1.Mechanism study of SIRT3 alleviating oxidative-stress injury in renal tubular cells by promoting mitochondrial biogenesis via regulating mitochondrial redox balance
Yaojun LIU ; Jun ZHOU ; Jing LIU ; Yunfei SHAN ; Huhai ZHANG ; Pan XIE ; Liying ZOU ; Lingyu RAN ; Huanping LONG ; Lunli XIANG ; Hong HUANG ; Hongwen ZHAO
Organ Transplantation 2026;17(1):86-94
Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H2O2 and divided into four groups: control (NC), 50 μmol/L H2O2, 110 μmol/L H2O2 and 150 μmol/L H2O2. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H2O2, and siSIRT3+H2O2. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O2•−) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H2O2 decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O2•− did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O2•− level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H2O2 group exhibited decreased cellular ATP levels, elevated mitochondrial O2•− levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H2O2 group showed a decrease in cellular ATP levels, an increase in mitochondrial O2•− levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H2O2 group, the siSIRT3+H2O2 group showed a decrease in cellular ATP levels, an increase in mitochondrial O2•− levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.
2.Clinical study of salvage second allogeneic hematopoietic stem cell transplantation in 17 cases
Wenqiong WANG ; Wei LIU ; Huihui LIU ; Xiaoying YANG ; Shuanglian XIE ; Hongtao LING ; Yiming ZHAO ; Yujun DONG
Organ Transplantation 2026;17(1):124-132
Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.
3.Study on the apoptosis-inducing effect of esculetin on acute myeloid leukemia HL-60 cells via regulating the AKT/SKP2/MTH1 pathway
Weihua SONG ; Fuying CHU ; Wei XIE ; Jinliang CHEN ; Ping ZHAO ; Hong QIU ; Jian TAO ; Xiang CHEN
China Pharmacy 2026;37(1):36-41
OBJECTIVE To investigate the apoptosis-inducing effect of esculetin (Esc) on acute myeloid leukemia (AML) HL-60 cells by regulating the protein kinase B (AKT)/S-phase kinase-associated protein 2 (SKP2)/MutT homolog 1 (MTH1) pathway. METHODS AML HL-60 cells were randomly divided into control group (routine culture), Esc low-concentration group (L-Esc group, 25 μmol/L Esc), Esc medium-concentration group (M-Esc group, 50 μmol/L Esc), Esc high-concentration group (H-Esc group, 100 μmol/L Esc), and high-concentration of Esc+ SC79 (AKT agonist) group (100 μmol/L Esc+5 μmol/L SC79). Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species (ROS) in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3], AKT/SKP2/MTH1 pathway-related proteins (p-AKT, AKT, SKP2, MTH1), along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase (PI3K), cyclin-dependent kinase inhibitor 1 (P21) and cyclin-dependent kinase inhibitor 1B (P27). RESULTS Compared with control group, the cell viability, colony number, and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2, MTH1 and Bcl-2 were significantly decreased (P<0.05), while ROS level, apoptosis rate, and the expression levels of Bax, cleaved caspase-3, P21 and P27 proteins were significantly increased (P<0.05). Moreover, the effects of Esc exhibited concentration-dependence (P<0.05). Compared with H-Esc group, above indexes of high-concentration of Esc+ SC79 group were reversed significantly (P<0.05). CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway, thus inhibiting the proliferation of HL-60 cells.
