises are priority units for future workplace health promotion intervention.

ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.