ObjectiveTo investigate the epidemiological and clinical characteristics of human bocavirus (HBoV) in hospitalized children with acute lower respiratory tract infection (ALRTI) at a single-center children’s hospital in Shanghai, thereby providing evidence for the diagnosis, treatment, and prevention of HBoV infection. MethodsA retrospective study was conducted on 19 537 hospitalized children with ALRTI at Shanghai Children’s Hospital from January 2021 to December 2023. Multiplex polymerase chain reaction (PCR) combined with capillary electrophoresis was used to detect HBoV and 12 other common respiratory viruses /atypical pathogens. The positive detection rate, demographic characteristics (sex, age), temporal distribution (year, season) of HBoV, as well as the clinical characteristics of severe and non-severe pneumonia were analyzed. ResultsThe overall HBoV-positive rate was 2.57% (503/19 537), with 59.44% (299/503) being single infections and 40.56% (204/503) being co-infections. The positive detection rate was significantly higher in boys than that in girls (2.78% vs 2.33%, χ²=3.88, P=0.049). The highest infection rate was observed in toddlers, followed by infants (χ²=379.57, P<0.001). The positive rate peaked in 2021 and reached its lowest point in 2023 (χ²=45.49, P<0.001), with epidemics mainly prevalent in summer and autumn. The main clinical symptoms were cough (90.06%, 453/503), fever (75.94%, 382/503), and wheezing (39.96%, 201/503). Children with severe pneumonia showed a higher incidence of wheezing compared with the non-severe group (P<0.001), while underlying diseases and co-infections had no significant association with disease severity (P>0.05). ConclusionHBoV was an important pathogen of ALRTI in children, predominantly affecting infants and toddlers, with higher susceptibility in boys and seasonal peaks in autumn and summer. The main clinical manifestations included cough, fever, and wheezing, with wheezing being more prevalent in children with severe pneumonia.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

OBJECTIVES: To explore the active components that mediate the therapeutic effect of Centella asiatica on psoriasis and their therapeutic mechanisms. METHODS: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in Centella asiatica and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis. In a RAW264.7 macrophage model of LPS-induced inflammation, the anti-inflammatory effect of 7.5, 15, 30, and 60 μmol/L quercetin, asiaticoside, and asiatic acid, which were identified as the main active components in Centella asiatica, were tested by measuring cellular production of NO, TNF‑α and IL-6 using Griess method and ELISA and by detecting mRNA expressions of IL-23, IL-17A, TNF-α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727) with RT-qPCR and Western blotting. RESULTS: A total of 139 targets of Centella asiatica and 4604 targets of psoriasis were obtained, and among them CASP3, EGFR, PTGS2, and ESR1 were identified as the core targets. KEGG analysis suggested that quercetin, asiaticoside, and asiatic acid in Centella asiatica were involved in cancer and IL-17 and MAPK signaling pathways. In the RAW264.7 macrophage model of inflammation, treatment with quercetin significantly reduced cellular production of NO, TNF‑α and IL-6, and lowered mRNA expressions of IL-23, IL-17A, TNF‑α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727). CONCLUSIONS Quercetin, asiaticoside and asiatic acid are the main active components in Centella asiatica to mediate the therapeutic effect against psoriasis, and quercetin in particular is capable of suppressing cellular production of NO, TNF‑α and IL-6 and regulating the IL-23/IL-17A inflammatory axis by mediating STAT3 phosphorylation to inhibit inflammatory response.
Quercetin/pharmacology* ; Psoriasis/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice ; Animals ; Centella/chemistry* ; Triterpenes/pharmacology* ; Phosphorylation ; Interleukin-17/metabolism* ; Interleukin-23/metabolism* ; RAW 264.7 Cells ; Pentacyclic Triterpenes/pharmacology* ; Macrophages/drug effects* ; Signal Transduction ; Plant Extracts

OBJECTIVE Aimed to investigate the impact of comorbid asthma on chronic rhinosinusitis with nasal polyps(CRSwNP)and identify key proteins and signaling pathways.METHODS Proteomic methods were employed to analyze differentially expressed proteins(DEPs)in nasal lavage fluid(NLF)from control,CRSwNP,and CRSwNP with asthma groups.DIA quantitative analysis technology was used to assess the gradient changes of DEPs among the three groups to determine key proteins affected by comorbid asthma in CRSwNP.RESULTS Compared to the control group,1 377 and 1 006 DEPs were identified in the CRSwNP and CRSwNP with asthma groups,respectively.Peroxiredoxin-5(PRDX5),Ran-Binding Protein 1(RanBP1)(upregulated),and Keratin 9(KRT9)(downregulated)were identified as key proteins affecting CRSwNP with asthma.CONCLUSION Comorbid asthma may promote the occurrence and development of nasal polyps through specific key proteins and signaling pathways,providing new molecular insights into the interaction between CRSwNP and asthma.

