Objective To evaluate the sensitivity of combination of itraconazole and amphotericin B to20clinical isolates of Cryptococcus neoformans and their in vitro interactions.Methods The sensitivity of combination of itraconazole and amphotericin B and their in vitro interactions were determined with20clinical isolates of C.neoformans by a checkerboard titration broth microdilution-based method in accord with the recommendations of the National Committee for Clinical Laboratory Standards(NCCLS),USA.Results When both drugs were given in combination,there was significant reduction of geometric means of MICs for itraconazole(from0.2730to0.1195?g/mL)and for amphotericin B(from0.6830to0.2102?g/mL).Synergistic effects were found in35%of isolates,additive effects in55%of isolates,and indifferent effects in10%of isolates.Antagonistic effects were not observed.The colony formation unit(cfu)per millilitre was significantly decreased in an isolate which was treated with different concentrations of the combination of both drugs,in comparison to that with the corresponding concentrations of individual drug.Conclusion The combination of itraconazole and amphotericin B is significantly more active against C.neoformans in vitro than individual drug alone.

Objective To design and synthesis novel triazole antifungal derivatives with dithiocarbamates side chain and study the antifungal activities .Methods Nine title compounds were synthesized and characterized by 1 H NMR ,MS spectra . The in vitro antifungal activities of all the compounds were evaluated against eight human pathogenic fungi .Results The title compounds exhibited strong antifungal activities .Some compounds showed excellent activities against Candida albicans with the MIC80 values less than 0 .125 g/ml ,6d was 64 times higher than that of Itraconazole .Conclusion The introduction of the propyl ,sulphur and benzyl moiety to the side chain could affect the antifungal activities .

Objective:To construct a Nomogram model in predicting recurrence-free survival (RFS) and overall survival (OS) at six months, one year and two years after hepatocellular carcinoma (HCC) resection by using inflammatory markers combined with other routine clinical indicators.Methods:The data of 314 patients with HCC who underwent first time hepatectomy at Beijing Chaoyang Emergency Rescue Center and Air Force Characteristic Medical Center from January 2013 to January 2018 were analyzed. HCC patients who underwent hepatectomy at the First Medical Center of PLA General Hospital from January 2011 to January 2016 ( n=106) were used as the external validation group. Univariate and multivariate Cox proportional risk model was used to analyze independent risk factors of recurrence and death in HCC patients. A Nomogram model was constructed based on independent risk factors. Validation of the efficacy of the Nomogram model was done based on external data. Results:In the experimental group, 174 patients relapsed. The median RFS was 26 months. The 6 months, 1 year and 2 years RFS were 26.8%, 43.9%, and 68.8%, respectively. A total of 142 patients had died. The median survival time was 30 months. The 6 months, 1 year and 2 years OS were 5.9%, 23.6% and 63.1%, respectively. In the external validation group, 63 patients had developed recurrence, with a median RFS time of 28 months. The 6 months, 1 year and 2 years RFS were 26.4%, 45.3%, 54.7%, respectively. The median survival time was 31 months. The 6 months, 1 year and 2 years OS were 7.5%, 25.5%, 46.6%, respectively. Tumor size (>6.0 cm, HR: 1.447), vascular invasion ( HR: 1.408), TBil (>0.94 mg/dl, HR: 1.949), NLR (>2.54, HR: 2.843), AGR (≤0.88, HR: 2.447) were independent risk factors of HCC recurrence ( P<0.05). Tumor size (>6.0 cm, HR: 2.207), vascular invasion ( HR: 1.529), and NLR (>2.54, HR: 2.708) were independent risk factors of death for HCC patients ( P<0.05). The C-indexes of half-year, one-year and two-year RFS were 0.764 (95% CI: 0.677-0.854), 0.710 (95% CI: 0.615-0.824) and 0.673 (95% CI: 0.601-0.786), respectively. The C-indexes of half-year OS, one-year OS and two-year OS were 0.729 (95% CI: 0.648-0.841), 0.708 (95% CI: 0.608-0.813) and 0.664 (95% CI: 0.618-0.771), respectively. Conclusion:In this study, the construction of a Nomogram model in predicting prognosis of HCC patients was helpful to guide clinicians in improving preoperative treatment plans and in providing ideas for individualized treatment of patients.

