AIM:To study the effect of gossypol on the cognitive function of type 2 diabetic rats,and to explore its mechanism. METHODS:Thirty male Sprague-Dawley rats were divided into three groups randomly:normal group,type 2 diabetic group and gossypol treated group. After fed with high-fat diet for 4 weeks,the later two groups were injected with streptozotocin intraperitoneally to establish type 2 diabetic rat model. The animals in gossypol treated group were given gossypol at dosage of 15 mg/kg once per day for 4 weeks by gavage. Since 5th week,the times of gavages were changed into once per week at the same dosage and lasted to 12th week. Learning and memory abilities of rats were assayed with Morris water maze test. The concentration of blood glucose was measured by biochemical method. The levels of serum corticosterone and insulin were detected by enzyme-linked immunosorbent assay and radioimmunoassay,respectively. The protein expressions of 11?-HSD1 and GR in cerebral cortex and hippocampus were determined by Western blotting. The morphological changes of cerebral cortex and hippocampus were observed under light microscope and transmission electronic microscope,respectively. RESULTS:Compared to normal group,the karyopyknosis,dilation of golgiosome and mitochondria swelling of neuron from cerebral cortex and hippocampus were prominent in diabetic group. The concentrations of blood glucose,serum corticosterone and insulin increased significantly (P

AIM:To observe the effect of the extract of Ginkgo biloba(EGB)on pituitary-testicular axis and the mRNA expressions of luteinizing hormone receptor(LHR)and steroidogenic acute regulatory protein(StAR).METHODS:Thirty male Sprague-Dauley rats were divided into three groups randomly:normal control group,type II diabetic group and EGB treatment group.After fed with high-fat diet for 4 weeks,the later two groups were injected with strepozotocin intraperitoneally to induce type II diabetes mellitus.The EGB treatment group was given EGB at the dose of 50 mg/kg once a day for 12 weeks by intragastric administration.The normal control and diabetic group were given normal saline of equal volume per day for 12 weeks.The indices of blood glucose,insulin and low-density lipoprotein-cholesterol(LDL-c)were measured.The morphologic change of testicular tissue was observed under light microscopy(LM)and transmission electron microscopy(TEM)respectively.The concentrations of blood luteinizing hormone(LH)and testosterone(T)were assayed by the technique of enzyme linked immunosorbent assay(ELISA).The mRNA expressions of LHR and StAR from Leydig cells were detected by RT-PCR.RESULTS:The concentrations of blood glucose,insulin and LDL-c increased obviously,and the testis weights lessened obviously in type II diabetic groups compared to those in normal control groups.Rare spermatogenic cells of seminiferous tubule and germinal arrest were observed in diabetic group under LM.Ultrastructural analysis of testicular tissue by TEM showed dilation of the endoplasmic reticulum and mitochondrial swelling in Leydig cell and sertoli cell in diabetic group.The level of blood LH and T decreased in typeⅡ diabetic groups in comparison with that in the normal control group.Compared to normal groups,the mRNA expression of StAR in type Ⅱ diabetic groups decreased,while the mRNA expression of LHR increased.After the treatment of EGB,the pathological change of testis was relieved,the concentrations of blood glucose,insulin and LDL-c were decreased,the level of blood LH and T,and the mRNA expression of StAR were increased,and the mRNA expression of LHR descended compared to type Ⅱ diabetic groups.CONCLUSION:EGB may increase the LH-induced testosterone production by correcting metabolic disorder of glucose and lipid,improving the function of pituitary-testicular axis and regulating the expression of LHR and StAR mRNA.

