Objective To study the mechanism of endoplamic reticulum stress(ERS)pretreatment induced by 2-DG on the auditory cortex injury after focal cerebral ischemia-reperfusion injury in rats. Methods The SD rats were randomly divided into 3 groups,sham group,I/R group,and ERS pretreatment group. Tread occlusion was used to prepare the model of MCAO in the mice for 60 min followed by reperfusion for 24 h. Neurological assessment was exercised and brain infarction volume was evaluated. The auditory brainstem response was tested. The pathological changes were observed by HE staining. Neurocyte apoptosis was observed by Tunel ,and the apop-tosis index(AI)was determined. Expression of GRP78 and Caspase-12 were detected by immunohistochemistry. Results Compared with the sham group,the neurological scores,ratio of infarct volume and the hearing thresh-olds in I/R group increased significantly. HE staining showed the normal structure disappeared ,and apoptotic index increased significantly. Expression of GRP78 and Caspase-12 protein significantly up-regulated. Compared with I/R group,the indicators above showed improvement to some degrees. Conclusions The ERS pretreatment can alleviate the ischemia-reperfusion injury and neuron apoptosis in auditory cortex ,and reduce the possibility of hearing loss.

Objective To produce a plastic ampoule with an opening that fits syringe adapters to allow solutions to be drawn up without needles (to avoid needle stick and sharps injuries) and to test the effectiveness of the new design in terms of residual fluid volume and risk of microorganism contamination. Methods Evaluation study based on laboratory research was adopted. For the experimental group, 30 ampoules based on the new design were produced by 3D printing. The ampoules were sterilized and filled with 2 ml sterile water. The sterile water was drawn up without the use of needles, and the wastage fluid (i.e., 2 ml minus the quantity drawn up) was calculated. A 1 ml aliquot of sterile water from each ampoule was dropped onto a nutrient agar plate, and the number of colony-forming units was assessed after 48 h. For each ampoule, the experiment was performed twice. Sixty 2 ml glass-packaged sterile water injections constituted the control group. The fluid was drawn up with a needle, and the superfluous fluid and number of colony-forming units were assessed, as in the experimental group. Results The mean wastage fluid was 0.06 ml, 95% CI was 0.05-0.07 ml in the experimental group and the superfluous fluid was 0.06 ml, 95% CI was 0.06-0.07 ml in the control group, there was no significant difference between the two groups (Z=-1.194, P=0.233). The number of colony-forming units was 8 in the experimental group and 4 in the control group, there was no significant difference between the two groups (P=0.224). Conclusions The newly designed plastic ampoule opening could help health workers to avoid needle stick and sharps injuries when drawing up solution. The wastage fluid and microorganism contamination levels met the required standards, indicating that the new design is suitable for clinical application.

Objective To study the effect and mechanism of endoplamic reticulum stress on the auditory cortex injury after focal cerebral ischemia-reperfusion injury in rats.Methods 30 healthy male adult SD rats were chosen and randomly divided into 2 groups,ischemia-reperfusion(I/R) group and sham operated control,with each group 15 rats.The rats in I/R group were operated for suture-occluded method to establish middle cerebral artery occlusionmodel(MCAO),with ischemia for 60 mins followed by reperfusion for 24 h.And the control group was only to be isolated cervical vessels,with no thread embolism inserted.The auditory brainstem response (ABR) was tested before operation and at 24 h post-operation respectively.The neurological deficits,ratio of infarct volume were evaluated.The pathological changes were observed by HE.Neurocyte apoptosis were observed by Tunel,and the AI were determined.The expression of GRP78,Caspase-12 were detected by immunohistochemistry and Western blotting.Results Compared with the sham group,the neurological function scores,the infarct volume of brain of I/R group increased significantly.The threshold of ABR elevated significantly and AI rised in I/R group.HE staining showed that the neurons in the sham group were arranged in order,the shape was normal,but in the I/R group the normal structure disappeared,the nuclei were condensed.The expression of GRP78,Caspase-12 protein were significantly up-regulated.All of the differences above have statistical significance(P＜0.05).Conclusion The mechanism of hearing loss after focal cerebral ischemia-reperfusion injury in rats is perhaps related to endoplamic reticulum stress,and GRP78,Caspase-12 participate in the process of neuron apoptosis on auditory cortex caused by ERS.