Objective:To investigate the mechanism of depression between social capital and cognitive function of the elderly in nursing institutions, and provide new ideas for improving the cognitive function of the elderly.Methods:This study was a cross-sectional survey. Using the convenient sampling method to collect the general information questionnaire, the Geriatric Depression Scale (GDS), Social Capital Scale and Montreal Cognitive Assessment Scale (MoCA) of 218 elderly people from three elderly nursing institutions including Shenyang Health Care Centre, Songpu Nursing Home and Colourful Sunshine City Pension Service Centre in Shenyang from July 2020 to January 2021.Results:A total of 218 questionnaires were distributed and 202 valid questionnaires were recovered. The effective recovery rate was 92.7%. The scores of the cognitive function, depression and social capital of the elderly were (23.60 ± 4.25), (6.38 ± 4.35) and (75.41 ± 8.61). Depression scores were negatively correlated with social capital scores and cognitive function scores ( r = - 0.401, - 0.481, both P<0.05); there was a positive correlation between social capital scores with cognitive function scores ( r = 0.338, P<0.05). There was a mediating effect of depression between social capital and cognitive function, accounting for 42.1%. Conclusions:While improving the cognitive function of the elderly in nursing institutions by improving the level of social capital, it is necessary to pay attention to the mediatingeffect of depression, strengthen the psychological counseling of the elderly, promote mental health, and further reduce the occurrence and development of cognitive decline in the elderly.

Objective To observe the effects of electroacupuncture on the motor function and mitochondrial dynamics of skeletal muscle of SAMP8 mice;To explore the mechanism of electroacupuncture in improving the motor dysfunction of Alzheimer disease(AD)from the perspective of mitochondrial dynamics.Methods Totally 18 SAMP8 mice were divided into model group and electroacupuncture group,with 9 mice in each group,and the SAMR1 mice with the same age were set as control group."Baihui","Dazhui"and"Shenshu"were selected in the electroacupuncture group,and electroacupuncture was performed daily for 20 min,8 d as a course of treatment.Each course of treatment was separated by 2 d,for a total of 3 courses of treatment.The model group and the control group were not intervened.The motor function of mice was tested by grip strength test,suspension test,hind limb extension test and Morris water maze experiment.The morphology and structure of gastrocnemius were observed by HE staining,ATP content in gastrocnemius was determined by colorimetry,the mRNA expression of optic atrophy 1(OPA1),mitofusin 2(MFN2)and dynamin-related protein 1(DRP1)in gastrocnemius were detected by real-time quantitative PCR,the expressions of OPA1,MFN2 and DRP1 in gastrocnemius were detected by Western blot.Results Compared with the control group,the grip strength,the score in suspension test,and the average speed and maximum speed of Morris water maze experiment of mice in model group significantly decreased(P<0.01);the arrangement of fibers in the gastrocnemius muscle tissue was disordered,the gaps become wider,and the distribution of nuclei was uneven;the ATP content in the gastrocnemius muscle tissue was significantly decreased(P<0.01),the mRNA and protein expressions of OPA1 and MFN2 were significantly decreased(P<0.01),and the expression of DRP1 mRNA and protein significantly increased(P<0.01).Compared with the model group,the grip strength,the score in suspension test,and the average speed and maximum speed of Morris water maze experiment in electroacupuncture group significantly increased(P<0.01);the arrangement of gastrocnemius muscle tissue was relatively neat,the gaps become narrower,and the distribution of nuclei was more uniform;the ATP content in gastrocnemius muscle tissue significantly increased(P<0.01),while the mRNA and protein expressions of OPA1 and MFN2 significantly increased(P<0.05,P<0.01),the expression of DRP1 mRNA and protein significantly decreased(P<0.01).Conclusion Electroacupuncture can improve the skeletal muscle morphological structure and motor dysfunction of SAMP8 mice,and the mechanism may be related to the correction of skeletal muscle mitochondrial dynamic imbalance and the increase of skeletal muscle ATP content.

