Objective: To analyze the epidemiological characteristics and trends of other infectious diarrhea among children under 18 years old in Guangzhou City from 2014 to 2020, and to explore the correlation between climatic factors and the incidence of the disease, so as to provide reference for the early prevention of infectious diseases. Methods: The data of cases of other infectious diarrhea and meteorological data of children under 18 years old in Guangzhou City from 2014 to 2020 were collected through the Chinese Infectious Disease Reporting System and the Guangzhou Meteorological Bureau. The correlation between meteorological factors and the incidence of other infectious diarrhea was analyzed using negative binomial regression. Results: A total of 104 566 cases of other infectious diarrhea among children under 18 years old were reported in Guangzhou City from 2014 to 2020, with a male to female ratio of 1.48∶1. The incidence rate was the highest in 2017 (980.83 per 100 000) and the lowest in 2020 (388.22 per 100 000). The peak of incidence occurred from October to March of the following year. Children under 5 years old accounted for 87.95% of all cases. The number of cases of other infectious diarrhea was negatively correlated with the temperature of the previous 6 days ( IRR = -0.07 ), and positively correlated with the temperature difference on the day of onset ( IRR =0.02) (both P <0.05). It was also positively correlated with the wind speed of the previous 7 days ( IRR=0.07, P <0.05), but there was no statistically significant correlation with the relative humidity on the day of onset ( IRR=-0.00, P >0.05). Conclusions Low temperature, large temperature difference, and high wind speed can increase the risk of other infectious diarrhea. It is necessary to strengthen the prediction and early warning in conjunction with meteorological changes, and warn kindergartens and schools to enhance preventive measures against the clustering of other infectious diarrhea cases.

Neurofibromatosis type 1 (NF1) presents with a diverse range of symptoms that can affect the skin, bones, eyes, central nervous system, and other organs. This article reports the diagnosis and treatment process of a patient with NF1 complicated by bilateral severe-to-profound sensorineural hearing loss. Genetic testing revealed a heterozygous variant of NF1 NM_ 000267.3: c.4054_ 4058del(p.Ser1352LeufsTer20, supporting the diagnosis of NF1. After thorough evaluation, a right cochlear implantation was performed, yielding satisfactory postoperative results. This case suggests that NF1 patients may exhibit phenotypic heterogeneity and atypicality, providing a reference for clinicians in the diagnosis and treatment of such patients.

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

OBJECTIVES: To investigate the role of DTX2 in regulating biological behaviors of oxaliplatin-resistant colorectal cancer cells (CRC/OXA cells). METHODS: CCK8 assay was used to determine the inhibition rate of oxaliplatin-treated CRC cells. A CRC/OXA cell line was constructed, in which DTX2 expression level was detected. The cells were transfected with a DTX2-shRNA plasmid or co-transfected with DTX2-shRNA and pcDNA-Notch2, and the changes in cell proliferation, migration and invasion ability were evaluated using plate cloning assay, scratch assay and Transwell invasion assay. The expression levels of Notch2, NICD and epithelial-mesenchymal transition (EMT) proteins of the transfected cells were detected with Western blotting. In a nude mouse model bearing SW620/OXA cell xenografts, the effects of DTX2 knockdown and Notch2 overexpression in the implanted cells on tumor growth and protein expressions were tested. RESULTS: The IC₅₀ of oxaliplatin was 6.00 μmol/L in SW620 cells and 8.00 μmol/L in LoVo cells. CRC/OXA cells showed a significantly increased expression of DTX2. DTX2 knockdown in CRC/OXA cells significantly inhibited cell proliferation, migration and invasion, and these effects were reversed by co-transfection of the cells with pcDNA-Notch2. DTX2 knockdown significantly reduced the expression levels of Notch2, NICD and vimentin proteins and increased E-cadherin expression in CRC/OXA cells, and co-transfection with pcDNA-Notch2 potently attenuated the changes in these proteins. In the tumor-bearing mice, DTX2 overexpression obviously promoted the growth of SW620/OXA cell xenograft, enhanced the protein expressions of Notch2, NICD and vimentin, and lowered the expression of E-cadherin. CONCLUSIONS High expression of DTX2 promotes proliferation, migration, invasion and EMT of CRC/OXA cells through the Notch2 signaling pathway, suggesting the potential of DTX2 as a target to improve the efficacy of oxaliplatin.
Epithelial-Mesenchymal Transition ; Humans ; Cell Proliferation ; Oxaliplatin ; Colorectal Neoplasms/metabolism* ; Animals ; Drug Resistance, Neoplasm ; Receptor, Notch2/metabolism* ; Cell Line, Tumor ; Mice, Nude ; Cell Movement ; Organoplatinum Compounds/pharmacology* ; Neoplasm Invasiveness ; Mice

