Objective To understand the molecular characteristics of Streptomycin(SM)resistance in multidrug-resistant tuberculosis(MDR-TB)in Jiangxi Province,and to explore the relationship between SM resistant genes(rpsL,rrs and gidB)mutations and SM resistant phenotypes in Beijing genotype TB.Methods 106 non-replicated MDR-TB isolates were collected from Gaoxin Branch of The First Affiliated Hospital of Nanchang University and Jiangxi Provincial Chest Hospital from January to December 2021,and tested for drug-resistance phenotypes,whether they were Beijing genotype or not and the characteristics of rpsL,rrs and gidB gene mutations.Chi-square test was performed to determine whether rpsL,rrs and gidB mutations were related to genotypes and drug-resistance phenotypes.Results Among 106 cases of MDR-TB,76 cases were resistant to SM.A total of 58 cases had rpsL 43A>G mutation,8 cases had 88A>G mutation,5 cases had rrs mutation,and 3 cases had gidB mutation.Statistical analysis showed that the coincidence rate of gene mutation and phenotypic drug-resistance detection was 89.6%,and the specificity and sensitivity were 86.7%and 90.8%,respectively.The isolated rate of Beijing genotype TB was 88.7%,and the drug-resistant gene mutations were mainly concentrated in rpsL and rrs,while the drug-resistant mutations of non-Beijing genotype were mainly concentrated in gidB;in addition,Beijing genotype bacteria were more prone to gene mutations(P = 0.013),but there was no difference in phenotypic drug-resistance.Conclusions Mutations in rpsL,rrs,and gidB genes have a good coincidence rate with phenotypic drug-resistance,and molecular biology can be used to detect directly drug-resistance genes to predict bacterial resistance;TB genotypes are strongly associated with streptomycin resistance characteristics.

Objective:To analyze germline pathogenic mutations in patients with upper tract urothelial carcinoma(age≤60 years old), and to explore the clinicopathological characteristics of germline pathogenic mutation carriers.Methods:The data of 124 patients (age≤60 years old) with upper tract urothelial carcinoma who underwent germline genetic testing at Fudan University Shanghai Cancer Center from September 2008 to February 2023 were retrospectively analyzed. There were 86 males and 38 females, and the median age was 55.0(49.8, 58.0)years old. The primary tumors were located in the renal pelvis in 81 cases (65.3%), the ureter in 34 cases (27.4%), and both in 9 cases (7.3%). There were 13 patients (10.5%) with low-grade UTUC and only 8 patients (6.5%) with carcinoma in situ. Twelve patients (9.7%) had a history of bladder cancer and 12 (9.7%) had a history of malignancy other than bladder cancer. Whole gene exome sequencing or target region sequencing was performed to explore germline mutations associated with patients with UTUC. The germline genetic testing data were interpreted in accordance with the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP)2015 edition guideline to clarify the germline pathogenic mutation rate and elucidate the clinicopathological characteristics of germline pathogenic mutation carriers. Germline pathogenic mutation rates were further compared with those of healthy East Asian populations to analyze germline mutations associated with the risk of carcinogenesis in UTUC.Results:In this study, 31 germline pathogenic mutations were detected in 28 (22.6%) of 124 patients with UTUC. There were no statistically significant differences in age [54.0 (47.0, 58.0) years old vs. 56.0 (50.8, 58.0) years old], gender (male/female: 21/7 vs. 65/31), history of bladder cancer (0 vs. 12/96), T-stage (T 3-4: 12/28 vs. 41/96), and proportion of histologic high-level (26/28 vs. 85/96) between patients with and without germline pathogenic mutations ( P>0.05). The 31 germline pathogenic mutations were located in 22 genes, including BRCA2 (4, 12.9%), MSH2 (3, 9.7%), RAD54L (2, 6.5%), BRCA1 (2, 6.5%), BRIP1 (2, 6.5%), NOTCH3 (2, 6.5%), XRCC2 (1, 3.2%), VEGFA (1, 3.2%), TBX3 (1, 3.2%), RET (1, 3.2%), PRKN (1, 3.2%), PALB2 (1, 3.2%), NTRK1 (1, 3.2%), NCOA3 (1, 3.2%), MSH6 (1, 3.2%), LRP1B (1, 3.2%), KMT2D (1, 3.2%), KMT2A (1, 3.2%), FANCA (1, 3.2%), BARD1 (1, 3.2%), ARID1A (1, 3.2%), and AR (1, 3.2%). The germline pathogenic mutation rates of 124 patients were compared with those of the healthy East Asian population. The results showed that germline pathogenic mutations in BRCA2 ( OR = 11.9, 95% CI 3.8 - 37.7, P<0.001), MSH2 ( OR = 11.9, 95% CI 3.2-44.5, P<0.001), RAD54L ( OR=14.2, 95% CI 2.7-73.8, P=0.002) and BRCA1 ( OR=11.8, 95% CI 2.4-59.1, P=0.003) genes significantly increase the risk of developing UTUC. Conclusions:The rate of germline pathogenic mutations in ≤60 years old UTUC patients in this study was 22.6%, and germline pathogenic mutations carrying germline BRCA2, MSH2, RAD54L or BRCA1 genes significantly increased the risk of developing UTUC.

