1.Potential mechanism of metabolic syndrome related cognitive impairment:Mediation effect of thyroid-stimulating hormone in schizophrenia patients
Liying AI ; Qinghui ZHANG ; Yuhan WANG ; Nanlian WANG ; Keyan XIA ; Hua HU
Journal of Army Medical University 2025;47(22):2814-2823
Objective To investigate the correlation between thyroid hormone levels and cognitive function in schizophrenia(SCZ)patients with metabolic syndrome(MetS),as well as the mediating role of thyroid hormones in the relationship between MetS-related indicators and cognitive function.Methods A cross-sectional trial was conducted on 120 SCZ inpatients and outpatients(40 cases of MetS and 80 cases of non-MetS)and 80 healthy controls admitted in the Chongqing Mental Health Center from August 2023 to December 2024.Thyroid function indicators[Thyroid-stimulating hormone(TSH),triiodothyronine(T3),thyroxine(T4),free triiodothyronine(FT3),and free thyroxine(FT4)],MetS-related parameters[blood glucose,triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and waist circumference],Positive and Negative Syndrome Scale(PANSS)score,and Montreal Cognitive Assessment(MoCA)scores were collected.One-way ANOVA or Kruskal-Wallis rank sum test was applied to analyze the differences among the 3 groups,and LSD test or Bonferroni correction was performed for post hoc analysis.Pearson correlation analysis was conducted to assess the relationship between thyroid hormone levels and metabolic parameters as well as cognitive/clinical scale scores(MoCA,PANSS)in the MetS group.Results The MetS group exhibited significantly lower FT4 level(P<0.05)and MoCA score(P=0.001),but higher TSH level(P<0.05)and PANSS negative symptom score(P<0.001)when compared to the non-MetS group.Correlation analysis indicated that in the MetS group,TSH level was positively correlated with TG(r=0.672,P<0.001)and PANSS negative symptom score(r=0.458,P<0.05),and negatively with HDL-C(r=-0.377,P=0.017)and MoCA score(r=-0.667,P<0.001);FT4 level was positively correlated with MoCA score(r=0.534,P<0.001).In the non-MetS group,TSH level was positively correlated with PANSS negative symptom score(r=0.267,P=0.017)and negatively with HDL-C(r=-0.236,P=0.036),T3 was positively with waist circumference(r=0.268,P=0.017).No correlation was observed in FT4 level with HDL-C(r=-0.207,P=0.067)or MoCA score(r=0.216,P=0.055).Mediation analysis revealed that TSH partially mediated the association between TG and MoCA score,with a mediation effect accounting for 29.91%of the total effect.The mediating effect was not significant in the non-MetS group.Conclusion Abnormal elevation of TSH may serve as a critical link between MetS and cognitive impairment in SCZ patients,which providing novel insights into the mechanisms underlying cognitive dysfunction in the patients.
2.TRIB3 targeting AKT phosphorylation regulates polarization of RAW264.7 macrophages under high glucose condition
Wei LUO ; Yue ZHOU ; Liying WANG ; Xian LI ; Lei AI
Immunological Journal 2024;40(2):138-144
This study was performed to explore the downstream mechanism of TRIB3 mediated macrophage pro-inflammatory M1 polarization under high glucose condition.RAW264.7 were divided into CON-DMSO group,CON-SC79 group,HG-DMSO group,and HG-SC79 group.Western blot was used to detect the protein expressions of TRIB3,AKT and p-AKT.Then,RAW264.7 were divided into control vector-DMSO group,TRIB3 overexpress-DMSO group,control vector-SC79 group,TRIB3 overexpress-SC79 group,control vector-MK2206 group,and TRIB3 overexpress-MK2206 group.CCK-8 was used to detect cells activity;phase contrast microscope was used to observe cell morphology;Western blot was used to detedcted the protein expressions of TRIB3,AKT,p-AKT,iNOS and Arg-1.ELISA was used to detedcted the protein secretion of IL-1β and IL-10.Data showed that TRIB3 was significantly increased and p-AKT/AKT was significantly decreased in HG group as compared with the CON group.Compared with corresponding control vector group,TRIB3 was significantly increased and p-AKT/AKT was significantly decreased in TRIB3 overexpress group.Compared with corresponding DMSO group,p-AKT/AKT was significantly increased in SC79 group,and was significantly decreased in MK2206 group.Compared with TRIB3 overexpress-DMSO group,TRIB3 overexpress-SC79 group showed significant reduction in spindle shaped and irregular shaped cells,significantly decreased iNSO and IL-1β,and significantly increased IL-10.TRIB3 overexpress-MK2206 group showed further increase in spindle and irregular shaped cells,significantly decreased Arg-1 and IL-10,and significantly increased IL-β.In conclusion,TRIB3 activated under high glucose condition exerts pro-inflammatory effect by targeting AKT phosphorylation to induce M1 polarization and inhibit M2 polarization in macrophages.
