Objective To investigate the role of the TNFRSF12A molecule in the pathogenesis of liver cancer.Methods Through comprehensive analysis of the Cancer Genome Atlas Program(TCGA)database and single-cell sequencing data,we studied the expression of TNFRSF12A in liver cancer and its correlation with prognosis.HPA database was utilized to analyze the subcellular localization of TNFRSF12A,and GO and KEGG analyses were performed by DAVID.TIME 2.0 was employed to analyze the correlation between TNFRSF12A and immune cell infiltration in liver cancer tissues.Results TNFRSF12A was found to be highly expressed in liver cancer tissues,significantly correlating with patient survival prognosis(OS:HR=1.61,P=0.007 0;RFS:HR=1.45,P=0.037 0;PFS:HR=1.30,P=0.099 0;DSS:HR=1.67,P=0.027 0),as well as age(P=0.046 7)and BCLC stage(P=0.045 6).TNFRSF12A co-expressed with tumor stem cell markers(CD24,SOX4,ANPEP),indicating a strong link to malignancy.Furthermore,molecular functional analysis unveiled that IL-2R primarily existed in the cell cytoplasm and played a role in processes such as cell apoptosis,invasion,and protein binding.Moreover,TNFRSF12A was associated with Treg cells and immune cell infiltration,further suggesting its role in tumor immune regulation.Conclusion TNFRSF12A exhibits a significant elevation within liver tumors and shows a notable correlation with patients'prognosis.Tumor cells engage in interactions with cytokines produced by Tregs,thereby reshaping the tumor microenvironment.The potential clinical significance of TNFRSF12A as a prognostic marker for tumors holds promise in offering novel avenues for personalized treatment and prognosis prediction.

Objective:To investigate the clinicopathological features and genetic mutation status of pulmonary intravascular large B cell lymphoma.Methods:The clinicopathological data of eight patients diagnosed with pulmonary intravascular large B cell lymphoma, from April 2018 to May 2023, were retrospectively analyzed. The genetic profile of six patients was detected via next-generation sequencing (NGS) and followed up.Results:All patients included one male and seven females, with a median age of 64 years (ranging from 45 to 66 years). Respiratory symptoms were the most common (7 cases), B symptoms in two cases, hemophagocytic syndrome in two cases. Multiple diffuse ground-glass opacities in both lungs were observed based on the high-resolution chest CT scan. Six cases of mild to moderate ventilation or diffusion dysfunction were observed based on the pulmonary function tests. Moreover, two cases of hypoxemia and two cases with type Ⅰ respiratory failure were recorded. The serum lactate dehydrogenase level increased (7/8), β2-MG level increased (2/8), neuron-specific enolase level increased (7/8), total number of peripheral blood lymphocytes decreased (7/8), and clinical stages were all stage Ⅳ. The neoplastic lymphoid cells were lodged in the lumina of venules and capillaries of the alveolar septum; the tumor cells were large, with prominent nucleoli and frequent mitotic figures. The malignant cells were detected in the extravascular surrounding lung tissue in all cases. The tumor cells expressed mature B cell-associated antigens CD20 and CD79a, and the vascular endothelial markers CD31 and CD34 showed that the tumor cells were filled in the blood vessels, infiltrated blood vessel walls, and perivascular areas. One case was germinal center-type, seven cases were non-germinal center-type, two cases were double-expressing lymphoma, and all cases were EBER-negative. Furthermore, the top five genes with mutation frequencies detected by NGS were MYD88 (5/6), PIM1 (5/6), CD79B (4/6), TCF3 (4/6), and TP53 (3/6). Of the eight cases, seven patients received R-CHOP-based chemotherapy, six cases had complete remission after chemotherapy, one case died, and one case was lost to follow-up.Conclusions:Pulmonary vascular large B cell lymphoma is rare, which shares similar patterns with interstitial lung disease on imaging. Transbronchial lung biopsy is an effective method to confirm the diagnosis. Immunochemotherapy with BTK inhibitors can provide a survival advantage for patients in the future based on molecular typing.

