ObjectiveTo investigate the association between single and combined exposure to arsenic （As）， mercury （Hg）， and cadmium （Cd） in urine and hearing loss in adults. MethodsA total of 400 adult patients were recruited for the study， comprising 200 participants in the normal hearing group and 200 in the hearing loss group. General demographic information of the study subjects was collected by a self-administered questionnaire， morning urine samples were tested for As， Hg， and Cd concentrations， and hearing status was assessed by Pure Tone Audiometry. A binary Logistic regression model was used to explore the association between the concentrations of the three metals in urine and hearing loss， and a Bayesian kernel-machine regression （BKMR） model was used to further explore the association between the concentrations of the three metal mixtures and hearing loss. ResultsAfter correction for urinary creatinine， As， Hg， and Cd concentrations were higher in the hearing loss group than those in the normal hearing group （P<0.05）. Binary Logistic regression indicated that concentrations of As， Hg， and Cd were positively associated with hearing loss， and the risk of hearing loss was significantly higher in the second quartile of Cd concentration compared to the first quartile （OR=2.000， 95%CI： 1.009-3.964）. BKMR modeling analysis showed that the combined exposure levels of As， Hg， and Cd significantly increased the risk of hearing loss， with Cd being the most important contributor （posterior inclusion probability=0.412）， and that there were potential interactions between As and Cd， and Cd and Hg. ConclusionCombined exposure to As， Hg， and Cd in urine is significantly associated with adult hearing loss， with Cd being the primary contributor in the exposure combination. The interactions between As and Cd， as well as Cd and Hg， may have adverse effects on hearing loss.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.

Objective:To analyze the relationship between the optimal surgical margin value and clinical prognosis of transoral robotic surgery（TORS） in treating human papillomavirus（HPV） -positive oropharyngeal squamous cell carcinoma. Methods:A single-center, prospective, observational cohort study was conducted, enrolling patients with early and moderated stage（≤T3 stage） oropharyngeal carcinoma undergoing TORS between July 2020 and April 2024. The proposed optimal surgical margin cutoff value for TORS was set as 2 mm. The primary objectives were to evaluate the optimal clear margin for TORS and its association with overall survival（OS） and progression-free survival（PFS）. Logistic regression was used to analyze correlations between surgical margins and clinical variables, while Cox regression models assessed the impact of surgical margins on OS and PFS. Results:A total of 90 patients（60 males, 66.7%） were included, all had squamous cell carcinoma, with a mean age of 58.0±9.0 years（range: 39-84 years） old. The 1, 2 and 3-year OS rates were 92.3%, 89.9% and 85.0%, respectively, while the 1, 2 and 3-year PFS rates were all 90.1%. For surgical margins ≤2 mm, the 1, 2 and 3-year OS rates were 80.8%, 69.3% and 69.3%, respectively, and PFS rates were 77.9% across three time points. For surgical margins>2 mm, the 1, 2 and 3-year OS rates were 96.5%, 96.5% and 90.6%, respectively, with PFS rates of 94.6%. Logistic regression showed no correlation between surgical margins and tumor type, T/N stage, smoking, alcohol use, or gender（P>0.05）. Cox analysis identified surgical margins>2 mm as a significant factor improving PFS（HR=0.14, 95%CI 0.02-0.90, P=0.038）. Conclusion:This systematic analysis suggests setting a 2 mm and longer as clear surgical margin for TORS. Margins>2 mm are associated with superior postoperative PFS rate and prolonged PFS time in HPV-positive oropharyngeal carcinoma patients.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Carcinoma, Squamous Cell/virology* ; Human Papillomavirus Viruses/isolation & purification* ; Margins of Excision ; Oropharyngeal Neoplasms/virology* ; Papillomavirus Infections/virology* ; Prognosis ; Prospective Studies ; Robotic Surgical Procedures/methods*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

Methods: From March 2020 to March 2023, 100 inpatients with DS were classified into groups A, B, C, and D based on the CARDS classification system. Preoperative radiological data were analyzed to measure the severity of central canal stenosis, facet joint arthropathy, intervertebral disc herniation, and spinal epidural lipomatosis, osteophyte formation, range of motion (ROM), and computed tomography value of the vertebral bodies. The radiological characteristics and clinical contraindications for OLIF were compared among the groups. Results: Of the 100 patients, 51% had clinical contraindications for OLIF, which included 85%, 25%, 62.5%, and 20% of patients in groups A, B, C, and D, respectively. Compared with group B, group A demonstrated greater severity of central canal stenosis, whereas group C showed a higher degree of facet joint arthropathy. More patients in groups A and C had severe central canal stenosis. Regarding the ROM results, group A had segmental stiffness, whereas group D presented relatively unstable slip segments. Conclusions Patients with different DS subtypes have varied radiological characteristics. Groups B and D are suitable candidates for OLIF. Most patients in group A are unsuitable for OLIF because of bony hyperplasia, severe spinal stenosis, and segmental stiffness.

