1.Supramolecular prodrug inspiried by the Rhizoma Coptidis-Fructus Mume herbal pair alleviated inflammatory diseases by inhibiting pyroptosis
Wenhui QIAN ; Bei ZHANG ; Ming GAO ; Yuting WANG ; Jiachen SHEN ; Dongbing LIANG ; Chao WANG ; Wei WEI ; Xing PAN ; Qiuying YAN ; Dongdong SUN ; Dong ZHU ; Haibo CHENG
Journal of Pharmaceutical Analysis 2025;15(2):411-424
Sustained inflammatory responses are closely related to various severe diseases,and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment.Natural products have garnered considerable concern for the treatment of inflammation.Huanglian-Wumei decoction(HLWMD)is a classic prescription used for treating inflammatory diseases,but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated.Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory,we successfully obtained berberine(BBR)-chlorogenic acid(CGA)supramolecular(BCS),which is an herbal pair from HLWMD.Using a series of characterization methods,we confirmed the self-assembly mechanism of BCS.BBR and CGA were self-assembled and stacked into amphiphilic spherical supra-molecules in a 2:1 molar ratio,driven by electrostatic interactions,hydrophobic interactions,and π-πstacking;the hydrophilic fragments of CGA were outside,and the hydrophobic fragments of BBR were inside.This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules.Compared with free molecules,BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide(LPS)-induced pyroptosis.Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB(NF-κB)p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.
2.Perturbation response scanning of drug-target networks:Drug repurposing for multiple sclerosis
Yitan LU ; Ziyun ZHOU ; Qi LI ; Bin YANG ; Xing XU ; Yu ZHU ; Mengjun XIE ; Yuwan QI ; Fei XIAO ; Wenying YAN ; Zhongjie LIANG ; Qifei CONG ; Guang HU
Journal of Pharmaceutical Analysis 2025;15(6):1277-1290
Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.
3.Comprehensive Evaluation of the Medical Service Capacity of the First Batch of County-Level Medical Subcenters in Guizhou Province
Keren ZHANG ; Juan JIN ; Xing CUI ; Xingyue ZHU ; Xun HE ; Xiaofan YAN
Chinese Health Economics 2025;44(3):89-93
Objective:To comprehensively evaluate the medical service capacity of 50 first batch county medical sub-centers in Guizhou Province,it provides the basis and references for further research on the construction of county medical sub-centers in Guizhou province and improvement of the medical service capacity of township health centers(community health service centers)in Guizhou Province.Methods:Through TOPSIS method,RSR method and the fuzzy combination method,the medical service capacity of the primary medical institutions in the county medical sub-center was evaluated.Results:Among the first batch of 50 county-level secondary medical centers,the top three in terms of medical service capabilities were G18,G6,and G36,while the last three were G27,G15,and G22.Conclusion:There were significant differences in the medical and health service capacity among the 50 sub-centers.It is suggested to continue to increase the support for sub-centers,formulate relevant policies according to local conditions and time conditions,and improve the medical service capacity of sub-centers.
4.Development and Validation of a Risk Prediction Model for Sudden Cardiac Arrest in Children With Congenital Heart Disease After Surgery
Yafei LIU ; Haiying XING ; Qian ZHANG ; Wolei FENG ; Fangfei ZHU ; Yanjiao WANG ; Shiqiong LIU ; Yan MA
Chinese Circulation Journal 2025;40(3):254-260
Objectives:To develop a risk prediction model for sudden cardiac arrest(CA)in children with congenital heart disease(CHD)after surgery and validate its predictive efficacy,providing a reference for the prevention of CA and risk stratification.Methods:Medical records were retrospectively analyzed from 5 029 children who were hospitalized in Fuwai Hospital,Chinese Academy of Medical Sciences from January 1,2020 to May 31,2022 and underwent CHD surgery.The patients were divided into two groups:those who experienced CA after surgery(n=33)and those who did not(n=4 996).A random forest model for predicting the risk of postoperative CA was established on the training dataset using R software,and the predictive effect of the model was evaluated on the validation dataset using indicators of predictive accuracy,sensitivity,specificity,positive predictive value,negative predictive value.Results:The incidence of CA in this center was 0.66%,survival rate is 72.73%.Using the random forest algorithm,the importance of risk factors for sudden CA after CHD surgery was ranked by variable importance scoring,with the following top 6 important predictive variables:blood pressure,lactate levels,heart rate,cardiac rhythm,arterial oxygen partial pressure,and blood oxygen saturation on the first day after surgery.The model established by the random forest algorithm on the training set was validated on the test set,yielding a predictive accuracy of 99.8%,specificity of 87.5%,sensitivity of 99.9%,kappa coefficient of 0.8225,positive predictive value of 99.9%,and negative predictive value of 77.8%.Conclusions:The established prediction model of sudden CA in children with CHD after surgery had good performance.It might help medical staffon decision making of early intervention,preventing the occurrence of CA,and improving the outcomes of children with high risk of CA post surgery.
