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

Aim To study the proliferation,invasion and migration ability of Quaking(QKI)in gastric cancer(GC)via elucidating the molecular mechanisms associated with QKI in the occurrence and development of GC through bioinformatics.Methods Differential expression analysis of QKI was performed across vari-ous human cancer samples by merging data from the TCGA and GTEx databases.The correlation was ana-lyzed between QKI protein expression and tumor muta-tion burden(TMB)score,microsatellite instability(MSI)score,and ESTIMATE score,and the correla-tion was also explored between QKI protein expression and overall survival(OS),disease free survival(DFS),and progression free survival(PFS).EMT related genes that could encode DECircRNAs were ob-tained through bioinformatics analysis to construct a QKI-EMT-circRNAs regulatory network.The differenti-ally expressed circRNAs and EMT related genes in TMK1 cells were verified.The proliferation,invasion and migration ability of the QKI was studied by using the knockdown system.Results QKI was differential-ly expressed in the vast majority of tumors and was closely related to TMB,MSI,and tumor microenviron-ment(TME);QKI emerged as a high-risk factor for predicting OS,DFS,and PFS in individuals with com-mon human cancers.QKI regulated the splicing of 6 EMT related gene transcripts to form eight circRNAs,all of which were significantly associated with the prog-nosis of gastric cancer patients.Cell experiments showed that compared to normal gastric epithelial cells,only hsa_ccirc_0004015,CALD1,and CDK14 were down-regulated in TMK1 cells.Knocking down QKI inhibited the proliferation,invasion and migration ability of TMK1 cells.Conclusion QKI exerts regu-latory control over the transcription of six EMT-related genes,resulting in the formation of circRNAs,thereby promoting the pathogenesis and progression of GC.QKI is highly expressed in TMK1 cells,and knock-down of QKI can inhibit the proliferation,invasion and migration ability of TMK1 cells.

OBJECTIVE: Aeromonas has recently been recognized as an emerging human pathogen. Aeromonas-associated diarrhea is a phenomenon occurring worldwide. This study was designed to determine the prevalence, genetic diversity, antibiotic resistance, and pathogenicity of Aeromonas strains isolated from food products in Shanghai. METHODS: Aeromonas isolates ( n = 79) collected from food samples were analyzed using concatenated gyrB- cpn60 sequencing. The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing. Pathogenicity was assessed using β-hemolytic, extracellular protease, virulence gene detection, C. elegans liquid toxicity (LT), and cytotoxicity assays. RESULTS: Eight different species were identified among the 79 isolates. The most prevalent Aeromonas species were A. veronii [62 (78.5%)], A. caviae [6 (7.6%)], A. dhakensis [3 (3.8%)], and A. salmonicida [3 (3.8%)]. The Aeromonas isolates were divided into 73 sequence types (STs), of which 65 were novel. The isolates were hemolytic (45.6%) and protease-positive (81.0%). The most prevalent virulence genes were act (73.4%), fla (69.6%), aexT (36.7%), and ascV (30.4%). The results of C. elegans LT and cytotoxicity assays revealed that A. dhakensis and A. hydrophila were more virulent than A. veronii, A. caviae, and A. bivalvium. Antibiotic resistance genes [ tetE, blaTEM, tetA, qnrS, aac(6)-Ib, mcr -1, and mcr-3] were detected in the isolates. The multidrug-resistance rate of the Aeromonas isolates was 11.4%, and 93.7% of the Aeromonas isolates were resistant to cefazolin. CONCLUSION The taxonomy, antibiotic resistance, and pathogenicity of different Aeromonas species varied. The Aeromonas isolates A. dhakensis and A. hydrophila were highly pathogenic, indicating that food-derived Aeromonas isolates are potential risks for public health and food safety. The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China.
Aeromonas/genetics* ; Animals ; Anti-Bacterial Agents/pharmacology* ; Caenorhabditis elegans ; Cefazolin ; China/epidemiology* ; Diarrhea ; Drug Resistance, Multiple, Bacterial/genetics* ; Genetic Variation ; Humans ; Peptide Hydrolases/genetics* ; Virulence/genetics*

