Objective: To analyze respiratory syncytial virus(RSV) outbreaks surveillance results and the epidemiological characteristics in kindergarten and school in Shenzhen during 2017-2023 , so as to provide a scientific reference for control and prevention of RSV. Methods: Epidemiological data and surveillance results of RSV outbreaks in kindergarten and school from 2017 to 2023 were collected for descriptive analyses. Results: A total of 31 RSV outbreaks were identified in kindergarten and school in 2017-2023 in Shenzhen, 346 cases were reported, the average incidence rate was 22.02%. The most annual RSV outbreaks were reported in 2020 with 14 outbreaks, followed by 8 outbreaks in 2023. A total of 64.52% of RSV outbreaks were identified in kindergarten with rest occurring in primary school or middle school. The greatest monthly count of outbreak was 18 (58.06%) in September, followed by 3 outbreaks (9.68%) in March and October. A total of 244 swab samples were collected, 169 samples were positive for respiratory viruses, the positive rate was 69.26%, 121 samples were positive for RSV,from 31 respiratory syncytical virus outbreaks 57 and samples were positive for other respiratory viruses(9 samples were positive for two respiratory viruses). A toral of 14(45.16%) outbreaks are caused by RSV alone, 17 outbreaks (54.84%) were caused by RSV and other respiratory viruses. Conclusions Most RSV outbreaks in kindergarten and school are reported after 2020 in Shenzhen, most RSV outbreaks occur in kindergarten, peak seasons of RSV outbreaks are autumn and spring.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

OBJECTIVE To compare the efficacy of ceftazidime and avibactam （CZA） monotherapy and combination therapy in the treatment of carbapenem-resistant Gram-negative bacteria （CRGNB） infections， and analyze the influencing factors. METHODS The data of patients with CRGNB infection who received CZA treatment from January 2020 to March 2025 were collected retrospectively. The patients were divided into the CZA monotherapy group （52 cases） and the CZA combination therapy group （85 cases） according to treatment regimen. The therapeutic effects of the two groups were compared， and the drug susceptibility results of isolated strains were recorded. The multivariate Logistic regression model was used to analyze the factors influencing clinical efficacy of CRGNB patients. RESULTS The bacterial clearance rate of patients was significantly higher in the CZA combination therapy group than in the CZA monotherapy group （P＝0.012）. However， when comparing the 30-day mortality rate and the clinical response rate between the two groups， no statistically significant differences were observed （P＞0.05）. Among the isolates， carbapenem-resistant Klebsiella pneumoniae had the highest sensitivity to tigecycline （87.3%） and carbapenem-resistant Pseudomonas aeruginosa showed 90.9% sensitivity to amikacin. Five isolates were resistant to CZA. The multivariate Logistic regression showed， lung infection， receiving continuous renal replacement therapy （CRRT）， and inadequate treatment courses were significantly correlated with clinical treatment failure （P＜0.05）. CONCLUSIONS For CRGNB infection， the clinical efficacy of CZA combination therapy is similar to that of monotherapy， but the combination therapy has a higher bacterial clearance rate. Lung infections， receiving CRRT and inadequate treatment courses （No. are independent risk factors for clinical treatment failure.

Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Immunotherapy is an important breakthrough in canc-er treatment.Unfortunately,low drug concentration in tumor sites almost ineffectively initiates immune responses and thereby severely limits immune therapy applications in clinics.Nanoma-terials are well-recognized drug delivery system in cancer thera-py.Nanographene oxide(NGO)have shown immense perti-nence for anti-cancer drug delivery owing to their ultra-high sur-face area,chemical stability,good biocompatibility and excel-lent photosensitivity.In addition,functionalized modifications on the surface of NGO increase tumor targeting and minimize cy-totoxicity.This study focuses on reviewing the literature and up-dates on NGO in drug delivery and discussing the possibilities and challenges of NGO in cancer synergetic therapy.

