1.Mechanism of Yishen Qubi Tongluo Formula (益肾祛痹通络方) in the Treatment of Rheumatoid Arthritis:Based on Network Pharmacology,Molecular Docking and Experimental Verification
Liuping XU ; Canyu YANG ; Ying LU ; Lisha MO ; Qiang CHI ; Yuan XIA ; Shuijuan LIU ; Mingliang QIU
Journal of Traditional Chinese Medicine 2026;67(5):557-566
ObjectiveTo explore the mechanism of Yishen Qubi Tongluo Formula (益肾祛痹通络方, YQTF) in the treatment of rheumatoid arthritis(RA). MethodsNetwork pharmacology was employed to retrieve and screen the active components and potential targets of YQTF as well as RA-related targets using databases including TCMSP, BATMAN, ETCM and GEO. The intersection of targets related to active components and RA-related targets was identified, and a protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed, and a drug-active component-common target network of YQTF in the treatment of RA was established. The core components of YQTF were molecularly docked with key targets. Human rheumatoid arthritis synovial fibroblast cell line MH7A was divided into blank group, model group, methotrexate group and YQTF group. The blank group was cultured with 10% fetal bovine serum, while the other three groups were stimulated with 10 μg/L of recombinant human tumor necrosis factor-α (TNF-α) for 24 h to establish the RA cell model. On this basis, the methotrexate group was treated with methotrexate suspension at a concentration of 20 μmol/L, and the YQTF group was treated with 10% YQTF-medicated serum. After 48 h of intervention, the levels of TNF-α and interleukin-17A(IL-17A)contents in cell supernatants were detected by enzyme-linked immunosorbent assay (ELISA), and mRNA expressions of phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT) and mammalian target of rapamycin(mTOR) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). ResultsNetwork pharmacological analysis identified 209 active components and 583 potential target genes of YQTF, as well as 818 RA-related targets. A total of 29 common targets were obtained from the intersection of drug-related targets and RA-related targets. Quercetin,β-sitosterol, kaempferol, stigmasterol and luteolin were the core active components of YQTF for the treatment of RA, while matrix metalloproteinase-9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2), Toll-like receptor 4 (TLR4), tumor protein p53 (TP53) and transcription factor AP-1 subunit JUN were the key targets. The GO and KEGG pathway enrichment analysis showed that the involved biological processes and pathways were mainly associated with antioxidant responses, PI3K-AKT signaling pathway and Toll-like receptor (TLR) signaling pathway. Molecular docking results showed that MMP9 and PTGS2 exhibited high binding affinities with quercetin, β-sitosterol, kaempferol, stigmasterol and luteolin; TLR4 exhibited high binding activities with β-sitosterol, stigmasterol and luteolin; and TP53 showed high binding affinity with luteolin. The results of cell experiments showed that compared with the control group, the contents of TNF-α and IL-17A as well as the mRNA expressions of AKT and mTOR in the model group significantly increased (P<0.05 or P<0.01). Compared with the model group, all the above indicators significantly decreased in the YQTF group, while the contents of TNF-α and the mRNA expression of AKT significantly decreased in the methotrexate group (P<0.05 or P<0.01). ConclusionThe mechanism of YQTF in the treatment of RA may be associated with reducing inflammatory cytokine secretion and inhibiting the activation of the PI3K-AKT-mTOR signaling pathway.
2.Assessment of ochratoxin A exposure in the diets of pregnant women in Shanghai
Kailin LI ; Renjie QI ; Hua CAI ; Xia SONG ; Jingjin YANG ; Danping QIU ; Zhenni ZHU ; Yi HE ; Baozhang LUO ; Hong LIU
Shanghai Journal of Preventive Medicine 2026;38(3):181-186
ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE1), and the margin of exposure for carcinogenic toxicity (MOE2). An MOE1 greater than 200 and an MOE2 greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP50 values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)-1, respectively, and the P95 values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)-1, respectively. For pregnant women in Shanghai in 2023, the P50 values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)-1, respectively, and the P95 values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.
