ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg^-1·d^-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg^-1·d^-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.

Objective:To compare the effect of hearing improvement after canal wall down mastoidectomy and tympanoplasty(CWDM) and canal wall up mastoidectomy and tympanoplasty(CWUM).Methods:88 patients who underwent CWDM or CWUM in 2014-2017 with complete follow-up data were retrospectively studied. There were 45 males and 43 females, aged 12-68 years old, and the average follow-up time was 12.3 months. Among them, 42 cases underwent CWDM and 46 cases underwent CWUM. A series of improvements were made in the clinical practice of CWDM: (1) to expand the indications properly, including limited lesions with sclerotic mastoid and narrow tympanic sinus; (2) to form disciform cavity strictly during operation in order to retain the appropriate height of facial nerve crest; (3) to avoid the cleaning of mastoid cavity in the post-operation follow up, thus the operative cavity was effectively constricted; and (4) to transfer the temporal muscle flap in pneumatic mastoid to reduce the cavity. The condition of dry ear and the size of cavity were observed after operation. The average pure tone threshold (PTA) before/after operation and threshold changes of each frequency were compared between the two groups. SPSS 19.0 software was used to analyze the data.Results:The mastoid cavity of CWDM was significantly narrowed after operation and the width of the external auditory canal was close to the CWUM group. The postoperative PTA of the CWDM and CWUM group was reduced by 11.4 dB and 10.4 dB respectively, with no significant difference ( t=0.290, P=0.770). The average value of bone conduction threshold after operation was reduced by 1.8 dB and 1.9 dB respectively, with no significant difference ( t=-0.076, P=0.940). The mean value of ABG after operation was shortened by 9.6 dB and 8.4 dB respectively, with no significant difference ( t=-0.370, P=0.712). The threshold decrease of 1 000 Hz of CWUM was slightly better than that of CWDM, and the threshold decreases of the other frequencies of CWDM were slightly better than those of CWUM, however, the differences were not statistically significant ( P>0.05). Conclusion:Through the adjustment of indications and a series of intraoperative and postoperative improvements, CWDM can achieve the same effect of postoperative hearing improvement as CWUM.

Objective To investigate the prognostic value of preoperative neutrophil lymphocyte ratio (NLR) in patients with gastrointestinal stromal tumors (GIST).Methods The clinical-pathological data from 85 GIST cases were collected from the Second Affiliated Hospital of Wenzhou Medical University and retrospectively analyzed from June 2009 to December 2013.According to the exclusion criteria,79 cases were enrolled.Preoperative neutrophil and lymphocyte count was collected and NLR was calculated.According to the receiver operating characteristic (ROC) curve of NLR,GIST patients were divided into low NLR group (NLR ＜ 2.30) and high NLR group (NLR ≥ 2.30).Clinic-pathological features and five year disease free survival (DFS) were compared between the two groups.Results There was a statistical significant difference in tumor size and tumor risk between high NLR group and low NLR group (respectively,x2 =9.517,12.411,all P ＜ 0.05).Univariate analysis showed that the five year disease free survival rate of low NLR and high NLR group were 78％ and 32％ (x2 =18.749,P =0.000).By multivariate analysis a high NLR was identified as an independent risk factor of poorer prognosis for patients with GISTs (RR:3.516,95％CI:1.453-8.506,P=0.005).Conclusion A high preoperative NLR is an independent risk factor for the prognosis of GISTs.

