ObjectiveNonalcoholic fatty liver disease （NAFLD） is a metabolic stress liver injury. Ferroptosis is involved in the occurrence and development of NAFLD. Exploring the efficacy and mechanism of schisandrin B in treating NAFLD facilitates the development of strategies for the prevention and treatment of NAFLD. MethodsThe molecular structure of schisandrin B was obtained by searching against PubChem， and the related targets were predicted by SwissTargetPrediction. The active ingredients and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the high-throughput experiment- and reference-guide database of traditional Chinese medicine （HERB）. GeneCards and FerrDb were searched for the targets of NAFLD and ferroptosis. The common targets were taken as the core targets， and the protein-protein interaction network of the core targets was established. DAVID was used for gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses. Finally， molecular docking was performed between schisandrin B and core targets， and the binding energy was calculated. C57BL/6 mice were fed with a methionine and choline-deficiency （MCD） diet for the modeling of NAFLD. Mice were randomized into normal， model， positive drug （essentiale）， and low- and high-dose schisandrin B groups. The body mass and liver index of mice were measured after drug administration. The levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the serum and those of total cholesterol （TC）， triglyceride （TG）， malondialdehyde （MDA）， glutathione （GSH）， and Fe²⁺ in the liver homogenate were measured by biochemical assay kits. The pathological changes of the liver tissue were observed by hematoxylin-eosin （HE） and red oil O staining. Enzyme-linked immunosorbent assay was employed to determine the levels of interleukin （IL）-6， IL-1β， tumor necrosis factor （TNF）-α， and 4-hydroxynonenal （4-HNE） in the serum. Western blotting and real-time PCR were employed to determine the protein and mRNA levels， respectively， of solute carrier family 7 member 11 （SLC7A11）， solute carrier family 3 member 2 （SLC3A2）， glutathione peroxidase 4 （GPX4）， transferrin， and ferritin heavy chain （FTH） in the liver tissue. ResultsA total of 2 370， 2 547， and 1 451 targets of schisandrin B， NAFLD， and ferroptosis were obtained， in which 90 common targets were shared by the three. Enrichment analyses predicted 505 GO terms and 92 KEGG pathways. Molecular docking suggested that schizandrin B had strong binding affinity with the key targets of ferropstosis （SLC7A11 and SLC3A2）. Animal experiments showed that schizandrin B significantly decreased the liver index， lowered the levels of ALT， AST， TC， TG， IL-6， IL-1β， and TNF-α， alleviated hepatocyte ballooning and inflammatory cell infiltration， and reduced lipid accumulation in the liver of NAFLD mice. In addition， schisandrin B significantly lowered the levels of MDA， 4-HNE， and Fe²⁺， elevated the level of GSH， up-regulated the protein and mRNA levels of SLC7A11， SLC3A2， and GPX4， and down-regulated the protein and mRNA levels of transferrin in the liver tissue. ConclusionSchisandrin B can alleviate NAFLD by inhibiting ferroptosis in hepatocytes.

Objective To analyze the trends in the disease burden of pertussis in China from 1990 to 2021, and to provide a basis for the development of effective prevention and control strategies. Methods Using the 2021 Global Burden of Disease Study (GBD) database, the incidence, mortality, and disability-adjusted life years (DALYs), as well as the age-standardized rates of pertussis in China from 1990 to 2021 were analyzed. Descriptive statistical methods were employed to analyze the characteristics of the pertussis disease burden, and the Joinpoint regression model was used to analyze the trends in pertussis disease burden. Results From 1990 to 2021, the incidence, mortality, and DALYs of pertussis in China decreased from 1 503 800 cases, 10 951 deaths, and 954 900 person-years to 65 400 cases, 548 deaths, and 46 500 person-years, representing a decrease of 95.65%, 95.00%, and 95.13%, respectively. The corresponding age-standardized rates also decreased by 93.58%, 92.47%, and 92.53%, respectively. The Joinpoint regression model revealed a significant downward trend in the age-standardized incidence, mortality, and DALYs rates for pertussis (AAPCs were -8.32%, -9.65%, and -9.58%, respectively, P<0.001). The disease burden was slightly higher in females than in males, with the majority of cases occurring in children under 10 years old, particularly in infants under 1 year old, where the burden was the heaviest. As age increased, the disease burden decreased. Conclusion Between 1990 and 2021, the overall disease burden of pertussis in China showed a significant downward trend, with gender and age differences. Special attention should be given on the prevention and control of pertussis in children under 10 years old, especially in infants under 1 year old.

