OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

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*

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

AIM To simultaneously determine the contents of neochlorogenic acid,caffeic acid,chlorogenic acid,cryptochlorogenic acid,hydroxysafflor yellow A,ferulic acid,senkyunolide I,senkyunolide H and senkyunolide A in Fuyang Granules,and to make chemical pattern recognition.METHODS The UHPLC was performed on a 35℃thermostatic Waters Acquity UPLC?BEH C18 column(150 mm×2.1 mm,1.7 μm),with the mobile phase comprising of acetonitrile-0.01%phosphoric acid flowing at 0.4 mL/min in a gradient elution manner,and the detection wavelengths were set at 278,322,325,390 nm.Then heatmap clustering analysis and principal component analysis were adopted.RESULTS Nine constituents showed good linear relationships within their own ranges(r>0.999 0),whose average recoveries were 93.89%-102.25%with the RSDs of 0.85%-2.88%.Different batches of samples from the same enterprises demonstrated consistent overall qualities,while the overall qualities of samples from different enterprises exhibited obvious differences.CONCLUSION This simple and accurate method can be used for the quality control of Fuyang Granules.

Objective To explore the application value of pathogen-targeted next-generation sequencing(tNGS)technology in patients with suspected pulmonary infections.Methods A retrospective analysis was conducted on the clinical data of 80 patients with suspected pulmonary infections admitted to the Department of Respiratory and Critical Care Medicine at the Third People's Hospital of Hubei Province from January 2021 to July 2023.All patients underwent bronchoalveolar lavage fluid(BALF)tNGS and conventional pathogen detection.Demographic characteristics of the patients were analyzed,and the distribution of pathogens detected by tNGS and conventional methods were compared.The clinical data of patients diagnosed with single pulmonary infections and those with mixed infections were also compared.Results Among the 80 patients,74 were diagnosed with infections.Most of the infected patients had underlying conditions,mainly chronic heart disease(42.5%),chronic respiratory disease(35%),and diabetes(20%).The tNGS test results led to changes in treatment strategy for 35 patients(43.8%).A total of 45 types of pathogens were detected,with 169 strains identified by tNGS and 63 strains by conventional methods.Within pathogens detected by both methods,bacteria were detected the most.The order of pathogen types detected by tNGS was bacteria>viruses>fungi>atypical pathogens>Mycobacterium tuberculosis.The order of pathogen types detected by conventional methods was fungi>viruses>bacteria>atypical pathogens>Mycobacterium tuberculosis.The consistency between the two pathogen detection methods was poor(kappa value 0.172,P=0.020).The number of positive cases and the positive detection rates for bacteria,viruses,and atypical pathogens detected by tNGS were significantly higher than those of conventional methods(P<0.05),but there was no statistically significant difference in the positive detection rates for fungi and Mycobacterium tuberculosis between the two methods(P>0.05).Using clinical diagnosis as the gold standard,the sensitivity of tNGS detection was significantly higher than that of conventional methods(P=0.026),while there was no statistically significant difference in specificity between the two methods(P>0.05).Among the 74 confirmed pulmonary infection cases,6 had no clear pathogen,23 had single infections,and 45 had mixed infections.Among the mixed infections,the most common combination was bacterial-viral mixed infections(12/45,26.7%).The mortality rate and hospitalization duration of patients with mixed infections were significantly higher than those with single infections(P<0.05);there were no statistically significant differences in gender,age,underlying conditions,white blood cell count,and neutrophil percentage between the two groups(P>0.05).Conclusions tNGS technology has higher pathogen detection sensitivity compared to conventional methods,especially for bacteria,viruses,atypical pathogens,and rare pathogens.This technology is beneficial for identifying mixed infections and can serve as a supplement to conventional pathogen detection methods in clinical practice.

