Combined with method of ketoconazole resistance screening, a 7alpha,15alpha-diOH-DHEA high-producing mutant Colletotrichum lini ST-1 was obtained by compound mutation of NTG and low energy N+ ion beam implantation. With the substrate concentration of 10 g/L DHEA, the molar yield of 7alpha,15alpha-diOH-DHEA reached 34.2%, increased by 46.2% than that of the original strain. Then we optimized the medium. First, Plackett-Burman design was used to evaluate the effects of medium components on molar yield of the product. Results show that glucose, yeast extract and MgSO4 x 7H2O were the important parameters for the biotransformation process. Subsequently, the path of steepest ascent was used to approach the optimal levels. To obtain the optimal levels, central composite design and response surface analysis were carried out. The optimal medium was as follows (g/L): glucose 26.34, yeast extract 12.15, corn flour 3.00, FeSO4 x 7H2O 0.015, MgSO4 x 7H2O 0.14, KH2PO4 0.90. Under the optimal conditions, the molar yield of 7alpha,15alpha-diOH-DHEA reached 49.3%, which was 44.2% higher than that of using the medium before optimization.
Biotransformation ; Colletotrichum ; metabolism ; Dehydroepiandrosterone ; chemistry ; Fermentation ; Hydroxylation ; Industrial Microbiology ; Mutation

Objective: To understand delay in treatment student tuberculosis (TB) patients in Wuhan from 2011 to 2018, and to provide a reference for prevention and control measures of tuberculosis in schools. Methods: The medical cases of students with tuberculosis in Wuhan recorded by the national tuberculosis management information system during 2011-2018 were analyzed for the delay and change trend of medical treatment of students with tuberculosis, and Logistic regression was used to analyze influencing factors. Results: The median number of student TB patients seeking treatment in Wuhan was 9(3,21) days, and 51.14% of student TB patients were delayed. From 2011 to 2018, the overall delay rate of TB patients in students decreased slowly and then gradually increased, decrea sing from the highest rate (56.4%) in 2011 to the lowest one (45.6%) in 2014, and then gradually increased to 53.8% in 2018, there was no significant difference in the delay rate between the first and the second four years(χ2=2.84, P=0.09); The delay rate of different gender students was the same as that of the whole. The fluctuation of female students was slightly obvious, but the difference was not statistically significant(χ2=0.07, P>0.05); Among the students of different age groups, the delay rate of 13-18 years old was the lowest(χ2=87.23, P<0.01). The delay rate of 19-22 years old and university groups of different school levels showed a slow decline, while that of other age groups and other school level groups showed an overall upward trend. The results of multivariate logistic regression analysis showed that the main factors affecting the delay rate of medical treatment were the remote urban area(OR=1.84, 95%CI=1.56-2.16), the ethnic minorities (OR=2.73, 95%CI=1.46-5.09) and the age of 13-18(OR=0.57, 95%CI=0.33-1.00). Conclusion Delay in treatment of TB patients in Wuhan is not optimistic, with more than half of the students have delayed in treatment, the main factors that affect the high rate of TB patients’ treatment delay are the students in the far urban areas and ethnic minorities. It is very important to take targeted prevention and control measures to guide the students to actively seek medical treatment according to the time, the place and the person.

Objective: To determine the knowledge, attitudes and practices (KAP) regarding tuberculosis prevention and control among college students in Wuhan, China, while analyzing the factors affecting tuberculosis prevention behavior. Methods: Referring to the National KAP Questionnaire for Tuberculosis Prevention and Control among College Students, which was designed by China Center for Disease Control and Prevention, 22 colleges and universities in Wuhan were selected using a judgment sampling method, and a questionnaire survey was carried out through the online questionnaire platform. The formation of tuberculosis prevention and control behavior among this population was analyzed by single factor and multi factor Logistic regression. Results: The total awareness rate of KAP regarding tuberculosis prevention and control among college students in Wuhan was 79.69%; the awareness rate of core knowledge was 79.28%, and the passing rate was 92.46%. The correct attitude holding rate was 89.69%, while the passing rate was 90.56%. In respect to correct behavior, the formation rate was 72.11%, with a passing rate of 96.62%. The multivariate Logistic regression analysis showed that the following factors were more likely to promote tuberculosis prevention and control behaviors that met the target: female college students ( OR =1.86); college students whose father had a primary school education level, junior high school and equivalent, high school and equivalent, and junior high school students ( OR =2.94, 3.05, 3.17, 3.24 ); no history of tuberculosis ( OR =3.32); the passing knowledge of core knowledge ( OR =9.91), and the passing attitude holding score ( OR =7.35)( P <0.05). Conclusion The overall awareness rate of KAP regarding tuberculosis prevention and control among college students in Wuhan is acceptable,the mainly influenced factors are gender, history of tuberculosis, awareness rate of core knowledge about prevention and control, attitudes and cognition, and parents educational background.

