1.Mechanistic study of Tripterygium wilfordii multiglucoside in improving nephrotic syndrome via regulating the HIF-1α/miR-155-5p/Nrf2 pathway
Yifan TAO ; Chundong SONG ; Xu WANG ; Chong ZHANG ; Ying SU ; Xidong JIA ; Haoran JIANG
China Pharmacy 2026;37(5):602-606
OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside (TWM) on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group (distilled water), prednisone group (10 mg/kg), and TWM high- and low-dose groups (10 and 5 mg/kg, respectively). Additionally, blank group (distilled water) without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage, once a day, for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed; the levels of 24-hour urinary protein (24 h-UTP) and serum biochemical indicators [albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), cholesterol (CHOL), and triglyceride (TG)] in rats were determined; the levels of oxidative stress indicators [superoxide dismutase (SOD), malondialdehyde (MDA)] in kidney tissue of rats were determined; expressions of hypoxia-inducible factor-1α (HIF-1α)/microRNA-155-5p (miR-155-5p)/nuclear factor erythriod 2- related factor 2 (Nrf2) signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group, the rats in the model group exhibited disordered renal tissue structure, with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP, serum levels of SCr, BUN, CHOL and TG, MDA content, mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly ( P <0.05). Serum level of ALB, SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly ( P <0.05). Compared with the model group, TWM high-dose and low-dose groups exhibited significant improvements in renal injury, with notable reversals in the levels of the above quantitative indicators ( P <0.05). CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.
2.Genomic characterization of Legionella pneumophila isolated from industrial circulating cooling water
Man YU ; Ying TANG ; Xiangjun ZHANG ; Chenyi TAO ; Yong NING ; Yi XU ; Xiaodong JIA ; Xia ZHANG
China Occupational Medicine 2026;53(1):50-57
Objective To analyze the genomic characteristics of Legionella pneumophila (L. pneumophila) isolated from industrial circulating cooling water in workplace. Methods A total of 20 L. pneumophila strains isolated from industrial circulating cooling water collected from eight chemical enterprises were selected as the research subjects. Whole-genome sequencing was performed on the strains, followed by multilocus sequence typing (MLST), whole-genome single nucleotide polymorphism analysis, virulence factor profiling, and antibiotic resistance gene detection. Results The dominant MLST typing among the 20 L. pneumophila strains was ST2. Serogroup 1 (Lp1) strains exhibited high genetic diversity. Strains from different enterprises showed substantial genomic diversity, suggesting possible inter-enterprise dissemination. Each isolate harbored 175-295 virulence genes; among them, virulence genes were identified, and 139 genes were detected in all the 20 strains. These genes primarily included those related to the Dot/Icm type Ⅳ bacterial secretion system, flagellar synthesis and motility, and type Ⅳ pili. The number of virulence genes carried by L. pneumophila strains of different ST types differed (P<0.01), with unidentified sequence types harboring more virulence genes than other STs (P<0.01). A total of four resistance genes were predicted, including aminoglycoside phosphotransferase-encoding gene APH(9)-Ia, carbapenemase-encoding gene OXA-29, and efflux pump genes-encoding genes LpeA and LpeB, with detection rates of 100.00%, 100.00%, 10.00%, and 10.00%, respectively. These genes may confer resistance to cephalosporins, penicillins, and aminoglycosides, and all strains were multidrug resistance. Conclusion L. pneumophila isolated from industrial recirculating cooling water exhibits high genetic diversity, strong pathogenicity, and significant multidrug resistance potential.
