ObjectiveTo investigate the whole genomic characteristics and phylogenetic relationships of clinical isolates of enteroaggregative Escherichia coli (EAEC) in diarrhea outpatients in Pudong New Area, Shanghai. MethodsBased on the diarrheal disease surveillance network in Pudong New Area, Shanghai, whole-genome sequencing was performed on a total of 55 EAEC strains isolated from fecal samples of the diarrhea outpatients from January 2015 to December 2019. The genome analyses based on raw sequencing data encompassed genome size, coding genes, dispersed repeat sequences, genomic islands, and protein coding regions, and pan-genome analyses were conducted simultaneously. Contigs sequences assays were performed to analyze molecular characteristics including serotypes, antibiotic resistance genes, and virulence factors. The phylogenetic clusters and multilocus sequence typing (MLST) were identified, and a phylogenetic tree was constructed. ResultsEAEC exhibited an open pan-genome. The predominant serotype of EAEC in diarrhea outpatients in Pudong New Area was O130:H27, and the carriage rate of β-lactam resistance genes was the highest (67.27%, 37/55). A total of 29 virulence factors and 106 virulence genes were identified, phylogenic group B1 was the predominant group, and clonal group CC31 was the dominant clonal group. The strain distribution was highly heterogeneous. ConclusionThe genomic characteristics of EAEC displayed significant strain polymorphism. It is necessary to develop effective strategies for differential diagnosis and improve detection capabilities for infection with EAEC of different serotypes and genotypes.

Objective:To explore the clinical characteristics and healthcare burden in patients with McCune-Albright syndrome (MAS).Methods:A cross-sectional study was conducted at the Children′s Hospital, Zhejiang University School of Medicine. Clinical and healthcare burden data were systematically collected through structured questionnaires in 164 children with MAS from February 2022 to May 2023. According to the clinical characteristics, patients were categorized into 3 groups: monosymptomatic, bisymptomatic and trisymptomatic groups. Patients were also divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Comparative analyses of clinical characteristics and healthcare burden were conducted across age, sex, and symptom categories.Results:The cohort comprised 59 males (36.0%) and 105 females (64.0%) with an age of 4.6 (2.0, 7.4) years. Age stratification revealed 117 cases (71.3%) aged 0-<7 years, 29 cases (17.7%) aged 7-<10 years, and 18 cases (11.0%) aged 10-<18 years. Among monosymptomatic (67 cases, 40.9%), the cohort comprised 32 females (47.8%) and 35 males (52.2%), predominantly presenting with fibrous dysplasia (57 cases, 85.1%). This subgroup showed peak prevalence in the 0-<7 years age range (29 cases (50.9%)). The bisymptomatic cohort (56 cases, 34.1%) consisted of 39 females (69.6%) and 17 males (30.4%), predominantly manifesting fibrous dysplasia with skin hyperpigmentation (25 cases, 44.6%). Peak prevalence occurred in the 0-<7 years subgroup(16 cases (64.0%)). The trisymptomatic cohort (41 cases, 25.0%) consisted of 34 females (82.9%) and 7 males (17.1%), with peak prevalence occurring in the 0-<7 years subgroup (36 cases (87.8%)). The diagnostic journey analysis revealed 94 cases (57.3%) required 1-3 referrals, and 34 cases (20.7%) necessitated >3 referrals from symptom onset to definitive diagnosis. Healthcare expenditure analysis revealed 69 families (42.1%) incurred direct medical costs of 10 000-100 000 CNY, with 11 families (6.7%) exceeding >100 000 CNY. Direct non-medical costs reached of 10 000-100 000 CNY for 62 families (37.8%) and >100 000 CNY for 4 families (2.4%). Productivity loss affected 58 families (35.4%) at 10 000-100 000 CNY and 8 families (4.9%) above 100 000 CNY during the study period.Conclusion:MAS requires increased attention to skeletal manifestations, especially in children aged 0-<7 years. Moreover, the significant financial burden on families necessitates a society-wide support system.

