Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA_A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA_A receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABA_A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.

Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus, the pathological mechanism of which remains unclear yet. Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases. However, the lipidome signature of human myometrium, which could be crucial in the development of adenomyosis, remains unknown. In this study, we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultra-performance liquid chromatography (UPLC) coupled with triple quadrupole (QqQ)-mass spectrometry (MS). A total of 317 lipid species were successfully quantified in the myometrial tissues from women with (n = 38) or without (n = 65) adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital (Bejing, China). Up to 83 lipid species showed significant alternations in content between the two groups. These lipid aberrations involved multiple metabolic pathways, and emphasized inflammation, cell migration, and immune dysregulation upon adenomyosis. Moreover, receiver operating characteristic (ROC) curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve (AUC) of 0.906. Desorption electrospray ionization MS imaging (MSI) further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue. Collectively, these results extremely improved our understanding on the molecular basis of adenomyosis, and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis.

Objective To evaluate the long-term efficacy of tumor necrosis factor-α(TNF-α)inhibitor(TNFi)in the treatment of ankylosing spondylitis(AS)complicated with osteoporosis(OP)and the impact on bone metabolism,bone density,and inflammatory factors.Methods The data of 158 patients with AS and OP,who were admitted to Department of Rheumatology and Immunology of The First Affiliated Hospital of Naval Medical University(Second Military Medical University)from Jan.1,2010 to Dec.31,2017,were retrospectively collected.The patients were divided into bisphosphonate group(n=54),TNFi group(n=58),and TNFi+bisphosphonate group(n=46)according to the treatment methods.All patients were treated with calcium combined with calcitriol as the background treatment.After 5 years of treatment,Bath ankylosing spondylitis disease activity index(BASDAI)and Bath ankylosing spondylitis functional index(BASFI)scores were evaluated,and inflammatory indexes,bone metabolism markers,and bone mineral density were detected.Results After 5 years of treatment,the BASDAI and BASFI scores,erythrocyte sedimentation rate(ESR),C reactive protein(CRP),TNF-α,and interleukin-17A of the TNFi+bisphosphonate group and TNFi group were significantly lower than those before treatment(all P＜0.05);in the bisphosphonate group only ESR and CRP were significantly lower than those before treatment(both P＜0.05),and the other inflammatory indexes and BASDAI and BASFI scores showed no significant changes(all P＞0.05).The bone mineral density of the 3 groups after 5 years of treatment was significantly higher than that before treatment(all P＜0.05),and the bone mineral density of the TNFi+bisphosphonate group was significantly higher than that of the other 2 groups(both P＜0.05).After 5 years of treatment,the levels of parathyroid hormone(PTH),procollagen type 1 N-terminal propeptide(P1NP)and β-C-terminal telopeptide of type Ⅰ collagen(β-CTX)in the TNFi+bisphosphonate group and bisphosphonate group were significantly decreased compared with those before treatment(all P＜0.05),while the levels of N-terminal midfragment of osteocalcin(N-MID)and 25-hydroxy-vitamin D(25VitD)were significantly increased(all P＜0.05);in the TNFi group only PTH and P1NP levels were significantly decreased(both P＜0.05),while β-CTX,N-MID and 25VitD levels showed no significant differences(all P＞0.05).Conclusion Long-term use of TNFi in patients with AS and OP can effectively reduce disease activity,improve physical function,decrease the level of inflammatory factors,alleviate abnormal bone metabolism,and increase bone mineral density;and the combined use of TNFi and bisphosphonates has better efficacy.

