1.Analysis of risk factors and construction of risk prediction model for batroxobin-related severe hypofibrinogenemia
Le CAI ; Yuqing ZHAO ; Jiazhu CUI ; Xiao WEN ; Daihong GUO ; Man ZHU
China Pharmacy 2026;37(4):462-467
OBJECTIVE To investigate the clinical characteristics and risk factors for batroxobin-related severe hypofibrinogenemia (HFIB) and construct a risk prediction model. METHODS A retrospective analysis was conducted on inpatients treated with batroxobin in the First Medical Center of a tertiary hospital from January 1, 2020, to December 31, 2024. Patients were categorized into non-severe HFIB group and severe HFIB group based on the severity of HFIB. Univariate and multivariate Logistic regression analyses were performed to identify the independent influencing factors for batroxobin-related severe HFIB. A nomogram was developed using the “rms” package in R 4.5 software. The predictive performance of the model was evaluated using the receiver operating characteristic curve. Calibration was assessed via the Bootstrap resampling method, and goodness-of-fit was evaluated with the Hosmer-Lemeshow test. RESULTS A total of 1 472 patients were included in this study. Of these, 1 445 developed HFIB, yi elding an incidence of 98.17%. Furthermore, 895 were classified as severe HFIB, accounting for 60.80% of the cohort. Multivariate Logistic regression analysis showed that increased age, high initial dose per 10 kg body weight, use of maintenance dose, and concomitant glucocorticoid use were independent risk factors for batroxobin-related severe HFIB, while high baseline fibrinogen (FIB) level was identified as a protective factor. The model demonstrated an area under the curve of 0.760 (95% CI: 0.735-0.785). The mean absolute error of the calibration curve was 0.006. The P value of the Hosmer-Lemeshow test was 0.609. CONCLUSIONS Batroxobin can rapidly and significantly reduce FIB levels and carries a risk of inducing severe HFIB. Patients with advanced age, high initial dose per 10 kg body weight, use of maintenance dose and concomitant glucocorticoid use had a higher risk of batroxobin-related severe HFIB, while high baseline FIB level had a lower risk of batroxobin-related severe HFIB. The risk prediction model developed based on these factors can be used to predict the likelihood of batroxobin-related severe HFIB.
2.Establishment of a high-risk medication list and preventive and therapeutic measures for drug-induced hypofi-brinogenemia based on the Delphi method
Xiao WEN ; Le CAI ; Ning LIU ; Ao GAO ; Man ZHU
China Pharmacy 2026;37(7):848-853
OBJECTIVE To establish a high-risk medication list and preventive and therapeutic measures for drug-induced hypofibrinogenemia, and to provide a reference for the prevention and treatment of this condition. METHODS By integrating domestic and international case reports, retrospective case-control studies, and spontaneous adverse drug reaction reporting databases, 19 domestically marketed high-risk drugs for drug-induced hypofibrinogenemia were identified. Based on the clinical characteristics and mechanisms of these drugs, relevant risk factors were systematically reviewed, and existing treatment options were summarized, leading to the preliminary development of recommended preventive and therapeutic measures. A two-round Delphi consultation was conducted to evaluate, revise, and ultimately reach consensus on the preliminary findings, using a mean importance score of ≥3.5 points for indicators and a coefficient of variation <0.3 as screening criteria. RESULTS The coefficient of expert authority for both rounds of expert consultation was 0.904. In the first round, the Kendall coordination coefficients (Kendall’s W ) for the high-risk medication list and the proposed preventive and therapeutic measures were 0.390 and 0.223 ( P <0.05), respectively. In the second round, the Kendall’s W were 0.227 and 0.200 ( P <0.05), respectively. After two rounds of expert consultation and discussion, 11 high-risk drugs for drug-induced hypofibrinogenemia, represented by hemocoagulase and certain anti-infective agents, were ultimately identified, along with 5 preventive and therapeutic measures spanning the entire process of “pre-medication assessment, intra-medication monitoring, and bleeding event management”. CONCLUSIONS This study has established a scientific and reliable high-risk medication list, and corresponding preventive and therapeutic measures for drug-induced hypofibrinogenemia, providing a theoretical basis and practical support for the early identification, stratified management, and precise intervention of this condition.