OBJECTIVE: To evaluate the early effectiveness of transosseous suture fixation in treating recurrent acute patellar dislocation with patellar osteochondral fractures (OCFs). METHODS: A retrospective analysis was conducted on 19 patients with recurrent acute patellar dislocation and patellar OCFs, who underwent transosseous suture fixation between January 2018 and December 2022 and were followed up 2 years. The cohort included 8 males and 11 females, aged 13-21 years (mean, 16.2 years). Patients experienced 2-5 times of patellar dislocation (mean, 3.2 times). The interval from the last dislocation to operation ranged from 3 to 15 days (mean, 9.6 days). Preoperative imaging revealed the intra-articular osteochondral fragments and medial patellofemoral ligament (MPFL) injury. Clinical outcomes were evaluated using the visual analogue scale (VAS) score for pain, the International Knee Documentation Committee (IKDC) score, the Hospital for Special Surgery (HSS) knee score, the Lysholm score, and the Tegner score. Postoperative complications were recorded. During follow-up, the knee X-ray films, CT, and MRI were taken to evaluate fragment healing, displacement, and the morphology and tension of the MPFL reconstruction graft. RESULTS: All incisions healed primarily, and no complication occurred such as infection, joint stiffness, patellofemoral arthritis, or redislocation. Patients were followed up 24-60 months (mean, 43.5 months). At 12 months postoperatively and the last follow-up, significant improvements ( P<0.05) were observed in VAS, Lysholm, IKDC, HSS, and Tegner scores compared to preoperative values. Further improvements were observed at last follow-up compared with the 12 months postoperatively, and the differences were significant ( P<0.05). Imaging studies demonstrated satisfactory osteochondral fragment positioning with stable fixation. At last follow-up, all fragments had healed, and MPFL reconstruction grafts exhibited optimal morphology and tension. No joint adhesion or fragment displacement occurred. CONCLUSION For recurrent acute patellar dislocation with patellar OCFs, transosseous suture fixation proves to be both safe and effective, achieving satisfactory early effectiveness.
Humans ; Male ; Female ; Patellar Dislocation/surgery* ; Adolescent ; Young Adult ; Retrospective Studies ; Patella/surgery* ; Suture Techniques ; Treatment Outcome ; Recurrence ; Fracture Fixation, Internal/methods* ; Fractures, Bone/surgery* ; Follow-Up Studies

The immunosuppressive tumor micro-environment significantly limits the efficacy of im-munotherapy.Tumor-associated macrophages(TAMs),the most abundant immune cells in the tu-mor microenvironment,often exhibit an immuno-suppressive M2 phenotype,contributing to this im-munosuppressive landscape.Modulating TAMs to adopt anti-tumor phenotypes can enhance immu-notherapy outcomes and inhibit tumor progression.In recent years,tumor immunotherapy leveraging engineered bacteria has garnered considerable at-tention.Bacteria possess the ability to target tu-mors,preferentially colonizing tumor regions,and contain abundant pathogen-associated molecular patterns that effectively activate TAMs within the immunosuppressive tumor environment.This acti-vation enhances the tumoricidal and clearance ca-pabilities of TAMs.With the rapid advancements in synthetic biology,engineered bacteria have emerged as a potent therapeutic modality for im-munotherapy,leading to increased focus on the regulation of TAMs by engineered bacteria.This pa-per first outlines clinical studies on targeted TAMs therapy and engineered bacteria-based tumor ther-apy.It then reviews recent advancements in bacte-rial regulation of TAMs,detailing how engineered bacteria enhance TAM recruitment,improve TAM phagocytosis,and remodel TAM phenotypes.Mod-ulating TAMs with engineered bacteria presents a promising therapeutic strategy and introduces a novel approach in tumor immunotherapy.