Objective:To investigate the correlation between preoperative ultrasound parameters,serum albumin (ALB),low-density lipoprotein (LDL) levels and the maturation of radial-cephalic fistula (RCF) in patients with end-stage renal disease (ESRD). Methods:A total of 130 ESRD patients who admitted to the First Affiliated Hospital of Henan University of Science and Technology from January 2022 to September 2023 and established RCF access for the first time were selected as the study subjects. All patients underwent ultrasound examinations on upper limb blood vessels and heart before fistula surgery,and serum ALB and LDL levels of them also were measured. According to the postoperative fistula maturation,the patients were divided into the fistula maturation group (102 cases) and the poor fistula maturation group (28 cases). And then,the correlations between the preoperative ultrasound parameters,serum ALB level,serum LDL level,and the fistula maturation in the two groups were compared and analyzed. Results:The cephalic vein dilation,radial artery diameter and serum ALB levels in the RCF maturation group were higher than those in the poor fistula maturation group,and the serum LDL level was lower than that in the poor fistula maturation group (t=3.810,3.401,3.405,-2.846,P<0.05),respectively. The area under curve (AUC) value of receiver operating characteristic (ROC) curve of laboratory dual indicators (LDL+ALB) was 0.745 (95％CI:0.647-0.842) in predicting RCF maturation,and the sensitivity and specificity of that were respectively 77.50％ and 67.90％. The AUC value of ultrasound dual parameters (cephalic vein dilation+radial artery diameter) was 0.809 (95％CI:0.728～0.891) in predicting RCF maturation,and the sensitivity and specificity of that were respectively 68.60％ and 82.10％. The AUC value of ultrasound dual parameters combined with laboratory dual indicators was 0.905 (95％CI:0.847～0.962) in predicting RCF maturation,and the sensitivity and specificity of that were respectively 76.50％ and 92.90％. The Delong test showed that the AUC value of ultrasound dual parameters combined with laboratory dual indicators was better than that of single ultrasound dual parameters and single laboratory dual indicators in predicting RCF maturation (Z=-2.899,-3.609,P<0.05). Conclusion:The combination of cephalic vein dilation,radial artery diameter,serum ALB and LDL has higher predictive value for fistula maturation in ESRD patients.

Objective To analyze the relationship between clinical drug utilization and the risk of nosocomial infections among hospitalized patients,and provide evidence for the prevention and control of nosocomial infections.Methods This study adopted a retrospective case-control design.The case group included 209 patients with nosocomial infection reported from January 2023 to December 2023 in a tertiary hospital.The control group included 209 patients without nosocomial infection during the same period.The patients in the control group were selected by stratified sampling based on Charlson Comorbidity Index(CCI).Results Univariate analysis showed that proton pump inhibitors,antacids,immunosuppressants and prior antimicrobial combination therapy increased the risk of nosocomial infection(P＜0.05).Multivariate log-binomial regression analysis showed that proton pump inhibitors,immunosuppressive drugs,and prior antimicrobial combination therapy were correlated with nosocomial infection.The corresponding relative risk(RR)was 1.31(95％CI:1.07-1.60),1.40(95％CI:1.02-1.91),and 1.66(95％CI:1.01-2.74),respectively.Further analysis indicated that the patients with nosocomial infection had longer time in use of proton pump inhibitors and prior antimicrobial combination therapy than the patients in the control group(Z=-6.331,P＜0.001;Z=-2.667,P=0.008).The trend Chi-square test showed that there was a dose-response relationship for proton pump inhibitors(x2=73.869,P＜0.001),immunosuppressive drugs(x2=16.530,P＜0.001),and prior antimicrobial combination therapy(x2=35.107,P＜0.001).Conclusions The use of immunosuppressants,proton pump inhibitors and antimicrobial combination therapy increases the risk of nosocomial infections in hospitalized patients.The prolonged use of these drugs will further increase the risk of nosocomial infection.

