1.Exploring Chemical Constituent Distribution in Blood/Brain(Hippocampus) and Emotional Regulatory Effect of Raw and Vinegar-processed Products of Citri Reticulatae Pericarpium Viride
Yi BAO ; Yonggui SONG ; Qianmin LI ; Zhifu AI ; Genhua ZHU ; Ming YANG ; Huanhua XU ; Qin ZHENG ; Yiting HUANG ; Zihan GAO ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):189-197
ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride(CRPV), and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts, as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards, databases, and relevant literature were utilized for compound annotation, with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups, including the blank group, model group, diazepam group(2.5 mg·kg-1), raw CRPV low/high dose groups(0.6, 1.2 g·kg-1), and vinegar-processed CRPV low/high dose groups(0.6, 1.2 g·kg-1), with 10 mice per group. Except for the blank group, all other groups underwent chronic restraint stress(2 h·d-1) for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling, with a total treatment duration of 10 d. Following model-based drug administration, mice underwent open-field, forced swimming, and elevated plus maze tests. After anesthesia with isoflurane, whole brains were collected from each group of mice, and hippocampi were dissected. Reactive oxygen species(ROS) level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei(NeuN) and peroxisome proliferator-activated receptor alpha(PPARα) expressions in hippocampal tissue. Then, pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders, exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV, with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds, including 20 flavonoids, 20 flavonoid glycosides, 3 triterpenes, 3 phenolic acids, 1 alkaloid, and 6 other compounds. Twenty-one components were detected in blood(15 methoxyflavones, 4 flavonoid glycosides, and 2 phenolic acids), with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues(all common to both forms). In regulating emotional disorders, Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology, particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS(P<0.05). ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing, but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway, thereby negatively regulating ROS generation in the hippocampus, reducing oxidative stress, and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards, pharmacodynamic material research, and active drug development of raw and vinegar-processed CRPV.
2.Effect of fluoride exposure on endoplasmic reticulum-mitochondrial calcium transfer and apoptosis in primary nerve cells
Yongheng LU ; Shuang ZHU ; Feiyan ZHAO ; Fujun AI ; Yanjie LIU ; Yangting DONG ; Zhizhong GUAN ; Na WEI
Chinese Journal of Tissue Engineering Research 2026;30(1):111-119
BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90%,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P<0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P<0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P<0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P<0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P<0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P<0.05),the mitochondrial membrane potential decreased(P<0.01),and the degree of damage in the high-fluoride group was more obvious(P<0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.
3.Effect of fluoride exposure on endoplasmic reticulum-mitochondrial calcium transfer and apoptosis in primary nerve cells
Yongheng LU ; Shuang ZHU ; Feiyan ZHAO ; Fujun AI ; Yanjie LIU ; Yangting DONG ; Zhizhong GUAN ; Na WEI
Chinese Journal of Tissue Engineering Research 2026;30(1):111-119
BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90%,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P<0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P<0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P<0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P<0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P<0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P<0.05),the mitochondrial membrane potential decreased(P<0.01),and the degree of damage in the high-fluoride group was more obvious(P<0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.
4.Screening of Antidepressant Active Components from Curcumae Rhizoma and Its Mechanism in Regulating Nrf2/GPX4/GSH Pathway
Yonggui SONG ; Delin DUAN ; Meixizi LAI ; Yali LIU ; Zhifu AI ; Genhua ZHU ; Huanhua XU ; Qin ZHENG ; Ming YANG ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):211-221
ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma, and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione(GSH) peroxidase 4(GPX4)/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma, including curcumol, curgerenone, curdione, curzerene, curcumenol, curcumenone, dehydrocurdione, isocurcumenol, furanodienone, furanodiene and zederone, were detected using 1,1-diphenyl-2-picrylhydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt(ABTS) radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress(CUMS), and W1118 wild-type male D. melanogaster were randomly divided into blank group, model group, curcumol group, curgerenone group, curdione group, curzerene group, curcumenol group,curcumenone group, dehydrocurdione group, isocurcumenol group, furanodienone group, furanodiene group, zederone group and fluoxetine group(10 μmol·L-1). The treatment groups received a dose of 0.1 g·L-1 of 11 characteristic components from Curcumae Rhizoma, while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test, climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry(LC-MS) was used to detect the levels of 5-hydroxytryptamine(5-HT) and dopamine(DA) in the brain of D. melanogaster, and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators, resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition, a mouse depression model was established by CUMS, and C57BL/6J mice were randomly divided into blank group, model group, low and high dose groups of curzerene(0.5, 1 mg·kg-1), and fluoxetine group(10 mg·kg-1) to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species(ROS) in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate(ATP), superoxide dismutase(SOD), catalase(CAT) and GSH. Transmission electron microscope(TEM) was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein, and Nrf2 inhibitor(ML385) was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction(Real-time PCR) was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals, and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group, the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center(P<0.01), as well as a significant increase in immobility time in the forced swimming and tail suspension tests(P<0.01), and the ROS content in hippocampus significantly elevated(P<0.01), while the ATP content significantly reduced(P<0.01). In the hippocampal neurons of the model group, mitochondrial cristae were disordered, with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased(P<0.05), and the antioxidant enzymes SOD, CAT and GSH contents were also significantly reduced(P<0.05, P<0.01), and the gene expression levels of GPX1, GPX4 and GPX7 were significantly decreased(P<0.01). Compared with the model group, the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center(P<0.05), as well as a significant decrease in immobility time in the forced swimming and tail suspension tests(P<0.05, P<0.01). The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced(P<0.01), while the ATP content was significantly increased(P<0.05). The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated, and the expression level of Nrf2 protein was significantly increased(P<0.05). The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.01), while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.05), while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.