Aim To explore the effect of CXCL7/CX-CR2 axis on obesity-related cognitive dysfunction at both animal and cellular levels.Methods The novel object recognition test was performed to assess the cog-nition.After the preparation of the frozen sections,the activation of microglia and astrocytes in hippocampi and the level of PSD95 were determined by immunoflu-orescence staining.The content of CXCL7 in hipp-ocampi was determined by enzymelinked immunosor-bent assay.The dendritic spine density of hippocampal neurons was observed by Golgi staining.Furthermore,HT22 cells were treated with the recombinant mouse CXCL7 and/or si-RNA targeting CXCR2.After the treatment,the levels of CXCL7 and PSD95 were ob-served by immunocytochemistry staining.Results Compared with animals in the control group,there was significantly decreased discrimination index,increased activation of microglia and astrocytes,decreased con-tent of PSD95,decreased density of dendritic spine,and increased content of CXCL7 in hippocampi in the DIO group.Compared with animals in the DIO group,there were significantly increased discrimination index in the AWL group.In HT22 cells,the level of PSD95 significantly decreased in the Ctrl+CXCL7 group com-pared with the control group.This decrease was attenu-ated in the si-CXCR2+CXCL7 group compared with the Ctrl+CXCL7 group.Conclusion Chronic high-fat diet induces neuroinflammation and subsequently induces cognitive dysfunction,which may be related to the synaptic plasticity mediated by the CXCL7/CXCR2 axis.

In order to elucidate the therapeutic effect and mechanism of action of Zhengqing Fengtongning Sustained-release Tablets on knee osteoarthritis, this study created a knee osteoarthritis model using 0.2 mL 40 g·L~(-1) papain and randomly divided the rats into the model group, high-dose and low-dose groups of Zhengqing Fengtongning Sustained-release Tablets, and celecoxib group. All groups were given the drug for four weeks, with the diameter of their knee joint being measured during this period. Hematoxylin-eosin staining and Senna solid green staining were utilized to observe the pathology of knee joint tissue in SD rats. The initial therapeutic impact of Zhengqing Fengtongning Sustained-release Tablets on knee osteoarthritis in rats was assessed by monitoring the levels of interleukin-1β(IL-1β) and interleukin-6(IL-6) in the plasma. Using a combination of non-targeted metabolomics and 16S rRNA techniques, researchers determined the variations in endogenous molecules and intestinal flora in rats and identified potential biomarkers. The results showed that Zhengqing Fengtongning Sustained-release Tablets improved the diameter of knee joint swelling, ameliorated the pathological damage of cartilage tissue, and reduced the plasma levels of IL-1β and IL-6 in rats with knee osteoarthritis. Metabolomics analysis identified 22 potential biomarkers associated with the modulatory effects of Zhengqing Fengtongning Sustained-release Tablets, including 5-hydroxytryptamine, corticosterone, methylmalonic acid, and other biomarkers, which were mainly involved in eight metabolic pathways, including tryptophan metabolism, vitamin K metabolism, steroid synthesis, and so on. The results of intestinal flora showed a decrease in the diversity of intestinal flora in the model group, an increase in the diversity of intestinal flora, and an improvement in the microecology of intestinal flora. Significant differences were found in Lachnospiraceae＿NK4A136＿group, Helicobacter, Lactobacillus, Bacteroides, and Parabacteroides. Finally, the results of the combined analysis showed that 22 biomarkers were correlated with five genera. The above results indicate that Zhengqing Fengtongning Sustained-release Tablets can improve the tissue morphology and structure of knee joints, reduce the level of plasma inflammatory factors, regulate the diversity of intestinal flora, and balance the metabolic pathways of steroid synthesis, vitamin K metabolism, and tryptophan metabolism to exert a therapeutic effect on knee osteoarthritis.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Rats, Sprague-Dawley ; Gastrointestinal Microbiome/drug effects* ; Osteoarthritis, Knee/genetics* ; Metabolomics ; Delayed-Action Preparations/administration & dosage* ; Male ; Tablets ; Humans ; Interleukin-1beta/blood* ; Interleukin-6/blood*

