1.Dynamic changes of neuronal cells at different time points following cerebral ischemia-reperfusion injury in rats
Xu-Huan ZOU ; Rui LAN ; Xue-Qin FU ; Wei-Wei WANG ; Man-Man WANG ; Chen TANG ; Shuang LIU ; Hong-Yu LI ; Xiao-Ming SHEN
Chinese Pharmacological Bulletin 2024;40(6):1056-1066
Aim To investigate the dynamic changes of neuronal cells at different time points following acute cerebral ischemia-reperfusion injury by establishing a model of brain ischemia-reperfusion injury.Methods Thirty male Sprague-Dawley(SD)rats were ran-domly divided into six groups:sham group and cere-bral ischemia-reperfusion injury(IR)groups at differ-ent time points.Focal cerebral ischemia-reperfusion injury model was established using the middle cerebral artery occlusion(MCAO)technique.The Longa sco-ring method was used to assess neurobehavioral scores in rats.After successful model preparation,routine paraffin sections were made,and TUNEL staining and immunohistochemistry staining with NeuN antibody were performed to observe cell apoptosis and neuronal cell survival,respectively.Immunohistochemistry stai-ning was also performed to investigate the changes in glial fibrillary acidic protein(GFAP)as a marker for astrocytes,ionized calcium-binding adapter molecule 1(IBA-1)as a marker for microglia,and CD31 as a marker for endothelial cells at different time points.Results No significant changes were observed in neu-ronal cells of the sham group at different time points.In the cerebral ischemia-reperfusion injury groups,cell apoptosis was activated at IR3h and increased in quan-tity with morphological damage as time progressed.Ne-uN+neurons showed signs of ischemic injury after IR3h,with abnormal cell morphology.From 12 h,Ne-uN+neurons decreased in a time-dependent manner and reached their peak severity at 24 h.GFAP+astro-cytes decreased significantly after IR3h,while poorly labeled GFAP+astrocytes increased at IR 6 h and al-most disappeared in the infarcted area at 24 h and 48 h.The number of IBA-1+microglia-positive cells de-creased at IR3h,and their volume increased at IR6h.Microglial cell death was observed in the infarcted area at IR12h.CD31+endothelial cells around the infarc-ted cortex and striatum increased significantly after IR3h and persisted until 48 h.Conclusions After cerebral ischemia-reperfusion injury,the number of ap-optotic cells increases with the prolongation of time,and NeuN+neurons exhibit the most severe damage at 24 h.GFAP+astrocytes and microglial cells gradually die over time.The number of CD31+endothelial cells increases significantly around the infarcted cortex and striatum after 3 h of reperfusion and persists until 48 h.
2.Research progress of non-coding RNAs in regulating endothelial to mesenchymal transition in diseases
Wei QIN ; Zhi-Jie LUO ; Rui-Xue RONG ; Xue-Ying CHEN
Chinese Pharmacological Bulletin 2024;40(7):1215-1221
Endothelial to mesenchymal transition(EndMT)is a process in which endothelial cells lose their endothelial pheno-type and function and gain mesenchymal phenotype and func-tion.During the embryonic period,EndMT is an essential mech-anism for the development of heart valves,pulmonary arteries and aorta.In recent years,numerous studies have shown that EndMT is also involved in the occurrence and development of cardiovascular diseases such as atherosclerosis,cardiac fibrosis,pulmonary hypertension,and cerebrovascular malformation.In addition,EndMT is also an important mechanism of other organ fibrosis and tumors.Non-coding RNAs(ncRNAs)refer to RNAs that are transcribed from the genome but do not translate into proteins.Studies have shown that the abnormal expression of ncRNAs can participate in various diseases by regulating End-MT.Such ncRNAs with regulatory functions mainly include mi-croRNA(miRNA),long non-coding RNA(lncRNA)and cir-cular RNA(circRNA).This review summarizes the molecular mechanisms by which ncRNAs regulate EndMT in various disea-ses,looking forward to the application prospects of ncRNAs in the treatment of EndMT-related diseases.
3.A novel nomogram-based model to predict the postoperative overall survival in patients with gastric and colorectal cancer
Siwen WANG ; Kangjing XU ; Xuejin GAO ; Tingting GAO ; Guangming SUN ; Yaqin XIAO ; Haoyang WANG ; Chenghao ZENG ; Deshuai SONG ; Yupeng ZHANG ; Lingli HUANG ; Bo LIAN ; Jianjiao CHEN ; Dong GUO ; Zhenyi JIA ; Yong WANG ; Fangyou GONG ; Junde ZHOU ; Zhigang XUE ; Zhida CHEN ; Gang LI ; Mengbin LI ; Wei ZHAO ; Yanbing ZHOU ; Huanlong QIN ; Xiaoting WU ; Kunhua WANG ; Qiang CHI ; Jianchun YU ; Yun TANG ; Guoli LI ; Li ZHANG ; Xinying WANG
Chinese Journal of Clinical Nutrition 2024;32(3):138-149
Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.