3.Role of connexin43 in sevoflurane-induced cognitive dysfunction in aged rats
Yang YU ; Dengyan ZHU ; Jianjun YANG ; Yanqiu AI ; Liying BAI
Chinese Journal of Anesthesiology 2020;40(8):945-949
Objective:To evaluate the role of connexin43 (Cx43) in sevoflurane anesthesia-induced cognitive dysfunction in aged rats.Methods:Fifty-two healthy male Sprague-Dawley rats, aged 18 months, weighing 400-500 g, were divided into 4 groups ( n=13 each) using a random number table method: control group (C group), sevoflurane group (SEV group), sevoflurane plus sh-NC group (SEV+ sh-NC group) and sevoflurane plus sh-Cx43 group (SEV+ sh-Cx43 group). Sevoflurane anesthesia model was established by inhaling 3% sevoflurane for 6 h. In SEV+ sh-NC group and SEV+ sh-CX43 group, sh-NC 5 nmol and sh-CX43 5 nmol were transfected into the lateral ventricles, respectively, at 1 day before sevoflurane anesthesia.Morris water maze test was performed at 30 min before anesthesia and 1, 2 and 3 days after the end of anesthesia, and the rats were sacrificed at each time point after Morris water maze test, the brains were removed, and the hippocampi were isolated for microscopic examination of the pathological changes and for determination of the expression of Cx43, cleaved caspase-3 and cleaved caspase-9 (by using Western blot), and contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group C, the escape latency was significantly prolonged, and the number of crossing the original platform was reduced, and the expression of CX43, cleaved caspase-3 and cleaved caspase-9 was up-regulated, and the contents of IL-1β, TNF-α and IL-6 were increased in group SEV ( P<0.05). Compared with group SEV, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the expression of CX43, cleaved caspase-3 and cleaved caspase-9 was down-regulated, the contents of IL-1β, TNF-α and IL-6 were decreased ( P<0.05), and the hippocampal pathological injury was reduced in group SEV+ sh-CX43, and no significant change was found in the indicators mentioned above in group SEV+ sh-NC ( P>0.05). Conclusion:Cx43 is involved in the pathophysiological mechanism of sevoflurane-induced cognitive dysfunction probably by inducing neuroinflammatory responses and cell apoptosis in aged rats.
4.Analysis of monosaccharide compositions of different components of Panax japonicus polysaccharides
Jie CHEN ; Jing WANG ; Jia LI ; Siyu SHEN ; Lifeire AI ; Liying HE ; Haiyan ZOU
International Journal of Traditional Chinese Medicine 2019;41(8):858-862
Objective To analyze the monosaccharide composition and the relative content of different alcohol precipitations of Panax japonicus polysaccharides.Methods The four components of Panax japonicus polysaccharides were isolated by stepwise ethanol precipitation method.The four components of Panax japonicus polysaccharides were hydrolyzed with trifluoroacetic acid (TFA) and derivated by l-phenyl-3-methyl-5-pyrazolo (PMP),respectively.The monosaccharide composition and relative content were analyzed using LC-FT-ICR-MS and HPLC-UV method.Results The four components of Panax japonicus polysaccharides consisted of glucose,rhamnose,galacturonic acid,galactose,arabinose,and glucose was the main monosaccharide.With the increase of ethanol concentration,the relative content of Ara increased gradually,as while the GalA decreased.Conclusions Precolumn derivation HPLC method was successfully applied for the determination of the monosaccharides in Panax japonicus polysaccharides,and there were differences in the four ethanol precipitations of Panax japonicus polysaccharides.The study can provide a basis for the separation of Panax japonicus polysaccharides.
