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1.
Phys Rev Lett ; 132(20): 206401, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38829092

ABSTRACT

Coexisting orders are key features of strongly correlated materials and underlie many intriguing phenomena from unconventional superconductivity to topological orders. Here, we report the coexistence of two interacting charge-density-wave (CDW) orders in EuTe_{4}, a layered crystal that has drawn considerable attention owing to its anomalous thermal hysteresis and a semiconducting CDW state despite the absence of perfect Fermi surface nesting. By accessing unoccupied conduction bands with time- and angle-resolved photoemission measurements, we find that monolayers and bilayers of Te in the unit cell host different CDWs that are associated with distinct energy gaps. The two gaps display dichotomous evolutions following photoexcitation, where the larger bilayer CDW gap exhibits less renormalization and faster recovery. Surprisingly, the CDW in the Te monolayer displays an additional momentum-dependent gap renormalization that cannot be captured by density-functional theory calculations. This phenomenon is attributed to interlayer interactions between the two CDW orders, which account for the semiconducting nature of the equilibrium state. Our findings not only offer microscopic insights into the correlated ground state of EuTe_{4} but also provide a general nonequilibrium approach to understand coexisting, layer-dependent orders in a complex system.

2.
ESMO Open ; 9(6): 103472, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38833972

ABSTRACT

BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.

3.
Tech Coloproctol ; 28(1): 64, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844577

ABSTRACT

BACKGROUND: This study aimed to investigate the safety and feasibility of indocyanine green near-infrared fluorescence (ICG-NIR) fluorescence-guided video-endoscopic inguinal lymphadenectomy (VEIL) for rectal cancer with inguinal lymph node metastasis (ILNM). METHODS: A retrospective analysis was conducted on 11 patients with rectal cancer who underwent ICG-NIR fluorescence-guided VEIL, assessing various parameters such as operation time, intraoperative bleeding, number of harvested lymph nodes, intraoperative and postoperative complications, and follow-up. RESULTS: Regarding surgical procedures for ILNM, unilateral surgery was performed in 7 cases (54.5%) and bilateral surgery in 4 cases (45.5%). Among these 15 ICG-NIR-guided VEIL surgeries in 11 patients, positive fluorescence visualization was achieved in 13 operations (86.7%). The median estimated blood loss was 10 ml, and the median operation time was 90 min. One case (6.7%) required conversion to open surgery. The median duration of the drain tube was 12 days, and the median length of postoperative hospital stay was 20 days. Postoperative complications were observed, including incisional infection in 2 cases (18.2%), lymphatic leakage in 5 cases (45.5%), urinary infection in 1 case (9.1%), and pneumonia in 3 cases (27.3%). Complications such as skin necrosis, lower limb venous thrombosis, lower limb swelling, or impaired movement were observed during the postoperative follow-up period. No cases of primary lesion, groin, or pelvic lymph node recurrence were observed. CONCLUSION: ICG-NIR fluorescence-guided VEIL is a safe and feasible surgical treatment for rectal cancer with ILNM. ICG fluorescence guidance holds promise as a more personalized and precise approach for VEIL in rectal cancer surgery.


Subject(s)
Feasibility Studies , Indocyanine Green , Inguinal Canal , Lymph Node Excision , Lymphatic Metastasis , Operative Time , Rectal Neoplasms , Video-Assisted Surgery , Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Male , Lymph Node Excision/methods , Female , Middle Aged , Retrospective Studies , Aged , Video-Assisted Surgery/methods , Inguinal Canal/surgery , Postoperative Complications/etiology , Adult , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymph Nodes/diagnostic imaging , Coloring Agents , Fluorescence
4.
PLoS One ; 19(6): e0301691, 2024.
Article in English | MEDLINE | ID: mdl-38829846