Objective:To investigate the effect of adenosine deaminase acting on RNA 1 (ADAR1) on 5-serotonin-2c receptor in alleviating aggression in socially isolated mice.Methods:Sixty healthy male BALB / c mice aged 21 days were randomly divided into six groups: social isolation group, social control group, ADAR1 inducer social isolation group, ADAR1 inhibitor social isolation group, ADAR1 inducer social control group and ADAR1 inhibitor control group.The mice fed in single cage for 4 weeks were used as social isolation model while the mice fed in group were used as control group.ADAR1 inducer (5.0×10 4 U/kg) and inhibitor (10 mg/kg) were given intraperitoneally to mice in the ADAR1 inducer social isolation group and the ADAR1 inhibitor social isolation group respectively.The aggressive behavior of mice was evaluated by resident-intruder test.The expression of ADAR1 and 5-serotonin-2c receptors in the brain of mice was detected by immunohistochemistry and Western blot. Results:The attack latency of social isolation group was significantly lower than that of social control group ((43.15±6.99) s, (542.40±30.50) s; t=15.906, P<0.01), and the latency of attack ((256.70±29.49) s) in the ADAR1 inducer social isolation group was significantly higher than that in the social isolation group ( t=7.046, P<0.01). The latency of attack ((15.25±2.18)s) in the ADAR1 inhibitor social isolation group was significantly lower than that in the social isolation group ( t=3.809, P<0.01). The optical density of ADAR1 immunoreactive cells in the amygdala of the social isolation group mice was significantly lower than that in the corresponding brain area of the social control group (BLA: (0.038±0.002), (0.074±0.004); LaDL: (0.033±0.002), (0.060±0.002); LaVM: (0.045±0.003), (0.073±0.004); Lavl area: (0.044±0.003), (0.070±0.003); t=8.428, 9.037, 6.462, 5.698, all P<0.01). The optical density of ADAR1 immunoreactive positive cells in the amygdala (BLA: (0.060±0.003), LaDL: (0.042±0.002), LaVM: (0.056±0.004), Lavl: (0.054±0.003) in the ADAR1 inducer social isolation group was significantly higher than those in the corresponding brain area of the social isolation group mice ( t=6.055, 2.876, 2.312, 2.492; all P<0.05). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in amygdala of social isolation group were significantly lower than those of social isolation group ( t=11.37, 12.65; P<0.01). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in the amygdala of the ADAR1 inducer social isolation group were significantly higher than those of the social isolation group ( t=3.02, 4.401; P<0.05). Conclusion:ADAR1 inducer alleviates the aggressive behavior of social isolated BALB / c mice by enhancing the protein expression of 5-serotonin-2c receptor in the amygdala of social isolated BALB/c mice.

