Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

AIM To investigate the effects of Changpu Yujin Decoction(CPYJD)on striatal mitophagy and PINK1/Parkin signaling pathway in a rat model of Tourette syndrome(TS).METHODS Thirty-six SPF male SD rats were randomly assigned to the control group(n=9)and the TS modeling group(n=27).Rats in the modeling group received daily intraperitoneal injections of 3,3'-iminodipropionitrile(IDPN)(300 mg/kg)for 7 consecutive days to establish the TS model.Post-modeling,successfully induced TS rats were re-randomized into model group(no treatment),tiapride group(47.91 mg/kg)and CPYJD group(77.28 g/kg).All groups received their respective interventions via intragastric administration daily for 28 days.Following drug administration,behavioral scores were assessed in each group.Pathological alterations in the striatum were examined using HE staining,while ultrastructural changes were evaluated by transmission electron microscopy(TEM).Neuronal apoptosis was quantified via TUNEL staining,and ROS levels in striatum were measured by ELISA.Co-localization of PINK1 and LC3B was assessed using immunofluorescence(IF).Finally,mRNA and protein expressions of PINK1,Parkin,Beclin-1,P62 and LC3B(LC3B-Ⅱ/Ⅰ ratio)were analyzed by RT-qPCR and Western blot.RESULTS Compared to the control group,the model group demonstrated significantly increased behavioral scores(P＜0.01),elevated neuronal apoptosis rate and higher ROS levels in the striatum(P＜0.01);severe neuronal and mitochondrial damage in the striatum;significantly reduced mRNA and protein expressions of PINK1,Parkin,Beclin-1 and LC3B(LC3B-Ⅱ/Ⅰ ratio)in the striatum(P＜0.01);markedly upregulated P62 mRNA and protein expressions(P＜0.01).Compared to the model group,both the tiapride and CPYJD intervention groups exhibited significantly reduced behavioral scores(P＜0.01);decreased neuronal apoptosis rate and lower ROS levels(P＜0.01);improved pathological alterations in the striatal neurons and mitochondria;increased mRNA and protein expressions of PINK1,Parkin and Beclin-1 in the striatum(P＜0.05,P＜0.01);and decreased P62 mRNA and protein expressions(P＜0.01).Furthermore,the rats in the CPYJD group specifically showed elevated LC3B mRNA level and LC3B-Ⅱ/Ⅰ protein ratio in striatum(P＜0.05,P＜0.01).CONCLUSION The effect of CPYJD intervention in TS rats may involve activation of mitophagy through regulation of the PINK1/Parkin signaling pathway,improving mitochondrial function,reducing ROS levels,and thereby protecting neurons.

Objective To explore the relationship between continuous glucose monitoring(CGM)parameters with diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 355 T2DM patients who were hospitalized in the Department of Endocrinology of Wuhan Central Hospital,Tongji Medical College,Huazhong University of Science and Technology,from August 2022 to February 2024 were included.According to uninary albumin/creatinine rate(UACR)and estimated glomerular filtration rate(eGFR)levels,the patients were divided into T2DM group(n=207)and DKD group(DKD,n=148).The general clinical data and CGM parameters of the two groups were compared.Results Age,systolic pressure,DM duration,proportion of Ins use,proportion of cerebral infarction and lumen infarction,proportion of lower limb arterial plaque formation,serum troponin I,D-dimer,erythrocyte deposition rate,UACR,blood urea nitrogen(BUN),serum creatinine,blood uric acid,mean glucose value(MG),blood glucose management index(GMI),time glucose below target range(TBR),glucose above target range time(TAR)and mean blood glucose fluctuation range(MAGE)were higher than those in T2DM group(P<0.05),while the proportion of fatty liver,eGFR,total bilirubin,direct bilirubin,indirect bilirubin,alanine aminotransferase,white ball ratio of liver function and TIR were lower than those in T2DM group(P<0.05).Pearson and spearman correlation analysis showed that HbA1c was negatively correlated with TIR(P<0.05),and positively correlated with TAR,MG,FPG,GMI,coefficient of variation,standard deviation,maximum blood glucose fluctuation and MAGE(P<0.05).Logistic regression analysis showed that TIR(OR 1.029,95%CI 1.012～1.047)and TAR(OR 0.974,95%CI 0.958～0.990)were the influencing factors for DKD in T2DM patients.ROC curve analysis showed that the area under the curve predicted by TIR for DKD was 0.651,with the sensitivity 64.2%,the specificity 60.9%,and the truncation value 53.46%.Conclusions TIR and TAR are the influencing factors of DKD in T2DM patients,and other CGM indicators such as MG,GMI and MAGE are related to HbA1c.