ABSTRACT

Atrial Fibrillation (AF), a type of heart arrhythmia, becomes more common with aging and is associated with an increased risk of stroke and mortality. In light of the urgent need for effective automated AF monitoring, existing methods often fall short in balancing accuracy and computational efficiency. To address this issue, we introduce a framework based on Multi-Scale Dilated Convolution (AF-MSDC), aimed at achieving precise predictions with low cost and high efficiency. By integrating Multi-Scale Dilated Convolution (MSDC) modules, our model is capable of extracting features from electrocardiogram (ECG) datasets across various scales, thus achieving an optimal balance between precision and computational savings. We have developed three MSDC modules to construct the AF-MSDC framework and assessed its performance on renowned datasets, including the MIT-BIH Atrial Fibrillation Database and Physionet Challenge 2017. Empirical results unequivocally demonstrate that our technique surpasses existing state-of-the-art (SOTA) methods in the AF detection domain. Specifically, our model, with only a quarter of the parameters of a Residual Network (ResNet), achieved an impressive sensitivity of 99.45%, specificity of 99.64% (on the MIT-BIH AFDB dataset), and an [Formula: see text] score of 85.63% (on the Physionet Challenge 2017 AFDB dataset). This high efficiency makes our model particularly suitable for integration into wearable ECG devices powered by edge computing frameworks. Moreover, this innovative approach offers new possibilities for the early diagnosis of AF in clinical applications, potentially improving patient quality of life and reducing healthcare costs.


Subject(s)
Atrial Fibrillation , Electrocardiography , Neural Networks, Computer , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Humans , Electrocardiography/methods , Algorithms , Databases, Factual
5.
BMC Oral Health ; 24(1): 535, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711116

ABSTRACT

BACKGROUND: Periodontitis is a complex chronic inflammatory disease that is particularly associated with health-related conditions such as smoking, excessive drinking and depression. This research aimed to investigate the interaction between these lifestyles factors on periodontitis risk. METHODS: This study included participants who participated in the National Health and Nutrition Examination Survey in the United States between 2009 and 2014. They had completed oral health-periodontal examination, Smoking-Cigarette Use Questionnaire, Alcohol Use Questionnaire, and Patient Health Questionnaire. Periodontal clinical attachment loss (CAL) of 3 mm or more and Patient Health Questionnaire-9 (PHQ-9) of 10 scores or more were used to identify periodontitis and depression, respectively. Daily alcohol consumption in the past year was classified into three levels: low (1 drink or less), moderate (between 1 and 3 drinks), and heavy drinking (4 drinks or more), while smoking was defined as having smoked at least 100 cigarettes in one's lifetime. Then, the logistic regression combined with interaction models were used to analyze the independent and combined effects of smoking, drinking and depression on periodontitis risk. RESULTS: The results indicated a statistically significant multiplicative interaction between smoking and depression in relation to the development of periodontitis, both in the overall population (P = 0.03) and among male participants (P = 0.03). Furthermore, among individuals experiencing depression, smoking was found to significantly increase the prevalence of periodontitis by 129% in the younger age group compared to non-smokers (odds ratio [OR]: 2.29; 95% confidence interval [CI]: 1.10 to 4.76). However, the interaction between smoking and alcohol consumption was only significant among females (P < 0.05). There was a dose-dependent relationship between drinking frequency and smoking on periodontitis prevalence. In the smoking population, occasional drinking (OR: 1.70; 95% CI: 1.22 to 2.37) and regular drinking (OR: 2.28; 95% CI: 1.68 to 3.11) significantly increased the prevalence of periodontitis compared to individuals without these two factors. CONCLUSION: These results suggested that there were interactive effects between smoking, drinking and depression on periodontitis risk and policies aimed at healthy behaviours and mental health may be beneficial for our oral health.


Subject(s)
Alcohol Drinking , Depression , Smoking , Humans , Male , Female , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Smoking/adverse effects , Smoking/epidemiology , Middle Aged , Adult , Depression/epidemiology , United States/epidemiology , Risk Factors , Periodontitis/epidemiology , Nutrition Surveys , Aged , Periodontal Diseases/epidemiology , Young Adult , Surveys and Questionnaires
6.
Eur Rev Med Pharmacol Sci ; 28(8): 3144-3153, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38708473