Purpose To explore the value of contrast-enhanced ultrasound(CEUS)in the differential diagnosis of gallbladder polypoid lesions(GPLs)(diameter≥10 mm).Materials and Methods A prospective enrollment of 229 patients with GPLs who underwent cholecystectomy in 17 hospitals from December 1 2021 to June 30 2024 was conducted to analyze the relationship between general data,conventional ultrasound,CEUS characteristics and the nature of GPLs.Multivariate Logistic regression was employed to identify independent risk factors for neoplastic polyps,the differential diagnostic value of different indicators was compared.Results Among 229 patients with GPLs,there were 108 cases of cholesterol polyps,102 cases of adenoma and 19 cases of gallbladder cancer.Age(Z=-4.476,P<0.001),polyp number(χ2=15.561,P<0.001),diameter(Z=-8.149,P<0.001),echogenicity(χ2=9.241,P=0.010),vascularity(χ2=23.107,P<0.001),enhancement intensity(χ2=47.610,P<0.001),enhancement pattern(χ2=6.468,P=0.011),vascular type(χ2=84.470,P<0.001),integrity of gallbladder wall(χ2=7.662,P=0.006)and stalk width(Z=-9.831,P<0.001)between cholesterol polyps and neoplastic polyps were statistically significant.Age,location,diameter,echogenicity,enhancement pattern,vascular type and stalk width between adenoma and gallbladder cancer were statistically significant(Z=-4.333,-3.902,-5.042,all P<0.05).Multivariate Logistic regression analysis showed that hyper-enhancement,branched vascular type and stalk width were independent risk factors for neoplastic polyps(OR=4.563,5.770,3.075,all P<0.001).The combination of independent risk factors was better than single factor and diameter in the differential diagnosis of cholesterol polyps and neoplastic polyps(all P<0.01).Conclusion CEUS can effectively identify the nature of GPLs and provide a valuable imaging reference for the selection of treatment methods.

Objective:To systematically evaluate the effect of cognitive behavioral therapy (CBT) in elderly patients with depression.Methods:The randomized controlled trials on the effect of CBT in elderly patients with depression, published until December 15, 2022, were searched in PubMed, CINHAL, Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, WanFang Data, and VIP. Two researchers independently screened the literature, extracted data, and used the revised Cochrane risk of bias tool for randomized trials (ROB 2.0) to evaluate the quality of the included studies. Statistical analysis was conducted using Stata 16.0, and the quality of evidence was rated using Appraisal of Guidelines for Research and Evaluation (GRADE) predictor software.Results:A total of 11 randomized controlled trials were included, with a total of 833 elderly patients with depression. Randomized effect models were used to analyze outcome indicators such as depression, anxiety, and quality of life by combining effect quantities. Meta-analysis and GRADE evidence quality showed that compared to the control group, medium quality evidence showed that CBT could relieve depression in elderly depression patients with a statistical difference [ SMD=-1.58, 95% CI (-2.16, -0.99), P<0.05]. Low quality evidence suggested that CBT could alleviate anxiety in elderly depression patients also with a statistical difference [ SMD=-2.25, 95% CI (-4.04, -0.47), P<0.05]. Very low quality evidence indicated that CBT did not significantly improve the quality of life in elderly depression patients compared to conventional or pharmacological treatment [ SMD=-0.09, 95% CI (-2.07, 1.88), P>0.05] . Conclusions:Existing evidence suggests that CBT can alleviate depression and anxiety in elderly depression patients, but its improvement in quality of life is not yet significant. Treatment feedback and forms of CBT may become a research focus in recent years on intervention for elderly depression patients.

