Abstract: Objective　In order to understand and master the prevalence of different genotypes and the rate of different drug-resistant Mycobacterium tuberculosis genotypes in Hainan Province, 136 drug-resistant Mycobacterium tuberculosis strains collected in Hainan province in 2022 were genotyped, and to provide scientific basis for tuberculosis prevention and control strategy in Hainan Province. Methods　A total of 136 drug-resistant Mycobacterium tuberculosis strains were collected in Hainan Province. The clinical isolates were genotyped using the Spoligotyping technique, and the drug resistance rates of different genotypes of Mycobacterium tuberculosis were statistically analyzed. Results　Among the 136 strains of drug-resistant Mycobacterium tuberculosis, 54.41% (74/136) belonged to the Beijing types, 27.94% (38/136) to non-Beijing types and newly identified genotypes accounted for 17.65% (24/136). The Beijing type included two genotypes, SIT1 and SIT269 genotypes, accounting for 52.94% (72/136) and 1.47% (2/136) respectively. Among the non-Beijing genotypes, the T type (T1, T2, T3) accounted for 21.32% (29/136), the U type accounted for 6.62% (9/136). Clustering analysis of genotyping results revealed two major clusters, Beijing type and non-Beijing type, as well as several scattered novel genotypes. Clustering analysis of Spoligotyping results classified the 136 drug-resistant strains into 3 clusters, with a clustering rate of 75.74% (103/136). The rates of mono-resistance (MR), poly-resistance (PR), multi-drug resistance (MDR), and other types of drug resistance in Beijing type and non-Beijing type were 41.89% (31/74), 13.51% (10/74), 24.33% (18/74), 20.27% (15/74) and 36.84% (14/38), 15.79% (6/38), 26.32% (10/38), 21.05% (8/38) respectively. Chi-square test results showed no statistically significant differences in drug resistance rates between the Beijing and non-Beijing types (P>0.05). Conclusion　The genotype of Mycobacterium tuberculosis in Hainan Province showed genetic polymorphism, with the main epidemic genotype being SIT1 in the Beijing type. Monitoring of Mycobacterium tuberculosis in this genotype should be strengthened.

Objective To understand the drug resistance surveillance situation of Mycobacterium tuberculosis in Hainan Province from 2018 to 2022, analyze the drug resistance status and trends of Mycobacterium tuberculosis in Hainan Province, and provide scientific basis for the formulation of tuberculosis prevention and treatment strategies. Methods A total of 2 481 sputum culture-positive isolates from pulmonary tuberculosis patients collected from 2018 to 2022 were subjected to strain identification and drug sensitivity testing. Strain identification was performed using the p-nitrobenzoic acid (PNB) inhibition test, and the sensitivity test for six anti-tuberculosis drugs, including Rifampicin (RFP), Isoniazid (INH), Streptomycin (SM), Ethambutol (EMB), Ofloxacin (OFX), and Kanamycin (KM), was conducted using the solid culture proportion method. The drug sensitivity results were statistically analyzed. Results Of the 2 481 isolates, 2 211 were identified as Mycobacterium tuberculosis complex (MTBC). The overall drug-resistance rate was 19.9% (441/2 211). The drug resistance rates for initial-treatment and retreatment patients were 15.7% (271/1 729) and 35.3% (170/482) respectively, with a statistically significant difference (χ2=90.65, P<0.01). The mono-resistance rate (MR) was 6.0% (132/2 211), with monoresistance rates of 5.6% (97/1 729) for initial-treatment patients and 7.3% (35/482) for retreatment patients, with no statistically significant difference (χ2=1.83, P>0.05). The overall poly-resistance rate (PR) was 4.1% (91/2 211), with polyresistance rates of 3.5% (61/1 729) for initial-treatment patients and 6.2% (30/482) for retreatment patients. The overall multidrug-resistance rate (MDR) was 8.0% (176/2 211), with multidrug resistance rates of 4.2% (72/1 729) for initial-treatment patients and 21.6% (104/482) for retreatment patients. According to the χ2 test, the retreatment group had significantly higher rates of polyresistance and multidrug resistance than the initial-treatment patient group, with statistically significant differences (χ2=6.94, P<0.01; χ2=155.98, P<0.01). The resistance rates to individual drugs in descending order were 11.6% (251/2 211) to INH, 11.4% (255/2 211) to RFP, 8.6% (191/2 211) to SM, 8.2% (181/2 211) to OFX, 4.0% (88/2 211) to EMB, and 1.6% (35/2 211) to KM. Conclusions The overall drug-resistance rate, poly-resistance rate, and multidrug resistance rate of Mycobacterium tuberculosis in retreatment patients in Hainan Province are higher than those in initial-treatment patients. Standardized treatment and management of TB patients are particularly important.

