OBJECTIVES: Recent evidence suggests that the gut may be a primary site of metformin action. However, studies on the effects of metformin on gut microbiota remain limited, and its impact on gut microbial metabolites such as short-/medium-chain fatty acids is unclear. This study aims to investigate the effects of metformin on gut microbiota, short-/medium-chain fatty acids, and associated metabolic benefits in high-fat diet rats. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 3 groups: 1) Normal diet group (ND group), fed standard chow; 2) high-fat diet group (HFD group), fed a high-fat diet; 3) high-fat diet + metformin treatment group (HFD+Met group), fed a high-fat diet for 8 weeks, followed by daily intragastric administration of metformin solution (150 mg/kg body weight) starting in week 9. At the end of the experiment, all rats were sacrificed, and serum, liver, and colonic contents were collected for assessment of glucose and lipid metabolism, liver pathology, gut microbiota composition, and the concentrations of short-/medium-chain fatty acids. RESULTS: Metformin significantly improved HFD-induced glucose and lipid metabolic disorders and liver injury. Compared with the HFD group, the HFD+Met group showed reduced abundance of Blautia, Romboutsia, Bilophila, and Bacteroides, while Lactobacillus abundance significantly increased (all P<0.05). Colonic contents of butyric acid, 2-methyl butyric acid, valeric acid, octanoic acid, and lauric acid were significantly elevated (all P<0.05), whereas acetic acid, isoheptanoic acid, and nonanoic acid levels were significantly decreased (all P<0.05). Spearman correlation analysis revealed that Lactobacillus abundance was negatively correlated with body weight gain and insulin resistance, while butyrate and valerate levels were negatively correlated with insulin resistance and liver injury (all P<0.05). CONCLUSIONS Metformin significantly increases the abundance of beneficial bacteria such as Lactobacillus and promotes the production of short-/medium-chain fatty acids including butyric, valeric, and lauric acid in the colonic contents of HFD rats, suggesting that metformin may regulate host metabolism through modulation of the gut microbiota.
Animals ; Metformin/pharmacology* ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects* ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Fatty Acids, Volatile/metabolism* ; Fatty Acids/metabolism*

Basic research and interdisciplinary application of traditional Chinese medicine （TCM） have been continuously extended and rapidly developed with the continuous funding and promotion of basic research on TCM supported by the National Natural Science Foundation of China （NSFC）， and the overall level of basic research on TCM has been significantly improved， which has made important contributions to the diagnosis and treatment mechanism of TCM by "clarifying， identifying， and interpreting"， providing benchmark guarantees for basic research and industry development of TCM. This article focused on the application and funded projects of NSFC in 2023 under the H31 application code of TCM. It analyzed the project types， branch codes， research question categories， supporting units and regions， research directions， and keywords and summarized the characteristics of the currently funded projects in H31. At the same time， it analyzed the relevant problems in the project application process and put forward several suggestions， so as to provide a reference for scholars in the field of TCM. In 2023， a total of 8 334 applications for three types of projects （general projects， projects for young scholars， and regional projects） under the H31 code have been received by NSFC， which is the highest number in the past five years. However， the proportion of funding is still on a downward trend， and there is fierce competition among applicants. Finally， 804 projects for the three categories under the H31 code have been funded. The total funding decreased in 2022， and the average funding amount of the general project and the regional project has dropped to the lowest in the past five years. It is found that the development of branch research and the research questions under the H31 code is unbalanced. Few projects have focused on the original theory of TCM. Some projects are detached from the characteristics and research laws of TCM. Most researchers lack innovative research ideas， and the applications they write are filled with routines and patterns. In addition， the issue of scientific integrity remains a primary principle for project applicants.

Objective To investigate the effect of early glucose metabolism abnormality on skeletal muscle content of young men.Methods 88 males who underwent physical examinations in our hospital from September 2020 to September 2021 were divided into normal blood glucose group(NGT,n=47)and IGR group(n=41),according to their FPG and 2 hPG levels.FPG,FIns and visceral fat area(VFA)were measured.HOMA-IR,HOMA-β,skeletal muscle index(SMI)and body fat ratio(BFR)were calculated.Results Compared with NGT group,the males in IGR group showed elevated BMI,WC,FPG,2 hPG,HOMA-IR and VFA(P＜0.05),but decreased HDL-C and SMI(P＜0.05).Pearson correlation analysis showed that SMI was negatively correlated with BMI,WC,FPG,2 hPG,HOMA-IR,VFA and BFR in young men(P＜0.05 or P＜0.01).Logistic regression analysis showed that BMI was the influencing factor of FPG,while SMI was the influencing factor of 2 hPG.Conclusions In young men with abnormal glucose metabolism,the postprandial blood glucose significantly increase with the decrease of skeletal muscle content,and fasting blood glucose is mainly affected by BMI.

