Background The moderation role of environmental factors in the spread of hand-foot-and-mouth disease (HFMD) has attracted much attention, but the existing conclusions are inconsistent. For example, some scholars believe that high temperature, high humidity, and high concentrations of fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂) increase the risk of HFMD, but other scholars have reached the opposite conclusion, or believe that there is no significant relationship. Objective Based on distributed lag nonlinear model (DLNM), to investigate the relationship between the incidence of HFMD and meteorological and air pollutant variables in Lianyungang City, and to provide scientific basis for early warning. Methods Daily data of meteorological factors and air pollutants in Lianyungang City from 2021 to 2024 were retrieved. Meteorological factors included average daily temperature, average wind speed, average air pressure, and relative humidity. Air pollutant indicators included PM_2.5, inhalable particulate matter (PM₁₀), carbon monoxide (CO), sulfur dioxide (SO₂), NO₂, and ozone (O₃). Spearman correlation analysis was used to analyze their correlations with HFMD, and the R package (version 4.3.1) dlnm was used to construct a DLNM model. Results During the study period, a total of 10503 cases were reported, with a male to female ratio of 1.47∶1 and the highest proportion of scattered children (49.97%). The Spearman correlation analysis results showed that daily average temperature (r=0.40), relative humidity (r=0.17) and O₃ (r=0.14) were positively correlated with the incidence of HFMD (all Ps<0.01), while average air pressure (r=−0.34), PM_2.5 (r=−0.24), PM₁₀ (r=−0.24), CO (r=−0.22), and NO₂ (r=−0.06) were negatively correlated with it (all Ps<0.05). There was no statistical relationship of SO₂ and average wind speed with the incidence of HFMD (both Ps>0.05). The cumulative risk effect was greatest when the daily average temperature was 28.50 ℃ (CRR=4.63, 95%CI: 2.68, 8.01). The average wind speed below 0.50 m·s⁻¹ and in the range of 2.50-3.50 m·s⁻¹ showed an acute risk effect, and low pressure (below 1016.00 hPa) could immediately increase the risk of the disease. The cumulative risk effect was greatest when the relative humidity was 100% (CRR=3.16, 95%CI: 1.77, 5.65). The greatest cumulative protective effects of PM_2.5 and PM₁₀ were present at concentrations of 158.00 μg·m⁻³ (CRR=0.12, 95%CI: 0.01, 0.99) and 561.50 μg·m⁻³ (CRR=0.01, 95%CI: 0.01, 0.99) respectively. The protective effect of CO was the strongest at the highest concentration (67.00 μg·m⁻³) (RR=0.67, 95%CI: 0.34, 0.64). The cumulative protective effects of SO₂ and NO₂ were both most significant at the concentration of 0.50 μg·m⁻³. Low concentrations of O₃ (below 48.00 μg·m⁻³) showed a risk effect, and the single-day protective effect was significant when the concentration was 141.00 μg·m⁻³. Conclusion There is a nonlinear and hysteretic relationship between environmental factors and the incidence of HFMD. A rational and efficient early warning and prevention and control system can be constructed accordingly.

This article reports the diagnosis and treatment of one patient with fascioliasis of the common bile duct, aiming to provide reference for the clinical diagnosis and treatment of this disease. The patient sought medical attention due to long-term symptoms such as abdominal pain, abdominal distension, nausea, and vomiting. Imaging examinations displayed dilatation of the common bile duct and intrahepatic bile ducts, and the patient was admitted to the hospital with a diagnosis of “common bile duct stone”. Through endoscopic retrograde cholangiopancreatography and choledochoscopy, two worms were collected from the common bile duct, which were identified as Fasciola hepatica by high-throughput sequencing.

