Ag85B with c-di-AMP as mucosal adjuvant showed immunotherapeutic effects on persistent Mycobacterium tuberculosis infection in mice

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.

Acute sarcoidosis Löfgren Syndrome treated by Chinese medicinal formula based on Syndrome Differentiation: a case - based review / Tratamiento de síndrome de Löfgren de sarcoidosis con fórmula medicinal china basada en diferenciación de síndrome: una revisión basada en casos

Löfgren syndrome (LS) is a unique acute manifestation of sarcoidosis and characterized by erythema nodosum, bilateral hilar lymphadenectasis, and/or bilateral ankle arthritis or periarthritis. A 37 - year - old female patient with LS presented with fever accompanied by multiple joint swelling and pain, nodular skin erythema, and bilateral hilar lymphadenectasis. The patient had received treatment involving non - steroidal anti - inflammatory drugs and glucocorticoids in other hospitals, but the effects were poor, and the conditions reemerged. The LS duration has lasted for more than 3 months. Following traditional Chinese medicine (TCM) treatment, syndrome differentiation as well as giving patients oral Chinese medicine decoction, the symptoms of the patient were rapidly relieved within one week and did not recur during a six - month follow - up period. This case is the first clinical report of acute sarcoidosis LS treated using T CM and reflects the significant advantages of this form of therapy in emergency treatment

El síndrome de Löfgren (LS) es una manifest ación única y aguda de sarcoidosis, caracterizada por eritrema nodoso, linfadenectasis hilar bilateral, y/o a r tritis de tobillo bilateral o periartritis. Una paciente de 37 años de sexo femenino con LS se presentó con fiebre, acompañada de inflamación y do lor múltiple de articulaciones, eritrema nodular cutáneo, y linfadenectasis hilar bilateral. La paciente recibió un tratamiento que consistió en antiinflamatorios no esteroidales y glucocorticoides en otros hospitales, pero los efectos fueron leves y las c ondiciones reemergieron. El LS ha durado más de tres meses. Siguiendo el tratamiento de medicina tradicional china (MTC), la diferenciación de síndrome, así como darles a los pacientes una decocción de medicina china por vía oral, los síntomas de la pacien te rápidamente fueron aliviados en el curso de una semana y no recidivaron durante los seis meses de un seguimiento. El caso es el primer reporte clínico de tratamiento de sarcoidosis aguda asociada a LS usando TCM y refleja las significativas ventajas de esta forma de terapia en el tratamiento de emergencia.

Application of value contrast-enhanced ultrasound microangiography, elastography and conventional ultrasound-guided prostate cancer puncture biopsy in the diagnosis of prostate diseases / 现代泌尿外科杂志

【Objective】 To explore the application value of transrectal contrast-enhanced ultrasound (CEUS) microangiography, elastography and conventional ultrasound-guided prostate cancer puncture biopsy in the diagnosis of prostate diseases, so as to provide reference for the early diagnosis of prostate cancer. 【Methods】 A total of 156 patients suspected of prostate cancer treated in our hospital during Jan.2021 and Dec.2022 were selected.The patients were divided into group A (n=52, conventional ultrasound), group B (n=49, elastography) and group C (n=55, CEUS microangiography) according to the puncture methods.The positive rate of puncture and diagnostic value of the three methods were analyzed. 【Results】 The positive rate of puncture was 24.18% in group B and 25.71% in group C, which was significantly higher than that in group A (13.15%, P<0.05).The diagnostic accuracy of prostate cancer was 93.88% in group B and 94.55% in group C, higher than that in group A (75.00%, P=0.002).In group B, the Emax and Emean of malignant lesions were (65.56±14.43) kPa and (59.59±11.02) kPa, respectively, which were higher than those of benign lesions (P<0.001).The difference in blood flow grade detected by CEUS microangiography was statistically significant between benign and malignant lesions, and grade 3 blood flow accounted for 95.65% of malignant lesions.The area under the receiver operating characteristic (ROC) curve (AUC) of Emean in elastography in the diagnosis of prostate cancer was 0.810 (95%CI: 0.690-0.930, P<0.05).The AUC of CEUS microangiography in the diagnosis of prostate cancer was 0.965 (95%CI: 0.913-1.000, P<0.05). 【Conclusion】 Compared with conventional ultrasound-guided prostate cancer puncture biopsy, CEUS microangiography and elastography guided prostate cancer puncture biopsy have better application value in the diagnosis of prostate diseases, which can provide semi-quantitative/quantitative parameter basis for the diagnosis of prostate diseases.

