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1.
BMC Gastroenterol ; 24(1): 350, 2024 Oct 06.
Article in English | MEDLINE | ID: mdl-39370515

ABSTRACT

OBJECTIVE: Submucosal infiltration of less than 200 µm is considered an indication for endoscopic surgery in cases of superficial esophageal cancer and precancerous lesions. This study aims to identify the risk factors associated with submucosal infiltration exceeding 200 micrometers in early esophageal cancer and precancerous lesions, as well as to establish and validate an accompanying predictive model. METHODS: Risk factors were identified through least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. Various machine learning (ML) classification models were tested to develop and evaluate the most effective predictive model, with Shapley Additive Explanations (SHAP) employed for model visualization. RESULTS: Predictive factors for early esophageal invasion into the submucosa included endoscopic ultrasonography or magnifying endoscopy> SM1(P<0.001,OR = 3.972,95%CI 2.161-7.478), esophageal wall thickening(P<0.001,OR = 12.924,95%CI,5.299-33.96), intake of pickled foods(P=0.04,OR = 1.837,95%CI,1.03-3.307), platelet-lymphocyte ratio(P<0.001,OR = 0.284,95%CI,0.137-0.556), tumor size(P<0.027,OR = 2.369,95%CI,1.128-5.267), the percentage of circumferential mucosal defect(P<0.001,OR = 5.286,95%CI,2.671-10.723), and preoperative pathological type(P<0.001,OR = 4.079,95%CI,2.254-7.476). The logistic regression model constructed from the identified risk factors was found to be the optimal model, demonstrating high efficacy with an area under the curve (AUC) of 0.922 in the training set, 0.899 in the validation set, and 0.850 in the test set. CONCLUSION: A logistic regression model complemented by SHAP visualizations effectively identifies early esophageal cancer reaching 200 micrometers into the submucosa.


Subject(s)
Esophageal Neoplasms , Neoplasm Invasiveness , Humans , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Risk Factors , Male , Female , Middle Aged , Logistic Models , Machine Learning , Esophageal Mucosa/pathology , Esophageal Mucosa/diagnostic imaging , Aged , Precancerous Conditions/pathology , Precancerous Conditions/surgery , Precancerous Conditions/diagnostic imaging , Endosonography , Tumor Burden , Esophagoscopy
2.
Cancer Immunol Immunother ; 73(12): 250, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39358470

ABSTRACT

Patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) show varied responses to PD-1 monoclonal antibody (mAb) containing regimens. The mechanisms and predictive biomarkers for the efficacy of this regimen are unclear. This study retrospectively collected r/r DLBCL patients who received PD-1 mAb and rituximab regimens as salvage therapy. Clinical and genomic features were collected, and mechanisms were explored by multiplex immunofluorescence and digital spatial profiling. An artificial neural network (ANN) model was constructed to predict the response. Between October 16th, 2018 and May 4th, 2023, 50 r/r DLBCL patients were collected, 29 were response patients and 21 were non-response patients. CREBBP (p = 0.029) and TP53 (p = 0.015) alterations were statistically higher in non-response patients. Patients with PD-L1 CPS ≥ 5 were correlated with a longer overall survival (OS) than those with PD-L1 CPS < 5 (median OS: not reached vs. 9.7 months, hazard ratio [HR]: 3.8, 95% confidence interval [CI] 0.64-22.44, p = 0.016). Immune-related pathways were activated in response patients. The proportion and spatial organization of tumor-infiltrating immune cells affect the response. PD-L1 CPS level, age, and alterations of TP53, MYD88, CREBBP, EP300, GNA13 were used to build an ANN predictive model that showed high prediction efficiency (training set area under curve [AUC] of 0.97 and test set AUC of 0.94). The proportion and spatial distribution of tumor-infiltrating immune cells may be related to the function of immune-related pathways, thereby influencing the efficacy of PD-1 mAb containing regimens. The ANN predictive model showed potential value in predicting the responses of r/r DLBCL patients received PD-1 mAb and rituximab regimens.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Programmed Cell Death 1 Receptor , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Female , Middle Aged , Retrospective Studies , Aged , Adult , Rituximab/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/immunology , Biomarkers, Tumor , Prognosis , Immune Checkpoint Inhibitors/therapeutic use , Antibodies, Monoclonal/therapeutic use , Neural Networks, Computer , Drug Resistance, Neoplasm , Aged, 80 and over , Genomics/methods , Multiomics
3.
J Virol ; : e0069524, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39254312

