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.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.
4.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.
5.Etiological characteristics of Salmonella enterica serovar Goldcoast isolates from Yangzhou,according to whole-genome sequencing
Ya-wen XU ; Yan WANG ; Rong-rong XU ; Rong-rong LU ; Hang-ning YING ; Le ZHOU
Chinese Journal of Zoonoses 2025;41(6):597-602
Salmonella enterica serovar Goldcoast isolates from Yangzhou were analyzed for assessment of their pathogenic and ge-nomic characteristics.From 2017 to 2023,eight strains were detected through foodborne disease surveillance and health check-ups.These strains exhibited resistance to two to seven antibiotic classes,and all strains bore a T57S mutation in the parC gene.Notably,50%(4/8)of the strains carried sulfonamide resistance genes(sul1 or sul3),and 37.5%(3/8)were positive for extended-spectrum beta-lactamase(ESBL)genes,including blaCTX-M-55 and blaTEM-1.Multilocus sequence typing(MLST)revealed that ST358(five strains)and ST2529(three strains)were the predominant sequence types,corresponding to CRISPR Ⅰ and Ⅱ groups,respectively.Single nucleotide polymorphism(SNP)phylogenetic analysis indicated a close genetic relationship between the case isolate Sal-2214 and strains from multiple regions,with a SNP difference≤20,thus suggesting potential inter-regional transmission.For example,one isolate from the stool of a 4-year-old child with diarrhea(Sal-2214)carried the beta-lactam resistance gene(blaCTX-M-55)and exhib-ited high resistance to cefotaxime(CTX)and ceftazidime(CAZ).These findings indicated that S.enterica Goldcoast emerged in Yang-zhou from 2022,and was characterized by multidrug resistance and a genetic relationship with strains from coastal regions.These find-ings highlight the need for enhanced resistance monitoring and trace-back studies to better understand the epidemiology and control the potential spread of this pathogen.
6.Establishment and validation of a predictive model for increased drainage volume after open transforaminal lumbar interbody fusion
Yin HU ; Hai-long YU ; Hong-wen GU ; Kang-en HAN ; Shi-lei TANG ; Yuan-hang ZHAO ; Zhi-hao ZHANG ; Jun-chao LI ; Le XING ; Hong-wei WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(11):981-986
Objective To analyze the risk factors for increased drainage volume after open transforaminal lumbar interbody fusion(TLIF),and to establish a predictive model and then validate it.Methods The clinical data of 680 patients who underwent open TLIF at the General Hospital of Northern Theater Command from January 2016 to December 2019 were collected and the patients were randomly divided into the training group(n=476)and the validation group(n=204).Taking the predictive factors screened out by LASSO regression analysis as independent variables,a multivariate Logistic regression predictive model was constructed.The model was internally validated through the receiver operating characteristic(ROC)curve,Hosmer-Lemeshow goodness-of-fit test,and calibration curve,and its clinical utility was assessed via decision curve analysis(DCA).Results LASSO regression analysis screened out four predictive variables:age,number of surgical segments,operative duration,and intraoperative blood loss.The multivariate Logistic regression predictive model demonstrated that age≥60 years,number of surgical segments≥4,operative duration≥2 hours,and intraoperative blood loss≥200 mL were independent influencing factors for the increased postoperative drainage volume in patients undergoing TLIF(P<0.05).ROC curve analysis revealed an area under the curve(AUC)of 0.816(95%CI:0.798 to 0.867)in the training group and 0.783(95%CI:0.685 to 0.823)in the validation group,indicating that the predictive model had good discriminatory ability.Additionally,the Hosmer-Lemeshow goodness-of-fit test and calibration curve indicated that the predictive model had a good degree of fit,and the predicted probability was basically consistent with the actual probability,demonstrating a good calibration.The DCA results confirmed that this predictive model could be applied in clinical practice.Conclusion The risk factors for increased drainage volume after open TLIF include age,number of surgical segments,operative duration,and intraoperative blood loss.The predictive model established based on these factors demonstrates good performance,and it can be applied in clinical guidance for the selection of drainage tube removal time after TLIF.
7.Clinical Efficacy of CAG Regimen Combined with Venetoclax,Chidamide,and Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia
Qing-Yang LIU ; Yu JING ; Meng LI ; Sai HUANG ; Yu-Chen LIU ; Ya-Nan WEN ; Jing-Jing YANG ; Wen-Jing GAO ; Ning LE ; Yi-Fan JIAO ; Xia-Wei ZHANG ; Li-Ping DOU
Journal of Experimental Hematology 2025;33(4):945-950
Objective:To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax,chidamide,and azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:15 elderly AML patients aged ≥ 60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax,chidamide and azacitidine,and the efficacy,treatment-related adverse events,overall survival(OS)and event-free survival(EFS)were analyzed.Results:After one course of treatment,11 out of 15 patients achieved complete response(CR),3 patients achieved CR with incomplete hematologic recovery(CRi),and 1 patient died due to prior infection before efficacy evaluation,and the overall response rate(ORR)was 93.3%(14/15).The median follow-up time was 131(19-275)days,with median OS and EFS both remaining unreached.Next-generation sequencing(NGS)analysis showed that among the 15 patients,13 were detected with gene mutations,and there were 7 genes with mutation frequencies of more than 10%,including ASXL1(4 cases),RUNX1(4 cases),BCOR(3 cases),DNMT3A(3 cases),STAG2(2 cases),IDH1/2(2 cases),and TET(2 cases).Among the 13 patients with detectable mutations,12 patients achieved composite response(CR+CRi).The average recovery time of white blood cell count was 14.6 days after chemotherapy,and the average recovery time of platelets was 7.7 days after chemotherapy.The main adverse event was myelosuppression,with 10 patients accompanied by infection.Except for 1 patient who died due to septic shock during chemotherapy,no patients experienced serious complications such as heart,liver,or kidney damage during the treatment process.Conclusion:The CACAG+V regimen,which combines the CAG regimen with venetoclax,chidamide,and azacitidine,can be applied in the treatment of elderly AML patients,demonstrating good safety and induction remission rate.
