Objective To establish the pharmacokinetic model of linezolid in neonates,and to optimize the administration regimen. Methods A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy,and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected,and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features. Results The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination,and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h,respectively. The results of goodness of fit,visualization verification,and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows:6 mg/kg,q8h,at 28 weeks of gestational age (GA);8 mg/kg,q8h,at 32 weeks of GA;9 mg/kg,q8h,at 34-37 weeks of GA;11 mg/kg,q8h,at 40 weeks of GA. Conclusions The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

Objective:To screen high-risk population of chronic obstructive pulmonary disease (COPD) and to analyze the risk factors in Haicang District of Xiamen City.Methods:A questionnaire survey was conducted from February 2023 to May 2023 among residents who visited or underwent physical examinations at five community health service centers in Haicang District of Xiamen City selected by cluster sampling method. The self-designed general information questionnaire, COPD population screening questionnaire (COPD-PS) and COPD screening questionnaires (COPD-SQ) were applied in the survey. Individuals with COPD-PS scale>5 or COPD-SQ scale>16 were defined as COPD high-risk group. The association of COPD risk with gender, age, smoking, family history of COPD, history of tuberculosis, history of COVID-19 infection, and using coal/woodstove for cooking or heating was analyzed with chi-square test and binary logistic regression analysis.Results:A total of 4 260 questionnaires were distributed and 4 221 valid questionnaires were collected with a recovery rate of 99.6%. Among all respondents there were 1 904 males (45.11%) and 2 317 females (54.89%); and 217 individuals aged 40-<50 (5.14%), 434 aged 50-<60 (10.28%), 2 194 aged 60-<70 (51.98%), 1 302 aged 70-<80 (30.85%) and 74 aged≥80 (1.76%). The results showed that there were 269 respondents (6.4%) scored≥5 on the COPD-PS scale, 534 residents (12.7%) scored≥16 on the COPD-SQ scale, 646 (15.3%) scored≥5 on the COPD-PS scale or≥16 on the COPD-SQ scale. Male gender ( OR=2.592, 95% CI:2.135-3.146), second-hand smoke exposure ( OR=3.763, 95% CI:2.944-4.810), frequently catching cold before the age of 14 ( OR=3.804, 95% CI:2.927-4.944), history of tuberculosis ( OR=2.575, 95% CI:1.224-5.418), hypertension ( OR=1.547, 95% CI:1.277-1.875), and diabetes ( OR=1.791, 95% CI:1.027-3.121) were independently associated with the high-risk of COPD, while the history of COVID-19 ( OR=0.583, 95% CI:0.476-0.714) was a protective factor for COPD risk. Conclusion:Males, exposure to second-hand smoke, frequently catching cold before the age of 14, history of tuberculosis, hypertension, and diabetes will increase the risk of COPD, while the history of COVID-19 is a protective factor.

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.
Mice ; Animals ; Humans ; Hepatitis, Autoimmune/pathology* ; Signal Transduction ; Disease Models, Animal ; Stem Cells

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.