Background Recent advances in understanding the toxic effects of inorganic arsenic have revealed that arsenic exposure impacts multiple endocrine organs, thereby altering their functions. However, the mechanisms underlying arsenic-induced thyroid injury remain unclear. Objective To investigate the mechanisms by which sodium arsenite (NaAsO₂) affects the proliferation and apoptosis of normal thyroid cells (Nthy-ori3-1) through the estrogen receptor (ER)-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods Nthy-ori3-1 cells were cultured in vitro and divided into the following groups: a control group (complete medium without drugs, 0 μmol·L⁻¹), and NaAsO₂-treated groups at 1, 2, and 4 μmol·L⁻¹. Additionally, 1 μmol·L⁻¹ of the ER inhibitor ICI182780 was used to intervene in the NaAsO₂ exposure groups, resulting in the following combinations: 1 μmol·L⁻¹ NaAsO₂ + ICI182780, 2 μmol·L⁻¹ NaAsO₂ + ICI182780, and 4 μmol·L⁻¹ NaAsO₂ + ICI182780. The median lethal concentration of NaAsO₂ was determined using cell viability assay. Cell viability was assessed at 24, 36, and 48 h using Cell Counting Kit-8 (CCK-8) assay. Colony formation ability was evaluated via plate cloning assay. Apoptosis was detected using Hoechst 33342 staining. Protein and mRNA expression levels of ERα, ERβ, c-MYC, Bax, Bcl-2, PI3K, p-PI3K, AKT, and p-AKT were measured using Western blot (WB) and real-time quantitative PCR (qRT-PCR), respectively. Results The median lethal concentration of NaAsO₂ was determined to be 4.034 μmol·L⁻¹. CCK-8 assay at 24, 36, and 48 h revealed that, compared with the control group, the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups significantly inhibited Nthy-ori3-1 cell proliferation (P < 0.001). The plate cloning assays demonstrated a concentration-dependent reduction in colony formation ability (P < 0.001). Following the ICI182780 intervention, the cell viability and colony formation ability in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups were significantly restored compared with the corresponding NaAsO₂-only groups (P < 0.001, P < 0.01). The Hoechst 33342 staining indicated that compared with the control group, the nuclear staining intensity and apoptosis levels in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups increased in a concentration-dependent manner (P < 0.001). However, the ICI182780 intervention reduced the apoptosis levels in the NaAsO₂-treated groups compared with their NaAsO₂-only counterparts (P < 0.001). The WB analysis showed that, compared with the control group, the protein expression of ERα, ERβ, c-MYC, Bcl-2, p-PI3K, and p-AKT in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups decreased manner (P < 0.001, P < 0.01), while the Bax expression increased in a concentration-dependent (P < 0.001); the PI3K and AKT protein levels showed no significant differences (P > 0.05). In the ICI182780-treated NaAsO₂ groups, the ERα, ERβ, c-MYC, Bcl-2, p-PI3K, and p-AKT protein expression increased (P < 0.001, P < 0.01), the Bax expression decreased (P < 0.001), and the PI3K and AKT levels remained unchanged (P > 0.05) compared with the corresponding NaAsO₂-only groups. The mRNA expression patterns of ERα, ERβ, c-MYC, Bcl-2, and Bax were consistent with the WB results. Conclusion NaAsO₂ inhibits proliferation and promotes apoptosis in Nthy-ori3-1 cells in a dose-dependent manner. The underlying mechanism likely involves NaAsO₂-mediated suppression of the ER-PI3K/AKT signaling pathway, which subsequently regulates downstream proliferation- and apoptosis-related genes.

