[The influence of interaction between polygenic risk score and intestinal fungal microbiota on the risk of schizophrenia].

Objective: To investigate the effect of interaction between polygenic risk score (PRS) and intestinal fungal microbiota on the risk of Schizophrenia (SCH). Methods: A case-control study was carried out. Drug-naïve, first-episode SCH patients were selected from the Psychiatric Department of the First Affiliated Hospital of Zhengzhou University between October 2017 and October 2019. Meanwhile, healthy controls (HCs) were recruited from local communities through online advertisement or physical examination center. Intestinal fungal microbiota was characterized by the 18S rRNA sequencing platform. The association of fungal microbial dysbiosis (F_MD) index, α-diversity indices and PRS with SCH was detected by logistic regression analysis. Results: A total of 137 SCH patients (62 males and 75 females) and 76 HCs (31 males and 45 females) were included in the study. The age of SCH patients and HCs was (22.5±7.5) years and (22.8±2.3) years, respectively. The results of logistic regression analysis revealed that PRS (OR=1.111, 95%CI: 1.036-1.178, P=0.002) and the increase of F_MD index (OR=1.200, 95%CI: 1.124-1.281, P<0.001) were risk factors for developing SCH. The increase of fungal α-diversity Shannon (OR=0.813, 95%CI: 0.755-0.874, P<0.001) index, Simpson index (OR=0.218, 95%CI: 0.091-0.523, P<0.001) and abundance of key Aspergillus (OR=0.928, 95%CI: 0.864-0.996, P=0.040) decreased the risk of SCH. Aspergillus abundance was positively correlated with cognitive domains including working memory (r=0.280, P=0.001), verbal learning (r=0.253, P=0.003), reasoning and problem solving (r=0.191, P=0.028). Conclusion: The increase of PRS may increase the risk of SCH. The increase of fungal α-diversity indices and Aspergillus abundance may decrease the risk of SCH. The interaction between PRS and intestinal fungi (Shannon index, Simpson index and Aspergillus) is a related factor for the risk of SCH.

[Establishment of diagnostic model for schizophrenia based on neurotrophic factor and other biomarkers].

Objective: To construct a diagnostic model of schizophrenia (SCZ) based on biomarkers such as serum neurotrophic factor. Methods: Patients of schizophrenia (SCZ group) and healthy controls (HC group) who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2019 were prospectively selected. In the SCZ group, the mental symptoms were assessed by the positive and negative symptom scale (PANSS), cognitive function was assessed by the MATRICS consensus cognitive battery (MCCB), brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), fasting glucose (FGB) and fasting insulin (FINS) levels were detected, and insulin resistance (HOMA-IR) was calculated. The same methods were used to evaluate cognitive function, measure BDNF, GDNF, FGB and FINS levels, and calculate HOMA-IR in HC group. The indexes with statistically significant differences between the two groups were selected to be included in the model. The diagnostic model was constructed by machine learning and verified by cross-validation method, the receiver operating curve (ROC) was plotted, and the area under the curve (AUC), sensitivity and specificity were calculated. Results: (1) A total of 142 patients (70 males and 72 females) with schizophrenia were finally included, and aged (25±4) years. Meanwhile, 140 healthy controls (72 males and 68 females) were also enrolled, and aged (26±4) years. In SCZ group, scores in all areas of cognitive function were lower than those in HC group (all P<0.001), the levels of serum BDNF and GDNF [(6.7±1.8) ng/ml and (405±93) pg/ml] were also lower than those in HC group [(12.3±3.2) ng/ml and (574±139) pg/ml] (both P<0.001), but the levels of FINS and HOMA-IR [(8.4±0.8) µU/ml and 1.7±0.3] were higher than those in HC group [(6.7±0.9) µU/ml and 1.4±0.3] (both P<0.001). (2) Correlation analysis showed that the level of serum BDNF had a negative correlation with negative symptom scores and total scores (r=-0.31, P<0.001; r=-0.17, P=0.040), but had a positive correlation with attention/alertness (CPT-IP) T scores, working memory (WSM-Ⅲ) T scores and visual learning (BVMT) T scores in SCZ group (r=0.39, 0.37 and 0.29, all P<0.001). The level of serum GDNF also had a positive correlation with CPT-IP T scores, WSM-Ⅲ T scores and BVMT T scores (r=0.32, P<0.001; r=0.23, P=0.007; r=0.40, P<0.001). The values of HOMA-IR had a positive correlation with social cognition (MSCEIT) T scores in SCZ group (r=0.18, P=0.033). (3) AUC of the early diagnosis model constructed by combining BDNF, GDNF and HOMA-IR was 0.890 (95%CI: 0.832-0.940), the accuracy was 0.89, the sensitivity and specificity was 0.94 and 0.82, respectively. Conclusion: The final diagnostic model based on biomarkers of serum neurotrophic factor has good diagnostic efficiency for SCZ, but large-scale independent sample verification is still needed.

HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma

Objectives High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. Methods HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. Results The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). Conclusions HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration (AU)

[Effect of the correlation between gut microbiota and folic acid in first-episode schizophrenia].

Objective: To explore the effects of gut microbiota and the serum level of folicacid on psychiatric symptoms in first-episode, drug-free schizophrenic (SCZ) patients. Methods: A total of 100 first-episode, drug-free SCZ patients (SCZ group) from the First Affiliated Hospital of Zhengzhou University and 90 demographically matched healthy individuals (healthy control group) were enrolled. The serum level of folic acid was measured by the electrochemical luminescence method.Positive and Negative Syndrome Scale (PANSS) was used to assess the psychiatric symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate cognitive function. Bacterial DNA was extracted from the fecal samples for high-through put sequencing of the 16S rRNA.The effects of gut microbiota and folic acid on the psychiatric symptoms and cognitive function in SCZ patients were explored. Results: A total of 41 males and 59 females, with an age of (22.6±8.2) years were included in the patient group, and 32 males and 58 females with an age of (23.0±3.0) years were included in the healthy control group. The fasting folic acid level inserum of the SCZ group was lower than that of healthy control group [6.92(4.98, 8.49) µg/L vs 8.93(7.13, 13.37) µg/L,P<0.001]. The relative abundance of genus Bifidobacterium[0.005(0.003, 0.013) vs 0.014(0.004, 0.031)] and genus Bacteroides[0.015(0.001, 0.091) vs 0.083(0.029, 0.193)]was lower in the SCZ group than that of the healthy control group (both P<0.001). In comparison with the healthy control group, scores of cognitive function in the seven domains were significantly lower in the SCZ group (all P<0.05). In the patient group, the serum level of folic acid was negatively related to the negative symptom score(r=-0.378, P<0.001), but had a positive correlation with the score of speed of processing (r=0.310, P=0.011).In the SCZ group, the relative abundance of the genus Bifidobacterium was positively correlated with the serum level of folic acid (r=0.374,P<0.001) and the score of speed of processing(r=0.330,P=0.003) respectively, but was negatively correlated with the general psychopathology score (r=-0.326, P=0.001). The results of multiple linear regression analysis showed that the interaction term between folic acid and genus Bifidobacteriumin in SCZ patients were correlated with the general psychopathology score, with a regression coefficient of -29.240 (F=8.655, P=0.007). There was no statistical correlation between the aforementioned interaction term and cognitive function (both P>0.05). Conclusion: In first-episode, drug-free SCZ patients, there were decreases in the serum folic acid level and the relative abundance of genus Bifidobacterium, which were related to the psychiatric symptoms, suggesting that these two substances can be used as potential objective indicators for evaluating psychiatric symptoms.

HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma.

OBJECTIVES: High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. METHODS: HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. RESULTS: The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). CONCLUSIONS: HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration.