3.Mechanism of alpha-mangostin improving apoptosis and inflammatory response in rat chondrocytes
Xiao-yuan MENG ; Meng-yu AN ; Zhi-gang WANG ; Le MA
Journal of Regional Anatomy and Operative Surgery 2025;34(9):759-764
Objective To explore the effects of alpha-mangostin(α-MG)on the in vitro osteoarthritis(OA)in rat chondrocytes induced by lipopolysaccharide(LPS)and the M1 polarization of macrophages.Methods An in vitro OA model of rat chondrocytes was induced by LPS.Both rat chondrocytes and macrophages were divided into the control group(normal culture),LPS group(stimulated with 1 μg/mL LPS for 24 hours),LPS+α-MG group(stimulated with 40 μmol/L α-MG combined with 1 μg/mL LPS for 24 hours),LPS+α-MG si-NC group(transfected with 70 μg/mL si-NC and stimulated with 40 μmol/L α-MG and 1 μg/mL LPS for 24 hours),and LPS+α-MG+si-BDNF group(transfected with 70 μg/mL si-BDNF and stimulated with 40 μmol/L α-MG and 1 μg/mL LPS for 24 hours).CCK-8 assay was used to detect the proliferative viability of chondrocytes and macrophages in each group,and flow cytometry was used to detect the apoptosis of chondrocytes and the polarization of macrophages.ELISA was used to detect the levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α of chondrocytes in each group.Western blot was used to detect the expression of BDNF,PI3K,and Akt in chondrocytes and macrophages.Results In chondrocytes,compared with the control group,the LPS group had decreased cell proliferation rate,increased cell apoptosis rate,down-regulated expression of BDNF,PI3K and Akt proteins,and up-regulated levels of IL-1β,IL-6 and TNF-α(P<0.05);compared with the LPS group,the LPS+α-MG group showed increased cell proliferation rate,decreased cell apoptosis rate,up-regulated expression of BDNF,PI3K and Akt proteins,and down-regulated levels of IL-1β,IL-6 and TNF-α(P<0.05);compared with the LPS+α-MG+si-NC group,the LPS+α-MG si-BDNF group demonstrated decreased cell proliferation rate,increased cell apoptosis rate,down-regulated expression of BDNF,PI3K and Akt proteins,and increased levels of IL-1β,IL-6 and TNF-α(P<0.05).In macrophages,compared with the control group,the LPS group had decreased cell proliferation rate,increased proportion of M1 cells,and down-regulated expression of BDNF,PI3K and Akt proteins(P<0.05);compared with the LPS group,the LPS+α-MG group showed increased cell proliferation rate,decreased proportion of M1 cells,and up-regulated expression of BDNF,PI3K and Akt proteins(P<0.05);compared with the LPS+α-MG+si-NC group,the LPS+α-MG+si-BDNF group showed decreased cell proliferation rate,increased proportion of M1 cells,and down-regulated expression of BDNF,PI3K and Akt proteins(P<0.05).Conclusion α-MG inhibits the M1 polarization of macrophages to improve the apoptosis and inflammation of rat chondrocytes by activating the BDNF/PI3K/Akt signaling pathway.
4.Diagnostic and prognostic value of the inflammatory load index in patients with gastric cancer
Jinhu TUO ; Yimin SHEN ; Le ZHANG ; Haipeng LIU ; Xiao CHEN
Journal of Clinical Surgery 2025;33(10):1086-1090
Objective To explore the value of inflammatory load index(IBI)in the diagnosis and prognosis of gastric cancer patients.Methods Clinical data of patients who underwent gastric cancer surgery in the Department of General Surgery of the Second Hospital of Lanzhou University from January 2016 to December 2018 were retrospectively analyzed,and the patients were divided into the high IBI group and the low IBI group based on the optimal cut-off value of IBI.ROC curve was used to determine the optimal cut-off value of IBI,and the survival curve was constructed using the Kaplan-Meier method,and the differences between groups were examined using the Log-rank test.Cox regression analysis was performed to study the prognostic factors of gastric cancer patients.Results The best cut-off value for IBI diagnosis was 8.796,and the best cut-off value for prognosis was 28.75.IBI was related to the clinical case characteristics of gastric cancer patients,such as surgical access,the degree of differentiation,CK7,CK20,LMP-1,and Ki-67(P<0.05).The results of univariate analysis showed that intraoperative bleeding,preoperative CEA,preoperative CA125,preoperative CA199,IBI,tumor diameter size,margins of incision,vascular invasion,nerve invasion,pT stage and pN stagewere the influencing factors on the prognosis of gastric cancer patients(P<0.05).The results of multifactorial regression analysis showed that intraoperative bleeding,preoperative CEA,preoperative CA199,IBI,tumor diameter size,pT stage and pN stagewere independent risk factors affecting the prognosis of gastric cancer patients(P<0.05).The median OS of patients in the high IBI group and low IBI group were 32.9 months and 74.8 months,respectively,with statistically significant differences(P<0.001).Conclusion IBI is an independent risk factor for poor prognosis of patients with gastric cancer,and it has a good predictive value in diagnosis and prognosis.