ABSTRACT

OBJECTIVE: Multicause-of-death methods were used to analyze mortality and leading causes of death associated with polymyalgia rheumatica (PMR) in the United States from 1999 to 2020. MATERIALS AND METHODS: We analyzed mortality data from the Centers for Disease Control and Prevention (CDC) Data analysis system and selected death certificates that listed PMR as the cause of death based on the International Statistical Classification of Diseases and Related Health Problems (ICD-10) category code. Relevant mortality rates, number of deaths and historical trends were analyzed. The number of PMR-related deaths and age-standardized mortality rate (ASMR) trend charts were made using Excel 2010 version and trend lines were added. RESULTS: Over the last 22 years, the total number of PMR-related deaths in the United States was 15,421 women (89.8%), a ratio of about 1:9 men to women. When PMR is listed as the underlying cause of death, the ASMR for women and men (per 100,000 people) is approximately 1.8-5.1:1, and when it is listed as the non-underlying cause of death, it is 1.8-3.3:1. PMR deaths are more frequent in individuals aged 70 years and above, with patients aged 80 years and above being most affected. Among different ethnicities, the highest number of deaths was found in Caucasians, followed by Black or African American. When it comes to causes of death, heart disease still ranks first, followed by cancer. In addition, we also found that when PMR combined with malignant tumors as a multiple cause of death, the number of female deaths was higher than that of male deaths, the overall number of deaths of both showed an upward trend, and the overall ASMR of both showed a downward trend. CONCLUSIONS: In the past 22 years, we have observed a low mortality rate of PMR in the United States. However, for patients with PMR, especially elderly women, medical workers should be vigilant and pay attention to whether they are combined with other complications, such as malignant neoplasms, and make timely diagnosis and treatment to further reduce the mortality rate of patients with PMR.


Subject(s)
Cause of Death , Polymyalgia Rheumatica , Humans , Polymyalgia Rheumatica/mortality , United States/epidemiology , Female , Male , Aged , Aged, 80 and over , Middle Aged
7.
Zhonghua Zhong Liu Za Zhi ; 46: 1-11, 2024 May 20.
Article in Chinese | MEDLINE | ID: mdl-38764329

ABSTRACT

Objective: To provide supports for the cancer prevention and control strategies in China by comparing the disease burden, epidemic trends, 5-year relative survival rate and major determinants of common cancers between China and the United States. Methods: A descriptive secondary analysis was conducted using data extracted from the GLOBOCAN database, the Surveillance, Epidemiology, and End Results database, Global Burden of disease 2019 database, and previous studies. The main indicators included the cases of malignant tumors in different sites, the cases of deaths, the age-standardized incidence (world standard incidence) and mortality (world standard mortality), the 5-year relative survival rate, and population attributable fraction (PAF). Results: In 2022, an estimated 4.825 million new cases and 2.574 million deaths of malignant neoplasms in China. The world standard incidence rate (201.6/100 000) in China was lower than that in the United States (367.0/100 000), and the world standard mortality rate (96.5/100 000) was higher than that in the United States (82.3/100 000). Lung cancer ranked first in the disease burden of malignant tumors in China, the new cases and deaths accounted for 22.0% and 28.5% of all malignant tumors, respectively. The top three malignant tumors in China were breast cancer (11.5%), prostate cancer (9.7%) and lung cancer (9.5%), which were also among the top five causes of death. However, the second to fifth leading causes of death from malignant tumors in China were digestive system tumors (liver cancer 12.3%, stomach cancer 10.1%, colorectal cancer 9.3%, and esophageal cancer 7.3%). From 2000 to 2018, the world standard incidence of malignant tumors showed an increasing trend and the world standard mortality of malignant tumors showed a decreasing trend in China, while the world standard incidence and mortality of malignant tumors in the United States showed a significant decreasing trend after 2000. The incidence of breast cancer, colorectal cancer and thyroid cancer increased rapidly in China, while the incidence and mortality of stomach cancer, liver cancer and esophageal cancer decreased, but they still had a heavy disease burden. From 2003 to 2015, the overall 5-year relative survival rate of malignant tumors increased from 30.9% to 40.5% in China. However, with the exception of esophageal cancer, the 5-year relative survival rates of other major malignant tumors were lower than those in the United States. In 2019, the PAF of malignant tumors death attributable to potential modifiable risk factors was 48.3% in China, which was similar to the United States (49.8%). Of these, smoking was the most important attributable risk factor, and the PAF was more than 30% both in China and the United States. In addition, about 18.8% of malignant tumors were caused by preventable chronic infections, such as hepatitis B virus and Helicobacter pylori, while less than 4% of malignant tumors in the United States were caused by infection. Conclusions: China has made great progress in the prevention and treatment of malignant tumors, but it still faces a serious disease burden. The cancer spectrum is changing from developing countries to developed countries. We should pay attention to modifiable factors, take comprehensive measures, and prevent cancer scientifically.