3.Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture-dislocation in adults (version 2025)
Qingde WANG ; Tongwei CHU ; Jian DONG ; Liangjie DU ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Yong HAI ; Da HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Fang LI ; Feng LI ; Li LI ; Weishi LI ; Fangcai LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Xuhua LU ; Keya MAO ; Xuexiao MA ; Yong QIU ; Limin RONG ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Bing WANG ; Linfeng WANG ; Yu WANG ; Qinghe WANG ; Jigong WU ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Yong YANG ; Qiang YANG ; Cao YANG ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Zezhang ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Yan ZENG ; Dingjun HAO ; Baorong HE ; Wei MEI
Chinese Journal of Trauma 2025;41(3):243-252
Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.
4.Interaction between influenza A virus nucleoprotein and TRIM25 protein
Xin-yan HU ; Qian-yun LIU ; Le-le AN ; Qiu-ju LAN ; Xiao-xia MA
Chinese Journal of Zoonoses 2025;41(3):219-226
This study was aimed at exploring the interaction between the nucleoprotein(NP)of influenza A virus(IAV)and TRIM25.The physicochemical properties and protein structure of IAV NP protein were analyzed through bioinformatics methods.The interaction between IAV NP and TRIM25 proteins was simulated with molecular docking techniques,and the in-teraction sites were predicted.With the cDNA of the A/Puerto Rico/8/1934(H1N1)PR8 strain as the template,the NP pro-tein was cloned into the eukaryotic expression vector pCMV-C-Flag through PCR amplification,the eukaryotic expression re-combinant plasmid pCMV-Flag-NP was constructed,and the expression was further verified.The protein expression levels of pCMV-Flag-NP and pCMV-HA-TRIM25 were detected at various time periods.The interaction between NP protein and TRIM25 protein was verified by co-immunoprecipitation.The co-localization of NP protein and TRIM25 protein in cells was ob-served with laser confocal microscopy.Bioinformatics analysis revealed that the NP protein consists of 498 amino acids and 20 amino acids,and is an unstable hydrophilic protein.The NP protein has multiple phosphorylation sites,as well as N-glycosyla-tion and O-glycosylation sites,but no transmembrane domain or signal peptide domain.Additionally,the NP protein's second-ary structure consists of a high proportion of alpha-helices and random coils.The molecular docking prediction results indicated that IAV NP interacts with TRIM25 protein and has multiple potential interaction sites,including the 233rd alanine,234th ala-nine,236th lysine,and 440th alanine of the NP protein.After successfully constructing and expressing the IAV NP protein,we verified the interaction between IAV NP and TRIM25 protein by immunoprecipitation and laser confocal microscopy obser-vations.Our results together suggested that the structure of the IAV NP protein is closely related to its function,and its im-portance to the virus is clear.In addition,the interaction between IAV NP and TRIM25 protein may be associated with TRIM25's anti-influenza virus mechanism.Further in-depth research may provide new ideas for anti-influenza virus strategies.
5.Study on in vitro cytotoxicity of novel iron-based biodegradable biomaterials
Xiao-xiao GAI ; Yi-xin ZHU ; Xiao-xia SUN ; Qiu-jin QU ; Gui ZHANG ; Cheng-hu LIU
Chinese Medical Equipment Journal 2025;46(3):35-41
Objective To propose an in vitro cytotoxicity evaluation method for novel iron-based biodegradable mateirals focusing on their degrading characteristics.Methods Half-finished scaffolds of nitrided iron tubes with a higher iron content of over 99%and a nitrogen content of 0.03%to 0.20%were selected as test samples,and based on the treatment mode were divided into an anaerobic treatment group,a non-anaerobic treatment group,a non-anaerobic treatment with removed iron particle group and a non-anaerobic treatment with plate-washing group.The anaerobic treatment group was processed in an anaerobic workstation;the conventional treatment group underwent standard handling in a biosafety cabinet;the conventional treatment with removed iron particle group was subjected to iron particle elimination using a Midimacs Starting Kit manual sorter after conventional treatment;and the conventional treatment with plate-washing group was rinsed with 0.9%sodium chloride injection before tetrazolium salt reagent treatment.Different extraction media(simulated body fluid,cell culture medium,phosphate buffer and 0.9%sodium chloride injection)were used for the immersion treatment of the test samples in each group to compare the effects of the degradation products on the survival rate of L929 cells.Results The anaerobic treatment group and the conventional treatment with removed iron particle group exhibited no detectable cytotoxicity.Trypan blue staining revealed significant cytotoxicity in the conventional treatment group,while false-negative results emerged due to interactions between the tetrazolium salt reagent and degradation products.In the non-anaerobic treatment with washing plate group,the false negative from iron particles was eliminated while potential cytotoxicity was showen,and the result accuracy was affected because some cells were washed out.Conclusion The proposed method can be used for the in vitro cytotoxicity evaluation,and facilitates the safety evaluation of the application of such materials.[Chinese Medical Equipment Journal,2025,46(3):35-41]
6.A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement.