Nonalcoholic fatty liver disease (NAFLD) is regarded as the most common liver disease with no approved therapeutic drug currently. Silymarin, an extract from the seeds of Silybum marianum, has been used for centuries for the treatment of various liver diseases. Although the hepatoprotective effect of silybin against NAFLD is widely accepted, the underlying mechanism and therapeutic target remain unclear. In this study, NAFLD mice caused by methionine-choline deficient (MCD) diet were orally administrated with silybin to explore the possible mechanism and target. To clarify the contribution of peroxisome proliferator-activated receptor α (PPARα), PPARα antagonist GW6471 was co-administrated with silybin to NAFLD mice. Since silybin was proven as a PPARα partial agonist, the combined effect of silybin with PPARα agonist, fenofibrate, was then evaluated in NAFLD mice. Serum and liver samples were collected to analyze the pharmacological efficacy and expression of PPARα and its targets. As expected, silybin significantly protected mice from MCD-induced NAFLD. Furthermore, silybin reduced lipid accumulation via activating PPARα, inducing the expression of liver cytosolic fatty acid-binding protein, carnitine palmitoyltransferase (Cpt)-1a, Cpt-2, medium chain acyl-CoA dehydrogenase and stearoyl-CoA desaturase-1, and suppressing fatty acid synthase and acetyl-CoA carboxylase α. GW6471 abolished the effect of silybin on PPARα signal and hepatoprotective effect against NAFLD. Moreover, as a partial agonist for PPARα, silybin impaired the powerful lipid-lowering effect of fenofibrate when used together. Taken together, silybin protected mice against NAFLD via activating PPARα to diminish lipid accumulation and it is not suggested to simultaneously take silybin and classical PPARα agonists for NAFLD therapy.

OBJECTIVE: To investigate the correlation between the quadriceps cross-sectional area (CSA) and quadriceps muscle volume (QMV) at different horizontal levels from the upper edge of the patella, and to determine the best observation position. METHODS: Thigh magnetic resonance imaging (MRI) images of 22 Chinese young men [age: (29±6) years] with anterior cruciate ligament (ACL) rupture were examined. The CSA was measured at 18, 15, and 12 cm above the upper edge of the pate-lla (denoted by CSA-18, CSA-15 and CSA-12 respectively), and the QMV and CSA were determined by semiautomatic segmentation. A curve model was established to estimate QMV. Bland-Altman analysis was performed to determine the confidence limits of the volumes. RESULTS: On the unaffected side, the mean QMV was (1 944.45±323.77) cm³. The quadriceps CSA at the upper edge of the patella at 18, 15, and 12 cm was (80.80±12.16) cm², (77.53±12.03) cm², and (72.68±10.51) cm², respectively. The coefficients of determination (R²), ascertained using curve estimation models, for the 3 positions were 0.819, 0.755, and 0.684 (P < 0.001), and the standard deviations of the volume estimated value (SEE) were 7.4%, 8.7%, and 9.8%. The fitting equations of the three horizontal positions were all good, but the fitting degree of CSA-18 was the highest. The Bland-Altman scatter plot showed that the arithmetic means of the QMV at 18, 15 and 12 cm from the upper edge of the patella 0.8 cm³, -1.1 cm³, and 0.9 cm³ and 95% limits of agreement (LoA) were (-268.8, 270.5), (-315.2, 313.1), and (-355.7, 357.5), respectively. The estimated QMV was in good agreement with the measured value. The difference between the estimated CSA-18 and measured values was the smallest. The results on the affected side were consistent. CONCLUSION The correlation between QMV and CSA in the young men with the upper edge of patella as baseline was reliable and consistent. Among them, CSA-18 had the highest correlation with the QMV. However, different observation sites could be selected for different injuries of the quadriceps.
Adult ; Anterior Cruciate Ligament Injuries/surgery* ; Anterior Cruciate Ligament Reconstruction ; Humans ; Magnetic Resonance Imaging ; Male ; Patella ; Quadriceps Muscle/diagnostic imaging* ; Young Adult