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

This study investigated the effects and action mechanism of tannins from Galla chinensis cream(TGCC) on the skin wound of rat tail. Male Sprague Dawley(SD) rats were randomly divided into a control group, model group, model+low-dose TGCC(50 mg per rat) group, model+high-dose TGCC group(100 mg per rat), and model+TGC+FAK inhibitor(Y15) cream(100 mg+10 mg per rat) group, with 10 rats in each group. After the rat tail skin injury model was successfully constructed, in the treatment group, corresponding drugs were applied to the wound surface, while in the control and model groups, the same amount of cream base as the TGCC group was applied by the same method. Then, sterile gauze was wrapped around the wound edge, and these operations were performed three times a day for 28 consecutive days. The wound healing status at the third, seventh, eleventh, fourteenth, twenty-first, and twenty-eighth days was recorded, and the wound healing rate and healing time were calculated. On the day after the last dose of medication, rat serum and tail skin wound tissue were collected for analyzing the activities of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), creatinine(CREA), urea, reactive oxygen species(ROS), interferon gamma(IFN-γ), interleukin(IL)-1β, IL-6, IL-4, IL-10, tumor necrosis factor(TNF)-α, as well as catalase(CAT), glutathione(GSH), lactate dehydrogenase(LDH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC), platelet endothelial cell adhesion molecule-1(CD31), and leukocyte differentiation antigen 34(CD34) in the wound tissue of rat tail skin. Hematoxylin-eosin, Masson, and sirius red staining were used to observe the morphological changes in the wound tissue of rat tail skin. The thickness of the epidermis, the number of fibroblasts and blood vessels, and the contents of collagen fibers, typeⅠ collagen(COLⅠ), and COLⅢ were calculated. The mRNA expressions of keratin 10(KRT10), KRT14, vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), epidermal growth factor(EGF), CD31, CD34, matrix metallopeptidase-2(MMP-2), MMP-9, COLⅠ, COLⅢ, desmin, fibroblast specific protein 1(FSP1), IFN-γ, IL-1β, TNF-α, IL-4, IL-6, and IL-10 in skin wound tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expressions of KRT10, KRT14, VEGF, FGF, EGF, MMP-2, MMP-9, COLⅠ, COLⅢ, desmin, FSP1, focal adhesion kinase(FAK), phosphorylated focal adhesion kinase(p-FAK), phosphatidylin-ositol-3-kinase(PI3K), phosphorylated phosphatidylin-ositol-3-kinase(p-PI3K), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results manifest that TGCC can dramatically elevate the healing rate of rat tail wounds and shorten wound healing time. Besides, it can reduce serum ROS levels, the contents of MDA, MPO, and LDH in the rat skin wound tissue, as well as the serum IFN-γ, IL-1β, IL-6, and TNF-α levels and the mRNA expression levels of IFN-γ, IL-1β, IL-6, and TNF-α in the skin wound tissue. It can elevate the activities of CAT, GSH, SOD, and T-AOC in wound tissue, the IL-4 and IL-10 contents in serum, and the mRNA expressions of IL-4 and IL-10 in the wound tissue. In addition, TGGC can inhibit inflammatory cell infiltration and increase the epidermal thickness, counts of fibroblasts and blood vessels, and contents of collagen fibers, COLⅠ, and COLⅢ. Besides, TGCC can elevate the mRNA and protein expressions of epidermal differentiation markers(KRT10 and KRT14), endothelial cell markers(CD31 and CD34), angiogenesis and fibroblast proliferation, differentiation markers(VEGF, FGF, EGF, COLⅠ, COLⅢ, desmin, and FSP1), reduce the mRNA and protein expressions of gelatinases(MMP-2 and MMP-9), and increase protein expressions of p-FAK, p-PI3K, p-Akt, p-mTOR, as well as ratios of p-FAK/FAK, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. These results suggest that TGCC can significantly facilitate skin wound healing, and its mechanism may be related to the activation of the FAK/PI3K/Akt/mTOR signaling pathway, inhibition of inflammatory cell infiltration in skin wound tissue, elevation of epidermal thickness, counts of fibroblasts and vessels, and contents of collagen fiber, COLⅠ, and COLⅢ, and reduction of MMP-2 and MMP-9 expressions, thus accelerating wound healing.
Animals ; Male ; Wound Healing/drug effects* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Skin/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Tannins/pharmacology* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Focal Adhesion Kinase 1/genetics*