3.4-Phenylbutyrate ameliorates lipopolysaccharide-induced bile acid metabolism disorder in maternal mice
Xinru LIANG ; Ying SUN ; Shuangrui BAO ; Tong ZHAN ; Hongyan WU ; Wenkang TAO ; Lun ZHANG ; Jianqing WANG ; Cheng ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(7):1183-1190
ObjectiveTo explore the ameliorative effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA) on bile acid metabolism disorders induced by bacterial lipopolysaccharide (LPS) in late-pregnant mice, and to clarify the regulatory mechanism of endoplasmic reticulum stress (ERS) in intrahepatic cholestasis of pregnancy (ICP). MethodsTwenty-four pregnant mice were divided into control group, LPS group, 4-PBA group, and LPS+4-PBA group. On the 16th day of pregnancy, the LPS group received intraperitoneal injection of LPS (200 μg/kg) and the 4-PBA group received injection of 4-PBA (150 mg/kg). In the LPS+4-PBA group, 4-PBA was intraperitoneally injected first, followed by LPS administration 1 h later. Serum total bile acid (TBA), liver injury markers, bile acid profiles, and the expression of key genes and proteins were detected 6 h after LPS treatment. ResultsLPS exposure increased serum TBA levels in pregnant mice(P<0.05), activated ERS markers and inflammatory factors, and downregulated bile acid transporters and the expression of the rate limiting enzyme CYP7A1(all P<0.05). 4-PBA intervention effectively inhibited ERS, reduced TBA levels(P<0.05), and upregulated Ntcp, Bsep, Mdr3, and Mrp3 gene expression(all P<0.05). ConclusionERS plays an important role in LPS interference with the homeostasis of bile acid metabolism during pregnancy. Inhibiting ERS can improve bile stasis by regulating bile acid transporters, providing a theoretical basis for targeted therapy of ICP.
4.Construction Method of Drug Adverse Reaction Knowledge Graph Based on Knowledge-Driven Technology Path
Wei REN ; Yan XU ; Qing WANG ; Zitong PEI ; Tao WANG ; Ying LIU ; Yexiang ZHANG
Herald of Medicine 2025;44(4):565-569
Objective In view of the potential threat of adverse drug reaction(ADR)to patients'health and the limitations of traditional monitoring methods,this study investigates the construction method of an ADR knowledge graph based on a knowledge-driven technology path to promote the intelligent upgrading of pharmacovigilance field.Methods In this study,an adverse drug reaction knowledge base was established,and the data within the knowledge base were preprocessed.The BERT-CRF model was utilized to identify and extract the relevant entities,relationships and attribute information,and knowledge alignment was carried out by combining the rule method and statistical method.The knowledge fusion data was stored in the Neo4j graph database to construct the knowledge graph.Results Based on the established knowledge base,this study explored the method of constructing knowledge graph of adverse drug reaction by knowledge-driven technology,laying the groundwork for data mining and the development of intelligent auxiliary system tools based on knowledge graph.Conclusions The study on the construction method of an ADR knowledge graph based on a knowledge-driven technology path provides a new perspective and technical path for the intelligent upgrading of pharmacovigilance field.It holds important theoretical and practical significance for improving drug safety,protecting patients'health,and promoting the healthy development of pharmaceutical industry.
5.Clinical effects of Pinggan Xifeng Huatan Tongluo Decoction on elderly patients with acute cerebral infarction complicated with hypertension
Ying-lu JIANG ; Miao-miao ZHANG ; Tao ZHANG ; Xue-jun LI
Chinese Traditional Patent Medicine 2025;47(10):3274-3278
AIM To explore the Clinical effects of Pinggan Xifeng Huatan Tongluo Decoction on elderly patients with acute cerebral infarction complicated with hypertension.METHODS Eighty-six patients were randomly assigned into control group(43 cases)for intervention of conventional treatment,and observation group(43 cases)for intervention of both Pinggan Xifeng Huatan Tongluo Decoction and conventional treatment.The changes in clinical effects,TCM symptom effects,TCM symptom score,NIHSS score,FMA score,ambulatory blood pressure indices(SBP,DBP,pulse pressure difference,variation coefficient for systolic blood pressure,variation coefficient for diastolic blood pressure),cerebral hemodynamic indices(PSV,EDV,PI,RI),Leptin,RBP4 and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rates of clinic and TCM symptoms than the control group(P<0.05).After the treatment,the two groups displayed decreased TCM symptom score,NIHSS score,ambulatory blood pressure indices,PSV,EDV,RI,Leptin,RBP4(P<0.05),and increased FMA score,PI(P<0.05),especially for the observation group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the elderly patients with acute cerebral infarction complicated with hypertension,Pinggan Xifeng Huatan Tongluo Decoction can safely and effectively relieve clinical symptoms,enhance anti-hypertensive effect,improve the perfusion of cerebral blood flow,and reduce the levels of serum leptin and RBP4.