4.Epidemic characteristics and food traceability of listeriosis in China,and the United States,and implications for China
Zhi-Fang ZHANG ; Xue-Jie LIU ; Sheng-Gen WU ; Qu-Wen LI ; Wei-Wei CHEN ; Yan-Qin DENG
Chinese Journal of Zoonoses 2024;40(7):636-643
This study analyzed and compared the epidemiological characteristics of foodborne listeriosis in the United States and China,to provide evidence for optimizing the listeriosis surveillance program in China.Descriptive statistical analysis was performed on the listeriosis monitoring data from 2009 to 2021 registered in the FDOSS system and the attribution estimates of Listeria monocytogenes(L.monocytogenes)from 2013 to 2021 published by IFSAC.Sporadic and outbreak data on listeriosis in China from the CNKI,Wanfang Medical,and CQVIP databases were collected.From 2009 to 2021,a total of 1 037 listeriosis cases were reported in the United States,including 902 hospitalizations and 165 deaths.The peak of cases caused by Lm con-taminated food was in July.The number of cases,hospitalizations,and deaths accounted for 18.4%(191/1 037),20.5%(185/902),and 22.4%(37/165)of the total,respectively.Most listeriosis outbreaks were attributed to three food groups:dairy products,vegetable crops,and fruits,with attribution percentages ranging from 73.8%to 89.6%.The overall incidence of list-eriosis in China was not high:619 cases were reported from 2009 to 2021,and only 177 cases were recorded in detailed inci-dence years;the maximum number of cases in 2018 was 26.A total of 220 cases were reported with detailed onset months;the highest number of cases in April was 30.Data on listeriosis cases in China are incomplete and sporadic,and only seven cases have been successfully traced to food.Listeriosis surveillance systems in the United States are relatively complete,and there are more foodborne outbreaks.Dairy products,vegetable row crops,and fruits are the most likely causes of disease outbreaks.Although only sporadic cases have been reported in China,China should take actions such as gradually improving multi-department coop-eration mechanisms,achieving data sharing and deepening data mining,and accelerating progress in the detection technology of food-borne pathogenic microorganisms,to ensure food safety and public health.
5.Molecular Diagnosis and Pedigree Analysis of Rare Mutations in Non-coding Region of HBA2 Gene
Li-Zhu CHEN ; Ti-Zhen YAN ; Jun HUANG ; Qing-Yan ZHONG ; Xue QIN ; Ning TANG ; Shi-Qiang LUO
Journal of Experimental Hematology 2024;32(3):940-944
Objective:To perform molecular diagnosis and pedigree analysis for one case with α-thalassemia who does not conform to the genetic laws,and explore the effects of a newly discovered rare mutation(HBA2:c.*12G>A)on clinical phenotypes.Methods:Blood samples of the proband and her family members were collected for blood routine analysis,and the hemoglobin components were analyzed by capillary electrophoresis.The common α-and β-globin gene loci in Chinese population were detected by conventional techniques(Gap-PCR,RDB-PCR).The α-globin gene sequences(HBA1,HBA2)were analyzed by Sanger sequencing.Results:By analyzing the test results of proband and her family members,the genotype of the proband was-α3,7/HBA2:c.*12G>A,her father was HBA2:c.*12G>A heterozygous mutation carrier.Conclusion:This study identifies a rare α-globin gene mutation(HBA2:c.*12G>A)that has not been reported before.It is found that heterozygous mutation carriers present with static α-thalassemia.
