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Cunzi Li,1 Lan Zhou,2,3 Hongyan Sun,2 Ming Ming Yang2 1The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, 518020, People’s Republic of China; 2Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, People’s Republic of China; 3Post-Doctoral Scientific Research Station of Basic Medicine, Jinan University, Guangzhou, 510632, People’s Republic of ChinaCorrespondence: Ming Ming Yang, Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), No. 1017 Dongmen North Road, Luohu District, Shenzhen, 518020, People’s Republic of China, Tel +86 22944163, Email ming4622@163.comAbstract: Age-related macular degeneration (AMD) is a degenerative ocular disease primarily affecting central vision in the elderly. Its pathogenesis is complex, involving cellular senescence and immune homeostasis dysregulation. This review investigates the interaction between these two critical biological processes in AMD pathogenesis and their impact on disease progression. Initially, cellular senescence is analyzed, with particular emphasis on retinal damage induced by senescent retinal pigment epithelial cells. Subsequently, the occurrence of immune homeostasis dysregulation within the retina and its mechanistic role in AMD areis explored. Furthermore, the paper also discusses in detail the interplay between cellular senescence and immune responses, forming a vicious cycle that exacerbates retinal damage and may influence treatment outcomes. In summary, a deeper understanding of the interrelation between cellular senescence and immune dysregulation is vital for the developing innovative therapeutic strategies for AMD.Keywords: age-related macular degeneration, cellular senescence, immune homeostasis dysregulation

Chao Liu,1,* Zhi Mao,1,* Mengmeng Yang,1 Hongjun Kang,1 Hui Liu,1 Liang Pan,1 Jie Hu,1 Jun Luo,2 Feihu Zhou1 1Department of Surgical Intensive Care Unit, Chinese People’s Liberation Army General Hospital, Beijing, 2Department of Surgical Intensive Care Unit, Xuanhan People’s Hospital, Sichuan, People’s Republic of China *These authors contributed equally to this work Background: Skin and soft tissue infections (SSTIs) are significant indications for antibiotic treatment. Daptomycin, a novel antibiotic, has been registered and licensed to be used in the treatment of these infections. However, its efficacy and safety remain controversial. Objective: The objective of this study was to conduct a systematic review with trial sequential analysis (TSA) to evaluate the efficacy and safety of daptomycin for the treatment of SSTIs and to analyze whether the available sample size has been large enough and is conclusive. Methods: PubMed, the Cochrane Library, and EMBASE were searched for published randomized controlled trials (RCTs) that compared daptomycin with other antibiotics in adult patients with SSTIs up to February 2016.Results: This meta-analysis included eight randomized controlled trials (n=2,002). There was no difference in either the clinical success rate (intention-to-treat population: relative risk [RR] =1.04, 95% confidence interval [CI] =0.99–1.10, P=0.12; clinically evaluable population: RR =1.00, 95% CI =0.97–1.04, P=0.82) or the microbiological success rate (RR =1.00, 95% CI =0.95–1.06, P=0.92) between the daptomycin and comparator groups for treating SSTIs, which was confirmed by TSA. Compared with vancomycin, daptomycin exhibited no advantage in increasing the clinical success rate (RR =1.03, 95% CI =0.95–1.13, P=0.47), and this was also confirmed by TSA. All-cause mortality, overall treatment-related adverse events, and creatine phosphokinase events were similar between these two groups. Conclusion: Daptomycin and comparator drugs are equally efficacious with regard to clinical and microbiological success for patients with SSTIs, and TSA showed that no additional randomized controlled trials are required. Although daptomycin is a good alternative when other antibiotics are contraindicated for patients with SSTIs and it can serve as a first-line treatment for SSTIs, clinicians should be aware of potential adverse events, such as daptomycin-induced acute eosinophilic pneumonia and creatine phosphokinase, when treating patients with daptomycin. Keywords: daptomycin, skin and soft tissue infections, vancomycin, meta-analysis, trial sequential analysis

Since the 1990s, researchers have been seeking approaches for applying artificial intelligence (AI) to prenatal ultrasound. With the breakthrough of cloud computing technology and the development of deep learning technology, AI in prenatal ultrasound has already entered the clinical application stage in recent years. How does AI combine with clinical prenatal ultrasound? Is the clinical application of AI in prenatal ultrasound effective? What can we expect from AI in prenatal ultrasound? This review introduces the latest developments in this field and explores the challenges and opportunities brought by AI to prenatal ultrasound.