Objective To explore the effects of ADAR1 inducer and inhibitor on cognition and ADAR1 expression of isolated BALB/c mice.Methods Sixty healthy BALB/c mice were divided into 6 groups according to randomized design with 10 animals each group,the gregarious control group (GH),social isolation model group (SI),ADAR1 inducer treated gregarious group (GH+IFN-γ),ADAR1 inhibitor treated gregarious group (GH+EHNA),ADAR1 inducer treated isolation group (SI+IFN-γ) and ADAR1 inhibitor treated isolation group (SI+EHNA).Mice in drug treatment groups were treated with ADAR1 inducer (5.0? 104 U/kg,20 ml/kg,ip) and inhibitor (10 mg/kg,20 ml/kg,ip).Objection recognition test was used to measure cognition.Immunohistochenmistry was used to measure ADARI immunoreactivity and Western blotwas used to measure ADAR1 protein expression.Results In the objection recognition test,the non-spatial discrimination index of mice in SI group (-0.16±0.09) was significantly lower than that of GH group (0.41 ±0.17,P＜0.01),the non-spatial discrimination index of mice in SI+IFN-γ group (0.20±0.09) and in SI+ EHNA group (-0.29±0.12) was higher (P＜0.01) and lower (P＜0.05) than that of the SI group respectively.The immunohistochemistry results showed that the ADAR1 immunoreactivity in hippocampus of mice in SI group (Hilus:(0.013±0.003),CAI:(0.021±0.005)) decreased significantly compared to those of GH group(Hilus:(0.021 ±0.002),(0.047±0.004);both P＜0.05).And GH+IFN-γgroup mice showed increased ADAR1 immunoreactivity obviously in Hilus ((0.013±0.003) vs (0.023±0.004),P＜0.01) and in CA1 ((0.021±0.005) vs (0.040±0.005),P＜0.01) compared with that of SI group,ADAR1 inducer recovered the above abnornal ADAR1 immunoreactivity.Western blot results showed that the ADAR1 protein expression of mice in SI group (0.48 ±0.07) in hippocampus was significantly decreased (P＜0.01) compared to that of GH group (1.00 ±0.00).The level of ADAR1 protein in SI+IFN-γgroup(0.82 ±0.04) increased compared with that of SI group.Conclusions Four weeks of social isolation can reduce the non-spatial cognitive ability of BALB/c mice and decrease the expression of ADAR1 in the hippocampus.The ADAR1 inducers and inhibitors can reverse and aggravate the cognitive impairment caused by social isolation respectively.The related mechanisms may be related to the expression of ADAR1.

s] Objective To evaluate the effect of comprehensive schistosomiasis control measures with focus on total removal of cattle and sheep in Junshan District,Yueyang City. Methods The retrospective review and field survey were implemented in the pilot villages in Junshan District. The data of Schistosoma japonicum infection status of human,cattle,sheep and Oncome-lania hupensis snails,and density of snails were gathered and modeled in the period of 2006 to 2016. Results The prevalence of schistosome infection in residents in the pilot villages decreased from 3.44％ in 2006 to 0.59％ in 2012(F = 14.501,P =0.013). After removal of all the cattle and sheep in 2013,the prevalence of schistosome infection in the residents decreased to zero in 2016(F=14.148,P=0.033). The density of living snails decreased from 0.8833/0.1 m2 in 2006 to 0.3088/0.1 m2 in 2012(F=76.250,P=0.005). Conclusion The comprehensive schistosomiasis control strategy with focus on cattle and sheep removal is remarkably effective.