ABSTRACT

Enterovirus 71 (EV71) belongs to the family of Picornaviridae; it could cause a variety of illnesses and pose a great threat to public health worldwide. Currently, there is no specific drug treatment for this virus, and a better understanding of virus-host interaction is crucial for novel antiviral development. Here, we find that the class III phosphatidylinositol 3-kinase, VPS34, is an essential host factor for EV71 infection. VPS34 inhibition with either shRNA or specific chemical inhibitor significantly reduces EV71 infection. Meanwhile, EV71 infection upregulates phosphatidylinositol 3-phosphate (PI3P) production in viral replication organelles (ROs), while the depletion of PI3P by phosphatase overexpression inhibits EV71 infection. In addition, the PI3P-binding protein, double FYVE-containing protein 1 (DFCP1), is also required for an efficient replication of EV71. DFCP1 could interact with viral 2C protein and facilitate viral association with lipid droplets (LDs), which are important lipid sources for viral RO biogenesis. Taken together, these results indicate that EV71 virus exploits the VPS34-PI3P-DFCP1-LDs pathway to promote viral RO formation and viral infection, and they also illuminate novel targets for antiviral development.IMPORTANCEEnterovirus 71 (EV71) is a major pathogen that causes hand-foot-and-mouth disease (HFMD) and other serious complications, which are big threats to children under 5 years old. Unravelling the interactions between virus and the host cells will open new avenues in antiviral research. Here, we found the class III phosphatidylinositol 3-kinase, VPS34, and its effector, double FYVE-containing protein 1 (DFCP1), were essential for EV71 infection, both of which could support EV71 viral replication by enhancing the biogenesis of viral replication organelles (ROs). As DFCP1 localizes to lipid droplets, hijacking of these host factors will enable viral utilization of lipids from LDs for the generation of membrane structures during RO biogenesis. In addition, the VPS34 kinase inhibitor was found to be potent against EV71 infection; therefore, this study also brings up a novel target for future anti-EV71 drug development.

4.
Adv Sci (Weinh) ; : e2406242, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39258724

ABSTRACT

Multimodal machine learning, as a prospective advancement in artificial intelligence, endeavors to emulate the brain's multimodal learning abilities with the objective to enhance interactions with humans. However, this approach requires simultaneous processing of diverse types of data, leading to increased model complexity, longer training times, and higher energy consumption. Multimodal neuromorphic devices have the capability to preprocess spatio-temporal information from various physical signals into unified electrical signals with high information density, thereby enabling more biologically plausible multimodal learning with low complexity and high energy-efficiency. Here, this work conducts a comparison between the expression of multimodal machine learning and multimodal neuromorphic computing, followed by an overview of the key characteristics associated with multimodal neuromorphic devices. The bio-plausible operational principles and the multimodal learning abilities of emerging devices are examined, which are classified into heterogeneous and homogeneous multimodal neuromorphic devices. Subsequently, this work provides a detailed description of the multimodal learning capabilities demonstrated by neuromorphic circuits and their respective applications. Finally, this work highlights the limitations and challenges of multimodal neuromorphic computing in order to hopefully provide insight into potential future research directions.

5.
BMC Health Serv Res ; 24(1): 756, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38907246

ABSTRACT

BACKGROUND: This study reviews the research status of Diagnosis-related groups (DRGs) payment system in China and globally by analyzing topical issues in this field and exploring the evolutionary trends of DRGs in different developmental stages. METHODS: Abstracts of relevant literature in the field of DRGs were extracted from the China National Knowledge Infrastructure (CNKI) database and the Web of Science (WoS) core database and used as text data. A probabilistic distribution-based Latent Dirichlet Allocation (LDA) topic model was applied to mine the text topics. Topical issues were determined by topic intensity, and the cosine similarity of the topics in adjacent stages was calculated to analyze the topic evolution trend. RESULTS: A total of 6,758 English articles and 3,321 Chinese articles were included. Foreign research on DRGs focuses on grouping optimization, implementation effects, and influencing factors, whereas research topics in China focus on grouping and payment mechanism establishment, medical cost change evaluation, medical quality control, and performance management reform exploration. CONCLUSIONS: Currently, the field of DRGs in China is developing rapidly and attracting deepening research. However, the implementation depth of research in China remains insufficient compared with the in-depth research conducted abroad.