Background: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. Methods: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. Discussion: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

Summary: The most devastating and catastrophic deterioration of myocardial ischemia-reperfusion injury (MIRI) is cardiomyocyte death. Here we aimed to evaluate the role of lncRNA-ZFAS1 in MIRI and delineate its mechanism of action. The level of lncRNA-ZFAS1 was elevated in MIRI hearts, and artificial knockdown of lncRNA-ZFAS1 in mice improved cardiac function. Notch1 is a potential target of lncRNA-ZFAS1, and lncRNA-ZFAS1 could bind to the promoter region of Notch1 and recruit DNMT3b to induce Notch1 methylation. Nicotinamide mononucleotide could promote the expression of Notch1 by competitively inhibiting the expression of DNMT3b and improving the apoptosis of cardiomyocytes and cardiac function.

To describe the impact of delayed call time for chest pain in the salvage of ST-segment elevation myocardial infarction (STEMI) patients and its associated independent risk factors, and to identify risk factors associated with cumulative morbidity and mortality in STEMI patients at 4 years after percutaneous coronary intervention (PCI). Retrospective analysis of 398 patients diagnosed with STEMI and treated with emergency PCI within 24 hours of symptom onset in Fuyang People's Hospital from April 2018 to April 2021. The enrolled patients were divided into ≤60 minutes group (193 cases), and > 60 minutes group (205 cases), according to the delayed call time of patients with chest pain. Analysis of basic clinical data, rescue time, and major cardiovascular adverse events in the 2 groups. Multifactorial logistic regression analysis of independent correlates of delayed chest pain calls and Cox proportional risk regression modeling of risk factors for cumulative morbidity and mortality at 4 years after surgery. Compared to the delayed call time ≤ 60 minutes group, the > 60 minutes group had a higher proportion of females, a history of diabetes, rural remote areas, and farmer occupation ( P 60 minutes for chest pain. In the delayed call time ≤60 minutes group, the time from symptom onset-to-balloon (S0-to-B) and from symptom onset-to-first medical contact (SO-to-FMC) were smaller than in the delayed call time >60 minutes group ( P 60 minutes ( P 60 minutes, left main + 3 branch lesions, and cardiac function Killip ≥ III were all risk factors for cumulative morbidity and mortality at 4 years after PCI in patients with STEMI. Delayed call time for chest pain >60 minutes, left main + 3 branch lesions, and cardiac function Killip ≥ III are all risk factors for cumulative morbidity and mortality in STEMI patients at 4 years after PCI. Reducing the delayed call time for chest pain can improve the long-term prognosis of patients.

Background Rehabilitation is crucial to recovering patients’ dysfunction, improving their life quality, and promoting an early return to their family and society. In China, most patients in rehabilitation units are patients transferred from neurology, neurosurgery, and orthopedics, and most of these patients face problems such as continuously bedridden or varying degrees of limb dysfunction, all of which are risk factors for deep venous thrombosis. The formation of deep venous thrombosis can delay the recovery process and result in significant morbidity, mortality, and higher healthcare costs, so early detection and individualized treatment are needed. Machine learning algorithms can help develop more precise prognostic models, which can be of great significance in the development of rehabilitation training programs. In this study, we aimed to develop a model of deep venous thrombosis for inpatients in the Department of Rehabilitation Medicine at the Affiliated Hospital of Nantong University using machine learning methods. Methods We analyzed and compared 801 patients in the Department of Rehabilitation Medicine using machine learning. Support vector machine, logistic regression, decision tree, random forest classifier, and artificial neural network were used to build models. Results Artificial neural network was the better predictor than other traditional machine learnings. D-dimer levels, bedridden time, Barthel Index, and fibrinogen degradation products were common predictors of adverse outcomes in these models. Conclusions Risk stratification can help healthcare practitioners to achieve improvements in clinical efficiency and specify appropriate rehabilitation training programs.