6.Comparison and Analysis of Tumorigenicity of Tumor Cells in Bile between PTBD and ERBD of Hilar Cholangiocarcinoma
Kai-Hua ZHU ; De-Xiang ZHANG ; Ying TAO ; Shu-Long ZHANG ; Kun FAN ; Hou-Bao LIU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(1):112-124
Hilar cholangiocarcinoma is insidious in onset and often causes obstructive jaundice due to bile stasis,leading to impaired liver function.For tumors with malignant obstructive jaundice,biliary drainage is often performed before surgery in clinical practice.Currently,the commonly used drainage methods are percutaneous transhepatic biliary drainage(PTBD)and endoscopic retrograde biliary drain-age(ERBD),but there are controversies over the advantages and disadvantages of the two drainage methods.PTBD drainage can often lead to tumor implantation metastasis,but the underlying mechanism remains unclear.We detected tumor cells in PTBD and ERBD bile samples from hilar cholangiocarcino-ma patients,subsequently explored their tumorigenicity and mechanisms through tumorsphere assay in vitro and xenograft tumor models in vivo.The experiments included benign gallstones group(30 cases)as a negative control,PTBD group(14 cases)and ERBD group(13 cases).Tumorsphere formation was i-dentified in 3 cases(23%)among the 13 cases of ERBD group,in 6 cases(42%)among the 14 cases of PTBD group,but there were no tumor cells or formed tumorspheres in the 30 cases of benign gallstone group.The tumor sphere formation ability of cells in the PTBD group was significantly higher than that in ERBD group.Subcutaneous xenograft tumor assays showed that tumor growth in the PTBD group was sig-nificantly higher than that in the ERBD group.Tumor cells in PTBD bile possessed stronger tumorigenici-ty compared with the ERBD group.Mechanically,stem cell transcription factor Nanog mRNA levels were significantly higher in the PTBD group compared to the ERBD group.Both tumorsphere formation and xenograft tumor growth were reduced by Nanog knockdown in three cases of the PTBD group,indicating the important roles of Nanog in tumorigenicity of PTBD group tumor cells.The half-life of Nanog mRNA was longer in PTBD group cells than in ERBD group cells,suggesting potential post-transcriptional regu-lation on Nanog mRNA.The Nanog m6A level was higher in PTBD group tumor cells compared to the ERBD group.Analysis of methyltransferases and demethylases,ALKBH5(α-ketoglutarate dependent dioxygenase alkb family homolog 5)mRNA levels were lower in the PTBD group than in the ERBD group and significantly correlated with the m6A level of Nanog.ALKBH5 knockdown led to an increase in the m6A level of Nanog,while ALKBH5 overexpression decreased the m6A level of Nanog.Dual-luciferase activity assays demonstrated that ALKBH5 knockdown significantly enhanced luciferase activity,whereas ALKBH5 overexpression reduced it.Further studies confirmed that ALKBH5 knockdown upregulated both the mRNA and protein levels of Nanog,whereas overexpressing ALKBH5 downregulated them.ALKBH5 mediated the demethylation modification of Nanog mRNA,and the lower levels of ALKBH5 expression in the PTBD group promoted Nanog's m6A modification.Overexpressing ALKBH5 decreased tumorsphere growth,while ALKBH5 knockdown increased it,which was subsequently reduced by the simultaneous Nanog knockdown again.In sum,tumor cells in PTBD and ERBD drainage bile from hilar cholangiocar-cinoma patients exhibited tumorigenicity.Compared to the ERBD group,tumor cells in PTBD bile with lower ALKBH5 expression levels enhanced Nanog's m6A modification to upregulate Nanog expression levels,resulting in stronger tumorigenicity.These findings are significant for elucidating propensity to tumor implantation metastasis from PTBD drainage.