Objective:To explore the application effects of the mode of "Multidisciplinary integration, Doctors & patients co-teaching, Simulated practice" in the teaching of spinal surgery.Methods:A total of 64 eight-year program clinical medical students who practiced in Peking Union Medical College Hospital in 2021 were taken as research objects and randomly divided into experimental group ( n=33) and control group ( n=31). The experimental group received the new teaching mode of "Multidisciplinary integration, Doctors & patients co-teaching, Simulated practice", and the control group received regular teaching mode. At the end of teaching, the teaching effects were evaluated from several aspects, including the scores of theoretical examinations, anatomical marks identification tests, and anonymous questionnaires. SPSS 22.0 software was used for paired t-test and two independent-samples t-test. Results:The theoretical test scores [(51.25±6.99) points] and anatomical structure identification scores [(37.56±1.83) points] of the experimental group were higher than those of the control group [(42.46±6.13) points and (30.37±3.46) points], and the differences were statistically significant ( P<0.001). The effective recovery rate of the questionnaire was 100%. The results of the questionnaire showed that the experimental group was significantly higher than the control group in terms of teaching attractiveness, attention, learning interest, learning efficiency, anatomical identification ability, problem-finding and problem-solving ability and overall teaching method satisfaction ( P<0.05). Conclusion:The teaching mode of "Multidisciplinary integration, Doctors & patients co-teaching, Simulated practice" can effectively improve students' theoretical knowledge, learning interest, learning efficiency, operation proficiency and problem-finding and problem-solving ability, which is worth promoting.

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

OBJECTIVE To develop a long-acting light-protective nanogel with both physical barrier and chemical clearance functions， and evaluate its performance. METHODS The photoprotective nanogel composed of mussel mucin and sodium hyaluronate was constructed based on a fullerenol-cerium oxide composite nano system， namely fullerenol-cerium oxide nanogel （FCN）， and was characterized. The antioxidant capacity of FCN was evaluated using in vitro free radical scavenging experiments； its UV shielding ability was assessed by using an SPF value detector； its biosafety was assessed according to the requirements of the Guidelines for Drug Safety Evaluation； skin adhesion was assessed using small animal 3D live imaging technology； its sun protection ability was assessed through skin sunscreen detection and histopathological observation. RESULTS The average particle sizes of cerium oxide and fullerenol nanoparticles in FCN were about 20 and 10 nm， respectively， and FCN exhibited good UV absorption and free radical scavenging abilities. SPF value of FCN was 58.95±0.82， and the ultraviolet A protection level value was 6.21±0.15. No pathogenic colonies such as Staphylococcus aureus， were detected in the nanogel， and the contents of lead， arsenic， mercury and cadmium all met the standards for pharmaceutical excipients； FCN group did not show any irritating reactions such as erythema， edema， or desquamation； blood biochemical indicators of the FCN group were within the normal reference range. The material clearance rate of mice in the artificial sweat flushing group was less than 30%， while the material clearance rate of mice in the dry cleaning group reached about 92%. The mice in the protective group did not show obvious erythema or ulcer formation throughout the experiment. Histopathology showed that the fibers were arranged in an orderly manner， and the number of collagen fibers was close to that of the control group. CONCLUSIONS The FCN formulation constructed in this study meets the relevant requirements of the Chinese Pharmacopoeia， has good safety and skin compatibility， and achieves dual synergistic protection of UV shielding and free radical scavenging.

Objective: To analyze the clinical features, the efficacy of131I therapy and its effect on granulopoiesis in Graves′ hyperthyroidism(hyperthyroidism) patients with neutropenia. Methods: 144 hyperthyroidism patients were retrospectively studied after131I therapy, among which 42 cases(HT group) accompanied neutropenia due to hyperthyroidism itself, 52 cases(ATD group) appeared neutropenia after anti-thyroid drug(ATD)treatment, and the remaining 50 cases(control group) were hyperthyroidism patients with normal neutrophil count. The clinical features, the efficacy of131I treatment for hyperthyroidism and the change of neutrophil count after131I treatment were analyzed and compared in three groups. Results: Mild neutropenia was commoner in both the HT group and the ATD group. The curative rate of hyperthyroidism in the HT group, the ATD group and the control group were80. 95%, 84. 62% and 84. 00%, respectively. There was no significant difference in the efficacy of131I therapy among the three groups. Compared with the baseline value before treatment, neutrophil count increased in all three groups 2-4 weeks after131I treatment(allP<0. 05). The neutrophil recovery rates of the HT group and the ATD group were 61. 90% and 84. 62%, respectively. The ATD group had a higher recovery rate(P<0. 05). Conclusion Mild neutropenia is commoner in hyperthyroidism patients with neutropenia due to either hyperthyroidism itself or ATD treatment. Normative131I treatment for hyperthyroidism patients with neutropenia is safe and effective.