Subject(s)
Diagnosis-Related Groups , China
6.
ACS Appl Mater Interfaces ; 16(22): 28853-28860, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38781477

ABSTRACT

Perovskite quantum dots (PeQDs) have great application prospects in fields such as displays and solar cells due to their adjustable band gap, high absorption coefficient, high carrier mobility, and solution processability. However, the ionic crystal characteristic of PeQDs and their surface ligands have led to problems such as solvent sensitivity, poor crystal stability, and difficulty in adjusting the photoelectric properties, which are challenges in high-quality PeQDs. Here, to solve the problem of fluorescence degradation caused by phase change and loss of surface ligands during the purification process of CsPbI3 QDs, this work develops a purification strategy that finely regulates the polarity of the purification solvent, to obtain high-purity perovskite. This strategy can tune the surface ligand concentration and optoelectronic properties while maintaining the crystal stability. The optimized purification process enables the quantum dots to maintain the same level of luminescence performance as the original solution (PLQY is ∼90%). Meanwhile, the electrical properties are improved to significantly increase the exciton recombination rate under an electrical drive. Finally, a highly efficient QLED with an external quantum efficiency of exceeding 23% can be achieved. This scheme for fine purification of CsPbI3 QDs will provide some inspiration for the development of efficient PeQDs and the realization of high-performance optoelectronic devices.

7.
Int J Gen Med ; 17: 2151-2161, 2024.
Article in English | MEDLINE | ID: mdl-38766597

ABSTRACT

Background: Previous studies have confirmed that high apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio was associated with increased mortality from heart failure (HF). Furthermore, the association of plasma apoB/apoA1 ratio with clinical characteristics and adverse cardiac remodeling is still limited in chronic HF with mildly reduced ejection fraction (HFmrEF) elderly patients. Therefore, this study investigated the association of apoB/apoA1 ratio with clinical characteristics and adverse cardiac remodeling in chronic HFmrEF elderly patients. Methods: A total of 587 Chinese elderly (≥65 years) with coronary heart disease (CHD), HFmrEF (EF 40-50%) and related blood biochemical data were collected retrospectively. The cross-sectional data of echocardiographic and blood parameters were compared between binary apoB/apoA1 groups. Results: In the elderly CHD patients with chronic HFmrEF, the univariate correlation analysis showed that apoB/apoA1 was correlated with younger age, increased prevalence of type 2 diabetes, erythrocytes, platelet/lymphocyte ratio (PLR), D-dimer, fibrinogen, high sensitivity C-reactive protein and uric acid, and adverse cardiac remodeling (All P < 0.05). However, multivariate logistic binary regression analysis found that high apoB/apoA1 ratio (≥0.62) was independently correlated with younger age, increased erythrocytes, PLR, D-dimer and uric acid, and adverse cardiac remodeling (All P < 0.05). Conclusion: In this retrospective study, the high apoB/apoA1 ratio is found to be associated with younger age, increased erythrocytes, PLR, D-dimer and uric acid, and adverse cardiac remodeling in Chinese CHD elderly with chronic HFmrEF.

8.
J Cardiovasc Dev Dis ; 11(5)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38786962

ABSTRACT

Background: This study aims to explore the relationship of the low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein (HDL-C) ratio with glycated hemoglobin (HbA1c), renal dysfunction, coronary heart disease (CHD) and cardiac structure and function in elderly patients with hypercholesterolemia. Methods: A total of 1129 hospitalized Chinese elderly (aged ≥ 65 years) with hypercholesterolemia were collected retrospectively. The patients were divided into low (<2.63), moderate (≥2.63 to <3.33) and high (≥3.33) LDL-C/HDL-C ratio groups according to the tertiles of LDL-C/HDL-C. Results: Regression analysis of the LDL-C/HDL-C ratio with metabolic and echocardiographic parameters revealed that a high LDL-C/HDL-C ratio (≥3.33) was associated independently with male gender, elevated HbA1c, decreased estimated glomerular filtration rate (eGFR), prevalent CHD and left ventricular dilatation (all p < 0.05). Conclusions: A high LDL-C/HDL-C ratio was associated with male gender, increased HbA1c, decreased eGFR, CHD and enlarged left ventricle in elderly with hypercholesterolemia.