OBJECTIVE To assess the correlation between the steady-state minimal concentration （cmin） and 24 h area under the drug concentration-time curve （AUC24）/minimal inhibitory concentration （MIC） ratio （AUC24/MIC） of vancomycin in pediatric patients， and analyze independent risk factors for treatment failure. METHODS Data of hospitalized children treated with vancomycin and receiving therapeutic drug monitoring in our hospital from January 2021 to July 2024 were retrospectively collected and divided into success group and failure group according to whether the treatment was successful or not. Spearman correlation analysis was used to analyze the correlation between cmin and AUC24/MIC of vancomycin， and one-way and multifactorial Logistic regression analyses were used to screen the independent risk factors for vancomycin treatment failure. RESULTS A total of 59 children were included， with 41 in the success group and 18 in the failure group. Compared with the failure group， AUC24/MIC of vancomycin was significantly higher in the success group （P＝0.038）， but there was no statistically significant difference in the cmin of the two groups （P＞0.05）； cmin of vancomycin was significantly positively correlated with AUC24/MIC （r＝0.499， P＜0.001）， but it has a certain efficacy in predicting the achievement of the AUC24/MIC standard （≥400） （area under the receiver operator characteristic curve＝0.696）， with an optimal cutoff value of 6.05 mg/L determined by the Youden index. The efficacy of AUC24/ MIC in predicting treatment failure was superior to cmin （areas under the receiver operator characteristic curve were 0.671 vs. 0.523， P were 0.038 vs. 0.684）， with higher sensitivity （83.3% vs. 66.7%）. Hypoproteinemia and AUC24/MIC≤369.1 were independent risk factors for vancomycin treatment failure （P＜0.05）. The incidence of nephrotoxicity was 3.4%. CONCLUSIONS There is a significant positive correlation between cmin and AUC24/MIC of vancomycin in pediatric patients； hypoproteinemia and AUC24/MIC≤369.1 are independent risk factors for vancomycin treatment failure in children.

The accurate and timely detection of biochemical coagulation indicators is pivotal in pulmonary and critical care medicine. Despite their reliability, traditional laboratories often lag in terms of rapid diagnosis. Point-of-care testing (POCT) has emerged as a promising alternative, which is awaiting rigorous validation. We assessed 226 samples from patients at the First Affiliated Hospital of Guangzhou Medical University using a Beckman Coulter AU5821 and a PUSHKANG POCT Biochemistry Analyzer MS100. Furthermore, 350 samples were evaluated with a Stago coagulation analyzer STAR MAX and a PUSHKANG POCT Coagulation Analyzer MC100. Metrics included thirteen biochemical indexes, such as albumin, and five coagulation indices, such as prothrombin time. Comparisons were drawn against the PUSHKANG POCT analyzer. Bland-Altman plots (MS100: 0.8206‒0.9995; MC100: 0.8318‒0.9911) evinced significant consistency between methodologies. Spearman correlation pinpointed a potent linear association between conventional devices and the PUSHKANG POCT analyzer, further underscored by a robust correlation coefficient (MS100: 0.713‒0.949; MC100: 0.593‒0.950). The PUSHKANG POCT was validated as a dependable tool for serum and whole blood biochemical and coagulation diagnostics. This emphasizes its prospective clinical efficacy, offering clinicians a swift diagnostic tool and heralding a new era of enhanced patient care outcomes.
Humans ; Point-of-Care Testing ; Critical Care ; Blood Coagulation Tests/methods* ; Male ; Blood Coagulation ; Female ; Middle Aged ; Reproducibility of Results ; Prothrombin Time ; Aged ; Adult ; Point-of-Care Systems

Colonic mucosal healing is the ultimate goal of ulcerative colitis (UC) treatment, but it remains difficult to realize. Given the higher incidence of UC in males and the beneficial effect of estrogen on UC, we conducted this study to examine the therapeutic potential of estrogen receptor β (ERβ), the primary ER subtype in colon, on mucosal healing in UC. Our study is the first to report that ERβ activation degree was positively correlated with mucosal healing in patients with UC. Furthermore, ERβ activation enhanced mucosal healing in mice with dextran sulfate sodium-induced and biopsy-induced colonic injuries. Mechanistically, ERβ activation promoted autophagy of colonic epithelial cells by inhibiting branched-chain amino acid transport, leading to focal adhesion kinase (FAK) activation. Activated FAK promoted focal adhesion turnover and colonic epithelial cell migration, ultimately facilitating mucosal healing. ERβ ^-/- colitis mice exhibited impaired mucosal healing compared to wild-type littermates, highlighting the crucial effect of ERβ. Importantly, combination with ERβ-agonist diarylpropionitrile enhanced the amelioration of 5-aminosalicylic acid, a standard UC treatment agent, against mouse colitis. These findings attest to the crucial role of ERβ activation in colonic mucosal healing and may further inform the development of novel strategies for UC treatment.