[Effect of clinical characteristics on relapse of alcohol dependence: a prospective cohort study].

OBJECTIVE: To investigate whether craving and demographic factors to predict relapse in alcohol dependence. METHODS: This study was a prospective cohort study. From August 2017 to August 2018, 158 Han male inpatients who met the diagnositic and statistical manual disorders-fourth version(DSM-IV) alcohol dependence diagnostic criteria were recruited from three mental hospitals in China. The participants were interviewed at baseline and followed up by telephone after 3 months for assessment. The baseline assessment after the acute withdrawal period included demographic data and alcohol-related data, clinical institute withdrawal assessment-advanced revised (CIWA-Ar), withdrawal and cue-induced craving on visual analog scale (VAS), Michigan alcoholism screening test (MAST), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and alcohol urge questionnaire (AUQ). According to the follow-up results, "relapse" was defined as the consumption of beverages containing ethanol at any time during the follow-up study, and "time to relapse" was defined as the number of days from the first drinking to the baseline. Whether relapse occurred and the time to relapse were the primary endpoints. Cox proportional hazard regression model was used to analyze the factors affecting the relapse of alcohol dependence. RESULTS: In the study, 158 alcohol dependence patients were finally included, age from 21 to 60 years, with the mean age of (40.31±9.14) years. The relapse rate was 63.7% three months after baseline assessment. According to Cox univariate analysis and multivariate analysis, the age (OR=0.975, P=0.030) and CIWA-Ar scores (OR=1.126, P=0.010) significantly predicted relapse. And there was no significant difference in education level, marital status, withdrawal and cue-induced craving on VAS, SAS and SDS between the relapse group and the non-relapse group (P>0.05). CONCLUSION: Age and severity of alcohol-dependent withdrawal symptoms during hospitalization are significantly related to relapse for alcohol in alcohol-dependent patients. To be exact, the older age is a protective factor, that is to say, the younger patients are prone to relapse, while the risk of relapse is raised by the higher severity of withdrawal symptoms. However, neither cue-induced nor withdrawal craving can predict relapse of alcohol-dependent patients.

MiR-1294 acts as a tumor suppressor in clear cell renal cell carcinoma through targeting HOXA6.

OBJECTIVE: Renal cancer represents about 3% of all human cancers. Clear cell renal cell carcinoma (ccRCC) is the main type of renal cancer. MicroRNAs (miRNAs) have been reported to play crucial roles in the carcinogenesis of human cancers. This study was aimed to investigate the expression of miR-1294 and the mechanisms underlying miR-1294-mediated ccRCC progression. MATERIALS AND METHODS: The miR-1294 expression levels in ccRCC cell lines were analyzed by quantified real time-PCR (qRT-PCR). The effect of the miR-1294 expression on the overall survival of ccRCC patients was analyzed by the Kaplan-Meier Plotter. Cell proliferation, colony growth, and cell invasion were examined by cell counting kit-8 assay, colony formation assay, and transwell invasion assay, respectively. The luciferase activity reporter assay and Western blot assay were conducted to validate the connection between miR-1294 and homeobox A6 (HOXA6). RESULTS: MiR-1294 was downregulated in ccRCC cell lines and correlated with the poor overall survival of ccRCC patients. The overexpression of miR-1294 inhibits ccRCC cell proliferation, colony growth, and cell invasion. HOXA6 was validated as a target of miR-1294 and negatively regulated by miR-1294. The overexpression of HOXA6 attenuated the miR-1294-mediated effects on ccRCC cellular functions. CONCLUSIONS: Our results indicated that miR-1294 functions as a tumor suppressor in ccRCC. MiR-1294 suppressed cell proliferation, colony formation, and invasion in ccRCC partially via targeting HOXA6.

[Correlation among serum levels of Irisin, insulin resistance and abdominal obesityin patients with first-episode schizophrenia].