Objective To analyze the levels of serum thrombin-activatable fibrinolysis inhibitor ( TAFI) in patients with chronic hepatitis B ( CHB ) with different degrees of hepatic fibrosis , and to evaluate the value of TAFI in the evaluation of liver fibrosis .Methods Forty six patients with CHB who underwent liver biopsy from June 2016 to March 2017 in Zhejiang Provincial People' s Hospital were enrolled.According to liver fibrosis stage (S0-4), they were divided into mild liver fibrosis group (S0-1, n=16), significant liver fibrosis group (S2, n=15) and severe liver fibrosis group (S3-4, n=15).At the same time, 16 healthy subjects were randomly selected as health controls in the physical examination center of the hospital .Serum TAFI levels were analyzed in each group , and the receiver operating curve ( ROC) was used to evaluate the diagnostic value of TAFI in CHB patients with significant liver fibrosis and severe liver fibrosis (S≥2).The SPSS 23.0 software was used to analyze the data .Results Serum TAFI levels in the mild liver fibrosis group , significant liver fibrosis group , severe liver fibrosis group and health controls were (63.4 ±18.2), (43.8 ±20.4), (27.5 ±19.2) and (71.3 ±25.6) ng/mL, the difference between the four groups was statistically significant (F=13.512, P<0.01).The level of TAFI in the significant liver fibrosis group was lower than that in the healthy control group and the mild liver fibrosis group (t=3.283 and 2.822, P<0.01).The level of TAFI in the severe fibrosis group was lower than that in the significant liver fibrosis group (t=2.260, P<0.05).Serum TAFI levels were negatively correlated with liver fibrosis stage (r=-0.562, P<0.01).The area under the ROC curve of TAFI for predicting liver fibrosis (S≥2) was 0.832, and the sensitivity and specificity were 81.3％and 78.3％, respectively. Compared with the APRI score and the FIB4 index, the difference was not statistically significant ( P >0.05).Conclusion The serum TAFI level is negatively correlated with the degree of liver fibrosis in CHB patients, which has a good diagnostic value for liver fibrosis (S≥2) in patients with CHB.

OBJECTIVE: The pathogenesis of depression is not fully understood yet, but studies have suggested higher circulating C reactive protein (CRP) level might relate to depression occurrence. However, due to high variability of patients’ individual condition, the results to date are inconsistent. Considering CRP single-nucleotide polymorphisms (SNPs) could also regulate plasma CRP levels, in the present study, we hypothesized that inherited CRP allelic variations may co-vary with depressive symptomatology. METHODS: We recruited 60 depression patients with family depression history and 60 healthy control volunteers into this project. We detected circulation CRP level as well as genome CRP SNPs from participants of this project. RESULTS: We have found a significantly higher circulating CRP level in patients with a positive family history. Furthermore, we also identified some certain inherited CRP SNPs (A allele in rs1417938 and C allele in rs1205) could up regulate serum CRP level and distributed more in depression patients with family history. CONCLUSION: Our finding may raise new evidence that genetically increased serum CRP level through SNPs variation is likely to induce family inherited depression.
Alleles ; C-Reactive Protein* ; Depression* ; Genome ; Humans ; Plasma ; Polymorphism, Single Nucleotide ; Volunteers

