1.Role of endoplasmic reticulum stress-mediated DEAD-box helicase 3 X-linked in a mouse model of concanavalin A-induced immune-mediated liver injury
Zhenzhen PAN ; Ling XU ; Xianru ZHU ; Zihao FAN ; Yaling CAO ; Yinkang MO ; Sai YAN ; Feng REN
Journal of Clinical Hepatology 2026;42(1):134-142
ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked (DDX3X) in immune-mediated liver injury (ILI), and to clarify its mechanism by regulating endoplasmic reticulum stress (ERS)-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A (ConA) via the caudal vein to establish a model of ILI, PBS (control group) and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice (DDX3XΔHep and DDX3X-flox mice (DDX3Xfl/fl), respectively.. The log-rank survival analysis, measurement of the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and HE staining of liver tissue were performed to assess liver injury, and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid (4-PBA, 100 mg/kg) was performed to inhibit ERS. Serum samples (n=30) and liver tissue samples (n=6) were collected from healthy controls, chronic hepatitis B (CHB) patients, and hepatitis B virus-associated liver failure (HBV-LF) patients; ELISA was used to measure the serum level of DDX3X, and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice, the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury (P<0.05), and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% (compared with 20% in the DDX3Xfl/fl group), with significant reductions in the serum levels of ALT and AST (P<0.000 1) and the expression levels of the ERS markers GRP78 and CHOP (P<0.05). After ERS was inhibited by 4-PBA, there was alleviation of liver injury (with reductions in ALT and AST, P <0.001) and a reduction in DDX3X expression (P<0.01). The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls (all P<0.01), and there was a significant increase in the serum level of DDX3X in HBV-LF patients (P<0.000 1). ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway (GRP78/CHOP), and its expression is associated with the progression of hepatitis B. Therefore, it can be used as a potential therapeutic target.
2.Expert Consensus on Clinical Application of Qidong Yixin Oral Liquid
Changkuan FU ; Xiaochang MA ; Mingjun ZHU ; Yue DENG ; Hongxu LIU ; Mingxue ZHANG ; Ying CHEN ; Yan ZHOU ; Ling ZHANG ; Jianhua FU ; Wei YANG ; Yu'er HU ; Ming CHEN ; Yanming XIE ; Yuanyuan LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):147-158
The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis (VMC). It has the functions of tonifying Qi, nourishing the heart,calming the mind, and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However,the understanding of its efficacy evidence, advantageous aspects, dosage and administration, and medication safety remains insufficient in clinical practice. Therefore,the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid (hereinafter referred to as consensus) was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine,successively completing multiple tasks such as the consensus project initiation,determination of clinical problems,evidence search and evaluation,formation of recommendation opinions and consensus suggestions,solicitation of opinions,peer review, submission for review and release, and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions,clarifying the clinical positioning,efficacy advantages,syndrome differentiation,dosage and administration,combination therapy,timing of medication,adverse reactions,contraindications, and precautions of Qidong Yixin oral liquid,indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease,providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23, 2024. Standard number:GSCACM-376-2024.
