1.Endogenous FGF21 attenuates blood-brain barrier disruption in penumbra after delayed recanalization in MCAO rats through FGFR1/PI3K/Akt pathway.
Wen ZHENG ; Wenjun LI ; Yini ZENG ; Hui YUAN ; Heng YANG ; Ru CHEN ; Anding ZHU ; Jinze WU ; Zhi SONG ; Wenguang YAN
Journal of Central South University(Medical Sciences) 2023;48(5):648-662
OBJECTIVES:
Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke. Previous studies revealed that delayed recanalization might cause serious ischemia/reperfusion injury. However, plenty of evidences showed delayed recanalization improved neurological outcomes in acute ischemic stroke. This study aims to explore the role of delayed recanalization on blood-brain barrier (BBB) in the penumbra (surrounding ischemic core) and neurological outcomes after middle cerebral artery occlusion (MCAO).
METHODS:
Recanalization was performed on the 3rd day after MCAO. BBB disruption was tested by Western blotting, Evans blue dye, and immunofluorescence staining. Infarct volume and neurological outcomes were evaluated on the 7th day after MCAO. The expression of fibroblast growth factor 21 (FGF21), fibroblast growth factor receptor 1 (FGFR1), phosphatidylinositol-3-kinase (PI3K), and serine/threonine kinase (Akt) in the penumbra were observed by immunofluorescence staining and/or Western blotting.
RESULTS:
The extraversion of Evans blue, IgG, and albumin increased surrounding ischemic core after MCAO, but significantly decreased after recanalization. The expression of Claudin-5, Occludin, and zona occludens 1 (ZO-1) decreased surrounding ischemic core after MCAO, but significantly increased after recanalization. Infarct volume reduced and neurological outcomes improved following recanalization (on the 7th day after MCAO). The expressions of Claudin-5, Occludin, and ZO-1 decreased surrounding ischemic core following MCAO, which were up-regulated corresponding to the increases of FGF21, p-FGFR1, PI3K, and p-Akt after recanalization. Intra-cerebroventricular injection of FGFR1 inhibitor SU5402 down-regulated the expression of PI3K, p-Akt, Occludin, Claudin-5, and ZO-1 in the penumbra, which weakened the beneficial effects of recanalization on neurological outcomes after MCAO.
CONCLUSIONS
Delayed recanalization on the 3rd day after MCAO increases endogenous FGF21 in the penumbra and activates FGFR1/PI3K/Akt pathway, which attenuates BBB disruption in the penumbra and improves neurobehavior in MCAO rats.
Animals
;
Rats
;
Blood-Brain Barrier/metabolism*
;
Brain Ischemia
;
Claudin-5/metabolism*
;
Infarction, Middle Cerebral Artery/metabolism*
;
Ischemic Stroke/metabolism*
;
Occludin/metabolism*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Rats, Sprague-Dawley
;
Receptor, Fibroblast Growth Factor, Type 1/metabolism*
;
Reperfusion Injury/metabolism*
2.Incidence of leptospirosis in Fujian province, 2015-2020.
