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.

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.

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

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.

Objective:To investigate the immunological mechanism by which grifola frondosa extract improves colonic tissue inflammation in rats with ulcerative colitis(UC)through the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)signaling pathway.Methods:Forty male SD rats were randomly divided into five groups:blank group,model group,sulfasalazine treatment group(SASP group),grifola frondosa extract treatment group(GF group),and sulfasalazine combined with grifola frondosa extract treatment group(SASP+GF group).UC model was established using a 3%dextran sulfate sodium(DSS)free drinking method.After one week,each treatment group received sulfasalazine 0.3 g/(kg·d),grifola frondosa extract 10 mg/(kg·d),and combination of both drugs by gavage.During the experiment,the general condition of the rats was observed,the disease activity index(DAI)score was re-corded and the protein content and positive expression levels of SPHK1,S1P,tumor necrosis factor receptor-associated factor 2(TRAF2)and TNF-α in rat colon tissue were detected by immunohistochemistry.mRNA and protein expression levels of SPHK1,S1P,TRAF2 and TNF-α in rat colon tissue were measured by RT-qPCR and Western blot.Results:Compared with the blank group,the general condition of the model group rats were poor,the DAI score was significantly increased,and the protein positive expres-sion,mRNA and protein expression levels of SPHK1,S1P,TRAF2 and TNF-α in colon tissue were significantly increased(P<0.01).Compared with the model group,the general condition of the rats in each treatment group improved significantly,the DAI score was decreased(P<0.01),and the positive expression of each target protein was significantly reduced(P<0.01),especially in the GF group and SASP+GF group;the mRNA and protein expression levels of SPHK1 and TRAF2 were reduced to varying degrees(P<0.01 or P<0.05),while the mRNA and protein expression levels of S1P and TNF-α only decreased significantly in the GF group and SASP+GF group(P<0.01).Compared with the SASP group,the GF group only showed a decrease in SPHK1 protein expression,TNF-α mRNA,and protein expression levels,while the SASP+GF group showed significant reductions in all targets(P<0.01 or P<0.05).Compared with the GF group,the SASP+GF group showed significant reductions in SPHK1 protein positive expression and content,S1P mRNA expression levels,and TNF-α protein content(P<0.05 or P<0.01).Conclusion:Grifola frondosa extract may alleviate co-lonic tissue inflammation in rats with UC by inhibiting the activation of the SPHK1/S1P pathway,restoring intestinal mucosal barrier function,and improving symptoms of UC.

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.

Objective To explore the effects of probiotic-assisted conventional treatment on in-testinal flora,blood glucose homeostasis and neurological function in patients with type 2 diabetes mellitus complicated with stroke.Methods A total of 93 patients with type 2 diabetes mellitus com-plicated by stroke were selected as the study subjects and randomly divided into control group(n=46)and experimental group(n=47)using random number table method.The control group received conventional therapy,while the experimental group received probiotics(oral Bifidobacterium,Lacto-bacillus,and Enterococcus triple viable tablets,4 tablets/time,twice daily)in addition to convention-al therapy.Both groups were treated continuously for 7 days.The intestinal flora(counts of Bifidobacterium,Lactobacillus and Bacteroides),inflammatory markers[tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and high-sensitivity C-reactive protein(hs-CRP)],glycemic pa-rameters[fasting blood glucose(FBG),glycosylated hemoglobin(HbA1c),largest amplitude of glycemic excursions(LAGE),average blood glucose(BGL-ave),standard deviation of mean blood glucose(BGL-sd),and coefficient of variation of blood glucose(BG-cv)],and neurological function[National Institutes of Health Stroke Scale(NIHSS)score,improvement rate of neurological func-tion,proportion of patients with modified Rankin Scale(mRS)score ≤ 3,and Loewenstein Occupa-tional Therapy Cognitive Assessment(LOTCA)score]were compared between the two groups after treatment.Results After treatment,the counts of intestinal flora(Bifidobacterium,Lactobacillus,and Bacteroides)in both groups were higher than those before treatment,and the counts in the ex-perimental group were higher than those in the control group,with statistically significant differences(P＜0.05).The levels of TNF-α,IL-6 and hs-CRP in both groups were lower than those before treatment,and the levels in the experimental group were lower than those in the control group,with statistically significant differences(P＜0.05).The levels of FBG and HbA1c in both groups were lower than those before treatment.The FBG level,LAGE,BGL-sd,and BG-cv in the experimental group were lower than those in the control group,with statistically significant differences(P＜0.05),but there were no statistically significant differences in HbA1c and BGL-ave between the two groups(P＞0.05).After treatment,the NIHSS score in the experimental group was lower than that in the control group,while the LOTCA score and improvement rate of neurological function were higher than those in the control group,with statistically significant differences(P＜0.05).There was no statistically significant difference in the proportion of patients with an mRS score ≤3 between the two groups(P＞0.05).Conclusion Probiotic-assisted conventional treatment can regulate the number of intestinal flora in patients with type 2 diabetes mellitus complicated with stroke,relieve inflammatory responses,stabilize blood sugar levels,and improve neurological function.