3.Explainable Machine Learning Model for Predicting Prognosis in Patients with Malignant Tumors Complicated by Acute Respiratory Failure: Based on the eICU Collaborative Research Database in the United States
Zihan NAN ; Linan HAN ; Suwei LI ; Ziyi ZHU ; Qinqin ZHU ; Yan DUAN ; Xiaoting WANG ; Lixia LIU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):98-108
To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework. Clinical data of patients with malignant tumors and ARF were extracted from the eICU Collaborative Research Database in the United States, including demographic characteristics, comorbidities, vital signs, laboratory test indicators, and major interventions within the first 24 hours after ICU admission.The study outcome was ICU death.Enrolled patients were randomly divided into a training set and a validation set at a ratio of 7:3.Predictor variables were selected using least absolute shrinkage and selection operator (LASSO) regression.Five machine learning algorithms-extreme gradient boosting (XGBoost), support vector machine (SVM), Logistic regression, multilayer perceptron (MLP), and C5.0 Decision Tree-were employed to construct predictive models.Model performance was evaluated based on the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and other metrics.The optimal model was further interpreted using the Shapley additive explanations (SHAP) algorithm. A total of 3196 patients with malignant tumors complicated by ARF were included.The training set comprised 2, 261 patients and the validation set 935 patients; 683 patients died during ICU stay, while 2513 survived.LASSO regression ultimately selected 12 variables closely associated with patient ICU outcomes, including sepsis comorbidity, use of vasoactive drugs, and within the first 24 hours after ICU admission: minimum mean arterial pressure, maximum heart rate, maximum respiratory rate, minimum oxygen saturation, minimum serum bicarbonate, minimum blood urea nitrogen, maximum white blood cell count, maximum mean corpuscular volume, maximum serum potassium, and maximum blood glucose.After model evaluation, the XGBoost model demonstrated the best performance.The AUCs for predicting ICU mortality risk in the training and validation sets were 0.940 and 0.763, respectively; accuracy was 88.3% and 81.2%;sensitivity was 98.5% and 95.9%.Its predictive performance also remained optimal in sensitivity analyses.SHAP analysis indicated that the top five variables contributing to the model's predictions were minimum oxygen saturation, minimum serum bicarbonate, minimum mean arterial pressure, use of vasoactive drugs, and maximum white blood cell count. This study successfully developed a mortality risk prediction model for ICU patients with malignant tumors complicated by ARF based on a large-scale dataset and performed explainability analysis.The model aids clinicians in early identification of high-risk patients and implementing individualized interventions.
4.Effects of oral non-peptidic thrombopoietin receptor agonists on hepatic enzyme in adult patients with immune thrombocytopenia:a meta-analysis
Tiantian LU ; Nan SHEN ; Suyue ZHU ; Jingjing YAN
China Pharmacy 2026;37(4):510-515
OBJECTIVE To systematically evaluate the effects of oral non-peptidic thrombopoietin receptor agonists (TPO-RAs) on hepatic enzyme in adult patients with immune thrombocytopenia. METHODS A comprehensive literature search was conducted in PubMed, Web of Science, CNKI, Wanfang database and the Chinese Medical Association Journal Full-Text Database to collect randomized controlled trials (RCTs) comparing oral non-peptidic TPO-RAs (intervention group) with placebo or conventional therapy (control group). All databases were searched from their inception to June 2025. After literature screening, data extraction and quality assessment of the included studies, meta-analysis was conducted using RevMan 5.4.1 software. RESULTS Twelve RCTs comprising 1 388 patients were included, with 971 in the intervention group and 417 in the control group. Meta-analysis results showed that there were no significant differences between the two groups in terms of the incidence of hepatic enzyme elevation[OR=1.24, 95%CI (0.77, 1.99), P =0.37 ] , the incidence of hepatic enzyme elevation in patients treated for ≥6 weeks[OR=1.21, 95%CI (0.73, 1.99), P =0.46 ] , and the incidence of severe hepatic enzyme elevation[OR=1.39, 95%CI(0.46, 4.20), P =0.55 ] . Subgroup analysis showed that there were no significant differences in the incidence of hepatic enzyme elevation between the intervention group and control group among patients using eltrombopag[OR=1.57,95%CI(0.85,2.87), P =0.15 ] , avatrombopag[OR=0.88,95%CI (0.09,8.46), P =0.91 ] , and hetrombopag[OR=1.04,95%CI(0.30,3.65), P =0.95 ] , respectively. CONCLUSIONS Oral non-peptidic TPO-RAs do not significantly increase the risk of hepatic enzyme elevation in adult patients with immune thrombocytopenia, and show an overall favorable hepatic safety profile.
