OBJECTIVE To evaluate the mechanisms underlying the antidepressant effect of ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor(SNRI),in general and its ability to enhance monoaminergic transmission and suppress neuroinflammation in particular.METHODS① Male ICR mice were divided into vehicle(distilled water),duloxetine(DLX,10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following ig administration,the antidepressant effect of ZBH2012001 was evaluated using the tail suspension test(TST)and forced swimming test(FST).② Radioligand binding assay was conducted to evaluate the affinity of ZBH2012001 for human serotonin transporters(hSERTs)and human norepinephrine transporters(hNETs).③ Mice were divided into vehicle(distilled water),DLX(10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following drug administration,the 5-hydroxytryptophan(5-HTP)-induced head-twitch test or yohimbine-induced lethality test were performed to evaluate the effect of ZBH2012001 on the function of the 5-hydroxytryptamine(5-HT)and norepinephrine(NE)systems.④ Mice were divided into vehicle(distilled water+0.1%acetic acid),reserpine model(distilled water+reserpine 5 mg·kg-1),DLX(DLX 20 mg·kg-1+reserpine 5 mg·kg-1)and ZBH2012001(ZBH2012001 5,10 and 20 mg·kg-1+reserpine 5 mg·kg-1)groups.One hour following drug administration,reserpine was injected intraperitoneally to establish a monoamine-depletion model.The ptosis,akinesia,and hypothermia assays were performed to evaluate the effect of ZBH2012001 on the down-regulation of the reserpine-induced monoamine system.The TST in mice was used to evaluate the effect of ZBH2012001 on reserpine-induced depressive-like behavior while high-performance liquid chromatography with electrochemical detection(HPLC-ECD)was used to measure the levels of monoamines and their metabolites in the hippocampal tissue of reserpine-induced monoamine-depletion mice.ELISA was employed to detect the contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.Western blotting was used to assess the expressions of ionized calcium-binding adapter molecule-1(Iba-1)and nuclear factor-kappa B(NF-κB)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.RESULTS ① Compared with the vehicle group,ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the immobility time both in the TST in mice(P<0.01,respectively),and ZBH2012001(20 mg·kg-1)and in the FST in mice(P<0.05).② ZBH2012001 competitively inhibited the binding of[3H]-imipramine to hSERTs and[3H]-nisoxetine to hNETs,with the half maximal inhibitory concentration(IC50)values of 84.95 and 712.90 nmol·L-1,respectively.③Com-pared with the vehicle group,ZBH2012001(10 and 20 mg·kg-1)significantly increased the head twitches induced by 5-HTP in mice(P<0.01,respectively)and increased the mortality rate in mice induced by yohimbine(P<0.05,P<0.01).④ In the reserpine-induced monoamine-depletion model in mice,compared with the vehicle group,mice in the reserpine model group exhibited ptosis,akinesia and hypothermia feature(P<0.01,respectively),significantly prolonged immobility time in the TST(P<0.01),significantly decreased the levels of NE,5-HT and dopamine(DA)(P<0.05,P<0.01),significantly increased the metabolic conversion rate of 5-HT and DA(P<0.01,respectively),significantly elevated levels of TNF-α and IL-6(P<0.05,respectively),and significantly increased expressions of Iba-1 and NF-κB(P<0.05,respectively)in the hippocampus.Compared with the model group,ZBH2012001(5,10 and 20 mg·kg-1)significantly antagonized ptosis and hypothermia behaviors induced by reserpine(P<0.01,respectively),ZBH2012001(10 and 20 mg·kg-1)significantly shortened the immobility time in reserpine-treated mice(P<0.05,P<0.01),ZBH2012001(20 mg·kg-1)significantly increased the levels of NE and 5-HT in the hippocampus of reserpine-treated mice(P<0.05,respectively),decreased the metabolic conversion rate of 5-HT(P<0.05),significantly reduced the contents of TNF-α and IL-6 in the hippocampus of reserpine-treated mice(P<0.05,respectively),ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the expression of Iba-1 protein in the hippocampus of reserpine-treated mice(P<0.01,respec-tively),and ZBH2012001(20 mg·kg-1)significantly reduced the expression of NF-κB protein in the hippocampus of reserpine-treated mice(P<0.05).CONCLUSION ZBH2012001 exerts its antidepres-sant effect through a dual mechanism involving monoamine enhancement and inflammation suppres-sion.