ObjectiveTo explore the effects of social isolation on the cognition and expression of 5-HT2C receptor(5-HT2CR) and adenosine deaminase that act on RNA 1(ADAR1) in BALB/c mice.MethodsThe healthy BALB/c mice were isolated for 2,4,and 8 weeks individually since postnatal 21 days respectively to set up isolation mice model,the same age mice without isolation were regarded as control group.The new object location and the new object recognition tests were used to measure the spatial and non-spatial cognitive function,and western blot was used to measure the protein expression of 5-HT2CR and ADAR1.ResultsThe new object location test showed that the spatial discrimination index (DI) of BALB/c mice isolated for 2 weeks was decreased significantly compared with the control group(control group was (0.075±0.340),isolation group was (-0.653±0.308),P<0.05),and no obvious difference was found for the group isolated for 4 and 8 weeks.The new object recognition test showed that the non-spatial DI of BALB/c mice isolated for 2 and 4 weeks were decreased significantly compared with the control group(control 2 weeks group was (0.088±0.210),isolation 2 weeks group was (-0.945±0.194),P<0.05;control 4 weeks group was (0.105±0.267),isolation 4 weeks group was (-0.506±0.215),P<0.05),and no obvious difference was found for the group isolated for 8 weeks.Compared with the control group the expression of 5-HT2CR and ADAR1 in the hippocampus were decreased significantly for the group isolated for 2 weeks.(5-HT2CR:control group was (1.025±0.144),isolation group was (0.891±0.026),P<0.05.ADAR1: control group was (0.839±0.120),isolation group was (0.629±0.094),P<0.05).ConclusionsTwo week social isolation results in the decrease of spatial and non-spatial cognitive function in BALB/c mice,in the meanwhile,social isolation stress results in the obvious decrease of 5-HT2C receptor and ADAR1 protein expression in the hippocampus of BALB/c mice.

Objective To explore the effect of depression on loneliness in medical students',and the mediating effects of introverted personality and social support.Methods EPQ,UCLA,SSRS,and POMS questionnaire were used,and surveyed data was collected from Dalian Medical University medical students.Results The scores of depressive mood,introverted personality,social support and loneliness were (17.77±4.45),(11.97±5.21),(34.52±6.15) and (38.02±6.36).Depression was positively related to loneliness and introverted personality (r=0.286,0.508,P＜0.01),and social support was negatively related to loneliness (r =-0.443,P＜0.01).Introverted personality was positively related to loneliness(r=0.401,P＜0.01).The total effect value was 0.670.The mediating effect of introversion as mediator variable was 0.221,accounting for 33％ of the total effect.Social support as intermediary variable,intermediary effect value was 0.449,accounting for 67％ of the total effect.Standard value of mediating effect between depression and introverted personality showed as 0.508 (95％CI=0.475-0.725,P＜0.0i),standard value of mediating effect between depression and social support showed as-0.150 (95％CI=0.989-1.469,P＜0.01),introverted personality was the mediating variant of depression and loneliness,standard value of mediating effect was 0.156 (95％ CI=0.080-0.232,P＜0.01),social support was the mediating variant of depression and loneliness,standard value of mediating effect was 0.317 (95％ CI=0.177-0.457,P＜0.01).Conclusions Introverted personality and social support play an intermediary role between depression and loneliness.