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with "stopping" and "continuation" criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation. Please cite this article as: Zhang C, Nie YS, Zhang CT, Yang HJ, Zhang HR, Xiao W, Cui GF, Li J, Li SJ, Huang QS, Yan SY. An adaptive Bayesian randomized controlled trial of traditional Chinese medicine in progressive pulmonary fibrosis: Rationale and study design. J Integr Med. 2025; 23(2): 138-145.
Female ; Humans ; Male ; Bayes Theorem ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pulmonary Fibrosis/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Adaptive Clinical Trials as Topic

OBJECTIVE: This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction (MI) in patients with both coronary heart disease (CHD) and type 2 diabetes (T2D). METHODS: We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen, China. Patients were categorized into 6 groups based on baseline fasting plasma glucose (FPG) levels and diabetes duration (from the date of diabetes diagnosis to the baseline date) to examine their combined effects on subsequent MI. Cox proportional hazards regression models were used, with further stratification by age, sex, and comorbidities to assess potential interactions. RESULTS: Over a median follow-up of 2.4 years, 2,110 patients experienced MI. Compared to those with optimal glycemic control (FPG < 6.1 mmol/L) and shorter diabetes duration (< 10 years), the fully-adjusted hazard ratio ( HR) (95% Confidence Interval [95% CI]) for those with a diabetes duration of ≥ 10 years and FPG > 8.0 mmol/L was 1.93 (95% CI: 1.59, 2.36). The combined effects of FPG and diabetes duration on MI were largely similar across different age, sex, and comorbidity groups, although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation. CONCLUSION Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D. Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
Humans ; Diabetes Mellitus, Type 2/blood* ; Male ; Female ; Middle Aged ; Aged ; Coronary Disease/complications* ; Myocardial Infarction/etiology* ; Retrospective Studies ; China/epidemiology* ; Glycemic Control ; Blood Glucose ; Adult ; Risk Factors ; Time Factors

AIM To investigate the effects of Changpu Yujin Decoction(CPYJD)on striatal mitophagy and PINK1/Parkin signaling pathway in a rat model of Tourette syndrome(TS).METHODS Thirty-six SPF male SD rats were randomly assigned to the control group(n=9)and the TS modeling group(n=27).Rats in the modeling group received daily intraperitoneal injections of 3,3'-iminodipropionitrile(IDPN)(300 mg/kg)for 7 consecutive days to establish the TS model.Post-modeling,successfully induced TS rats were re-randomized into model group(no treatment),tiapride group(47.91 mg/kg)and CPYJD group(77.28 g/kg).All groups received their respective interventions via intragastric administration daily for 28 days.Following drug administration,behavioral scores were assessed in each group.Pathological alterations in the striatum were examined using HE staining,while ultrastructural changes were evaluated by transmission electron microscopy(TEM).Neuronal apoptosis was quantified via TUNEL staining,and ROS levels in striatum were measured by ELISA.Co-localization of PINK1 and LC3B was assessed using immunofluorescence(IF).Finally,mRNA and protein expressions of PINK1,Parkin,Beclin-1,P62 and LC3B(LC3B-Ⅱ/Ⅰ ratio)were analyzed by RT-qPCR and Western blot.RESULTS Compared to the control group,the model group demonstrated significantly increased behavioral scores(P＜0.01),elevated neuronal apoptosis rate and higher ROS levels in the striatum(P＜0.01);severe neuronal and mitochondrial damage in the striatum;significantly reduced mRNA and protein expressions of PINK1,Parkin,Beclin-1 and LC3B(LC3B-Ⅱ/Ⅰ ratio)in the striatum(P＜0.01);markedly upregulated P62 mRNA and protein expressions(P＜0.01).Compared to the model group,both the tiapride and CPYJD intervention groups exhibited significantly reduced behavioral scores(P＜0.01);decreased neuronal apoptosis rate and lower ROS levels(P＜0.01);improved pathological alterations in the striatal neurons and mitochondria;increased mRNA and protein expressions of PINK1,Parkin and Beclin-1 in the striatum(P＜0.05,P＜0.01);and decreased P62 mRNA and protein expressions(P＜0.01).Furthermore,the rats in the CPYJD group specifically showed elevated LC3B mRNA level and LC3B-Ⅱ/Ⅰ protein ratio in striatum(P＜0.05,P＜0.01).CONCLUSION The effect of CPYJD intervention in TS rats may involve activation of mitophagy through regulation of the PINK1/Parkin signaling pathway,improving mitochondrial function,reducing ROS levels,and thereby protecting neurons.