8.
Nat Commun ; 15(1): 4581, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811546

ABSTRACT

The anomalous strange metal phase found in high-Tc cuprates does not follow the conventional condensed-matter principles enshrined in the Fermi liquid and presents a great challenge for theory. Highly precise experimental determination of the electronic self-energy can provide a test bed for theoretical models of strange metals, and angle-resolved photoemission can provide this as a function of frequency, momentum, temperature and doping. Here we show that constant energy cuts through the nodal spectral function in (Pb,Bi)2Sr2-xLaxCuO6+δ have a non-Lorentzian lineshape, consistent with a self-energy that is k dependent. This provides a new test for aspiring theories. Here we show that the experimental data are captured remarkably well by a power law with a k-dependent scaling exponent smoothly evolving with doping, a description that emerges naturally from anti-de Sitter/conformal-field-theory based semi-holography. This puts a spotlight on holographic methods for the quantitative modelling of strongly interacting quantum materials like the cuprate strange metals.

10.
Article in English | MEDLINE | ID: mdl-38821723

ABSTRACT

Gliomas are the most common primary malignant tumors of the brain, accounting for about 80% of all central nervous system malignancies. With the development of molecular biology, the molecular phenotypes of gliomas have been shown to be closely related to the process of diagnosis and treatment. The molecular phenotype of glioma also plays an important role in guiding treatment plans and evaluating treatment effects and prognosis. However, due to the heterogeneity of the tumors and the trauma associated with the surgical removal of tumor tissue, the application of molecular phenotyping in glioma is limited. With the development of imaging technology, functional magnetic resonance imaging (MRI) can provide structural and function information about tumors in a noninvasive and radiation-free manner. MRI is very important for the diagnosis of intracranial lesions. In recent years, with the development of the technology for tumor molecular diagnosis and imaging, the use of molecular phenotype information and imaging procedures to evaluate the treatment outcome of tumors has become a hot topic. By reviewing the related literature on glioma treatment and molecular typing that has been published in the past 20 years, and referring to the latest 2020 NCCN treatment guidelines, summarizing the imaging characteristic and sensitivity of radiotherapy and chemotherapy of different molecular phenotypes of glioma. In this article, we briefly review the imaging characteristics of different molecular phenotypes in gliomas and their relationship with radiosensitivity and chemosensitivity of gliomas.

11.
J Endocrinol Invest ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38795312

ABSTRACT

BACKGROUND: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. METHODS: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. RESULTS: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). CONCLUSIONS: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

12.
Mar Pollut Bull ; 203: 116461, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38754320

ABSTRACT

Microplastics (MPs) pose significant risks to marine ecosystems and human health, necessitating accurate predictions of their distributions in aquatic environments for effective risk mitigation. However, understanding MP transport dynamics is challenging because of the inadequate representation of MP characteristics such as size, shape, and density in numerical models. Further, the accuracy of the MP vertical profiles in existing models has not been thoroughly validated. Thus, we developed an MP transport model within the Finite Volume Community Ocean Model framework (FVCOM-MP) by integrating MP characteristics. We validated FVCOM-MP against experimental and analytical data, focusing on various MP transport modes and transitions. FVCOM-MP successfully replicates MP profiles in different transport modes, including the bedload, surface load, suspended load, and mixed load modes. Additionally, we introduce phase diagrams for classifying MP transport modes based on particle characteristics, enhancing our understanding of MP dynamics in aquatic systems. The transport modes for a number of real-world MP particles, including fishing line, plastic bag/bottle fragments, synthetic fibers, tire wear particles, polyvinyl chloride and expanded polystyrene pellets, were analyzed with these phase diagrams.