Objective To investigate the potential genetic mechanisms of insomnia and anxiety and the bidirectional causal relationship between them using Linkage Disequilibrium Score Regression （LDSC） and Mendelian Randomization （MR）. Methods Based on the data from genome-wide association studies， LDSC was used to analyze the genetic correlation of insomnia with anxiety and its subtypes. The inverse variance weighted （IVW） method was used as the main analytical method， supplemented by MR-Egger regression， weighted median， the simple model method， and weighted model. The Cochran’s Q test was used for heterogeneity testing， MR-Egger was used for pleiotropy testing， and the leave-one-out method was used for sensitivity analysis. Results The LDSC analysis revealed the genetic correlation of insomnia with anxiety and its subtypes. The results of IVW analysis showed that insomnia had a causal relationship with the increased risk of anxiety （OR=1.448，95%CI 1.025‒2.045，P=0.036，PFDR=0.178） and generalized anxiety disorder （OR=2.098，95% CI 1.105‒3.986， P=0.024， PFDR=0.314）. Conversely， the reverse MR analysis showed a causal relationship between generalized anxiety disorder and the increased risk of insomnia （OR=1.010， 95% CI 1.003‒1.017， P=0.008， PFDR=0.329）. No significant horizontal pleiotropy was detected for the instrumental variables （P>0.05）， and the sensitivity analysis showed that the results of MR analysis were stable. Conclusion Insomnia may be used as a risk factor for anxiety， and there is a genetic correlation between the two diseases.
Insomnia ; Anxiety

Objective To analyze the problems and differences in workplace on-site sampling and testing skills in external quality assessment in laboratory among occupational health technical service institutions. Methods A total of 108 occupational health technical service institutions nationwide, participated in the external quality assessment in laboratory of the on-site individual sampling operation skills for silica dust (hereinafter refer to as "silica dust sampling assessment") and on-site detection operation skills for carbon monoxide (hereinafter refer to as " carbon monoxide sampling assessment") in 2023, were selected as the research subjects. The result of the assessment was analyzed. Results The qualification rate of the institutions for the silica dust sampling assessment was 98.1%. The unqualified rate of institutions in the Pearl River Delta region was lower than that in non-Pearl River Delta regions (0.0% vs 11.1%, P<0.017). The excellence rate was higher in public institutions than that in private enterprises (73.5% vs 40.0%, P<0.017). The unqualified rate of institutions with permit was lower than that of institutions without permit (0.0% vs 13.3%, P<0.05). The qualification rate of the institutions for the carbon monoxide sampling assessment was 79.4%. The proportion of the institutes, whose results of carbon monoxide standard gas (gas bag) deviation was >±20.0% was higher in private enterprises than that in public institutions (32.8% vs 7.1%, P<0.017). In terms of the normativity of on-site individual sampling for silica dust, the rates of conducting air tightness checks before sampling, correct disassembly and installation and correct placement direction of dust sampling heads, and correct flow for calibration based on the provided dust sampling heads were low, at 53.7%, 33.3%, and 14.8%, respectively. In terms of the normativity of on-site detection of carbon monoxide, the accuracy rate of converting results by on-site detection individuals was low, at only 57.8%. ConclusionIt is necessary to further strengthen the training of theoretical knowledge and practical skills of individuals in occupational health technical service institutions in Guangdong Province, especially to enhance the capacity of occupational health technical services in non-Pearl River Delta regions of the province.

Objective To investigate whether modification with IL-21 and CCL19 enhances killing and tumor-infiltrating efficiency of NKP30 CAR-T cells in lung cancer.Methods The modified IL-21-CCL19 NKP30 CAR-T cells expressing IL-21 and CCL19 fusion gene was constructed based on NKP30 CAR-T cells and stimulated with CD3CD28 antibodies and IL-2.The immunophenotype and migration of the cells in the presence of IL-21 were investigated using flow cytometry and migration experiments.Lactate dehydrogenase(LDH)release and sphere formation assays were used to assess the killing and infiltration capabilities of CAR-T cells,and the secretion levels of IFN-γ,IL-21 and CCL19 were determined with enzyme-linked immunospot assay(ELISPOT)and ELISA.A zebrafish model bearing HCG-27 cell xenograft was established by microinjection of the tumor cells into the yolk sac followed 24 h later by injection of the immune cells at the same site,and the fluorescence signals were captured using a fluorescent microscopy.Results The NKP30 ligand B7H6,which was almost undetectable in normal tissues and blood cells,was highly expressed(over 90%)in lung cancer cells.Compared with NKP30 CAR-T cells and conventional T cells,IL-21-CCL19 NKP30 CAR-T cells exhibited stronger proliferative and migration capabilities with the formation of central memory T cells.The reduced expressions of CTLA4 and PD1 in the constructed cells resulted in enhanced killing efficiency against lung cancer cells accompanied by significantly increased production of IFN-γ,IL-21 and CCL19.In the zebrafish models,CAR-T cells exhibited stronger cytotoxicity and proliferative abilities than typical T cells,but these differences were not statistically significant between the two CAR-T cells.Conclusion Modification of NKP30 CAR-T cells with IL-21 and CCL19 facilitates their access into solid tumors for more effective tumor cell killing while producing a large number of memory T cells.