4.Impact of visceral fat area on significant liver fibrosis in patients with nonalcoholic fatty liver disease and establishment of a predictive model
Jingkai YUAN ; Fengming ZHAO ; Huangqi LIN ; Meijie SHI ; Huanming XIAO ; Yubao XIE ; Xiaoling CHI
Journal of Clinical Hepatology 2026;42(2):312-318
ObjectiveTo investigate whether visceral fat area (VFA) is an independent risk factor for significant liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) based on clinical data, and to establish an effective diagnostic model. MethodsA total of 222 NAFLD patients who attended Department of Hepatology, Guangdong Provincial Hospital of Traditional Chinese Medicine, from January 2021 to April 2025 were enrolled, and according to liver stiffness measurement (≥8 kPa or not), they were divided into significant fibrosis group and non-significant fibrosis group. Propensity score matching (PSM) was performed at a ratio of 1∶1 to balance the baseline data between the two groups. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was used to determine the correlation of VFA and other indicators with significant liver fibrosis; univariate and multivariate logistic regression analyses were used to identify whether VFA was an independent risk factor for significant liver fibrosis in NAFLD patients, and the receiver operating characteristic (ROC) curve was plotted to assess the predictive performance of related indicators. ResultsA total of 45 patients with significant liver fibrosis and 177 patients without significant liver fibrosis were enrolled, and after PSM, 90 patients (45 pairs) were finally included in analysis. Compared with the non-significant fibrosis group, the significant fibrosis group had significantly higher levels of body mass index (BMI), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), uric acid (UA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), controlled attenuation parameter (CAP), and VFA, as well as a significantly higher proportion of patients with visceral fat obesity or three or more metabolic risk factors (all P<0.05). VFA, BMI, AST, and HbA1c were strongly correlated with significant liver fibrosis (all r>0.5, all P <0.05), and ALT, GGT, UA, FBG, and CAP were significantly positively correlated with significant liver fibrosis (r=0.3 — 0.5, all P<0.05). VFA (odds ratio [OR]=1.040, 95% confidence interval [CI]: 1.018 — 1.062, P<0.05), FBG (OR=2.372, 95%CI: 1.199 — 4.691, P<0.05), and AST (OR=1.032, 95%CI: 1.003 — 1.058, P<0.05) were independent risk factors for significant liver fibrosis in NAFLD patients. The new diagnostic model based on VFA, FBG, and AST (with an area under the ROC curve [AUC] of 0.907) had a significantly better performance than aspartate aminotransferase-to-platelet ratio index (AUC=0.834), fibrosis-4 (AUC=0.660), triglyceride-glucose index (AUC=0.656), and NAFLD fibrosis score (AUC=0.768) in predicting significant liver fibrosis in NAFLD patients (all P<0.05). ConclusionVFA is an independent risk factor for significant liver fibrosis in NAFLD patients, and the noninvasive diagnostic model based on VFA, FBG, and AST can effectively predict the onset of significant liver fibrosis in NAFLD patients.
5.Society of Critical Care Medicine 2024 Guidelines on Adult ICU Design: An Interpretation
Hui ZHANG ; Jianhua SUN ; Wanchen ZHAO ; Lingli XIE ; Cong MA ; Yifan FANG ; Jing CAI ; Na GUO
Medical Journal of Peking Union Medical College Hospital 2026;17(2):421-428
This article provides a systematic interpretation and review of the
6.Risk Factors Analysis and Predictive Model Construction for Acute Kidney Injury Following Amphotericin B Deoxycholate Use in Hospitalized Patients
Hao XIE ; Yixun SHI ; Zhiqing XU ; Minquan LI ; Xiaoli DU ; Gang CHEN ; Bin ZHAO
Medical Journal of Peking Union Medical College Hospital 2026;17(2):429-437
To investigate the risk factors for acute kidney injury (AKI) following the use of amphotericin B deoxycholate and to develop a predictive model to guide clinical monitoring and intervention. A retrospective analysis was conducted on hospitalized patients who received amphotericin B deoxycholate between January 2014 and September 2024. Patients were divided into a training set and a validation set. Demographic data, laboratory findings, and medication orders were collected. Based on the occurrence of AKI during treatment and within 7 days after discontinuation, patients were classified into an AKI group and a non-AKI group. Univariate analysis was used to screen for potential risk factors, multivariate logistic regression was employed to construct a predictive model, and model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow test. The training set included 473 patients, comprising 255 males (53.91%) and 218 females (46.09%), with a median age of 52(35, 62) years. The AKI group consisted of 191 cases (40.38%), and the non-AKI group consisted of 282 cases (59.62%). The validation set included 114 patients, comprising 80 males (70.18%) and 34 females (29.82%), with a median age of 43.5 (31.0, 58.5) years. The AKI group consisted of 42 cases (36.84%), and the non-AKI group consisted of 72 cases (63.16%). Univariate analysis revealed statistically significant differences between the two groups in 23 factors (all Admission to the ICU, elevated serum creatinine at admission, and comorbid cardiac insufficiency as potential risk factors for AKI, while prophylactic use of diphenhydramine/promethazine or sodium bicarbonate showed a protective association. A predictive model with good discrimina-tion and calibration was developed, which may provide a basis for early identification of high-risk patients and timely adjustment of treatment strategies in clinical practice.