5.The impact mechanism of smart service construction on patient experience in Beijing municipal hospitals:A perspective based on the Technology Acceptance Model(TAM)
Yang JI ; Pan WANG ; Le-le LI ; Xiao-rui ZHU
Chinese Journal of Health Policy 2025;18(3):57-64
The intelligent development of the medical field is burgeoning,and smart healthcare has become a crucial driver for enhancing medical service efficiency and improving patient experience.However,the specific pathways through which smart healthcare improves patient experience have not been fully explained.To address this gap,this study utilizes micro-level individual data collected by the Beijing Hospitals Authority in 2023 from patients in municipal hospitals,employing the Technology Acceptance Model(TAM)to investigate the impact mechanisms of smart service construction on patient experience.The results indicate that smart services significantly improve patient experience by enhancing perceived ease of use,with this effect being particularly prominent during the treatment stage.Additionally,smart services demonstrate potential advantages in alleviating the"digital divide,"with a more pronounced optimization effect on the healthcare experience of elderly populations.Highly educated groups exhibit greater satisfaction and perceived benefits from smart services.
6.Establishment and application of a method for detecting Toxoplasma gondii based on recombinant polymerase amplification technology
Shao-zheng SONG ; Le-ying GU ; Ying-chao WU ; Ya-qin MENG ; Kang-ying YU ; Xiao-hua HUANG
Chinese Journal of Zoonoses 2025;41(2):107-112
To establish a method for detecting Toxoplasma gondii based on recombinant polymerase amplification(RPA)technology and apply it to clinical sample validation of pet cats.Using the 529 repeat sequence of the Toxoplasma gondii gene as the target gene sequence,primers and probes were designed,and the Rep-529 recombinant plasmid was constructed as the standard.A fluorescent RPA reaction system was established.Dilute the plasmid standard 10 times to different concentrations as the detection template for sensitivity testing;Specific testing was conducted using genomic DNA from several parasitic spe-cies,including Toxoplasma gondii,Cryptosporidium,Neosporidium,Trichinella spiralis,Giardia flagellata,Babesia bo-vis and Theileria annulata as templates;Simultaneously,fluorescence RPA and RT-PCR were used to detect 52 positive and 40 negative cats clinical samples,and the coincidence rate of the detection results of the two methods were compared and ana-lyzed.The RPA reaction system was successfully established using PTRep recombinant plasmid as the standard,ToxD-F/ToxD-R as the primer,and RepD-P as the fluorescent probe.The reaction temperature was constant at 39 ℃,the reaction time was 30 minutes,and the detection sensitivity was 1 copy/μL.There is no significant cross reaction with parasites such as Cryptosporidium,Neosporidium,Trichinella spiralis,Giardia,Babesia bovis and Theileria annulata,and the specificity is good.A total of 92 clinical fecal samples from cats were tested,and the positive coincidence rate of fluorescence RPA detection method was higher than that of conventional RT-PCR method(98.08%vs.82.69%),and the difference of the positive rate was not statistically significant(X2=1.392,P>0.05).The fluorescence RPA detection method for Toxoplasma gondii suc-cessfully established in this study has the characteristics of being fast,sensitive,specific,accurate,and reliable.It can be used as a rapid clinical detection kit for Toxoplasma gondii in cats and other animals,providing new technical support for the subsequent epidemiological monitoring and precise clinical diagnosis of toxoplasmosis in cats,other animals,and humans in the future.
7.Genetic imputation of lung cancer transcriptome,proteome and multiomics illuminates new therapeutic targets
Jian-le YANG ; Ting-yang LI ; Wen-feng GOU ; Bing-xiao ZHANG ; Yi-liang LI ; Wen-bin HOU
Chinese Pharmacological Bulletin 2025;41(6):1064-1071
Aim To infer novel therapeutic and phar-macological targets related to lung cancer treatment through multiomics approaches,so as to provide new directions for developing more personalized and effec-tive treatment strategies.Methods Genome-wide as-sociation study(GWAS)data analysis,pan-cancer,single-cell,transcriptomics,and protein-protein interac-tion analysis were employed in this study.Results We analyzed biomarkers and therapeutic targets associ-ated with lung cancer.The study identified key bio-markers closely related to lung cancer progression and explored the interrelationships between these biomark-ers and viral infections.According to KEGG pathway annotation,the number of genes related to metabolic processes increased significantly.In particular,metab-olites such as alanine and isoleucine emerged as pivotal factors in therapeutic interventions.The IgD+CD24+and IgD+CD24-B cell subsets were identified as cen-tral elements in immune evasion and treatment re-sponse.Concurrently,the Lachnospiraceae and Prevo-tella were shown to modulate host immune responses and the tumor microenvironment by regulating short-chain fatty acid levels,thereby opening novel avenues for cancer research.Conclusions Through mul-tiomics analysis combined with transcriptomics and pro-teomics analysis,we identify several potential therapeu-tic targets for lung cancer,providing key insights for developing novel treatment strategies.
