Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

AIM:To analyze the association between mobile phone addiction and high myopia among college students.METHODS:We conducted a cross-sectional questionnaire survey in December 2022 on all students of a university in Shaanxi Province, and the questionnaire included socio-demographic characteristics, mobile phone addiction, high myopia, and lifestyle. Binary Logistic regression model was used to analyze the association between mobile phone addiction and high myopia among college students.RESULTS:A total of 19 952 college students were included. The prevalence of high myopia was 7.31%. The rate of mobile phone addiction was 25.68%, and the mobile phone addiction score was 37.59±13.38. The incidence of high myopia among college students with mobile phone addiction was higher than non-mobile phone addiction(P<0.001). After adjusting for socio-demographic characteristics and lifestyle, the risk of high myopia among college students with mobile phone addiction was 1.274 times(95%CI:1.131-1.434)higher than non-mobile phone addiction. For each point increase of total mobile phone addiction score, withdrawal symptoms score, salience score, social comfort score, and mood changes score, the risk of high myopia among college students increased by 0.9%(95%CI:1.005-1.013), 2.0%(95%CI:1.010-1.030), 2.6%(95%CI:1.010-1.043), 4.8%(95%CI:1.030-1.066), and 3.3%(95%CI:1.014-1.052), respectively.CONCLUSION:Mobile phone addiction is significantly associated with the increased risk of high myopia among college students, and early intervention of mobile phone use may reduce the risk of high myopia among college students.

Aim To investigate the effect of Senecio scandens Buch.-Ham on inflammatory pain mediated by mast cell P2X7 receptor.Methods Using the ATP-induced foot inflammatory pain,immunofluores-cence and toluidine blue staining techniques were used to investigate whether Senecio scandens has inhibitory effect on P2X7 receptor on mast cells.Using the calci-um ion imaging experimental technology,to explore whether Senecio scandens inhibit the intracellular cal-cium ion enrichment caused by activation of P2X7 re-ceptor on mouse peritoneal mast cell.The whole-cell patch clamp technique was used to investigate whether senecio scandens could inhibit the inward current in-duced by activation of P2X7 receptor on mouse perito-neal mast cell.Results In vivo,Senecio scandens alle-viate ATP induced inflammatory pain(3.9 g·kg-1:P＜0.05),and significantly inhibited the infiltration of P2X7 receptor-positive mast cells(3.9 g·kg-1:P＜0.05).Knockout of mast cell can reduce the analgesic effect of Senecio scandens(3.9 g·kg-1:P=0.645).In vitro.The experiment results show that senecio scandens can significantly inhibit the calcium influx(300 mg·L-1:P＜0.05;1 g·L-1:P＜0.01;3 g·L-1:P＜0.01)and the inward current mediated by P2X7 receptor in mast cell(1 g·L-1:P＜0.01).Conclusion Senecio scandens alleviate inflammatory pain by inhibiting mast cell P2X7 receptor.

OBJECTIVE To explore the current status of surveillance data of nosocomial infections in a three-A hos-pital of Jiangsu Province and find out the problems in prevention and control of the nosocomial infection so as to provide scientific bases for formulating targeted prevention strategies.METHODS The related data of all infection cases from Changzhou First People's Hospital between 2014 and 2023 were exported from information real-time surveillance system and were analyzed by using Excel 2021 and R 4.3.2 software.RESULTS The average incidence rate of hospital-associated infection was 1.32％from 2014 to 2023,declining from 2.11％in 2014 to 0.97％in 2023,and it showed a downward trend(Z=-30.010,P＜0.001).The incidence rate of hospital-associated infec-tion was 19.86％in neurosurgery department(Z=-3.041,P=0.002),10.27％in hematology department(Z=5990,P＜0.001),8.85％in neurology department(Z=-1.437,P=0.151),7.00％in critical care medicine de-partment(Z=5.907,P＜0.001),6.28％in gastrointestinal surgery department(Z=-4.435,P＜0.001),thorac-ic surgery department(Z=1.696,P=0.090),4.52％in cardiothoracic surgery department(Z=13.218,P＜0.001),2.95％in oncology department(Z=9.064,P＜0.001).Among the patients with hospital-associated infec-tions,the patients with lower respiratory tract infection accounted for 46.71％(the highest),increasing from 34.94％to 51.67％(Z=12.532,P＜0.001),the patients with upper respiratory tract infection 10.37％(Z=-10.229,P＜0.001),the patients with urinary tract infection 6.92％(Z=1.489,P=0.137),the patients with urinary catheter-related infection 3.71％(Z=13.218,P=0.317).Totally 13,593 strains of pathogens were isola-ted,65.26％of which were gram-negative bacteria and did not show a significant changing trend,24.62％were gram-positive bacteria,and 10.12％were fungi;Klebsiella pneumoniae(15.76％)and Acinetobacter baumannii(15.34％)were the predominant species of the gram-negative bacteria;Staphylococcus aureus(8.37％)and Corynebacterium striatum(3.60％)were dominant among the gram-positive bacteria;Candida albicans(5.13％)and Candida tropicalis(0.96％)were the major species of the fungi.The percentage of central venous catheteriza-tion was the highest(27.04％)among the risk factors for the hospital-associated infection,increasing from 14.87％to 21.75％(Z=17.482,P＜0.001).CONCLUSIONS The control of hospital-associated infection has been made remarkable achievement.It is necessary to strengthen the construction of infection control team,push for-ward the whole process and delicacy management,normalize the use of antibiotics,reduce the unnecessary inva-sive procedures and shorten the duration of invasive operations so as to further improve the medical quality.

