1.Effects of Yishen paidu formula on renal fibrosis in rats with chronic renal failure by regulating the ROS/TXNIP/NLRP3 pathway
Li FENG ; Bowen PENG ; Bin PENG ; Xue FENG ; Shuangyi ZHU ; Wei XIONG ; Xi HU ; Xiaohui SUN
China Pharmacy 2026;37(2):174-179
OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure (CRF) through the reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. METHODS Rats were randomly divided into control group, model group, Yishen paidu formula low-dose (Yishen paidu formula-L) group, Yishen paidu formula high-dose (Yishen paidu formula- H) group, Yishen paidu formula-H+pcDNA-NC group, and Yishen paidu formula-H+ pcDNA-TXNIP group, with 10 rats in each group. Except for control group, all other rats were fed a diet containing 0.5% adenine to establish a CRF model; the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein, once daily, for 8 consecutive weeks. After the last administration, the levels of serum creatinine (Scr), blood urea nitrogen (BUN), ROS, superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were measured in each group. Pathological changes in renal tissue were observed, and the protein expression levels of Collagen Ⅲ, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group, the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr, BUN, ROS, MDA, TNF- α, IL-6 and IL-1β, and the protein expressions of Collagen Ⅲ, α-SMA, TGF-β1, TXNIP and NLRP3 were significantly decreased, while SOD levels were significantly increased (P<0.05). Moreover, the changes were more pronounced in the Yishen paidu formula-H group (P<0.05). Compared with Yishen paidu formula-H+pcDNA-NC group, above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly (P<0.05). CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.
2.Research progress on the mechanism of traditional Chinese medicine regulating metabolic reprogramming to improve breast cancer
Zhenyu ZHANG ; Weixia CHEN ; Bo FENG ; Jilei LI ; Sizhe WANG ; Meng ZHU ; Chunzheng MA
China Pharmacy 2026;37(2):250-256
Metabolic reprogramming, as one of the core hallmarks of malignant tumors, plays a key role in the occurrence, development and treatment of breast cancer (BC). Abnormal changes in glucose metabolism, amino acid metabolism, lipid metabolism, as well as the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) pathways significantly influence the pathogenesis and progression of BC. Studies have shown that various active components of traditional Chinese medicine (TCM) (such as berberine, matrine, quercetin, curcumin, etc.) and their compound formulations (e.g. Xihuang pill, Danzhi xiaoyao powder, Yanghe decoction, etc.) can inhibit the proliferation and migration of BC cells and induce apoptosis by regulating key metabolic pathways such as glycolysis, lipid synthesis, and amino acid metabolism. TCM demonstrates multi-target and holistic regulatory advantages in intervening in BC metabolic reprogramming, showing significant potential in modulating key molecules like hypoxia inducible factor-1α, hexokinase-2, pyruvate kinase M2, lactate dehydrogenase A, glucose transporter-1, fatty acid synthase, and signaling pathways such as AKT/mTOR. However, current researches still focus predominantly on glucose metabolism, with insufficient mechanistic studies on lipid metabolism, amino acid metabolism, the TCA cycle, and OXPHOS. The precise targets, molecular mechanisms, and clinical translation value of these interventions require further validation and clarification through more high-quality experimental studies and clinical trials.
3.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.
4.Mechanism of Gushining Granules in Attenuating Dexamethasone-induced Apoptosis of Bone Marrow Mesenchymal Stem Cells via Activating PI3K/Akt/Bad Signalling Pathway
Chengyu CHU ; Lei ZHU ; Long LIANG ; Feng WANG ; Xuejian YU ; Wenwu LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):115-122
ObjectiveTo establish steroid-induced osteonecrosis of the femoral head (SANFH) cell model by using dexamethasone (DEX)-induced bone marrow mesenchymal stem cells (BMSCs) and demonstrate that Gushing Granules (GSNs) exert an improving effect by activating the phosphatidylinositol-3-kinase/protein kinase B/B-lymphoma-2 gene related promoter (PI3K/Akt/Bad) signalling pathway. MethodsFirstly, SD rats were orally administered with drugs at a dose of 0.9 g·kg-1 to prepare GSN-containing serum, and CCK-8 screening was used to determine the optimal dosage and duration of action. Then, BMSCs were cultured and treated with 1×10-6 mol·L-1 DEX, 10% GSN-containing serum, and inhibitor LY294002 of PI3K/Akt signalling pathway for 24 hours to model and group SANFH cells. Cell viability and proliferation were detected by using CCK-8 assay kit and EdU staining kit. Flow cytometry was used to detect cell apoptosis. An alkaline phosphatase (ALP) assay kit was employed to detect ALP expression. In order to detect the PI3K/Akt/Bad signalling pathway and protein and mRNA expression of apoptosis-related proteins such as apoptosis regulatory factors B-cell lymphoma-2 gene (Bcl-2), and Bcl-2-associated X protein (Bax), osteocalcin (OCN), and Collagen Ⅰ, we used Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsThe CCK-8 assay kit determined that the optimal dosage for GSN-containing serum is 10%, and the duration of action is 48 hours. After modelling and