BACKGROUND: Lead is a persistent inorganic environmental pollutant with global implication for human health. Among the diseases associated with lead exposure, the damage to the central nervous system has received considerable attention. It has been reported that long-term lead exposure increases the risk of meningioma; however, the underlying mechanism remains poorly understood. Clinical studies have indicated that loss-of-function and mutations in the neurofibromin-2 (NF2) gene play a crucial role in promoting meningioma formation. METHODS: The effect of Pb on meningioma were tested in-vitro and in-vivo. Two human meningioma cell lines were used in this study, including NF2-wildtype IOMM-Lee cell and NF2-null CH157-MN cell. Cell viability, cell cycle and cell size were examined after Pb exposure. The expression of Merlin, mammalian sterile 20-like kinases 1 and 2 (MST1/2) and Yes-associated protein (YAP) from these two meningioma cells were analyzed by Western blot. A xenograft mouse model was constructed by subcutaneous injection of IOMM-Lee meningioma cells. RESULTS: This study demonstrated that treatment with lead induce dose-dependent proliferation in IOMM-Lee cell (with an EC₅₀ value of 19.6 µM). Moreover, IOMM-Lee cell exhibited augmented cell size in conjunction with elevated levels of phosphorylated histone H3, indicative of altered cell cycle progression resulting from lead exposure. However, no significant change was observed in the CH157-MN cell. Additionally, the Merlin-Hippo signaling pathway was inactivated with decreased Merlin and phosphorylation levels of MST1/2 and YAP, leading to increased YAP nuclear translocation in IOMM-Lee cells. However, there was no change in the Merlin-Hippo signaling pathway in CH157-MN cells after lead treatment. The administration of Pb resulted in an acceleration of the subcutaneous IOMM-Lee meningioma xenograft growth in mice. CONCLUSIONS Overall, the current study elucidates the potential mechanism by which lead exposure promotes the proliferation of meningioma with NF2 expression for the first time.
Meningioma/genetics* ; Neurofibromin 2/genetics* ; Humans ; Cell Proliferation/drug effects* ; Animals ; Signal Transduction/drug effects* ; Mice ; Hippo Signaling Pathway ; Lead/adverse effects* ; Cell Line, Tumor ; Protein Serine-Threonine Kinases/genetics* ; Meningeal Neoplasms ; Environmental Pollutants/adverse effects* ; Female

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To explore the value of dual-layer detector spectral CT quantitative parameters in evaluating the treatment response of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).Methods:The study was a cross-sectional study. From May 2021 to March 2023, a total of 52 patients with LARC who received complete nCRT and were pathologically confirmed rectal adenocarcinoma at the Guangdong Province Hospital of Traditional Chinese Medicine were retrospectively enrolled. Each patient underwent spectral CT examination before and after nCRT, including plain scan, arterial phase (AP), and venous phase (VP) scans. According to the tumor regression grade, the patients were divided into the good response ( n=20) and the poor response group ( n=32). Measurements of the primary tumor′s spectral CT parameters, including effective atomic number (Z eff) at plain scan, iodine concentration (IC), CT values of 40 keV and 100 keV virtual monochromatic image (VMI) at dual-enhanced phases, were taken before and after nCRT. Additionally, the normalized iodine concentration (NIC), spectral curve slope (λHU), and the change rate of the above parameters before and after nCRT were calculated. The independent sample t-test or Mann-Whitney U test was used to compare the differences between the two groups. The receiver operating characteristic (ROC) curve was used to assess the efficacy of various metrics in evaluating the tumor treatment response of nCRT. A binary logistic regression analysis of combined parameter results was performed for the parameters with the areas under curve (AUC)>0.75, and the AUC of the combined parameter was evaluated. Results:There were significant differences in NIC AP and λHU VP before nCRT, NIC VP and λHU VP after nCRT, and the change rates of Z eff, NIC AP, NIC VP and λHU AP between the good response group and the poor response group ( P<0.05). The remaining parameters showed no statistically significant difference ( P>0.05). The ROC curve results showed that the AUCs of the above 8 parameters for evaluating tumor treatment response of nCRT were 0.702, 0.655, 0.695, 0.769, 0.738, 0.807, 0.791, and 0.677, respectively. The AUC of the combined model of the three parameters with AUC>0.75 (λHU VP after nCRT, the change rate of NIC AP and NIC VP) was 0.869, with 80.0% sensitivity and 84.4% specificity. Conclusion:The quantitative parameters derived from spectral CT may provide new markers for evaluating the response to nCRT treatment in patients with LARC. The multi-parameter combined model can improve diagnostic efficacy.

Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective:To explore the clinical and genetic characteristics of a child with autosomal recessive primary microcephaly (MCPH).Methods:A case study has been carried out on a boy who had presented at the Inner Mongolia Maternity and Child Health Care Hospital for microcephaly and mental deficiency in September 2022. Prenatal ultrasound images were retrospectively analyzed, and whole exome sequencing and Sanger sequencing were carried out for his family. A literature review was also carried out using keywords such as " ASPM gene", "microcephaly", "prenatal diagnosis", "primary microcephaly", " ASPM", "MCPH5", "MCPH", "autosomal recessive microcephaly", and "prenatal diagnosis on ultrasonography" on the PubMed database, Wanfang Data and China National Knowledge until September 2023. This study was approved by Medical Ethics Committee of the Inner Mongolia Maternity and Child Health Care Hospital (Ethics No. 2021-093-1). Results:The proband had shown progressive reduction in biparietal diameter (BPD) and head circumference (HC) during the fetal period. He was found to harbor compound heterozygous variants of the ASPM gene, which included a paternally derived c. 8044C>T (p.R2682X) and a maternally derived c.8652dup (p.A2885Sfs*35). Both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4; PVS1+ PM2_Supporting+ PM3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). For other fetuses in his family, prenatal ultrasound and genetic testing were all normal. Literature research has identified 11 relevant articles, which included 14 MCPH cases. All of the MCPH5 cases had shown various degrees of reduced BPD/HC on fetal imaging (100%, 15/15). Developmental delay, intellectual disability, and attention deficits were noted in all survived cases, with one case having seizures (12.5%, 1/8). Their genotypes had included homozygotes (46.2%, 6/13) and compound heterozygotes (53.8%, 7/13) for nonsense variants (45%, 9/20) and frameshifting variants (55%, 11/20). Conclusion:The compound heterozygous variants c. 8044C>T (p.R2682X) and c. 8652dup (p.A2885Sfs*35) of the ASPM gene probably underlay the reduced BPD and HC in this proband with MCPH.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective:To analyze the current status of salary system reform in public hospitals in Mianyang City, Sichuan Province, and provide reference for the deepening of salary system reform in public hospitals.Methods:From April to May 2023, a self-designed survey questionnaire was used to conduct a survey of medical staff in five municipal tertiary public hospitals through the Wenjuanxing platform. The survey questionnaire mainly included the basic information of the survey subjects, the implementation status of the salary system, and employee satisfaction with salary. In May 2023, semi-structured interviews were conducted with relevant personnel from government departments and public hospitals involved in the reform. The interview content included the reform measures taken and their impact, changes in medical staff salaries after the reform, and the current difficulties faced by the reform. Descriptive analysis was conducted on the data, and Chi-square test was used to compare the count data. Kendall′s tau-b test was used to analyze the correlation between salary level and basic information of the survey subjects.Results:In the reform of the salary system in public hospitals in Mianyang City, measures such as system construction, total salary quota determination and dynamic control, and salary management for non-establishment employees have been mainly adopted. 826 valid questionnaires were collected, with an effective response rate of 94.5%. The annual income level was positively correlated with age, education level, years of work experience, and professional title level ( r=0.420, P<0.001; r=0.245, P<0.001; r=0.364, P<0.001; r=0.504, P<0.001). Compared with the personnel in the same positions at the same level of hospitals in other cities and states in Sichuan Province, 274 people (33.2%) were quite satisfied or very satisfied with the current salary level; 350 people (42.3%) were quite satisfied or very satisfied with the salary distribution mechanism, and 441 people (53.4%) were quite satisfied or very satisfied with non-economic salaries. The proportion of survey respondents who believe that the existing salary structure and performance evaluation methods could reflect their actual work value was 464 people (56.2%) and 423 people (51.2%), respectively. A total of 10 people were interviewed, with 4 individuals believing that the salary level has increased after the reform, but the change was not significant compared to before the reform; 8 individuals believed that the current reform does not involve the reform of the salary structure; 6 individuals believed that the internal performance based salary distribution mechanism in hospitals was not sound; 3 individuals believed that there was insufficient attention to the reform of non-economic compensation; 7 individuals believe that the difficulties in the salary system reform were mainly concentrated on the unified understanding of policies, how to determine the increase in the total salary quota, and how to reasonably distribute it internally. Conclusions:Mianyang City has scientifically determined the total salary and implemented dynamic control, enhancing the public welfare nature of public hospitals, while also taking into account the salary management of employees both inside and outside the establishment, promoting equal pay for equal work. However, there were also issues such as disagreements on the dynamic adjustment of the total salary, an imperfect internal distribution mechanism within hospitals, and an incomplete salary system reform. It is necessary to further strengthen top-level design, reasonably increase salary levels, improve the internal distribution mechanism, and optimize the salary structure to continue deepening the reform of the salary system in public hospital.

Objective:To explore the assessment value of liver enzyme changes before and after hepatectomy on the prognosis of patients with primary hepatocellular carcinoma(HCC). Methods:A retrospective analysis was conducted on the clinical data of 421 patients with primary HCC who received at the First and Second Affiliated Hospitals of Xi'an Jiaotong University from January 2016 to December 2020.The univariate and multivariate COX regression analyses were used to screen the risk factors affecting the prognosis of patients with primary HCC,and the optimal cut-off value was selected to group the most valuable indicators among them,further analyzing the different factors among subgroups.The Kaplan-Meier method was used to assess the prognosis of the subgroups,and the survival curves were plotted and statistically tested. Results:Multivariate COX regression analysis revealed that Barcelona Clinic Liver Cancer(BCLC)stage,tumor number,alpha-fetoprotein(AFP),the quantitative change of γ-glutamyl transpeptidase(GGT)and total bilirubin(TBIL)before and after surgery were independent risk factors affecting the prognosis of patients with primary HCC(P＜0.01),and there were differences in hepatitis B virus surface antigen(HBsAg),TNM stage,BCLC stage,tumor size,tumor number,tumor differentiation degree,AFP,surgery type,intraoperative bleeding volume,postoperative albumin-bilirubin(ALBI)and white blood cell count between the high and low GGT variation groups(P＜0.05).Kaplan-Meier survival analysis showed that the prognosis of patients with primary HCC between the high and low GGT variation groups was significantly different,with a hazard ratio of 2.603 for mortality and 1.449 for recurrence(both P＜0.01). Conclusion:The quantitative change of GGT before and after hepatectomy has an evaluation value for the prognosis of patients with primary HCC,and the quantitative change of GGT greater than 29.5 is an independent risk factor for the prognosis of patients with primary HCC.