Objective To explore the value of combined detection of serum pyruvate dehydrogenase kinase isoenzyme 4(PDK4),2,4-dienoyl coenzyme A reductase 1(DECR1)and matrix metalloproteinase 1(MMP1)in the diagnosis,clinical grading and prognosis of diabetes cardiomyopathy(DCM).Methods A sum of 26 patients with diabetes cardiomyopathy(DCM group)and 120 patients with diabetes non cardiomyopathy(control group)who were admitted to Shaanxi Provincial People's Hospital from October 2021 to October 2023 were selected.The expression levels of PDK4,DECR1 and MMP1 proteins in serum were measured by enzyme-linked immunosorbent assay(ELISA)to evaluate the diagnostic value of these three detection indicators in DCM.Results Compared with the Control group,the levels of serum PDK4(131.38±10.20 pg/ml vs 82.69±8.17 pg/ml),DECR1(152.06±12.57 pg/ml vs 86.14±9.55 pg/ml)and MMP1(40.27±4.02 μg/ml vs 17.77±0.98 μg/ml)protein in the diabetes cardiomyopathy(DCM)group were significantly higher,and the differences were statistically significant(t=36.24,47.63,12.29,all P＜0.001).In the DCM group,the protein expression levels of serum PDK4,DECR1 and MMP1 were correlated with NYHA cardiac function grading,while the protein expression levels were significantly increased with the grade increasing,and the differences between the groups were statistically significant(F=24.12,30.04,12.66,all P＜0.001).In the DCM group,compared with the mild group,the expression levels of serum PDK4(164.92±1.35pg/ml vs 122.48±8.78pg/ml),DECR1(192.17±9.11pg/ml vs 124.36±10.83pg/ml)and MMP1(84.44±7.38 μg/ml vs 39.41±3.05 μ g/ml)proteins were significantly increased in patients with moderate to severe illness,and the differences were statistically significant(t=26.33,47.12,15.41,all P＜0.001).The accuracy(x2=18.23,21.37,22.07),specificity(x2=9.72,13.43,15.12)and sensitivity(x2=12.07,16.07,17.55)of serum PDK4,DECR1 and MMP1 were significantly higher than those of single Test(all P＜0.05),the results of ROC curve analysis showed that the AUC of combined detection was 0.955,which was significantly higher than that of single detection(Z=16.67,17.09,20.44,all P＜0.05).Conclusion Serum PDK4,DECR1 and MMP1 are related to the diagnosis,clinical grading and prognosis of diabetes cardiomyopathy.The combined detection of the three is helpful to the differential diagnosis of diabetes cardiomyopathy.

Objective: To investigate the role of human papillomavirus (HPV) 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein (hnRNP) E2 and their interaction effects in the progression of the cervical cancer. Methods: Women with normal cervix (NC), low cervical intraepithelial neoplasia (CIN Ⅰ) and high cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) from the cervical lesions cohort in Jiexiu County of Shanxi Province from June 2014 to September 2014, and patients with cervical squamous cell carcinoma (SCC) treated at the Second Hospital of Shanxi Medical University in the same period were enrolled in this study. There were 257 participants, about 67 NC cases (26.07%), 69 CIN Ⅰ cases (26.85%), 68 CIN Ⅱ/Ⅲ cases (26.46%), and 53 SCC cases (20.62%), respectively. The information of demographic characteristics, life health habits and cervical lesions were collected by using the structured questionnaire. Cervical exfoliated cells and cervical biopsy tissues were collected to detect the infection of HPV16 and the protein expression levels of hnRNP E2, HPV16 E2 and E6. According to the median-value of the protein expression levels of hnRNP E2, HPV16 E2 and E6 and E2/E6 ratio in the NC group, the study participants were divided into the high and low expression groups/ratio groups. The multivariate logistic regression model was used to analyze the correlation between HPV16 early gene E2 and E6, hnRNP E2 and cervical cancer. The interaction effect was analyzed by using the generalized multifactor dimensionality reduction (GMDR) model. Results: The ages of NC, CIN Ⅰ, CIN Ⅱ/Ⅲ and SCC groups were (47.00±9.07), (47.64±7.35), (46.37±8.67) and (51.26±8.03) years old, respectively. The multivariate logistic regression model analysis showed that the HPV16 E2 low expression, E6 high expression and E2/E6 low ratio could increase the risk of CIN Ⅱ/Ⅲ, about OR (95%CI) values 11.11 (1.63-75.56), 8.00 (1.28-50.04), and 9.75 (1.22-77.72), respectively and SCC, about OR (95%CI) values 14.22 (2.11-95.88), 10.33 (1.67-64.00), and 12.38 (1.56-97.91), respectively. The hnRNP E2 low expression could increase the risk of CIN Ⅱ/Ⅲ and SCC, about OR (95%CI) values 3.35 (1.39-8.10) and 5.53 (1.54-19.88). The result of GMDR showed that there were interaction effects of the hnRNP E2 low expression, HPV16 E2 low expression and HPV16 E6 high expression in both CIN Ⅱ/Ⅲ and SCC groups. Conclusion The HPV16 E2 low expression, HPV16 E6 high expression and hnRNP E2 low expression could increase the risk of high-grade cervical intraepithelial neoplasia and cervical cancer, and they might have an important interaction effect in the progression of the cervical cancer.

