1.Gut microbiota-derived short-chain fatty acids ameliorate methamphetamine-induced depression- and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner.
Kaikai ZHANG ; Lijian CHEN ; Jianzheng YANG ; Jiali LIU ; Jiahao LI ; Yi LIU ; Xiuwen LI ; Long CHEN ; Clare HSU ; Jiahao ZENG ; Xiaoli XIE ; Qi WANG
Acta Pharmaceutica Sinica B 2023;13(12):4801-4822
Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout (Sigmar1-/-) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy.
2.Clinical factors in predicting extreme preterm birth after cerclage.
Xuping YE ; Yuezhou YANG ; Jun LI ; Kaikai CHANG ; Huan XU
Chinese Medical Journal 2023;136(3):370-372
3.Effect of air-oxygenated normothermic mechanical perfusion on rat kidney recovery following ischemic injury from donation after cardiac death
Zhu CHEN ; Kaikai CHI ; Peng LU ; Yabin GAO ; Qing ZHANG ; Kang YANG ; Zheng WANG
Chinese Journal of Organ Transplantation 2022;43(2):95-101
Objective:To develop an ex vivo normothermic mechanical perfusion(NMP)and compare the effect of air-oxygenated NMP versus oxygen-oxygenated NMP on reducing renal injury from donor after cardiac death(DCD).Methods:All kidneys from DCD rats were subjected to 30 min in situ warm ischemia after cardiac attest.And harvested kidneys were stored for 8h under static cold preservation after NMP for 2h.In experimental groups, kidneys were subjected to either air-oxygenated NMP(group A, n=6)or oxygen-oxygenated NMP(group O, n=6). Sham operation(group C, n=6)and DCD kidneys under static cold preservation without NMP(group SCS, n=6)were employed as controls.The evaluation parameters included creatinine(Cr), aspartate amino transferase(AST)and lactate dehydrogenase(LDH)in perfusate, pathological changes by hematoxylin-eosin(HE)staining, histological criteria, expressions of myeloperoxidase and intercellular adhesion molecular-1(ICAM-1)by immunohistochemistry and Western blot, tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)by enzyme-linked immunoadsorbent assay and level of malondialdehyde(MDA)by thiobarbital method and activity of superoxide dismutase(SOD)by WST-8 in renal tissues.Differences between two groups were analyzed by two-tailed unpaired Student's test and differences among more than two groups by one-way ANOVA.Results:Renal arterial oxygen tensions in NMP perfusate were(576.3±68.2)mmHg with oxygen-oxygenation and(137.0±39.1)mmHg with air-oxygenation.There was significant difference( P<0.05). The pathological injury scores in groups SCS, O and A by HE staining were(7.0±0.1), (5.0±0.9)and(2.5±0.5); injury scores and the expressions of renal proximal tubular epithelial cell vacuolar degeneration in groups O and A were lower than those in group SCS( P<0.05)and injury score in group A was lower than group O( P<0.05). In perfusate, the levels of △Cr, △AST and △LDH in groups O and A were(43.9±52.8)μmol/L and(12.6±3.5)μmol/L, (532.3±52.8)U/L and(49.1±50.4)U/L and(9998.0±2014.4)U/L and(1477.0±810.4)U/L.There were significant differences( P<0.05). In perfused kidneys, the MDA level and SOD activity in groups O and A were(0.192±0.018)mmol/g, (0.162±0.023)mmol/g, (0.6±0.3)×10 3 U/g, (1.7±0.4)×10 3 U/g; TNF-α and IL-6 levels in groups O and A were(124.376±19.635)and(89.331±13.123)ng/g, and(4.038±1.026)×10 3 and(1.774±0.518)×10 3 ng/g.After air-oxygenated NMP, lower renal damage indices were characterized by a lower MDA level and a higher SOD activity, the lower levels of TNF-α and IL-6 and the lower expressions of MPO and ICAM-1 than those in oxygen-oxygenated NMP( P<0.05). Conclusions:NMP with air-oxygenation mimics renal perfusion under physiological conditions and decreases oxidative stress and inflammation injury.It may confer a better retrieval in DCD kidney against warm ischemia injury.
4.Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks.