Objective: To explore the possible role of Irisin in antipsychotic drug-induced insulin resistance and abdominal obesity in patients with schizophrenia and to provide a theoretical basis for the prevention of antipsychotic drug-induced obesity. Methods: Fifty-five patients with first-episode schizophrenia, from the First Affiliated Hospital of Zhengzhou University, between January 2016 and December 2017, were admitted as well as fifty healthy controls during the same period. Serum Irisin levels were measured by enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose (FBG), fasting insulin (INS), homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride (TG), total cholesterol (TCHO), highdensity lipoprotein (HDL), low density lipoprotein (LDL) were detected. Results: The average Irisin level ((233±228) mmol/L) was higher than that in the normal control group ((124±89) mmol/L) (P<0.05).Repeated measurement analysis of variance showed that the average levels of the height, waist, FBG, INS, TCHO, TG, HDL, LDL, BMI, HOMA-IR and Irisin at the end of the 12(th) and 24(th) week's treatment were higher than baseline (P<0.05). After correlation analysis, the level of Irisinat baseline was positively correlated with HOMA-IR (r=0.383, P<0.05). At the 12(th) week, the level of Irisin was positively correlated with waist circumference, and HOMA-IR (r=0.360, r=0.475, all P<0.05). Multiple linear regression analysis showed that at the 12(th) week's treatment, compared with the baseline period, changes of Irisin was positively correlated with waist circumference and HOMA-IR, respectively (ß=0.453, ß=0.420, both P<0.05). Conclusion: Irisin may be involved in the process of metabolic regulation and bean early predictor of antipsychotic drug-induced insulin resistance and abdominal obesity.

[Effects of oxidative stress on cognitive impairment in first episode schizophrenia].

Objective: To observe the relationship between serum oxidative stress as well as brain-derived neurotrophic factor (BDNF) and cognitive function in first-episode drug-free schizophrenics, and to explore the possible effect of oxidative stress in cognitive impairment of first-episode schizophrenia. Methods: A total of 125 first-episode drug-free schizophrenics (schizophrenia group) from the First Affiliated Hospital of Zhengzhou University and 80 healthy individuals (control group) were enrolled. The serum concentration of oxidized glutathione (GSSG) was measured by the Microenzyme method the serum concentration of nitric oxide (NO) was measured by one-step method, the BDNF level was measured by enzyme linked immunosorbent assay and Matrics Consensus Cognitive Battery(MCCB) was used to evaluate the cognitive function. Results: (1)The serum level of BDNF in schizophrenia group (2 763±1 728 pg/ml) was significantly lower than that in control group (4 165±1 299 pg/ml)(P<0.001). And the serum levels of GSSG and NO in schizophrenia group ((36±9), (81±65) µmol/L) were significantly higher than that in control group ((27±11), (24±16) µmol/L) (P<0.001). In comparison with the control group scores were significantly lower in the seven domains of cognitive function in the schizophrenia group (all P<0.001). (2)After controlling the confounding factors like age, gender, cultural differences and course of disease by partial correlation analysis, the correlation analysis showed that: serum level of BDNF in schizophrenia group had positive correlation with Information processing rate T points, attentional facilitating T points, working memory T points and Reasoning and problem solving T points (r=0.417, 0.206, 0.247, 0.318, all P<0.05). In schizophrenia group the serum level of GSSG had a negative correlation with information processing rate T points and reasoning and problem solving T points (r=-0.321, -0.231, all P<0.05). The serum level of NO was negatively related to Information processing rate T points working memory T points Verbal learning T points(r=-0.201, -0.193, -0.237, all P<0.05). Conclusions: Oxidative stress may be involved in the cognitive impairment of schizophrenia Oxidation products are risk factors for cognitive impairment of schizophrenia and BDNF is a protective factor of cognitive function.

[Correlation of serum level of homocysteine and insulin resistance with cognitive dysfunction in first-episode schizophrenics].