Guo Ying XU ; Han Song ZHU ; Wei Jun LIU ; Zhi Wei ZENG ; Jia Xiong WANG ; Teng Wei HAN ; Shu Heng ZHOU ; Jing LIU ; Fang Zhen XIAO
Chinese Journal of Epidemiology 2022;43(4):548-553
Objective: To analyze the incidence of leptospirosis in Fujian province from 2015 to 2020 and provide the scientific evidences for the risk assessment, prevention and control of leptospirosis. Methods: The incidence data of leptospirosis in Fujian during 2015-2020 were collected from China Information System for Disease Control and Prevention for a descriptive analysis, and software ArcGIS 10.3.1 was used for spatial autocorrelation analysis, and rats were captured in 17 surveillance areas during the same period, and the rat organs were collected for pathogen culture, the level of Leptospira antibody was detected in serum samples of rats, healthy population and the serum samples of patients sent by the hospitals. The infection status of Leptospira in human and rats were analyzed. Results: The incidence of leptospirosis in Fujian showed a downward trend from 2015 to 2020. A total of 176 cases of leptospirosis were reported. There were obvious seasonality and bimodal distribution. The majority of cases were farmers, accounting for 49.43% (87/176). Most cases were aged 30-69 years (85.80%, 151/176). The male to female ratio of the cases was 3.51∶1 (137∶39). Spatial autocorrelation analysis showed that leptospirosis had high or low clustering areas. From 2015 to 2020, the average capture rate of rats in 17 surveillance areas was 6.96% (1 519/21 838), Rattus losea, Rattus flavipectus and Niviventer fulvescens were the main species. The average positive rate of Leptospira antibody in rats was 28.64% (252/880). Java and Autumnalis were the predominant serogroups, accounting for 56.75% (143/252) and 17.46% (44/252), respectively. The average positive rate of Leptospira antibody in healthy population was 16.13% (254/1 575), and Autumnalis and Australis were the predominant serogroups, accounting for 71.65% (182/254). The confirmation rate of leptospirosis in patient serum samples sent by the hospitals was 2.23% (188/8 431), Autumnalis (56.38%, 106/188) and Hebdomadis (19.68%, 37/188) were the major serogroups. Conclusions: The incidence of leptospirosis in Fujian showed a downward trend from 2015 to 2020, there were obvious area clustering and seasonality. The high clustering areas were mainly distributed in northern, western and central Fujian. Java and Autumnalis were the predominant serogroups in rats. The infection rate in healthy population decreased year by year. Autumnalis and Hebdomadis were the main serogroups in population in Fujian.
Animals
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Antibodies, Bacterial
;
Female
;
Humans
;
Incidence
;
Leptospira
;
Leptospirosis/epidemiology*
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Male
;
Rats
;
Serogroup
3.Controversy and progress on whether to retain left colonic artery in radical resection of rectal cancer.
Chao Hui ZHEN ; Jin Feng ZHU ; Ruo Dai WU ; Biao ZHENG ; Heng Liang ZHU ; Zhi Wu ZENG ; Rui LIANG ; Shi Jian YI ; Zhong LIU ; Peng GONG
Chinese Journal of Gastrointestinal Surgery 2021;24(8):735-740
Japanese Society for Cancer of the Colon and Rectum (JSCCR) guideline 2019 recommended that lymph node dissection for advanced rectal cancer should include the lymphatic adipose tissue at the root of the inferior mesenteric vessels, but the ligation site of the inferior mesenteric artery (IMA) was not determined, and the NCCN guideline did not indicate clearly whether to retain the left colonic artery (LCA). Controversy over whether to retain LCA is no more than whether it can reduce the incidence of anastomotic complications or postoperative functional damage without affecting the patients' oncological outcome. Focusing on the above problems, this paper reviews the latest research progress. In conclusion, it is believed that the advantages of retaining LCA are supported by most studies, which can improve the blood supply of the proximal anastomosis, and technically can achieve the same range of lymph node dissection as IMA high ligation. However, whether it affects the survival of patients, reduces the incidence of anastomotic leakage, and improves the quality of life of patients, more high-quality evidence-based medical evidence is still needed.
Arteries
;
Humans
;
Laparoscopy
;
Mesenteric Artery, Inferior/surgery*
;
Quality of Life
;
Rectal Neoplasms/surgery*
4.Association of Polygenic Risk Score with Age at Onset and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease in a Chinese Cohort.
Wei-Wei LI ; Zhen WANG ; Dong-Yu FAN ; Ying-Ying SHEN ; Dong-Wan CHEN ; Hui-Yun LI ; Ling LI ; Heng YANG ; Yu-Hui LIU ; Xian-Le BU ; Wang-Sheng JIN ; Fan ZENG ; Zhi-Qiang XU ; Jin-Tai YU ; Li-Yong CHEN ; Yan-Jiang WANG
Neuroscience Bulletin 2020;36(7):696-704
To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.
5.Age and menopausal status are important factors influencing the serum human epididymis secretory protein 4 level: a prospective cross-sectional study in healthy Chinese people.