Revolutionizing early Alzheimer's disease and mild cognitive impairment diagnosis: a deep learning MRI meta-analysis / Revolucionando a doença de Alzheimer precoce e o diagnóstico de comprometimento cognitivo leve: uma metanálise de aprendizagem profunda por ressonância magnética

Abstract Background The early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains a significant challenge in neurology, with conventional methods often limited by subjectivity and variability in interpretation. Integrating deep learning with artificial intelligence (AI) in magnetic resonance imaging (MRI) analysis emerges as a transformative approach, offering the potential for unbiased, highly accurate diagnostic insights. Objective A meta-analysis was designed to analyze the diagnostic accuracy of deep learning of MRI images on AD and MCI models. Methods A meta-analysis was performed across PubMed, Embase, and Cochrane library databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on the diagnostic accuracy of deep learning. Subsequently, methodological quality was assessed using the QUADAS-2 checklist. Diagnostic measures, including sensitivity, specificity, likelihood ratios, diagnostic odds ratio, and area under the receiver operating characteristic curve (AUROC) were analyzed, alongside subgroup analyses for T1-weighted and non-T1-weighted MRI. Results A total of 18 eligible studies were identified. The Spearman correlation coefficient was -0.6506. Meta-analysis showed that the combined sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.84, 0.86, 6.0, 0.19, and 32, respectively. The AUROC was 0.92. The quiescent point of hierarchical summary of receiver operating characteristic (HSROC) was 3.463. Notably, the images of 12 studies were acquired by T1-weighted MRI alone, and those of the other 6 were gathered by non-T1-weighted MRI alone. Conclusion Overall, deep learning of MRI for the diagnosis of AD and MCI showed good sensitivity and specificity and contributed to improving diagnostic accuracy.

Resumo Antecedentes O diagnóstico precoce da doença de Alzheimer (DA) e do comprometimento cognitivo leve (CCL) continua sendo um desafio significativo na neurologia, com métodos convencionais frequentemente limitados pela subjetividade e variabilidade na interpretação. A integração da aprendizagem profunda com a inteligência artificial (IA) na análise de imagens de ressonância magnética surge como uma abordagem transformadora, oferecendo o potencial para insights diagnósticos imparciais e altamente precisos. Objetivo Uma metanálise foi projetada para analisar a precisão diagnóstica do aprendizado profundo de imagens de ressonância magnética em modelos de DA e CCL. Métodos Uma metanálise foi realizada nos bancos de dados das bibliotecas PubMed, Embase e Cochrane seguindo as diretrizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), com foco na precisão diagnóstica do aprendizado profundo. Posteriormente, a qualidade metodológica foi avaliada por meio do checklist QUADAS-2. Medidas diagnósticas, incluindo sensibilidade, especificidade, razões de verossimilhança, razão de chances diagnósticas e área sob a curva característica de operação do receptor (area under the receiver operating characteristic curve [AUROC]) foram analisadas, juntamente com análises de subgrupo para ressonância magnética ponderada em T1 e não ponderada em T1. Resultados Um total de 18 estudos elegíveis foram identificados. O coeficiente de correlação de Spearman foi de -0,6506. A metanálise mostrou que a sensibilidade e a especificidade combinadas, a razão de verossimilhança positiva, a razão de verossimilhança negativa e a razão de chances de diagnóstico foram 0,84, 0,86, 6,0, 0,19 e 32, respectivamente. A AUROC foi de 0,92. O ponto quiescente do resumo hierárquico da característica de operação do receptor (hierarchical summary of receiver operating characteristic [HSROC]) foi 3,463. Notavelmente, as imagens de 12 estudos foram adquiridas apenas por ressonância magnética ponderada em T1, e as dos outros 6 foram obtidas apenas por ressonância magnética não ponderada em T1. Conclusão Em geral, a aprendizagem profunda da ressonância magnética para o diagnóstico de DA e CCL mostrou boa sensibilidade e especificidade e contribuiu para melhorar a precisão diagnóstica.