Objective: To explore the relationship of serum level of homocysteine (Hcy) and insulin resistance with cognitive function in first-episode drug-free schizophrenics. Methods: A total of 80 first-episode drug-free schizophrenics (schizophrenia group) from the First Affiliated Hospital of Zhengzhou University and 70 healthy individuals (control group) were enrolled.The serum concentration of Hcy was measured by the enzymatic cycling assay, the concentration of serum fast blood-glucose(FPG) by glucose oxidase method and fast insulin (FINS) by electrical chemiluminescence immunoassay.Then insulin resistance index was calculated in the form of HOMA-IR.Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate the cognitive function. Results: (1) The serum level of Hcy in schizophrenia group [(24±6) µmoL/L]was significantly higher than that in control group[(16±4) µmoL/L] (P<0.001). And the serum level of FINS in schizophrenia group [(8.0±2.1) mU/L] was significantly higher than that in control group[(6.0±1.3) mU/L] (P<0.001). The HOMA-IR of schizophrenia group (1.6±0.5) was higher than that of control group (1.3±0.4) (P<0.001). The serum level of Hcy in schizophrenia group had positive correlations with serum FINS level, HOMA-IR and negative symptoms (r=0.365, 0.354 and 0.233, all P<0.05). In comparison with the control group , scores were significantly lower in the seven domains of cognitive function in the schizophrenia group (all P<0.05). (2) In schizophrenia group, the serum level of Hcy had a negative correlation with Information processing rate P points, Attentional facilitating P points , and Verbal learning P points (r=-0.231, -0.339, -0.255, all P<0.05); the serum level of FINS was negatively related to Attentional facilitating P points, Working memory P pointsand Visual memory P points (r=-0.317, -0.309, -0.318, all P<0.05); HOMA-IR had a negative correlation with Attentional facilitating P points, Working memory P points, and Visual memory P points (r=-0.286, -0.224, -0.266, all P<0.05). After the influencing factors were adjusted by multiple regression, the associations of serum Hcy level with Information processing rate P points, Attentional facilitating P points and Verbal learning P points were still evident, and HOMA-IR was still related with Attentional facilitating P points and Visual memory P points (all P<0.05). Conclusion: The increase of serum Hcy and insulin resistance in first-episode schizophrenics, both have some relevance with cognitive dysfunction.

[Interaction between TRPC1 and STIM1 in calcium sensing receptor mediated calcium influx and nitric oxide production in human umbilical vein endothelial cells].