Jianbing WU ; Duorui JI ; Weijie JIAO ; Jian JIA ; Jiayi ZHU ; Taijun HANG ; Xijing CHEN ; Yang DING ; Yuwen XU ; Xinglong CHANG ; Liang LI ; Qiu LIU ; Yumei CAO ; Yan ZHONG ; Xia SUN ; Qingming GUO ; Tuanjie WANG ; Zhenzhong WANG ; Ya LING ; Wei XIAO ; Zhangjian HUANG ; Yihua ZHANG
Acta Pharmaceutica Sinica B 2025;15(2):1070-1083
Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.
7.Integrative transcriptomic and epigenomic analysis identifies BCL6B as a novel regulator of human pluripotent stem cell to endothelial differentiation.
Yonglin ZHU ; Jinyang LIU ; Jia WANG ; Shuangyuan DING ; Hui QIU ; Xia CHEN ; Jianying GUO ; Peiliang WANG ; Xingwu ZHANG ; Fengzhi ZHANG ; Rujin HUANG ; Fuyu DUAN ; Lin WANG ; Jie NA
Protein & Cell 2025;16(11):985-990
8.Study on in vitro cytotoxicity of novel iron-based biodegradable biomaterials
Xiao-xiao GAI ; Yi-xin ZHU ; Xiao-xia SUN ; Qiu-jin QU ; Gui ZHANG ; Cheng-hu LIU
Chinese Medical Equipment Journal 2025;46(3):35-41
Objective To propose an in vitro cytotoxicity evaluation method for novel iron-based biodegradable mateirals focusing on their degrading characteristics.Methods Half-finished scaffolds of nitrided iron tubes with a higher iron content of over 99%and a nitrogen content of 0.03%to 0.20%were selected as test samples,and based on the treatment mode were divided into an anaerobic treatment group,a non-anaerobic treatment group,a non-anaerobic treatment with removed iron particle group and a non-anaerobic treatment with plate-washing group.The anaerobic treatment group was processed in an anaerobic workstation;the conventional treatment group underwent standard handling in a biosafety cabinet;the conventional treatment with removed iron particle group was subjected to iron particle elimination using a Midimacs Starting Kit manual sorter after conventional treatment;and the conventional treatment with plate-washing group was rinsed with 0.9%sodium chloride injection before tetrazolium salt reagent treatment.Different extraction media(simulated body fluid,cell culture medium,phosphate buffer and 0.9%sodium chloride injection)were used for the immersion treatment of the test samples in each group to compare the effects of the degradation products on the survival rate of L929 cells.Results The anaerobic treatment group and the conventional treatment with removed iron particle group exhibited no detectable cytotoxicity.Trypan blue staining revealed significant cytotoxicity in the conventional treatment group,while false-negative results emerged due to interactions between the tetrazolium salt reagent and degradation products.In the non-anaerobic treatment with washing plate group,the false negative from iron particles was eliminated while potential cytotoxicity was showen,and the result accuracy was affected because some cells were washed out.Conclusion The proposed method can be used for the in vitro cytotoxicity evaluation,and facilitates the safety evaluation of the application of such materials.[Chinese Medical Equipment Journal,2025,46(3):35-41]
9.Expressions of miR-29b and Klotho in peripheral blood of chronic obstructive pulmonary disease patients complicated with pulmonary infection and their clinical significance
Zhenzhen GUI ; Jie QIU ; Jie LIU ; Xia CAO
Chinese Journal of Nosocomiology 2025;35(6):840-844
OBJECTIVE To explore the expression levels of microribonucleic acid(miR)-29b and soluble Klotho protein in peripheral blood of the chronic obstructive pulmonary disease(COPD)patients complicated with pulmo-nary infection and analyze the clinical significance.METHODS The clinical data were retrospectively collected from 139 patients with COPD who were treated in Ningxia Medical University General Hospital from Feb.2022 to Feb.2024.The patients were divided into the infection group with 41 cases and the no infection group with 98 cases ac-cording to the status of pulmonary infection.The distribution of pathogens isolated from the patients of the infec-tion group was observed.The levels of serum miR-29b and Klotho were compared between the infection group and the no infection group or of the infection group before and after the anti-infection treatment.The efficiencies of ser-um miR-29b and Klotho in prediction of pulmonary infection