With the improvement in survival of patients with tumors, and continuous advancement of diagnostic technology and treatment modalities, instances of multiple primary malignancies (MPMs) are becoming an increasingly common phenomenon. The occurrence of esophageal-relevant MPMs increases the difficulty of diagnosis and treatment, and the overall prognosis is poor. Esophageal cancer related-MPMs tend to occur in areas such as the head, neck, stomach, and lungs. “Field cancerization” is one theoretical basis for the disease, and chemoradiotherapy, environmental life factors, and gene polymorphism are etiological factors. However, the influence of new therapeutic methods on MPM is still unclear, and the relationship between gene polymorphism and MPMs related to esophageal cancer needs further elucidation. Additionally, there is a lack of unified standards for diagnosis and treatment. Therefore, this study aimed to review the causes, clinical features, and prognostic factors of MPMs related to esophageal cancer.

To assess the prevalence and management of atrial thrombus in patients with nonvalvular atrial fibrillation (NVAF) and identify the risk factors of the nonresolution of atrial thrombus. This single-center retrospective observational study consecutively enrolled patients with NVAF and atrial thrombus detected using transesophageal echocardiography (TEE) or cardiac computed tomography angiography (CTA) from January 2012 to December 2020. Patients with prior left atrial appendage (LAA) intervention were excluded. The primary endpoint was the presence of atrial thrombus, while the secondary endpoint was the complete resolution of atrial thrombus. The prevalence of atrial thrombus in patients with NVAF was 1.4%. Ninety patients with atrial thrombus (mean age 62.8 ± 11.9 years and 61.1% men) were finally analyzed. Atrial thrombus was in the LAA in 82 (91.1%) patients. During follow up, 60% of the patients showed complete resolution of atrial thrombus. Congestive heart failure (odds ratio [OR]: 8.94; 95% confidence interval [CI]: 1.67-47.80) and a history of ischemic stroke (OR: 8.28; 95% CI: 1.48-46.42) were independently associated with the risk of the nonresolution of atrial thrombus. The presence of atrial thrombus in patients with NVAF who received anticoagulation therapy is non-negligible. Even in anticoagulated patients, TEE or cardiac CTA might still be needed. Congestive heart failure and a history of ischemic stroke are risk factors of the nonresolution of atrial thrombus.

Study Design: A retrospective study. Objective: To develop a new MRI scoring system to assess patients' clinical characteristics, outcomes and complications. Methods: A retrospective 1-year follow-up study of 366 patients with cervical spondylosis from 2017 to 2021. The CCCFLS scores (cervical curvature and balance (CC), spinal cord curvature (SC), spinal cord compression ratio (CR), cerebrospinal fluid space (CFS). Spinal cord and lesion location (SL). Increased Signal Intensity (ISI) were divided into Mild group (0-6), Moderate group (6-12), and Severe group (12-18) for comparison, and the Japanese Orthopaedic Association (JOA) scores, visual analog scale (VAS), numerical rating scale (NRS), Neck Disability Index (NDI) and Nurick scores were evaluated. Correlation and regression analyses were performed between each variable and the total model in relation to clinical symptoms and C5 palsy. Results: The CCCFLS scoring system was linearly correlated with JOA, NRS, Nurick and NDI scores, with significant differences in JOA scores among patients with different CC, CR, CFS, ISI scores, with a predictive model (R2 = 69.3%), and significant differences in preoperative and final follow-up clinical scores among the 3 groups, with a higher rate of improvement in JOA in the severe group (P <.05), while patients with and without C5 paralysis had significant differences in preoperative SC and SL (P <.05). Conclusion: CCCFLS scoring system can be divided into mild (0-6). moderate (6-12), severe (12-18) groups. It can effectively reflect the severity of clinical symptoms, and the improvement rate of JOA is better in the severe group, while the preoperative SC and SL scores are closely related to C5 palsy. Level of Evidence: III [ABSTRACT FROM AUTHOR]