Subject(s)
Environmental Monitoring , Microplastics , Water Pollutants, Chemical , Water Pollutants, Chemical/analysis , Particle Size , Models, Theoretical , Plastics , Models, Chemical
13.
J Hosp Infect ; 149: 108-118, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38782057

ABSTRACT

BACKGROUND: In Taiwan, sequence type (ST) 239 and ST59 were two major clones among meticillin-resistant Staphylococcus aureus (MRSA) clinical isolates in the past two decades. USA300 (ST8) prevailed in the Americas but not in outside areas. Recently USA300 (ST8) emerged and was increasingly identified in Taiwan; we thus conducted an island-wide study to explore the role of USA300 among MRSA isolates. METHODS: One hundred MRSA bloodstream isolates identified in 2020 from each of the six participating hospitals in Taiwan were collected and characterized. The first 10 ST8 isolates from each hospital were further analysed by whole-genome sequencing. RESULTS: Of the 590 confirmed MRSA isolates, a total of 22 pulsotypes and 21 STs were identified. The strain of pulsotype AI/ST8 was the most common lineage identified, accounting for 187 isolates (31.7%) and dominating in five of six hospitals, followed by pulsotype A/ST239 (14.7%), pulsotype C/ST59 (13.9%) and pulsotype D/ST59 (9.2%). Of the 187 pulsotype AI/ST8 isolates, 184 isolates were characterized as USA300 and clustered in three major sub-pulsotypes, accounting for 78%. Ninety per cent of the 60 ST8 isolates for whole-genome sequencing were clustered in three major clades. CONCLUSIONS: In 2020, USA300 became the most common clone of MRSA in Taiwan, accounting for >30% of MRSA bloodstream isolates island wide. Most of USA300 isolates circulating in Taiwan might have been imported on multiple occasions and evolved into at least three successful local clades. MRSA USA300 has successfully established its role in Taiwan, an area outside of the Americas.

14.
Clin Radiol ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38763807

ABSTRACT

PURPOSE: To create a reliable radiomic nomogram for the prediction of the International Society of Urological Pathology (ISUP) grading ≥ 3 prostate cancer (PCa) patients. METHODS: patients with verified PCa were obtained from three different hospitals. The patients were divided into training, internal validation, and two external validation groups. A radiomic signature (rad-score) extracted from T2WI, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps were constructed in the training cohort. Eight clinical features were performed to develop a clinical model using univariate and multivariate logistic regression. The combined model incorporated the radiomic signature and clinical model. The model's performance was assessed by the receiver operating characteristic (ROC) curve. RESULTS: Rad-score, magnetic resonance imaging T-stage, and ADC value were significant predictors of ISUP ≥ 3 PCa. A nomogram of these three factors was shown to have greater diagnostic accuracy than using only the radiomic signature or clinical model alone. The area under the ROC curve was 0.85, 0.88, 0.81, 0.81 for the training, internal, and two external validation cohorts, respectively. In the stratified analysis based on the MR scanner model, the area under the ROC curve of predicting ISUP ≥ 3 PCa for GE, Siemens, and combined groups were 0.84, 0.83, and 0.84, respectively, in the combined training group and an internal validation group. CONCLUSIONS: The proposed nomogram has the potential to predict the differentiation degree of ISUP PCa patients.

15.
J Physiol Pharmacol ; 75(1)2024 02.
Article in English | MEDLINE | ID: mdl-38583438

ABSTRACT

Kinetochore scaffold 1 (KNL1) is indispensable for generating motile micro-tubule attachments and isolating chromosomes. KNL1 is highly expressed in multiple middle-route tissues and promotes tumor development. However, how it functions in non-small cell lung cancer (NSCLC) is unclear. Real-time quantitative PCR (RT-qPCR) and Western blotting (WB) were used to determine KNL1 expression in NSCLC tissues and cells. The sh-KNL1 or oe-KNL1 was transfected into NSCLC cells. The colony formation assay, cell counting kit-8 (CCK-8) assay, and flow cytometry were used to evaluate cell proliferation and apoptosis. A transwell assay was used to monitor invasion and migration. The CCK-8 assay was used to measure NSCLC cell sensitivity to chemotherapy drugs. WB confirmed the protein levels of apoptosis-related proteins, cell cycle-associated proteins, and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/nuclear factor kappaB (NF-κB) pathway. A PI3K/AKT/NF-κB pathway inhibitor was used to intervene in NSCLC cell transfection along with oe-KNL1, thus revealing the function of the pathway in carcinogenicity mediated by KNL1. In result KNL1 expression was substantially increased in NSCLC tissues and cells. High-level KNL1 expression is related to the poor prognosis of NSCLC patients. KNL1 silencing bolstered promoted NSCLC cell apoptosis and inhibited proliferation, cell cycle progression, invasion, and EMT, whereas KNL1 silencing had the opposite effect. KNL1 knockdown increased NSCLC cell sensitivity to chemical drugs. KNL1 promoted PI3K/AKT/NF-κB pathway activation, while PI3K/AKT/NF-κB pathway inhibition weakened the procancer effect mediated by KNL1 overexpression but had little influence on KNL1 levels. We conclude that KNL1 activates the PI3K/AKT/NF-κB pathway to increase NSCLC progression and attenuate NSCLC sensitivity to chemotherapy drugs.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Apoptosis Regulatory Proteins/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Kinetochores/metabolism , Kinetochores/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinase/genetics , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinase/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism
16.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(4): 376-382, 2024 Apr 12.
Article in Chinese | MEDLINE | ID: mdl-38599816