Objective To evaluate the potential use of a probe melting analysis (PMA) assay in detecting the embB mutations which confer resistance against ethambutol in Mycobacterium tuberculosis. Methods The analysis sensitivity and specificity of PMA were investigated by detecting a serially diluted H37 Rv DNA and a reference panel from National Institute for the Control of Pharmaceutical and Biological Product. Six hundred and thirteen sputum samples were collected from the Xiamen Center for Disease Control and Prevention, Xiamen First Hospital and Center for Zhangzhou Disease Control and Prevention from September 2009 to April 2010. The PMA assay was then evaluated by detecting 613 clinical isolates and the results were compared with the sequencing results. Results The PMA assay could specifically detect Mycobacterium tuberculosis and had a limit of detection of 3 copies per reaction. The assay results with 613 clinical isolates showed that PMA gave a 100% concordance with sequencing in the 583 qualified samples, among which 34 were mutations at embB 306,23 at embB 378-380, 3 at embB 406 and 3 at embB 497. Conclusions PMA assay is a sensitive and specific method enabling efficient detection of common embB mutations causing ethambutol-resistance. The rapidness of this method together with its reliability would facilitate its use in routine testing.

Objective To observe the blood biochemical and histological changes before and after pancreas freezing, to provide evidence for cryosurgery for pancreatic cancer. Methods Fifteen healthy pigs were divided into deep frozen group (n = 5), shallow frozen group (n = 5), non-frozen group (n = 3) and normal group (n = 2). After anesthesia and Iaparotomy, a probe of the Argon-Helium Surgical System was inserted into the pancreas, 100% and 10% argon output power were used in deep and shallow frozen group, respectively;and the temperature were - 130 ～ - 140℃ and - 110 ～ - 120℃, respectively;which results in an ice-ball with 15 ～ 20 mm in diameter. Then helium gas was inputted to increase the temperature to 10 ～ 20℃ for three minutes;then the whole process was repeated. A probe was inserted into the pancreas in the non-frozen group only and only laparotomy was performed in non-grozen group normal group and normal group. Serum amylase, IL-6, CRP levels before and after the experiment was determined;the pigs were sacrificed at day 7 and the pancreas was harvested for light microscope and electron microscope examination. Results The frozen pancreatic tissue became pitchy necrosis zone, and it could be distinguished from non-frozen tissue;there were obvious tissue necrosis in the center and para-center of frozen area, and the ultra-structure were destroyed and disappeared, mitochondria degranulation and rough endoplasmic reticulum degrannlation were observed. Serum amylase was elevated in 13 (86.7%) pigs and most returned to normal at 6th day. Serum IL-6 was slightly elevated in 5 (33.3%) pigs. There was no significant difference among all the groups in term of serum CRP. All the pigs were alive until the time of sacrifice. Conclusions Cryosurgery has affirmative fatal ablative effects on pancreatic tissue, and it is safe with no serious complications.

Objective To observe the adverse reaction, tumor response and short term outcomes of percutaneous cryoablation for locally advanced pancreatic cancer, and investigate its feasibility. Methods Fifty-nine consecutive patients with locally advanced, unresectable pancreatic cancer underwent percutaneous cryoablation at our hospital from Sept. 2008 to Sept. 2009, were prospectively studied. Percutaneous cryoablation was performed with an argon/helium-based cryosurgical system under the guidance of ultrasound.Freezing probe was inserted into the center of pancreatic mass and two cycles of freezing were performed with each cycle for 5 min and temperature at-160℃, then the temperature was returned to normal for 10 min.Serum amylase was detected before operation and 1 to 7 days postoperatively. CT or PET-CT scanning was performed for evaluation of tumor response every 4 to 6 weeks after cryoablation. Survival was assessed by Kaplan-Meier method. Results 59 patients had a total of 76 biopsy-proven tumors, which were located at the pancreas head (n = 56), body (n = 7), and tail (n = 13). The median size of tumor was 4.5 cm (range 3 ～6 cm). Nineteen patients had liver metastases. Postoperative abdominal pain occurred in 45 cases (76.3%),fever occurred in 29 cases (49.2%) and elevation of serum amylase occurred in 34 cases (57.6%). Severe complications including intra-abdominal bleeding, pancreatic leaks, ileus, and metastasis by probe tract occurred in 5 cases (8.5%). There was no death associated with cryoablation. The median hospital stay was 21 days. 2 patients (3.4%) achieved complete response, 23 patients (39.0%) achieved partial response,30patients (50.8%) had stable disease, 4 patients(6.8%) had progressive disease. The median survival was 8.4 months. The overall survival at 3, 6 and 12 months was 89.7%, 61.1% and 34.5%, respectively.Conclusions Ultrasound-guided percutaneous cryoablation appears to be a safe and feasible, minimally invasive technique for locally advanced pancreatic cancer.