Objective: To investigate the potential independent risk factors of body mass rebound following laparoscopic sleeve gastrectomy (LSG) and construct a nomogram prediction model based on these factors. Methods: In this retrospective observational study, patients with obesity who had undergone LSG at the Department of Gastrointestinal Surgery of the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University between January 2015 and July 2017 were retrospectively enrolled. These patients were divided according to their status of postoperative body mass rebound. The inclusion criteria were patients aged between 16 and 65 years who had undergone LSG bariatric surgery with surgical indications according to the 2014 Chinese Guidelines for the Surgical Management of Obesity and Type 2 Diabetes Mellitus. The exclusion criteria were patients who had undergone other bariatric surgeries, who were taking weight-loss drugs or drugs that affected their body weight, who had severe gastroesophageal reflux and hiatal hernia, who were pregnant, who had incomplete clinical data, and who were lost to follow-up or were followed up for <3 years. In total, 241 patients with obesity (69 males and 172 females) who had undergone LSG surgery were enrolled. The mean age and body mass index (BMI) were (29.9±5.8) years and (40.8±4.8) kg/m², respectively. The patients were followed up till July 2022, with a focus on their body weight. Postoperative body mass rebound was defined as a percentage increase of ≥10% from the nadir body mass, which was the lowest body mass during the 3-year follow-up period. The body weight rebound following LSG and its influencing factors were observed, based on which a nomogram model was constructed and evaluated. The relationships between the patients' basic data, clinical indicators, preoperative hematological indicators, postoperative indicators, and body weight rebound following LSG were analyzed via univariate analysis. Independent risk factors were further screened by multivariate logistic regression analysis. Factors with a statistically significant difference were included into the nomogram prediction model. Moreover, the model was internally (modeling set) and externally (validation set, 80 baseline data-matched patients with obesity from our center) validated using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) via R software. ROC curve analysis was used to analyze the predictive and cutoff values of the measurement data for body mass rebound. Results: Overall, 90 patients (37.3%) exhibited postoperative body weight rebound, with the lowest BMI of (29.5±2.6) kg/m² and time to reach the lowest BMI of (15.4±2.3) months; 151 patients (62.7%) did not exhibit body weight rebound, with the lowest BMI of (29.8±2.3) kg/m² and time to reach the lowest BMI of (14.7±2.1) months. The results of univariate analysis showed that BMI, depression, anxiety, C-reactive protein (CRP) levels, systemic immune inflammatory index (SII), prognostic nutritional index (PNI), and albumin/fibrinogen ratio (AFR) were associated with body weight rebound following LSG with statistically significant differences (all P<0.05). The results of multivariate regression analyses suggested that depression [odds ration (OR) = 1.31, 95% confidence interval (CI): 1.08-1.62, P=0.010], preoperative CRP levels of ≥8 mg/L (OR = 1.34, 95% CI: 1.09-1.69, P=0.007), SII (OR = 0.58, 95% CI: 0.41-0.86, P=0.013), PNI (OR = 2.06, 95% CI: 1.03-4.21, P=0.007), and AFR (OR: 0.49, 95% CI: 0.33-0.69, P=0.011) were five independent risk factors for body mass rebound. A nomogram prediction model was constructed based on the multivariate analysis results. The scores of PNI, SII, AFR, CRP, and depression were 92.5, 100, 72.5, 25, and 27.5, respectively. The total score was calculated by adding the individual scores of each risk factor, which was used to calculate the probability of body mass rebound following LSG. The evaluation results of the nomogram model showed a C-index of 0.713 and 0.762, sensitivity of 0.656 and 0.594, and specificity of 0.715 and 0.909 in the modeling and validation sets, respectively. The calibration curve analysis and DCA indicated that the nomogram model has a good predictive value for body mass rebound after LSG. Conclusion: Preoperative depression, CRP of ≥8 mg/L, SII, PNI, and AFR were independent risk factors for body mass rebound following LSG. Hence, the nomogram prediction model based on these factors can effectively predict body mass rebound in patients undergoing LSG.
Adolescent ; Adult ; Aged ; Anti-Obesity Agents ; C-Reactive Protein ; Diabetes Mellitus, Type 2 ; Factor Analysis, Statistical ; Female ; Fibrinogen ; Gastrectomy/methods* ; Humans ; Laparoscopy/methods* ; Male ; Middle Aged ; Nomograms ; Obesity ; Retrospective Studies ; Risk Factors ; Weight Loss ; Young Adult