Antimicrobial resistance in and multilocus sequence typing of Campylobacter jejuni in meat and meat products / 预防医学

Objective@#To investigate the antimicrobial resistance in and multilocus sequence typing (MLST) of Campylobacter jejuni in meat and meat products in Liaoning Province, so as to provide insights into the management of C. jejuni infection. @*Methods@#Nine C. jejuni isolates from meat and meat products in 2020 were subjected to whole genome sequencing, and the minimum inhibitory concentration was measured with the agar dilution method. MLST of C. jejuni isolates was performed with the microbial resistance mechanism traceability reference database and analysis system.@*Results@#Six drug-resistant C. jejuni isolates were detected, and there were four multidrug-resistant isolates. There were six C. jejuni isolates resistant to tetracycline, five isolates resistant to nalidixic acid, four isolates resistant to ciprofloxacin, two isolates resistant to florfenicol, one isolate resistant to gentamicin and one isolate resistant to streptomycin. Nine C. jejuni isolates showed sensitive to azithromycin, chloramphenicol and clindamycin. MLST identified six ST types in nine C. jejuni isolates, with ST45 and ST2274 as the predominant type, and detected one isolate with unclassified ST type. Phylogenetic analysis showed that KW028 and KW029 of ST45 type were closely related and had high homology, and KW040 and KW042 of ST2274 type were closely related with high homology, while KW007 of ST6701 type was closely related to KW040 and KW042 of ST2274 type, with only one pgm housekeeper gene in difference. @*Conclusions@#High resistance to tetracycline, nalidixic acid and ciprofloxacin was detected in nine C. jejuni isolates from meat and meat products, and ST45 and ST2274 were predominant ST types of C. jejuni.

Effects of preoperative lipid metabolism indexes on the prognosis of patients with non-muscular invasive bladder cancer / 现代泌尿外科杂志

【Objective】 To investigate the effects of preoperative lipid metabolism level on the postoperative prognosis of non-muscular invasive bladder cancer (NMIBC). 【Methods】 Clinical data of NMIBC patients who underwent surgical treatment in our hospital during Mar.2014 and May 2021 were retrospectively analyzed. Based on receiver operating characteristic (ROC) curve, the optimal cutoff values of all lipid metabolism indicators were determined and patients were classified accordingly. The independent risk factors for postoperative recurrence were identified with Cox regression model. The survival was analyzed with Kaplan-Meier, and recurrence-free survival (RFS) was compared using log-rank tests. A recurrence risk prediction model was established based on the high-density lipoprotein (HDL) and other clinic pathological factors and the accuracy of prediction was evaluated with the area under the ROC curve (AUC). 【Results】 Cox multivariate analysis showed HDL, tumor number, tumor size and histological grade were independent risk factors for recurrence (P<0.05). Kaplan-Meier analysis showed that RFS was significantly longer in the high-HDL group than in the low-HDL group (P<0.001). Incorporating HDL, tumor number, tumor size, histological grade, and tumor stage into the recurrence risk model, the AUC was 0.706, and internal cross validation showed the AUC was 0.711. 【Conclusion】 Preoperative HDL is an independent risk factor affecting the RFS of patients with NMIBC, and combining it with clinic pathological factors will improve the prediction of tumor recurrence.