9.
Biochem Biophys Res Commun ; 722: 150172, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-38805788

ABSTRACT

BACKGROUND: Colon cancer is a prevalent invasive neoplasm in the gastrointestinal system with a high degree of malignancy. Despite extensive research, the underlying mechanisms of its recurrence and metastasis remain elusive.Rho GTPase activating protein 4 (ARHGAP4), a member of the small GTPases protein family, may be closely related to tumor metastasis, and its expression is increased in colon cancer. However, the role of ARHGAP4 in colon cancer metastasis is uncertain. This study investigates the impact of ARHGAP4 on the metastasis of colon cancer cells. Our objective is to determine the role of ARHGAP4 in regulating the invasive behavior of colon cancer cells. METHODS: We downloaded colon adenocarcinoma (COAD) data from the Cancer Genome Atlas (TCGA), and performed differential analysis and survival analysis. By using the CIBERSORT algorithm, we evaluated the proportion of infiltrating immune cells in colon cancer. We further analyzed whether ARHGAP4 is associated with T cell exhaustion. Finally, we investigated the impact of ARHGAP4 knockdown on the migration and invasion of colon cancer cells through in vitro cell experiments. Additionally, we utilized western blotting to assess the expression of protein related to the TGF-ß signaling pathway and epithelial-mesenchymal transition (EMT). RESULTS: We found that ARHGAP4 is upregulated in colon cancer. Subsequent survival analysis revealed that the high-expression group had significantly lower survival rates compared to the low-expression group. Immune infiltration analysis showed that ARHGAP4 was not only positively correlated with CD8+ T cells, but also positively correlated with T cell exhaustion markers programmed cell death 1 (PDCD-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte activating 3 (LAG-3). In vitro cell experiments, the knockdown of ARHGAP4 inhibited the migration and invasion of colon cancer cells. Among EMT-related proteins, when ARHGAP4 was knocked down, the expression of E-cadherin was increased, while the expression of N-cadherin and Vimentin was decreased. Meanwhile, the expression of TGF-ß1, p-Smad2, and p-Smad3, which are associated with the TGF-ß/Smad pathway, all decreased. CONCLUSION: ARHGAP4 promotes colon cancer metastasis through the TGF-ß/Smad signaling pathway and may be associated with T cell exhaustion. It plays an important role in the progression of colon cancer and may serve as a potential target for diagnosis and treatment of colon cancer.


Subject(s)
Colonic Neoplasms , Epithelial-Mesenchymal Transition , GTPase-Activating Proteins , Signal Transduction , Transforming Growth Factor beta , Humans , Colonic Neoplasms/pathology , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , GTPase-Activating Proteins/metabolism , GTPase-Activating Proteins/genetics , Transforming Growth Factor beta/metabolism , Epithelial-Mesenchymal Transition/genetics , Cell Line, Tumor , Cell Movement/genetics , Neoplasm Metastasis , T-Lymphocytes/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Neoplasm Invasiveness , Gene Expression Regulation, Neoplastic , T-Cell Exhaustion
10.
Target Oncol ; 19(3): 383-400, 2024 May.
Article in English | MEDLINE | ID: mdl-38643457

ABSTRACT

BACKGROUND: The clinical and genetic characteristics, as well as treatment outcomes, of diffuse large B-cell lymphoma (DLBCL) patients with different MYD88 and CD79B mutation status merit further investigation. OBJECTIVE: This study aims to investigate the distinctions in clinical manifestations, genetic characteristics, and treatment outcomes among MYD88-CD79Bco-mut, MYD88/CD79Bsingle-mut, and MYD88-CD79Bco-wt DLBCL patients. PATIENTS AND METHODS: Clinical and genetic characteristics, along with treatment outcomes among 2696 DLBCL patients bearing MYD88-CD79Bco-mut, MYD88/CD79Bsingle-mut, and MYD88-CD79Bco-wt treated with R-CHOP/R-CHOP-like regimens from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and six external cohorts were analyzed. Potential molecular mechanisms were investigated through Gene Set Enrichment Analysis and xCell methodology. RESULTS: In the MCD subtype, patients with MYD88-CD79Bco-mut showed comparable progression-free survival (PFS) and overall survival (OS) compared to MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt. However, in the non-MCD subtype, patients with MYD88-CD79Bco-mut exhibited significantly inferior OS than MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt, while there was no significant OS difference between MYD88/CD79Bsingle-mut and MYD88-CD79Bco-wt (median OS: 68.8 [95% CI 22-NA] vs NA [95% CI 112-NA] vs 177.7 [95% CI 159-NA] months; MYD88-CD79Bco-mut vs MYD88/CD79Bsingle-mut: p = 0.02; MYD88-CD79Bco-mut vs MYD88-CD79Bco-wt: p = 0.03; MYD88/CD79Bsingle-mut vs MYD88-CD79Bco-wt: p = 0.33). Regarding patients with MYD88-CD79Bco-mut, there was no significant difference in PFS and OS between the MCD and non-MCD subtypes. Within the MYD88-CD79Bco-mut group, patients with PIM1mut had better PFS than PIM1wt (median PFS: 8.34 [95% CI 5.56-NA] vs 43.8 [95% CI 26.4-NA] months; p = 0.02). Possible mechanisms contributing to the superior PFS of PIM1mut patients may include activated lymphocyte-mediated immunity and interferon response, a higher proportion of natural killer T cells and plasmacytoid dendritic cells, as well as suppressed angiogenesis and epithelial-mesenchymal transition, along with lower fibroblast and stromal score. CONCLUSIONS: In the MCD subtype, patients with MYD88-CD79Bco-mut showed comparable PFS and OS compared to MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt, while in the non-MCD subtype, they exhibited significantly inferior OS. There was no significant disparity in PFS and OS of MYD88-CD79Bco-mut between the MCD and non-MCD subtypes. The presence of PIM1mut within the MYD88-CD79Bco-mut group correlated with better PFS, which may result from an intricate interplay of immune processes and tumor microenvironment alterations.