Objective To retrospectively analyze the allergen detection results of 1 193 patients with allergic rhinitis(AR)in Fengtai district of Beijing,and provide clinical evidence for the prevention and diagnosis of AR.Methods 1 193 patients diagnosed with AR and undergone the detection of serum specific IgE against allergens at the Department of Otolaryngology,Dongfang Hospital,Beijing University of Chinese Medicine from January to December 2022 were included,and the correlations between the allergen test results and the patients'gender and age,and season were analyzed.Results Among the 1 193 patients,a total of 947 patients had positive serum allergy test results,with a positive detection rate of 79.38%.The main allergens of the AR patients in Fengtai district of Beijing were Cyperus/Birch,Artemisia,and Candida/Penicillium nodosum/Mycosphaerella/Streptomyces/Aspergillus niger.The positive rate of allergens in male AR patients(82.15%)was higher than that in females(77.23%),and the difference was statistically significant(P<0.05).The highest positive rate(85.35%)of allergens was found in autumn,and there was a statistically significant difference in the positive rates of allergens between different seasons(P<0.05).The positive rate(95.68%)of allergens was the highest in the≤14-year-old group,and there was a statistically significant difference in the positive rates of allergens among patients of different age groups(P<0.001).Conclusion The allergens of AR patients in Fengtai district of Beijing have difference and diversity,and the difference is related to gender,season and age.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective To establish and validate a model that can predict the risk of death during hospitalization in elderly patients with sepsis. Methods A total of 238 hospitalized patients with sepsis in the Intensive Care Unit of the First Hospital Affiliated to Harbin Medical University from January 2019 to December 2022 were retrospectively included, and they were divided into death group with 68 cases (28.57%) and survival group with 170 cases (71.43%) according to the prognosis during hospitalization as the primary outcome indicator. Multivariate Logistic regression was used to screen the independent risk factors for death during hospitalization in sepsis patients, and a model for predicting the risk of death during hospitalization in sepsis patients was established based on these factors. The performance of the prediction model was evaluated by the receiver operating characteristic (ROC) curve, and the results were expressed by the area under the curve (AUC); external validation was performed based on the clinical data of 176 sepsis patients from January 2016 to December 2018. Results Univariate analysis showed that when compared with the survival group, the death group had higher ratios of patients aged over 70 years, ratio of injury (AKI) in stage Ⅲ, higher levels of red cell distribution width (RDW), fibrinogen, lactate, blood creatinine, the National Early Warning Score (NEWS) and the quick Sequential Organ Failure Assessment (qSOFA) score, but lower levels of oxygenation index and albumin, and the differences were statistically significant (P < 0.05). Multivariate Logistic regression analysis showed that age over 70 years old (OR=1.426, 95%CI, 1.055 to 1.928), lactate>6 mmol/L (OR=1.436, 95%CI, 1.105 to 1.867), RDW>16% (OR=1.354, 95%CI, 1.080 to 1.698), AKI in stage Ⅲ (OR=1.982, 95%CI, 1.407 to 2.791), and qSOFA score>2 points (OR=1.853, 95%CI, 1.255 to 2.738) were the independent risk factors for death during hospitalization in patients with sepsis (P < 0.05). Based on the regression analysis results, a risk equation for death in patients with sepsis was established, and consistency index (C_index)=-1.694+0.355×age+0.303×RDW+0.362×lactate+0.684×AKI in stage Ⅲ+0.617×qSOFA score. The ROC curve showed that the AUC of C_index for predicting death during hospitalization in patients with sepsis was 0.882 (95%CI, 0.834 to 0.929) with a sensitivity of 83.82% and a specificity of 77.06% by internal validation, and 0.823 (95%CI, 0.757 to 0.889) with a sensitivity of 74.13% and a specificity of 81.36% by external validation. Conclusion Age, lactate, RDW, AKI staging and qSOFA score are correlated with the risk of death in elderly patients with sepsis, and the model constructed based on these parameters may help predict the risk of all-cause death during hospitalization in elderly patients with sepsis.

