Background: and Purpose Bilirubin has potent antioxidant, anti-inflammatory, and neuroprotective effects. Herein, we investigated whether total bilirubin (TBIL) modifies the association between hypertension and cerebral small vessel disease (CSVD). Methods: Data were obtained from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. TBIL and direct bilirubin (DBIL) levels were assayed using fasting venous blood samples. Indirect bilirubin (IBIL) was calculated by subtracting DBIL from TBIL. TBIL was stratified as ≤17 μmol/L and >17 μmol/L based on the biological relevance of Gilbert’s syndrome. Hypertension was defined as blood pressure ≥140/90 mm Hg, self-reported hypertension history, or current use of antihypertensive agents. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated using magnetic resonance imaging and used to rate CSVD burden according to the criteria proposed by Wardlaw et al. and Rothwell et al. Results: This study included 3,061 participants, with a mean age of 61.2±6.7 years and 46.5% males. After adjusting for confounders, hypertension was associated with increased odds of presence of CSVD (Wardlaw: odds ratio [OR]=1.86, 95% confidence interval [CI] 1.41–2.44, P<0.001; Rothwell: OR=1.84, 95% CI 1.43–2.38, P<0.001) and higher modified total CSVD burden (common OR: 1.85, 95% CI 1.45–2.36, P<0.001) in participants with TBIL ≤17 μmol/L but not in TBIL >17 μmol/L (P for interaction <0.05). Johnson–Neyman analyses showed cut-off concentrations of 22.3–22.4 μmol/L for effect modification by TBIL. IBIL contributed to effect modification, whereas DBIL did not. Conclusions Mildly elevated TBIL may modify the association between hypertension and CSVD.

ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

Objective: To explore the prevalence of screening myopia and depressive symptom among primary and secondary school students in Xuzhou, and to explore the association of sleep and screen time on the coexistence of screening myopia and depressive symptom, so as to provide scientific references for developing intervention strategies to address the development of myopia and promote mental health in children and adolescents. Methods: From September to October 2024, a stratified cluster random sampling method was used to select 6 605 students in grade 4 to 12 in 2 urban and 2 suburban districts in Xuzhou. The students health condition and influencing factors questionnaire were used to assess students basic information, sleep time, and screen time. The Center for Epidemiological Studies Depression Scale (CES-D) was used to assess primary and secondary school students depressive symptom.Unaided distance visual acuity examination was conducted, and refractive assessment was performed using an automated refractometer without cycloplegic agents. The Chi-square test and multiple Logistic regression analysis were used to evaluate the association of sleep and screen time with the coexistence of screening myopia and depressive symptom. Results: The detection rates of screening myopia, depressive symptom, and screening myopia and depressive symptoms co morbidity among primary and secondary school students in Xuzhou were 60.35%, 4.45% and 18.61% respectively. Results from the multinomial Logistic regression analysis, using the healthy group as the reference and after adjusting for confounding factors, showed that students with insufficient sleep duration were more likely to have depressive symptom ( OR=1.57, 95%CI =1.08-2.27) and the coexistence of screening myopia and depressive symptom ( OR=1.85, 95%CI =1.45-2.36). Students with daily screen time≥2 h were more likely to have depressive symptom only ( OR=1.41, 95%CI =1.04-1.93) and the coexistence of screening myopia and depressive symptom ( OR=1.31, 95%CI =1.06-1.61). Further stratified analysis based on sufficient and insufficient sleep duration revealed that only in the insufficient sleep duration group, students with daily screen time≥2 h had an increased risk of depressive symptom only ( OR=1.49, 95%CI =1.07-2.07) and the coexistence of screening positive myopia and depressive symptom ( OR=1.40, 95%CI =1.11- 1.77 ) (all P <0.05). Conclusions Primary and secondary school students with insufficient sleep duration and daily screen time≥2 h have higher risks of depressive symptoms and the coexistence of screening myopia and depressive symptoms. It is recommended to ensure adequate sleep duration and limit screen time for children and adolescents.