Objective To investigate whether modification with IL-21 and CCL19 enhances killing and tumor-infiltrating efficiency of NKP30 CAR-T cells in lung cancer.Methods The modified IL-21-CCL19 NKP30 CAR-T cells expressing IL-21 and CCL19 fusion gene was constructed based on NKP30 CAR-T cells and stimulated with CD3CD28 antibodies and IL-2.The immunophenotype and migration of the cells in the presence of IL-21 were investigated using flow cytometry and migration experiments.Lactate dehydrogenase(LDH)release and sphere formation assays were used to assess the killing and infiltration capabilities of CAR-T cells,and the secretion levels of IFN-γ,IL-21 and CCL19 were determined with enzyme-linked immunospot assay(ELISPOT)and ELISA.A zebrafish model bearing HCG-27 cell xenograft was established by microinjection of the tumor cells into the yolk sac followed 24 h later by injection of the immune cells at the same site,and the fluorescence signals were captured using a fluorescent microscopy.Results The NKP30 ligand B7H6,which was almost undetectable in normal tissues and blood cells,was highly expressed(over 90%)in lung cancer cells.Compared with NKP30 CAR-T cells and conventional T cells,IL-21-CCL19 NKP30 CAR-T cells exhibited stronger proliferative and migration capabilities with the formation of central memory T cells.The reduced expressions of CTLA4 and PD1 in the constructed cells resulted in enhanced killing efficiency against lung cancer cells accompanied by significantly increased production of IFN-γ,IL-21 and CCL19.In the zebrafish models,CAR-T cells exhibited stronger cytotoxicity and proliferative abilities than typical T cells,but these differences were not statistically significant between the two CAR-T cells.Conclusion Modification of NKP30 CAR-T cells with IL-21 and CCL19 facilitates their access into solid tumors for more effective tumor cell killing while producing a large number of memory T cells.

Objective:To explore the application value of preoperative high-resolution magnetic resonance imaging(MRI)enhanced examination in the preoperative diagnosis of tumor node metastases(TNM)staging of rectal tumor.Methods:A total of 80 patients with rectal tumor admitted to Guang'an People's Hospital from June 2021 to September 2022 were selected.All patients underwent high-resolution MRI enhanced examinations before surgery and they were confirmed by postoperative pathological examination.The consistency of MRI T staging,N staging and postoperatively pathological staging results was analyzed.Results:The postoperative pathological staging results showed that 14 cases were at T1 stage,and 29 cases were at T2 stage,and 25 cases were at T3 stage,and 12 cases were at T4 stage,and 28 cases were at N0 stage,and 33 cases were at N1 stage and 19 were at N2 stage in the 80 patients.The diagnostic accuracies of T staging and N staging of high-resolution MRI routine and enhanced examinations were respectively 86.25%(69/80)and 90.00%(72/80)(Kappa=0.806,0.847,P<0.05).The consistency rate between preoperative high-resolution MRI detection and postoperative pathology for metastatic lymph nodes of 80 patients was 88.75%(71/80).The analysis found that metastatic lymph nodes mostly concentrated in the diameter range of 0.8-1.0 cm,accounting for 66.41%.With the increasing of N staging and T staging,the volume transfer constant(Ktrans)of the region of interest(ROI)of tumor increased successively.The Ktrans value of metastatic lymph nodes was significantly higher than that of non-metastatic lymph nodes,and the difference was statistically significant(t=14.890,P<0.05).Conclusion:Preoperative high-resolution MRI routine and enhanced examination has highly consistency with postoperative pathological TN staging of rectal tumor.The improvement of high-resolution MRI enhanced examination is helpful to assess the progression of patients'tumors and to determine treatment plans for them.