Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To investigate the influencing factors of the course of perioperative prophylactic antibiotics in patients undergoing total hip arthroplasty,and explore management strategies for enhancing perioperative prophylactic medication administration.Methods The clinical data for patients undergoing total hip arthroplasty at Affiliated Hospital of Chengdu University from January,2020 to September,2024 were retrospectively collected.Patients were divided into a 24 h group and a 48-72 h group based on the duration of prophylactic antibacterial therapy.The general characteristics,surgical-related indicators,preoperative and postoperative laboratory test results,and surgical outcome measures between the two groups of patients were compared.Multivariate Logistic regression analysis was performed to identify influencing factors associated with prolonged duration of prophylactic antibacterial therapy.Results A total of 126 patients who underwent total hip arthroplasty were enrolled,including 74 cases in the 24 h group and 52 cases in the 48-72 h group.Univariate analysis results showed that there were statistically significant differences in the following indicators between the two groups:surgical cause,surgical duration,intraoperative blood loss,drainage duration of plasma drainage tubes,preoperative white blood cell count,and preoperative neutrophil count(P<0.05).The results of multivariate Logistic regression analysis showed that the reason for surgery and the duration of plasma drain tube drainage were the influencing factors of antimicrobial treatment course for total hip arthroplasty(P<0.05).The results of receiver operating characteristic curve analysis showed that the prediction model(constructed based on the drainage time of plasma drainage tube)for prophylactic antimicrobial treatment course to 48-72 h was 0.721.When the drainage time of plasma drainage tubes was≥40.56 h,the risk of requiring prophylactic antimicrobial therapy for an extended course of 48-72 h increased significantly.Conclusion The patient's surgical reason and the duration of plasma drain drainage may be related to the prophylactic antimicrobial course of more than 24 hours.Clinical pharmacists may utilize this parameter as a patient-specific characteristic,with the support of information systems,the hierarchical patient management can be implemented,thereby enhancing the effectiveness of medication surveillance and progressively elevating the 24 h discontinuation rate of perioperative prophylactic antibiotics.

ObjectiveTo establish an adjusted Serfling regression model to estimate the excess cases and the excess epidemic period of hand-foot-mouth disease (HFMD) in Beijing from 2011 to 2019, so as to provide data support and decision-making basis for HFMD prevention and control. MethodsThe weekly number of HFMD cases in Beijing from 2011 to 2019 was utilized for adjusted the Serfling regression model. Then the adjusted model was used to fit the baseline and epidemic threshold of HFMD in Beijing from 2011 to 2019, calculating the excess cases and determining the excess epidemic period. ResultsA total of 279 306 cases of HFMD were reported in Beijing from 2011 to 2019, with the climax of the disease occurring in summer and autumn. After adjusting the fitting R² of the Serfling regression model to 0.773, a total of 10 excess epidemic periods totaling 92 weeks were estimated, mainly occurring in summer. The highest number of excess cases during an excess epidemic period was found in 2014 (1 272 cases, 95%CI: 990‒1 554), accounting for 65.04% of the actual cases (95%CI: 50.62%‒79.46%). ConclusionThe adjusted Serfling regression model fits well and can be utilized for early warning of HFMD and estimating the disease burden caused by HFMD.

[Objective] To investigate the non-pathological influencing factors of the unqualified alanine aminotransferase (ALT) in the initial screening of blood donors in Changchun and the laboratory re-examination, so as to provide evidence for reducing the deferral of blood donors and the discarding of blood due to ALT disqualification. [Methods] The unqualified results of ALT from the laboratory of our center from September 1, 2023 to October 31, 2024 were collected. The unqualified rates of ALT were statistically analyzed according to the blood collection sites and the initial screening detection equipment. The samples after ALT pre-donation screening were tested in the laborator, and the unqualified rates of ALT in the initial screening and the laboratory, the non-conformity rate of the results and the distribution range of ALT values were statistically analyzed according to the blood collection sites and the initial screening detection equipment. A questionnaire survey was conducted on the blood donors before blood collection to statistically analyze the influence of the blood donors' living habits and diet on ALT test results. [Results] The statistical analysis of the unqualified rate of ALT in the laboratory showed statistically significant differences in the ALT disqualification rates among different blood collection sites and different initial screening detection devices (P<0.05). Comparison of the ALT unqualified rate for the same type of equipment at different sites showed that for Equipment 1, there were differences between the combined blood collection house and the whole blood house, and between the combined blood collection house and the blood donation vehicle (P<0.05); for Equipment 2, there were differences between the combined blood collection house and the blood donation vehicle, and between the whole blood house and the blood donation vehicle (P<0.05); there were no significant differences among other groups with the same equipment. The initial screening and the laboratory test results for the same samples were compared, with unqualified rates of ALT of 16.29% and 13.01%, respectively. There were statistically significant differences in the unqualified rates of ALT among different blood collection sites (P<0.05), but no significant differences in the ALT test results among different detection equipment (P>0.05).. The non-conformity rate between the initial screening and the laboratory results was 5.26%, of which 81.15% (99/122) were unqualified in the initial screening but qualified in the laboratory. There were statistically significant differences in those unqualified in the initial screening but qualified in the laboratory among different blood collection sites and different detection equipment (P<0.05). The median ALT level in the initial screening was 29.0 U/L (with a 5%-95% range of 14-75 U/L), and the median ALT level in the laboratory was 19 U/L (with a 5%-95% range of 8-65 U/L). The results of the questionnaire survey showed that 33.3% (2/6) of those who consumed alcohol within 24 hours before blood donation had unqualified ALT, and 10% (1/10) of those who stayed up late the night before blood donation had unqualified ALT. [Conclusion] The unqualified rates of ALT in the initial screening before blood collection and the laboratory re-examination of blood donors in Changchun are closely related to the blood collection sites, detection equipment, detection environment, detection personnel, samples, ALT thresholds and detection time. Drinking alcohol and staying up late within 24 hours before blood donation increase the risk of unqualified ALT detection.

