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: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

ObjectiveTo compare the clinical features of patients with hepatitis B virus （HBV）-related early-onset liver cancer and those with late-onset liver cancer， to assess the severity of the disease， and to provide a theoretical basis for the early diagnosis and treatment of liver cancer. MethodsA retrospective analysis was performed for 695 patients who were diagnosed with HBV-related liver cancer for the first time in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2019 to August 2023， among whom 93 had early-onset liver cancer （defined as an age of50 years for female patients and40 years for male patients） and 602 had late-onset liver cancer （defined as an age of ≥50 years for female patients and ≥40 years for male patients）. Related clinical data were collected， including demographic data， clinical symptoms at initial diagnosis， comorbidities， smoking history， drinking history， family history， routine blood test results， biochemical parameters of liver function， serum alpha-fetoprotein（AFP）， virological indicators， coagulation function， and imaging findings. The pan-inflammatory indices neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， and lymphocyte-to-monocyte ratio （LMR） were calculated， as well as FIB-4 index， aspartate aminotransferase-to-platelet ratio index （APRI）， S index， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， albumin-bilirubin （AIBL） grade， and Barcelona Clinic Liver Cancer （BCLC） stage. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or Fisher’s exact test were used for comparison of categorical data between two groups. ResultsThere were significant differences between the two groups in the proportion of male patients and the incidence rates of diabetes， hypertension， and fatty liver disease （χ²=6.357， 15.230， 11.467， and 14.204， all P0.05）， and compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly higher proportion of patients progressing to liver cancer without underlying cirrhosis （χ²=24.657， P0.001） and a significantly higher proportion of patients with advanced BCLC stage （χ²=6.172， P=0.046）. For the overall population， the most common clinical symptoms included abdominal distension， abdominal pain， poor appetite， weakness， a reduction in body weight， edema of both lower limbs， jaundice， yellow urine， and nausea， and 55 patients （7.9%） had no obvious symptoms at the time of diagnosis and were found to have liver cancer by routine reexamination， physical examination suggesting an increase in AFP， or radiological examination indicating hepatic space-occupying lesion； compared with the late-onset liver cancer group， the patients in the early-onset liver cancer group were more likely to have the symptoms of abdominal distension， abdominal pain， and jaundice （all P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly larger tumor diameter （Z=2.845， P=0.034）， with higher prevalence rates of multiple tumors and intrahepatic， perihepatic， or distant metastasis （χ²=5.889 and 4.079， both P0.05）， and there were significant differences between the two groups in tumor location and size （χ²=3.948 and 11.317， both P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had significantly lower FIB-4 index， proportion of patients with HBsAg ≤1 500 IU/mL， and levels of LMR and Cr （all P0.05）， as well as significantly higher positive rate of HBeAg and levels of log₁₀ HBV DNA， AFP， WBC， Hb， PLT， NLR， PLR， TBil， ALT， Alb， and TC （all P0.05）. ConclusionCompared with late-onset liver cancer， patients with early-onset liver cancer tend to develop liver cancer without liver cirrhosis and have multiple tumors， obvious clinical symptoms， and advanced BCLC stage， which indicates a poor prognosis.

Objective:To investigate the effect of peripheral white blood cell(WBC) count on adverse pregnancy outcomes.Methods:A retrospective analysis was conducted on pregnant women who delivered at Minhang Hospital affiliated with Fudan University between January 2013 and June 2020. Demographic data, WBC counts, and diagnostic information on gestational diabetes mellitus(GDM), gestational hypertension, and preeclampsia/eclampsia were extracted from electronic medical records. Logistic regression models were used to evaluate the association between WBC counts in the first(WBC-1) and second trimesters(WBC-2) and metabolically related pregnancy outcomes.Results:A total of 24 143 pregnant women were included, with a mean age of(29.1±4.9) years and a mean pre-pregnancy body mass index(BMI) of(21.1±2.8) kg/m 2. The mean WBC counts in the first and second trimesters were 8.1×10 9/L and 8.9×10 9/L, respectively. The incidence rates of GDM, gestational hypertension, and preeclampsia/eclampsia were 5.6%, 4.8%, and 1.8%, respectively. After adjusting for relevant confounders, a core standard deviation( s) increase in WBC-1 was associated with a 6%, 18%, and 14% increased risk of GDM, gestational hypertension, and preeclampsia/eclampsia, respectively( P<0.001). Similarly, a one s increase in WBC-2 was associated with a 10% increased risk for all three adverse outcomes( P<0.001). Conclusion:Elevated peripheral WBC levels in the first and second trimesters are independently associated with increased risk of adverse pregnancy outcomes, independent of traditional risk factors.

