Objective: To enhance the recognition of necrotizing sialometaplasia (NS) by elucidating its clinical, pathological characteristics and key diagnostic points, providing a basis for the diagnosis and treatment of the disease. Methods: This study has been reviewed and approved by the Medical Ethics Committee, and informed consent has been obtained from patients. Review the data of a patient with NS occurring at the junction of the right soft and hard palate, and comprehensively analyze its diagnostic process based on its clinical manifestations, imaging, and histopathological examination results. And review the relevant literature on the disease. Results: This study describes a 24-year-old male patient with a documented betel nut habit (2 pieces/day for >6 months), who presented with a bone-deep, irregular crateriform ulcer (3 mm × 6 mm × 5 mm) localized to the right hard-soft palate junction. Spiral CT showed a local soft tissue defect with no apparent underlying bone destruction. Histopathology demonstrated chronic inflammation of the mucosal and minor salivary gland tissues, with no evidence of malignancy. A final diagnosis of NS was established. The ulcer healed completely three weeks after initiation of local anti-inflammatory therapy. A literature review indicates that NS is a rare, benign salivary gland disorder, typically occurring at the hard-soft palate junction in middle-aged men (40-60 years). Its etiology remains unclear, but it is widely attributed to salivary lobe infarction following mechanical trauma-induced ischemia. Due to its clinical resemblance to malignancy, it is often misdiagnosed. Treatment entails local anti-inflammatory measures and meticulous wound care aimed at promoting mucosal healing. Conclusion NS is a self-limiting, benign condition that poses a significant diagnostic challenge due to its close clinical simulation of malignancy. Thus, accurate diagnosis requires a combined assessment of clinical presentation, radiological features, and pathological findings. Treatment is predicated based on a conservative strategy with an emphasis on symptomatic management.

Objective To compare the clinical efficacy of low-molecular-weight heparin anticoagulant drugs in the treatment of venous thrombosis caused by viral pneumonia.Methods The clinical data of 355 patients diagnosed with viral pneumonia patients in the First People's Hospital of Yunnan Province from December 2022 to February 2023 were collected by retrospective analysis.The patients were classified into moderate group(n=1 14),severe group(n=116),and critical group(n=125)based on the severity of viral pneumonia.The changes in coagulation indicators of the patients after treatment with low molecular weight heparin sodium injection,low molecular weight heparin calcium injection,and enoxaparin sodium injection were compared among three groups.Results Compared with before treatment,there was no statistically significant difference in white blood cells count among three groups of patients after treatment(P＞0.05);The hypersensitive C-reactive protein levels of patients in moderate group and critical group decreased(P＜0.05);The levels of D-dimer decreased in severe group and critical group of patients(P＜0.05).After treatment with low-molecular-weight heparin calcium injection,the activated partial thromboplastin and prothrombin time of patients in severe group were shortened compared to before treatment,and the D-dimer levels of patients in severe group and critical group were reduced compared to before treatment,with statistical significance(P＜0.05);After treatment with low-molecular-weight heparin sodium and enoxaparin,only critical group showed a significant decrease in D-dimer levels(P＜0.05).Conclusion Low-molecular-weight heparin calcium injection has a stronger alleviating effect on blood hypercoagulability caused by elevated D-dimer levels than low-molecular-weight heparin sodium and enoxaparin,which is beneficial for relieving patients' hypercoagulability.

