Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxy-matrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mecha-nism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological pre-diction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-κB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Aim To verify the therapeutic effect of the Qushi Huoxue decoction(QSHXF)on a mouse model of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and experimental approaches,to examine the changes in the PI3K-AKT-lipid metabo-lism signaling pathway,and to elucidate its molecular mechanisms.Methods The potential active ingredi-ents and targets of the QSHXF were identified using the TCMSP platform.NAFLD-related genes were sourced from the GeneCards,PharmGkb,TTD,and OMIM data-bases.The intersection of drug targets and NAFLD treatment targets was analyzed to identify the key tar-gets of the QSHXF in treating NAFLD.The STRING database and Cytoscape 3.9.1 software were utilized to construct networks linking traditional Chinese medicine active ingredients to disease targets and PPI networks,allowing for the screening of key active ingredients and core targets.GO and KEGG enrichment analyses of the intersecting targets were conducted using R version 4.2.2.The NAFLD model was established by feeding mice a methionine-choline deficient diet for a duration of five weeks.Following successful modeling,low,me-dium,and high doses of the QSHXF were administered for intervention over a period of six weeks.The efficacy was verified and the underlying mechanisms were ex-plored using methods such as HE staining,Oil Red O staining,and Western blot analysis.Results The net-work pharmacology prediction indicated that QSHXF might effectively treat NAFLD through key components such as quercetin and kaempferol,as well as core tar-gets including STAT3,AKT1,and HIF1A.KEGG en-richment analysis further suggested that QSHXF might exert its therapeutic effects on NAFLD via signaling pathways such as AGE-RAGE and PI3K-AKT.Verifi-cation through animal experiments demonstrated that QSHXF could significantly reduce hepatic steatosis and lipid droplet accumulation in NAFLD mice.Specifical-ly,it markedly decreased serum levels of TC,TG,ALT,AST,and LDL,while increasing HDL levels.Addition-ally,the treatment significantly reduced the protein ex-pression levels of p-PI3K,p-AKT,SREBP-1c,FASN,and ACC1 in the liver.Conclusions QSHXF can sig-nificantly enhance liver function,improve blood lipid levels,and alleviate hepatic steatosis in NAFLD mice,with its mechanism potentially linked to the inhibition of the PI3K-AKT-lipid metabolism signaling pathway.

Aim To verify the therapeutic effect of the Qushi Huoxue decoction(QSHXF)on a mouse model of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and experimental approaches,to examine the changes in the PI3K-AKT-lipid metabo-lism signaling pathway,and to elucidate its molecular mechanisms.Methods The potential active ingredi-ents and targets of the QSHXF were identified using the TCMSP platform.NAFLD-related genes were sourced from the GeneCards,PharmGkb,TTD,and OMIM data-bases.The intersection of drug targets and NAFLD treatment targets was analyzed to identify the key tar-gets of the QSHXF in treating NAFLD.The STRING database and Cytoscape 3.9.1 software were utilized to construct networks linking traditional Chinese medicine active ingredients to disease targets and PPI networks,allowing for the screening of key active ingredients and core targets.GO and KEGG enrichment analyses of the intersecting targets were conducted using R version 4.2.2.The NAFLD model was established by feeding mice a methionine-choline deficient diet for a duration of five weeks.Following successful modeling,low,me-dium,and high doses of the QSHXF were administered for intervention over a period of six weeks.The efficacy was verified and the underlying mechanisms were ex-plored using methods such as HE staining,Oil Red O staining,and Western blot analysis.Results The net-work pharmacology prediction indicated that QSHXF might effectively treat NAFLD through key components such as quercetin and kaempferol,as well as core tar-gets including STAT3,AKT1,and HIF1A.KEGG en-richment analysis further suggested that QSHXF might exert its therapeutic effects on NAFLD via signaling pathways such as AGE-RAGE and PI3K-AKT.Verifi-cation through animal experiments demonstrated that QSHXF could significantly reduce hepatic steatosis and lipid droplet accumulation in NAFLD mice.Specifical-ly,it markedly decreased serum levels of TC,TG,ALT,AST,and LDL,while increasing HDL levels.Addition-ally,the treatment significantly reduced the protein ex-pression levels of p-PI3K,p-AKT,SREBP-1c,FASN,and ACC1 in the liver.Conclusions QSHXF can sig-nificantly enhance liver function,improve blood lipid levels,and alleviate hepatic steatosis in NAFLD mice,with its mechanism potentially linked to the inhibition of the PI3K-AKT-lipid metabolism signaling pathway.