Objective: To analyze the epidemiological characteristics of pulmonary tuberculosis among students in Wuhan from 2011 to 2020, and to provide a basis for the scientific development of interventions and strategies. Methods: Epidemiological distribution, time of onset and treatment, as well as treatment outcomes of student tuberculosis in Wuhan from 2011 to 2020 registered in the national tuberculosis information management system were described. Results: During 2011-2020, 4 337 student tuberculosis patients in Wuhan were registered. The average annual incidence rate was 22.44/10 million, and the annual decreasing rate of 7.86% The incidence of male and female patients was 1.76:1, and the incidence rate of male was higher than that of female( χ 2=184.18, P <0.01). Most of patients aged 19-22 years old, accounting for 47.89%; Tuberculosis reports were highest during March to May, and September to November, and lowest during January to February, and July to August. Student patients were mainly concentrated in Hongshan District, Jiangxia District and Wuchang District, where schools were more distributed in Hongshan District, Dongxihu District, Wuchang District and Xinzhou District. The median duration from tuberculosis onset to treatment was 9(3, 21) days, which varied significantly by region, age, nationality, and patient residence ( Z =-9.25, 47.14, 9.88,43.96, P <0.01). The treatment and outcome of student tuberculosis patients were varied significantly by year and nationality( P <0.05). Conclusion The incidence of student tuberculosis in Wuhan City showed a slow downward trend. Most of student tuberculosis are college and high school students. Time and place of case detection are relatively fixed. The time of treatment and the outcome of treatment vary significantly. Tuberculosis prevention and control strategies should be formulated according to the local conditions according to the tuberculosis distribution characteristics, as well as enhancing surveillance, health promotion, active discovery and supervision management of tuberculosis in school settings.

Objective: To analyze the epidemiological characteristics and assoicated factors of tuberculosis (TB) aggregation in schools in Wuhan from 2017 to 2020, and to provide scientific basis for school based TB prevention and control strategies. Methods: Questionnaire star was used to collect data on tuberculosis prevention and control in various schools in Wuhan. Multivariate logistic regression analysis was used to analyze the influencing factors of tuberculosis aggregation in schools. Results: A total of 37 outbreaks of tuberculosis aggregation in schools were reported in Wuhan from 2017 to 2020, which involved 28 different schools, including 24 colleges and universities and 4 senior high schools, 176 cases were reported, among which 39 were positive for pathogens and 17 cases of rifampicin resistant, and the median duration of single cluster epidemic was 48 (28, 368) days, universities were more prone to cluster outbreaks than middle schools ( χ 2=75.27, P <0.01), the incidence in male was higher than that of in female in cluster outbreak ( χ 2=22.82, P =0.00). The results of multivariate Logistic regression analysis showed that boarding school ( OR =5.12), TB screening at school entry ( OR =3.27), etiology tracking and registrationin school ( OR =7.28), treatment and isolation of sick students on time ( OR =9.12), whether the dormitories and classrooms were often ventilated ( OR =4.97), and whether the management of school suspension and return was strictly implemented ( OR =4.68) were associated with the occurrence of TB cluster outbreak( P <0.05). Conclusion Schools should actively strive for policies and funding, strictly implement TB screening and physical examination for freshmen, as well as the management of contact tracing and registeration, targeted TB health education, guidance for teachers and students for cleaning, disinfection and hand hygiene, timely treatment and reporting of suspected symptoms, to prevent the occurrence of TB clustering outbreaks.