Objective To explore the effect ofpolycyclic aromatic hydrocarbons (PAHs) and p16,FHIT gene CpG island methylation,as well as their interaction in cervical intraepithelial neoplasias.Methods Objects of this study were from a cohort of cervical lesions study in Yangqu county of Shanxi province.All the patients were diagnosed pathologically,that including 83 patients with high-grade cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ),86 patients with low-grade cervical intraepithelial neoplasia (C1N Ⅰ) and another 91 women under normal cervical (NC) condition.1-hydroxy pyrene in the urine was detected by high performance liquid chromatography (HPLC)while CpG island methylation status of tumor suppressor gene p16 and FHIT were measured by methylation-specifc polymerase chain reaction (MSP).Data were analyzed with Kruskal-Wallis H test,chi-square test and trend of chi-square test.Logistic regression models were used to estimate the odds ratio (OR) and corresponding 95％ confidence intervals (95％CI) between influencing factors and the cervical disease by using the SPSS statistical software (version 20.0).The interaction under study was evaluated by using the generalized multifactor dimensionality reduction (GMDR) model.Results Level of 1-hydroxy pyrene (H=50.743,P＜0.001) and the high exposure rate of 1-hydroxy pyrene (trend x2=20.146,P＜0.001) were gradually increasing along with the severity of cervical intraepithelial neoplasia.The CpG island methylation rates ofpl6,FHIT in CIN] and CIN Ⅱ/Ⅲl group were higher than that in NC group,and gradually increasing along with the severity of cervical intraepithelial neoplasia (trend x2=9.75,P=0.002;trend x 2 =10.39,P=0.001).Results from the GMDR model showed that interaction existed among the high exposure of l-hydroxy pyrene and the CpG island methylation ofpl6,FHIT in CIN Ⅰ and CIN Ⅱ]/Ⅲ group.Conclusion Under the high exposure of 1-hydroxy pyrene and the CpG island methylation of p16,FHIT appeared to have increased the risk of cervical intraepithelial neoplasia and causing synergistic effect in cervical intraepithelial neoplasia.

Objective To explore the effect of Src on cervical cancer cells through ERK signal transduction pathway.Methods Experimental study was carried out in vitro.Cervical cancer cell lines Hela (HPV-positive) and C33A (HPV-negative) were treated with Src kinase inhibitor PP2.Then,the cell cycle and apoptosis of each group were evaluated by using flow cytometry (FCM).Western blotting and Real-time PCR were used to detect the levels of the expression of ERK 1/2,c-Fos and c-Jun mRNA and protein respectively.The database was established and analyzed with SPSS statistical software (version 20.0).Results After down-regulating Src,the cell proliferation was inhibited and cell apoptosis was induced.The proportions of G0/G 1 stage of Hela and C33A cell in cell cycle increased while G2/M and S stages decreased.Meanwhile,the mRNA levels of ERK 1,ERK 2,c-Fos and c-Jun increased.And the expression levels of ERK 1/2,phosphorylated ERK 1/2 (p-ERK 1/2)and phosphorylated c-Fos (p-c-Fos) protein decreased,while c-Jun and phosphorylated c-Jun (p-c-Jun)protein expression increased.In addtion,the change level of Hela cell,p-ERK 1/2 and c-Fos protein were lower than that of C33A cell before and after the Src inhibition.Conclusions Src,involved in regulating the expression of key factors of the ERK signal transduction pathway including p-ERK 1/2 and p-c-Fos,might be capable of promoting the proliferation of cervical cancer cells and inhibiting their apoptosis.The infection with HPV might have adjustable effect on this process.