1.A case of neurobrucellosis in children and literature review
XIN Guoyan ; GAO Xin ; ZHU Jiaying
China Tropical Medicine 2024;24(2):228-
An analysis was conducted on the clinical manifestations, auxiliary examinations, diagnosis and treatment process, treatment, and prognosis of a child with neurobrucellosis. 408 relevant literature on neurobrucellosis from January 2012 to December 2022 were searched through Chinese and English databases such as CNKI, Wanfang Data, and Biomedical Literature Database (PubMed). Literature was screened based on inclusion and exclusion criteria, A total of 14 children with neurobrucellosis were selected for analysis, with an average age of onset of 10 years old. Among the patients, there were 3 cases of middle cranial nerve injury, 2 cases of ataxia, 1 case of myelitis, 2 cases of mental symptoms, 1 case of optic disc edema, 1 case of sagittal sinus thrombosis, and the rest were manifested as meningitis and encephalitis. The imaging results suggested that there was often no specific area of invasion, with magnetic resonance imaging (MRI) commonly involving the cortex, central half oval, and basal ganglia. Extensive white matter changes were also frequently observed, which is consistent with the findings of this case report. Neurobrucellosis has diverse clinical manifestations and lacks specificity. It is mainly diagnosed based on comprehensive analysis of neuropsychiatric symptoms, cerebrospinal fluid and serological results, imaging characteristics, etc. Early diagnosis and treatment are of great significance in preventing complications of neurobrucellosis.
2.Targeting a novel inducible GPX4 alternative isoform to alleviate ferroptosis and treat metabolic-associated fatty liver disease.
Jie TONG ; Dongjie LI ; Hongbo MENG ; Diyang SUN ; Xiuting LAN ; Min NI ; Jiawei MA ; Feiyan ZENG ; Sijia SUN ; Jiangtao FU ; Guoqiang LI ; Qingxin JI ; Guoyan ZHANG ; Qirui SHEN ; Yuanyuan WANG ; Jiahui ZHU ; Yi ZHAO ; Xujie WANG ; Yi LIU ; Shenxi OUYANG ; Chunquan SHENG ; Fuming SHEN ; Pei WANG
Acta Pharmaceutica Sinica B 2022;12(9):3650-3666
Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.
3.Multi-disciplinary team of human herpes virus-6B encephalitis after liver transplantation
Yafei GUO ; Jizhou WANG ; Zebin ZHU ; Cui CHEN ; Guoyan LIU ; Sen QUN ; Kexue DENG ; Dehao HUANG ; Lianxin LIU
Organ Transplantation 2021;12(4):465-
Objective To evaluate the role of multi-disciplinary team (MDT) in improving the diagnosis and treatment of human herpes virus-6B (HHV-6B) encephalitis after liver transplantation. Methods MDT consultation was delivered for one rare case of HHV-6B encephalitis after liver transplantation to establish an effective individualized treatment regime. Results On the 16 d after liver transplantation, the patient developed headache, and suddenly presented with unresponsiveness, unconsciousness, coma complicated with involuntary limb twitching on the 18 d. Blood ammonia level was increased. Brain CT scan showed cerebral ischemic changes. Electroencephalography prompted the epileptic seizure. After MDT consultation, the possibility of nervous system infection after liver transplantation was considered, and medication therapy was given to control the epileptic seizure. Cerebrospinal fluid examination via lumbar puncture hinted increased intracranial pressure. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) of the cerebrospinal fluid demonstrated that the patient was tested positive for HHV-6B nucleic acid, which confirmed the diagnosis of HHV-6B encephalitis. The immunosuppressant regime was adjusted, intravenous ganciclovir was given for antiviral treatment, and active interventions were delivered to prevent and treat relevant complications. Epileptic seizure disappeared after 4 d, and neurological symptoms were significantly alleviated after 2 weeks. After 4-week antiviral treatment, the patient was tested negative for virology testing, and the neurological function was restored to normal. Conclusions HHV-6B encephalitis rarely occurs after adult liver transplantation, which is primarily associated with the virus reactivation after use of immunosuppressant. MDT pattern may be employed to deepen the understanding of the patient's condition, formulate more effective individualized treatment regime, and enhance the clinical efficacy and safety.