Diabetes is a long-term chronic disease, and cardiovascular disease is the leading cause of death. Diabetic cardiomyopathy (DCM), one of the cardiovascular complications of diabetes, has many uncertain factors. Epicardial fat, as the heart fat bank, functions as fatty tissue and is the heart’s endocrine organ. The existence of diabetes affects the distribution of heart fat and promotes the secretion of adipokine. In different pathological conditions, it can promote the secretion of pro-inflammatory adipokine, reactive oxygen species, oxidative stress, and even autophagy, thus affecting cardiac function. In this paper, we will elaborate on the mechanism of epicardial fat in the pathogenesis of diabetic cardiomyopathy.

Background: Anlotinib is used as a third-line treatment for advanced non-small-cell lung cancer (NSCLC), but has limited clinical benefits and several side effects, such as diarrhea and acneiform skin rash. Traditional Chinese Medicine (TCM) is commonly used to treat cancers in China. Chinese herbal medicines may have the potential as adjuvant therapies to reduce toxicity and improve the efficacy of treatments for NSCLC. Given the positive outcomes of basic research, we plan to evaluate whether the addition of the Chinese herbal medicine Yifei Sanjie formula (YFSJF) to anlotinib can improve the progression-free survival (PFS) of advanced NSCLC patients. Methods: A multicenter, randomized, double-blind, placebo-controlled parallel-group controlled pilot trial will be performed. Forty eligible patients will be randomized in a ratio of 1:1 to the intervention (YFSJF + anlotinib) and control (placebo + anlotinib) groups. Participants will be advised to take 12 mg/day of anlotinib on days 1 to 14 of each 21-day cycle. YFSJF or placebo will be administered (15 g twice daily) during each cycle until progression of disease (PD). The primary outcome will be progression-free survival (PFS), and the secondary outcomes will be overall survival (OS), the objective response rate (ORR), and patient-reported outcomes (PRO). Tumors will be assessed based on RECIST v. 1.1 after every 2 cycles of treatment. The M. D. Anderson Symptom Inventory-Lung Cancer (MDASI-LC) will be used to evaluate PRO at baseline and weekly thereafter until PD. Discussion: This will be the first trial to evaluate the effectiveness and safety of TCM combined with anlotinib for the treatment of NSCLC. The results of this randomized controlled trial will fill a gap in the research by showing whether YFSJF combined with anlotinib can improve PFS in NSCLC patients. Trial Registration: The study was registered on June 8th, 2021 on Chinese Clinical Registry; registration number ChiCTR2100047143. ( https://www.chictr.org.cn/index.aspx ). Ethics and Dissemination: The Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine approved the study protocol (approval no.: K2020151, 2021/08/19). The study will also be supervised and managed by the Ethics Committee.