ABSTRACT

Tuberculosis, caused by infection with Mycobacterium tuberculosis (MTB), remains a global public health challenge. Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains make tuberculosis more difficult to control. New tools to study the biology of MTB can identify novel targets for drug discovery. Recently, the Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) combined with next-generation sequencing has provided many novel insights into the physiology and genetics of MTB. This review summarizes the application and optimization of CRISPRi in MTB biology.


Subject(s)
Extensively Drug-Resistant Tuberculosis , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Humans , Mycobacterium tuberculosis/genetics , Antitubercular Agents/therapeutic use , Clustered Regularly Interspaced Short Palindromic Repeats , Tuberculosis, Multidrug-Resistant/drug therapy , Extensively Drug-Resistant Tuberculosis/drug therapy , Biology , Microbial Sensitivity Tests
17.
Zhonghua Zhong Liu Za Zhi ; 46(4): 354-364, 2024 Apr 23.
Article in Chinese | MEDLINE | ID: mdl-38644271

ABSTRACT

Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (<60, 60-<70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.


Subject(s)
Early Detection of Cancer , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/blood , Prostate-Specific Antigen/blood , Aged , Middle Aged , Early Detection of Cancer/methods , Age Factors , ROC Curve , China , Sensitivity and Specificity , Mass Screening/methods , Area Under Curve
18.
Zhonghua Yi Xue Za Zhi ; 104(14): 1132-1137, 2024 Apr 09.
Article in Chinese | MEDLINE | ID: mdl-38583042

ABSTRACT

Objective: To explore the efficacy of short-term personalized vestibular rehabilitation supervised by special personnel (ST-PVR) versus fixed vestibular rehabilitation (FVR) on decompensated recurrent peripheral vertigo. Methods: A randomized controlled trial was carried out. Patients diagnosed with decompensated recurrent vertigo in the clinic of Eye & ENT Hospital, Fudan University from January to December 2018 were randomly allocated into FVR and ST-PVR groups via computer-generated randomization. The FVR group received fixed scheme involving gaze stabilization exercises, habituation exercises, balance and gait training, while the ST-PVR group received individualized training programs based on symptoms and vestibular function examination results, with adjustments made according to the progress of recovery. Patient symptoms and vestibular function improvement were assessed using the dizziness handicap inventory (DHI), activities-specific balance confidence (ABC), self-rating anxiety scale (SAS), caloric test, and sensory organization test (SOT) at 2, 4, and 8 weeks of treatment. Results: A total of 44 patients were included, including 16 males and 28 females, with an average age of (50.6±13.5) years. There were 21 cases in the FVR group and 23 cases in the ST-PVR group. In the ST-PVR group, DHI score (49.5±26.8 vs 61.3±21.4, P=0.046) and SAS score (39.1±7.8 vs 44.3±6.6, P=0.021) significantly improved after 2 weeks of treatment, while significant improvement occurred only after 8 weeks of treatment in the FVR group (DHI score: 28.1±15.9 vs 53.1±18.5, P=0.001; SAS score: 35.3±6.7 vs 43.1±8.4, P=0.010). There was no significant change of ABC score in the FVR group after 8 weeks of treatment (86.5±12.9 vs 83.4±18.1, P=0.373), while a significant improvement was observed in the ST-PVR group after 4 weeks of treatment (83.6±15.2 vs 78.4±15.1, P=0.015). The caloric test results showed that after 8 weeks of treatment, the proportion of patients with unilateral weakness<25% increased in both groups [FVR group: 57.1% (12/21) vs 9.5% (2/21), P=0.001; ST-PVR group: 52.2% (12/23) vs 17.4% (4/23), P=0.014]. In the ST-PVR group, the proportion of patients with dominant preference≤25% significantly increased [91.3% (21/23) vs 60.9% (14/23), P=0.016], while there was no significant change in the FVR group [61.9 (13/21) vs 57.1% (12/21), P=0.500]. The proportion of patients with SOT score≥70 in the ST-PVR group increased significantly after 2 weeks of treatment [69.6% (16/23) vs 30.4% (7/23), P=0.009], while the FVR group showed a significant increase only after 8 weeks of treatment [81.0% (17/21) vs 42.9% (9/21), P=0.012]. Conclusion: Both FVR and ST-PVR effectively promote vestibular compensation by improving objective vestibular functions and relieving subjective symptoms and anxiety of the patients with decompensation recurrent vertigo, while ST-PVR might shorten the recovery time and increase balance confidence.