5.Changing prevalence and antibiotic resistance profiles of carbapenem-resistant Enterobacterales in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Wenxiang JI ; Tong JIANG ; Jilu SHEN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yuanhong XU ; Ying HUANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yingchun XU ; Xiaojiang ZHANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Hong ZHANG ; Chun WANG ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(4):445-454
Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43%(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38%,9.73%,and 8.47%,respectively.The prevalence of CRE strains in Escherichia coli was 1.99%.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)%,followed by blood(20.88±3.40)%and urine(18.40±3.45)%.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)%.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.
6.Changing distribution and antibiotic resistance profiles of the respiratory bacterial isolates in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Ying FU ; Yunsong YU ; Jie LIN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE ; Wenhui HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(4):431-444
Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6%of the isolates were Gram-negative bacteria and 17.4%were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)%and(94.0±0.1)%,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P<0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9%.The prevalence of penicillin-resistant S.pneumoniae was 1.4%.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8%and 41.3%,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7%,20.8%,9.4%,29.8%,and 73.3%,respectively.The prevalence of β-lactamase was 96.1%in Moraxella catarrhalis and 60.0%in Haemophilus influenzae.The H.influenzae isolates from children(<18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P<0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.
7.MRI subtraction technique for evaluating efficacy of systemic therapy for advanced hepatocellular carcinoma and predicting prognosis after combining with surgery
Tao XIANG ; Bing YUAN ; Xiaohui LI ; Jinghui DONG ; Zhenyu ZHU ; Dingkun LIU ; Jian YANG ; Danni AI ; Jiangtao LIU ; Feng DUAN
Chinese Journal of Interventional Imaging and Therapy 2025;22(3):210-215
Objective To explore the value of MRI subtraction technique(ST)for evaluating the efficacy of systemic therapy for advanced hepatocellular carcinoma(HCC)and predicting prognosis after combining with surgery.Methods Totally 35 patients with 39 HCC lesions who received systemic therapy+radical resection were retrospectively collected.Based on preoperative MRI,tumor activity ratio(recorded as tumor activityST)was obtained with ST,while tumor activity value(recorded as tumor activitypathology)was obtained through postoperative pathology,and their correlation was analyzed.The patients were regularly followed up after surgery,and the survival data were recorded.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of tumor activityST for predicting patients'survival status.Then the patients were divided into survival benefit group and no survival benefit group according to the cut-off value,and survival analysis was conducted.Results Tumor activityST was positively correlated with tumor activitypathology(r=0.900,P<0.001).The median follow-up time was 32.93 months,during which 8 patients died,and the median survival time was 29.9 months.The area under the curve(AUC)of tumor activityST for predicting patients'survival status was 0.67,and the cut-off value was 0.36.Thirty patients with tumor activityST<0.36 were enrolled in survival benefit group,while 5 patients≥0.36 were collected in no survival benefit group.The overall survival in survival benefit group was longer than that in no survival benefit group(P<0.001).Conclusion MRI ST could be used to non-invasively evaluate the efficacy of systemic therapy for advanced HCC and predict prognosis after combining with surgery.