AIM:To study the effect and mechanism of extract of ginkgo biloba(EGB) on liver glucocorticoid receptor(GR) expression in type 2 diabetic rats.METHODS:Thirty male Sprague-Dawley rats were divided randomly into three groups:normal control group(n=10),type 2 diabetic group(n=10) and ginkgo biloba treated group(n=10).After fed with high-fat feeding for 4 weeks,the later two groups were injected with streptozotocin at a dose of 30 mg/kg intraperitoneally to induce type 2 diabetic rat model.The EGB treated group was gavaged with EGB at the dose of 50 mg?kg-1?d-1 for 12 weeks.At the end of experiment,the rats were sacrificed,the blood glucose,serum lipid and blood insulin were measured.The morphology of liver tissue was observed under light microscopy with HE staining.GR mRNA expression in liver was measured by RT-PCR.The level of GR protein expression in liver tissue was detected by immunohistochemistry.RESULTS:EGB reduced the levels of blood glucose,blood lipids,blood insulin in diabetic rats.EGB also relieved fatty degeneration and necrosis of the hepatic cells,ameliorated infiltration of inflammatory cells in the liver;and decreased GR expression at both mRNA and protein levels in diabetic liver.CONCLUSION:EGB may inhibit GR expression in liver of type 2 diabetic rats,which results in decreasing the level of blood glucose,blood lipid,blood insulin and relieving the liver damage in type diabetic rats.

Objective To explore the safety and short?term efficacy of irreversible electroporation (IRE)ablation which is a novel ablation technology in unresectable hepatic neoplasms. Methods Patients with pathologically diagnosed as liver cancer or liver metastases were prospectively enrolled. The patients were not suitable for surgery with PS score ≤ 2. Exclusion criteria included who was not tolerate general anesthesia, severe liver and kidney dysfunction, and with cardiac pacemaker. A total of 16 patients were included in this study. There was 12 males and 4 females, aged 40 to 86 years with mean age (60 ± 10)y. Ultrasound and CT guided percutaneous IRE ablation was performed. Perioperative hemodynamic changes were reviewed. Liver and kindey function before and 7 d after ablation was compare by t test. The adverse reactions within 30 d after ablation treatment were recorded. CT and MR scans within 1 month were performed and the 30 d curative effect was evaluated by the modified RECIST criteria. Results All patients received IRE treatment successfully, and some patients experienced adverse reactions within 30 days after ablation, including abdominal pain in 7 cases, peritoneal effusion in 5 cases, hydrothorax in 4 cases, fever in 3 cases, cough, nausea and vomiting in 2 cases, biliary tract infection and thrombocytopenia in 1 case. After symptomatic treatment, these symptoms were improved. Severe complications, such as massive haemorrhage and bile leakage didn't occur. At 30 days after ablation, the curative effects were evaluated. Complete response (CR) was achieved in 1 patient , partial response (PR) was achieved in 12 patients, stable disease (SD) was in 2 patients , and progressive disease(PD) was 1 patients . The tumor relief rate (complete response+partial response) was 81.3%. Conclusions IRE ablation in the treatment of unresectable hepatic malignant tumor could have many advantages, including high safety, mild adverse reactions, and short?term efficacy. However, its long?term effect still need further observation.