Background: Bushen Zhuanggu Formula (BZF), derived from the classic Yougui Pills, has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head (NONFH), particularly by promoting bone repair. However, its underlying mechanisms remain unclear. Objective: This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH. Materials and methods: A total of 518 potential BZF targets were identified from the ETCM v2.0 database. Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls. A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis. In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH. Results: Network analysis identified key pathways associated with blood circulation obstruction, immune-inflammatory imbalance, and abnormal bone metabolism. Protein kinase C alpha (PKCA), Ras proto-oncogene (RAS), mitogen-activated protein kinase 3(ERK), ETS proto-oncogene 1 (ETS1), and receptor activator of nuclear factor-κB ligand (RANKL) formed a signaling axis implicated in NONFH pathogenesis. BZF treatment alleviated joint inflammation, preserved trabecular bone morphology, reduced bone loss, and promoted bone repair. Mechanistically, BZF significantly downregulated the expression of PKCA, RAS, ERK, ETS1, and RANKL, improved blood circulation, and inhibited osteoclast activation while promoting osteoblast activation. Conclusion: BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis, thereby reversing dysregulated bone metabolism.

OBJECTIVE To explore the current status of surveillance data of nosocomial infections in a three-A hos-pital of Jiangsu Province and find out the problems in prevention and control of the nosocomial infection so as to provide scientific bases for formulating targeted prevention strategies.METHODS The related data of all infection cases from Changzhou First People's Hospital between 2014 and 2023 were exported from information real-time surveillance system and were analyzed by using Excel 2021 and R 4.3.2 software.RESULTS The average incidence rate of hospital-associated infection was 1.32％from 2014 to 2023,declining from 2.11％in 2014 to 0.97％in 2023,and it showed a downward trend(Z=-30.010,P＜0.001).The incidence rate of hospital-associated infec-tion was 19.86％in neurosurgery department(Z=-3.041,P=0.002),10.27％in hematology department(Z=5990,P＜0.001),8.85％in neurology department(Z=-1.437,P=0.151),7.00％in critical care medicine de-partment(Z=5.907,P＜0.001),6.28％in gastrointestinal surgery department(Z=-4.435,P＜0.001),thorac-ic surgery department(Z=1.696,P=0.090),4.52％in cardiothoracic surgery department(Z=13.218,P＜0.001),2.95％in oncology department(Z=9.064,P＜0.001).Among the patients with hospital-associated infec-tions,the patients with lower respiratory tract infection accounted for 46.71％(the highest),increasing from 34.94％to 51.67％(Z=12.532,P＜0.001),the patients with upper respiratory tract infection 10.37％(Z=-10.229,P＜0.001),the patients with urinary tract infection 6.92％(Z=1.489,P=0.137),the patients with urinary catheter-related infection 3.71％(Z=13.218,P=0.317).Totally 13,593 strains of pathogens were isola-ted,65.26％of which were gram-negative bacteria and did not show a significant changing trend,24.62％were gram-positive bacteria,and 10.12％were fungi;Klebsiella pneumoniae(15.76％)and Acinetobacter baumannii(15.34％)were the predominant species of the gram-negative bacteria;Staphylococcus aureus(8.37％)and Corynebacterium striatum(3.60％)were dominant among the gram-positive bacteria;Candida albicans(5.13％)and Candida tropicalis(0.96％)were the major species of the fungi.The percentage of central venous catheteriza-tion was the highest(27.04％)among the risk factors for the hospital-associated infection,increasing from 14.87％to 21.75％(Z=17.482,P＜0.001).CONCLUSIONS The control of hospital-associated infection has been made remarkable achievement.It is necessary to strengthen the construction of infection control team,push for-ward the whole process and delicacy management,normalize the use of antibiotics,reduce the unnecessary inva-sive procedures and shorten the duration of invasive operations so as to further improve the medical quality.