This study was aimed at understanding the detection rate,drug resistance characteristics,virulence characteris-tics,multi-locus sequence typing,and other molecular epidemic and pathogenic characteristics of Campylobacter jejuni and Campylobacter coli in children in Guangdong Province from 2020 to 2022.Anal swabs or stool samples of suspected infection cases in children from 2020 to 2022 were collected from two hospitals in Guangzhou,Guangdong Province.Campylobacter was isolated and cultured through the filtration method,and identified with a microbial mass spectrometry system;antibiotic resist-ance was analyzed with the agar dilution method;bacterial genome nucleic acids were extracted,and whole-genome sequencing was conducted;and drug resistance genes,virulence genes,multi-locus sequence typing,and phylogenetic analysis based on whole-genome single nucleotide polymorphisms were analyzed from whole-genome sequencing results.First,53 strains of Campy-lobacter were detected through continuous routine monitoring in this study,with a positive detection rate of 2.94％.Among them,Campylobacter jejuni accounted for 81.13％(43/53)and Campylobacter coli accounted for 18.87％(10/53).In addition,16 strains of Campylobacter were screened through multi-pathogen surveillance,including 11 strains of Campylobacter jejuni and 5 strains of Campylobacter coli.Drug resistance ex-periments and whole genome sequencing were conducted on 46 Campylobacter isolates,including 33 isolates of Campylobacter jejuni and 13 isolates of Campylobacter coli.The resistance rate of Campylobacter to erythromycin,a widely used clinical treatment,was21.73％(10/46);that to tetracycline was 80.43％(37/46);those to the quinolone antibiotics nalidixic acid and ciprofloxacin were 76.08％(35/46)and 71.73％(33/46)respectively;and that to chloramphenicol was lowest,at 2.17％(1/46).The drug resistance rate was generally higher for Campylobacter coli than Campylobacter jejuni,and the differences in the indicators of erythromycin,gentamicin,streptomycin,telithromycin,and clindamycin were statistically significant.A total of 30 isolates of multidrug-resistant Campylobacter were detected,including nine multidrug-resistant phenotypes.Whole-ge-nome sequence analysis indicated that 46 Campylobacter isolates carried antibiotic resistance genes for antibiotics such as quino-lones,tetracyclines,β-lactams,and aminoglycosides,and carried 128 virulence factor genes in five categories.All 46 isolates of Campylobacter were identified as 35 ST type through MLST typing,and phylogenetic analysis indicated no obvious dominant ST type.Campylobacter coli had more SNPs than Campylobacter jejuni.In conclusion,the positive detection rate of Campy-lobacter in Guangzhou City,Guangdong Province stabilized from 2020 to 2022,and the detection rate of Campylobacter jejuni was higher than that of Campylobacter coli.Campylobacter isolates were resistant to tetracyclines and quinolone,and showed a wide spectrum of multi-drug resistance,which was relatively severe among Campylobacter coli.Resistance genes and drug-resistant phenotypes were correlated and had predictive significance.The virulence genes of Campylobacter jejuni were more a-bundant than those of Campylobacter coli,possibly because of the higher detection rate and pathogenicity of Campylobacter jejuni.The phylogenetic tree showed clear branches with high genetic diversity and no clearly dominant clonal group.

Objective:To investigate the prognostic significance of DTA(DNMT3A,TET2,ASXL1)gene mutations in patients with non-M3 acute myeloid leukemia(AML).Methods:The clinical data of 180 newly diagnosed AML patients hospitalized in the First People's Hospital of Changzhou from January 2018 to April 2022 were retrospectively analyzed.Next-generation sequencing technology was used to detect 150 gene mutations in the patients,and log-rank tests and Cox regression models were used to analyze the prognostic factors.Results:DTA gene mutations were detected in 83(46.1％)of 180 AML patients.Compared to patients without DTA mutations,patients with DTA mutations were significantly older(P＜0.001).The median overall survival(OS)time and disease-free survival(DFS)time in the DTA mutation group were significantly shorter than those in the group without DTA mutation(both P＜0.05).Multivariate analysis showed that age ≥ 60 years(P＜0.001),with DTA mutation(P=0.018),and intermediate-risk(relative to favorable-risk)(P=0.005)were independent risk factors for OS in AML patients.Conclusion:AML patients with DTA mutations are relatively older,with shorter median OS time and DFS time,and poor prognosis.

Three novel sesquiterpenoid heterodimers,designated as auckcostusolides A-C(1-3),were isolated from Aucklandia costus leaves.The structures of compounds 1-3 were elucidated through comprehensive spectroscopic analysis,with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism(ECD)calculations.Notably,compounds 1 and 2,despite sharing identical planar structures derived from two identical sesquiterpenoids,exhibited oppos-ite configurations at C-11 and C-8'.This configurational difference can be attributed to distinct Diels-Alder cycloaddition processes between the sesquiterpenoid monomers.Additionally,the cytotoxic effects of compounds 1-3 were evaluated against colorectal can-cer HCT116 cells,fibrosarcoma HT1080 cells,and hepatocellular carcinoma HepG2 cells.Compounds 1-3 induced cell death was characterized by endoplasmic reticulum(ER)swelling and cytoplasmic vacuolization,typical morphological changes associated with paraptosis.Mechanistic studies revealed that compounds 1 and 3 triggered paraptosis-like cell death through the accumulation of react-ive oxygen species(ROS),activation of ER stress,and stimulation of the MAPK signaling pathway.

Objective: This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. Methods: Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. Results: In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. Conclusion In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.

Objective:To investigate the morphological and ultrastructural differences between normal and round-headed sperm and the outcomes of assisted reproduction in patients with partial globozoospermia.Methods:We collected clinical information and semen samples from 6 cases of partial globozoospermia confirmed in our hosptials from March 2023 to March 2024,performed Diff-Quik staining of the samples,observed the sperm morphology under the light microscope and transmission electron microscope,compared the ultrastructures between round-headed and normal spermatozoa,and analyzed the clinical outcomes of assisted reproduction in the pa-tients.Results:Under the light microscope,the the round-headed sperm had no acrosomal structure,some with tail abnormalities;while under the transmission electron microscope,they exhibited dissolved plasma membrane,acrosomal absence,small acrosomes,nucleoplasmic granulation,huge central vacuoles,swelling,absence or irregular arrangement of mitochondria in the neck,and disor-ganized or missed 9+2 microtubules in the tail.All the 6 patients underwent intracytoplasmic sperm injection(ICSI),and 1 of them achieved pregnancy.Conclusion:The sperm organelle is morphologically damaged and ultrastructurally abnormal in some patients with partial globozoospermia,which may be a key factor for their infertility,and ICSI can help some of them to achieve fertility.