7.Danggui Shaoyaosan Regulates Nrf2/SLC7A11/GPX4 Signaling Pathway to Inhibit Ferroptosis in Rat Model of Non-alcoholic Fatty Liver Disease
Xinqiao CHU ; Yaning BIAO ; Ying GU ; Meng LI ; Tiantong JIANG ; Yuan DING ; Xiaping TAO ; Shaoli WANG ; Ziheng WEI ; Zhen LIU ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):35-42
ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease (NAFLD) and explore the underlying mechanism based on the nuclear factor E2-related factor 2 (Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows: control, model, Yishanfu (0.144 g·kg-1), and low-, medium-, and high-dose (2.44, 4.88, and 9.76 g·kg-1, respectively) Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling, rats were treated with corresponding agents for 4 weeks. Then, the body weight and liver weight were measured, and the liver index was calculated. At the same time, serum and liver samples were collected. The levels or activities of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fe2+ in the serum and TC, TG, free fatty acids (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and Fe2+ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species (ROS) content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2, SLC7A11, GPX4, transferrin receptor 1 (TFR1), and divalent metal transporter 1 (DMT1) in the liver were determined by Western blot. ResultsCompared with the control group, the model group showed increases in the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), and decreases in the activities of SOD, GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.05, P<0.01). Meanwhile, the liver tissue in the model group presented steatosis, iron deposition, mitochondrial shrinkage, and blurred or swollen mitochondrial cristae. Compared with the model group, all doses of Danggui Shaoyaosan reduced the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), while increasing the activities of SOD and GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.01). Furthermore, Danggui Shaoyaosan alleviated steatosis, iron deposition, and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.
8.Impact of rigid container material type and loading volume on the sterilization of thoracoscopic instruments
Xue'e FANG ; Yanjun MAO ; Qiuping ZHU ; Yanni CAI ; Jing SHU ; Guifen ZHANG ; Yichun JIN ; Minye TANG ; Ying TAO ; Huiting HU
Shanghai Journal of Preventive Medicine 2025;37(8):697-699
ObjectiveTo explore the impacts of material type and loading volume of rigid containers on the hydrogen peroxide low temperature plasma sterilization of thoracoscopic instruments, to identify the best rigid containers and loading volume of thoracoscopic instruments. MethodsThoracoscopic instruments sterilized by STERRAD® 100NX hydrogen peroxide low temperature plasma in Shanghai Pulmonary Hospital affiliated to Tongji University from August to September 2024 were selected as the research items. According to the material of rigid containers, the instruments were divided into polyethylene case group (A), stainless steel case group (B) and silicone resin case group (C). In terms of the loading volume, the rigid containers were divided into (loading capacity <80%) groups of 8, 10 and 12 instruments. The results of physical monitoring, the first type of chemical indicator card monitoring, and the five types of card luminal chemical process challenge device (PCD) monitoring of the 9 groups of A8, A10, A12, B8, B10, B12, C8, C10 and C12 were compared and evaluated. ResultsCompared to A8, A10 A12, C8, C10 or C12 groups, the thoracoscope instruments in the stainless steel containers in B8, B10 or B12 group had higher hydrogen peroxide concentrations and shorter elapsed time in the pressure check phases 1 and phases 2, with the differences statistically significant (P<0.05), followed by the silicone resin case group and the polyethylene case group. The nine groups of physical parameter monitoring, the first type of chemical indicator monitoring, and the five types of chemical PCD monitoring for lumen sterilization achieved 100% qualification rates, and there were no significant differences in the qualified rates of sterilization among the 9 groups (P>0.05). ConclusionWhen using hydrogen peroxide low temperature plasma to sterilize thoracoscopic instruments, it is recommended to use stainless steel or silicone resin rigid containers with a controlled loading capacity (≤12) to ensure optimal sterilization quality.
9.Educational Practice of Undergraduate Course Cell Biology at The University of Chinese Academy of Sciences
Jun-Cheng ZHAO ; Ying ZHANG ; Lei ZHANG ; Tao-Tao WEI
Progress in Biochemistry and Biophysics 2025;52(10):2677-2684
Cell Biology is one of the most rapidly developing branches of modern life sciences, characterized by distinct interdisciplinary integration. It provides theoretical foundations, experimental skills, and cutting-edge perspectives for undergraduate and graduate students in bioscience and related majors. Against the backdrop of higher education reform in the new era, the Cell Biology teaching team at the University of Chinese Academy of Sciences (UCAS) has restructured the curriculum. The course focuses on the fundamental structures and life processes of cells while incorporating ideological and political elements to foster students’ scientific mindset, patriotic sentiment, and social responsibility. By optimizing teaching design, enhancing practical components, and innovating assessment methods, the course integrates knowledge transfer, skill development, and value education. This paper summarizes preliminary experiences from the teaching development and educational practice of the undergraduate Cell Biology course at UCAS, serving as a reference for collaborative research- and teaching-oriented courses in science and engineering.
10.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

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