Hong-Yan CHENG ; Lin ZENG ; Xue YE ; Rui-Qiong MA ; Zhi-Jian TANG ; Hong-Ling CHU ; Yi-Ming ZHAO ; Li-Rong ZHU ; Yu-Nong GAO ; Xiao-Hong CHANG ; Heng CUI
Chinese Medical Journal 2020;133(11):1285-1291
BACKGROUND:
Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people.
METHODS:
A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%-95%) were determined for reference ranges in different populations.
RESULTS:
There was a statistically significant difference in median HE4 levels between the post-menopausal (n = 2168) and pre-menopausal groups (n = 325) (36.46 vs. 24.04 pmol/L, Z = -14.41, P < 0.001). HE4 increased significantly with age in the post-menopausal groups (H = 408.18, P < 0.001) but not in the pre-menopausal subjects (Z = -0.43, P = 0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age.
CONCLUSIONS
Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.
6.Effect of Matrix Metallopeptidase 13 on the Function of Mouse Bone Marrow-derived Dendritic Cells.
Xiao-Dong LI ; Xin-Rui ZHANG ; Zhi-Hao LI ; Yang YANG ; Duo ZHANG ; Heng ZHENG ; Shu-Ying DONG ; Juan CHEN ; Xian-Dong ZENG
Chinese Medical Journal 2017;130(6):717-721
BACKGROUNDDendritic cells are professional antigen-presenting cells found in an immature state in epithelia and interstitial space, where they capture antigens such as pathogens or damaged tissue. Matrix metallopeptidase 13 (MMP-13), a member of the collagenase subfamily, is involved in many different cellular processes and is expressed in murine bone marrow-derived dendritic cells (DCs). The function of MMP-13 in DCs is not well understood. Here, we investigated the effect of MMP-13 on DC maturation, apoptosis, and phagocytosis.
METHODSBone marrow-derived dendritic cells were obtained from C57BL/6 mice. One short-interfering RNA specific for MMP-13 was used to transfect DCs. MMP-13-silenced DCs and control DCs were prepared, and apoptosis was measured using real-time polymerase chain reaction and Western blotting. MMP-13-silenced DCs and control DCs were analyzed for surface expression of CD80 and CD86 and phagocytosis capability using flow cytometry.
RESULTSCompared to the control DCs, MMP-13-silenced DCs increased expression of anti-apoptosis-related genes, BAG1 (control group vs. MMP-13-silenced group: 4.08 ± 0.60 vs. 6.11 ± 0.87, P = 0.008), BCL-2 (control group vs. MMP-13-silenced group: 7.54 ± 0.76 vs. 9.54 ± 1.29, P = 0.036), and TP73 (control group vs. MMP-13-silenced group: 4.33 ± 0.29 vs. 5.60 ± 0.32, P = 0.001) and decreased apoptosis-related genes, CASP1 (control group vs. MMP-13-silenced group: 3.79 ± 0.67 vs. 2.54 ± 0.39, P = 0.019), LTBR (control group vs. MMP-13-silenced group: 9.23 ± 1.25 vs. 6.24 ± 1.15, P = 0.012), and CASP4 (control group vs. MMP-13-silenced group: 2.07 ± 0.56 vs. 0.35 ± 0.35, P = 0.002). Protein levels confirmed the same expression pattern. MMP-13-silenced groups decreased expression of CD86 on DCs; however, there was no statistical difference in CD80 surface expression. Furthermore, MMP-13-silenced groups exhibited weaker phagocytosis capability.
CONCLUSIONThese results indicate that MMP-13 inhibition dampens DC maturation, apoptosis, and phagocytosis.