Objective:To explore the influencing of 18F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) indicators on microvascular invasion (MVI) of hepatocellular carcinoma and to construct a nomogram for predicting MVI. Methods:The data of 125 patients with hepatocellular carcinoma who underwent 18F-FDG PET/CT from January 2012 to March 2024 in the Second Xiangya Hospital of Central South University were retrospectively collected and analyzed. There were 108 males and 17 females, with the age of (51.8±7.6) years. The 125 patients were divided into MVI negative group ( n=51) and MVI positive group ( n=74) according to whether MVI was positive. The two groups were compared in terms of liver cirrhosis, aspartate transaminase (AST), γ-glutamyltransferase, carbohydrate antigen 125, Ki-67, maximum tumor diameter, tumor capsule, combined portal vein tumor thrombus, and 18F-FDG PET/CT indicators maximum standard uptake value (SUVmax), tumor metabolic volume, total glycolysis of lesions, tumor-liver ratio (TLR), and tumor-mediastinum ratio. Multivariate logistic regression was used to analyze the influencing factors of MVI, and a nomogram MVI prediction model was constructed. Results:Cirrhosis, AST >40 U/L, γ-glutamyltransferase >60 U/L, carbohydrate antigen 125>35 U/ml, Ki-67 >20%, maximum tumor diameter, tumor capsule, combined portal vein tumor thrombus, SUVmax >6.30, tumor metabolic volume >45.48, total glycolysis of lesions >253.22, TLR >2.39, tumor-mediastinum ratio >4.27 were associated with MVI in patients with hepatocellular carcinoma (all P<0.05). Multivariate logistic regression analysis showed that combined portal vein tumor thrombus ( OR=40.244, 95% CI: 5.276-306.986), SUVmax >6.30 ( OR=3.920, 95% CI: 1.841-8.346), tumor metabolic volume>45.48 ( OR=6.482, 95% CI: 2.914-14.415), TLR>2.39 ( OR=7.250, 95% CI: 3.247-16.188) were influencing factors of MVI in patients with hepatocellular carcinoma (all P<0.05). A nomogram for predicting MVI was constructed based on the multivariate results. Conclusion:18F-FDG PET/CT index SUVmax, tumor metabolic volume, and TLR are influencing factors for MVI of hepatocellular carcinoma patients. Based on these influencing factors, a nomogram model for predicting MVI can be constructed.