7.Establishment and validation of a prediction model for mineral and bone disorder in maintenance hemodialysis patients
Yanling HUANG ; Jiping SHEN ; Kai CAO ; Ping XIE ; Jinyuan ZHAO ; Rulian LIANG
Chinese Journal of Clinical Medicine 2026;33(1):58-64
Objective To explore the risk factors for mineral and bone disorder in maintenance hemodialysis patients, and to construct and validate a nomogram prediction model. Methods A total of 306 patients undergoing maintenance hemodialysis at Shanghai Eighth People’s Hospital from January 2021 to May 2025 were selected as study subjects and randomly divided into a training set (n=214) and a validation set (n=92) in a 7∶3 ratio. In the training set, patients were divided into a normal bone mineral metabolism group and an abnormal bone mineral metabolism group, and related factors were compared between the two groups. The multivariate logistic regression analysis was used to identify the influencing factors of mineral and bone disorder in maintenance hemodialysis patients in the training set, and a nomogram prediction model was constructed. ROC curves were drawn to evaluate the ability of the nomogram model for predicting mineral and bone disorder in these patients. Calibration curves and Hosmer-Lemeshow goodness-of-fit test were used to analyze the consistency of the predictive probability of nomogram model and actual probability of mineral and bone disorder in these patients. The decision curve was used to assess the clinical benefit using nomogram prediction model. Results Among the 306 hemodialysis patients, 254 patients had mineral and bone disorder, accounting for 83.01%. Among the 214 patients in the training set, 177 had mineral and bone disorder, accounting for 82.71%. In the training set, age, gender, body mass index (BMI), hypertension rate, dialysis age, blood urea nitrogen (BUN), hemoglobin (Hb), albumin (ALB), alkaline phosphatase (ALP), serum creatinine (SCr), uric acid (UA), estimated glomerular filtration rate (eGFR), and rate of taking phosphate binders were statistically significant different between the two groups (P<0.05). The multivariate logistic regression analysis showed higher age, female, hypertension, longer dialysis duration, decreased eGFR, and not taking phosphate binders were identified as risk factors for mineral and bone disorder in maintenance hemodialysis patients (P<0.01). The nomogram prediction model was constructed. The area under the ROC curve of the model for mineral and bone disorder in the training set and validation set was 0.895 (95%CI 0.850-0.941) and 0.881 (95%CI 0.830-0.932), respectively, with maximum Youden indice of 0.650 and 0.600, sensitivity of 0.856 and 0.849, and specificity of 0.794 and 0.751. The Hosmer-Lemeshow test showed the nomogram prediction model had good consistency in predictive probabilities with actual probabilities in training set and validation set. The decision curve showed the nomogram model could bring clinical net benefits when the threshold probabilities in the training set and validation set were less than 0.96 and 0.91. Conclusions The nomogram prediction model constructed based on six independent risk factors including age, gender, hypertension, dialysis duration, eGFR, and using phosphate binders or not, shows good discrimination and calibration, with good clinical predictive ability, which could provide guidance for the management of maintenance hemodialysis patients.
8.Interpretation of Evidence-to-decision Framework and Its Application in Pharmacovigilance Guidelines of Chinese Patent Medicines
Hongyan ZHANG ; Xin CUI ; Yuanyuan LI ; Zhifei WANG ; Mengmeng WANG ; Shuo YANG ; Xiaoxiao ZHAO ; Fumei LIU ; Yaxin WANG ; Rui MA ; Yanming XIE ; Lianxin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):220-228
To interpret the evidence-to-decision (EtD) framework and to illustrate its application in traditional Chinese medicine (TCM) guideline development using the example of the Pharmacovigilance Guideline of Chinese Patent Medicine, thereby providing methodological references for TCM guideline standardization. Based on the core three stages of the EtD framework (formulating the question, making an assessment of the evidence, and drawing conclusions), critical decision points and evaluation evidence within the evidence-translation process were systematically addressed, aligning with the purpose, scope, and key questions of the guideline. Qualitative research methods, such as the nominal group technique, were employed to formulate recommendations. The analysis was conducted based on the EtD framework. During question formulation, the specific characteristics and practical needs of pharmacovigilance for Chinese patent medicines were clarified, focusing on the core objective of safety assurance throughout the product lifecycle. In the evidence assessment, multi-source evidence was integrated, including policy documents, literature research, and expert consensus, completing the evidence evaluation. Finally, in recommendation-forming, dispersed research evidence and expert experience were synthesized into consensus, culminating in the guideline's completion through solicitation of opinions and peer review. The EtD framework provides a structured tool for evidence-to-decision translation in TCM guideline development, effectively enhancing the transparency and scientific rigor of the process. Therefore, it is recommended that TCM guideline development adopt the EtD framework to improve the evidence-to-decision process with TCM characteristics.