8.Distribution and resistance profiles of bacterial strains isolated from cerebrospinal fluid in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Juan MA ; Lixia ZHANG ; Yang YANG ; Fupin HU ; Demei ZHU ; Han SHEN ; Wanqing ZHOU ; Wenen LIU ; Yanming LI ; Yi XIE ; Mei KANG ; Dawen GUO ; Jinying ZHAO ; Zhidong HU ; Jin LI ; Shanmei WANG ; Yafei CHU ; Yunsong YU ; Jie LIN ; Yingchun XU ; Xiaojiang ZHANG ; Jihong LI ; Bin SHAN ; Yan DU ; Ping JI ; Fengbo ZHANG ; Chao ZHUO ; Danhong SU ; Lianhua WEI ; Fengmei ZOU ; Xiaobo MA ; Yanping ZHENG ; Yuanhong XU ; Ying HUANG ; Yunzhuo CHU ; Sufei TIAN ; Hua YU ; Xiangning HUANG ; Sufang GUO ; Xuesong XU ; Chao YAN ; Fangfang HU ; Yan JIN ; Chunhong SHAO ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Fang DONG ; Zhiyong LÜ ; Lei ZHU ; Jinhua MENG ; Shuping ZHOU ; Yan ZHOU ; Chuanqing WANG ; Pan FU ; Yunjian HU ; Xiaoman AI ; Ziyong SUN ; Zhongju CHEN ; Hong ZHANG ; Chun WANG ; Yuxing NI ; Jingyong SUN ; Kaizhen WEN ; Yirong ZHANG ; Ruyi GUO ; Yan ZHU ; Jinju DUAN ; Jianbang KANG ; Xuefei HU ; Shifu WANG ; Yunsheng CHEN ; Qing MENG ; Yong ZHAO ; Ping GONG ; Ruizhong WANG ; Hua FANG ; Jilu SHEN ; Jiangshan LIU ; Hongqin GU ; Jiao FENG ; Shunhong XUE ; Bixia YU ; Wen HE ; Lin JIANG ; Longfeng LIAO ; Chunlei YUE ; Wenhui HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(3):279-289
Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3%)and from outpatient and emergency care patients(4.7%).Overall,19.6%of the isolates were from children and 80.4%were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0%and 32.0%,respectively.Coagulase negative Staphylococcus accounted for 73.0%of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2%in children and 45.6%in adults.The prevalence of MRCNS was 67.6%in adults and 69.5%in children.A small number of vancomycin-resistant Enterococcus faecium(2.2%)and linezolid-resistant Enterococcus faecalis(3.1%)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2%and 76.4%in children,70.5%and 63.5%in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3%and 47.7%in children,6.4%and 47.9%in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0%and 37.1%in children,81.7%and 39.9%in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.
9.Changing antibiotic resistance profiles of the bacterial strains isolated from geriatric patients in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Xiaoman AI ; Yunjian HU ; Chunyue GE ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Hui LI ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(3):290-302
Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3%of the total number of clinical isolates from all patients.Overall,21.8%of the 514 715 strains were gram-positive bacteria,and 78.2%were gram-negative bacteria.Majority(90.9%)of the strains were isolated from inpatients.About 42.9%of the strains were isolated from respiratory specimens,and 22.9%were isolated from urine.More than half(60.7%)of the strains were isolated from male patients,and 39.3%isolated from females.About 51.1%of the strains were isolated from patients aged 65-<75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8%in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2%,1.5%)and linezolid-resistant strains(3.4%,0.3%)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3%,4.0%,and 1.7%in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2%)to imipenem and meropenem were 20.9%and 22.3%,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7%-7.8%of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6%)to imipenem and meropenem were 68.4%and 70.6%respectively,while 28.5%and 24.3%of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-<75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.
10.Efficacy and safety of daratumumab-based regimens for treatment of relapsed/refractory multiple myeloma
Shangyi AI ; Shaolong HE ; Tao WANG ; Qiujuan ZHU ; Zhilin GAO ; Jie ZHAO ; Weiwei TIAN
Journal of Leukemia & Lymphoma 2025;34(4):208-212
Objective:To investigate the efficacy and safety of daratumumab-based regimens for the treatment of relapsed/refractory multiple myeloma (RRMM).Methods:A retrospective case series study was conducted. Thirty-seven RRMM patients treated with daratumumab-based regimens at Shanxi Bethune Hospital from January 2017 to November 2023 were selected, and their efficacy and adverse reactions were analyzed.Results:The median age [ M ( Q1, Q3)] of 37 RRMM patients was 62 (56, 68) years, the median number of previous treatment lines was 2 (1, 3.5) lines, 12 cases (32.4%) had extramedullary lesions, 12 cases (32.4%) had lactate dehydrogenase (LDH) ≥ 245 U/L, and 11 cases (29.7%) had previously received the third-line or more treatment. Among 27 patients who completed fluorescence in situ hybridization testing, 8 cases (29.6%) had high-risk cytogenetical changes. The median time from diagnosis to use of daratumumab was 23.1 (5.9, 52.0) months. The overall response rate (ORR) of 37 RRMM patients after treatment was 75.7% (28/37), with ORR of 88.0% (22/25) and 50.0% (6/12) for patients without and with extramedullary lesions, respectively, and the difference was statistically significant ( P = 0.036). The median follow-up time was 12.3 (4.6, 22.7) months, the median progression-free survival (PFS) time was 7.8 months (95% CI: 2.0- 13.7 months), and the median overall survival (OS) time was 22.4 months (95% CI: 17.5-29.5 months). The median PFS time for patients without and with extramedullary lesions was 11.8 and 4.2 months, and the median OS time was 23.5 and 8.3 months, respectively, and the differences in PFS and OS between the two were statistically significant (both P < 0.05); the median PFS time for patients with LDH ≥ 245 U/L and < 245 U/L was 6.5 and 11.9 months, and the median OS time was 30.2 and 12.1 months, respectively, and the differences in PFS and OS between the two were statistically significant (both P < 0.05). The incidence of non-hematological adverse reactions was 32.4% (12/37), with the most common being infusion-related adverse reactions (29.7%, 11/37), all of which were grade 1-2; the incidence of ≥ grade 3 hematological adverse reactions was 13.5% (5/37), with thrombocytopenia being the most common (8.1%, 3/37). Conclusions:The ORR of RRMM patients treated with daratumumab-based regimens is high, and the adverse reactions are tolerable.

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