Animals ; Apoptosis ; drug effects ; physiology ; Bone Marrow Cells ; cytology ; Dendritic Cells ; cytology ; drug effects ; metabolism ; Female ; Lipopolysaccharides ; pharmacology ; Matrix Metalloproteinase 13 ; metabolism ; physiology ; Mice ; Mice, Inbred C57BL ; RNA, Small Interfering
7.Primary mucosal melanoma of the nasal cavity: a linicopathological analysis of 17 cases
Wen LIU ; Zhi ZENG ; Heng ZHOU ; Hao WU ; Jingping YUAN
Chinese Journal of Clinical and Experimental Pathology 2017;33(2):169-173
Purpose To study the clinicopathologic features and differential diagnosis of primary mucosal melanoma of the nasal cavity (PMMNC).Methods 17 cases of PMMNC diagnosed from January 2003 to September 2016 were studied by clinical pathological analysis and immunohistochemical staining,and relevant literatures were reviewed.Results 73% of the PMMNC was characterized by unilateral nasal congestion and intermittent epistaxis and 61% of the PMMNC occurred in the nasal septum and nasal side wall.Microscopically,the organizational structure and morphology were complex and diverse,which had several cell types including epithelioid cell type (6cases,35.3%),spindle cell type (3 cases,17.6%) and snall cell type (5 cases,29.4%),the other 3 cases (17.6%)were mixed cell type.Mitotic activity and tumor necrosis were more likely to be seen in PMMNC,among other clinicopathological features with a small amount of fibrous stroma and melanoma and rich blood vessels.The immunohistochemical study showed that the positive rate of S-100 and HMB-45 were both 93.8%(15 cases) and those of Melan-A and vimentin were both 87.5% (14 cases),while CK and EMA were both negative (16 cases).Conclusion PMMNC is a rare disease and the phenotype of S-100,HMB-45,Melan-A and vimentin are useful for diagnosis of PMMNC.
8.Radiofrequency catheter ablation of arrhythmias in pediatric patients guided by three-dimensional mapping system.
Shao-ying ZENG ; Ji-jun SHI ; Ju-heng YE ; Zhi-wei ZHANG ; Yu-fen LI
Chinese Journal of Pediatrics 2009;47(9):705-709
OBJECTIVETo explore safety, indications and advantages of mapping and ablation of arrhythmia in children guided by Carto and Ensite system.
METHODSGuided by Carto system, radiofrequency catheter ablation (RFCA) was performed on 8 pediatric patients with tachycardia whose mean age was (6.2 + or - 1.7) years, mean weight was (18.0 + or - 2.0) kg. Guided by Ensite system, RFCA was performed on 10 pediatric patients with arrhythmia, 8 of them were ablated guided by Ensite Array system: 6 cases with premature ventricular contractions (PVCs), 2 cases with right atrial tachycardia, their mean age was (11.3 + or - 1.2) years, and mean weight (40.0 + or - 5.0) kg. The other two cases with W-P-W syndrome were ablated guided by Ensite Navx system.
RESULTGuided by Carto system, 8 cases were successfully mapped and ablated: 6 cases had incision atrial tachycardia, 1 case had left atrial tachycardia and 1 case had right atrial tachycardia. In 1 case with incision atrial tachycardia the condition recurred after 3 months, and was ablated again successfully. Guided by Ensite Array system, 6 cases with PVCs (in 2 originating from the right ventricular inflow tract and in 4 originating from the right ventricular outflow tract) and 2 cases with right atrial tachycardia were successfully mapped and ablated, PVCs of the first 6 cases were reduced from (32 333 + or - 4509) 24 h to (0-4)/24 h after ablation. In 1 case with automatic atrial tachycardia, mapping could not be done by Ensite Array system, because P wave could not be identified from T wave. Single bolus of adenosine 20 mg was given within 30 s to let ventricles stop for 2 s (cardio-ventricular pacing standby) until T wave vanished, mapping and ablation were operated again successfully, but another atrial tachycardia occurred 1 day later. Guided by Ensite Navx system, 2 cases with W-P-W syndrome were successfully ablated, operation under X-rays lasted for 8 and 10 min. In none of the 9 patients the disease recurred after follow-up for 6 months.
CONCLUSIONCarto system is suitable for mapping and ablation in pediatric patients with continuous tachycardia, especially with incision atrial tachycardia; Ensite Array system fits children older than 10 years with right heart discontinuous arrhythmia; and Ensite NavX system can set up model and display endocardial anatomic structure quickly. Compared with two-dimensional mapping system, the three-dimensional mapping system (Carto and Ensite) can display the origin of arrhythmia and activation sequence clearly, decrease difficulty of operation efficiently and diminish operation time under X-ray.