Objective: To evaluate the correlation between type Ⅰ allergic reaction and pathogenesis of Meniere′s disease. Methods: A total of 35 (10 male vs. 25 female) patients aged between 21-66 years diagnosed with Meniere′s disease were recruited to this study, mean age of them was (47.3±13.6) years. The control group consisted of 15 inpatients (5 male vs. 10 female) with pharyngolaryngeal diseases but without otologic and rhinologic abnormity, mean age was 45.4±12.8 years. Allergic prevalence, serous total immunoglobulin E( tIgE ) levels, serous specific immunoglobulin E( sIgE ) levels and subtypes of T lymphocytes were measured and compared in patients with Meniere′s disease and the control group. Severity of vertigo, tinnitus and sensation of fullness were compared between Meniere′s disease patients with or without allergy. Results: Allergic prevalence were significantly different (Pearson chi-square 5.832, P<0.05) between patients with Meniere′s disease and the control group(57.1% vs. 20.0%). Patients with Meniere′s disease report higher level of serous tIgE compared with controls, the difference is statistically significant (Z=168.000, P<0.05). However, positive rates of sIgE of food allergens and inhalant allergens were not significantly different between patients with Meniere′s disease and the control group. Scores of vertiginous severity, dizziness handicap inventory (DHI) and tinnitus handicap inventory (THI) were significantly different between Meniere′s disease patients with or without allergy (P<0.05). Treg and Treg/Th17 levels (Z=26.000) were much higher in Meniere′s disease patients with allergy than in the controls(P<0.05). Conclusions Patients with Meniere′s disease report higher rate of allergy than the control group. Type Ⅰ allergic reaction is thought to be one of the possible reasons that may induce endolymphatic hydrops and lead to Meniere′s disease.

Objective To evaluate Chinese tinnitus handicap questionnaire (T HQ ) reliability and validity through clinical use and analysis .Methods A total of 230 tinnitus patients who were seen at our ENT clinic with tinnitus lasting longer than 3 months were administered with the THQ ,THI ,tinnitus questionnaire ,pure tone au‐diogram and tinnitus matching .Assessed THQ’s reliability and validity ,the relationship between THQ and its re‐lated factors .Results In the 206 tinnitus patients ,the Cronbach’sαwas 0 .93 ,split -half reliability was 0 .91 ,test-retest reliability was 0 .96 .In the 171 tinnitus patients ,the THI correlation coefficient was 0 .745 .The THQ scores were highly correlated with the hearing loss level of the worse ear .The age ,sex ,side ,complications ,dura‐tion and tinnitus matching were not correlated with THQ scores .Conclusion THQ Chinese version has good relia‐bility and validity .It is worthy of clinical application .

This study investigated the effects and molecular mechanisms of genistein in improving insulin resistance induced by free fatty acids (FFAs) in HepG2 hepatocytes. A model of insulin resistance in HepG2 cells was established by adding palmitic acid (0.5 mmol/L) to the culture medium and the cells were treated by genistein. Glucose consumption of HepG2 cells was determined by glucose oxidase method. The levels of c-jun N-terminal kinase (JNK) phosphorylation, insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation, JNK, IRS-1, phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 1 (GLUT1) proteins were detected by Western blotting. The results showed that after the treatment with palmitic acid for 24 h, the insulin-stimulated glucose transport in HepG2 cells was inhibited, and the glucose consumption was substantially reduced. Meanwhile, the expressions of IRS-1, PI-3K p85 protein and GLUT1 were obviously reduced, while the levels of JNK phosphorylation and IRS-1 Ser307 phosphorylation and the expression of JNK protein were significantly increased, as compared with cells of normal control. However, the aforementioned indices, which indicated the existence of insulin resistance, were reversed by genistein at 1-4 μmol/L in a dose-dependent manner. It was concluded that insulin resistance induced by FFAs in HepG2 hepatocytes could be improved by genistein. Genistein might reverse FFAs-induced insulin resistance in HepG2 cells by targeting JNK.

