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*

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.
Animals ; Male ; Rats ; Apoptosis ; Brain Ischemia/metabolism* ; Caspase 3 ; Interleukin-1 ; Interleukin-6 ; Rats, Sprague-Dawley ; Reperfusion Injury/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Flavonoids/pharmacology* ; Rhododendron/chemistry*

Tanshinones are one of the main effective components of Salvia miltiorrhiza, which play important roles in the treatment of cardiovascular diseases. Microbial heterogony production of tanshinones can provide a large number of raw materials for the production of traditional Chinese medicine(TCM) preparations containing S. miltiorrhiza, reduce the extraction cost, and relieve the pressure of clinical medication. The biosynthetic pathway of tanshinones contains multiple P450 enzymes, and the catalytic element with high efficiency is the basis of microbial production of tanshinones. In this study, the protein modification of CYP76AK1, a key P450-C20 hydroxylase in tanshinone pathway, was researched. The protein modeling methods SWISS-MODEL, Robetta, and AlphaFold2 were used, and the protein model was analyzed to obtain the reliable protein structure. The semi-rational design of mutant protein was carried out by molecular docking and homologous alignment. The key amino acid sites affecting the oxidation activity of CYP76AK1 were identified by molecular docking. The function of the obtained mutations was studied with yeast expression system, and the CYP76AK1 mutations with continuous oxidation function to 11-hydroxysugiol were obtained. Four key amino acid sites that affected the oxidation acti-vity were analyzed, and the reliability of three protein modeling methods was analyzed according to the mutation results. The effective protein modification sites of CYP76AK1 were reported for the first time in this study, which provides a catalytic element for different oxidation activities at C20 site for the study of the synthetic biology of tanshinones and lays a foundation for the analysis of the conti-nuous oxidation mechanism of P450-C20 modification.
Oxidoreductases ; Biosynthetic Pathways ; Molecular Docking Simulation ; Reproducibility of Results ; Salvia miltiorrhiza/chemistry* ; Amino Acids/metabolism* ; Plant Roots/genetics*

In recent years,the number of patent applications for traditional Chinese medicine( TCM) inventions has increased rapidly,but the authorization rate has declined. Listed TCM enterprises are a group of active innovators in this field,so this paper analyzes their patent quality by combining patent application and authorization with R&D investment of enterprises in order to explore a practical way to improve the quality of TCM patents. The conclusions are as follows: the R&D investment of listed TCM enterprises is insufficient and the gap between enterprises is large; the number of patent applications is within a reasonable range,but some enterprises still have abnormal patent applications,and patent quality needs to be improved; in addition,the patent operation capacity of enterprises still needs to be improved. In this phenomenon,enterprises should improve R&D investment,strengthen the level of technological innovation,improve the ability of patent operation,and consciously eliminate the output of " abnormal patents"; the patent administrative department should optimize policy direction which is beneficial to the improvement of patent quality,grasp the normal and reasonable examination scale,and jointly improve the quality of TCM patents.
Drugs, Chinese Herbal ; Inventions ; Medicine, Chinese Traditional

OBJECTIVETo analyze the risk factors and prognosis of hepatic chronic GVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSThe clinical data of 147 patients undergoing allo-HSCT from January 2013 to December 2016 were analyzed, the correlation between recipient age and sex, disease state, matched degree of HLA, donor sex, stem cell sources, ATG in GVHD prophylaxis, liver dysfunction during conditioning period, pre-transplant HBsAg, prior aGVHD and hepatic cGVHD were studied, and the correlation between hepatic cGVHD and prognosis were analysed.

RESULTSThirty-two patients had hepatic cGVHD, cumulative incidence of 26.4%. In univariate analysis, pre-transplant HBsAgand liver dysfunction during conditioning period were not significantly related with hepatic cGVHD (P>0.05). In multivariate analysis, prior acute GVHD (HR=2.087, P=0.045) was the independent risk factor for hepatic cGVHD, ATG (HR=0.231, P=0.000) was significantly related with a lower incidence of hepatic cGVHD. In univariate analysis, patients with hepatic cGVHD had a lower 2 years relapse rate (P=0.038).

CONCLUSIONPrior acute GVHD is the independent risk factor for hepatic cGVHD, the ATG can significantly reduce the incidence of hepatic cGVHD. Hepatic cGVHD has been found to relate with a lower 2 years relapse rate.

The United States Patent and Trademark Office(USPTO) issued Interim Guidance on Patent Subject Matter Eligibility on December 16， 2014， bringing certain effects to the review rules on patent application of Chinese medicine compositions. Based on the Interim Guidance， cases analysis was used in this paper to analyze the patent subject matter issues of traditional Chinese medicine compositions in the United States. The researches have shown that the application documents should be properly written in the United States when the patent for Chinese medicine compositions is applied， which can improve the probability of authorization.
Drugs, Chinese Herbal ; chemistry ; standards ; Medicine, Chinese Traditional ; standards ; Patents as Topic ; Research ; United States

Objective To discuss the correlation between SIRT3 protein and clinicopathological parameters of gastric carcinoma.Methods Immunohistochemistry and Western blot were used to detect the expression of SIRT3 in the gastric carcinoma and normal gastric tissue.The correlation between the expression of SIRT3 and clinicopathological parameters was analyzed.Results The immunohistochemistry showed that the positive expression rate of SIRT3 protein in gastric carcinoma tissue (53.8 ％,43/80) was obviously lower than that in normal gastric tissue (86.0 ％,43/50),and the expression of SIRT3 protein showed close relationship with invasion depth,lymph node metastasis and TNM stage (P ＜ 0.05),rather than the age,gender,tumor size,or differentiation status (P ＞ 0.05).The Western blot showed that the expression rate of SIRT3 protein (SIRT3/β-actin) in gastric carcinoma tissue (0.655±0.317) was lower than that in normal gastric tissue (0.803±0.329) (P ＜ 0.05).Conclusion The expression of SIRT3 protein is lower in gastric cancer than that in normal gastric tissue,and relates to invasion depth,lymph node metastasis and TNM stage.SIRT3 may inhibit the occurrence and development of gastric cancer.