Fecal rotavirus and adenovirus antigen detection and clinical analysis of children with acute gastroenteritis in a hospital of Beijing City from 2019 to 2022 / 中华预防医学杂志

As a single-center retrospective study, we analyzed the results of rotavirus and human adenovirus antigens in stool samples with colloidal gold immunochromatography method in children with acute gastroenteritis under the age of five who were treated in our hospital from 2019 to 2022. After excluding nonconforming cases and duplicate cases, 2 896 cases were included, of which 559 cases were detected with at least one viral antigen. According to the test results, they were divided into RV positive group, HAdV positive group and RV & HAdV double positive group. The gender, age, seasonal distribution, clinical symptoms and related laboratory tests were compared and analyzed with χ2 test, analysis of variance and nonparametric test. Among the single samples from 2 896 children, the positive rate of RV antigen was 6.21% (180/2 896), the positive rate of HAdV antigen was 10.91% (316/2 896), and the double positive rate of RV & HAdV was 2.18% (63/2 896). The positive rate of HAdV antigen in 2021 was 16.11%, a significant increase compared with 6.20% in 2020. RV infection has obvious seasonality, and spring and winter are the seasons with high incidence of infection (χ2=74.018, P<0.001), while HAdV infection has no obvious seasonality (χ2=2.110, P=0.550), showing sporadic infection throughout the year. The proportions of fever and vomiting symptoms in children with RV infection were significantly higher than those in the HAdV infection group (χ2=40.401, P<0.001; χ2=32.593, P<0.001), but the positive rate of white blood cells in the stool was significantly lower than that in the HAdV infection group (χ2=13.741,P<0.01). In summary, paying attention to the epidemiological changes of RV and HAdV is of great significance for clinical diagnosis and treatment and disease prevention and control.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Cardiac Structural and Functional Features in Patients With Type 2 Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction:A Study Based on Propensity Score Matching / 中国医学科学院学报

Objective To investigate the cardiac structural and functional characteristics in the patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM),and predict the factors influencing the characteristics. Methods A total of 783 HFpEF patients diagnosed in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from April 2009 to December 2020 were enrolled in this study.Echocardiography and tissue Doppler technique were employed to evaluate cardiac structure and function.According to the occurrence of T2DM,the patients were assigned into a HFpEF+T2DM group (n=332) and a HFpEF group (n=451).Propensity score matching (PSM)(in a 1∶1 ratio) was adopted to minimize confounding effect.According to urinary albumin excretion rate (UAER),the HFpEF+T2DM group was further divided into three subgroups with UAER<20 μg/min,of 20-200 μg/min,and>200 μg/min,respectively.The comorbidities,symptoms and signs,and cardiac structure and function were compared among the groups to clarify the features of diabetes related HFpEF.Multivariate linear regression was conducted to probe the relationship of systolic blood pressure,blood glucose,glycosylated hemoglobin,and UARE with cardiac structural and functional impairment. Results The HFpEF+T2DM group had higher prevalence of hypertension (P=0.001) and coronary heart disease (P=0.036),younger age (P=0.020),and larger body mass index (P=0.005) than the HFpEF group,with the median diabetic course of 10 (3,17) years.After PSM,the prevalence of hypertension and coronary heart disease,body mass index,and age had no significant differences between the two groups(all P>0.05).In addition,the HFpEF+T2DM group had higher interventricular septal thickness (P=0.015),left ventricular posterior wall thickness (P=0.040),and left ventricular mass (P=0.012) and lower early diastole velocity of mitral annular septum (P=0.030) and lateral wall (P=0.011) than the HFpEF group.Compared with the HFpEF group,the HFpEF+T2DM group showed increased ratio of early diastolic mitral filling velocity to early diastolic mitral annular velocity (E/e') (P=0.036).Glycosylated hemoglobin was correlated with left ventricular mass (P=0.011),and the natural logarithm of UAER with interventricular septal thickness (P=0.004),left ventricular posterior wall thickness (P=0.006),left ventricular mass (P<0.001),and E/e' ratio (P=0.049). Conclusion The patients with both T2DM and HFpEF have thicker left ventricular wall,larger left ventricular mass,more advanced left ventricular remodeling,severer impaired left ventricular diastolic function,and higher left ventricular filling pressure than the HFpEF patients without T2DM.Elevated blood glucose and diabetic microvascular diseases might play a role in the development of the detrimental structural and functional changes of the heart.