OBJECTIVE AMPK activator,act as exer-cise mimetics,effective in preventing or ameliorating met-abolic diseases,including obesity and diabetes.Systemic activating of AMPK represents an important therapeutic strategy to treat metabolic diseases.However,whether far-infrared(FIR)hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regu-lation,and its underling mechanisms remain unclear.METHODS The mice were subjected to hyperthermia in the FIR chamber(30±1)℃for 14 d.Exercise endurance was determined using a treadmill.Blood flow were mea-sured by the laser speckle contrast imaging.Combina-tion of microbiomic and metabolomic analysis,diversity of microbiota and metabolic profiling in muscle were detected.The microbiota disorder model via treatment with different cocktails of antibiotics(ABX).RESULTS The material characterization shows that the graphene synthesized by chemical vapour deposition(CVD)is dif-ferent from carbon fi ber,with single-layer structure and high electrothermal transform efficiency.The emission spectra generated by graphene-FIR device would maxi-mize matching those adsorbed by tissues(≈8.0 μm).Gra-phene-FIR improves core and epidermal temperature,and increases blood flow in femoral muscle and abdo-men.The diversity of gut microbiota was increased by graphene-FIR exposure.Graphene-FIR reduced the bac-teroidetes/firmicutes(B/F)ratio and increased the abun-dance of short-chain fatty acids(SCFA)-producing bac-teria,including Allobaculum,Blautia and Anaerostipes.Additionally,graphene-FIR stimulated the expression of SCFAs-sensing receptor(GPR 43),p-AMPK Thr172 and GLUT4,and increased the AMP/ATP ratio,thus enhanc-ing muscle glucose uptake.Metabolomic analyses revealed the significant changes in 25 metabolites,with twenty increased(eg.creatinine and phosphate)and five decreased(eg.lactic acid),and the marked impact of five metabolic pathways,including galactose metabo-lism,glycolysis,gluconeogenesis,fatty acid biosynthesis,butanoate metabolism,pyruvate metabolism.Further-more,a microbiota disorder model also demonstrates that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4.CON-CLUSION Our results provide convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis.These novel insights into graphene-FIR therapy suggest a potential as an exercise mimetic for the treatment of metabolic disease in clinical.

Objective:To study the pathogenic spectrum of enterovirus (EV) in the samples of child influenza-like(ILI)cases in Hangzhou city .Methods:In 2019, 1 060 throat swab specimens of ILI cases were collected for serotyping of influenza virus and EVs by real-time RT-PCR. The positive rates of influenza virus and EV in spring, summer, autumn and winter were compared by chi-square test with SPSS16.0 software. Specific primers were synthesized and used to amplify the VP1 fragments of EV. PCR products were sequenced and the results were compared with the reference sequences by using Basic Local Alignment Search Tool (BLAST) to identify the serotypes of isolated EV. The clinical diagnoses of EV positive cases were classified and analyzed.Results:A total of 1 060 specimens were collected and 283(26.70%) were positive for influenza virus, 75(7.08%) were positive for EV, 3(0.28%)were positive for influenza virus and EV. The comparison of positive detection rate of spring, summer, autumn and winter showed that influenza virus were prevalent in winter and spring. EV were mostly popular in the summer months. VP1 sequences of 51 EV were successfully amplified and BLAST analysis revealed that these strains belonged to 10 serotypes, including five serotypes of EV-A species, four serotypes of EV-B species and one serotype of EV-D. The ten serotypes of EV, including coxsackievirus (CV)A2, A4, A5, A6, A9, A10, and echovirus (ECHO)7, ECHO11, ECHO18, and EV-D68 were obtained and the percentages of positive were 16.00%, 16.00%, 5.33%, 12.00%, 5.33%, 1.33%, 1.33%, 5.33%, 4.00% and 1.33%, respectively. The phylogram of EV VP1 sequence showed that 51 EV strains in Hangzhou had different degrees of variation compared with the reference strains. Acute upper respiratory tract infection was the main clinical diagnosis in EV positive children, with 44 cases (58.67%). Acute tonsillitis was followed by 14 cases (18.67%). Followed by herpetic pharyngitis, acute bronchitis, asthmatic bronchitis, pneumonia, accounting for 12.00%, 8.00%, 1.33%, 1.33%, respectively.Conclusions:EV causing influenza-like illness in children in Hangzhou in 2019 belonged to 10 serotypes, CVA2 and CVA4 were the predominant serotypes, and the positive rate of EV detection was higher in summer.