6.Clinical Characteristics and Prognosis of Myelodysplastic Syndromes Patients with RUNX1 Gene Mutation
Yi CHEN ; Yue-Ru JI ; Jing-Yi ZHANG ; Wei-Wei QIN ; Cang-Chun LIU ; Li LIU ; Xue-Qian YAN
Journal of Experimental Hematology 2024;32(4):1173-1180
Objective:To investigate the clinical characteristics and survival analysis of myelodysplastic syndromes(MDS)with RUNX1 gene mutation.Methods:Clinical data of 177 newly diagnosed MDS patients admitted to the Department of Hematology,the Second Affiliated Hospital of Air Force Military Medical University from October 1,2015 to October 31,2022 were retrospectively analyzed.Gene mutation detection was performed by second-generation sequencing technology,and clinical characteristics and prognosis of patients with RUNX1 gene mutation were analyzed.Results:A total of 30 cases(16.95%)of RUNX1 gene mutations were detected,including 15 missense mutations(50.0%),9 frameshift deletion mutations(30.0%),4 splice site mutations(13.3%),1 insertion mutation(3.3%),and 1 nonsense mutation(3.3%).Patients with RUNX1 mutations had a median age of 68.5 years at diagnosis(range:62.25-78.50 years old).There were no significantly differences between RUNX1 mutations and wild type patients in age distribution,gender,peripheral blood white blood cell count,hemoglobin level,bone marrow and peripheral blood blasts ratio,IPSS-R cytogenetics,IPSS-R stage,etc.(P>0.05).However,there were statistically significant differences in platelet count and whether complicated karyotype.Compared with patients without RUNX1 gene mutation,patients with RUNX1 gene mutation had lower platelet count(P=0.018),and were less likely to have complicated karyotype at initial diagnosis(P=0.01).Cox proportional hazards model analysis showed that when other co variates remained unchanged,the higher the platelet count,the better the survival of patients(HR=0.995,95%CI:0.990-0.999,P=0.036);In the IPSS-M prognostic stratification,keeping other covariates unchanged,the risk of progression or death of myelodysplastic syndrome was significantly lower in the medium to high-risk and low-risk groups compared with the high-risk group(HR=0.149,95%CI:0.031-0.721,P=0.018;HR=0.026,95%CI:0.003-0.234,P=0.001).Survival analysis showed that MDS patients with RUNX1 gene mutation had worse overall survival time(P<0.001).Patients with RUNX1 mutation had worse OS than non-mutation patients in the early WHO group.RUNX1 mutation and IPSS-M risk stratification mean OS and mean LFS were worse in low-risk patients than in non-mutated patients.Conclusion:RUNX1 gene mutation is an adverse prognostic factor in MDS patients,especially in the IPSS-M prognosis stratification group of low-risk,medium-low risk,medium-high risk and WHO classification of early patients.
7.Action mechanism of Huotu Jiji Pellets in the treatment of erectile dysfunction:An exploration based on network pharmacology and molecular docking
Xue-Qin CHEN ; Xuan ZHOU ; Hong-Ping SHEN ; Jia-Yi SONG ; Yun-Jie CHEN ; Yuan-Bin ZHANG ; Yi-Li CAI ; Yi YU ; Ya-Hua LIU
National Journal of Andrology 2024;30(3):241-248
Objective:To explore the potential action mechanism of Huotu Jiji Pellets(HJP)in the treatment of erectile dys-function(ED)based on network pharmacology and molecular docking.Methods:We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine(TCMIP)and the therapeutic target genes of ED from the data-bases of Genecards.Then we obtained the common targets of HJP and ED using the Venny software,constructed a protein-protein in-teraction(PPI)network of HJP acting on ED,and screened out the core targets with the Cytoscape software.Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software.Results:A total of 64 effective compounds,822 drug-related targets,1 783 disease-related targets and 320 common targets were obtained in this study.PPI network analysis showed that the core targets of HJP for ED included ESR1,HSP90AA1,SRC,and STAT3.GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus,positive regulation of kinase activity,and positive regu-lation of MAPK cascade.KEGG pathway enrichment analysis suggested that PI3K-Akt,apoptosis,MAPK,HIF-1,VEGF,autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED.Molecular docking prediction exhibited a good doc-king activity of the key active molecules of HJP with the core targets.Conclusion:This study showed that HJP acted on ED through multi-components,multi-targets and multi-pathways,which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.
8.Design of adjustable medical nursing support
Xiao-Chun JIAO ; Qin ZHOU ; Xiao-Qin CAO ; Meng-Dong LIU ; Bao-Li CHEN ; Jiao XUE
Chinese Medical Equipment Journal 2024;45(8):110-112
Objective To design an adjustable and removable nursing support for dressing patients with lower extremity injuries.Methods The adjustable nursing support was composed of a supporting plate,a cylinder,an upper adjustment mechanism and a lower fixation mechanism.The supporting plate was used to hold the leg of the patient,which had a curved st ruc t u re with a length from 40 to 80 cm;the cylinder was internally snap-fitted with a second slip sleeve to facilitate the adjustment of the support plate;the upper adjustment mechanism mainly consisted of a second sliding bar,a second cross bar and an adjustment plate;the lower fixation mechanism was mainly composed of a first clamping plate and a second clamping plate.Results The adjustable nursing support could be firmly fixed on the sickbed,and its height and angle could be adjusted according to the patient's wound position and subjective comfort.Conclusion The adjustable nursing support gains advantages in safety and patient comfort,and can be used for the dressing of patients with lower extremity injuries.[Chinese Medical Equipment Journal,2024,45(8):110-112]