The evaluation of megakaryocytes is an important part of the work up on bone marrow smear examination. It has significance in the differential diagnosis, therapeutic efficacy assessment, and predication of prognosis of many hematologic diseases. The process of manual identification of megakaryocytes are tedious and lack of reproducibility; therefore, a reliable method of automated megakaryocytic identification is urgently needed. Three hundred and thirty-three bone marrow aspirate smears were digitized by Morphogo system. Pathologists annotated megakaryocytes on the digital images of marrow smears are applied to construct a large dataset for testing the system's predictive performance. Subsequently, we obtained megakaryocyte count and classification for each sample by different methods (system-automated analysis, system-assisted analysis, and microscopic examination) to study the correlation between different counting and classification methods. Morphogo system localized cells likely to be megakaryocytes on digital smears, which were later annotated by pathologists and the system, respectively. The system showed outstanding performance in identifying megakaryocytes in bone marrow smears with high sensitivity (96.57%) and specificity (89.71%). The overall correlation between the different methods was confirmed the high consistency ( r ≥ 0.7218, R 2 ≥ 0.5211) with microscopic examination in classifying megakaryocytes. Morphogo system was proved as a reliable screen tool for analyzing megakaryocytes. The application of Morphogo system shows promises to advance the automation and standardization of bone marrow smear examination.

Objective: Postoperative readmissions are considered an indicator of healthcare quality. The purpose of this study was to assess the factors associated with readmission following pulmonary resection for lung cancer. Methods: A comprehensive search was performed in PubMed, Web of science, the Cochrane Library, and databases of CNKI and Wanfang. We collected the factors associated with readmission following pulmonary resection from the included studies, and data analysis was conducted with STATA SE12.0 software. Results: A total of 11 studies (386 012 participants) were included. The meta-analysis results showed that age (standardized mean difference [SMD] = 0.093), male sex (odds ratio [OR] = 1.260), Charlson score (SMD = 1.408), forced expiratory volume in 1 second predicted (SMD = −0.203), congestive heart failure (OR = 1.708), peripheral vascular disease (OR = 1.436), and histology (OR = 0.804) were associated with readmission ( P

Pancreatic cancer has the highest mortality rate of all major cancers, with a 5-year survival rate of about 10%. Early warning signs and symptoms of pancreatic cancer are vague or nonexistent, and most patients are diagnosed in Stage IV, when surgery is not an option for about 80%–85% of patients. For patients with inoperable pancreatic cancer, current conventional treatment modalities such as chemotherapy and radiotherapy (RT) have suboptimal efficacy. Tumor progression is closely associated with the tumor microenvironment, which includes peripheral blood vessels, bone marrow-derived inflammatory cells, fibroblasts, immune cells, signaling molecules, and extracellular matrix. Tumor cells affect the microenvironment by releasing extracellular signaling molecules, inducing peripheral immune tolerance, and promoting tumor angiogenesis. In turn, the immune cells of the tumor affect the survival and proliferation of cancer cells. Myeloid-derived suppressor cells are key cellular components in the tumor microenvironment and exert immunosuppressive functions by producing cytokines, recognizing other immune cells, and promoting tumor growth and metastasis. Myeloid-derived suppressor cells are the main regulator of the tumor immune response and a key target for tumor treatments. Since the combination of RT and immunotherapy is the main strategy for the treatment of pancreatic cancer, it is very important to understand the immune mechanisms which lead to MDSCs generation and the failure of current therapies in order to develop new target-based therapies. This review summarizes the research advances on the role of Myeloid-derived suppressor cells in the progression of pancreatic cancer and its treatment application in recent years.

Previous studies have suggested that Hestia criteria could effectively identifying patients with acute pulmonary embolism (PE) who were at low risk of mortality for outpatient treatment or early discharge. But the performance of Hestia criteria in stratifying patients at different risk class is still unknown. We sought to comprehensively evaluate the prognostic impact of Hestia criteria for PE. The literatures search was conducted in PubMed, Web of Science and EMBASE from 1 August 2011 to 31 October 2021. Finally, Eight studies with 4110 patients were included in our meta-analysis. Overall, the pool percentage of patients classified as low-risk group and high-risk group were 41.4%% and 58.6% respectively, and the all-course mortality rates of each group were 2.3% and 10.6%, respectively. The pooled rate of PE-related composite adverse outcomes in high-risk group was increasingly higher than in low-risk group (15.7% vs 4.4%). High risk group was also markedly associated with overall mortality (OR: 7.21, 95%CI: 4.96-10.46, p