Objective To explore the diagnostic value of serum levels of fibroblast growth factor 22(FGF22)and CXC chemokine ligand 16(CXCL16)in patients with Parkinson's disease(PD)in cognitive impairment.Methods A total of 125 PD patients admitted to Handan Traditional Chinese Medicine Hospital from June 2022 to June 2023 were selected as the research subjects,and they were separated into a non cognitive impairment group(n=38)and a cognitive impairment group(n=87)based on whether they had cognitive impairment.Enzyme-linked immunosorbent assay(ELISA)was applied to determine the levels of serum FGF22 and CXCL16 in each group.Spearman correlation was applied to analyze the correlation among serum FGF22 and CXCL16 expression levels,Unified Parkinson's Disease Rating Scale(UPDRS)and Montreal Cognitive Assessment(MoCA)scores.Multivariate logistic regression was applied to analyze the factors affecting cognitive impairment in PD patients.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic efficacy of FGF22 and CXCL16 for cognitive impairment in PD patients.Results Compared with the non cognitive impairment group,the expression level of serum FGF22(184.16±14.62ng/ml vs 203.24±12.15ng/ml)in cognitive impairment group and the MoCA score(23.91±3.14 分 vs 26.54±2.31 分)were decreased(t=7.048,4.460,all P＜0.05),while the expression levels of CXCL16(2.59±0.46ng/ml vs 2.06±0.34ng/ml)and the UPDRS score(41.43±5.62 score vs 32.46±4.28 score)were increased(t=6.376,8.782,all P＜0.05),and the differences were statisaically significant.According to Spearman correlation analysis,the expression level of serum FGF22 was negatively correlated with UPDRS score(r=-0.435,P＜0.05),but positively correlated with MoCA score(r=0.742,P＜0.05).The expression level of CXCL16 in serum was positively correlated with UPDRS score(r=0.532,P＜0.05),but negatively correlated with MoCA score(r=-0.623,P＜0.05).Multivariate logistic analysis showed that FGF22 and MoCA scores were protective factors for cognitive impairment in PD patients(all P＜0.05),while CXCL16 and UPDRS scores were risk factors for cognitive impairment in PD patients(all P＜0.05).The combination of serum FGF22 and CXCL16 in the diagnosis of cognitive impairment in PD patients had better AUC than their respective alone diagnoses(Z=2.919,2.437,P=0.003,0.015),with a sensitivity and a specificity of 93.10％and 73.68％,respectively.Conclusion The levels of serum FGF22 and CXCL16 were closely related to cognitive impairment in PD patients,and the combination of the two could better diagnose whether PD patients have cognitive impairment.

Objective:To investigate the mechanism of miR-218-5p regulating the glycolytic process in human non-small cell lung cancer A549 cells by targeting phosphodiesterase 7A(PDE7A).Methods:A549 cells were routinely cultured,and miR-218-5p mimic,mimic-NC,PDE7A overexpression plasmid(PDE7A-oe)and PDE7A control plasmid(PDE7A-NC)were transfected into A549 cells using Lipo3000,and recorded as the miR-218-5p mimic group,the mimic-NC group,the PDE7A-oe group and the PDE7A-NC group.The transfection efficiency was verified by qPCR assay;the expressions of glycolysis key enzyme proteins were detected by WB assay;the 2-deoxyglucose and lactate contents in A549 cells of each transfection group were detected by glucose assay and lactate production assay;the target binding relationship between miR-218-5p and PDE7A was verified by dual-luciferase reporter gene assay,and the data from the TCGA database were used to analyze the expression level of PDE7A mRNA in lung cancer tissues.Results:miR-218-5p was successfully overexpressed in A549 cells(P<0.01).Overexpression of miR-218-5p significantly inhibited the expressions of PDE7A,HK2,PKM2 proteins(all P<0.01),glucose uptake and lactate production(both P<0.01)in A549 cells.Overexpression of PDE7A significantly promoted the expressions of PDE7A,HK2,and PKM2 proteins(all P<0.01),as well as glucose uptake and lactate production(both P<0.01)in A549 cells.miR-218-5p in A549 cells could directly bind to the 3′-UTR of PDE7A mRNA.Database data analysis showed that PDE7A mRNA was highly expressed in lung squamous cell carcinoma tissues(P<0.01).Conclusion:miR-218-5p targets PDE7A to regulate the expression levels of HK2 and PKM2 in A549 cells,which in turn inhibits the glycolytic process.miR-218-5p/PDE7A may be a potential target for clinical diagnosis and treatment of NSCLC.