9.Influencing factors of postpartum lower limb deep vein thrombosis in puerpera with gestational diabetes mellitus and construction of nomogram model
Chinese Journal of Postgraduates of Medicine 2024;47(9):808-813
Objective:To analyze the risk factors of postpartum lower limb deep vein thrombosis (DVT) in puerpera with gestational diabetes mellitus (GDM), and to construct a nomogram model.Methods:The clinical data of 163 puerpera with GDM in Tengzhou Central People′s Hospital from January 2021 to January 2023 were analyzed retrospectively. The puerpera were followed up for 2 months, in which 78 cases had postpartum lower limb DVT (DVT group) and 85 cases did not have postpartum lower limb DVT (non-DVT group). The basic data and perinatal indexes were recorded. The serum D-dimer level was detected by immunoturbidimetry, and serum C-reactive protein (CRP) level was detected by enzyme-linked immunosorbent assay. Multivariate Logistic regression was used to analyze the independent risk factors of lower limb DVT in puerpera with GDM. R3.6.3 software and "rms" package were used to construct a nomogram model for predicting lower limb DVT in puerpera with GDM, Hosmer-Lemeshow goodness of fit test and calibration curve were applied to evaluate the consistency of nomogram model, and receiver operating characteristic (ROC) curve was used to evaluate the discrimination of model.Results:The rates of body mass index before pregnancy ≥ 25 kg/m 2, history of hypertension, caesarean section, postpartum bed rest time ≥ 2 d, postpartum poor blood glucose control, history of lower limb varicose veins and D-dimer in DVT group were significantly higher than those in non-DVT group: 44.87% (35/78) vs. 27.06% (23/85), 39.74% (31/78) vs. 18.82% (16/85), 43.59% (34/78) vs. 25.88% (22/85), 34.62% (27/78) vs. 14.12% (12/85), 44.87% (35/78) vs. 20.00% (17/85), 35.90% (28/78) vs. 16.47% (14/85) and (582.74 ± 72.42) μg/L vs. (462.39 ± 57.65) μg/L, and there were statistical differences ( P<0.05 or <0.01); there were no statistical differences in age, smoking history, drinking history, birth history, lower limb lesional side, lower limb pain, lower limb swelling and CRP between the two groups ( P>0.05). Multivariate Logistic regression analysis result showed that body mass index before pregnancy ≥25 kg/m2, history of hypertension, caesarean section, postpartum bed rest time ≥ 2 d, poor postpartum blood glucose control, history of lower limb varicose veins and high level of D-dimer were the independent risk factors of lower limb DVT in puerperal with GDM ( OR = 3.267, 3.464, 5.078, 3.346, 3.174, 6.111 and 1.027; 95% CI 1.171 to 9.273, 1.183 to 10.146, 1.737 to 14.843, 1.064 to 10.523, 1.737 to 14.843, 1.727 to 21.629 and 1.017 to 1.036; P<0.05 or <0.01). A nomogram model was constructed based on body mass index before pregnancy, history of hypertension, caesarean section, postpartum bed rest time, postpartum blood glucose control, history of lower limb varicose veins and D-dimer. The ROC curve analysis result show that the nomogram model had good discrimination (the area under the curve was 0.930, 95% CI 0.880 to 0.964). The predicted value of calibration curve was basically consistent with the actual value, and the goodness of fit test of Hosmer-Lemeshow was in good agreement ( χ2 = 10.00, P = 0.265). Conclusions:The nomogram model based on the risk factors of postpartum lower limb DVT in puerperal with GDM has good consistency and discrimination, and it can effectively predict the occurrence of postpartum lower libm DVT in puerpera with GDM.
10.Progress in clinical application of individualized exercise prescription based on threshold in metabolic syndrome
Feng WANG ; Ruojiang LIU ; Jinmei QIN ; Wenxue CHEN ; Zhiqiang PEI ; Weizhen XUE
Chinese Journal of Arteriosclerosis 2024;32(11):1006-1012
Patients with metabolic syndrome(MS)are at potential risk for cardiovascular disease and have received increasing public and medical attention.Studies have shown that regular physical exercise can effectively regulate meta-bolic indicators such as blood pressure,blood sugar and blood lipids,and play a positive role in reducing the risk of cardio-vascular disease and improving the prognosis of patients.Exercise intensity has been identified as the most important as-pect in reducing the risk of cardiovascular death and all-cause mortality in exercise intervention.Therefore,the design of exercise prescription which is both scientific and satisfying individual differences has become the focus of research.Most of the current clinical studies are based on the percentage of exercise intensity as the basis for the formulation of standard-ized exercise prescription for MS patients,while the studies on the individualized threshold of exercise intensity based on cardiopulmonary exercise test(CPET)are still few.CPET has shown that individualized exercise prescription can effec-tively reduce body composition index,blood pressure and blood glucose,improve cardiorespiratory function,exercise en-durance and quality of life in MS patients.This paper reviewed the development of individualized exercise programs with different intensification according to threshold indexes in CPET,analyzed the intervention effects and possible mechanisms for MS patients and subgroups,and provided certain reference for the formulation and implementation of personalized exer-cise prescriptions for MS patients,and also provided references for in-depth research on individualized exercise intervention for MS.

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