4. Correlation between gut microbiota and neurological behavior in mice co-exposed to manganese and high-fat diet
Hao ZHU ; Fengwei ZHANG ; Xu HAN ; Guoyan ZHANG ; Xiujun ZHANG
China Occupational Medicine 2020;47(03):298-304
OBJECTIVE: To investigate the effects of manganese(Mn) and high fat diet(HFD) co-exposure on the neurological behavior and gut microbiota in mice, and to observe the correlation between them. METHODS: Specific pathogen free adult male C57 BL/6 mice were randomly divided into 4 groups. Mice in control group and Mn exposure group were fed with normal diet, while the HFD group and co-exposure group were fed with HFD. Both the Mn exposure group and the co-exposure group were exposed to 10 mg/(kg·d) manganese chloride by intraperitoneal injection, while the control group and HFD group were treated with 0.9% sodium chloride solution of the same volume, once per day for 60 consecutive days. At the end of exposure, the mice were subjected to experiments of neurological behaviors. Then, the mice were sacrificed and intestinal feces were collected. The relative abundance of gut microbiota(relative abundance>1.000%) was detected by high-throughput sequencing. RESULTS: After exposure, the body weight of the HFD group and the co-exposure group increased significantly(P<0.05), while that of the Mn exposure group decreased(P<0.05), compared with the control group. The latency, time in central, crossing, total distance and open arm time(OT%) of mice in the Mn exposure group were lower than that of the control group(P<0.05), and close arm time(CT%) prolonged(P<0.05). Compared with the control group and the HFD group, the latency, rearing, time in central, crossing, total distance, OT% and open arm entry(OE%) of mice in the co-exposure group decreased(P<0.05), and CT% increased(P<0.05). The total distance of mice in the co-exposure group was lower than that of the Mn exposure group(P<0.05). The relative abundance of Firmicutes increased(P<0.05), those of Bacteroidetes and Actinobacteria decreased in mice in the HFD group at the phylum level(P<0.05) compared with mice in the control group. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria increased(P<0.05), and Bacteroidetes and Actinobacteria decreased(P<0.05) in mice in the Mn exposure group. The relative abundance of Oscillospira, Bacteroides and Prevotella of mice in the HFD group reduced at the genus level(P<0.05) compared with the control group. The relative abundance of Lactobacillus increased in Mn exposure group(P<0.05), and Oscillospira, Bacteroides and Prevotella decreased(P<0.05). The relative abundance of Firmicutes, Cyanobacteria and Lactobacillus of mice in the co-exposure group increased(P<0.05), and those of the remaining 6 bacteria were lower(P<0.05) compared with mice in the other 3 groups. Among the mice of co-exposure group, the latency was positively correlated with Bacteroidetes(P<0.05). The rearing was positively correlated with Firmicutes(P<0.05) and negatively correlated with Actinobacteria(P<0.01). The OE% was negatively correlated with Firmicutes(P<0.05) and positively correlated with Actinobacteria(P<0.05). The crossing was positively correlated with Prevotella(P<0.05). CONCLUSION: Manganese combined with HFD had a synergistic effect on the abnormality of neurological behavior of mice. There are some correlation between the abnormality of neurological behavior and the homeostatic imbalance of intestinal flora in mice.