Objective To evaluate the relationship between 18F-FDG uptake and P-gp expression in Bcap37 or Bcap37/MDR1 tumor-bearing BALB/c nude mice.Methods Bcap37 or Bcap37/MDR1 cells were injected into BALB/c nude mice (1× 107cells/ml,0.2 ml/mouse) to construct mice models.Bcap37 (n=5) or Bcap37/MDR1 (n=5) tumor-bearing mice fasted for 6 h before imaging.After anesthesia,the mice were injected with 7.4 MBq of 18F-FDG via tail vein.The dynamic microPET scans were carried out for 90 min.On the microPET images,the ROI was drawn and the TAC was obtained.The next day,those 10 mice underwent dynamic microPET scans after injected with elacridar (GF120918) and 18F-FDG.Another 10 mice,5 with Bcap37 tumors and 5 with Bcap37/MDR1 tumors,were used.After 7.4 MBq 18F-FDG with or without 2.0 mg/kg GF120918 was administered via tail vein,microPET images were acquired at 60 min.ROI was drawn over the tumors and SUV was obtained.Two-sample t test was used to analyze the data.Results GF120918 did not significantly alter the 18F-FDG accumulation curve in Bcap37 tumors,but significantly enhanced the 18F-FDG accumulation in Bcap37/MDR1 tumors.GF120918 did not influence 18F-FDG uptake (SUV) in Bcap37 tumors (1.052±0.028,1.028±0.045,t =1.792,P＞0.05),but significantly increased the SUV in Bcap37/MDR1 tumors (1.015±0.043,0.712±0.031,t=3.365,P＜0.05);The SUV of 18 F-FDG in Bcap37 tumors was significantly higher than that in Bcap37/MDR1 tumors without injection of GF120918 (t =3.952,P＜0.05).The SUV was not significantly different when GF120118 was injected (t=1.835,P＞0.05).Conclusions 18F-FDG is a substrate of P-gp.18F-FDG imaging combined with GF120918 injection may be an effective noninvasive method for the detection of tumor's MDR.

Objective To evaluate the analytical performance of ARCHITECT-i2000SR chemiluminescence analyzer in detec-tion of HBsAg,HIV-antibody,TP-antibody and HCV-antibody.Methods Validated the precision,carryover,ference interval of alpha-fetoprotein and linearity performance of ARCHITECT-i2000SR.The same specimens were tested by both CMIA and ELISA,and the results were compared and analyzed.Results The precision,carryover and ference interval of alpha-feto-protein of HBsAg,HIV-antibody,TP-antibody and HCV-antibody were within the range provided by the manufacturer for ARCHITECT-i2000SR.The theoretical and measured values of HBsAg were:Y = 1.102X - 6.678 6 (r = 0.995 5,P <0.05),the range of linearity 1.08~208.6.The sesult was very good for the four blood index by both methods.Conclusion The basic performances of ARCHITECT-i2000SR were consistent with the data provided by the manufacturer,so it canbe used to inspect the clinical samples and the sasults were credible.

Objective To study the effect of social isolation( SI) on the exploratory behavior and working memory in mice. Methods The Kunming mice of postnatal 21 days were divided into the control group,SI 2 weeks group,SI 2 weeks gregarious group,SI 4 weeks group and SI 8 weeks group,according to randomized design with ten animals each. All isolated mice were isolated for 2, 4 and 8 weeks respectively, the gregarious group were housed under normal grouped housing enviroment after isolation until adult, the mice with the relative same age were control groups. All animals were measured for exploratory behavior and working memory by performing open field and T?maze after the treatment. Results In the open field,compared to the relative control group,the central area of the total time in the SI 4 weeks group(0.07±0.04) was less than the control (0.10±0.04) obviously. The central area percentage of total time in SI 8 weeks group (0.64±0.12) were more than the control (0.43±0.08). In the T?maze,the alteration times in SI 2 weeks group (first day (5.92±0.79),second day (6.67±1.3),third day (7.42±1.08),fourth day (8.17±1.27)) were less than the control (first day (6.80±1.14); second day (7.60± 0.84);third day (8.30±0.95);forth day (9.20±1.32)). However,the alteration times of gregarious group showed no obvious change. Both the alteration times of SI 4 weeks (8.18±1.99) in the second day and that of SI 8 weeks (8.29±3.04) in the forth day were more than the control (6.60±2.11) and (7.80±2.53) respectively.Conclu?sions Working memory of SI 2 weeks rats decrease,which can be improved by the resocialization.SI 4 weeks and 8 weeks rats show the decreasing exploring ability and increasing anxiety and work memory.