Objective To understand the distribution and changes in antimicrobial resistance of clinically isolated Pseudomonas aeruginosa(P.aeruginosa)in the member hospitals of Hunan Provincial Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods Antimicrobial susceptibility testing by disk diffusion or automa-ted instrument was performed on clinical isolates.Testing results were determined according to the standards of 2022 edition from American Clinical Laboratory Standards Institute(CLSI).Statistical analysis was performed by WHONET 5.6 software.Data were analyzed by trend test(Cochran-armitage)and Chi-square test with SPSS.Results A total of 176 441 strains of P.aeruginosa were surveilled by Hunan Provincial Antimicrobial Resistance Surveillance System from 2012 to 2021.99.4％of the strains were isolated from hospitalized patients,and about 70％of the strains were isolated from respiratory specimens.8.4％of P.aeruginosa were from children(0-17 years old),91.6％were from adults.Antimicrobial susceptibility testing results showed that P.aeruginosa was most sensitive to polymyxin B over 10 years,with a resis-tance rate of less than 6％.Resistance rates to piperacil-lin,piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,imipenem,amikacin,gentamicin,tobramycin,cip-rofloxacin,levofloxacin,and polymyxin B all showed downward trends.A total of 29 920 carbapenem-resistant P.aeruginosa(CRPA)strains were detected.The average isolation rate of CRPA in this province was 18.0％over 10 years.CRPA detection rate from adult was 18.5％,higher than that from children(12.3％),and both showing downward trends.Conclusion The resistance rate of clinically isolated P.aeruginosa in Hunan Province to most commonly used antimicrobial agents is decreasing.

OBJECTIVE: To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis. METHODS: A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared. RESULTS: The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×10⁹/L, among which 15 cases (68.18%) were >10×10⁹/L, and the median count of platelet (PLT) was 24(4-55)×10⁹/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively. CONCLUSION Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.
Middle Aged ; Humans ; Male ; Female ; Aged ; Leukemia, Myelomonocytic, Acute ; Retrospective Studies ; Leukemia, Myeloid, Acute/diagnosis* ; Prognosis ; Mutation ; Receptors, Colony-Stimulating Factor/genetics*

Abstract: Objective　To analyze the influencing factors of mother-to-child transmission of hepatitis B virus after combined immunological blockade, and to evaluate the effect of mother-to-child blockade, and to provide a basis for health policies and health interventions for preventing mother-to-child blockade of hepatitis B virus. Methods A total of 11 363 pairs of HBsAg positive pregnant women and their infants aged 7-12 months in Hainan Province from 2015 to 2020 were included in the study. The general situation, the situation of health care and delivery in this pregnancy and perinatal period, the detection of hepatitis B markers, the situation of antiviral therapy, the general situation of mother and infant during delivery and the implementation of blockade measures for mother-to-child transmission of hepatitis B were collected and analyzed. Results Among the 11 363 pairs of HBsAg positive pregnant women and their infants delivered in hospitals in Hainan province from 2015 to 2020, the positive rate of HBsAg in children at 7-12 months after birth was 1.47 %, and the difference in HBsAg positive rate of infants born in different years was not statistically significant (P>0.05). There were no significant differences in the positive rate of HBsAg among children born to pregnant women with different nationalities, educational levels, occupations, delivery modes, delivery places, obstetric operations and perineal laceration, abnormal perinatal period, children with different genders and premature delivery and perinatal (all P<0.05). There was significant difference in HBsAg positive rate among infants born to pregnant women of different ages, the positive rate of HBsAg of infants born to young pregnant women was higher than that of older pregnant women (P<0.05). The rate of antiviral therapy was low in HBeAg positive pregnant women, and the positive rate of HBsAg in their infants was 2.54%, which was higher than 0.83% in HBeAg negative pregnant women (P<0.05). Conclusions Combined immunological blockade with hepatitis B vaccine and hepatitis B immunoglobulin can effectively prevent the mother-to-child transmission of HBV. HBsAg-positive women can give birth at the right age, and HBeAg-positive pregnant women can be treated with antiviral therapy to block mother-to-child transmission, providing the important basis for the formulation of hepatitis B prevention and control strategies and measures.