5. Molecular epidemiological characteristics of Human Calicivirus in Kunming city, 2014-2015
Liying HE ; Yongming ZHOU ; Wenpeng GU ; Wanfu XU ; Shunxian ZHANG ; Lin AI ; Yan LU ; Liguang TIAN
Chinese Journal of Experimental and Clinical Virology 2017;31(6):525-529
Objective:
To investigate the molecular epidemiological characteristics of Human Calicivirus (HuCV) infection among children less than 5 years in Kunming city, Yunnan province, it might be provide effective evident for prevention and control the diarrhea related with HuCV infection.
Methods:
Four sentinel hospitals were recruited in the study from Kunming city, Yunnan province, 850 diarrhea cases and 170 non-diarrhea subject were recruited in this study from 2014 to 2015. RT-PCR was performed to screen HuCV infection, and gene sequencing was used to ensure positive infection subtypes and genotypes.
Results:
The positive rate of HuCV was higher in children with diarrhea than in non-diarrhea children (11.5%, 98/85; 4.7%, 8/170, χ2=7.083,
6.Expression of glucose-regulated protein 78 in ovarian cancer tissues and its clinical significance
Liying ZHANG ; Aili XU ; Dandan YUAN ; Limin AI ; Peiling LI
Chinese Journal of Postgraduates of Medicine 2014;37(15):1-3
Objective To explore the expression of glucose-regulated protein (Grp) 78 in ovarian cancer tissues and its clinical significance.Methods The expression of Grp78 in 60 cases of ovarian cancer tissue,15 cases of ovarian borderline tumor tissue,10 cases of normal ovarian tissue,10 cases of ovarian cyst tissue,was detected by immunohistochemistry,and analyzed the relationship between its expression and clinicopathological features of ovarian cancer.Results The expression of Grp78 in ovarian borderline tumor and ovarian cancer tissue was significantly higher than that in normal ovarian and ovarian cyst tissue[7/15 and 68.3% (41/60) vs.1/10 and 1/10] (P <0.05).The expression of Grp78 was positively correlated with clinicopathological staging and lymphatic metastasis of ovarian cancer (P < 0.05),negatively correlated with histological differentiation (P < 0.05).No correlation with age and ascites (P > 0.05).Conclusions The levels of Grp78 are elevated in ovarian cancer specimens; high expression of Grp78 maybe participate in the occurrence,development,and prognosis of ovarian cancer.Increased expression of Grp78 might be a useful marker for predicting the carcinogenesis and progression of ovarian cancer.
7.Small interfering RNA inhibits glucose regulated protein 94 expression in transplantable models of human ovarian carcinoma in nude mice
Liying ZHANG ; Aili XU ; Peiling LI ; Limin AI
Chinese Journal of Tissue Engineering Research 2014;(18):2897-2902
BACKGROUND:After glucose regulated protein 94 (GRP94) was knockout in model mice of transplanted tumor, cel ular adhesion is terminated, thus stimulating the proliferation of liver-derived cel s and promoting the development of liver cancer. We speculate that GRP94 plays a protective role against liver cancer.
OBJECTIVE:To investigate the expression of endoplasmic reticulum molecular chaperone GRP94 mRNA and protein with smal interfering RNA technique in nude mice model of transplantable human ovarian carcinoma, and to explore the effect of GRP94 mRNA and protein expression on the growth of transplanted tumor.