Objective:A novel grass-root community screening and management model of hepatitis B was developed in order to improve the diagnosis and treatment rate of hepatitis B in Guangzhou city.Methods:A three-tier collaborative framework［tertiary hospitals-center for disease control and prevention（CDC）-primary care clinics］implemented dual-track screening（fixed-site+mobile units）using rapid hepatitis B surface antigen（HBsAg）testing and structured surveys. Digital closed-loop management integrated screening，referral，and follow-up. Data were analyzed via SPSS 26.0.Results:Among 30 012 community-dwelling adults screened（Male∶Female=1∶1.68），overall HBsAg positive rate was 5.21%（1 565/30 012），peaking in the 50-59-year cohort（ χ2=271.80， P<0.001）. Hepatitis B knowledge awareness was critically low（39.24%）. Of 140 referred HBsAg-positive individuals，15 chronic carriers required no immediate antiviral therapy per guidelines. Treatment linkage surged from 32.8%（41/125）to 86.4%（108/125）post-intervention. aMAP hepatocellular carcinoma（HCC）risk stratification（n=82）revealed low（36.6%），intermediate（32.9%），and high-risk（30.5%）profiles. Conclusions:This coordinated，digitally-enhanced strategy significantly improved hepatitis B detection and treatment access. However，persistent knowledge gaps underscore the imperative for targeted community education and adherence support.

Objective To learn the current status of informational development in public TCM hospitals in China,and to provide references for promoting the informational development.Methods It makes a comprehensive assessment of the informational level in 2 539 public TCM hospitals nationwide with comprehensive index method,and then analyse the index.Results(1)The construction rate of telemedicine systems in tertiary public TCM hospitals reached 76.96%,and the rate in secondary hospitals is 57.63%.(2)In terms of functional level of electronic medical record application,34.42%of tertiary public TCM hospitals failed to meet the requirement of Level 4,and 40.92%of secondary hospitals failed to meet the requirement of Level 3.In terms of Interconnection standardization maturity level,86.72%of tertiary public TCM hospitals failed to meet the requirement of Level 4.(3)The informational level is not balanced among different typesand different regions in tertiary public TCM hospitals.In secondary public TCM hospitals,there are differences among types of hospitals.Conclusion There are advantages on the development of Internet consultation and telemedicine systems in public TCM hospitals.The standardization of information may be a key factor that affect the lack of data connectivity and smart hospital management.There are differences in the level of informatization among different types of hospitals.So TCM hospitals is recommended to explore the way of development that suit for them.Some hospitalswell-developed should lead the way of development.

Objective:To investigate the clinical characteristics of children with severe human metapneumovirus (HMPV) infection and identify the risk factors associated with critical illness.Methods:A retrospective cohort study was conducted, enrolling 157 hospitalized children with severe HMPV infection, who tested positive for HMPV nucleic acid via PCR-capillary electrophoresis fragment analysis of nasopharyngeal secretions at Shanghai Children′s Hospital from January 2021 to December 2023.Clinical features, co-infections, treatment, and outcomes were collected. Based on the diagnostic criteria for severe HMPV infection, the patients were categorized into a critical illness group and a non-critical illness group. Intergroup comparisons were performed using the χ2 test or the Mann-Whitney U test. Multivariate Logistic regression analysis was employed to identify risk factors for critical HMPV infection and to establish a predictive model.The performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis and calibration curves. Results:Among the 157 cases of severe HMPV infection, there were 67 males and 90 females, with an onset age of 39.0 (20.0, 55.5) months. Single-pathogen infection was observed in 125 cases (79.6%), while mixed infections accounted for 32 cases (20.4%).Severe pneumonia was diagnosed in 136 cases (86.6%).The predominant manifestations of severe HMPV infection included fever 152 cases (96.8%), cough 151 cases (96.2%), and wheezing 94 cases (59.9%).Sixty-eight patients (43.3%) required non-invasive respiratory support, 58 cases (36.9%) were admitted to the intensive care unit, and 22 cases (14.0%) underwent mechanical ventilation. Of the total, 149 cases (94.9%) were discharged with improvement, 8 cases (5.1%) were discharged against medical advice, and there were no fatal cases. The cohort was further stratified into a critical illness group 31 cases and a non-critical illness group 126 cases. Compared to the non-critical illness group, the critical illness group exhibited significantly higher rates of respiratory distress, lethargy, and intercostal retractions, along with a higher proportion of underlying comorbidities, and elevated levels of C-reactive protein and procalcitonin (all P<0.05).Conversely, albumin and hemoglobin levels were significantly lower in the critical illness group (both P<0.05). ROC curve analysis revealed that the optimal cutoff value for the duration of fever in predicting severe HMPV infection was 4.5 days.The multivariate binary Logistic regression analysis revealed that prolonged fever duration (>4.5 days) ( OR=28.00, 95% CI 5.09-153.93, P<0.001), anorexia ( OR=11.72, 95% CI 1.26-108.75, P=0.030), and immune dysfunction ( OR=36.71, 95% CI 1.55-867.31, P=0.026) were independent risk factors for severe HMPV infection. A predictive model for critical illness was constructed based on these independent risk factors. ROC curve analysis demonstrated excellent discriminative ability, with an area under the curve of 0.96 (95% CI 0.92-1.00, P<0.001). The optimal predictive probability threshold was 0.17, yielding a sensitivity of 0.93 and specificity of 0.92. The calibration curve closely approximated the ideal curve, indicating good model calibration ( P=0.157). Conclusions:Severe HMPV infection is predominantly observed as a single infection and is prone to progress to severe pneumonia, with fever, cough, and wheezing as the main clinical manifestations. A subset of cases progresses to critical illness, though the overall prognosis is favorable. Prolonged fever duration (>4.5 days), anorexia, and immune dysfunction were independent risk factors for critical illness.The risk prediction model constructed for pediatric critical HMPV infection demonstrated robust discriminative ability with excellent calibration.

Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.