This study aims to systematically review and evaluate the quality of clinical research on the treatment of adenomyosis(AM) with traditional Chinese medicine(TCM) in recent ten years, using evidence graphs. Computer searches were conducted on eight Chinese and English databases, commonly used guideline databases, and guideline-related websites, covering the period from January 1, 2014, to October 1, 2024. Two researchers independently screened, extracted information, and evaluated the quality of the evidence. The distribution and quality of the clinical research evidence were presented using both text and charts. A total of 565 articles were included in the study, comprising 523 intervention studies, 23 observational studies, 18 systematic reviews/Meta-analysis, and 1 guideline. The overall publication volume has shown a downward trend in past two years. The sample sizes of the intervention and observational studies primarily focused on 60 to 120 cases. The intervention schemes mainly involved multi-therapy combinations, including 33 classic prescriptions and 25 Chinese patent medicines. Among these, 48 studies related to 17 classic prescriptions and 45 studies related to 10 types of Chinese patent medicines involved TCM syndrome types. Randomized controlled trial(RCT) tended to focus on overall clinical efficacy and the degree of dysmenorrhea as key outcome measures. Methodological quality issues were found in 97 RCTs related to TCM decoctions and 131 RCTs related to Chinese patent medicines, primarily involving unclear explanations of some information. The AMSTAR scores for the 18 systematic reviews/Meta-analysis ranged from 1 to 8 points, with 16 studies suggesting "evidence of potential therapeutic efficacy". The recommended level for the one included guideline was B-level. TCM shows significant advantages in treating AM. Future clinical research should further standardize study designs, reference relevant reporting guidelines, improve the quality of clinical research, generate higher-level evidence-based results, and promote the high-quality development of clinical research on TCM for treating AM.
Humans ; Adenomyosis/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic

OBJECTIVE: To analyze the clinical features of acute myeloid leukemia patients with DEK-NUP214 fusion gene positive. METHODS: The DEK-NUP214 fusion gene was amplified by multi-nested PCR in 26 patients admitted to the First Affiliated Hospital of Soochow University from January 2018 to October 2023, and the disease course and post-transplant survival data were obtained by searching outpatient and inpatient medical records and telephone follow-up. RESULTS: The median follow-up time of pateints was 21.25（0.9-60.2） months. Among 26 patients with DEK-NUP214 fusion gene positive AML, 15 patients had FLT3-ITD gene mutation positive. One patient died after abandoning treatment due to non-remission of induction chemotherapy, one died due to infection, and 23 patients received allo-HSCT after achieving CR, of which one patient died within one month after transplantation due to multiple infections and one died due to severe pulmonary infection that did not respond to treatment. One patient received allo-HSCT in non-remission state and later died due to recurrence. CONCLUSION DEK-NUP214 fusion gene positive AML is a type of acute leukemia subtype with high risk and poor prognosis. Allo-HSCT treatment at the early stage of disease remission is the most effective way to improve the prognosis of patients.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Poly-ADP-Ribose Binding Proteins ; Oncogene Proteins, Fusion/genetics* ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins/genetics* ; Chromosomal Proteins, Non-Histone/genetics* ; Male ; Female ; Adult ; Mutation ; Hematopoietic Stem Cell Transplantation ; Middle Aged

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

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