ObjectiveTo investigate the effect and mechanism of Nongsuo Dangguiwan in improving ovarian oxidative stress in rats with ovarian dysfunction. MethodThirty-six adult female SD rats were randomly divided into normal group， model group， positive drug group （Femoston， 0.3 mg·kg^-1）， and high-， medium-， and low-dose groups of concentrated Nongsuo Dangguiwan （2.08， 4.16， 8.32 g·kg^-1）， with six rats in each group. Rats， except for those in the normal group， were injected with 80 mg·kg^-1 vinyl cyclohexene dioxide （VCD） per day for 14 consecutive days to induce ovarian dysfunction. From the 15th day， rats were treated with corresponding drugs by gavage， while those in the model group received 2 mL·kg^-1 saline， once daily for 28 consecutive days. The ovarian index， levels of related hormones including estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and anti-mullerian hormone （AMH） in serum， as well as superoxide dismutase （SOD） activity and glutathione （GSH） content in serum were measured by enzyme-linked immunosorbent assay （ELISA）. The malondialdehyde （MDA） content in serum was detected by the thiobarbituric acid （TAB） method. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. The expression of nuclear factor E₂-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， SOD2， and SOD1 in ovarian tissues was detected by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed a significant reduction in growing follicles in the ovary， loose arrangement of granulosa cells in the follicle， decreased body weight， ovarian index， and serum AMH and E₂ levels， increased LH and FSH levels （P<0.01）， reduced levels of SOD and GSH in serum （P<0.01）， and increased MDA level （P<0.01）. Compared with the model group， the groups with drug intervention showed increased ovarian index （P<0.05， P<0.01）， increased serum E₂ level （P<0.05， P<0.01）， decreased FSH， AMH， and LH levels （P<0.05， P<0.01）， increased number of growing follicles in the ovary， potentiated SOD activity in serum， increased GSH content， decreased MDA content （P<0.05， P<0.01）， and up-regulated expression levels of Nrf2， HO-1， SOD2， and SOD1 proteins in ovarian tissues （P<0.05， P<0.01）. ConclusionNongsuo Dangguiwan can regulate serum hormone levels， increase the expression of Nrf2， HO-1， SOD2， and SOD1 in ovarian tissues， and improve ovarian antioxidant capacity to resist oxidative stress injury， thereby improving ovarian reserve function.

Currently， evidence on the efficacy and risk of traditional Chinese medicine （TCM） injections is seriously insufficient， and it is difficult to evaluate TCM injections comprehensively， truly and objectively using available efficacy evaluation indicators. Therefore， establishing a clinical efficacy evaluation system that can effectively reflect TCM injections is imperative. Core outcome set （COS） has played an important role in screening TCM efficacy evaluation indicators， however， there are still certain problems， such as large differences in efficacy indicators， non-standardization， and lack of featured and specific TCM indicators. Mixed method research （MMR） has the advantages of looking at problems from both quantitative and qualitative perspectives. It is thereby proposed to use COS and MMR integrated model to establish a clinical efficacy evaluation indicator system that not only fully considers the cha-racteristics of TCM injections， but also highlights the efficacy and advantages of TCM injections from the perspective of TCM intervention. Simultaneously， an indicator screening method using MMR to optimize COS research model is formulated， which can provide ideas for the research on efficacy evaluation indicators of TCM injections.