Objective:To investigate the relationship between serum interacting protein kinase (RIPK)-3 levels and mycoplasma pneumoniae pneumonia (MPP) correlation between disease severity and lung function in children.Methods:A case-control study was conducted. A total of 147 children with MPP admitted to the Children's Hospital Affiliated to Xuzhou Medical University from April 2023 to March 2024 were selected, including 76 cases of mild MPP (mild MPP group) and 71 cases of severe MPP (severe MPP group). Additionally, 36 healthy children who underwent physical examinations during the same period were selected as the healthy control group. The levels of serum RIPK3, C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer of each group were compared, and the correlations between each index and the severity of MPP in children were analyzed. The lung function indicators, including the percentage of peak expiratory flow (PEF% pred) and the percentage of forced expiratory volume in one second (FEV1% pred), were compared between groups, and the correlations between these indicators and the serum RIPK3 levels in children with MPP were analyzed. Measurement data with normal distribution was expressed as " xˉ±s", one-way ANOVA was used on comparison between groups, LSD-t test was used on pairwise comparison.Measurement data with skewed distribution were expressed as M( Q1, Q3). The Kruskal-Wallis H test was used for comparisons among multiple groups, and the Dunn test was used for pairwise comparisons. Counting data was expressed as case(%), χ2 test was used on comparison between groups. The relationships between serum RIPK3, CRP, LDH, D-dimer and the severity of MPP in children were analyzed by Spearman correlation analysis. The relationships between serum RIPK3 levels and PEF% pred, FEV1% pred were analyzed by Pearson correlation analysis. Results:The levels of serum RIPK3, CRP, LDH and D-dimer in children with mild MPP and severe MPP were all higher than those in the healthy control group [(329.67±59.69), (406.77±47.47) ng/L vs. (103.16±15.93) ng/L, (13.49±4.76), (37.76±18.94) mg/L vs. (1.59±0.81) mg/L, (253.12±50.96), (501.96±167.55) U/L vs. (186.06±45.49) U/L, (0.90±0.19), (3.01±1.46) mg/L vs. (0.29±0.12) mg/L], and the levels in the severe MPP group were all higher than those in the mild MPP group (all P < 0.05). The levels of serum RIPK3, CRP, LDH and D-dimer in children with MPP were positively correlated with the severity of the disease (r values were 0.59, 0.76, 0.83, 0.67, all P < 0.001). The levels of PEF% pred and FEV1% pred in children with mild MPP and severe MPP were all lower than those in the healthy control group [(72.65±7.67)%, (59.93±10.17)% vs. (98.54±4.81)%, (73.79±6.56)%, (60.56±10.54)% vs. (98.08±4.65)%], and the levels in the severe MPP group were all lower than those in the mild MPP group (all P < 0.05). The level of serum RIPK3 in children with MPP was negatively correlated with the lung function indicators PEF% pred and FEV1% pred (r values were -0.78, -0.77, all P < 0.001). Conclusions:The serum RIPK3 level in children with MPP is positively correlated with the severity of their condition and negatively correlated with the lung function indicators PEF% pred and FEV1% pred.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective:To investigate the effect of curcumin on blood glucose levels in pregnant women at high risk of Gestational Diabetes Mellitus(GDM).Methods:One hundred and twenty-four pregnant women with high-risk factors for GDM were included in a cross-sectional study according to the inclusion and exclusion criteria.After undergoing an Oral Glucose Tolerance Test,participants were divided into the GDM group(n=61)and the non-GDM group(n=63).Subsequently,a randomized controlled trial was performed to compare Fasting Plasma Glucose(FPG)levels between the control group(n=8)and the intervention group(n=8).Results:The cross-sectional study revealed that the GDM group had significantly higher rates of pre-pregnancy BMI ≥ 24 kg/m2,early pregnancy HbA1c≥5.7％,impaired fasting glucose or glucose tolerance,and lack of exercise compared to the non-GDM group(P＜0.05).FPG levels in the GDM group were significantly higher than those in the non-GDM group at all stages of pregnancy.Multivariable linear regression analysis showed that the impact of high-risk factors on FPG gradually diminished as pregnancy progressed.In the randomized controlled experiment,all cases in the control group developed GDM;one case in the curcumin intervention group did not,whose intervention time was the earliest and longest.Pearson correlation analysis indicated a positive correlation between the duration of curcumin intervention and changes in FPG values,although the correlation was not statistically significant(P＞0.05).By the descriptive statistical analysis,within-group comparisons showed no significant differences in the median and percentiles of FPG values between the control group in late pregnancy and early pregnancy.However,the median and percentiles of FPG values were significantly lower post-intervention compared to curcumin pre-intervention.Between-group comparisons revealed that the mean FPG in the curcumin intervention group decreased significantly more than in the control group.These results suggested that curcumin might have a potential impact on FPG.No significant differences were observed in neonatal outcomes between the curcumin intervention and control groups.Conclusions:Pregnant women with high risk factors for GDM should be paid enough attention in clinical practice.All these results have demonstrated that curcumin has a positive regulatory effect on FPG in patients with GDM,which may provide a new adjunctive method for the treatment of GDM.