were analyzed by means of receiver operating charac-teristic(ROC)curves.RESULTS Totally 46 strains of pathogens were isolated from the infection group,67.39%of which were gram-negative bacteria,26.09%were gram-positive bacteria,and 6.52%were fungi.There were significant differences in the levels of serum miR-29b and Klotho between the infection group and the no infection group(P<0.05);the expression level of serum miR-29b of the patients in the infection group who were effective for the anti-infection treatment was lower after the treatment than before the treatment,while the expression level of Klotho was higher after the treatment than before the treatment(P<0.05);the expression level of miR-29b of the patients effective for the treatment was lower than that of the patients ineffective for the treatment,while the expression level of Klotho of the patients effective for the treatment was higher than that of the patients ineffective for the treatment(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of the joint detec-tion of serum miR-29b and Klotho was 0.927 in prediction of pulmonary infection in the COPD patients,higher than 0.837 and 0.852 of the single detection.CONCLUSIONS The COPD patients complicated with pulmonary in-fection show the high expression level of serum miR-29b and low expression level of Klotho.The joint detection of the two indexes has high efficiency in prediction of pulmonary infection in the COPD patients,which can be used as reliable indexes for assessment of the curative effect after the anti-infection treatment.
10.Clinical effect and safety of modified injection approach in temporal area depression
Mingzi ZHANG ; Zhijin LI ; Wenbo XIA ; Zikai QIU ; Xuda MA ; Sichao CHEN ; Loubin SI ; Zhifei LIU ; Xiaojun WANG
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(2):138-142
Objective:To investigate the clinical efficacy and safety of a modified injection technique for improving temporal concavity deformities.Methods:A prospective study was conducted on 157 female patients who underwent temporal concavity augmentation at the Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, from June 2019 to June 2022. The patients were aged from 32 to 48 (38.2±3.1) years. Granular fat was obtained through liposuction and purification. Using the midpoint of the frontotemporal line as the entry point, the granular fat tissue was injected evenly at multiple points under the skin and superficial temporal fascia. Additional granular fat was injected in the temporal edge area to ensure a smooth appearance. The visual analogue scale (VAS) was used to assess the patients' intraoperative pain levels. Follow-up visits were conducted for one year postoperatively to assess patient satisfaction with the improvement in temporal concavity, local pigmentation, and fine lines in the lateral orbital area based on preoperative and postoperative photographs. Complications, including swelling, ecchymosis, hematoma, fat embolism, infection, fat liquefaction, and subcutaneous induration, were recorded immediately after surgery and at the one-year follow-up.Results:All the 157 patients experienced mild swelling in the injection area postoperatively, which resolved within 3 to 6 days. Ecchymosis occurred in 15 patients and spontaneously resolved within 10 days. Eleven patients had asymmetry in the filled area, with 3 recovering after local massage and observation, and the remaining 8 undergoing a second fat grafting procedure. A total of 25 patients underwent more than two fat grafting procedures, including 4 who underwent three procedures. Mild local hematoma occurred in 3 patients postoperatively. The intraoperative pain VAS was (1.8±0.5) score. After treatment, the improvement scores for temporal concavity, local pigmentation, and fine lines in the lateral orbital area were (7.4±0.7), (6.8±0.7), and (7.9±0.7) scores, respectively. After one year of follow-up, no complications such as fat embolism, infection, fat liquefaction, or subcutaneous induration were observed in the 157 patients.Conclusion:The modified injection technique for improving temporal concavity deformities is safe and effective, with high patient satisfaction.

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