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairments, repetitive behaviors, and restricted interests. Studies have shown that it is more prevalent in males than females. Although this issue has attracted academic attention since the 20th century, the specific mechanisms underlying the gender differences in ASD remain unclear. This paper reviews the impact of gender differences in ASD, focusing on the female protective effect, DNA methylation, hormone levels, and clinical manifestations. It also discusses corresponding treatment options, particularly suggesting improvements in the diagnostic process, which is often overlooked, in order to provide valuable references for the clinical diagnosis and treatment of ASD.
Humans ; Autism Spectrum Disorder/genetics* ; Female ; Male ; DNA Methylation ; Sex Factors ; Sex Characteristics

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

Objectives: To elucidate the potential mechanisms of electroacupuncture (EA) in restoring detrusor-bladder neck dyssynergia (DBND) following suprasacral spinal cord injury (SSCI). Methods: A total of 52 specific pathogen-free (SPF) grade famale Sprague-Dawley (SD) rats (10 – 12 weeks, 250 – 280 g) were randomly assigned to either a sham group (n = 12) or a spinal cord injury model group (n = 40). In the model group, DBND was induced through Hassan Shaker spinal cord transection at T10 level, with 24 rats meeting inclusion criteria and subsequently randomized into DBND group (n = 12) and EA intervention group (DBND + EA group, n = 12). After spinal shock recovery (day 19 after modeling), DBND + EA group received EA treatment at Ciliao (BL32), Zhongji (RN3), and Sanyinjiao (SP6) acupoints for 20 min per session at 10/50 Hz frequencies, once daily for 10 d. Sham and DBND groups received anesthesia only without EA intervention. On day 29 post-modeling, all rats underwent urodynamic assessments, followed by hematoxylin and eosin (HE) staining, tandem mass tag (TMT) proteomics, and Western blot (WB) analysis of detrusor and bladder neck tissues. Differentially expressed proteins (DEPs) were defined as proteins with P < 0.05, unique peptides ≥ 2, and fold change > 1.2 or < 0.83. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using KOBAS 3.0 (P < 0.01), and protein-protein interaction (PPI) networks were analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) 11.5 and Cytoscape 3.9.1. Results: Compared with sham group, DBND group showed significantly elevated leak point pressure (LPP) and maximum cystometric capacity (MCC) (both P < 0.01). EA treatment significantly reduced both LPP and MCC compared with DBND group (P < 0.01 and P < 0.05, respectively). HE staining revealed that EA reduced detrusor fibrosis and improved bladder neck inflammation. TMT proteomics identified 30 overlapping DEPs in detrusor and 59 overlapping DEPs in bladder neck when comparing DBND + EA/DBND groups with sham group. In detrusor tissue, KEGG analysis revealed 10 significantly enriched pathways (P < 0.01), including mitogen-activated protein kinase (MAPK) signaling pathway. PPI analysis showed 22 of 30 DEPs were interconnected. In bladder neck tissue, 14 pathways were significantly enriched (P < 0.01), including relaxin signaling pathway, with 51 of 59 DEPs showing interconnections. Both TMT and WB validations demonstrated that compared with sham controls, DBND rats exhibited upregulated collagen type IV alpha 2 chain (Col4a2) and downregulated guanine nucleotide-binding protein G(z) subunit alpha (Gnaz) in detrusor tissue, while EA treatment normalized both proteins (both P < 0.05). In bladder neck tissue, DBND rats showed decreased expression of smoothelin (Smtn) and calcium-activated potassium channel subunit beta-1 (Kcnmb1) compared with sham controls (both P < 0.01), which were both upregulated following EA treatment (P < 0.01 and P < 0.05, respectively). Conclusion EA restores detrusor-bladder neck coordination in DBND through dual-target mechanisms. In detrusor tissue, EA modulates contraction via extracellular matrix remodeling, cyclic adenosine monophosphate (cAMP) signaling pathway regulation, and enhanced adenosine triphosphate (ATP) biosynthesis mediated by neurotransmitters. In bladder neck tissue, EA promotes relaxation by maintaining contractile phenotypes, reducing fibrosis, suppressing smooth muscle excitation, and regulating presynaptic neurotransmitter release. These findings provide mechanistic insights into EA's therapeutic role in managing DBND.