Objective:To investigate the predominant serotypes and diversification of Echovirus (ECHOV) from viral encephalitis children in Quzhou area of Zhejiang province and the molecular characteristics of the ECHOV VP1 genes.Methods:Cerebrospinal fluid samples from 53 children with viral encephalitis were collected for viral isolation/culture. Fluorescent RT-PCR or PCR was used to detect human enteroviruses (HEV) including ECHOV, coxsackievirus(CoV) and new enterovirus (EV), and japanese encephalitis virus(JEV), mumps virus(MuV), west Nile virus(WNV) and chikungunya virus(CHLKV) or herpes simplex virus(HSV) and cytomegalovirus(CMV) in the cerebrospinal fluid samples. The complete VP1 gene sequence of HEV-B group in the HEV-positive cerebrospinal fluid samples was amplified by RT-PCR and sequenced, and then the typing of Echovirus isolates was performed. The VP1 genotypes of Echovirus isolates, gene recombination, inheritance and evolution characteristics were analyzed using multiple bioinformatic software.Results:Six viral strains were isolated by cell culture using rhabdomyosarcoma (RD) cells but not human epithelial-2 (Hep-2) cells. Eleven cerebrospinal fluid samples were positive for HEV by RT-PCR but the detection result of all the other viruses were negative. In the 11 HEV-positive samples, 6 samples were positive for ECHOV (4 for ECHO6, 1 for ECHO7 and 1 for ECHO30 serotype), which was coincident with the isolation result , but CoV and EV were undetectable. The 4 ECHO6 isolates belonged to ECHO6-C2 subgenotype but can be divided into two epidemic clones (ECHO6-41/46 and ECHO6-45/48). The ECHO7 and ECHO30 isolates belonged to ECHO7-C and ECHO30-C genotypes. The VP1 gene recombination between the ECHO6 and ECHO30 isolates were found during their evolutionary process.Conclusions:ECHOV is the major pathogen of viral encephalitis children in the area, and there is a possibility of local outbreak or epidemic. Because of the possibility of recombination of the VP1 gene of ECHO6 and ECHO30 virus, ECHO6 may become the dominant ECHOV serotype.

Objective: To determine the epidemic characteristics of respiratory viruses, mycoplasma pneumonia(MP) and chlamydia pneumoniae(CP) in outpatients and hospitalized children with acute respiratory tract infections(ARI), to lay a foundation for the prevention and control of ARI. Methods: From 2011 to 2013, children with ARI, including outpatients and inpatients, were involved in this study. One nasopharyngeal aspirate or throat swab specimen was collected from each patient.Real time PCRs were performed to detect common respiratory tract viruses, MP and CP. Results: At least one pathogen was identified in each of 610 out of 908 patients and the overall positive rate was 67.2%. The positive rate in inpatient(76.7%)was higher than that in outpatient(43.0%) (χ²=94.79, P<0.001). Simultaneous detection of two or more viruses was found in 206 cases.Co-infection was more frequent in inpatients than in outpatients(29.0% VS 6.6%, P<0.001). Significant differences of the detection rate were observed in RSV, PIV, HRV, Flu, human bocavirus (hBoV), adenovirus (AdV), saffold virus(SAFV), MP and CP between the inpatient and outpatient group. Respiratory syncytial virus(RSV)(34.5%) was the most prevalent virus detected among hospitalized children, followed by MP(15.0%)and human rhinovirus(HRV)(14.6%). Whereas adenovirus(AdV) (15.2%)was the most frequently identified virus in the outpatient group, followed by influenza virus(Flu)(11.7%))and PIV(7.8%). Except for RSV and Flu, co-infection of the other pathogens was more frequent than its mono-infection in inpatients. Significant differences of the AdV co-infection rate were observed between the inpatient and outpatient group(χ²=18.90, P<0.001). Compared with mono-infection, co-infection has no significant effect on the clinical presentation. Conclusions The detection rate of respiratory pathogens was higher in inpatients than in outpatients with ARI, and co-infections were more popular in children hospitalized, it may show that co-infection had some correlation with disease severity.

Objective:To explore the feasibility and clinical efficacy of stratified suture of lateral pharyngeal wall(SSLPW) combined with soft palate radiofrequency coblation in the treatment of the patients with severe obstructive sleep apnea hypopnea syndrome(OSAHS).Methods:The clinical data of 21 severe OSAHS patients underwent lateral pharyngoplasty(LP) combined with soft palate radiofrequency coblation (LP group) and 39 severe OSAHS patients underwent SSLPW combined with soft palate radiofrequency coblation (SSLPW group) were selected.The apnea hypopnea index(AHI),lowest SaO2(LSaO2),Epworth sleepiness scale(ESS) scores,and related postoperative complications of the patients in two groups were analyzed before and after operation.The successful rates of operation of the patients in two were compared.Results:In LP group,1 patient was cured (5%),19 patients were improved markedly (90%),1 patient was effective (5%),and no patient was invalid;the successful rate was 95.2%(20/21).In SSLPW group,2 patients were cured (5.1%),33 patients were improved markedly (84.6%),4 patients were effective (10.3%),and no patients was invalid;the successful rate was 89.7%(35/39);there was no statistical difference in the successful rate of operation of the patients between two groups (P>0.05).There was statistically significant improvement of the subjective symptoms.All the patients returned to normal subjective swallowing functions without nasal pharyngeal reflux and dysphagia in one month follow-up after operation.Compared with before operation,the AHI and ESS scores of the patients in two groups after operation were decreased(P<0.05);the LSaO2 scores were increased(P<0.05).Conclusion:The AHI,LSaO2 and ESS scores are significantly improved in the OSAHS patients after treated with SSLPW combined with soft palate radiofrequency coblation.The method is a valid option for the severe OSAHS patients.