8.In vitro fluorescent substrate assay for the activity of leucine aminopeptidase(LAP)in Echinococcus multilocularis
Jia-yu CHEN ; Yao DAI ; Shun-juan WANG ; Yang XIAO ; Xin-zong YAN ; Tong LIU ; Zhi-hao YUAN ; Kai-li SHI ; Run-le LI ; Feng TANG
Chinese Journal of Zoonoses 2025;41(1):23-31
This study was aimed at developing an in vitro fluorescent substrate assay for the activity of leucyl aminopeptid-ase(LAP)from Echinococcus multilocularis and comparing it with the chemical chromogenic substrate enzyme activity assay.Through the establishment of reaction conditions for the fluorescent substrate-based in vitro enzyme activity assay,we com-pared the differences between the fluorescent substrate L-Leucine-7-amido-4-methylocoumarin(Leu-AMC)and the chemical chromogenic substrate L-Leucine-4-nitroanilide(Leu-pNA)through molecular docking,inhibition rates,and precision measures.Molecular docking revealed that the fluorescent substrate Leu-AMC had higher affinity for the protein than the chemical chromogenic substrate Leu-pNA.Through analysis of the effects of varying reaction conditions on fluorescence intensi-ty,we optimized the fluorescent substrate enzyme activity assay to demonstrate favorable performance at a reaction temperature of 37℃,a pH of 9.0,a protein concentration of 800 nmol/L,and a reaction duration of 60 minutes.Leu-AMC exhibited significant and distinct responses at a 5 μmol/L substrate concentration,under varying substrate conditions.The fluo-rescent substrate assay demonstrated more significant intergroup differences than the chemical chromogenic substrate assay when various inhibitors were added.This study established a fluorescence-based enzyme activity assay for leucyl aminopeptidase from Echinococcus multilocularis by using Leu-AMC as the substrate;this method demonstrated a more significant intergroup difference and sensitivity than the chemical chromogenic substrate assay.
9.Role of GLUT1-dependent glycolysis in attenuation of oxygen-glucose deprivation-reoxygenation injury by dexmedetomidine in HK-2 cells
Wei DING ; Wen-hui TAO ; Yu-le WU ; Jian-xiao WU ; Jing-yi GUO ; Li-fang XIE ; Bing-qian FAN ; Xue-song GU ; Yang LI ; Xian-wen HU
Chinese Pharmacological Bulletin 2025;41(3):444-450
Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P<0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P<0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P<0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P<0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.
10.Diagnostic and prognostic value of the inflammatory load index in patients with gastric cancer
Jinhu TUO ; Yimin SHEN ; Le ZHANG ; Haipeng LIU ; Xiao CHEN
Journal of Clinical Surgery 2025;33(10):1086-1090
Objective To explore the value of inflammatory load index(IBI)in the diagnosis and prognosis of gastric cancer patients.Methods Clinical data of patients who underwent gastric cancer surgery in the Department of General Surgery of the Second Hospital of Lanzhou University from January 2016 to December 2018 were retrospectively analyzed,and the patients were divided into the high IBI group and the low IBI group based on the optimal cut-off value of IBI.ROC curve was used to determine the optimal cut-off value of IBI,and the survival curve was constructed using the Kaplan-Meier method,and the differences between groups were examined using the Log-rank test.Cox regression analysis was performed to study the prognostic factors of gastric cancer patients.Results The best cut-off value for IBI diagnosis was 8.796,and the best cut-off value for prognosis was 28.75.IBI was related to the clinical case characteristics of gastric cancer patients,such as surgical access,the degree of differentiation,CK7,CK20,LMP-1,and Ki-67(P<0.05).The results of univariate analysis showed that intraoperative bleeding,preoperative CEA,preoperative CA125,preoperative CA199,IBI,tumor diameter size,margins of incision,vascular invasion,nerve invasion,pT stage and pN stagewere the influencing factors on the prognosis of gastric cancer patients(P<0.05).The results of multifactorial regression analysis showed that intraoperative bleeding,preoperative CEA,preoperative CA199,IBI,tumor diameter size,pT stage and pN stagewere independent risk factors affecting the prognosis of gastric cancer patients(P<0.05).The median OS of patients in the high IBI group and low IBI group were 32.9 months and 74.8 months,respectively,with statistically significant differences(P<0.001).Conclusion IBI is an independent risk factor for poor prognosis of patients with gastric cancer,and it has a good predictive value in diagnosis and prognosis.

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