Objective To observe the effects of electroacupuncture on the motor function and expressions of Irisin,Decorin and Myostatin in skeletal muscle of SAMP8 mice;To explore the mechanism of electroacupuncture in the treatment of the motor dysfunction of Alzheimer disease(AD).Methods Totally 247-month-old male SAMP8 mice were randomly divided into model group and electroacupuncture group,with 12 mice in each group,and the 12 male SAMR1 mice with the same age were set as the control group."Baihui","Dazhui"and"Shenshu"were selected in the electroacupuncture group,once a day,8 days as one course of treatment,with an interval of 2 days,for a total of 3 courses.The control group and the model group were not intervened.The motor function of mice was tested by grip strength test,pole climbing test and open field test,the mRNA expressions of Irisin,Decorin and Myostatin in quadriceps muscle were detected by RT-qPCR,and the protein expressions of Irisin,Decorin and Myostatin in quadriceps muscle were detected by immunohistochemistry and Western blot.Results Compared with the control group,the grip peak and duration of the mice in the model group decreased,head turning time and pole climbing time were prolonged(P<0.01),the mRNA and protein expressions of Irisin and Decorin decreased(P<0.05,P<0.01),and the expressions of Myostatin mRNA and protein increased(P<0.05).Compared with the model group,the grip peak and duration of the mice in the electroacupuncture group increased,head turning time and pole climbing time were decreased(P<0.05),the mRNA and protein expressions of Irisin and Decorin increased(P<0.05),and the expressions of Myostatin mRNA and protein decreased(P<0.05).Conclusion Electroacupuncture can improve the motor dysfunction of SAMP8 mice,and its mechanism may be related to regulating the expressions of Irisin,Decorin and Myostatin in skeletal muscle.

Objective:To systematically evaluate the methodological quality of screening guidelines for upper gastrointestinal cancer (including esophageal cancer and gastric cancer) both at home and abroad, and provide reference for the update of upper gastrointestinal cancer screening guidelines in China.Methods:Original articles and grey literature published as of 31 th Aug 2020 were retrieved using Chinese databases (CNKI, Wanfang, China Biomedical Literature Database and China Guideline Clearinghouse), PubMed, The Cochrane Library and Embase, as well as those from International Agency for Research on Cancer and the International Guide Collaboration Network. The inclusion criteria were being independent guidelines/recommendation documents for upper gastrointestinal cancer screening and meeting the definition of the institute of Medicine, USA. The exclusion criteria were being guideline abstracts, interpretation and evaluation literature, duplicate publications, updated original guidelines, and clinical treatment or practice guidelines for esophageal or gastric cancer. Appraisal of Guidelines for Research and Evaluation (AGREE Ⅱ) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) were used to compare and evaluate the quality and reporting standard of esophageal or gastric cancer screening guidelines. Results:A total of 6 esophageal cancer screening guidelines and 5 gastric cancer screening guidelines were included. The results of the AGREE Ⅱ quality evaluation showed that the overall quality of eleven guidelines varied, including two guidelines recommended for "A", one for "B", five for "C" and three for "D". The guidelines had higher scores in the areas of scope and purpose, and clarity. The esophageal cancer screening guidelines had different scores in the areas of rigor and independence. The gastric cancer screening guidelines generally had low scores in the areas of participants and application. The RIGHT evaluation results showed that the quality of eleven guidelines should be improved. The six items with poor report quality were background, evidence, recommendations, review and quality assurance, funding and conflict of interest statement and management and others.Conclusion:The quality of the included upper gastrointestinal cancer screening guidelines is general, and the standardization needs to be strengthened.