Objective:To compare the efficacy of early versus delayed reconstruction of anterior cruciate ligament (ACL) ruptures under arthroscopy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 260 young adults with ACL ruptures admitted to 940th Hospital of Joint Logistic Support Force of PLA from January 2022 to June 2024, including 171 males and 89 females, aged 18-45 years [(25.6±5.9)years]. Left knee was involved in 127 patients, while the right in 133 patients. All the patients underwent arthroscopic ACL reconstruction with autologous tendon grafts, of whom 130 patients were treated within 3 months after injury (early reconstruction group) but other 130 treated at 3 months after injury (delayed reconstruction group). The operative duration and intraoperative bleeding were compared between the two groups. The incidence of medial meniscus (MM) and lateral meniscus (LM) tears and the incidence of corresponding types of tears were recorded intraoperatively in the two groups. Tegner score and Lysholm score preoperatively, at 3 months postoperatively, and at the last follow-up were detected. Visual analogue scale (VAS) scores at 3 months postoperatively and at the last follow-up and postoperative complication rate were compared between the two groups.Results:All the patients were followed up for 6-15 months [(9.1±3.2)months]. There were no significant differences in operative duration or intraoperative bleeding between the two groups ( P>0.05). The incidence of MM tears in the early reconstruction group was 22.3% (29/130), lower than 34.6% (45/130) in the delayed reconstruction group ( P<0.05). There was no significant difference in the incidence of LM tears between the two groups ( P>0.05). The incidence of MM bucket-handle tears in the early reconstruction group was 2.3% (3/130), lower than 9.2% (12/130) in the delayed reconstruction group ( P<0.05), while no significant difference in the incidence of other types of meniscus tears was found between the two groups ( P>0.05). There were no significant differences in Tegner score or Lysholm score preoperatively between the two groups ( P>0.05). At 3 months postoperatively and at the last follow-up, the Tegner scores in the early reconstruction group were (7.4±1.3)points and (8.6±0.7)points, higher than (6.4±1.5)points and (7.9±0.6)points in the delayed reconstruction group and the Lysholm scores were (82.1±7.1)points and (90.7±3.8)points in the early reconstruction group, higher than (79.5±6.8)points and (86.3±4.0)points in the delayed reconstruction group ( P<0.01). There were no significant differences in VAS scores between the two groups at 3 months postoperatively or at the last follow-up ( P>0.05). The postoperative complication rate was 8.5% (11/130) in the early reconstruction group and 12.3% (16/130) in the delayed reconstruction group ( P>0.05). Conclusion:For young patients with ACL rupture, arthroscopic reconstruction within 3 months after injury can reduce the incidence of MM tear and bucket-handle tear and improve knee function without increasing the incidence of other complications when compared with delayed reconstruction at 3 months after injury.

Objective:To explore the clinical characteristics, treatment and prognosis of hard metal lung disease (HMLD), and to provide a theoretical reference basis for the prevention, control and intervention of HMLD in China.Methods:In April 2024, literatures related to HMLD and giant cell interstitial pneumonia (GIP) published before March 31, 2024 were retrieved in China National Knowledge Infrastructure (CNKI), Wanfang, VIP database, Embase and PubMed. The search terms in Chinese and English included hard metal lung disease, cobalt, tungsten carbide, giant cell interstitial pneumonia, hard metal, etc. Literature was screened and data were extracted. A systematic review was conducted to analyze the clinical characteristics, imaging, pulmonary function, pathological features, treatment and prognosis of HMLD.Results:A total of 55 literatures were included, including 1 cohort study, 4 cross-sectional studies, 4 case series reports and 46 case reports, involving a total of 227 patients with HMLD and GIP. There were 174 male cases, 51 female cases, and 2 cases whose gender was not mentioned. The age was (43.9±13.4) years old, and the dust exposure time was 7 (4, 13) years. The chest images of the patients showed ground glass shadow, micro-nodule shadow, grid shadow, honeycomb shadow, consolidation shadow, etc. Pulmonary function test showed restrictive ventilation dysfunction with gas exchange disorder. The pathological manifestations of lung tissue were typical GIP, but there were also hypersensitivity pneumonitis, common interstitial pneumonia, diffuse alveolar damage, non-specific interstitial pneumonia, and even honeycomb lung. Clinical diagnosis and treatment evaluation were performed by combining the occupational exposure history of hard metal dust or cobalt-containing dust, clinical manifestations, imaging, lung function and histopathology. Treatment involved cessation of exposure, with glucocorticoids alleviating symptoms and improving imaging and pulmonary function.Conclusion:HMLD can be caused by hard metal dust exposure. The clinical symptoms of HMLD are not specific, and the pathology shows typical GIP or other pulmonary interstitial changes. The treatment involves cessation of exposure and administration of glucocorticoids, and the overall prognosis is good.