Subject(s)
CD79 Antigens , Lymphoma, Large B-Cell, Diffuse , Mutation , Myeloid Differentiation Factor 88 , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Myeloid Differentiation Factor 88/genetics , CD79 Antigens/genetics , Prognosis , Male , Female , Treatment Outcome , Middle Aged , Aged , Adult
11.
J Org Chem ; 89(6): 3907-3911, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38427963

ABSTRACT

A catalytic enantioselective synthesis of bicalutamide derivatives with promising potentials in prostate cancer treatment has been disclosed. The key intermediates, α-hydroxy-ß-keto esters, were efficiently constructed through cinchoninium-mediated asymmetric oxohydroxylation of easily accessible alkenes with potassium permanganate. Good yields and high levels of asymmetric induction are achieved. This method provides a new synthetic route to bicalutamide analogues with high structural diversity, which will beneficially support subsequent structure-activity relationship studies and boost prostate cancer drug development.


Subject(s)
Anilides , Nitriles , Prostatic Neoplasms , Tosyl Compounds , Male , Humans , Molecular Structure , Stereoisomerism , Structure-Activity Relationship
12.
BMC Med Educ ; 24(1): 314, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38509547

ABSTRACT

BACKGROUND: Colleges and universities face an increased risk of public health emergencies. Among them, medical colleges and universities deserve more attention as they serve as the play a fundamental role in providing public health emergency services and in cultivating medical professionals. Effectively managing infectious disease prevention and control, as well as responding to public health emergencies in medical colleges and universities, is of great importance for enhancing the capacity of social emergency governance and improving the completeness of the public health system. This study aims to understand the management of public health emergencies in medical colleges in a city in southwest China, explore the factors associated with medical college students' evaluations, and provide recommendations for emergency management mechanisms in colleges and universities. METHODS: In total, 781 medical college students were selected through stratified random sampling and surveyed using a questionnaire. The main factors affecting students' evaluation of emergency management were analyzed using multiple linear regression and structural equation modeling. RESULTS: The overall emergency management situation in medical colleges was relatively complete, with satisfactory results. Medical college students' satisfaction with the timeliness of prevention measures was the highest, while the publicity and education were the lowest. Multiple linear regression analysis showed that grades, emergency education, -simulation training, -information reporting, and dynamic adjustment measures were associated with the evaluation of emergency management by medical students. CONCLUSIONS: Although the evaluation of emergency management in medical colleges was generally positive, certain limitations still existed. To improve the development of the public health system, colleges and universities should constantly reform and innovate emergency management mechanisms according to the important links in the prevention and control processes.