Purpose: This study aimed to compare and analyze the feasibility and long-term efficacy of prostatic capsule-sparing (PCS) and nerve-sparing (NS) radical cystectomy in the treatment of bladder cancer. Methods: From June 2004 to December 2021, our institution treated and followed 145 patients who underwent radical cystectomy with neobladder reconstruction for over a year. These patients were divided into 2 groups: PCS (n=74) and NS (n=71). To minimize potential biases, 1:1 propensity score matching was utilized to compare oncological outcomes, functional outcomes, and complications between the groups. Additionally, Kaplan-Meier analysis and the log-rank test were used to evaluate survival differences between the PCS and NS groups. Results: The median follow-up durations for PCS and NS were 155 and 122 months, respectively. After adjusting for propensity scores, a total of 96 patients (48 in each group) were included for further analysis. Kaplan-Meier curves showed no statistically significant differences in metastasis-free probability (P=0.206), cancer-specific survival (P=0.091), and overall survival (P=0.208). The daytime urinary control (UC) rate at 3, 6, and 12 months postoperatively was 72.9%, 91.7%, and 97.9% in the PCS group and 47.9%, 79.2%, and 91.7% in the NS group, respectively (P=0.012, P=0.083, and P=0.362). The nocturnal UC rate was 54.2%, 85.4%, and 95.8% in the PCS group, and 31.3%, 60.4%, and 83.3% in the NS group, respectively (P=0.023, P=0.006, and P=0.091). Regarding erectile function recovery, 62.5% of patients in the PCS group and 22.9% in the NS group returned to preoperative levels (P<0.001). Conclusions PCS outperformed NS in restoring UC and sexual function and did not affect oncological outcomes. However, PCS was associated with a higher risk of complications linked to bladder-neck obstruction.

Purpose: This study aimed to compare and analyze the feasibility and long-term efficacy of prostatic capsule-sparing (PCS) and nerve-sparing (NS) radical cystectomy in the treatment of bladder cancer. Methods: From June 2004 to December 2021, our institution treated and followed 145 patients who underwent radical cystectomy with neobladder reconstruction for over a year. These patients were divided into 2 groups: PCS (n=74) and NS (n=71). To minimize potential biases, 1:1 propensity score matching was utilized to compare oncological outcomes, functional outcomes, and complications between the groups. Additionally, Kaplan-Meier analysis and the log-rank test were used to evaluate survival differences between the PCS and NS groups. Results: The median follow-up durations for PCS and NS were 155 and 122 months, respectively. After adjusting for propensity scores, a total of 96 patients (48 in each group) were included for further analysis. Kaplan-Meier curves showed no statistically significant differences in metastasis-free probability (P=0.206), cancer-specific survival (P=0.091), and overall survival (P=0.208). The daytime urinary control (UC) rate at 3, 6, and 12 months postoperatively was 72.9%, 91.7%, and 97.9% in the PCS group and 47.9%, 79.2%, and 91.7% in the NS group, respectively (P=0.012, P=0.083, and P=0.362). The nocturnal UC rate was 54.2%, 85.4%, and 95.8% in the PCS group, and 31.3%, 60.4%, and 83.3% in the NS group, respectively (P=0.023, P=0.006, and P=0.091). Regarding erectile function recovery, 62.5% of patients in the PCS group and 22.9% in the NS group returned to preoperative levels (P<0.001). Conclusions PCS outperformed NS in restoring UC and sexual function and did not affect oncological outcomes. However, PCS was associated with a higher risk of complications linked to bladder-neck obstruction.

Purpose: This study aimed to compare and analyze the feasibility and long-term efficacy of prostatic capsule-sparing (PCS) and nerve-sparing (NS) radical cystectomy in the treatment of bladder cancer. Methods: From June 2004 to December 2021, our institution treated and followed 145 patients who underwent radical cystectomy with neobladder reconstruction for over a year. These patients were divided into 2 groups: PCS (n=74) and NS (n=71). To minimize potential biases, 1:1 propensity score matching was utilized to compare oncological outcomes, functional outcomes, and complications between the groups. Additionally, Kaplan-Meier analysis and the log-rank test were used to evaluate survival differences between the PCS and NS groups. Results: The median follow-up durations for PCS and NS were 155 and 122 months, respectively. After adjusting for propensity scores, a total of 96 patients (48 in each group) were included for further analysis. Kaplan-Meier curves showed no statistically significant differences in metastasis-free probability (P=0.206), cancer-specific survival (P=0.091), and overall survival (P=0.208). The daytime urinary control (UC) rate at 3, 6, and 12 months postoperatively was 72.9%, 91.7%, and 97.9% in the PCS group and 47.9%, 79.2%, and 91.7% in the NS group, respectively (P=0.012, P=0.083, and P=0.362). The nocturnal UC rate was 54.2%, 85.4%, and 95.8% in the PCS group, and 31.3%, 60.4%, and 83.3% in the NS group, respectively (P=0.023, P=0.006, and P=0.091). Regarding erectile function recovery, 62.5% of patients in the PCS group and 22.9% in the NS group returned to preoperative levels (P<0.001). Conclusions PCS outperformed NS in restoring UC and sexual function and did not affect oncological outcomes. However, PCS was associated with a higher risk of complications linked to bladder-neck obstruction.