Objective:To understand the current status of foreign dual-degree programs of Medical Doctor (MD) and Master of Public Health (MPH) and provide evidence-based decision-making reference for promoting the education of high-level applied public health talents in China.Methods:The list of involved institutions and information of foreign MD-MPH dual-degree programs was collected through literature retrieval, online information searching, and additional survey of key figures. We extracted the details of each project regarding professional fields, core competence, length of schooling, teaching and learning arrangement, internship eligibility, and graduation assessment. Python 3.8.0 was used for data cleaning, and the occurrence frequency of related items in each dimension was calculated.Results:A total of 99 MD-MPH programs from 104 foreign institutions were included, among which 97.1% of them were implemented in universities from the United States. The School of Public Health provided 42.4% (42/99) of the programs. Epidemiology was the major discipline set up among most programs, accounting for 12.0% (29/241) of all the specialties involved. Epidemiological research methods, health policy management and practice, and public health practice were the top 3 core competencies to be mastered. Of the 99 programs, 87 gave information on the length of the program, of which 74.7% (65/87) were five years, 6.9% (6/87) were four years, and 18.4% (16/87) included both 4-year and 5-year programs.Conclusions:The international MD-MPH programs were sophisticated and mainly organized by the School of Public Health alone or in conjunction with the School of Medicine. Epidemiology is the core course and competence objective, with a length of 4-5 years. Through learning experience from international MD-MPH programs and the Chinese unique medical development background, China should optimize its medical education system to develop a suitable talent training strategy for MD-MPH dual-degree programs in the new era.

Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epige-netic mark in cancer, its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive pri-mary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors. In contrast, the TET protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1 associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkers to predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.

BACKGROUND: Pancreatic stellate cells (PSCs) activation plays a critical role in the development of chronic pancreatitis. Previous studies confirmed that thromboxane A2 receptor (TxA2r) was overexpressed in activated PSCs in rats. The purpose of this study was to investigate the role of TxA2r in the activation of PSCs induced by 8-epi-prostaglandin F2α (8-epi-PGF2α). METHODS: TxA2r expression in both quiescent and activated PSCs was detected by immunocytochemistry and immunoblot assay. Isolated PSCs were treated with 8-epi-PGF2α (10, 10, 10 mol/L) for 48 h, and SQ29548 (10, 10, and 10 mol/L), a TxA2r-specific antagonist for 48 h, respectively, to identify the drug concentration with the best biological effect and the least cytotoxicity. Then isolated PSCs were treated with SQ29548 (10 mol/L) for 2 h, followed by 10 mol/L 8-epi-PGF2α for 48 h. Real-time polymerase chain reaction was performed to detect the messenger RNA (mRNA) levels of α-smooth muscle actin (α-SMA) and collagen I. Comparisons between the groups were performed using Student's t test. RESULTS: TxA2r was up-regulated in activated PSCs in vitro compared with quiescent PSCs (all P < 0.001). Compared with the control group, different concentrations of 8-epi-PGF2α significantly increased mRNA levels of α-SMA (10 mol/L: 2.23 ± 0.18 vs. 1.00 ± 0.07, t = 10.70, P < 0.001; 10 mol/L: 2.91 ± 0.29 vs. 1.01 ± 0.08, t = 10.83, P < 0.001; 10 mol/L, 1.67 ± 0.07 vs. 1.00 ± 0.08, t = 11.40, P < 0.001) and collagen I (10 mol/L: 2.68 ± 0.09 vs. 1.00 ± 0.07, t = 24.94, P < 0.001; 10 mol/L: 2.12 ± 0.29 vs. 1.01 ± 0.12, t = 6.08, P < 0.001; 10 mol/L: 1.46 ± 0.15 vs. 1.00 ± 0.05, t = 4.93, P = 0.008). However, different concentrations of SQ29548 all significantly reduced the expression of collagen I (10 mol/L: 0.55 ± 0.07 vs. 1.00 ± 0.07, t = 10.47, P < 0.001; 10 mol/L: 0.56 ± 0.10 vs. 1.00 ± 0.07, t = 6.185, P < 0.001; 10 mol/L: 0.27 ± 0.04 vs. 1.00 ± 0.07, t = 15.41, P < 0.001) and α-SMA (10 mol/L: 0.06 ± 0.01 vs. 1.00 ± 0.11, t = 15.17, P < 0.001; 10 mol/L: 0.28 ± 0.03 vs. 1.00 ± 0.11, t = 11.29, P < 0.001; 10 mol/L: 0.14 ± 0.04 vs. 1.00 ± 0.11, t = 12.86, P < 0.001). After being treated with SQ29548 (10 mol/L) and then 8-epi-PGF2α (10 mol/L), the mRNA levels of α-SMA (0.20 ± 0.08 vs. 1.00 ± 0.00, t = 17.46, P < 0.001) and collagen I (0.69 ± 0.13 vs. 1.00 ± 0.00, t = 4.20, P = 0.014) in PSCs were significantly lower than those of the control group. CONCLUSIONS The results show that 8-epi-PGF2α promoted PSCs activation, while SQ29548 inhibited PSCs activation induced by 8-epi-PGF2α. The result indicated that TxA2r plays an important role during PSC activation and collagen synthesis induced by 8-epi-PGF2αin vitro. This receptor may provide a potential target for more effective antioxidant therapy for pancreatic fibrosis.