Methods: From March 2020 to March 2023, 100 inpatients with DS were classified into groups A, B, C, and D based on the CARDS classification system. Preoperative radiological data were analyzed to measure the severity of central canal stenosis, facet joint arthropathy, intervertebral disc herniation, and spinal epidural lipomatosis, osteophyte formation, range of motion (ROM), and computed tomography value of the vertebral bodies. The radiological characteristics and clinical contraindications for OLIF were compared among the groups. Results: Of the 100 patients, 51% had clinical contraindications for OLIF, which included 85%, 25%, 62.5%, and 20% of patients in groups A, B, C, and D, respectively. Compared with group B, group A demonstrated greater severity of central canal stenosis, whereas group C showed a higher degree of facet joint arthropathy. More patients in groups A and C had severe central canal stenosis. Regarding the ROM results, group A had segmental stiffness, whereas group D presented relatively unstable slip segments. Conclusions Patients with different DS subtypes have varied radiological characteristics. Groups B and D are suitable candidates for OLIF. Most patients in group A are unsuitable for OLIF because of bony hyperplasia, severe spinal stenosis, and segmental stiffness.

Methods: From March 2020 to March 2023, 100 inpatients with DS were classified into groups A, B, C, and D based on the CARDS classification system. Preoperative radiological data were analyzed to measure the severity of central canal stenosis, facet joint arthropathy, intervertebral disc herniation, and spinal epidural lipomatosis, osteophyte formation, range of motion (ROM), and computed tomography value of the vertebral bodies. The radiological characteristics and clinical contraindications for OLIF were compared among the groups. Results: Of the 100 patients, 51% had clinical contraindications for OLIF, which included 85%, 25%, 62.5%, and 20% of patients in groups A, B, C, and D, respectively. Compared with group B, group A demonstrated greater severity of central canal stenosis, whereas group C showed a higher degree of facet joint arthropathy. More patients in groups A and C had severe central canal stenosis. Regarding the ROM results, group A had segmental stiffness, whereas group D presented relatively unstable slip segments. Conclusions Patients with different DS subtypes have varied radiological characteristics. Groups B and D are suitable candidates for OLIF. Most patients in group A are unsuitable for OLIF because of bony hyperplasia, severe spinal stenosis, and segmental stiffness.

Objective:To investigate the plasma level of interleukin(IL)-37 and assess its regulatory effects on monocyte activity in type 1 diabetes mellitus(T1DM) patients.Methods:This prospective study included 57 T1DM patients and 21 healthy controls who were continuously enrolled from December 2022 to January 2024 at Xinxiang Central Hospital. Plasma and peripheral blood mononuclear cells were isolated. IL-37 and soluble interleukin 1 receptor 8(IL-1R8) levels were measured by enzyme-linked immunosorbent assay(ELISA). Levels of IL-37 receptor subunits in monocytes were analyzed via flow cytometry. Purified monocytes were stimulated with recombinant IL-37 and co-cultured with a human pancreatic β-cell line to assess cytotoxicity, measured by target cell death and cytokine levels. Additionally, monocytes were co-cultured with autologous CD4 + T cells to evaluate antigen presentation by measuring interferon-γ(IFN-γ) and IL-17A secretion. Results:Plasma IL-37 level and IL-37 receptor subunit expression in monocytes were significantly lower in T1DM patients compared to controls(both P<0.001). However, there was no significant difference in soluble IL-1R8 levels between the groups( P=0.457). Monocytes from T1DM patients exhibited increased cytotoxicity, as indicated by higher target cell death and elevated levels of granzyme A, granzyme B, granzyme H, IL-1β, IL-6, and tumor necrosis factor-α( P<0.05). Additionally, monocyte-induced secretion of IFN-γ and IL-17A by CD4 + T cells was elevated in T1DM patients(all P<0.05). Stimulation of T1DM monocytes with recombinant IL-37 reduced target cell death and decreased granzyme B secretion compared to unstimulated monocytes(both P<0.05). However, IL-37 stimulation had no significant effect on other cytokine levels or monocyte-induced IFN-γ and IL-17A secretion( P>0.05). Conclusions:Monocytes exhibit enhanced cytotoxicity and antigen-presenting capacity in T1DM patients. IL-37 reduces monocyte cytotoxicity by inhibiting granzyme B secretion, but does not affect antigen presenting function in T1DM.