Objective:To investigate the application value of 68Ga-Pentixafor PET/CT targeting CXC subfamily receptor 4 (CXCR4) in the subtyping and precise localization of primary aldosteronism (PA). Methods:Thirty-three patients with PA confirmed by clinical examination and undergoing 68Ga-Pentixafor PET/CT and adrenal vein sampling (AVS) in the Second Xiangya Hospital between July 1st 2022 and July 1st 2023 were prospectively enrolled (24 males, 9 females, age (49.6±10.3) years). Patients with a dominant side identified by PET/CT or AVS underwent unilateral adrenalectomy, while those without a dominant side received medical treatment. According to the standard of PA surgical outcome (PASO), patients underwent surgery were divided into unilateral PA (UPA) and bilateral PA (BPA) based on the pathological and follow-up results. Those who received medical treatment were BPA. The diagnostic efficacy of 68Ga-Pentixafor PET/CT for UPA was calculated. The ROC curve was constructed to analyze the accuracy and optimal threshold of SUV max, the ratio of lesion SUV max to contralateral adrenal tissue SUV mean (LCR), and the ratio of lesion SUV max to liver SUV mean (LLR) in the diagnosis of PA subtype. The correlation between the quantitative parameters and the clinical features and lesion width of the patients was evaluated by Spearman rank correlation analysis. The differences of LCR and LLR between different efficacy groups were compared by the independent-sample t test. Results:A total of 20 patients underwent unilateral adrenalectomy. Nineteen patients were finally diagnosed with UPA and 14 with BPA. The agreement rate of PET/CT and AVS was 81.8%(27/33), and both methods independently detected UPA that was negative in the other examination. The sensitivity, specificity, and accuracy of 68Ga-Pentixafor PET/CT visual diagnosis of UPA were 18/19, 14/14, and 97.0%(32/33), respectively. ROC curve showed that the AUC of LLR for subtype diagnosis was 0.944, with the optimal threshold of 3.1. SUV max, LCR, and LLR were positively correlated with aldosterone concentration ( rs values: 0.35, 0.47, and 0.36, all P<0.05) and lesion width ( rs values: 0.43, 0.49, and 0.58, all P<0.05). The LCR (3.9±2.2 vs 1.6±0.3; t=2.00, P=0.041) and LLR( 8.7±4.1 vs 4.2±1.3; t=2.06, P=0.045) of the dominant side lesions in patients who achieved complete biochemical and clinical cure were higher than those in patients with partial improvement. Conclusions:68Ga-Pentixafor PET/CT imaging can be used in the diagnosis and precise localization of PA subtype. It also can detect patients with PA which can be surgically cured but not detected by AVS, and the quantitative analysis may be valuable for prognosis prediction.

Objective:To analyze the prevalence and clinical characteristics of pertussis in children with different cough durations.Methods:From January 2021 to October 2022, information on children aged 0-18 years who visited eight hospitals in Shandong Province due to cough was enrolled. Pertussis serological antibody testing and/or nucleic acid testing were performed. The prevalence and clinical characteristics of pertussis were compared among the acute cough group, protracted cough group, and chronic cough group using the χ2 test or Fisher′s exact test. Results:A total of 1 565 children with cough were included in the study, of which 348 (22.24%) were laboratory-confirmed pertussis. There was a significant difference in the laboratory-confirmed rate of pertussis among different cough groups ( χ2=83.424, P<0.001). The confirmation rate of pertussis in the protracted cough group (42.21%) was significantly higher than that in the acute cough group (16.49%, P<0.05) and chronic cough group (19.50%, P<0.05). In each cough group, the age of children was significantly associated with the confirmed rate of pertussis, and the confirmed rate was relatively high in children aged 3 months to <2 years. Pertussis vaccination was significantly associated with the confirmed rate in all groups, and the confirmed rate was higher in unvaccinated children. Among laboratory-confirmed pertussis cases, the incidence of typical symptoms such as paroxysmal cough, whoop, and post-tussive emesis or sleep disturbance was significantly higher than that in the non-confirmed cases. In the protracted and chronic cough groups, the proportion of non-confirmed cases complicated with asthma/cough variant asthma (CVA) was significantly higher than that in pertussis-confirmed cases. Conclusion:There are differences in the confirmation rate of pertussis among children with different cough durations. The confirmation rate is significantly associated with age, vaccination status, and clinical symptoms. Enhancing clinical vigilance against pertussis, conducting early diagnosis, and getting timely and standardized vaccination are crucial for effectively controlling pertussis and preventing outbreaks.