Research progress of celastrol on the prevention and treatment of metabolic associated fatty liver disease / 生理学报

Metabolic associated fatty liver disease (MAFLD) is a liver disease with hepatocyte steatosis caused by metabolic disorders, which is closely related to obesity, diabetes, metabolic dysfunction, and other factors. Its pathological process changes from simple steatosis, liver inflammation to non-alcoholic steatohepatitis (NASH), and then leads to liver fibrosis, cirrhosis, and liver cancer. At present, no specific therapeutics are available for treatment of MAFLD targeting its etiology. Celastrol is the main active component of the traditional Chinese medicine Celastrus orbiculatus Thunb. In recent years, it has been found that celastrol shows important medicinal value in regulating lipid metabolism, reducing fat and weight, and protecting liver, and then ameliorates MAFLD. This article reviews the related research progress of celastrol in the prevention and treatment of MAFLD, so as to provide a reference for the comprehensive development and utilization of celastrol.

The expression of Plakoglobin in residual cancer after neoadjuvant chemotherapy for breast cancer and its prognostic impact on patients / 中华肿瘤杂志

Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.

The expression of Plakoglobin in residual cancer after neoadjuvant chemotherapy for breast cancer and its prognostic impact on patients / 中华肿瘤杂志

Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.

Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia / 中华血液学杂志

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

Association between exposure to artificial light at night and the occurrence of menarche in Han girls / 中国学校卫生

Objective@#To analyze the association between the occurrence of menarche and the exposure to artificial light at night (ALAN) in female Han nationality girls aged 9-18 in China, so as to provide a reference for the research on the disturbance mechanism of ALAN on puberty, as well as provide a scientific evidence for controlling ALAN and making public sanitary policy.@*Methods@#A total of 74 483 Han girls aged 9-18 with complete records of menarche, height, and weight were included in the 2014 Chinese National Surveys on Students Constitution and Health. Pearson correlation was used to explore the correlation between the incidence of menarche and the exposure to artificial light at night in 11-year-old Han girls, and the third quantiles of the area covered by outdoor night lights (0.16, 0.60) and the third quantiles of the average night light intensity [0.97, 5.91 nw/(sr ·cm) 2] were used respectively to divide the study subjects into 3 groups, and the multifactor Logistic regression model was used to analyze the effect of artificial light at night exposure on menarche.@*Results@#In 2014, the median age of menarche of Chinese Han girls was 12.18 years old, and the incidence of menarche in the 11-year-old group was 26.31%. After controlling for body mass index, local population and the logarithmic values of per capita GDP, the incidence of menarche of 11-year-old Han girls was positively correlated with the local outdoor average night light coverage area ratio and the night average light intensity logarithmic adjustment value( r =0.29, 0.30, P <0.05).The higher the local outdoor night light coverage area ratio ( OR =1.28, 1.52) and the average night light intensity ( OR =1.47, 1.58), the higher the incidence of menarche in 11-year-old Han girls( P <0.05).@*Conclusion@#There is a positive correlation between artificial light at night exposure and the menarche rate of 11-year-old Han girls. Research on artificial light at night exposure may provide scientific evidence on puberty onset and its effects on population health.