5.Measurement and simulation of secondary neutron energy spectra and doses in proton therapy
Yang YAN ; Changsong HOU ; Zhen ZHANG ; Weiguo ZHU
Chinese Journal of Radiological Health 2026;35(1):23-28
Objective To evaluate the radiation dose levels induced by secondary neutrons at different locations inside proton therapy treatment rooms, and analyze the distribution characteristics of neutron energy spectra by combining experimental measurements with simulations, and to provide a theoretical basis and technical support for radiation protection design and management in proton therapy. Methods Multiple representative measurement points were established in the treatment rooms of two hospital-based proton therapy centers. The DIAMON neutron spectrometer was employed to perform in-situ measurements of secondary neutron doses and energy spectra. Three-dimensional simulation models of treatment rooms were constructed using the FLUKA code to simulate the generation and transport of secondary neutrons. Results Measurements showed that the neutron dose was highest near the target region, reaching up to
6.Research on the current situation and development suggestions of centralized (cloud) prescription review center of the close-knit county-level medical consortium in a city
Lu HE ; Mingyang ZHU ; Xiaolei HU ; Yan QIAN
China Pharmacy 2026;37(5):578-583
OBJECTIVE To investigate the actual construction and operation status of established and under-construction centralized (cloud) prescription review centers (shortened for “prescription review center”) of close-knit county-level medical consortium in a certain city, so as to provide reference for improving the construction quality of the prescription review center. METHODS An online questionnaire survey was conducted to collect the data from 51 established and under-construction prescription review center in the city, covering basic information, funding sources, talent management, system construction, review rule maintenance, prescription review practices, prescription evaluation, data utilization, and current challenges. The collected data were summarized and analyzed. RESULTS A total of 51 valid questionnaires were retrieved, covering 32 established and 19 under-construction prescription review center. Among the 32 established prescription review centers, the main funding sources for their construction came from government financial allocations, accounting for 56.25%. Only 25.00% of prescription review center had review pharmacists who fully met national qualification requirements, and just 55.00% updated more than 10 review rule entries per month on average. Outpatient prescription verification realized full coverage, but 37.50% of prescription review centers only supported rationality verification of single prescriptions, and 50.00% could not retrieve laboratory and examination results to assist in prescription review. Additionally, 40.62% of prescription review center had not regularly conducted prescription evaluations for primary care institutions. The data from prescription review center was mainly used to support medication monitoring. Among the 19 prescription review centers currently in the planning stage, 63.16% had no identified funding sources. CONCLUSIONS The operation and construction of prescription review center in the city face challenges, such as funding shortages, absence of collaborative incentive mechanisms, and insufficient manpower.It is suggested that the state should issue a unified standard for the construction of the prescription review center as soon as possible, and local health administrative departments should formulate supporting policies and clarify assessment indicators in combination with the actual situation of the region.
7.Effects and mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure
Meiling MAO ; Jianqi LU ; Zhide ZHU ; Yan PANG ; Liyu XIE ; Jiayong CHEN ; Xinyu WU ; Xiang XIAO ; Junshen LU ; Weiqi SHI
China Pharmacy 2025;36(2):160-165
OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure (CHF). METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group, Qiangxin decoction low-dose and high-dose groups (12.25, 24.50 g/kg, calculated by crude drug), and chemical medicine group (Sacubitril valsartan sodium tablets, 10.42 mg/kg), with 10 rats in each group; control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication, the contents of N-terminal pro-brain natriuretic peptide (NT-proBNP) and adenosine triphosphate (ATP) in serum and phosphatidic acid (PA) and cardiolipin (CL) in myocardial tissue were all detected; the pathological damage and collagen fibrosis of rat myocardial tissue were observed; the apoptosis of myocardial cells was determined; the ultrastructure of myocardial tissue was observed; the protein expressions of mitofusin 1 (Mfn1), Mfn2, optic atrophy protein 1 (OPA1) and dynamin-related protein 1 (Drp1) were all detected in myocardial tissue. RESULTS Compared with control group,the serum content of NT-proBNP, apoptotic rate of myocardial cells, and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly; serum content of ATP,contents of PA and CL, and relative expressions of Mfn1, Mfn2 and L-OPA1 proteins were all significantly reduced (P<0.05). There were abnormal membrane tissue structure in various layers of myocardial tissue, degeneration and necrosis of myocardial cells, and severe fibrosis; the mitochondria were swollen, with reduced or absent cristae, and uneven matrix density. After intervention with Qiangxin decoction, the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats (excluding CL content in the Qiangxin decoction low- dose group) were significantly reversed (P<0.05); the pathological damage of myocardial tissue had significantly improved, fibrosis had significantly reduced, mitochondrial morphology tended to be normal, cristae had increased, and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats, thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis, the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.