Objective To compare the ability and influence factors of three platelet function tests:light transmission aggregometry (LTA),thrombelastograph (TEG) and VerifyNow.Methods A total of 174 patients underwent percutaneous coronary intervention (PCI) and platelet function test were enrolled.Platelet function were tested by LTA,TEG and VerifyNow.Results Patients were found to be high platelet reactivity (HPR) by LTA (56.64％,64 cases/113 cases),TEG(60.38％,32 cases/52 cases),VerifyNow (17.24％,15 cases /87 cases).There were no significant differences observed between TEG and LTA (P ＞0.05).VerifyNow identified lower HPR proportion compared with TEG and LTA (all P ＜ 0.001).Conclusion Compared with LTA and TEG,VerifyNow identified lower HPR proportion and may overestimate the effectiveness of clopidogrel.We will follow the patients to study the predictive capability of three tests.

The aim of this study was to investigate the effect of WR2721(amifostine) against bone marrow hematopoietic damage of mice exposed to 6.5 Gy of (60)Co-γ ray. A total of 60 C57/BL6J mice was divided into 3 groups:normal group (mice were injected with physiological salt solution), irradiation group (mice were injected with physiologic salt solution before irradiation) and WR2721 group (mice were injected with WR2721 before irradiation). The WBC, neutrophil (Neut), Plt and RBC levels in peripheral blood of 3 group mice were counted within 60 days after irradiation; the bone marrow nuclear cells (BMNC) were counted at 2 and 24 hours after irradiation; the hematopoietic stem/progenitor cell (LK/LSK) level and colony formation capability were detected by flow cytometry at 2 and 24 hours after irradiation. The results indicated that the counts of WBC and neut at 4 and 18 days, Plt at 7-18 days and RBC at 10-30 day after irradiation in WR2721 group were higher than those in irradiation group (P < 0.05); the BMNC, LSK and LK levels obviously increased at 24 hours after irradiation (P < 0.05), the CFU-GEMM, CFU-GM, CFU-MK BFU-E and CFU-E all significantly increased at 2 and 24 hours after irradiation (P < 0.01), as compared with irradiation group. It is concluded that WR2721 can effectively alleviate early hematopoietic damage and promote the fast recovery of peripheral blood cells in mice exposed to γ-ray, suggesting that the WR2721 has significant radioprotective effect on hematopoietic system.
Amifostine ; pharmacology ; Animals ; Blood Cell Count ; Bone Marrow Cells ; cytology ; drug effects ; radiation effects ; Gamma Rays ; Hematopoietic Stem Cells ; cytology ; drug effects ; radiation effects ; Male ; Mice ; Mice, Inbred C57BL ; Radiation-Protective Agents ; pharmacology ; Whole-Body Irradiation