Cutibacterium avidum(C.avidum)is a Gram-positive bacterium belonging to Corynebacterium cutis,which mainly exists on the surface of human skin and rarely causes invasive infection of superficial or deep skin.At present,there is no unified expert consensus on the diagnosis,treatment and prognosis of C.avidum.This paper reports a patient with epidermoid cyst caused by C.avidum who recovered and was discharged after neurosurgical resection of superficial mass and antimicrobial treatment,aiming to enhance the clinical recognition on C.avidum infection and provide reference for the diagnosis and treatment of the disease.

Objective To explore the potential cuproptosis-related genes(CRGs)in patients with multiple myeloma(MM)and develop a prognostic model for improving prognosis and revealing features of the MM immune microenvironment.Methods ① Transcriptome sequencing data and clinical information were retrieved from the GSE4581 dataset in the Gene Expression Omnibus(GEO)database and the Cancer Genome Atlas-Multiple Myeloma Research Foundation(TCGA-MMRF)database.The 859 patients from the TCGA-MMRF database were assigned into a training set,and the other 414 ones from the GSE4581 dataset into a validation set.LASSO-Cox and multivariate Cox regression analyses were used to construct prognostic models and calculate risk scores.Based on the median risk score,they were categorized into high-and low-risk cohorts.Time-dependent receiver operating characteristic(ROC)and calibration curves were plotted to assess the predictive performance and accuracy of the model.The differences between the high-and low-risk cohorts were explored using Kaplan-Meier survival curve analysis and immune microenvironment correlation analysis.② RT-qPCR and Western blotting were used to verify the expression of prognostic model genes in MM cell lines and normal bone marrow single-nucleated cells,and CCK-8 assay,flow cytometry,and Western blotting were applied to verify the biological function of UBE2D1 in MM cells.Results ① LASSO-Cox and multivariate Cox regression analyses revealed that the model consisted of 4 genes,CDKN2A[HR=1.60(95%CI:1.24～2.05),P=2.5e-4],PDE3B[HR=1.33(95%CI:1.09～1.62),P=4.2e-3],UBE2D1[HR=1.65(95%CI:1.20～2.26),P=2.1e-3]and COA6[HR=1.35(95%CI:1.07～1.71),P=0.01].In the training set,the time-dependent ROC curves predicted that the area under curve(AUC)value of 1-,3-,and 5-year survival rate was 0.63,0.71,and 0.78,respectively,and in the validation set,the AUC value was 0.656,0.657,and 0.797,respectively.Calibration curve analysis showed excellent agreement in predicting 1-,3-,and 5-year prognosis.In the training set,Kaplan-Meier curves showed that patients in the high-risk cohort had a significantly shorter overall survival(OS)than the low-risk cohort[HR=2.18(95%CI:1.58～3.02),P<0.001],and in the validation set,the high-risk cohort still had a shorter OS than the low-risk cohort[HR=2.45(95%CI:1.49～4.05),P<0.001].Immune correlation analysis revealed that the ratios of immune cells,such as plasma cells and CD4+T cells were significantly lower in the high-risk cohort(P<0.05),and the risk scores were positively correlated with the expression of immune checkpoint CTLA-4,tumor-targeted therapeutic sites TNFSF4 and ENTPD1,and microenvironmental chemokines CXCL16,CCL8,and CCL16(P<0.05).② Remarkable differences were observed in the expression of all 4 prognostic model genes between the MM cell lines and normal bone marrow single-nucleated cells(P<0.05),and knockdown of UBE2D1 notably inhibited the proliferation of MM cells(P<0.05).Conclusion Our prognostic models based on CDKN2A,PDE3B,UBE2D1,and COA6 genes can predict the prognosis of MM patients.The risk scores of the genes are significantly correlated with immune infiltration in the tumor microenvironment,which providing new molecular markers for individualized therapy.

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

Cutibacterium avidum(C.avidum)is a Gram-positive bacterium belonging to Corynebacterium cutis,which mainly exists on the surface of human skin and rarely causes invasive infection of superficial or deep skin.At present,there is no unified expert consensus on the diagnosis,treatment and prognosis of C.avidum.This paper reports a patient with epidermoid cyst caused by C.avidum who recovered and was discharged after neurosurgical resection of superficial mass and antimicrobial treatment,aiming to enhance the clinical recognition on C.avidum infection and provide reference for the diagnosis and treatment of the disease.

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.