5.The mediating role of family cohesion between family expressiveness and preschool children's behavior
Guoyan LIU ; Jiexuan LI ; Limei XIAO ; Xiaohui ZHU ; Yanchun CAI
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(2):159-162
Objective:To explore the mediating role of family cohesion between family expressiveness and preschool children's behavior.Methods:Using the method of stratified cluster random sampling, the parents of 1 213 children in Shenzhen kindergartens were assessed by the Achenbach child behavior checklist (parent questionnaire) (CBCL, 4-16 years) and family environment scale-Chinese version (FES-CV). After the survey, SPSS 24.0 was used to conduct the data analysis and the Bootstrap method was used to test the mediation effect.Results:(1)The total score of children's behavior 147.0(135.0, 163.0) was found to be significantly negatively correlated with family expressiveness score 6.0 (5.0, 7.0) and family cohesion score 8.0 (6.0, 9.0), and the correlation coefficients were -0.145 and -0.187(both P<0.01). (2) Family expressiveness score was positively related to family cohesion score ( r=0.443, P<0.01). (3)The direct effect of family expressiveness on children's behavior was -0.072, and the 95% confidence interval was (-0.133, -0.010). Family cohesion had a mediating effect between family expressiveness and children's behavior, 95% confidence interval was (-0.129, -0.058), and the mediating effect accounted for 56.4% of the total effect. Conclusion:Family cohesion plays a partial mediating role between family expressiveness and children's behavior.
6.Expression of TMEM16 A as a calcium-activated chloride channel in Fis-cher rat thyroid follicular epithelial cells and its electrophysiologic pro-perties
Feng HAO ; Xuesong BAI ; Xiaohong JU ; Fang FANG ; Yuxuan ZANG ; Hangfei ZHU ; Guoyan XIANG ; Yunqiao ZHANG ; Zhonghai YUAN
Chinese Journal of Pathophysiology 2014;(9):1633-1639
AIM:To investigate the expression of transmembrane protein 16A(TMEM16A) in Fischer rat thy-roid follicular epithelial ( FRT) cells and its electrophysiologic properties .METHODS: The eukaryotic expression vector of pUB6/V5-TMEM16A was constructed and transfected into FRT cells by liposome-mediated transfection .In order to ob-tain the high efficiency of gene transfection and expression , the quantity and ratio of lipid/DNA complexes were optimized . The FRT cells stably expressing TMEM16A were gained by the selection with blasticidin and confirmed by the techniques of RT-PCR and immunofluorescence .The expression and location of TMEM 16A in the FRT cells were observed under an in-verted fluorescence microscope .TMEM16A protein was associated with calcium-dependent chloride current , as measured with halide-sensitive fluorescent protein and patch-clamp technique .RESULTS: The results of double digestion and se-quencing indicated that TMEM16A was cloned into pUB6/V5.The results of RT-PCR and immunofluorescence confirmed that TMEM16A was expressed in the FRT cells after transfection with TMEM16A.The classical calcium-activated chloride channel currents were recorded in the FRT cells stably expressing TMEM 16A by the technique of patch-clamp and halide-sensitive fluorescent protein YFP-H148Q/I152L.CONCLUSION:The protein expression of TMEM16A in the FRT cells was observed.TMEM16A is the molecular identity of calcium-activated chloride channels .
7.Clinical observation on the effet of edaravone combined with low-molecular-weight heparin on progressive cerebral infarction
Chinese Journal of Primary Medicine and Pharmacy 2012;(23):3545-3546
Objective To study the clinical effect of low-molecular-weight heparin combined with edaravone in the treatment of progressive cerebral infarction.Methods 60 patients with acute progressive cerebral infarction in 72 hours were randomly divided into treatment group received edaravone combined low-molecular-weight heparin(n=30)and control group received low-molecular-weight heparin(n=30).The primary efficacy was evaluated by NIHSS(the National Institutes of Health Stroke Scale).ADL(Activities of daily living)and clinical effect.Results Our study showed that the score of NIHSS on 7th day post-therapy and 14th day post-therapy in treatment group was lower than that in control group(t=15.987 and 11.756,both P<0.01).However,the score of ADL in the theatment group on 14th day post-therapy was higher than that of control group(t=62.56,P<0.01).The overall clinical responserate of treatment group was higher than that of control group(x2=13.695,5.769,all P<0.01).Conclusion Edaravone combined with low-molecular-weight heparin has remakable effect on the treatment of progressive cerebral infarcti.