Objective:To investigate the value of tumor volume to uterine volume ratio (N/U) combined with the expression of alpha-fetoprotein (AFP), sugar antigen 199 (CA199) and human epididymal secretory protein 4 (HE4) in evaluating the pathologic grade and prognosis of endometrial carcinoma (EC) .Methods:A total of 160 EC patients admitted to Linyi Central Hospital from Jan. 2021 to Dec. 2023 were divided into low-grade group and high-grade group according to FIGO grading method, and were divided into poor prognosis group and good prognosis group according to cancer death, recrudescence. The levels of N/U, AFP, CA199 and HE4 in patients with different pathologic grades and prognosis were compared. COX regression was used to analyze the influencing factors of EC adverse prognosis, ROC curve was used to analyze the value of N/U combined with serum AFP, CA199 and HE4 in predicting EC adverse prognosis, and a nomogram model was constructed.Results:Pathological examination of 160 EC patients showed that 12 cases were non-endometrioid adenocarcinoma, 148 cases were endometrioid adenocarcinoma, 41 cases were high-grade and 119 cases were low-grade.According to the follow-up, 94 of the 160 EC patients had good prognosis and 66 had poor prognosis. The levels of N/U, AFP, CA199 and HE4 in the poor prognosis group were higher than those in the good prognosis group ( P<0.05). COX regression analysis showed that high levels of N/U, AFP, CA199 and HE4 were all factors affecting the poor prognosis of EC patients ( P<0.05). The AUC value of combined detection of N/U, AFP, CA199 and HE4 in predicting adverse prognosis of EC patients was higher than that of single detection ( Z=3.140, 3.658, 4.277, 4.378, P<0.05) .The ROC curve AUC (95% CI) of the training set and the validation set were 0.84 (0.77-0.92) and 0.90 (0.81-0.98) respectively for the training set and the validation set to predict the adverse prognosis of EC patients. Calibration curve results showed that the calibration curve for EC patients predicted by the nomogram model was close to the ideal curve ( P=0.521, 0.743). The DCA curve shows that the probability threshold of the nomogram model has a higher positive net return at 20%~100%. Conclusion:The levels of N/U, AFP, CA199 and HE4 in EC patients are related to the pathologic grade, and the combined detection of these indicators can predict the poor prognosis of EC patients, and the nomogram model constructed based on these indicators has high predictive value.

Objective To investigate the seroprevalence of antibody against Toxoplasma gondii among patients with hematological malignancies, and compare it with that among health individuals, so as to provide insights into unraveling the pathogenesis of hematological malignancies. Methods A total of 225 patients with hematological malignancies in Department of Hematology, Xuzhou Central Hospital and 300 healthy individuals in the same hospital were enrolled from 2017 to 2024. Blood samples were collected from all subjects, and the serum IgG and IgM antibodies against T. gondii were detected using chemiluminescent immunoassay. Demographic and clinical features were collected from patients with hematological malignancies, including gender, age, contact with cats, consumption of raw or undercooked meat, type of malignancy, clinical symptoms, blood transfusion and treatment, and the seroprevalence of anti-T. gondii antibody was compared among patients with different characteristics. Results The age (t = 0.72, P > 0.05) and gender (χ² = 0.93, P > 0.05) were compared between patients with hematological malignancies and healthy individuals. The seroprevalence of T. gondii infection was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), and the seroprevalence of anti-T. gondii IgG antibody was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), while there was no significant difference in the seroprevalence of anti-T. gondii IgM antibody between patients with hematological malignancies and healthy individuals (1.33% vs. 0; corrected χ² = 2.02, P > 0.05). The seroprevalence of T. gondii infection was 23.08% among patients with leukemia, 16.67% among patients with lymphoma, 19.23% among patients with multiple myeloma, 24.00% among patients with myeloproliferative neoplasm, and 26.09% among patients with myelodysplastic syndrome (χ² = 1.44, P > 0.05), and was all higher than among healthy individuals (corrected χ² = 23.92, 10.74, 13.76, 12.84 and 14.54; all P values < 0.01). In addition, there were no significant differences in the detection of anti-T. gondii antibody among patients with hematological malignancies in terms of gender, age, contact with cats, consumption of raw or undercooked meat, chemotherapy or blood transfusion (χ² = 0.76, 1.97, 0, 2.81, 2.38 and 0.66; all P values > 0.05). Conclusions There is a high risk of T. gondii infection among patients with hematological malignancies, and intensified surveillance of T. gondii infection is recommended among patients with hematological malignancies.