Objective: To investigate the interaction of Ca(2+) protein TRPC1 and STIM1 in extracellular Ca(2+) -sensing receptor (CaR)-induced extracellular Ca(2+) influx and the production of nitric oxide (NO). Methods: Human umbilical vein endothelial cells (HUVECs) were cultured and incubated with CaR agonist spermine (activating store-operates cation channels (SOC) and receptor-operated channels (ROC)), CaR negative allosteric modulator Calhex231 (blocking SOC, activating ROC) and ROC analogue TPA (activating ROC, blocking SOC), protein kinase C (PKC) inhibitor Ro31-8220, PKCs and PKCµ inhibitor Go6967(activate SOC, blocking ROC), respectively. The interaction of TRPC1 and STIM1 was determined using the immunofluorescence methods. The interaction between TRPC1 and STIM1 were examined by Co-immuno precipitation. The HUVECs were divided into: TRPC1 and STIM1 short hairpin RNA group (shTRPC1+ shSTIM1 group), vehicle-TRPC1+ vehicle-STIM1 group and control group. The cells were incubated with four different treatments under the action of above mentioned interventions, intracellular Ca(2+) concentration ([Ca(2+) ](i)) was detected using the fluorescence Ca(2+) indicator Fura-2/AM, the production of NO was determined by DAF-FM. Results: (1) The expression of TRPC1 and STIM1 proteins levels in HUVECs: Under the confocal microscope, TRPC1 and STIM1 protein expression showed masculine gender, both located in cytoplasm in the normal control group. Post incubation with Calhex231+ TPA, Ro31-8220 and Go6967, TRPC1 and STIM1 positioned in cytoplasm was significantly reduced, and the combined TRPC1 and STIM1 was also significantly reduced. (2) The interaction of TRPC1 and STIM1 in HUVECs: The relative ratios of Calhex231+ TPA+ Spermine+ Ca(2+) group, Ro31-8220+ Spermine+ Ca(2+) group and Go6976+ Spermine+ Ca(2+) group STIM1/TRPC1 and TRPC1/STIM1 were as follows: (25.98±2.17)% and (44.10±4.01)%, (20.85±1.01)% and (46.31±3.47)%, (23.88±2.05)% and (39.65±2.91)%, which were significantly lower than those in the control group (100.00±4.66)% and (100.00±6.40)% and in the Spermine+ Ca(2+) group (106.04±2.45)% and (107.78±2.66)% (all P<0.05). (3) The influence of joint TRPC1 and STIM1 transfection to four different drugs treated HUVECs on [Ca(2+) ](i) and NO generation: The changes of two excitation fluorescence intensity ratio and NO net fluorescence intensity values were consistent, [Ca(2+) ](i) and NO net fluorescence intensity values were significantly lower in the experimental group than the control group and the vehicle group (all P<0.05), while which were similar between the vehicle group and control group (all P>0.05). Conclusions: Our results indicate that TRPC1 and STIM1 jointly regulate CaR-mediated Ca(2+) influx and nitric oxide generation in HUVECs in the form of binary complex.

[Correlations between hormone levels and psychiatric symptoms as well as cognitive function in drug-free first-episode schizophrenics].

OBJECTIVE: To explore hormone such as follicle-stimulating hormone (FSH), luteinizing (LH), prolactin (PRL), estradiol (E2), progesterone (PROG) and testosterone (TESTO) levels in first-episode drug-free schizophrenics, and the relationship between clinical symptoms and sex hormones, in order to further study the pathogenesis of schizophrenia. METHODS: Eighty-one first-episode drug-free schizophrenics including thirty-nine male and forty-two female from First Affiliated Hospital of Zhengzhou University and seventy healthy subjects (thirty male and forty female) were enrolled.Serum levels of hormone were measured using electrical chemiluminescence immunoassay, and Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate cognitive function. RESULTS: (1) The serum levels of PRL in male patients group ((24±9) ng/ml) was higher than that of control group ((10±3) ng/ml) (P<0.05), the serum levels of E2, TESTO of male patients group ((29±10) ng/ml), ((3.2±1.7) ng/ml) was lower than that of control group ((35±11) ng/ml), ((4.4±1.6) ng/ml) (P<0.05); The serum levels of PRL, TESTO of female patients group ((29±16) ng/ml), ((0.5±0.4) ng/ml) were dramatically higher than that of control group ((13±5) ng/ml), ((0.3±0.1) ng/ml) (P<0.05), the serum levels of E2 of female patients group ((51±40) ng/ml) was lower than that of control group ((63±66) ng/ml) (P=0.05). (2) The serum levels of PRL, E2, TESTO in male patients group were negatively associated with negative symptoms (r=-0.478,-0.443,-0.576, P<0.05), PRL were negatively related to positive symptoms (r=-0.542, P<0.05); In female patients group, the serum levels of PRL were negatively associated with negative symptoms (r=-0.343, P<0.05), the serum levels of E2 was negatively related to positive symptoms, general psychopathology grade, total PANSS grade (r=-0.351,-0.487,-0.405, P<0.05), TESTO had a positive correlation with positive symptoms (r=0.445, P<0.05). (3) In male patients group, PRL had an negative correlation with working memory P point, reasoning and problem solving P points (r=-0.384,-0.374, P<0.05), the serum levels of E2 was positively related to Information processing rate P points, Visual memory P points, Reasoning and problem solving P points (r=0.379, 0.336, 0.407, P<0.05), TESTO had a positive correlation with Information processing rate P points, Visual memory P points, Reasoning and problem solving P points (r=0.564, 0.513, 0.552, P<0.05). In female patients group, PRL had an negative correlation with working memory P point, Reasoning and problem solving P points and social cognition P points (r=-0.303,-0.358,-0.368, P<0.05), the serum levels of E2 was positively related to working memory, Reasoning and problem solving P points, social cognition P points (r=0.376, 0.453, 0.355, P<0.05). CONCLUSIONS: Our study shows that first-episode drug-free schizophrenics have hormone secretion abnormal, which suggests that hypothalamus-hypophysis-gonad axis may probably involve in physiopathologic mechanism of first-episode medicine-free schizophrenics.Slightly elevated serum PRL level may be the reaction of stress response in first-episode medicine-free schizophrenics.Endogenous testosterone and estradiol may protect cognitive function against recession, and declining of testosterone and estradiol in blood is the hazards of cognitive dysfunction in first-episode drug-free male schizophrenics. PRL, E2, TESTO may be one of the measurements of the severity of clinical symptoms.

Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling.

This study aims to investigate the mechanisms involved in the action of lutein (LU) alleviating arsenic-induced reproductive toxicity using mice model. Forty male Kunming mice were received following treatments by gavage: normal saline solution (control), arsenic trioxide (ATO; 5 mg/kg/day), LU (40 mg/kg/day), and ATO + LU (5 mg/kg/day + 40 mg/kg/day). At the end, the mice were killed by cervical dislocation and weighed. Pathological examination was done on the testis. The biomedical parameters including superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. The messenger RNA (mRNA) and protein expression of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST), nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1) in testis were detected by real-time polymerase chain reaction and Western blot. We found that there was a decrease in sperm count; testis somatic index; the activities of SOD, GSH, total antioxidative capacity (p < 0.01, respectively) in ATO-treated mice, while there was an increase in the levels of sperm abnormalities, MDA, and 8-OHdG than control (p < 0.01, respectively). The groups treated with ATO + LU showed recovery of the measured parameters between those of ATO or saline-treated group. The antagonized interaction between ATO and LU was statistically significant (p < 0.01). Mice treated with ATO + LU also showed greater mRNA expression of Nrf2, HO-1, NQO1, and GST than ATO or saline-treated groups. These findings suggest that LU alleviates reproductive toxicity induced by arsenic in male mice via Nrf2 signaling, which implicates a possible mechanism of LU in preventing the reproductive injury, and elucidates that consuming the rich plant sources of LU will alleviate the reproductive toxicity induced by chemicals.

Human papillomavirus type 16 infection may be involved in esophageal squamous cell carcinoma carcinogenesis in Chinese Kazakh patients.

The aim of this study was to investigate human papillomavirus type 16 (HPV16) prevalence in esophageal squamous cell carcinoma (ESCC) in Xinjiang Kazakh patients and its role in ESCC carcinogenesis. One hundred and fifty cases of ESCC and 150 cases of corresponding normal esophageal mucosa (CNGM) samples were collected from north Xinjiang where the Kazakh ethnic group has lived since ancient times. HPV16 infection in ESCC and CNGM was detected by genotype-specific polymerase chain reaction. HPV16 DNA was detected in 55 of 150 ESCC samples (36.7%) and 24 of 150 corresponding normal esophageal mucosa samples (16%) with significant differences (P < 0.001, odds ratio = 3.039, 95% confidence interval: 1.756-5.260). No statistically significant correlations were found between HPV16 infection and the age or gender of patients, tumor site, tumor cell differentiation, or lymph node metastasis (P > 0.05). HPV16 infection is common in cases of ESCC in the Kazakh ethnic group in Xinjiang and may be involved in ESCC carcinogenesis.