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

OBJECTIVE: To investigate the protective effect against intestinal mucosal injury in rats following traumatic brain injury (TBI) and explore the underlying mechanism. METHODS: SD rat models of TBI were established by fluid percussion injury (FPI), and the specimens were collected at 12, 24, 48, and 72 h after TBI. Another 15 rats were randomly divided into shamoperated group (n=5), TBI with saline treatment (TBI+NS) group (n=5), and TBI with PD treatment (TBI+PD) group (treated with 30 mg/kg PD after TBI; n=5). Body weight gain and fecal water content of the rats were recorded, and after the treatments, the histopathology of the jejunum was observed, and the levels of D-lactic acid (D-LAC), diamine oxidase (DAO), ZO-1, claudin-5, and reactive oxygen species (ROS) were detected. Lipid peroxide (LPO) and superoxide dismutase (SOD) 2 content, jejunal pro-inflammatory factors (IL-6, IL-1β, and TNF- α), Sirt1 activity, SOD2 and HMGB1 acetylation level were also determined after the treatments. RESULTS: The rats showed significantly decreased body weight and fecal water content and progressively increased serum levels of D-LAC and DAO after TBI (P < 0.05) with obvious jejunal injury, significantly decreased expression levels of ZO-1 and claudin-5, lowered SOD2 and Sirt1 activity (P < 0.05), increased expression levels of LPO, ROS, and pro-inflammatory cytokines, and enhanced SOD2 and HMGB1 acetylation levels (P < 0.05). Compared with TBI+NS group, the rats in TBI+PD group showed obvious body weight regain, increased fecal water content, reduced jejunal pathologies, decreased D-LAC and DAO levels (P < 0.05), increased ZO-1, claudin-5, SOD2 expression levels and Sirt1 activity, and significantly decreased ROS, LPO, pro-inflammatory cytokines, and acetylation levels of SOD2 and HMGB1 (P < 0.05). CONCLUSION PD alleviates oxidative stress and inflammatory response by activating Sirt1-mediated deacetylation of SOD2 and HMGB1 to improve intestinal mucosal injury in TBI rats.
Animals ; Brain Injuries, Traumatic ; Glucosides/pharmacology* ; HMGB1 Protein/metabolism* ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Stilbenes/pharmacology* ; Superoxide Dismutase/metabolism*

Objective To study and analyze the theory, policy framework, and core content of physical activity policies and physical activity guidelines. Methods Using a policy research and content analysis approach and the theory of the six components of World Health Organization (WHO) health service system, we specifically analyze the theory, framework, and core content of WHO Global Action Plan on Physical Activity and WHO Physical Activity Guidelines. Results The Global Plan of Action for Physical Activity 2018-2030 (Action Plan) is an international policy document on physical activity issued by WHO that incorporates physical activity within the context of the seven principles of human rights, the life span, evidence-based practice, proportional universality, policy coherence and integration of health into all policies, participation and empowerment, and multisectoral partnerships into health services and social development. The Action Plan consists of four strategic objectives and 20 policy actions, covering six areas of WHO health service system, and the integration of physical activity policies into health services is of great importance in promoting the achievement of the United Nations Sustainable Development Goal 3 of universal health coverage. As a technical document for the implementation of the Action Plan, 2020 WHO Guidelines on Physical Activity and Sedentary Behavior (Guidelines) adopted the PI/ECO approach to analyze the physical activity needs of various groups of people, and provide guidelines to increase physical activity and reduce sedentary behavior for children and adolescents, adults, older adults, pregnant and postpartum women, people with chronic diseases and people with disabilities. The guidelines cover duration, frequency, and intensity of physical activity, types of physical activity, critical and important health outcomes of physical activity, and health risk prevention and related considerations. The Guidelines implement the relevant guiding principles of the Action Plan and aim to improve overall population participation in physical activity at the micro level and improve critical and important health outcomes for the overall population. Conclusion As a health and development strategy, the Action Plan promotes the integration of physical activity into the health delivery system to facilitate the achievement of the United Nations 2030 Sustainable Development Goal 3 of universal health coverage.The four strategic objectives and 20 policy actions of the Action Plan can be integrated into these six areas based on the six components of WHO Health Service Delivery System: leadership and governance, financing, human resources, service delivery, medical technology, and health information. As a technical document to implement the Action Plan, the Guidelines are based on the PI/ECO approach framework and provide guidance on increasing physical activity and reducing sedentary behavior for children and adolescents, adults, older adults, pregnant and postpartum women, chronic patients, and persons with disabilities. The core content addresses the target populations, duration, frequency, and intensity of physical activity, types of physical activity, critical and important health outcomes of physical activity, and health risk prevention and related considerations.