Objective To determine the genotype and clustering characteristics of multidrug-resistant (MDR) mycobacterium tuberculosis in Wuhan City. Methods A total of 149 mycobacterium tuberculosis strains from MDR tuberculosis (MDR-TB) patients were genotyped by DTM-PCR, mycobacterial interspersed repetitive unit–variable number tandem repeat typing (MIRU-VNTR) and sequencing of drug-resistant associated genes. The Hunter-Gaston discriminatory index (HGDI), clustering rate and recent minimum estimated infection rate were calculated. Results The cumulative HGDI of all MIRU loci was 0.9944. Gene locus with the highest HGDI（0.6467）was QUB11b. Combing MIRU-VNTR and DTM-PCR, 111 unique genotypes and 11 clustered genotypes（38 strains）from 149 isolates were identified. The clustering rate was 25.50%, and the recent minimum infection rate was estimated to be 18.12%. After further genotyping by sequencing of drug-resistant associated genes, the results showed that 17 (44.74%) strains in each cluster shared the same mutation sites, while the other strains had different mutation sites. Conclusion The combination of DTM-PCR, 24 locus MIRU-VNTR typing and drug resistance gene sequencing demonstrates a relatively high discriminatory power, which is suitable for the genotyping of multi drug resistant mycobacterium tuberculosis in Wuhan. The epidemic of MDR-TB in Wuhan is mainly caused by reactivation, and the recent transmission rate is not high.

Objective To analyze and evaluate the implementation effect of tuberculosis prevention and control program in Wuhan, and to provide reference for scientific formulation of tuberculosis prevention and control measures. Methods Using the National Tuberculosis Information Management System, descriptive statistical analysis was carried out on the medical record information of pulmonary tuberculosis patients registered in Wuhan , 2016 - 2021. Results A total of 34 937 cases of pulmonary tuberculosis were registered in Wuhan , with an average annual incidence rate of 49.85/100 000. The incidence rate showed a downward trend year by year, with a statistically significant difference in 2016—2021 (χ²_trend = 708.387, P<0.001). The patients mainly came from referrals, accounting for 71.86%, and the proportion of referrals varied significantly among different years (χ²=355.541, P<0.001). The diagnosis type was mainly pathogenic negative, accounting for 49.12%. The proportion of pathogenic negative had statistically significant difference among different years (χ²=1 354.830, P<0.001). The proportion of patients cured and completed the course of treatment reached 93.98%, with statistically significant differences in the proportions among different years (cured, χ²=1 080.252, P<0.001; completed the treatment course, χ²= 933.655, P<0.001). The sputum examination rate of newly diagnosed patients in each year reached over 90%, and the overall completion rate reached over 95%. The proportion of positive pathogens showed an increasing trend year by year. Conclusion The overall epidemic situation of tuberculosis in Wuhan is declining year by year, and tuberculosis prevention and control work has achieved remarkable results. Active screening in key areas and populations should be strengthened, and prevention and control strategies should be formulated by emphasizing the key and difficult points.

Objective By analyzing the means of donor maintenance from the perspective of intensive care medicine,the difference of clinical indicators before and after donor treatment is obtained,summarizing the treatment experience and effect of clinical maintenance of donor donors,and providing more clinical evidence for the maintenance and treatment of organ donation donors.Methods A retrospective analysis was performed on 76 organ donors collected from the Department of Intensive Care Medicine,Army Medical Center,Chinese People's Liberation Army from January 2014 to December 2021,collected donor maintenance treatment,including mechanical ventilation,continuous renal replacement therapy(CRRT)treatment,enteral nutrition and parenteral nutrition,enteral and parenteral nutrition,plasma exchange,at the same time,the paired t test was used to compare the organ function before and after treatment.Results The lung,liver and kidney of 76 donors were evaluated before and after treatment to determine the number of eligible donors.The difference between the number of eligible donors of kidney and liver before and after treatment was statistically significant(P<0.05).There was no significant difference in lung evaluation(P>0.05).Conclusion Timely and effective organ support therapy for organ transplantation donors is beneficial to the recovery of organ function and improve the utilization rate of organ.