Analysis of molecular and clinical characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae in the intensive care unit / 中华预防医学杂志

To investigate the carbapenemases distribution of carbapenem-resistant Klebsiella pneumoniae (CRKP) in the intensive care unit, and the clinical characteristics between carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) and carbapenem-resistant non-hypervirulent Klebsiella pneumoniae (CR-non-hvKP) were compared. A total of 53 non-repetitive CRKP strains isolated from 49 patients in the intensive care unit of the Second Affiliated Hospital of Xi'an Jiaotong University from May 2020 to March 2021 were retrospectively studied. The carbapenemase inhibitor enhancement test was used for screening carbapenemase-producing strains, and the string test was carried out to screen the hypermucoviscosity phenotype. Using PCR to detect five main carbapenemase genes (blaKPC-2, blaNDM, blaIMP , blaVIM and blaOXA-48-like), common serotype (K1 and K2) and virulence gene (rmpA and iutA). Treated the strains with both rmpA and iutA genes as hypervirulent Klebsiella pneumonia (hvKP), and the whole genome sequencing of CR-hvKP was completed. At the same time, the clinical data of 49 patients were sorted out, and the differences in clinical characteristics of CR-hvKP and CR-non-hvKP infected patients were compared using the independent sample t test, Mann-Whitney U test, chi-square test or Fisher's exact probability test. CRKP isolated from the intensive care unit were extensively drug resistance and still had a good sensitivity to polymyxin B and tigecycline. Producing carbapenemases were the main resistance mechanism of CRKP (52/53, 98.1%). Of the 53 CRKP strains, except for 1strain that did not detect carbapenemase, at least one carbapenemase resistance gene was detected in the remaining 52 CRKP strains, of which 45 strains carried an enzyme, including 36 blaKPC-2 (36/53, 67.9%), 8 blaNDM (8/53, 15.1%), 1 blaIMP (1/53, 1.9%), and 7 strains carried with both blaKPC-2 and blaNDM (7/53, 13.2%). String test and virulence gene showed that 7 CR-hvKP strains (13.2%) were detected in 53 CRKP strains, and two of which were hypermucoviscosity phenotype. Sequencing results revealed that CR-hvKP were mainly ST11 type. Almost all patients with CR-hvKP infection were over 60 years old (7/7), with invasive treatment (7/7), pulmonary infection with hypermucoviscosity phenotype (2/7) and high mortality (5/7); and the percentage of neutrophils in patients with CR-hvKP infection (86.44±4.70) % was higher than those patients with CR-non-hvKP infection (78.90±19.15) %, the difference was statistically significant (t=-2.225, P=0.032). The CR-hvKP strains in the intensive care unit mainly produced KPC-2 enzyme, with K2 capsular serotype and ST11 type. It is necessary to strengthen the monitoring and control of the CR-hvKP strain to prevent the co-evolution of drug-resistant and hypervirulent strains.

Relationship between nutritional factors and clinical outcome in children with tuberculous meningitis / 中华儿科杂志