The effects of Cinnamon granules on pharmacokinetics of berberine in Rhizoma Coptidis granules in healthy male volunteers, and the compatibility mechanism of Jiao-Tai-Wan (JTW) composed of Rhizoma Coptidis granules and Cinnamon granules were investigated. The concentration of berberine in plasma of healthy male volunteers was determined directly by high performance liquid chromatography (HPLC) after an oral administration of Rhizoma Coptidis granules alone or combined with Cinnamon granules (JTW). The plasma concentration-time curves of berberine were plotted. The data were analyzed with Drug and Statistics (DAS) 2.0 pharmacokinetic program (Chinese Pharmacology Society) to obtain the main pharmacokinetic parameters. The results showed that the plasma concentration-time curve of berberine was described by a two-compartment model. The C(max), T(max), t(1/2) and CLz/F of berberine in Rhizoma Coptidis granules were 360.883 μg/L, 2.0 h, 3.882 h, 119.320 L·h(-1)·kg(-1) respectively, and those of berberine in JTW were 396.124 μg/L, 1.5 h, 4.727 h, 57.709 L·h(-1)·kg(-1) respectively. It was suggested that Rhizoma Coptidis granules combined with Cinnamon granules could increase the plasma concentration of berberine, promote berberine absorption and lengthen the detention time of berberine in healthy male volunteers.

This study investigated the effects and molecular mechanisms of genistein in improving insulin resistance induced by free fatty acids (FFAs) in HepG2 hepatocytes.A model of insulin resistance in HepG2 cells was established by adding palmitic acid (0.5 mmol/L) to the culture medium and the cells were treated by genistein.Glucose consumption of HepG2 cells was determined by glucose oxidase method.The levels of c-jun N-terminal kinase (JNK) phosphorylation,insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation,JNK,IRS-1,phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 1 (GLUT1) proteins were detected by Western blotting.The results showed that after the treatment with palmitic acid for 24 h,the insulin-stimulated glucose transport in HepG2 cells was inhibited,and the glucose consumption was substantially reduced.Meanwhile,the expressions of IRS-1,PI-3K p85 protein and GLUT1 were obviously reduced,while the levels of JNK phosphorylation and IRS-1 Ser307 phosphorylation and the expression of JNK protein were significantly increased,as compared with cells of normal control.However,the aforementioned indices,which indicated the existence of insulin resistance,were reversed by genistein at 1-4 μmol/L in a dose-dependent manner.It was concluded that insulin resistance induced by FFAs in HepG2 hepatocytes could be improved by genistein.Genistein might reverse FFAs-induced insulin resistance in HepG2 cells by targeting JNK.

The effects of Cinnamon granules on pharmacokinetics of berberine in Rhizoma Coptidis granules in healthy male volunteers,and the compatibility mechanism of Jiao-Tai-Wan (JTW) composed of Rhizoma Coptidis granules and Cinnamon granules were investigated.The concentration of berberine in plasma of healthy male volunteers was determined directly by high performance liquid chromatography (HPLC) after an oral administration of Rhizoma Coptidis granules alone or combined with Cinnamon granules (JTW).The plasma concentration-time curves of berberine were plotted.The data were analyzed with Drug and Statistics (DAS) 2.0 pharmacokinetic program (Chinese Pharmacology Society)to obtain the main pharmacokinetic parameters.The results showed that the plasma concentration-time curve of berberine was described by a two-compartment model.The Cmax,Tmax,t1/2 and CLz/F of berberine in Rhizoma Coptidis granules were 360.883 μg/L,2.0 h,3.882 h,119.320 L·h-1·kg-1 respectively,and those of berberine in JTW were 396.124 μg/L,1.5 h,4.727 h,57.709 L·h-1·kg-1 respectively.It was suggested that Rhizoma Coptidis granules combined with Cinnamon granules could increase the plasma concentration of berberine,promote berberine absorption and lengthen the detention time of berberine in healthy male volunteers.

Objective To evaluate the influences of laryngeal mask airway(LMA) combined with epidural anesthesia on hemodynamics in hypertensive patients.Methods 72 gynecological patients with stage Ⅰ to Ⅱ hypertension were randomly divided into four groups(n=18 for each):general anesthesia with tracheal intubation(group G) or LMA(group L),combination of epidural anesthesia and general anesthesia with tracheal intubation(group GE) or LMA(group LE).BP,HR,ECG,SpO2 were monitored in different time.Intraoperative awareness,the time of extubation or LMA removal and anesthetic dosages were recorded.Results During insertion of the tube or LMA,SBP,DBP,HR were significantly higher than those before anesthesia in group G and GE(P