Objective To understand the epidemiological characteristics and trends of postoperative pneumonia(POP)in tertiary general hospitals in Jiangsu Province,and provide theoretical basis for carrying out targeted pre-vention and control measures.Methods Surgery patients from 22 tertiary general hospitals in 12 cities in north,central,and south of Jiangsu Province from January 1,2022 to December 31,2023 were chosen as studied subjects,occurrence of POP was analyzed and compared.Results A total of 848 274 surgical procedures were performed in 22 hospitals,and 3 606 cases of POP occurred,with an incidence of 0.43％.The incidence in 2023 was 0.37％,which was lower than that in 2022(0.49％),with statistically significant difference(P＜0.001).The top three de-partments with high incidence of POP were neurosurgery(6.71％),cardiothoracic surgery(2.91％),and general surgery(0.77％).Among hospitals of different grades,the incidence of POP in tertiary first-class hospitals was 0.44％,which was higher than that in other tertiary hospitals(0.37％).There was no statistically significant difference in the incidence of POP between municipal and district/county hospitals(P＞0.05).The incidence of POP in hospitals with a bed:infection control full-time staff ratio＜200∶1 was lower than that in hospitals with the ratio ≥200∶1(0.39％vs 0.47％,P＜0.001),while the incidence of POP in hospitals with a proportion ≥30％of full-time staff being doctors was higher than that in hospitals with a proportion＜30％(0.45％vs 0.36％,P＜0.001).The incidence of POP in male patients was higher than that in female patients(0.62％vs 0.26％,P＜0.001).The incidence of POP in elderly patients aged≥65 was higher than that in patients aged＜65(0.73％vs 0.26％,P＜0.001).A total of 2 667 strains of infectious pathogens were detected,with the top three being Acine-tobacter baumannii,Klebsiella pneumoniae,and Pseudomonas aeruginosa,accounting for 28.95％,22.72％,and 15.45％,respectively.The detection rates of carbapenem-resistant Acinetobacter baumannii(CRAB),carba-penem-resistant Klebsiella pneumoniae(CRKP),and carbapenem-resistant Pseudomonas aeruginosa(CRPA)were 60.75％,21.45％,and 32.28％,respectively.The detection rate of CRKP decreased in 2023 compared with 2022,with statistically significant difference(P＜0.05).Conclusion The overall incidence of POP in tertiary general hos-pitals in Jiangsu Province is relatively low,but there are significant differences among different hospitals.There-fore,perioperative prevention and control measures should be carried out based on the epidemiological characteristics of patients.

Objective:To investigate the differences in protein profile expression in serum samples from children with corona virus disease 2019（COVID-19）related encephalopathy and to explore the underlying mechanisms.Methods:From December 1,2022 to January 31,2023,28 children with COVID-19 who were admitted to the Department of Pediatric Intensive Medicine at Shandong Provincial Hospital Affiliated to Shandong First Medical University were collected,including 21 patients with encephalopathy(COVID-19 with encephalopathy group) and seven patients without encephalopathy(COVID-19 without encephalopathy group).Three children from each group were selected for serum proteomic analysis using tandem mass spectrometry labeling proteomics technology.Proteins were considered significantly different if the fold change was >1.2 or <0.8，with P<0.05.Bioinformatics analysis，including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment were performed on differentially expressed proteins.Protein-protein interaction networks were analyzed using the STRING database.Selected proteins were further validated by enzyme-linked immunosorbert assay. Results:A total of 41 differentially expressed proteins were identified between the two groups.Among these，14 proteins were upregulated and 27 proteins were downregulated in COVID-19 patients with encephalopathy compared to those without encephalopathy.Bioinformatics analysis revealed that these proteins were primarily enriched in critical signaling pathways，including complement and coagulation regulation，neutrophil degranulation and activation，and platelet degranulation.Enzyme-linked immunosorbert assay validation confirmed significant differences in key coagulation-regulating proteins(von willebrand factor upregulated，serpin family F member 2 downregulated in COVID-19 patients with encephalopatly）between the two groups.Conclusion:Coagulation dysfunction may play a role in the development of COVID-19 associated encephalopathy in children，providing valuable insights for future research.