8.Analyzing Differences in Volatile Components of Citri Reticulatae Pericarpium Before and After Being Stir-fried with Halloysitum Rubrum Based on HS-GC-MS and Intelligent Sensory Technology
Li XIN ; Jiawen WEN ; Wenhui GONG ; Beibei ZHAO ; Shihao YAN ; Huashi CHEN ; Haiping LE ; Jinlian ZHANG ; Yanhua XUE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):157-162
ObjectiveTo analyze the differences in color, odor and volatile components of Citri Reticulatae Pericarpium(CRP) before and after being stir-fried with Halloysitum Rubrum, and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry(HS-GC-MS), and the volatile components were analyzed by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). According to the principle of variable importance in the projection(VIP) value>1.5, volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose, the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum, of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected, including α-pinene, β-myrcene, linalool, sabinene, ocimene isomer mixture, A-ocimene, and δ-elemene. After being processed with Halloysitum Rubrum, the brightness value(L*), yellow-blue value(b*) and total chromatic value(E*ab) of CRP were decreased(P<0.01), and red-green value(a*) was increased(P<0.01), the response values of S4, S5, S10 and S13 sensors were significantly increased(P<0.05), and the response values of S3 and S8 sensors were significantly decreased(P<0.05). Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L* and E*ab, but positively correlated with a*. Sabinene was positively correlated with L* and E*ab. Linalool was positively correlated with L* and E*ab, and negatively correlated with a*. The ocimene isomer mixture was positively correlated with the L*. ConclusionAfter being processed with Halloysitum Rubrum, the appearance color, odor and volatile components of CRP change significantly, and α-pinene, β-myrcene, sabinene, linalool and A-ocimene are the characteristic volatile components before and after processing, which can provide references for the quality evaluation and clinical application of CRP and its processed products.
9.Analyzing Differences in Volatile Components of Citri Reticulatae Pericarpium Before and After Being Stir-fried with Halloysitum Rubrum Based on HS-GC-MS and Intelligent Sensory Technology
Li XIN ; Jiawen WEN ; Wenhui GONG ; Beibei ZHAO ; Shihao YAN ; Huashi CHEN ; Haiping LE ; Jinlian ZHANG ; Yanhua XUE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):157-162
ObjectiveTo analyze the differences in color, odor and volatile components of Citri Reticulatae Pericarpium(CRP) before and after being stir-fried with Halloysitum Rubrum, and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry(HS-GC-MS), and the volatile components were analyzed by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). According to the principle of variable importance in the projection(VIP) value>1.5, volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose, the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum, of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected, including α-pinene, β-myrcene, linalool, sabinene, ocimene isomer mixture, A-ocimene, and δ-elemene. After being processed with Halloysitum Rubrum, the brightness value(L*), yellow-blue value(b*) and total chromatic value(E*ab) of CRP were decreased(P<0.01), and red-green value(a*) was increased(P<0.01), the response values of S4, S5, S10 and S13 sensors were significantly increased(P<0.05), and the response values of S3 and S8 sensors were significantly decreased(P<0.05). Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L* and E*ab, but positively correlated with a*. Sabinene was positively correlated with L* and E*ab. Linalool was positively correlated with L* and E*ab, and negatively correlated with a*. The ocimene isomer mixture was positively correlated with the L*. ConclusionAfter being processed with Halloysitum Rubrum, the appearance color, odor and volatile components of CRP change significantly, and α-pinene, β-myrcene, sabinene, linalool and A-ocimene are the characteristic volatile components before and after processing, which can provide references for the quality evaluation and clinical application of CRP and its processed products.
10.Regulated cell death in age-related macular degeneration: Regulatory mechanisms and therapeutic potential.
Le-Le ZHANG ; Jia-Mei YU ; Zhong-Xi FAN ; Wen-Qi XIE ; Liang ZOU ; Feiya SHENG
Journal of Pharmaceutical Analysis 2025;15(11):101285-101285
Age-related macular degeneration (AMD) represents a predominant cause of blindness among older adults, with limited therapeutic options currently available. Oxidative stress, inflammation, and retinal pigment epithelium injury are recognized as key contributors to the pathogenesis of AMD. Regulated cell death plays a pivotal role in mediating cellular responses to stress, maintaining tissue homeostasis, and contributing to disease progression. Recent research has elucidated several regulated cell death pathways-such as apoptosis, ferroptosis, pyroptosis, necroptosis, and autophagy-that may contribute to the progression of AMD owing to cell death in the retinal pigment epithelium. These discoveries open new avenues for therapeutic interventions in patients with AMD. In this review, we provide a comprehensive summary and analysis of the latest advancements regarding the relationship between regulated cell death and AMD. Moreover, we examined the therapeutic potential of targeting regulated cell death pathways for the treatment and prevention of AMD, highlighting their roles as promising targets for future therapeutic strategies.

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