Abstract: Objective　To investigate the antimicrobial activity of omadacycline (OMC) against clinical Streptococcus agalactiae (GBS) isolates, as well as its relationship with biofilm formation, resistance genes and virulence genes. Methods　A total of 136 strains of Streptococcus agalactiae isolated from Shenzhen Nanshan People's Hospital between 2015 to 2020. The minimum inhibitory concentration (MIC) of OMC against Streptococcus agalactiae was determined by broth microdilution. Crystal violet staining was used to detect the biofilm formation ability of GBS. Resistance genes (tetM, tetO, tetK, ermB, OptrA) and virulence genes (cpsⅢ, bca, fbsA, cpsA, scpB) were investigated by polymerase chain reaction (PCR). Results　Among the 136 clinical isolates of GBS, 20 strains (14.7%) were resistant to OMC, 64 (47.1%) were intermediate, and 52 (38.2%) were sensitive. Fifty-seven strains (41.9%) were biofilm-positive, 20 of which (35.1%) were sensitive to OMC. Seventy-nine strains (58.1%) were biofilm-negative, 32 of which (40.5%) were susceptible to OMC. There was a statistically significant difference in the sensitivity rates between the two groups of strains (χ2=63.062, P<0.001), but there was no significant difference in the sensitivity of OMC among the biofilm-positive strains (Fisher's exact test, P=0.824). The resistance rates of tetM, tetO, ermB and OptrA positive strains were higher than those of negative strains, while tetK was opposite. The presence of tetM (Z=0.815, P=0.415), tetO (Z=0.151, P=0.88), tetK (Z=0.567, P=0.571), ermB (Z=1.198, P=0.231) resistance genes in Streptococcus agalactiae had no significant impact on the sensitivity of OMC. However, the presence of the OptrA resistance gene showed a statistically significant effect on the sensitivity of OMC (Z=2.913, P=0.004). The virulence factors cpsⅢ, bca, fbsA, cpsA and scpB were all detected at a rate higher than 50%. The presence of the virulence genes cpsⅢ (Z=0.222, P=0.824), bca (Z=0.141, P=0.888), fbsA (Z=0.813, P=0.416), and cpsA (Z=1.615, P=0.106) in Streptococcus agalactiae had no significant impact on the sensitivity of OMC. However, there was a significant inter-group difference in the scpB virulence gene (Z=2.844, P=0.004), but the rank mean values and resistance rates of scpB-positive strains were lower than those of the negative strains. Conclusions　The formation of biofilm in Streptococcus agalactiae reduces its sensitivity to OMC, but there was no significant difference in the sensitivity to OMC among the biofilm-positive strains. The presence of resistance genes tetM, tetO, tetK, ermB, and virulence genes cpsⅢ, bca, fbsA, cpsA, scpB in Streptococcus agalactiae is not associated with OMC resistance, but the presence of the resistance gene OptrA is correlated with OMC resistance..