8.Expression of the estrogen receptor α and β in mouse thymus
Guoning GUO ; Guoyan ZHU ; Yongjun SHANG ; Liang WEN ; Shiwei XU
Chinese Journal of Immunology 2010;26(4):291-293
Objective: To detect estrogen receptor α and β(ER-α, ER-β)protein expression in different age of mouse thymus.Methods:Protein expression of ER-α and ER-β in thymus was analyzed via immunohistochemistry.Moreover,the relationship between ER-α and cytokeratin 18(epithelial cell marker)was further tested through fluorescence double-staining.Results: Immunohistochemical analysis revealed that both ER-α and β protein was found in nuclei of some thymocytes of 3 month mice.However,expression of ER-β was absence while ER-α was still positive in aged mice, such as 12 months and 16 months old.Double staining further confirmed that lots of ER-α/β positive cells were Foxp3 negative cells.Conclusion: Expression of ER-β is absent while ER-α is still positive in thymus of aged mice, which indicates ER-α is the critical estrogen receptor that involves in thymic involution.Moreover, ER-α/β do not participate in Treg development within thymus.
9.Clinical study of reattribution-cognitive-pharmacy model in the treatment for irritable bowel syndrome
Jianxin CAO ; Yulan WANG ; Xuexia REN ; Guoyan ZHU
Chinese Journal of Behavioral Medicine and Brain Science 2010;19(12):1069-1070
Objective To investigate clinical effect of reattribution-cognitive-pharmacy model (RCPM) in the treatment for irritable bowel syndrome(IBS). Methods 125 subjects with diarrhea predominant irritable bowel syndrome (IBS-D) were divided into two groups randomly. 62 patients in group A were treated with 10 ~ 20 mg of paroxetine without any other medication or psychological interview and 63 patients in group B received RCPM with interviewing once a week for 6 sessions and took 10 ~ 20 mg of paroxetine in the same way as group A after a week. The effect was evaluated at the end of 4 weeks and 12 weeks by a questionnaire. Results At the end of 4 weeks,29 patients in group A reported a reduction in abdominal pain,and 28 reported a reduction in stool frequency ,and 12 patients stopped taking paroxetine because of worrying about those side effect . In group B 48 reported a reduction in abdominal pain ,and 42 reported a reduction in stool frequency ,and 3 patients stopped taking paroxetine. At the end of 12 weeks,36 patients in group A reported a reduction in abdominal pain ,and 30 reported a reduction in stool frequency,and 14 patients stopped taking paroxetine because of worry about those side effect. In group B,54 cases reported a reduction in abdominal pain,and 45 reported a reduction in stool frequency,and 5 patients stopped taking paroxetine because of no obvious improvement. Conclusion RCPM can alleviate the abdominal pain and bowl movement frequency of IBS-D,and it seems better than paroxetine treatment alone. RCPM can improve compliance of paroxetine in patients with IBS-D.
10.Effects and mechanism of CD+4 CD+25 regulatory T cells in colitis treated by Yin Yang equilibrated preparation
Bin ZHU ; Sicai YIE ; Junfa XU ; Kangyin WU ; Guoyan HU ; Yu ZHOU
Chinese Journal of Primary Medicine and Pharmacy 2009;16(7):1209-1210
Objective To explore the effects and mechanism in patients with ulcerative colitis (UC) treated by Yin Yang equilibrated preparation. Method 82 patients with UC as treatment group and 35 health parsons as control group underwent the testing. The serum and mucosal of all testing persons were taken pre and post treatment to detect CD+4 CD+25 regulatory T cells(Tregs) by flow cytometry at the end of one month,treating with SASP and Yin Yang equilibrated preparation. Result Compared with normal control group,the proportion of CD+4 CD+25 Tregs was markedly decreased in PB and mucesal of group A and B(P <0.01). But it was significanfly increased in therapeutic groups of SASP and Yin Yang equilibrated preparation, and their CD+4 CD+25 Tregs in PB and mucosal were much more than the control group at the end of one month after treating with SASP and Yin Yang equilibrated preparation(P <0.01 or P< 0.05). Conclusion CD+4 CD+25 Tregs with strong immune suppression play a central role in the initia-tion and development of UC,and the Yin Yang equilibrated preparation might exert its therapeutic effects on UC by the regulation of number and function of CD+4 CD+25 Tregs.

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