Objective: To investigate the relationship between nutritional risk status and clinical outcome in children with tuberculous meningitis (TBM). Methods: The clinical data (basic information, clinical symptoms and laboratory test results) of 112 patients with TBM, who were admitted to Department of Pediatric Infectious Diseases of West China Second Hospital of Sichuan University,from January 2013 to December 2020 were retrospectively analyzed. The patients were divided into the nutritional risk group and the non-nutritional risk group according to the assessment of the nutritional risk by the STRONGkids Scale. The variables of basic information, clinical symptoms and laboratory test measurements etc. were compared between the two groups by using Student t test, Rank sum test or Chi-square test. Multivariate Logistic regression analysis were used to analyze nutritional risk factors. Results: Among 112 patient with TBM, 55 were males and 57 females. There were 62 cases in the nutritional risk group and 50 cases in the non-nutritional risk group. The proportion of cases with nutritional risk was 55.4% (62/112). Patients in the nutritional risk who lived in rural areas, had symptoms of brain nerve damage, convulsions, emaciation and anorexia, with a diagnosis time of ≥21 days, and the level of cerebrospinal fluid (CSF) protein were all higher than those in the non-nutritional risk group ((50 cases (80.6%) vs. 32 cases (64.0%), 20 cases (32.3%) vs.8 cases (16.0%), 33 cases (53.2%) vs. 15 cases (30.0%), 30 cases (48.4%) vs. 2 cases (4.0%), 59 cases (95.2%) vs. 1 case (2.0%),41 cases (66.1%) vs.18 cases (36.0%), 1 406 (1 079, 2 068) vs. 929 (683, 1 208) mg/L, χ2=3.91, 3.90, 6.10, 26.72, 98.58, 10.08, Z=4.35, all P<0.05). The levels of serum albumin,hemoglobin,lymphocyte count, white blood cell count, and CSF glucose were significantly lower in patients with nutritional risk ((36±5) vs. (41±4) g/L, (110±17) vs. (122±14) g/L, 1.4 (1.0, 2.0)vs. 2.3 (1.6, 3.8)×109/L, 7.8 (6.3, 10.0)×109 vs. 10.0 (8.3, 12.8)×109/L, 1.0 (0.8, 1.6) vs. 2.1 (1.3, 2.5) mmol/L, t=-6.15, -4.22, Z=-4.86, -3.92, -4.16, all P<0.05).Increased levels of serum albumin (OR=0.812, 95%CI:0.705-0.935, P=0.004) and lymphocyte count (OR=0.609, 95%CI:0.383-0.970, P=0.037) may reduce the nutritional risk of children with TBM; while convulsions (OR=3.853, 95%CI:1.116-13.308, P=0.033) and increased level of CSF protein (OR=1.001,95%CI:1.000-1.002, P=0.015) may increase the nutritional risk of children with TBM. Similarly, the rate of complications and drug-induced liver injury was higher in the nutritional risk group (47 cases (75.8%) vs. 15 cases(30.0%), 31 cases (50.0%) vs.8 cases (16.0%), χ2=23.50, 14.10, all P<0.05). Moreover, the length of hospital stay was also longer in the nutritional risk group ((27±13) vs. (18±7) d, t=4.38, P<0.05). Conclusions: Children with TBM have a high incidence of nutritional risk. Convulsive, the level of serum albumin, the level of lymphocyte count and CSF protein may affect the nutritional risk of children with TBM. The nutritional risk group has a high incidence of complications and heavy economic burden.It is necessary to carry out nutritional screening and nutritional support for children with TBM as early as possible.

Clinical analysis of 30 cases of basal ganglia germinoma in children / 北京大学学报(医学版)

OBJECTIVE@#To summarize and analyze the clinical characteristics of children with basal ganglia germinoma and to improve the level of early clinical diagnosis.@*METHODS@#The clinical data of children diagnosed with basal ganglia germinoma admitted to the Pediatric Surgery Ward of Peking University First Hospital from January 2013 to December 2020 were retrospectively analyzed, and descriptive statistics were used to analyze the clinical characteristics of children with basal ganglia germinoma.@*RESULTS@#A total of 30 patients were included in the study, 28 were male, 2 were female, the mean age at onset was (9.7±2.2) years, the median disease duration was 7 months, 27 had unilateral disease, and 3 had bilateral disease. The clinical manifestations were decreased limb muscle strength, cognitive function disorders, polydipsia, precocious puberty, intracranial hypertension, dysphonia and swallowing dysfunction. The serum and cerebrospinal fluid tumor marker alpha-fetoprotein (AFP) were normal in the 30 patients, and the serum and cerebrospinal fluid tumor marker β-human chorionic gonadotropin (β-HCG) were normal in 8 patients.The serum β-HCG was normal in 11 patients but the cerebrospinal fluid β-HCG was slightly elevated, and the serum and cerebrospinal fluid β-HCG were slightly elevated in 11 patients. A total of 33 lesions with irregular shapes were found by imaging examination, including 15 (45.5%) patchy lesions, 10 (30.3%) patchy lesions, and 8 (24.2%) round-like high-density lesions. Tumors showed obvious high-density shadows on computed tomography (CT) scan. Magnetic resonance imaging (MRI) scan of the tumors showed low or isointensity on T1WI and isointensity on T2WI, accompanied by mild peritumoral edema, hemispheric atrophy, cerebral peduncle atrophy, calcification, cystic degeneration, ventricular dilatation and wallerian degeneration. On contrast-enhanced scans, the tumor showed no enhancement or heterogeneous enhancement.@*CONCLUSION@#The main age of onset of germ cell tumors in the basal ganglia in children is about 10 years old, and males are absolutely dominant. The clinical features and imaging manifestations have certain characteristics. With both combined, the early diagnosis of germ cell tumors in the basal ganglia can be improved.