grouping the cells in each group, the detection results showed that the SANFH model group had significantly lower cell viability, cell proliferation, and ALP expression, as well as protein and mRNA expressions of PI3K, Akt, Bad, Bcl-2, OCN, and Collagen I compared to the blank group. The nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly increased (P<0.05,P<0.01). After treatment with GSN-containing serum, cell viability, cell proliferation, and ALP expression, as well as expressions of PI3K, Akt, Bad, Bcl-2, OCN, and Collagen Ⅰ nucleic acids and proteins were significantly increased, while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly decreased(P<0.05,P<0.01). Compared with the GSN drug-containing serum group, the simultaneous treatment with the inhibitor LY294002 and GSN drug-containing serum reversed the improvement effect of GSN. Specifically, the cell viability, cell proliferation, ALP expression, and the nucleic acid and protein levels of PI3K, Akt, Bad, Bcl-2, OCN, and Collagen Ⅰ were all significantly decreased, while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry were significantly increased (P<0.05, P<0.01). ConclusionGSNs antagonize DEX-induced apoptosis of BMSCs by activating the PI3K/Akt/Bad signalling pathway, providing a scientific theoretical basis for the clinical treatment of SANFH with GSNs.
5.Pharmacokinetic Analysis of Ziyuglycoside Ⅰ in Normal and Acute Kidney Injury Rats
Yunhui ZHANG ; Yanli LIU ; Qiongming XU ; Shuding SUN ; Hongjin ZHU ; Di ZHAO ; Suxiang FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):203-210
ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry(UPLC-Orbitrap Fusion Lumos Tribrid-MS), the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration, and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group, the model group received intraperitoneal cisplatin(10 mg·kg-1) to establish the acute kidney injury model, the normal group was given the same volume of saline. After successful modeling, rats in the normal and model groups were randomly divided into the normal low, medium and high dose groups(2.5, 5, 7.5 mg·kg-1) and the model low, medium and high dose groups(2.5, 5, 7.5 mg·kg-1), 6 rats in each group, and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then, the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS, and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software, and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ, its concentration increased first and then decreased, and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve(AUC0-t) and mean retention time(MRT0-t) of normal and model rats increased with the increased dose, and the clearance(CL) decreased with the increasing dose. Compared with the normal group, the AUC0-t was significantly increased(P<0.01), peak concentration(Cmax) and CL decreased in model rats at different doses, indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats, which may be due to the change of the body environment in the pathological state, then lead to changes in absorption and metabolic processes.
6.Over 20-year Follow-up Result of Total Knee Arthroplasty for Knee Arthropathy: A Single Center Cohort Study
Yiming XU ; Mingwei HU ; Wei ZHU ; Muyang YU ; Jin LIN ; Jin JIN ; Wenwei QIAN ; Bin FENG ; Xisheng WENG
Medical Journal of Peking Union Medical College Hospital 2025;16(1):35-41
To evaluate long-term survival and clinical outcomes of patients with knee osteo-arthritis undergoing total knee arthroplasty (TKA) through long-term follow-up. This study was based on a previous cohort study that had completed follow-up. We retrospectively collected clinical data of patients with knee arthropathy (including knee osteoarthritis and knee rheumatoid arthritis) who received the first TKA operation in Peking Union Medical College Hospital from 1993 to 2002 and were followed up for more than 20 years, and conducted a unified follow-up on them in November 10, 2024 (the last follow-up). Kaplan-Meier curve was used to evaluate the survival rate. Hospitals for special surgery (HSS) scores and joint range of motion (ROM) were compared before surgery, 10 years after surgery and at the last follow-up to evaluate the clinical efficacy of TKA. Likert scale was used to evaluate patient satisfaction at the last follow-up. A total of 226 patients (246 knees) received their first TKA in Peking Union Medical College Hospital from 1993 to 2002 and were followed up for more than 10 years. Among them, 104 patients (131 knees) were included in the study at the last follow-up, including 21 patients (24 knees) with prosthesis in place, 18 patients (18 knees) who underwent reoperation for various reasons, and 65 patients (89 knees) who died from non-TKA surgical causes. Up to the last follow-up, there were 29 patients (35 knees) with an average follow-up of more than 20 years, and 12 patients (16 knees) completed HSS score, ROM measurement and patient satisfaction evaluation. Kaplan-Meier curve showed that the 10-year, 15-year, 20-year, and 25-year survival rates were 93.6%, 92.4%, 89.8%, and 71.8%, respectively. The HSS score at the last follow-up was lower than that at 10- year postoperative follow-up[(84.69±11.03) scores TKA treatment for knee arthropathy has high long-term prosthesis survival rate, significant improvement of knee joint function and high patient satisfaction.