Arrhythmias, Cardiac ; physiopathology ; surgery ; Catheter Ablation ; methods ; Child ; Child, Preschool ; Electrophysiologic Techniques, Cardiac ; methods ; Humans ; Imaging, Three-Dimensional ; Treatment Outcome
9.Genetic polymorphism of 9 Y-STR loci with short fragment size alleles in unrelated male individuals from Zhuang ethnic group.
Qian LI ; Su-Qing GAO ; Heng-Cong LI ; Da-Ming WANG ; Jian-Qiang ZENG ; Zhi-Hui DENG
Journal of Experimental Hematology 2008;16(3):694-698
The aim of this study was to investigate the genetic polymorphism of Y-chromosome specific short tandem repeat (Y-STR) loci in Zhuang ethnic group of China. Nine Y-STR loci were amplified by single multiplex and the PCR products were detected by using ABI Prism(TM) 3100 DNA Sequencer. The allele frequencies and haplotype frequencies at 9 Y-STR loci were determined in a total of 85 unrelated male individuals from Zhuang ethnic group of China. The results indicated that in the 85 unrelated male individuals, except for the DYS426 locus with a low GD value, the GD values for other 8 Y-STR loci ranged from 0.4387 to 0.8129. A total of 70 haplotypes at 9 Y-STR loci were found, the haplotype diversity was 0.9926. It is concluded that the haplotype polymorphism of 9 Y-STR loci are highly polymorphic in Zhuang ethnic group and also significantly different from our previous reported data of unrelated male individnals in southern Chinese Han population.
Alleles
;
China
;
ethnology
;
Chromosomes, Human, Y
;
genetics
;
Genetic Loci
;
genetics
;
Humans
;
Male
;
Microsatellite Repeats
;
genetics
;
Polymorphism, Genetic
10.Cox regression analysis on influencing factors of coronary heart disease among people over 40 years of age.
Hao LIU ; Li-Guang ZHU ; Wei-Hong SU ; Ke-Jiang QIN ; Ming PANG ; Jian-Jian LU ; Guang-Wei WU ; Ji-Jin ZHU ; Xin-Zhi TAO ; Xing-San LI ; Zhi-Heng ZENG
Chinese Journal of Epidemiology 2005;26(12):964-966
OBJECTIVETo explore the affecting factors on coronary heart disease among people over 40 years of age in Guangxi area, China.
METHODSBaseline data was gathered through the Third National Blood Pressure Survey in 1991 in China. A total number of 11 818 adults over 40 years old had been studied in Guangxi province. Data of morbidity and mortality of coronary heart disease was obtained.
RESULTSCardiovascular events were related to systolic blood pressure, diastolic blood pressure, pulse pressure, smoking, BMI regardless of their myocardial infarct (MI) history. Cox regression analysis showed that the relative risk for cardiovascular events increased by 21 [95% confidence interval (CI): 9.06-48.44] times for those people having MI history. When pulse pressure, systolic blood pressure, diastolic blood pressure increased by every 10 mm Hg, the relative risk for cardiovascular events increased by 1.29 (95% CI: 1.11-1.49), 1.18 (95% CI: 1.02-1.22), 1.13 (95% CI: 1.05-1.28) respectively. There was 1.23 (95% Cl: 1.05-1.45) times higher in smoker than non-smoker on relative risk for cardiovascular events. When BMI increasing 1, the relative risk for cardiovascular events would increase 1.03 (95% CI: 1.01-1 .05) times.
CONCLUSIONHypertension, smoking, increase of BMI were the risk factors of coronary heart disease among people who were over 40 years of age.
Adult ; Body Mass Index ; China ; epidemiology ; Cohort Studies ; Confidence Intervals ; Coronary Disease ; epidemiology ; etiology ; Health Surveys ; Humans ; Hypertension ; complications ; Myocardial Infarction ; Proportional Hazards Models ; Risk Factors ; Smoking ; adverse effects

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