Subject(s)
Dizziness , Vestibule, Labyrinth , Male , Female , Humans , Adult , Middle Aged , Dizziness/diagnosis , Vertigo/diagnosis , Exercise Therapy/methods , Anxiety , Postural Balance
19.
Eur Rev Med Pharmacol Sci ; 28(7): 2817-2826, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38639521

ABSTRACT

OBJECTIVE: Testicular ischemia-reperfusion induced by testicular torsion-detorsion increases the level of reactive oxygen species, leading to testicular damage. Allicin, one of the most active ingredients in garlic, is a significant exogenous antioxidant. In the research, the efficacy of allicin in treating testicular ischemia-reperfusion injury was assessed. MATERIALS AND METHODS: The study included sixty Sprague-Dawley male rats. Three groups with 20 rats per group were created as follows: control group, testicular ischemia/reperfusion-induced group, and testicular ischemia-reperfusion plus treatment with allicin group. The control group underwent a sham operation of the left testis without other interventions. In the testicular ischemia/reperfusion-induced group, rat left testis was subjected to 720° torsion for two hours and then detorsion. In the allicin-treated group, in addition to testicular ischemia-reperfusion, 50 mg/kg of allicin was injected intraperitoneally, starting immediately following detorsion. Testicular tissue samples were obtained to measure the protein expression of xanthine oxidase, which is a major source of reactive oxygen species formation, malondialdehyde level (a reliable marker of reactive oxygen species), and testicular spermatogenic function. RESULTS: Testicular ischemia-reperfusion significantly increased the expression of xanthine oxidase and malondialdehyde levels in ipsilateral testes while reducing testicular spermatogenic function. The expression of xanthine oxidase and malondialdehyde levels were significantly lower in ipsilateral testes, whereas testicular spermatogenic function in the allicin-treated group was significantly higher compared with those in the testicular ischemia-reperfusion group. CONCLUSIONS: Our findings indicate that allicin administration improves ischemia/reperfusion-induced testicular damage by limiting reactive oxygen species generation via inhibition of xanthine oxidase expression.


Subject(s)
Disulfides , Reperfusion Injury , Spermatic Cord Torsion , Sulfinic Acids , Rats , Male , Animals , Humans , Spermatic Cord Torsion/drug therapy , Spermatic Cord Torsion/complications , Spermatic Cord Torsion/metabolism , Rats, Sprague-Dawley , Xanthine Oxidase/metabolism , Xanthine Oxidase/pharmacology , Reactive Oxygen Species/metabolism , Testis , Reperfusion Injury/metabolism , Antioxidants/pharmacology , Ischemia/metabolism , Malondialdehyde/metabolism
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(4): 486-489, 2024 Apr 10.
Article in Chinese | MEDLINE | ID: mdl-38678342

ABSTRACT

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.


Subject(s)
Early Detection of Cancer , Humans , China , Neoplasms/diagnosis , Mass Screening/methods
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