Background: The role of N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) in osteosarcoma (OS) has not been fully studied yet. We aimed to identify m6A-related lncRNAs that could act as prognostic biomarkers for OS. Methods: Pearson correlation was performed to identify m6A-related lncRNAs. Univariate and multivariate Cox regression analyses were performed to construct the risk model and assess whether the risk score was an independent prognostic factor for patients with OS. Gene Set Enrichment Analysis (GSEA) was performed to analyze the functions of genes in high-risk and low-risk groups. StarBase and Cytoscape were used to construct a competing endogenous RNA (ceRNA) network based on m6A-related prognostic lncRNA signature. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze the function of genes involved in the ceRNA network. Results: We extracted 122 common lncRNAs from TCGA and Gene Expression Omnibus (GEO) databases. Pearson correlation results revealed 59 significant m6A-related lncRNAs in The Cancer Genome Atlas (TCGA) database, from which 2 were screened to construct a risk signature in TCGA dataset, which was then validated in the GEO dataset. A corresponding risk score was calculated and shown to be an independent prognostic factor for patients with OS. Enrichment analysis indicated that cell proliferation-related biological processes were more common in the high-risk group, while immune-related biological processes were more common in the low-risk group. Moreover, we established a nomogram that had a good ability to predict the overall survival of patients with OS. Additionally, a ceRNA network based on small nucleolar RNA host gene 7 ( SNHG7 ) and small nucleolar RNA host gene 12 ( SNHG12 ) was constructed, with genes that were enriched in hepatocellular carcinoma, gastric cancer, and non-small-cell lung cancer pathways. Conclusion: Our study revealed the prognostic role of m6A-related lncRNAs in OS and identified SNHG7 and SNHG12 as potential biomarkers for predicting the prognosis of patients with OS. These findings have enriched our understanding of the role of m6A modification in the dysregulation of lncRNAs in OS.

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Accumulating evidence has shown that long noncoding RNAs (lncRNAs) serve important roles in the development of OSCC. The purpose of this study was to investigate the biological function and underlying regulatory mechanism of lncRNA homeobox A cluster antisense RNA2 (HOXA-AS2) in OSCC. RT-qPCR was performed to analyze the HOXA-AS2 expressions in human immortalized oral epithelial cell (HIOEC) line, human OSCC cell lines, and plasma. The expression of HOXA-AS2 and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) in Tca-8113 cells were knocked down or overexpressed by transfection with shRNA-HOXA-AS2 or pcDNA-EZH2, respectively. The interaction between HOXA-AS2 and EZH2 was validated by RNA immunoprecipitation assay. In addition, cell proliferation was assessed by CCK-8 and EdU assays. Cell cycle distribution was analyzed by flow cytometry. Cell migration and invasion were detected using wound healing and Transwell assays, respectively. Apoptosis was detected by TUNEL staining. The protein expression levels of cell cycle and apoptosis-related proteins were measured by western blot analysis. Compared with HIOEC cells, HOXA-AS2 expression in OSCC cells was upregulated. HOXA-AS2 knockdown significantly inhibited Tca-8113 cell proliferation, blocked the cell cycle by arresting cells in the G0/G1 phase, promoted apoptosis, and suppressed migration and invasion. In addition, HOXA-AS2 was predicted to directly target EZH2 and positively regulate EZH2 expression. EZH2 overexpression could reverse the inhibitory effect of HOXA-AS2 knockdown on the proliferation, migration, and invasion of Tca-8113 cells. In summary, the findings suggested that HOXA-AS2 may inhibit cell proliferation, invasion, and migration, induce cell cycle arrest in the G0/G1 phase, and increase cell apoptosis by targeting EZH2. The research indicated that HOXA-AS2/EZH2 axis may play a key role in the development of OSCC.