8.Effects and mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure
Meiling MAO ; Jianqi LU ; Zhide ZHU ; Yan PANG ; Liyu XIE ; Jiayong CHEN ; Xinyu WU ; Xiang XIAO ; Junshen LU ; Weiqi SHI
China Pharmacy 2025;36(2):160-165
OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure (CHF). METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group, Qiangxin decoction low-dose and high-dose groups (12.25, 24.50 g/kg, calculated by crude drug), and chemical medicine group (Sacubitril valsartan sodium tablets, 10.42 mg/kg), with 10 rats in each group; control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication, the contents of N-terminal pro-brain natriuretic peptide (NT-proBNP) and adenosine triphosphate (ATP) in serum and phosphatidic acid (PA) and cardiolipin (CL) in myocardial tissue were all detected; the pathological damage and collagen fibrosis of rat myocardial tissue were observed; the apoptosis of myocardial cells was determined; the ultrastructure of myocardial tissue was observed; the protein expressions of mitofusin 1 (Mfn1), Mfn2, optic atrophy protein 1 (OPA1) and dynamin-related protein 1 (Drp1) were all detected in myocardial tissue. RESULTS Compared with control group,the serum content of NT-proBNP, apoptotic rate of myocardial cells, and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly; serum content of ATP,contents of PA and CL, and relative expressions of Mfn1, Mfn2 and L-OPA1 proteins were all significantly reduced (P<0.05). There were abnormal membrane tissue structure in various layers of myocardial tissue, degeneration and necrosis of myocardial cells, and severe fibrosis; the mitochondria were swollen, with reduced or absent cristae, and uneven matrix density. After intervention with Qiangxin decoction, the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats (excluding CL content in the Qiangxin decoction low- dose group) were significantly reversed (P<0.05); the pathological damage of myocardial tissue had significantly improved, fibrosis had significantly reduced, mitochondrial morphology tended to be normal, cristae had increased, and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats, thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis, the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.
10.Traditional Chinese Medicine Treats Sepsis by Regulating PI3K/Akt Pathway: A Review
Zhu LIU ; Jiawei WANG ; Jing YAN ; Jinchan PENG ; Mingyao XU ; Liqun LI ; Sheng XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):314-322
Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms such as bacteria. In addition to the manifestations of systemic inflammatory response syndrome and primary infection lesions, critical cases often have manifestations of organ hypoperfusion. The morbidity and mortality of sepsis have remained high in recent years, which seriously affect the quality of life of the patients. The pathogenesis of sepsis is complicated, in which uncontrollable inflammation is a key mechanism. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway plays a key role in mediating inflammation in sepsis. The available therapies of sepsis mainly include resuscitation, anti-infection, vasoactive drugs, intensive insulin therapy, and organ support, which show limited effects of reducing the mortality. Therefore, finding new therapeutic drugs is a key problem to be solved in the clinical treatment of sepsis. In recent years, studies have shown that traditional Chinese medicine (TCM) can regulate the PI3K/Akt pathway via multiple pathways, multiple effects, and multiple targets to inhibit inflammation and curb the occurrence and development of sepsis, which has gradually become a hot spot in the prevention and treatment of sepsis. Moreover, studies have suggested that TCM has unique advantages in the treatment of sepsis. TCM can regulate the PI3K/Akt signaling pathway to inhibit inflammation, reduce oxidative stress, and control apoptosis in the prevention and treatment of sepsis. Despite the research progress, a systematic review remains to be performed regarding the TCM treatment of sepsis by regulating the PI3K/Akt signaling pathway. After reviewing relevant papers published in recent years, this study systematically summarizes the relationship between PI3K/Akt pathway and sepsis and the role of TCM in the treatment of sepsis, aiming to provide new ideas for the potential treatment of sepsis and the development of new drugs.

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