Objective:This study aimed to analyze the infection status of viral viruria within one year after kidney transplantation, its impact on renal allograft function, and associated risk factors.Methods:A retrospective case-control study was conducted, involving 370 patients who underwent allogeneic kidney transplantation at Renji Hospital, Shanghai Jiao Tong University School of Medicine, from January 1, 2020 to December 31, 2021. Urinary viral loads of BK virus (BKV), JC virus (JCV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were detected using PCR fluorescent probe assays. Patients were categorized into infection and non-infection groups. Glomerular filtration rate (GFR) and tacrolimus trough concentration was measured during infections, and clinical data were collected. Univariate analysis was performed to identify risk factors for viral viruria.Results:The 1-year patient survival rate and graft survival rate were both 98.6%. The incidence rates of viral viruria were as follows: JCV (42.7%), BKV (29.7%), CMV (11.6%), and EBV (2.9%), with statistically significant differences among viruses ( P<0.001). Single viral infection accounted for 48% of cases, while co-infections were predominantly BKV+JCV (9%). JCV infection rates remained consistently high throughout the year (22.4%-28.9%), whereas BKV infections peaked at 3 months postoperatively (20.5%). Co-infection with low-load JCV (>2 000 copies/ml) and CMV (>6 000 copies/ml) led to a significant decline in GFR at 6 months post-transplantation [median difference: 16.7 ml/(min×1.73 m2), P=0.019]. Univariate analysis revealed that elevated tacrolimus trough concentration was independent risk factor for BKV (4.90 vs. 4.30 ng/ml, Z=4.29, P<0.001) and JCV infections (5.30 vs. 4.80 ng/ml, Z=4.25, P<0.001). Conclusion:High incidences of JCV and BKV infections were observed post-kidney transplantation. Co-infection with low-load JCV and CMV accelerates renal function impairment, highlighting the critical role of tacrolimus concentration management in reducing viral infection risks.

Objective:To identify key risk factors for bloodstream infection (BSI) within 30 days after liver transplantation and to develop an etiological model to predict BSI pathogens based on these factors.Methods:A retrospective study enrolled 122 patients who underwent blood culture after liver transplantation at Renji Hospital, School of Medicine, Shanghai Jiao Tong University from July 2021 to March 2025. Patients were classified into a blood culture positive group ( n=87), comprising non-fermenting Gram-negative bacilli (e.g., Pseudomonas, Acinetobacter, n=8), fungi ( n=8), Staphylococcus ( n=27), Enterobacteriaceae ( n=30), and Enterococcus ( n=14) and a blood culture negative group ( n=35). Baseline variables and laboratory parameters obtained within 24 h of admission and during the postoperative course were subjected to univariate and multivariate analyses to identify risk factors and infection characteristics.Machine learning models for etiological prediction were then developed using these variables. Results:Among the 87 positive cultures, Enterobacterales (30/87, 34.48%) and Staphylococcus (27/87, 31.03%) were the main pathogens. Whithin these two categories of pathogens, Staphylococcus epidermidis and Klebsiella pneumoniae were the primary species, respectively. Autoimmune liver disease was more prevalent in the blood-culture-positive group than in the negative group ( χ2=4.05, P=0.044). The distribution of pathogenic bacteria causing BSI after liver transplantation has certain clinical characteristics. Six-eighths of patients with non-fermenting Gram-negative BSI had underlying malignancies.Among Enterococcal and Enterobacterales BSI cases, viral hepatitis (5/14; 8/30, 26.7%) and autoimmune hepatitis (2/14; 6/30, 20.0%) were more common. The area under curve values of the LightGBM, support vector machine (SVM), and neural network models were all greater than 0.90, indicating that these three models all have high predictive value for the types of pathogens causing bloodstream infections after liver transplantation. Conclusion:The etiological distribution of BSI after liver transplantation exhibits distinct clinical characteristics, LightGBM, SVM and neural network models effectively integrate multi-dimensional data to predict pathogen types, thereby informing infection-prevention and control strategies. Limitations include single-center design and small sample size. Multicenter prospective studies are warranted to validate the model′s efficacy in future research.