Systemic lupus erythematosus in a male teenager manifested with cardiogenic shock and extremities infarction / 世界急诊医学杂志（英文）

@#Systemic lupus erythematosus (SLE) is an autoimmune disease with multisystemic features and a variety of clinical characteristics. Typical clinical manifestations of SLE include alopecia, oral ulcers, cutaneous lesions, arthritis, renal injury, and cardiac damage.[1] Cardiac involvement is one of the common complications of SLE, which is mostly asymptomatic with only approximately 10% of cardiac injury patients experiencing symptoms such as shortness of breath and arrhythmia. However, cardiogenic shock is rare, especially as the initial manifestation of SLE.[2] Herein, we report a case of a 15-year-old male who presented with cardiogenic shock and was eventually diagnosed with SLE.

Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell / 中华肿瘤杂志

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.

Correlation analysis of Traditional Chinese Medicine physical fitness and cardiovascular health behaviors among college students / 中国学校卫生

Objective@#To analyze the correlation between Traditional Chinese Medicine (TCM) physical fitness and cardiovascular health behaviors among college students and to provide a reference for physical fitness management and primary prevention of cardiovascular diseases for college population.@*Methods@#From August to November 2021, 1 621 college students from three universities in Liaoning Province were selected by clustering random sampling method, and questionnaire survey was conducted using the TCM Physical Fitness Determination Scale and the cardiovascular health behavior index proposed by the American Heart Association to analyze the correlation between TCM physical fitness and cardiovascular health behavior among college students.@*Results@#Cigarette smoking was higher among male students (20.7%) and students majoring arts and sports(27.3%)( χ 2=184.99, 79.43, P < 0.05). Body mass index (BMI) was higher among male students (4.7%) and students majoring medicine(3.6%)( χ 2=64.11, 15.38 , P <0.05). Physical inactivity was more common among female students(39.6%), medical majors(45.2%), and students with a family history of cardiovascular disease(CVD)(33.4%)( χ 2=145.40, 189.91, 15.89, P <0.05). Unhealthy diet was more common among students with medical majors and no family history of CVD(45.8%, 43.1%)( χ 2=33.13, 15.57, P <0.05). Significant differences in TCM body composition were found among college students by gender, major, and family history of CVD( χ 2=101.22, 82.38, 90.42, P <0.01). Healthy diet (ideal) and physical exercise (ideal, average) were negatively associated with Qi deficiency ( OR =0.48, 0.19, 0.63), physical exercise (ideal, average) was negatively associated with Yang deficiency( OR =0.43, 0.68), BMI (ideal) and physical exercise (ideal) were negatively associated with Phlegm dampness( OR =0.21, 0.37), physical exercise (ideal) was negatively correlated with Damp heat and Blood stasis qualities ( OR =0.34, 0.20), and physical exercise (ideal, general) was negatively correlated with Qi yu qualities( OR =0.34, 0.51)( P <0.05).@*Conclusion@#TCM physical fitness is associated with cardiovascular health behavior, with varying effects of each indicator of cardiovascular health behavior on TCM physical fitness. Personalized cardiovascular interventions should be taken according to differential constitutions to provide reference for constitution regulation and cardiovascular disease prevention.