Subject(s)
Students, Medical , Humans , Public Health , Cross-Sectional Studies , Emergencies , Universities , China
13.
BMC Cancer ; 24(1): 204, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38350902

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is an aggressive tumor of the gastrointestinal tract, which is a major public health concern worldwide. Despite numerous studies, the precise mechanism of metastasis behind its progression remains elusive. As a member of the containing olfactomedin domains protein family, olfactomedin 2 (OLFM2) may play a role in tumor metastasis. It is highly expressed in colorectal cancer, and its role in the metastasis of CRC is still unclear. As such, this study seeks to explore the function of OLFM2 on CRC metastasis and its potential mechanisms. METHODS: Real-time fluorescence quantitative PCR and western blotting were used to study the expression of OLFM2 in human CRC and adjacent normal tissues. Knockdown and overexpression OLFM2 cell lines were constructed using siRNA and overexpression plasmids to explore the role of OLFM2 in the migration and invasion of CRC through transwell, and wound healing experiments. Finally, the expression of epithelial-mesenchymal transition (EMT) -related proteins and TGF-ß/Smad signaling pathway-related proteins was investigated using western blotting. RESULTS: In this study, we observed an elevation of OLFM2 expression levels in CRC tissues. To investigate the function of OLFM2, we overexpressed and knocked down OLFM2. We discovered that OLFM2 knockdown inhibited migration and invasion of colon cancer cells. Furthermore, E-cadherin expression increased while N-cadherin and Vimentin expression were opposite. It is no surprise that overexpressing OLFM2 had the opposite effects. We also identified that OLFM2 knockdown resulted in reduced TGF-ßR1 and downstream molecules p-Smad2 and p-Smad3, which are related to the TGF-ß / Smad pathway. In contrast, overexpressing OLFM2 significantly boosted their expression levels. CONCLUSION: The protein OLFM2 has been identified as a crucial determinant in the progression of CRC. Its mechanism of action involves the facilitation of EMT through the TGF-ß/Smad signaling pathway. Given its pivotal role in CRC, OLFM2 has emerged as a promising diagnostic and therapeutic target for the disease. These results indicate the potential of OLFM2 as a valuable biomarker for CRC diagnosis and treatment and highlight the need for further research exploring its clinical significance.


Subject(s)
Colorectal Neoplasms , Humans , Cell Line, Tumor , Cell Movement/genetics , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Signal Transduction , Smad Proteins/metabolism , Transforming Growth Factor beta/metabolism
14.
Medicine (Baltimore) ; 103(8): e37249, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38394530

ABSTRACT

BACKGROUND: Intestinal malrotation is an infrequent congenital anomaly primarily observed in neonates, and adult-onset cases are exceedingly rare. Studies on adult congenital intestinal malrotation are limited. METHODS: A case with congenital intestinal malrotation is reported in our study. The clinical data were collected and the treatment process and effect were evaluated. RESULTS: A 45-year-old female who had been experiencing vomiting for over 40 years was admitted to our hospital. According to the result of CT scan, intestinal volvulus accompanied by bowel obstruction was suspected. Then laparoscopic examination was applied to the patient and was ultimately diagnosed with adult congenital intestinal malrotation. We performed Ladd's procedure combined with gastrojejunostomy and Braun anastomosis. The patient recovered well and was successfully discharged from the hospital on the 13th day after surgery. After a 6-month follow-up, the symptom of vomiting was significantly alleviated and body weight was gained for 10 kg. She was very satisfied with the treatment. CONCLUSION: Adult congenital intestinal malrotation is a rare disease that is often misdiagnosed owing to nonspecific clinical manifestations. Therefore, awareness about this condition should be enhanced. Surgery remains the cornerstone of treatment for this disease. Combining gastrojejunostomy and Braun anastomosis with the traditional Ladd procedure can optimize surgical outcomes.


Subject(s)
Digestive System Abnormalities , Gastric Bypass , Intestinal Obstruction , Intestinal Volvulus , Infant, Newborn , Adult , Female , Humans , Middle Aged , Intestinal Volvulus/diagnosis , Intestinal Volvulus/surgery , Intestinal Volvulus/complications , Intestines/surgery , Intestinal Obstruction/surgery , Intestinal Obstruction/complications , Gastric Bypass/adverse effects , Vomiting/complications
15.
PLoS Pathog ; 20(1): e1011967, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38271479

ABSTRACT

Given the serious neurological complications and deaths associated with enterovirus 71 (EV71) infection, there is an urgent need to develop effective antivirals against this viral infection. In this study, we demonstrated that two Cathelicidin-derived peptides, LL-18 and FF-18 were more potent against EV71 infection than the parent peptide LL-37, which is the mature and processed form of Cathelicidin. These peptides could directly bind to the EV71 virus particles, but not to coxsackievirus, indicative of their high specificity. The binding of peptides with the virus surface occupied the viral canyon region in a way that could block virus-receptor interactions and inhibit viral uncoating. In addition, these peptide analogues could also relieve the deleterious effect of EV71 infection in vivo. Therefore, Cathelicidin-derived peptides might be excellent candidates for further development of antivirals to treat EV71 infection.