METHODS:The gene sequences of human GRP94 were obtained from Gene Bank. psiSTRIKETM/GRP94 was constructed, which is eukaryotic expression vector control ed by the U6 promoter of human RNA polymerase Ⅲ. The transplantable model of human ovarian carcinoma in nude mice was established using human ovarian cancer HO-8910 cel line. The eukaryotic expression vector was transfected into the transplanted tumors in nude mice, and the growth of the tumor was observed. The nude mice models were divided into three groups, specific smal interfering RNA group, non-specific smal interfering RNA group and saline control group. The volumes of the subcutaneous tumor were determined. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of GRP94 respectively.
RESULTS AND CONCLUSION:The recombinant plasmid of RNA interference specific for GRP94 was successful y constructed. The subcutaneous tumors appeared in al the nude mice 5 days after transplantation. The diameter of subcutaneous tumors was 7-10 mm 14 days after transplantation. The growth of subcutaneous tumors in nude mice with interference specific for GRP94 treatment was significantly decreased as compared with non-specific smal interfering RNA group and control group (P<0.05). The proliferation activity was inhibited by 65.1%. The expression of GRP94 mRNA and protein was significantly down-regulated after treatment of psiSTRIKETM/GRP94 (P<0.01). The transfection of psiSTRIKETM/GRP94 could significantly induce inhibitory effects on the growth of ovarian carcinoma in nude mice, and the underlying mechanism is associated with the down-regulated expression of GRP94 mRNA and protein.
8.Percutaneous dilatational tracheostomy for ICU patients with severe brain injury
Xiaoshun AI ; Dongyuan GOU ; Li ZHANG ; Liying CHEN
Chinese Journal of Traumatology 2014;(6):335-337
Objective: To sum up our experience in percutaneous dilatational tracheostomy (PDT) in ICU patient with severe brain injury.
Methods: Between November 2011 and April 2014, PDTs were performed on 32 severe brain injury patients in ICU by a team of physicians and intensivists. The success rate, efficacy, safety, and complications including stomal infection and bleeding, paratracheal insertion, pneumothorax, pneumomediastinum, tracheal laceration, as well as clinically significant tracheal stenosis were carefully monitored and recorded respectively.
Results: The operations took 4-15 minutes (mean 9.1 minutes±4.2 minutes). Totally 4 cases suffered from complications in the operations: 3 cases of stomal bleeding, and 1 case of intratracheal bloody secretion, but none required intervention. Paratracheal insertion, pneumothorax, pneumomediastinum, tracheal laceration, or clinically significant tracheal stenosis were not found in PDT patients. There was no procedure-related death occurring during or after PDT.
Conclusion: Our study demonstrats that PDT is a safe, highly effective, and minimally invasive procedure. The appropriate sedation and airway management perioperatively help to reduce complication rates. PDT should be performed or supervised by a team of physicians with extensive experience in this procedure, and also an intensivist with experience in difficult airway management.
9.Mrp14 is a potential biomarker for biliary tract neoplasms
Zhihui GAO ; Tao Lü ; Houbao LIU ; Liying WANG ; Xiliang ZHA ; Zhilong AI ; Tao SUO ; Saixiong TONG ; Bingsheng WANG
Chinese Journal of Hepatobiliary Surgery 2011;17(9):722-726
ObjectiveTo provide clues to find a biomarker for early diagnosis, prognosis and therapy, as well as to understand the molecular mechanisms governing cancer progression. Methods Surgical specimens were obtained from 87 patients with histopathologically proven malignant or benign lesions. The differential protein profiles of these malignant and benign specimens were detected using two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Western blotting and immuno-histochemistry were used to validate the results. RT-PCR was used to detect the gene expression in the tissues. ResultsMrp14 was found to be overexpressed in the tumor tissues of gallbladder cancer and extra-hepatic bile duct cancer, and in the bile of patients with malignant biliary tract tumours. The result was further verified using Western blot and immuno-histochemistry. RT-PCR confirmed the overexpression of Mrpl4 at the gene level. Mrp14 is a potential biomarker for biliary tract neoplasms. ConclusionsThis is the first report which described the overexpression of Mrp14 in biliary tract neoplasms and further studies are needed to confirm our findings. Mrp14 may be a potential hiomarker for biliary tract neoplasms. It may provide important clues on the molecular mechanisms governing cancer progression.

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