Objective:To evaluate the diagnostic performance of artificial intelligence-assisted diagnostic systems in cervical cytopathological examination.Methods:Cervical cytology slide data were retrospectively collected from four hospitals for the external validation of the developed artificial intelligence-assisted diagnostic system. Subsequently, prospective data collection was conducted for human-machine assisted studies.Results:In the retrospective study, a total of 3 162 valid samples were collected as external validation data. The system showed an area under the curve (AUC) of 0.890 (95% CI: 0.878-0.902), accuracy of 0.885 (95% CI: 0.873-0.896), sensitivity of 0.928 (95% CI: 0.914-0.941), and specificity of 0.852 (95% CI: 0.834-0.867). In the prospective study, 212 valid samples were collected, and five junior cytologists participated in the human-machine assisted study. Without artificial intelligence assistance, the average AUC for the five cytologists was 0.686 (95% CI: 0.650-0.722), the accuracy was 0.699 (95% CI: 0.671-0.727), the sensitivity was 0.653 (95% CI: 0.599-0.703), the specificity was 0.719 (95% CI: 0.685-0.750), the Fleiss κ value was 0.510, and the reading time was 223 seconds. With artificial intelligence assistance, the AUC, accuracy, sensitivity, and specificity increased by 0.166, 0.143, 0.225, and 0.107, respectively. Additionally, Fleiss κ was 0.730 and the reading time decreased by 188 seconds. All differences were statistically significant (all P<0.001). Conclusions:Artificial intelligence-assisted diagnosis system shows excellent performance and good generalizability, significantly improving the diagnostic accuracy, consistency, and efficiency of junior cytologists. It can be an effective auxiliary tool for junior cytologists in clinical practice.

Objective To explore risk factors for cardiac valve calcification (CVC) in maintenance hemodialysis (MHD) patients and evaluate its impact on cardiovascular events and mortality. Methods Retrospective selection of 223 patients with MHD admitted to the Department of Nephrology of Jinshan Hospital, Fudan University from June 30, 2019 to June 30, 2024, and enrollment completed within one week of June 30, 2019. Patients were divided into CVC and non-CVC groups. Baseline data and 5-year follow-up data were collected. The binary logistic regression analysis was performed to explore the risk factors for CVC. Kaplan-Meier survival curve was used to analyze the survival rate of patients. Cox proportional hazard regression model was applied to evaluate the impact of CVC on the survival rates of MHD patients. Results Totally, 223 MHD patients with an average age of (58.4±13.5) years and an average dialysis duration of (64.0±55.4) months were involved. Among them, 136(61.0%) were males, 117(52.5%) were complicated with CVC. Age, dialysis duration, diabetic kidney disease (DKD), the serum corrected total calcium and phosphate, intact parathyroid hormone (iPTH), high-sensitive C-reactive protein (hsCRP), and homocysteine (Hcy) were independent related factors for CVC (P＜0.05). Both all-cause mortality (46.6% vs 28.7%) and cardiovascular mortality (33.3% vs 16.0%) were significantly higher in the CVC group than those in the non-CVC group (P＜0.01). Conclusions Age, dialysis duration, the primary disease, calcium and phosphate, and inflammation- and nutrition-related serum indicators are associated with CVC in MHD patients. CVC significantly increases mortality risk of MHD patients.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

OBJECTIVE: To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC). METHODS: Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay. RESULTS: A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells. CONCLUSION C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
Stomach Neoplasms/pathology* ; Humans ; Prognosis ; Lysosomes/physiology* ; RNA-Seq ; Cell Death ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Cell Proliferation ; Single-Cell Gene Expression Analysis

Objective To investigate the recovery of plasma metabolism in asymptomatic and mild patients of coronavirus disease 2019(COVID-19)one year after recovery.Methods A total of 174 participants were recruited from the communities in Wuhan,including 80 healthy volunteers and the COVID-19 patients who had recovered for one year.According to the disease severity,the recovered COVID-19 patients were grouped as asymptomatic patients(n=80)and mild patients(n=14).The liquid chromatography mass spectrometry platform was employed to study the metabolomic characteristics of the plasma from all the participants.Results The plasma metabolites in asymptomatic patients and mild patients remained abnormal compared with those in healthy volunteers.Among the differential metabolites in asymptomatic patients and mild patients,some metabolites showed a downward trend only in mild patients,such as phosphatidylethanolamine[20∶3(5Z,8Z,11Z)/P-18∶0],sphingomyelin(d18∶1/24∶0),and cholesteryl(15∶0).The metabolic pathway involving the differential metabolites in mild patients was mainly glycerophospholipid metabolism.Conclusions Even one year after recovery,the mild COVID-19 patients still exhibit metabolic abnormalities.Hence,these patients may experience an extended period of time for recovery.
Humans ; COVID-19/metabolism* ; Metabolomics ; SARS-CoV-2 ; Metabolome ; Female ; Male ; Adult ; Middle Aged

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.