Xiaojin CHEN ; Tao GUO ; Kaikai ZHANG ; Jiacai CHEN ; Caifen WANG ; Xiaohong REN ; Qin WANG ; Yingchao YANG ; Chongjing LIU ; Wen TAN ; Shuangying GUI ; Li WU ; Jiwen ZHANG
Acta Pharmaceutica Sinica B 2021;11(9):2914-2923
Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The
5.Relationship between different obesity phenotypes and abnormal blood pressure in children and adolescents in Yinchuan city
Ping MA ; Qingmei YANG ; Kaikai LI ; Xiuying LIU ; Wenqing DING
Chinese Journal of Applied Clinical Pediatrics 2021;36(2):109-112
Objective:To investigate the relationship between different obesity phenotypes and abnormal blood pressure in children and adolescents in Yinchuan city, and to provide appropriate treatment and intervention measures for obese children and adolescents.Methods:The current research design was adopted to facilitate the cluster sampling.A total of 1 047 children and adolescents aged 12 to 18 in Yinchuan were enrolled in this study from September 2017 to September 2018.There were 530 males and 517 females, with an average age of (13.93±1.24) years old.The questionnaire survey, physical examination and laboratory testing were carried out.Statistical analysis was performed by using SPSS 19.0 software.Results:Among the children and adolescents with normal weight, the composition ratio of the metabolically unhealthy normal-weight (MUNW) phenotype was 7.6%.In the obese cases, the composition ratio of the metabolically healthy obesity (MHO) phenotype was 20.2%.The blood pressure of MUNW [systolic pressure SBP: (119±13) mmHg(1 mmHg=0.133 kPa); diastolic pressure(DBP)(74±10) mmHg] and metabolically unhealthy obesity (MUO) [SBP (127±10) mmHg; DBP(74±7) mmHg] phenotypes were significantly higher than those of the metabolically healthy normal-weight (MHNW) phenotype (all P<0.05). The blood pressure of the MUO [SBP(127±10) mmHg; DBP(74±7) mmHg] phenotype was significantly higher than that of the MHO phenotype ( P<0.05). After adjusting for age, gender, and family history of hypertension, MUNW and MUO phenotypes were 5.93 (95% CI: 3.10-11.36) and 11.63 (95% CI: 6.37-21.24) times more likely to develop blood pressure abnormalities than MHNW phenotypes, respectively ( P<0.001). The MHO phenotype was 0.63 (95% CI: 0.08-4.93) times more likely to develop blood pressure abnormalities than the MHNW phenotype ( P=0.66). Conclusions:The MHO phenotype does not increase the risk of abnormal blood pressure, while the MUNW phenotype does.Therefore, it is recommended to identify the MHO phenotype and MUNW phenotype in order to provide appropriate obesity treatment and interventions for children and adolescents.
6.The effect of rheumatic mitral valve repair using "standardized 4 steps"
Weihua ZHANG ; Meng WEN ; Tiejun WU ; Ming LI ; Yang LIU ; Kaikai FAN ; Chenhui QIAO
Chinese Journal of Thoracic and Cardiovascular Surgery 2020;36(10):585-588
Objective:To investigate the clinical effect of "standardized 4 steps" in rheumatic mitral valve repair.Methods:We retrospectively analyze the clinical data of 136 rheumatic mitral valve disease patients undergoing mitral valve repair with "standardized 4 steps" from June 2016 to July 2019 and investigate its clinical outcome. The clinical outcome was compared with those of patients undergoing rheumatic mitral valve replacement.Results:The perioperative mortality was 2.94% in patients with mitral valve repair. Compared with preoperative period, left atrial diameter was significantly reduced and the early diastolic blood flow velocity across mitral valve(E peak) was significantly decreased at 1-week postoperative and follow-up period. The elimination rate of atrial fibrillation was 80.7% during follow-up period. The early clinical outcome and related complications had no difference between mitral repair group and mitral valve replacement group. The main echocardiographic indexes in two groups also had no statistical significance.Conclusion:The early clinical outcome of rheumatic mitral valve repair with "standardized 4 steps" is satisfactory. Rheumatic mitral valve repair with "standardized 4 steps" is feasible, safe and effective.
7.Blood pressure and blood biochemical indexes between obese students and normal-weight middle school students in urban area of Yinchuan
LI Kaikai, SHANG Aili, JIA Leina, YANG Qingmei, MA Ping, DING Wenqing
Chinese Journal of School Health 2019;40(8):1203-1206
Objective:
To analyze the differences of cardiovascular(CV) risk factors between middle school students with normal weight but high body fat and students with normal weight and normal body fat in urban area of Yinchuan,to provide a theoretical basis for early detection of their invisible obesity and controlling CV metabolism disease.
Methods:
During 2017 to 2018, a total of 1 043 secondary school students in urban area of Yinchuan were selected through cluster sampling. Questionnaire survey, physical examination, body composition and blood lipid test were conducted among all the participants.745 middle school students with normal body mass index (BMI) were included in the analysis.