Objective To explore the current situation of medication safety behavior of elderly cancer patients and the path relationship of various influencing factors for improving medication safety behavior.Methods A total of 340 elderly cancer patients were investigated by a demographic questionnaire,the Medication Safety Behavior Scale,the Medication Literacy Scale,the Family Care Index Questionnaire,and the Chinese version of the Empowerment Scale for Cancer Patients from August to December 2024.The multiple linear regression analysis was applied to analyze influencing factors,and data were analyzed using SmartPLS 4.0 to construct a partial least squares structural equation model with path analysis.Results A total of 307 valid questionnaires were collected.The mean medication safety behavior score was 31.89±5.38.Residential area,drug literacy,family care,and health empowerment are factors that affect medication safety in elderly cancer patients,accounting for 37.3％of the total variation.The path analysis results indicated that health empowerment(β=0.480),medication literacy(β=0.154),and family care(β=0.227)positively correlate with medication safety behavior.Health empowerment played a partial mediating role between family care and medication safety behavior,as well as between medication literacy and medication safety behavior.The mediating effects are 0.125 and 0.332(P＜0.001),accounting for 35.51％and 68.31％of the total effect,respectively.Conclusion Medication safety behaviors among elderly cancer patients are at a median level and influenced by multiple factors.By improving their levels of health empowerment,healthcare professionals can motivate patients to take an active role in medication safety management.Further,promoting education on medication knowledge and teaching relevant medical skills,and together with guiding patients to perceive family care and support,can collectively improve their overall medication safety behaviors.

Objective:To analyze the influencing factors of China′s DRG payment system reform(DRG reform) and its hierarchical relationship, for references for the in-depth promotion of China′s medical insurance payment reform.Methods:Relevant literature on DRG reform in China from databases such as CNKI, Wanfang Database, Pubmed, etc, were obtained. Content analysis method was used to extract the influencing factors of DRG reform. The correlation between each influencing factor was determined through expert discussion. An interpretive structural model(ISM) was constructed to analyze the hierarchical relationship of factors influencing DRG reform.Results:After analysis, the influencing factors(12) of DRG reform in China were included such as medical level, hospital management, and medical staff′s cognition and behavior. Among them, the local situation was the deep-level factor affecting DRG reform, 9 factors such as data quality assurance and policy design/implementation were the middle-level factors, and patients′ interests/needs and disease grouping were the surface-level factors.Conclusions:There were many influencing factors on the reform of China′s DRG payment system. It was suggested that relevant management departments in various regions should focus on the actual situation of the locality, take data quality and policy design and implementation as the key points of reform, formulate a scientific and reasonable DRG grouping scheme, safeguard the interests of patients, so as to promote the deepening of DRG reform.

AIM:This study aims to investigate the expression and prognostic value of ubiquitin-conjugating enzyme E2C(UBE2C)in hepatocellular carcinoma(HCC),and to explore its impact on cancer stemness and the regulato-ry mechanisms.METHODS:(1)The TCGA and GEO databases were used to analyze UBE2C mRNA expression levels in HCC tissues and their correlation with prognosis using bioinformatics techniques,and these findings were further vali-dated in postoperative specimens from 107 HCC patients.The GEPIA database was used to analyze the correlation be-tween UBE2C and steroid receptor coactivator(SRC).(2)The CCK8,colony formation,wound healing,and spheroid formation assays were used to assess the effects of UBE2C on HCC cell proliferation,migration,and stemness.The inter-action between UBE2C and signal transducer and activator of transcription 3(STAT3),as well as its regulatory mecha-nism,was examined by Western blot and co-immunoprecipitation assays.(3)The subcutaneous xenograft model in nude mice was employed to validate the role of UBE2C in tumor growth in vivo.RESULTS:(1)Bioinformatics analysis re-vealed that UBE2C expression was significantly up-regulated in HCC tissues compared with adjacent normal tissues(P<0.05 in TCGA,and P<0.01 in GEO).Consistently,analysis of HCC specimens confirmed that high UBE2C expression was associated with shortened overall survival and disease-free survival of HCC patients(P<0.05).Furthermore,analysis using the GEPIA database revealed a positive correlation between UBE2C and SRC(P<0.01).(2)In vitro experiments demonstrated that UBE2C significantly promotes the proliferation and migration of HCC cells.Based on these findings,we presumed that UBE2C may regulate the phosphorylation of STAT3 at the Y705 site by modulating SRC activity,thereby in-fluencing the stemness characteristics of tumor cells.(3)In vivo experiments further confirmed that UBE2C inhibition sig-nificantly suppressed tumor growth.CONCLUSION:The UBE2C promoted proliferation and migration of HCC cells and regulated the stemness of HCC cells by interacting with STAT3.

Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.

Objective:This study aimed to evaluate whether intra-articular delivery of conditioned medium(CM)derived from stem cells of human exfoliated deciduous teeth(SHED)could influence the progression of condylar cartilage degeneration in a rat model of temporomandibular joint osteoarthritis(TMJ OA).Methods:Sixty 8-week-old male SD rats were randomly divided into control group(CON group),intraarticular injection of MIA induced TMJ OA model group(MIA group),and injection of SHED condi-tioned medium 1 week after MIA modeling for treatment group(SHED-CM group),with 20 animals in each group.Histological sec-tions,HE,Safranine O-solid green staining,Col Ⅱ immunohistochemical staining,and TUNEL staining were performed 2 and 4 weeks after the start of treatment.Western blotting and RT-qPCR were used to detect the key molecules of apoptosis,cleaved-CASP3,BAX and BCL2,pro-inflammatory related factors IL-1β,IL-6,TNFα,MMP3,ADAMTS5,and the MAPK pathway-related molecules p-ERK,ERK,p-P38 and P38.Results:Compared with the CON group and SHED-CM group,the condyle chondrocytes in the MIA group had disordered arrange-ment,interrupted layers,significantly thickened fibrous layers(P＜0.001),and significantly increased Mankin's OA histological score(P＜0.001).In the MIA group,both the Safranin O-positive area ratio and the proportion of ColⅡ-positive regions were markedly reduced compared with the CON and SHED-CM groups(P＜0.001).Conversely,the proportion of TUNEL-positive cells was substantially higher than in the other two groups(both P＜0.001).Western blot analysis further demonstrated that apoptotic markers(cleaved-CASP3,BAX/BCL2)and MAPK pathway-related proteins(p-ERK,ERK,p-P38,P38)were expressed at significantly elevated levels in the MIA group relative to CON and SHED-CM groups(BAX/BCL2:P＜0.05;cleaved-CASP3:P＜0.01;p-P38/P38:P＜0.001;p-ERK/ERK:P＜0.01).Similarly,qRT-PCR revealed upregulated expression of inflammatory mediators,including IL-1 β(P＜0.001),IL-6(P＜0.01),TNFα(P＜0.01),MMP3(P＜0.001),and ADAMTS5(P＜0.05),in the MIA group compared with the CON and SHED-CM groups.Conclusion:SHED-CM treatment can ef-fectively reverse MIA-induced condylar cartilage degeneration of TMJ OA in rats.

At present, acute brain injuries such as stroke and traumatic brain injury have become a serious burden on public health due to relatively limited treatment methods. As an emerging three-dimensional cell culture model, cerebral organoid can well redisplay the cellular diversity, tissue structure and functional characteristics of the human brain, providing an ideal platform for disease modeling, drug development and regenerative medicine research of acute brain injury. However, the construction and application of cerebral organoid are still in the exploratory stage at present, facing major technical bottlenecks such as insufficient vascularization, lack of immune microenvironment and tissue heterogeneity. This review summarizes the cultivation technique of cerebral organoid, highlights its application in acute brain injury, and analyzes its current technical bottleneck, so as to provide more reference basis for the development and application of this technology.