ObjectiveTo investigate the features of liver injury and related influencing factors in adolescents and adults with infectious mononucleosis (IM). MethodsA retrospective analysis was performed to investigate the features of liver injury in adolescents and adults with IM who were hospitalized in Peking University First Hospital from January 2005 to December 31 2018, and the patients were divided into subgroups based on age, Epstein-Barr virus (EBV) DNA level, and presence or absence of jaundice or infection with cytomegalovirus or hepatitis E virus (HEV). The t-test was used for comparison of continuous data meeting analytical conditions between two groups, and the Mann-Whitney U test was used for comparison of continuous data which did not meet analytical conditions between two groups; the chi-square test was used for comparison of categorical data between two groups, and the Fisher’s exact test was used for comparison of categorical data which did not meet the analytical conditions of the chi-square test. A logistic regression analysis was used for multivariate analysis. ResultsA total of 274 patients were enrolled, with 154 male patients (56.2%) and 120 female patients (43.8%), and the mean age of onset was 22.3±67 years. The incidence rate of liver injury ［defined as alanine aminotransferase (ALT) ＞50 U/L and/or aspartate aminotransferase (AST)＞40 U/L］ was 97.4% (267/274), and that of jaundice was 27.6% (74/268). The patients, aged ≥20 years, tended to have a higher level of gamma-glutamyl transpeptidase (GGT) (Z=2.070, P=0.038). Serum EBV DNA was measured for 167 patients, among whom 90 had positive results and 77 had negative results. The positive serum EBV DNA group had significantly higher levels of GGT (Z=3.005, P=0.003) and lactate dehydrogenase (Z=2.162, P=0.031) than the negative serum EBV DNA group. The patients with cytomegalovirus infection tended to have a higher level of alkaline phosphatase (Z=2.351, P=0.019), and the patients with HEV infection presented with a higher level of GGT (Z=1.988, P=0.047). AST (odds ratio ［OR］=1.006, 95% confidence interval ［CI］: 1.002-1.010, P=0.005) and ALP (OR=1.012, 95%CI: 1.005-1.020, P=0.001) were independent risk factors for jaundice. ConclusionThere is a high incidence rate of liver injury in adolescents and adults with IM, and the patients with an older age or positive serum EBV DNA tend to have more severe liver injury.

Objective:To analyze the effectiveness of antiviral therapy on adolescents and adults with infectious mononucleosis (IM).Methods:The clinical data of patients aged≥16 years old with IM who were hospitalized in Peking University First Hospital from January 1, 2005 to December 31, 2018 were analyzed retrospectively, and the patients were divided into antiviral treatment group and non-antiviral treatment group. The duration of hospitalization day, fever duration, ratio of lymphocytes and duration for normalization of Epstein-Barr virus (EBV) markers were compared between the two groups through single factor and propensity score matching analysis. Statistical analysis was conducted by independent sample t test, Mann-Whitney U test, chi-square test or Fisher exact probability method. Results:A total of 274 cases were enrolled and 176 cases (64.23%) were divided into antiviral treatment group and 98 cases (35.77%) into non-antiviral treatment group. The proportion of male (56.25%(99/176) vs 56.12%(55/98)), age (21.0(18.0, 26.0) years old vs 21.0(18.0, 27.0) years old), the ratio of fever (98.30%(173/176) vs 93.88%(92/98)), sore throat (90.34%(159/176) vs 88.78%(87/98)), lymphocyte ratio (0.648(0.568, 0.707) vs 0.663(0.581, 0.711)), atypical lymphocyte ratio (0.150(0.100, 0.235) vs 0.135(0.060, 0.250)) and serum EBV DNA level (2.71(2.70, 3.47) lg copies/mL vs 2.70(2.70, 3.28) lg copies/mL) were comparable between two groups at admission, and the differences were all not statistically significant(all P>0.05). The durations of hospitalization and fever in antiviral treatment group were 14.0(10.0, 18.0) d and (14.91±7.24) d, respectively, which were both significantly longer than those in non-antiviral treatment group (11.0(7.0, 15.0) d and (9.95±5.67) d, respectively). The differences were both statistically significant ( Z=-3.294 and t=-5.035, respectively, both P<0.01). Twenty-six patients each in the antiviral treatment group and non-antiviral treatment group were included in the propensity score matching assessment. The fever days of the two groups were 15.0(10.0, 18.0) d and 7.5(5.0, 12.5) d, respectively, and the hospitalization days were (15.4±5.5) d and (12.0±5.7) d, respectively. The differences were both statistically significant ( Z=-3.781 and t=-2.187, respectively, both P<0.05). However, there were no significant differences in the time required for the ratio of lymphocytes returning to normal, the time required for the ratio of atypical lymphocytes decreasing to <0.100, and the time required for serum EBV DNA becoming negative(all P>0.05). Conclusion:The antiviral treatment could not improve the prognosis of adolescent and adult IM patients.

The ability of prevention, treatment and management of infectious diseases is a basic requirement for general practitioners. This article introduces our experience in the infectious disease rotation for general practice residency training, focusing on the rotation management at different stages of training to explore how to improve teaching quality and the ability of trainers in a short period of the rotation.