BACKGROUND: The effect of air pollution on annual change rates in grip strength and body composition in the elderly is unknown. OBJECTIVES: This study evaluated the effects of long-term exposure to ambient air pollution on change rates of grip strength and body composition in the elderly. METHODS: In the period 2016-2020, grip strength and body composition were assessed and measured 1-2 times per year in 395 elderly participants living in the Taipei basin. Exposure to ambient fine particulate matters (PM_2.5), nitric dioxide (NO₂), and ozone (O₃) from 2015 to 2019 was estimated using a hybrid Kriging/Land-use regression model. In addition, long-term exposure to carbon monoxide (CO) was estimated using an ordinary Kriging approach. Associations between air pollution exposures and annual changes in health outcomes were analyzed using linear mixed-effects models. RESULTS: An inter-quartile range (4.1 µg/m³) increase in long-term exposure to PM_2.5 was associated with a faster decline rate in grip strength (-0.16 kg per year) and skeletal muscle mass (-0.14 kg per year), but an increase in body fat mass (0.21 kg per year). The effect of PM_2.5 remained robust after adjustment for NO₂, O₃ and CO exposure. In subgroup analysis, the PM_2.5-related decline rate in grip strength was greater in participants with older age (>70 years) or higher protein intake, whereas in skeletal muscle mass, the decline rate was more pronounced in participants having a lower frequency of moderate or strenuous exercise. The PM_2.5-related increase rate in body fat mass was higher in participants having a lower frequency of strenuous exercise or soybean intake. CONCLUSIONS Among the elderly, long-term exposure to ambient PM_2.5 is associated with a faster decline in grip strength and skeletal muscle mass, and an increase in body fat mass. Susceptibility to PM_2.5 may be influenced by age, physical activity, and dietary protein intake; however, these modifying effects vary across different health outcomes, and further research is needed to clarify their mechanisms and consistency.
Humans ; Hand Strength ; Aged ; Male ; Female ; Environmental Exposure/adverse effects* ; Follow-Up Studies ; Taiwan ; Air Pollution/adverse effects* ; Particulate Matter/adverse effects* ; Muscle, Skeletal/drug effects* ; Air Pollutants/adverse effects* ; Ozone/adverse effects* ; Aged, 80 and over ; Adipose Tissue/drug effects* ; Body Composition/drug effects* ; Nitrogen Dioxide/adverse effects*

Objective:To assess the epidemic characteristics of serum of viral hepatitis B infection ranging in age from 1 to 69 years old in Jilin province in 2024. The genotypes of hepatitis B virus-infected individuals were determined.Methods:In 2024，2 313 people ranging in age from 1 to 69 years old in Jilin province were selected by using multi-stage random sampling method for field epidemiological investigation of hepatitis B. The serum samples were collected and detected for the hepatitis B virus（HBV）surface antigen（HBsAg），HBV surface antibody（HBsAb），HBV core antibody（HBcAb），HBV E antigen（HBeAg）and HBV E antibody（HBeAb）by ELISA，and the data were analyzed by the national epidemiological dynamic data collection platform，SPSS 18.0 software. Genotyping is conducted based on the internationally recognized large S region gene fragment.Results:The vaccination rates for hepatitis B among people aged 1-4，5-14，15-29 and 30-69 were 97.00%，94.66%，74.59% and 2.88%，respectively. There were significant differences in hepatitis B vaccination rates across age groups surveyed in 2024（ χ2=1 041.41， P<0.05）. In 2024，the HBsAg carrying rate，HBsAb positive rate，HBV infection rate，HBeAb positive rate and HBeAg positive rate of people in Jilin province were 0. 86%，47.99%，2.25%，5.58% and 5.14%，respectively. The genotype of hepatitis B virus in the infected person is B2 and C2. Conclusions:In 2024，the indicators of HBV infection in Jilin province were good. The highest rate of hepatitis B infection was 11.54% in people with 30-69 years of age and the high vaccination rate of people should continue to be maintained，and the vaccination of hepatitis B vaccine for adults should be strengthened to reduce the risk of infection in these susceptible groups.

Objective To explore the relationship between continuous glucose monitoring(CGM)parameters with diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 355 T2DM patients who were hospitalized in the Department of Endocrinology of Wuhan Central Hospital,Tongji Medical College,Huazhong University of Science and Technology,from August 2022 to February 2024 were included.According to uninary albumin/creatinine rate(UACR)and estimated glomerular filtration rate(eGFR)levels,the patients were divided into T2DM group(n=207)and DKD group(DKD,n=148).The general clinical data and CGM parameters of the two groups were compared.Results Age,systolic pressure,DM duration,proportion of Ins use,proportion of cerebral infarction and lumen infarction,proportion of lower limb arterial plaque formation,serum troponin I,D-dimer,erythrocyte deposition rate,UACR,blood urea nitrogen(BUN),serum creatinine,blood uric acid,mean glucose value(MG),blood glucose management index(GMI),time glucose below target range(TBR),glucose above target range time(TAR)and mean blood glucose fluctuation range(MAGE)were higher than those in T2DM group(P<0.05),while the proportion of fatty liver,eGFR,total bilirubin,direct bilirubin,indirect bilirubin,alanine aminotransferase,white ball ratio of liver function and TIR were lower than those in T2DM group(P<0.05).Pearson and spearman correlation analysis showed that HbA1c was negatively correlated with TIR(P<0.05),and positively correlated with TAR,MG,FPG,GMI,coefficient of variation,standard deviation,maximum blood glucose fluctuation and MAGE(P<0.05).Logistic regression analysis showed that TIR(OR 1.029,95%CI 1.012～1.047)and TAR(OR 0.974,95%CI 0.958～0.990)were the influencing factors for DKD in T2DM patients.ROC curve analysis showed that the area under the curve predicted by TIR for DKD was 0.651,with the sensitivity 64.2%,the specificity 60.9%,and the truncation value 53.46%.Conclusions TIR and TAR are the influencing factors of DKD in T2DM patients,and other CGM indicators such as MG,GMI and MAGE are related to HbA1c.