Objective To explore the role of autophagy, apoptosis of neutrophils and neutrophils extracellular traps (NET) formation in systemic lupus erythematosus (SLE). Methods Thirty-six patients with SLE were recruited as research subjects, and 32 healthy controls matched accordingly were enrolled as control subjects. The expression levels of microtubule associated protein 1 light chain 3B (LC3B), autophagy-related gene5(ATG5), P62, B-cell lymphoma 2(Bcl2), Bcl2-related X protein (BAX) in neutrophils were detected by Western blot analysis. Flow cytometry was employed to analyze the expression of LC3B on neutrophils. The expression level of myeloperoxidase(MPO) in plasma was estimated by ELISA. Furthermore, neutrophils were cultured in vitro and stimulated by 100 nmol/L rapamycin and 10 μg/mL lipopolysaccharide (LPS) for 6 hours, respectively. And then, the expression levels of LC3B, ATG5, P62, Bcl2 and BAX in neutrophils were detected by Western blot analysis. The level of MPO in culture supernatant was detected by ELISA. The change of fluorescence intensity of NET in culture supernatant was assayed by Sytox^TM Green staining combined with fluorescence spectrophotometry. Results Compared with healthy controls, the levels of autophagy and apoptosis of neutrophils and NET formation in SLE patients were increased. The level of apoptosis and NET formation was positively associated with neutrophil autophagy. The level of autophagy showed an increase but had no effect on apoptosis and NET formation for neutrophil stimulated by rapamycin. The levels of autophagy and NET formation also increased with no significant effect on apoptosis for neutrophil induced by LPS. Conclusion The autophagy, apoptosis and NET formation of neutrophils increase in SLE patients. The activation of autophagy and NET in neutrophils possibly result from the inflammatory internal environment in SLE patients.
Humans ; Neutrophils ; Extracellular Traps/metabolism* ; Lipopolysaccharides/pharmacology* ; bcl-2-Associated X Protein/metabolism* ; Sirolimus/pharmacology* ; Lupus Erythematosus, Systemic ; Autophagy

ObjectiveTo explore the mechanism of Jianpi Yishen Huazhuo prescription in the improvement of ovarian function in polycystic ovary syndrome （PCOS）. MethodSeventy female SD rats in SPF grade were randomly divided into 6 groups， 15 in the blank group and 15 in the model group， 10 in the metformin group （0.1 g·kg^-1·d^-1）， and 10 in the low （1.275 g·kg^-1·d^-1）， medium （2.55 g·kg^-1·d^-1）， and high-dose （5.10 g·kg^-1·d^-1） Jianpi Yishen Huazhuo prescription groups. The blank group was given normal saline （10 mL·kg^-1·d^-1） by gavage and ordinary feed， and the other groups were given letrozole （1 mg·kg^-1·d^-1） by gavage combined with high-fat feed for 21 days to induce the model of PCOS. After modeling， the blank group and model group were given equal volume normal saline by gavage， and each drug group was given the corresponding dose of the drug by gavage for 30 days. The changes in body mass and fasting blood glucose （FPG） of rats before and after modeling were compared. Hematoxylin eosin （HE） staining was used to observe the morphological change in the ovaries of rats in each group. The serum levels of follicle stimulating hormone （FSH）， luteinizing hormone （LH）， testosterone （T）， anti-Mullerian hormone （AMH）， and estradiol （E₂） were measured by enzyme-linked immunosorbent assay （ELISA）， and the LH/FSH ratio was calculated. Immunohistochemical staining （IHC） and Western blot were used to detect the protein expression levels of nucleoside binding oligomerization domain protein like receptor 3 （NALP3）， apoptosis-associated speck-like protein （ASC）， cysteine protease-1 （Caspase-1）， nuclear transcription factor-κB （NF-κB）， interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and interleukin-6 （IL-6） in the rat ovaries. ResultAs compared with the blank group， large follicles with polycystic expansion were found in the ovaries of the model group， no dominant follicles were found， the granular layer of follicles decreased and arranged loosely， and the number of corpus luteum decreased significantly. Serum T， LH， AMH and LH/FSH increased in the model group （P<0.05， P<0.01）， while FSH and E₂ decreased （P<0.05， P<0.01）. The relative protein expression levels of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 increased （P<0.05， P<0.01） in the ovaries of the model group. Compared with the model group， the low， medium， and high-dose Jianpi Yishen Huazhuo prescription groups and the metformin group showed growing follicles and corpus luteum at all levels， the number of cystic expanding follicles decreased， the thickness of follicular granular layer increased， the number of follicular fluid increased， mature follicles were visible， and the local morphology of oocytes was complete. Serum T， LH， AMH， and LH/FSH in these groups decreased （P<0.05， P<0.01）， while E₂ and FSH increased （P<0.05）. The relative protein expressions of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 in the ovaries of these groups decreased （P<0.05， P<0.01）. There was no significant difference among the treatment groups. ConclusionBy inhibiting the activation of NLRP3 inflammasome， Jianpi Yishen Huazhuo prescription reduces the release of NALP3， ASC， Caspase-1， NF-κB， IL-18， IL-1β， and IL-6 inflammatory factors in ovarian tissues， regulates endocrine level， and effectively reduces PCOS inflammatory statu， so as to play a role in improving ovarian function.