BACKGROUND: Many studies have demonstrated the benefit of complete multivessel revascularization versus culprit-only intervention in patients of ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. However, only a few single-center retrospective studies were performed on small Chinese cohorts. Our study aims to demonstrate the advantage of multivessel percutaneous intervention (PCI) strategy on 30-day in-hospital outcomes to patients with STEMI and multivessel disease in larger Chinese population. METHODS: From the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, 5935 patients with STEMI and multivessel disease undergoing PCI and hospitalized for fewer than 30 days were analyzed. After 5: 1 propensity score matching, 3577 patients with culprit-only PCI and 877 with in-hospital multivessel PCI were included. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of myocardial infarction, all-cause death, stent thrombosis, heart failure, and stroke. RESULTS: Multivariable logistic regression analysis revealed that in-hospital multivessel PCI was associated with lower risk of 30-day MACCE (adjusted OR = 0.75, 95% CI: 0.57-0.98, P = 0.032) than culprit-only PCI and conferred no increased risk of all-cause death, myocardial infarction, stent thrombosis, stroke, or bleeding. Subgroup analysis showed that MACCE reduction was observed more often from patients with trans-femoral access (OR = 0.34, 95% CI: 0.15-0.74) than with trans-radial access (OR = 0.87, 95% CI: 0.66-1.16, P for interaction = 0.017). CONCLUSIONS The in-hospital multivessel PCI strategy was associated with a lower risk of 30-day MACCE than culprit-only PCI in patients with STEMI and multivessel coronary artery disease.

Scarring, naturally induced by fibroblasts(Fb) during wound healing, is an essential process in response to repair damaged tissue. Excessive Fb proliferation which produces the excessive collagen deposition, including increased extracellular matrix synthesis or insufficient decomposition, typically contributes to hypertrophic scar(HS) formation. Although exact mechanisms of HS are not yet fully understood, it is generally believed that dysfunction of Fb and regulation of signal pathways play an important role in HS formation. Biologically, Fb function is affected by various factors such as cytokines, extracellular matrix and itself. In addition, modifications of miRNA, ceRNA, lncRNA, peptides and histones participate in HS formation by affecting the biological function of Fb. Despite the clinical importance, very few therapeutic modalities are available to prevent HS. To achieve this, a deeper characterization of Fb is required to identify mechanisms of HS. To the aspect of HS prevention and treatment, we review recent findings, concentrating on Fb function and collagen secretion. The objective of this article is to frame the current understanding, gain the deeper insights into Fb function, and provide the more comprehensive cognition and perspective for prevention and treatment of HS.
Humans ; Cicatrix, Hypertrophic/metabolism* ; Collagen/therapeutic use* ; Fibroblasts ; Signal Transduction ; Extracellular Matrix/metabolism*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Aim To investigate the effect of arbutin on apoptosis of NRK-52e cells induced by LPS and the potential mechanism.Methods The model of NRK- 52e cells injury was constructed by LPS, and NRK-52e cells were divided into control, LPS ( 1 mg • L 1 ) , low dose arbutin (LPS, 1 mg • L 1 + arbutin, 5 (xmol • L_l ) , high dose arbutin ( LPS, 1 mg • L 1 + arbutin , 10 (xmol • L 1 ) and its corresponding inhibitor THC group ( 1 (xmol • L 1).The cell viability was detected ; the levels of ROS, apoptosis, Ca~' concentration and mitochondrial membrane potential ( MMP ) were detected by flow cytometry; the levels of key apoptosis proteins were detected by in cell western; the binding activity of arbutin with ER(3 was imitated by molecular docking technology, and verified by in cell western.Results Arbutin could effectively regulate the levels of ROS, Ca"+ , apoptosis proteins and ER(3 in NRK-52e cells induced by LPS and inhibit the de- cline of MMP, which is blocked by estrogen receptor inhibitor THC.In addition, arbutin has good binding activity with ERf}.Conclusion This study confirms that arbutin could inhibit LPS-induced apoptosis of NRK-52e cells through ER£.