Subject(s)
Enterovirus A, Human , Enterovirus Infections , Enterovirus , Humans , Cathelicidins/pharmacology , Virus Internalization , Antiviral Agents/metabolism
16.
BMC Infect Dis ; 24(1): 76, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38212685

ABSTRACT

BACKGROUND: Brucellosis poses a significant public health concern. This study explores the spatial and temporal dynamic evolution of human brucellosis in China and analyses the spatial heterogeneity of the influencing factors related to the incidence of human brucellosis at the provincial level. METHODS: The Join-point model, centre of gravity migration model and spatial autocorrelation analysis were employed to evaluate potential changes in the spatial and temporal distribution of human brucellosis in mainland China from 2005 to 2021. Ordinary Least Squares (OLS), Geographically Weighted Regression (GWR), and Multi-scale Geographically Weighted Regression (MGWR) models were constructed to analyze the spatial and temporal correlation between the incidence rate of human brucellosis and meteorological and social factors. RESULTS: From 2005 to 2021, human brucellosis in China showed a consistent upward trend. The incidence rate rose more rapidly in South, Central, and Southwest China, leading to a shift in the center of gravity from the North to the Southwest, as illustrated in the migration trajectory diagram. Strong spatial aggregation was observed. The MGWR model outperformed others. Spatio-temporal plots indicated that lower mean annual temperatures and increased beef, mutton, and milk production significantly correlated with higher brucellosis incidence. Cities like Guangxi and Guangdong were more affected by low temperatures, while Xinjiang and Tibet were influenced more by beef and milk production. Inner Mongolia and Heilongjiang were more affected by mutton production. Importantly, an increase in regional GDP and health expenditure exerted a notable protective effect against human brucellosis incidence. CONCLUSIONS: Human brucellosis remains a pervasive challenge. Meteorological and social factors significantly influence its incidence in a spatiotemporally specific manner. Tailored prevention strategies should be region-specific, providing valuable insights for effective brucellosis control measures.


Subject(s)
Brucellosis , Animals , Cattle , Humans , China/epidemiology , Spatial Analysis , Brucellosis/epidemiology , Spatial Regression , Cities , Incidence , Spatio-Temporal Analysis
17.
AIDS Care ; 36(4): 561-568, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38088933

ABSTRACT

This study used a self-administered questionnaire to investigate the relationship between HIV/AIDS knowledge, social discrimination, HIV self-efficacy, sexual behavioral characteristics and HIV testing behavior among young students with a history of sexual activity in Chongqing. Propensity score matching was used to construct a control group with similar demographic characteristics to the HIV testing group, only without HIV testing behaviors. Structural equation modeling was used to conduct chain-mediated effect analysis. The HIV testing rate among young students with a history of sexual behavior was 17.16%. Young students with HIV testing behavior had higher levels of HIV/AIDS knowledge, lower social discrimination, better self-efficacy, and no difference in sexual behavior characteristic scores between the two groups (P = 0.062). The mediated effect values of social discrimination and self-efficacy were 0.022 and 0.063, respectively, while their chain mediated effect value was 0.007. There was no mediated effect of sexual behavior characteristics. The level of young students' HIV/AIDS knowledge does not directly influence their HIV testing behavior but plays a complete chain mediating effect on HIV testing behavior through social discrimination and self-efficacy. HIV testing behavior should be promoted through the perspectives of enhancing HIV/AIDS knowledge level, reducing social discrimination, and improving self-efficacy.


Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Humans , HIV Infections/diagnosis , Self Efficacy , Mediation Analysis , Health Knowledge, Attitudes, Practice , Sexual Behavior , Surveys and Questionnaires , Students , HIV Testing , Social Discrimination
18.
Photochem Photobiol ; 100(2): 380-392, 2024.
Article in English | MEDLINE | ID: mdl-38041414