ObjectiveTo investigate the level of hepatitis B surface antibody (anti-HBs) among preschool children (aged 3‒6 years) and primary and secondary school students in Tonglu County, Zhejiang Province, to evaluate the effectiveness of hepatitis B vaccination, and to provide a basis for hepatitis B prevention and control in the region. MethodsAs part of the 2023 Tonglu County Urban and Rural Residents Health Examination Program, blood samples were collected during health check-ups. Fingertip blood samples were obtained from preschool children, while venous blood samples were collected from primary and secondary school children. The anti-HBs levels in blood (positive + / negative -) were qualitatively tested using hepatitis B surface antibody test kits (latex method). The differences in anti-HBs positivity rates among different age groups were analyzed. ResultsBetween April 1, 2023 and June 30, 2023, a total of 52 919 individuals were surveyed, including 11 973 preschool children and 40 946 primary and secondary school students. The overall anti-HBs positivity rate was 39.74%, with the highest positivity rate observed among preschool children (60.20%). Age was negatively correlated with the anti-HBs positivity rate (P<0.001). No significant gender differences in anti-HBs positivity rates were observed. The anti-HBs positive rate in rural areas was higher than that in urban areas, with statistically significant differences across school grade groups (primary grades 1‒3, grades 4‒6, middle school, and high school) (P<0.001). ConclusionThe anti-HBs positivity rate among preschool and school-age children in Tonglu County decreases with age and remains relatively low. It is recommended to strengthen the monitoring of hepatitis B antibody levels and promote health education among preschool and school-age children. Children who have not completed the full hepatitis B vaccination should receive timely catch-up vaccination.

Objective To investigate the relationships of the mRNA expression levels of mitochon-drial ribosomal large subunit protein 13(MRPL13),BCL2-associated protein A1(BCL2A1)and TP53 apoptosis-inducing protein 1(TP53AIP1)in the serum of breast cancer patients with their chemotherapy efficacy as well as immune function.Methods A total of 148 triple-negative breast cancer patients undergoing chemotherapy were selected as the study subjects.Based on chemotherapy efficacy,they were divided into responsive group(97 cases)and non-responsive group(51 cases).Sixty healthy individuals undergoing physical examinations during the same period were selected as the control group.The mRNA expression levels of MRPL13,BCL2A1 and TP53AIP1 in the serum of patients were detected.The concentrations of immunoglobulin M(IgM),immunoglobulin G(IgG)and im-munoglobulin A(IgA)in the serum of patients were measured,and the proportions of CD4+and CD8+cells in whole blood were determined.The mRNA expression levels of MRPL13,BCL2A1 and TP53AIP1 were compared between the breast cancer group and the control group.The mRNA ex-pression levels of MRPL13,BCL2A1 and TP53AIP1 were compared between the responsive and non-responsive groups.The differences in immune function indicators before and after chemotherapy be-tween the responsive and non-responsive groups,were compared.The correlations of the mRNA ex-pression levels of MRPL13,BCL2A1 and TP53AIP1 with immune indicators were analyzed.Factors influencing chemotherapy efficacy were screened.Results The mRNA expression levels of MRPL13 and BCL2A1 in the breast cancer group were higher than those in the control group,while the mRNA expression level of TP53AIP1 was lower,with statistically significant differences(P＜0.05).In the responsive group,the mRNA expression levels of MRPL13 and BCL2A1 were lower than those in the non-responsive group,while the mRNA expression level of TP53AIP1 was higher,with statistically significant differences(P＜0.05).After chemotherapy,the IgM concentration in the responsive group was higher than that in the non-responsive group,with a statistically significant difference(P＜0.05).The proportion of CD8+cells in the responsive group was lower than that in the non-responsive group,with a statistically significant difference(P＜0.05).The mRNA expres-sion level of MRPL13 was positively correlated with IgM,IgG and CD8+(r=0.672,0.716,0.824,P＜0.05).The mRNA expression level of BCL2A1 was positively correlated with IgA and CD4+(r=0.654,0.862,P＜0.05).The mRNA expression level of TP53AIP1 was negatively cor-related with CD4+and CD8+(r=-0.846,-0.792,P＜0.05).High expressions of MRPL13 and BCL2A1 were independent risk factors for chemotherapy efficacy in breast cancer patients(P＜0.05),while high expression of TP53AIP1 was protective factor(P＜0.05).Conclusion The mRNA expression levels of MRPL13,BCL2A1 and TP53AIP1 in the serum of triple-negative breast cancer patients undergoing chemotherapy are correlated with the levels of IgM,IgG and IgA,the proportions of CD4+and CD8+T cells,and chemotherapy efficacy.High expression of MRPL13 and BCL2A1 are independent risk factors for poor chemotherapy efficacy,while high expression of TP53AIP1 is a protective factor.

ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg^-1）， a domperidone group （3.0 mg·kg^-1）， a Fuzi Lizhong pillwan （0.8 g·kg^-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol^-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.