Objective To investigate the antimicrobial resistance profile of the clinical isolates collected from selected hospitals across China. Methods Twenty-nine general hospitals and five children's hospitals were involved in this program. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Results were interpreted according to CLSI 2017 breakpoints. Results A total of 190 610 clinical isolates were collected from January to December 2017, of which gram negative organisms accounted for 70.8％ (134 951/190 610) and gram positive cocci 29.2％ (55 649/190 610). The prevalence of methicillin-resistant strains was 35.3％ in S. aureus (MRSA) and 80.3％ in coagulase negative Staphylococcus (MRCNS) on average. MR strains showed much higher resistance rates to most of the other antimicrobial agents than MS strains. However, 91.6％ of MRSA strains were still susceptible to trimethoprim-sulfamethoxazole, while 86.2％ of MRCNS strains were susceptible to rifampin. No staphylococcal strains were found resistant to vancomycin. E. faecalis strains showed much lower resistance rates to most of the drugs tested (except chloramphenicol) than E. faecium. Vancomycin-resistant Enterococcus (VRE) was identified in both E. faecalis and E. faecium. The identified VRE strains were mainly vanA, vanB or vanM type based on phenotype or genotype. The proportion of PSSP or PRSP strains in the non-meningitis S.pneumoniae strains isolated from children decreased but the proportion of PISP strains increased when compared to the data of 2016. Enterobacteriaceae strains were still highly susceptible to carbapenems. Overall, less than 10％ of these strains (excluding Klebsiella spp.) were resistant to carbapenems. The prevalence of imipenem-resistant K. pneumoniae increased from 3.0％ in 2005 to 20.9％ in 2017, and meropenem-resistant K. pneumoniae increased from 2.9％ in 2005 to 24.0％ in 2017, more than 8-fold increase. About 66.7％ and 69.3％ of Acinetobacter (A. baumannii accounts for 91.5％) strains were resistant to imipenem and meropenem, respectively. Compared with the data of year 2016, P. aeruginosa strains showed decreasing resistance rate to carbapenems. Conclusions Bacterial resistance is still on the rise. It is necessary to strengthen hospital infection control and stewardship of antimicrobial agents. The communication between laboratorians and clinicians should be further improved in addition to surveillance of bacterial resistance.

Objective: To estimate the incidence and mortality of nasopharyngeal carcinoma in China based on cancer registration data in 2014, collected by the National Central Cancer Registry (NCCR). Methods: 449 cancer registries submitted nasopharyngeal carcinoma incidence and deaths occurred in 2014 to NCCR. After evaluating the data quality, 339 registries′ data were accepted for analysis and stratified by area (urban/rural) and age group. Combined with data on national population in 2014, the nationwide incidence and mortality of nasopharyngeal carcinoma were estimated. Chinese population census in 2000 and Segi′s population were used for age-standardized incidence and mortality rates. Results: The estimates of new nasopharyngeal carcinoma incident cases and deaths were 44.6 thousands and 24.2 thousands, respectively. The crude incidence rate was 3.26/100 000 (Male 4.51/100 000, Female 1.94/100 000). Age-standardized incidence rates by Chinese standard population (ASIRC, 2000) and by world standard population (ASIRW) were 2.48/100 000 and 2.33/100 000, respectively. Male to female ratio was 2.32∶1. The ASIRC in urban and rural areas were all 2.48/100 000. The crude mortality rate of nasopharyngeal carcinoma was 1.77/100 000 (Male 2.55/100 000, Female 0.95/100 000). Age-standardized mortality rates by Chinese standard population (ASMRC, 2000) and by world standard population(ASMRW) were 1.23/100 000 and 1.20/100 000, respectively. The ASMRC in urban and rural areas were all 1.23/100 000. The cumulative incidence and mortality rates(0-74 years old)were 0.25% and 0.14%, respectively. Conclusions Incidence and mortality of nasopharyngeal carcinoma in China in 2014 were at high levels in the world. Corresponding prevention and control measures should be established according to the epidemic characteristics and risk factors of nasopharyngeal carcinoma.

Adipic acid is a high-value-added dicarboxylic acid which is primarily used in the production of nylon-66 for manufacturing polyurethane foam and polyester resins. At present, the biosynthesis of adipic acid is hampered by its low production efficiency. By introducing the key enzymes of adipic acid reverse degradation pathway into a succinic acid overproducing strain Escherichia coli FMME N-2, an engineered E. coli JL00 capable of producing 0.34 g/L adipic acid was constructed. Subsequently, the expression level of the rate-limiting enzyme was optimized and the adipic acid titer in shake-flask fermentation increased to 0.87 g/L. Moreover, the supply of precursors was balanced by a combinatorial strategy consisting of deletion of sucD, over-expression of acs, and mutation of lpd, and the adipic acid titer of the resulting E. coli JL12 increased to 1.51 g/L. Finally, the fermentation process was optimized in a 5 L fermenter. After 72 h fed-batch fermentation, adipic acid titer reached 22.3 g/L with a yield of 0.25 g/g and a productivity of 0.31 g/(L·h). This work may serve as a technical reference for the biosynthesis of various dicarboxylic acids.
Escherichia coli/metabolism* ; Metabolic Engineering ; Bioreactors ; Fermentation ; Adipates/metabolism*