ABSTRACT

We have employed the highly accurate multistate complete active space second-order perturbation theory (MS-CASPT2) method to investigate the photoinduced excited state relaxation properties of one unnatural base, namely Z. Upon excitation to the S2 state of Z, the internal conversion to the S1 state would be dominant. From the S1 state, two intersystem crossing paths leading to the T2 and T1 states and one internal conversion path to the S0 state are possible. However, considering the large barrier to access the S1 /S0 conical intersection and the strong spin-orbit coupling between S1 and T2 states (>40 cm-1 ), the intersystem crossing to the triplet manifolds is predicted to be more preferred. Arriving at the T2 state, the internal conversion to the T1 state and the intersystem crossing back to the S1 state are both possible considering the S1 /T2 /T1 three-state intersection near the T2 minimum. Upon arrival at the T1 state, the deactivation to S0 can be efficient after overcoming a small barrier to access T1 /S0 crossing point, where the spin-orbit coupling (SOC) is as large as 39.7 cm-1 . Our present work not only provides in-depth insights into the photoinduced process of unnatural base Z, but can also help the future design of novel unnatural bases with better photostability.

19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(6): 1852-1859, 2023 Dec.
Article in Chinese | MEDLINE | ID: mdl-38071072

ABSTRACT

OBJECTIVE: To retrospectively analyze the efficacy and complications of our institution's modified nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) in treating intermediate-risk acute myeloid leukemia (AML) - first complete remission (CR1) and prognostic factors. METHODS: Clinical data of 50 intermediate-risk AML-CR1 patients who underwent matched related NST at the Fifth Medical Center of Chinese People's Liberation Army General Hospital from August 2004 to April 2021 were collected, the hematopoietic recovery, donor engraftment and complications were observed, and overall survival (OS) rate, leukemia-free survival (LFS) rate, treatment-related mortality (TRM), and cumulative relapse rate were calculated. Statistical analysis of factors affecting prognosis was also preformed. RESULTS: The median times for neutrophil and platelet recovery after transplantation were 10 (6-16) and 13 (6-33) days, respectively. One month after transplantation, 22 patients (44%) achieved full donor chimerism (FDC), and 22 patients (44%) achieved mixed chimerism (MC), among whom 18 cases gradually transited to FDC during 1-11 months, 4 cases maintained MC status. The overall incidence of acute graft-versus-host disease (aGVHD) was 36%, with a rate of 18% for grade II-IV aGVHD and a median onset time of 45 (20-70) days after transplantation. The overall incidence of chronic GVHD (cGVHD) was 34%, with 20% and 14% of patients having limited or extensive cGVHD, respectively. The incidence rates of infections, interstitial pneumonia, and hemorrhagic cystitis were 30%, 10%, and 16%, respectively. The 5-year OS rate, LFS rate, TRM, and cumulative relapse rate were 68%, 64%, 16%, and 20%, respectively. The increase of the number of CD34+ cells infused had shortened the recovery time for neutrophils and platelets (r =0.563, r =0.350). The number of CD34+ cells infused significantly influenced the occurrence of extensive cGVHD (OR =1.36, 95%CI : 1.06-1.84, P =0.024). CONCLUSION: Modified NST is effective in treating intermediate-risk AML-CR1 patients, however, further expansion of sample size is needed to study prognostic factors.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/complications , Prognosis , Recurrence , Retrospective Studies
20.
Cereb Cortex ; 33(21): 10723-10735, 2023 10 14.
Article in English | MEDLINE | ID: mdl-37724433

ABSTRACT

Based on acoustoelectric effect, acoustoelectric brain imaging has been proposed, which is a high spatiotemporal resolution neural imaging method. At the focal spot, brain electrical activity is encoded by focused ultrasound, and corresponding high-frequency acoustoelectric signal is generated. Previous studies have revealed that acoustoelectric signal can also be detected in other non-focal brain regions. However, the processing mechanism of acoustoelectric signal between different brain regions remains sparse. Here, with acoustoelectric signal generated in the left primary visual cortex, we investigated the spatial distribution characteristics and temporal propagation characteristics of acoustoelectric signal in the transmission. We observed a strongest transmission strength within the frontal lobe, and the global temporal statistics indicated that the frontal lobe features in acoustoelectric signal transmission. Then, cross-frequency phase-amplitude coupling was used to investigate the coordinated activity in the AE signal band range between frontal and occipital lobes. The results showed that intra-structural cross-frequency coupling and cross-structural coupling co-occurred between these two lobes, and, accordingly, high-frequency brain activity in the frontal lobe was effectively coordinated by distant occipital lobe. This study revealed the frontooccipital long-range interaction mechanism of acoustoelectric signal, which is the foundation of improving the performance of acoustoelectric brain imaging.


Subject(s)
Brain , Frontal Lobe , Frontal Lobe/diagnostic imaging , Brain Mapping
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