OBJECTIVE Aimed at investigating whether reflux pharyngitis is an independent risk factor for the failure of type Ⅰ tympanoplasty for chronic otitis media.This is achieved by analyzing the relationship between the postoperative tympanic membrane healing in patients who underwent type Ⅰ tympanoplasty and pharyngolaryngeal reflux finding score(RFS).METHODS Patients who underwent type Ⅰ tympanoplasty in the Department of Otolaryngology Head and Neck Surgery,Nanshan People's Hospital,Shenzhen,China,from January 2023 to July 2024 were retrospectively included.All the patients received preoperative perfect nasal endoscopy,laryngoscopy,evaluation by the RFS questionnaire,preoperative otoscopy for tympanoplasty,pure tone hearing threshold,and temporal bone thin-layer CT examination.Postoperative otoscopic examination was performed to observe tympanic membrane healing and followed up for 3 months.The patients were divided into surgery success group and failure group based on the criterion of whether a complete tympanic membrane was formed by endoscopic examination within 3 months.The RFS scores of the two groups were statistically analyzed.RESULTS A total of 135 patients with an average age of 44.78 years(±12.22 years)took part in this study,with 60 males and 75 females included,and 68 left ears and 67 right ears involved.There were 120 patients in the surgery success group,and 15 patients in the failure group.Statistical analysis revealed that the RFS score of the patients in the tympanoplasty failure group was remarkably higher than that of the patients in the tympanoplasty success group.Moreover,there were significantly more cases with suspected reflux pharyngitis in the surgery failure group(P=0.007).Reflux-induced tympanic membrane lesion and reperforation mostly occurred in the central part of the tympanic membrane graft.CONCLUSION Reflux pharyngitis has been implicated with tympanoplasty failure,and thus may be a causative factor.Additionally,the RFS can be used to screen patients with chronic suppurative otitis media for suspected reflux pharyngitis.Findings from this work indicate that perioperative anti-reflux therapy,combined with dietary and lifestyle counselling for the patients who suffer from reflux pharyngitis and are about to undergo the tympanoplasty surgery may improve surgical success rate.

Purpose This study aims to analyze the clinical,pathological,and molecular genetic characteristics of nodal follicular helper T-cell lymphoma,follicular type(nTFHL-F).Methods 7 cases of nTFHL-F were re-viewed.Clinical data were collected,tissue morphology was summarized,and immunohistochemical staining and mo-lecular testing were performed.Results The median age of patients was 62 years with a male-to-female ratio of 6:1.The initial symptoms included neck lymphadenectasis in 6 cases and abdominal discomfort in one.Six cases were in ad-vanced stages,while 1 case was in the localized stage.The tumors exhibited a vague,irregular follicular nodular pat-tern,without significant polymorphic inflammatory background or high endothelial vascular proliferation.Five cases showed a progressive transformation resembling germinal center pattern,and two cases exhibited a follicular lymphoma-like growth pattern.Tumor cells presented three distinct morphologies:centrocyte-like appearance,monocytoid B cell-like appearance,and atypical cells with abundant,transparent cytoplasm.Tumor cells expressed at least three follicu-lar T-cell markers.Testing for ITK::SYK gene fusion was negative in all cases(0/7).Next generation sequencing i-dentified mutations in TET2 gene in two cases(2/2),the RHOA gene in one case(1/2),and VAV1 gene in one case(1/2).The follow-up duration ranged from 2 to 64 months,with three deaths(3/7),and a median survival time of 37 months.Conclusion nTFHL-F predominantly occurs in middle-aged to elderly males,presenting with advanced clinical stages,and has a poor prognosis.nTFHL-F is closely associated with nodal follicular helper T-cell lymphoma,angioimmunoblastic type,and mya coexist within the same individual.