7.Early Postoperative Safety of Total Hip Arthroplasty in Systemic Lupus Erythematosus Patients
Xingdong YANG ; Muyang YU ; Yiming XU ; Wei ZHU ; Mingwei HU ; Xisheng WENG ; Bin FENG
Medical Journal of Peking Union Medical College Hospital 2025;16(1):42-49
To analyze the occurrence of early complications after total hip arthroplasty (THA) in patients with systemic lupus erythematosus (SLE). The data of patients who underwent THA at Peking Union Medical College Hospital from June 2012 to April 2024 were retrospectively and consecutively collected. The patients were categorized into SLE group and control group based on the presence or absence of SLE. Using propensity score matching, we matched patients in the two groups at a 1∶1 ratio according to gender, age, and surgical side. Subsequently, we compared the clinical characteristics, incidence of major complications within 30 days postoperatively, and allogeneic blood transfusion rates between the two groups. A total of 270 patients in the SLE group who met the inclusion and exclusion criteria were selected. Within 30 days postoperatively, 18 cases (6.67%) experienced major complications, including 2 cases (0.74%) of upper respiratory tract infection, 2 cases (0.74%) of pulmonary infection, 3 cases (1.11%) of urinary tract infection, 2 cases (0.74%) of other systemic infection, 5 cases (1.85%) of poor wound healing, 1 case (0.37%) of wound infection, 1 case (0.37%) of gastrointestinal complications, 1 cases (0.37%) of shock, and 1 case (0.37%) of SLE flare-up. The allogeneic blood transfusion rate was 22.59% (61/270). After propensity score matching, 163 cases from SLE and control groups were included for analysis. (1) Regarding medical complications, compared with control group, SLE group showed significant differences in osteoporosis, respiratory system disorders, gastrointestinal diseases, urinary system disorders, hematologic abnormalities, and secondary or concomitant rheumatic diseases (all The incidence of major complications within 30 days following THA in patients with SLE was significantly higher than that in non-SLE patients, while the rate of allogeneic blood transfusion remained comparable. To ensure the safety of THA surgery for patients with SLE, it is important to optimize the patient's condition and achieve stabilization prior to surgery. Additionally, strict perioperative management must be forced.
8.Research progress of anti-inflammation therapy and immunotherapy for acute pancreatitis
Chinese Journal of Clinical Medicine 2025;32(1):120-124
At present, the incidence and mortality rate of severe acute pancreatitis is 15%-20% and about 20%, respectively, which can lead to local and systemic complications of patients and huge medical costs. The occurrence of acute pancreatitis is closely related to inflammatory response. This article reviews the progress of anti-inflammation therapy and immunotherapy of acute pancreatitis, aiming to provide reference for treatment in patients with acute pancreatitis.
9.Clinical practice guidelines for intraoperative cell salvage in patients with malignant tumors
Changtai ZHU ; Ling LI ; Zhiqiang LI ; Xinjian WAN ; Shiyao CHEN ; Jian PAN ; Yi ZHANG ; Xiang REN ; Kun HAN ; Feng ZOU ; Aiqing WEN ; Ruiming RONG ; Rong XIA ; Baohua QIAN ; Xin MA
Chinese Journal of Blood Transfusion 2025;38(2):149-167
Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.
10.Serological and genetic analysis of a novel 27delC variant in A subgroup: a case report
Yingjun ZHANG ; Yuli ZHU ; Zhihui FENG ; Shuhong YU
Chinese Journal of Blood Transfusion 2025;38(2):280-283
[Objective] To conduct serological identification and molecular mechanism study on a ambiguous ABO blood group. [Methods] Standard serological techniques were used for the forward and reverse typing of ABO blood type. ABO gene coding and regulatory regions were analyzed by PCR after DNA extraction. Monoclonal sequencing was used to detect the haplotypes of the DNA sequence, and bioinformatics analysis was applied to predict the possible translation outcomes of the mutated DNA sequence. [Results] The sample’s red blood cells showed mixed field agglutination with anti-A, and the serum agglutinated with B cells, exhibiting serological characteristics of subtype A. Direct sequencing and monoclonal sequencing analysis of the ABO gene confirmed one allele as O02, the other had a c.27delC mutation compared with A102, which could cause the translation sequence to terminate prematurely at the 19th amino acids. Analysis and prediction suggested that the mutation might affect the function of the transferase through mechanisms such as shifting the initiation codon, altering the reading frame and affecting the splice sites. [Conclusion] This case is a rare A subtype caused by the c.27delC variation, and the impact on the glycosyltransferase may involve multiple mechanisms, which require further research and exploration.

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