Background: and Purpose Cerebral venous flow alterations potentially contribute to age-related white matter changes, but their role in small vessel disease has not been investigated. Methods: This study included 297 patients with hypertensive intracerebral hemorrhages (ICH) who underwent magnetic resonance imaging. Cerebral venous reflux (CVR) was defined as the presence of abnormal signal intensity in the dural venous sinuses or internal jugular vein on time-of-flight angiography. We investigated the association between CVR, dilated perivascular spaces (PVS), and recurrent stroke risk. Results: CVR was observed in 38 (12.8%) patients. Compared to patients without CVR those with CVR were more likely to have high grade (>20 in the number) dilated PVS in the basal ganglia (60.5% vs. 35.1%; adjusted odds ratio [aOR], 2.64; 95% confidence interval [CI], 1.25 to 5.60; P=0.011) and large PVS (>3 mm in diameter) (50.0% vs. 18.5%; aOR, 3.87; 95% CI, 1.85 to 8.09; P<0.001). During a median follow-up of 18 months, patients with CVR had a higher recurrent stroke rate (13.6%/year vs. 6.2%/year; aOR, 2.53; 95% CI, 1.09 to 5.84; P=0.03) than those without CVR. Conclusions CVR may contribute to the formation of enlarged PVS and increase the risk of recurrent stroke in patients with hypertensive ICH.

This study aims to investigate mechanism of "Ephedrae Herba-Descurainiae Semen Lepidii Semen" combination(MT) in the treatment of bronchial asthma based on network pharmacology and in vivo experiment, which is expected to lay a theoretical basis for clinical application of the combination. First, the potential targets of MT in the treatment of bronchial asthma were predicted based on network pharmacology, and the "Chinese medicine-active component-target-pathway-disease" network was constructed, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the potential targets. Molecular docking was used to determine the binding activity of key candidate active components to hub genes. Ovalbumin(OVA, intraperitoneal injection for sensitization and nebulization for excitation) was used to induce bronchial asthma in rats. Rats were classified into control group(CON), model group(M), dexamethasone group(DEX, 0.075 mg·kg~(-1)), and MT(1∶1.5) group. Hematoxylin and eosin(HE), Masson, and periodic acid-Schiff(PAS) staining were performed to observe the effect of MT on pathological changes of lungs and trachea and goblet cell proliferation in asthma rats. The levels of transforming growth factor(TGF)-β1, interleukin(IL)6, and IL10 in rat serum were detected by enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein levels of mitogen-activated protein kinase 8(MAPK8), cyclin D1(CCND1), IL6, epidermal growth factor receptor(EGFR), phosphatidylinositol 3-kinase(PI3 K), and protein kinase B(Akt) by qRT-PCR and Western blot. Network pharmacology predicted that MAPK8, CCND1, IL6, and EGFR were the potential targets of MT in the treatment of asthma, which may be related to PI3 K/Akt signaling pathway. Quercetin and β-sitosterol in MT acted on a lot of targets related to asthma, and molecular docking results showed that quercetin and β-sitosterol had strong binding activity to MAPK, PI3 K, and Akt. In vivo experiment showed that MT could effectively alleviate the symptoms of OVA-induced asthma rats, improve the pathological changes of lung tissue, reduce the production of goblet cells, inhibit the inflammatory response of asthma rats, suppress the expression of MAPK8, CCND1, IL6, and EGFR, and regulate the PI3 K/Akt signaling pathway. Therefore, MT may relieve the symptoms and inhibit inflammation of asthma rats by regulating the PI3 K/Akt signaling pathway, and quercetin and β-sitosterol are the candidate active components.
Animals ; Asthma/drug therapy* ; Cyclin D1 ; Dexamethasone/adverse effects* ; Drug Combinations ; Drugs, Chinese Herbal/therapeutic use* ; Eosine Yellowish-(YS)/adverse effects* ; Ephedra ; ErbB Receptors ; Hematoxylin/therapeutic use* ; Interleukin-10 ; Interleukin-6 ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Molecular Docking Simulation ; Network Pharmacology ; Ovalbumin/adverse effects* ; Periodic Acid/adverse effects* ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt/metabolism* ; Quercetin ; RNA, Messenger ; Rats