5.Expert consensus on pre-hospital emergency management of heatstroke(2024 edition)
Tao WANG ; Yue ZHAO ; Meng WANG ; Hai-Yan ZHU ; Chen LI ; Yu-Jian CHEN ; Qin-Rui XING ; Qing SONG
Medical Journal of Chinese People's Liberation Army 2025;50(3):245-253
Heatstroke,especially in high-temperature and high-humidity environments,is a life-threatening acute heat-injury disease that seriously endangers human health.Timely and effective on-site treatment is crucial for patients'survival and prognosis.Early recognition,rapid assessment,and on-site cooling are the core of pre-hospital treatment of heatstroke.Currently,there is a lack of standardized application procedures for pre-hospital emergency care of heatstroke.Therefore,the"Expert Consensus on Pre-hospital Emergency Management of Heatstroke(2024 edition)"was initiated by the Expert Group on Heatstroke Prevention of the People's Liberation Army and developed in collaboration with experts from local pre-hospital emergency care,emergency departments,and intensive care units.This consensus focuses on heatstroke prevention,on-site and ambulance-based treatment,and early emergency room interventions,and puts forward 10 evidence-based recommendations,aiming to provide a reference for scientific and standardized pre-hospital emergency care of heatstroke.
6.Effects of alcoholism on nonalcoholic fatty liver disease
Hao-qing ZHU ; Yan-ling WU ; Ji-xing NAN ; Li-hua LIAN
Chinese Pharmacological Bulletin 2025;41(7):1227-1230
NAFLD is the most prevalent chronic liver disease,which has become a world public health issue and the incidence rate is also showing an increasing trend.A series of liver disea-ses,such as simple fatty liver disease,NASH,liver cirrhosis,liv-er failure and liver cancer,can be collectively referred to as NAFLD.Through the study of numerous factors that influence the production of NAFLD,it has been found that the main patho-logical mechanism is excessive synthesis of fat,which is difficult to be transported into the blood,causing massive lipid accumula-tion.Alcohol has a direct damaging effect on liver and will in-hibit the breakdown of liver fat,eventually forming AFLD.How-ever,it is still controversial whether alcohol has a synergistic effect on NAFLD onset.This article provides a review on the effect of alcohol intake on NAFLD and its potential mechanisms of action.
7.Creation and Exploration of the"Organized Fill-in-the-Blank Format"Disci-pline Construction Model for Forensic Medicine in the New Era
Zhi-Wen WEI ; Hong-Xing WANG ; Jun-Hong SUN ; Hao-Liang FAN ; Hong-Liang SU ; Le-Le WANG ; Wen-Ting HE ; Zhe CHEN ; Jie ZHANG ; Xiang-Jie GUO ; Ji LI ; Geng-Qian ZHANG ; Xin-Hua LIANG ; Jiang-Wei YAN ; Qiang-Qiang ZHANG ; Cai-Rong GAO ; Ying-Yuan WANG ; Hong-Wei WANG ; Jun XIE ; Bo-Feng ZHU ; Ke-Ming YUN
Journal of Forensic Medicine 2025;41(1):25-29
Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.
8.Clinical trial on alendronate sodium combined with teriparatide in the treatment of patients with postmenopausal osteoporosis patients
Yan ZHU ; Lei-yu QIU ; Huan-xing LU
The Chinese Journal of Clinical Pharmacology 2025;41(1):26-30
Objective To explore the clinical efficacy and safety of alendronate sodium tablet combined with injection of recombinant teriparatide and calcium carbonate D3 tablet in the treatment of postmenopausal osteoporosis(PMDP).Methods The patients with postmenopausal osteoporosis were divided into control group and treatment group according to the cohort method according to the treatment regimen.The control group was treated with calcium carbonate D3 tablet(600 mg,1 tablet a day)and alendronate sodium tablet(70 mg,once a week),while the treatment group was given injection of reacombinant teriparatide(200 U/20 μg,20 μg every day)on the basis of the control group.Both groups were continuously treated for 6 months.The clinical efficacy was compared after 6 months of treatment.The bone mineral density(BMD)of lumbar spine,total hip and femoral neck and levels of bone metabolism indicators[osteocalcin(OCN),tartrate-resistant acid phosphatase-5b(TRAP-5b),procollagen type Ⅰ amino-terminal propeptide(PINP),C-terminal cross-linked peptide of type Ⅰ collagen(CTX-Ⅰ)]before treatment and after 6 months of treatment and bone pain[visual analogue scale(VAS)]and quality of life[European Foundation Osteoporosis Quality of Life Questionnaire(ECOS-16)]before treatment and after 3 and 6 months of treatment were recorded,and the adverse drug reactions within 6 months of treatment were