9.Compilation Instruction and Key Point Interpretation for Guidelines for Construction of Traditional Chinese Medicine Pharmacovigilance System in Medical Institutions
Shuoshuo WEI ; Fumei LIU ; Li ZHANG ; Yuanyuan LI ; Zhifei WANG ; Xiaoxiao ZHAO ; Xin CUI ; Ruili WEI ; Shuo YANG ; Yanming XIE ; Lianxin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):229-237
The Guidelines for Construction of Traditional Chinese Medicine Pharmacovigilance Systems in Medical Institutions (T/CACM 1563.2-2024) were the first special guideline in China to systematically assist medical institutions in establishing a pharmacovigilance system tailored to the characteristics of traditional Chinese medicine (TCM). This guideline was jointly developed with 23 authoritative medical and research institutions in China, under the lead of the Institute of Basic Clinical Medicine, China Academy of Chinese Medical Sciences. The purpose of this guideline was to standardize pharmacovigilance work throughout the entire lifecycle of TCM (including research and development, marketing, and application) and to establish a four-dimensional framework of "organizational structure, institutional system, information platform, and vigilance activities". Key components included the establishment of a TCM Safety Committee, the construction of nine core systems, the development of an information platform that complies with International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2B standards, alongside the risk monitoring, identification, assessment, and control during clinical trials and post-marketing phases. Therefore, this guideline filled a significant gap in the systemic standards for TCM safety management within medical institutions. Strictly adhering to domestic and international laws and regulations, the guideline compilation involved multiple rounds of expert interviews, systematic evidence integration, and broad consensus. This guideline was specified to be applicable to medical institutions at all levels, primarily addressing core issues, including the difficulty in adverse reaction identification, low reporting rates, and incomplete risk management chains due to the complex composition and diverse application of TCM. The compilation process was scientific and rigorous, ensuring alignment with current national laws and regulations, and was registered internationally. In the future, implementation will be promoted through standardized training, tiered dissemination, as well as a post-effect evaluation and dynamic revision mechanism starting two years after publication. All these aimed to enhance medical institutions' proactive capabilities in preventing and controlling TCM safety risks, ensure patient medication safety, and promote the high-quality development of TCM.
10.Compilation Instruction for Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines
Hongyan ZHANG ; Zhifei WANG ; Shuo YANG ; Ruili WEI ; Wenqian PENG ; Yuanyuan LI ; Xin CUI ; Xiaoxiao ZHAO ; Fumei LIU ; Mengmeng WANG ; Yanming XIE ; Lianxin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):245-251
To standardize the clinical application of oral Chinese patent medicines (CPMs), and address the safety issues arising from their dosage form characteristics, irrational clinical use, and the lack of targeted pharmacovigilance systems, the China Association of Chinese Medicine organized the formulation and release of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines, aiming to inform the safe clinical use of oral CPMs and related pharmacovigilance work. According to the principles of GB/T1.1—2020 and the Drug Administration Law of the People's Republic of China (2019 revision), the Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, led a drafting group comprising 18 institutions. After multiple rounds of expert interviews, literature retrieval, evidence screening, and extensive solicitation of opinions, the Guidelines were registered internationally. Systematic standardization focused on safety monitoring, risk identification, assessment, control, and other aspects. The Guidelines clarified the characteristics of oral CPMs in terms of safety monitoring, known risks, and potential risks, compared to non-oral CPMs. Then, risk control measures were proposed, including medication in special populations and irrational medication. As a special guideline for pharmacovigilance in the clinical application of oral CPMs, the Guidelines systematically construct a technical system in line with the characteristics of traditional Chinese medicine (TCM), which is essential for improving the clinical safety management of oral CPMs and provides an important reference for medical institutions, pharmaceutical manufacturers, and regulatory authorities.

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