Results:
Nearly 31.1% students with normal BMI had high body fat, with girls significantly higher than that in boys across different age groups(χ2=10.37,106.49,P<0.01). Total cholesterol (TC) in boys with normal-weight obesity was higher than that in the normal group, while diastolic blood pressure (DBP), triglyceride (TG), TC and lowdensity lipoprotein cholesterol (LDL-C) in girls with normal-weight obesity were significantly higher than that in the normal group, with statistically significant differences (t=-2.37,-3.82,-3.48,-4.46,-4.68,P<0.01). The detection rates of high blood pressure, high TC level and high LDL-C level in normalweight obese girls were all higher than those in normal group (χ2=4.17,8.77,5.91,P<0.05). The detection rate of CV risk factors ≥2 in normal-weight obesity group was higher than that in the normal group, and the difference was statistically significant(χ2=7.05,P<0.01).
Conclusion
Normal-weight obesity among middle school students in urban area of Yinchuan is prevalent, which is mainly concentrated in female students. Moreover, cardiovascular risk factors are more common among those normal-weight obese students compared with normal students. Interventions for preventing and controlling normal-weight obesity should be developed and implemented as early as possible.
8.Association of cardiovascular disease risk factors with fat mass percentage and waist circumference in children and adolescents in Yinchuan City
LI Kaikai, SHANG Aili, LIU Xiuying, YANG Qingmei, MA Ping, DING Wenqing
Chinese Journal of School Health 2019;40(6):888-892
Objective:
To analyze the association between fat mass percentage (FMP) and waist circumference (WC) with cardiovascular risk factors in children and adolescents in Yinchuan City, and to provide a reference for preventing and contyolling the risk factors of cardiovascular diseases among children and adolescents.
Methods:
A questionnaire survey, physical examination, body composition determination and biochemical tests were conducted among 1 043 children aged 12-18 years in Yinchuan selected through a convenient cluster sampling method.
Results:
Among boys and girls, both FMP and WC were associated with high rate of high blood pressure and high TG in children and adolescents(P<0.01). The increased risk of metabolic abnormalities by FMP and WC were 1.14-2.36 times and 1.32-2.09 times, respectively. About 4.9%-22.1% of cardiovascular disease risk was explained by the combination of FMP and WC, which was significantly higher than separate interpretation of FMP or WC (3.5%-22.0%). Standardized regression coefficient for TC and LDL-C (0.25 and 0.22) was greater than WC (0.17 and 0.14) by FMP, and the absolute value of the standardized regression coefficient for SBP, DBP, TG, HDL-C was less than WC by FMP. The predictive risk for high blood pressure, high TG, high TC, low HDL-C and high LDL-C by combination of FMP and WC was 3.67(95%CI=2.42-556), 3.09(95%CI=2.04-4.69), 3.37(95%CI=1.38-8.28), 2.00(95%CI=1.35-2.98) and 4.73(95%CI=2.15-10.44) times higher than different combinations risk groups(P<0.01).
Conclusion
The ability of fat mass percentage and waist circumference to predict the risk of cardiovascular risk factors is similar. It might be used as a predictor of cardiovascular risk factors in children and adolescents. It is recommended to combine FMP with WC to predict the risk of cardiovascular disease among children and adolescents.
9. Analysis of individual dose monitoring results among radiation workers in a first-class hospital at Grade 3 from 2010 to 2017
Xiaojun ZHU ; Qiaoqiao DU ; Zhaohui LU ; Kaikai YUAN ; Haizhen YANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2018;36(11):827-829
Objective:
To understand the occupational external exposure dose among radiation workers in a first
10.Identification of determinants that mediate binding between Tembusu virus and the cellular receptor heat shock protein A9
Dongmin ZHAO ; Qingtao LIU ; Xinmei HUANG ; Huili WANG ; Kaikai HAN ; Jing YANG ; Keran BI ; Yuzhuo LIU ; Lijiao ZHANG ; Yin LI
Journal of Veterinary Science 2018;19(4):528-535
Heat shock protein A9 (HSPA9), a member of the heat shock protein family, is a putative receptor for Tembusu virus (TMUV). By using Western blot and co-immunoprecipitation assays, E protein domains I and II were identified as the functional domains that facilitate HSPA9 binding. Twenty-five overlapping peptides covering domain I and domain II sequences were synthesized and analyzed by using an HSPA9 binding assay. Two peptides showed the capability of binding to HSPA9. Dot blot assay of truncated peptides indicated that amino acid residues 19 to 22 and 245 to 252 of E protein constitute the minimal motifs required for TMUV binding to HSPA9. Importantly, peptides harboring those two minimal motifs could effectively inhibit TMUV infection. Our results provide insight into TMUV-receptor interaction, thereby creating opportunities for elucidating the mechanism of TMUV entry.
Blotting, Western
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Heat-Shock Proteins
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Hot Temperature
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Humans
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Immunoprecipitation
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Peptides
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Protein Structure, Tertiary


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