compared.Results Fifty-two cases in treatment group and 64 cases in control group were enrolled.After treatment,the total effective rates in treatment group and control group were 87.80%(36 cases/41 cases)and 68.29%(28 cases/41 cases),respectively(P<0.05).The BMD values of lumbar spine in treatment group and control group after treatment were(0.69±0.15)and(0.79±0.18)g·cm-2;the BMD values of total hip were(0.70±0.11)and(0.77±0.15)g·cm-2;the BMD values of femoral neck were(0.79±0.19)and(0.87±0.15)g·cm-2,respectively;the OCN levels were(7.42±1.53)and(5.37±1.16)μg·L-1;the PINP levels were(85.31±5.66)and(76.30±5.49)ng·mL-1;the TRAP-5b levels were(3.27±0.46)and(5.16±0.72)U·L-1;the CTX-Ⅰ levels were(3.37±0.54)and(5.08±0.70)ng·mL-1;the VAS scores were(1.48±0.13)and(2.07±0.24)points;the ECOS-16 scores were(24.84±4.62)and(32.71±6.07)points,and there were statistical differences in the above indicators between treatment group and control group(all P<0.05).The main adverse drug reactions in treatment group were rash,dizziness and limb pain,and the main adverse drug reactions in control group were rash,dizziness,nausea,and limb pain,and the total incidence rates of adverse reactions in treatment group and control group were 12.20%(5 cases/41 cases)and 19.51%(8 cases/41 cases)(P>0.05).Conclusion Alendronate sodium tablet combined with injection of recombinant teriparatide and calcium carbonate D3 tablet has a significant short-term efficacy on PMOP patients,and it can help to enhance the bone mineral density,reduce the symptoms of bone pain,and relieve the osteoporosis.
9.Evidence-based guideline for diagnosis and early fixation of severe open tibiofibular fractures (version 2025)
Yongjun RUI ; Yongqing XU ; Qingtang ZHU ; Xin WANG ; Zhao XIE ; Shanlin CHEN ; Jingyi MI ; Xianyou ZHENG ; Juyu TANG ; Xiaoheng DING ; Aixi YU ; Tao SONG ; Jianxi HOU ; Jian QI ; Xinyu FAN ; Jun FEI ; Lin GUO ; Xingwen HAN ; Weixu LI ; Aiguo WANG ; Yun XIE ; Tao XING ; Meng LI ; Baoqing YU ; Yan ZHUANG ; Xiaoqing HE ; Tao SUN ; Pengcheng LI ; Jihui JU ; Hongxiang ZHOU ; Haidong REN ; Guangyue ZHAO ; Gang ZHAO ; Yongwei WU ; Jun LIU ; Yunhong MA ; Yapeng WANG
Chinese Journal of Trauma 2025;41(11):1021-1034
Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.
10.Prognostic value of prolymphocyte percentage in chronic lymphocytic leukemia
Zhaoliang ZHANG ; Jiahao ZHOU ; Lingxiao XING ; Yan WANG ; Tonglu QIU ; Rong WANG ; Hui WANG ; Lei FAN ; Huayuan ZHU ; Yi MIAO ; Jianyong LI
Chinese Journal of Hematology 2025;46(2):140-146
Objective:To investigate the impact of peripheral blood prolymphocyte percentage on the prognosis of patients with chronic lymphocytic leukemia (CLL) .Methods:This study included 300 patients diagnosed with CLL at the Department of Hematology of Jiangsu Provincial People’s Hospital from October 2011 to December 2020. The association between prolymphocyte percentage and other parameters was analyzed, and the optimal cutoff prolymphocyte percentage was determined by X-tile analysis. Further survival analysis and prognostic model construction were used to validate the predictive value of prolymphocyte percentage.Results:Of the 300 eligible patients with CLL who were enrolled, 50 received Bruton tyrosine kinase inhibitors (BTKi) as first-line treatment. The group with higher prolymphocyte percentage comprised more patients in the advanced stages ( P=0.010) and had higher β 2-microglobulin ( P<0.001), unmutated immunoglobulin heavy-chain variable region gene ( P<0.001), and TP53 aberration ( P=0.004). The optimal cutoff percentage of prolymphocytes was 1%. Patients with a prolymphocyte percentage >1% had significantly shorter treatment-free survival (TFS) ( P<0.001) and overall survival time ( P=0.007) than patients with a prolymphocyte percentage ≤1%. On multivariate analysis, prolymphocyte percentage >1% tended to have an independent prognostic value for TFS [ HR=1.405 (95% CI 0.971~2.032), P=0.071]. Compared with the nomogram of CLL international prognostic index (CLL-IPI) alone, the nomogram of CLL-IPI combined with prolymphocyte percentage showed better discrimination (area under the curve: 0.778 vs. 0.637; P=0.006). In addition, patients with a prolymphocyte percentage >1% were more likely to progress after BTKi treatment ( P=0.038) . Conclusion:Peripheral blood prolymphocyte percentage was associated with various clinical and biological parameters and prognosis among patients with treatment-naive CLL.

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