[ABSTRACT]OBJECTIVETo estimate different dimensions of maxillary sinus measured on cone-beam computerized tomography (cone-beam CT), and determine the differences in side and gender.METHODScone-beam CT image data from 200 normal adults was selected and analyzed by Invivo Dental software. The craniocaudal diameter, anteroposterior diameter, width and volume of maxillary sinus were measured as well as the thickness of the orbital floor. Statistical analysis was performed with SPSS 11.5.RESULTSThere were no statistically significant differences in the craniocaudal diameter, anteroposterior diameter, width and volume of maxillary sinus between sides (P>0.05, respectively). Significant differences were noted in the craniocaudal diameter and volume of bilateral maxillary sinus and the width of right maxillary sinus based on gender (P<0.05, respectively). There were no significant differences in the width of left maxillary sinus, the anteroposterior diameter of bilateral maxillary sinus and the osseous thickness of the orbital floor (P>0.05, respectively).CONCLUSIONOur findings indicate that cone-beam CT can be used to measure different dimensions of maxillary sinus and provide imaging anatomical data for clinical treatment.

The development and compilation of Evidence-based Guidelines of Clinical Practice with Acupuncture and Moxibustion: Adult Bronchial Asthma are introduced from three aspects, named the guideline methodology, the guideline structure and the guideline content. Based on the acupuncture-moxibustion practice and clinical research, the evidence-based medicine method is adopted. During the development and compilation of the guideline, the characteristics and advantages of acupuncture and moxibustion are specially considered in the treatment of this disease; the latest optimum evidences at home and abroad, experts' experience and patients' value are closely integrated with each other. Additionally, the worldwide accepted assessments of evidence quality and the recommendation (GRADE system) are combined with the clinical evidences of the ancient and modern famous acupuncture-moxibustion experts, and the clinical research evidences are with the experts' consensus to the large extent. The purpose of the guideline is to provide the maximal guidance to the clinical physicians.
Asthma ; therapy ; Evidence-Based Medicine ; standards ; Humans ; Moxibustion ; standards ; Practice Guidelines as Topic ; Reference Books

Objective To investigate the epidemiological characters of human metapneumovirus (hMPV) infection in children with influenza-like illness (ILI).Methods A total of 1 164 throat swabs were collected from children with ILI symptoms in Children's Hospital,Zhejiang University School of Medicine from January 2011 to December 2012.hMPV was detected by using nucleic acid assay,the fusion (F) protein gene of hMPV was amplified by RT-PCR,gene sequencing was performed and the sequences were compared with those in GenBank.Positive rates of hMPV in different age groups were compared with Chi-square test.Results Among 1 164 samples,hMPV was positive in 73 (6.27％) samples.hMPV infection was the most popular in ＞2-4 y age group (33/220,15.0％),and the positive rates of hMPV in different age groups were of statistical significance (x2 =40.69,P ＜ 0.05).hMPV infection occurred throughout the year,but it was most common in winter and spring.The highest incidence of hMPV infection was observed in December 2012 (12/51,25.53％).Among 24 samples of hMPV,14 were with genotype B1,2 were with genotype B2,and 8 were with genotype A2.The most common genotype was B1 in 2011 (10/12),and A2 in 2012 (8/12).Homology between nucleotide sequences of the 24 samples of hMPV were 81.6％ to 100.0％.Conclusions hMPV infection exists in children with ILI in Hangzhou,and the epidemic seasons are winter and spring.hMPV infection is more likely to be found in children aged 2 to 4 years old,and different genotypes may predominated alternately.

Little is known about whether tamoxifen (TAM) can affect resting state microglia apoptosis and about the cellular mechanism that may account for this. To explore this question, we incubated the microglia cell line BV-2 cells with TAM at different concentrations. Cell viability was assessed by the MTT assay, and flow cytometric analysis was performed to detect the cell apoptosis rate. Furthermore, mitochondrial membrane potential (Δψm) was tested by flow cytometry, and Bax, Bcl-2, Fas, and Fas-L expression was detected by Western blot. The results demonstrated that TAM decreased cell viability and induced apoptosis of BV-2 cells in a concentration- and time-dependent manner. In addition, disruption of Δψm was followed by up-regulated expression of pro-apoptotic Bax, Fas and Fas-L, and down-regulated expression of anti-apoptotic Bcl-2. These results indicate that TAM may induce apoptosis of BV-2 cells through both mitochondria- and death receptor-mediated pathways.