To explore the possible single nucleotide polymorphisms (SNPs) sites in the promoter region of fibrinogen B β (FGB), and construct logistic regression model and haplotype model, so as to reveal the influence of FGB promoter SNPs on susceptibility, hemodynamics and coagulation function of lower extremity deep venous thrombosis (LEDVT) in the genetic background. LEDVT patients (120) and healthy people (120) were taken as case and control objects, respectively. SNPs and their genotypes of FGB promoter were detected by promoter sequencing and PCR-RFLP. The parameters of coagulation system were evaluated. There were 6 SNPs in FGB promoter, which were β-148C/T, β-249C/T, β-455G/A, β-854G/A, β-993C/T and β-1420G/A. The genotype and allele frequency of β-1420 G/A, β-455G/A, β-249c/T and β-148C/T were significantly different between the LEDVT group and the control group, but not β-993C/T and β-854G/A. In addition, we found that the higher the content of Fibrinogen (FG), the higher the risk of LEDVT. The risk of LEDVT increased by 4.579 times for every unit increase of fibrinogen. We also found that FG, PT and APTT in LEDVT group were higher than those in control group, while TT was lower than those in control group; Furthermore, there was no significant difference in all coagulation indexes among 6 SNP genotypes in LEDVT group, while a significant difference was found between the 2 genotypes of β-993C/T in the control group. β-993C/T may indirectly affect the susceptibility of LEDVT by improving the basic level of plasma FG.

Background: Long non-coding RNA bladder cancer associated transcript 1 (BLACAT1) is oncogenic in several types of cancers. However, little is known concerning its expression and function in prostate cancer. Methods: Paired prostate cancer samples were collected, and the expression levels of BLACAT1, miR-29a-3p and disheveled segment polarity protein 3 (DVL3) were examined by quantitative real-time polymerase chain reaction (qRT-PCR); BLACAT1 shRNAs were transfected into PC-3 and LNCaP cell lines, and proliferative ability was detected by cell counting kit-8 (CCK-8) assay; qRT-PCR and Western blot were used to analyze the changes of miR-29a-3p and DVL3; dual-luciferase reporter gene assay was used to determine the regulatory relationships between miR-29a-3p and BLACAT1, and miR-29a-3p and DVL3. Results: BLACAT1 expression was significantly up-regulated in cancerous tissues of prostate cancer samples and positively correlated with the expression of DVL3, while negatively associated with miR-29a-3p. After the transfection of BLACAT1 shRNAs into prostate cancer cells, the proliferative ability and metastatic ability of cancer cells were significantly inhibited; BLACAT1 shRNAs could reduce the expression of DVL3 on both mRNA and protein expressions levels, the luciferase activity of BLACAT1 reporter was inhibited by miR-29a-3p, and DVL3 was validated as a target gene of miR-29a-3p. Conclusion: BLACAT1 expression is abnormally up-regulated in prostate cancer tissues. BLACAT1 can modulate the proliferative and metastatic ability of prostate cancer cells and have the potential to be the “ceRNA” to regulate the expression of DVL3 by sponging miR-29a-3p.

The microRNA-200 (miR-200) family has been reported to be vital for the inhibition of epithelial-to-mesenchymal transition (EMT) in tumor cells. The miR-200 family represents a complex multi-factorial regulatory network which has not been well described in breast cancer. This study aimed to clarify the underlying regulatory association between IL-8 and miR-200 family in the process of EMT in breast cancer cell. In estrogen-receptor (ER) positive breast cancer cell line MCF-7, IL-8 overexpression cells were performed by lentivirus transfection as endogenous regulation with additional exogenous IL-8 stimulation. Transient overexpressions of miR-200 family were performed after endogenous or exogenous IL-8 overexpression in MCF-7 cells. IL-8 knockdown cells were constructed via siRNA and shRNA transfection in triple negative breast cancer cell line MDA-MB-231. N-cadherin, vimentin and ZEB2 were down-regulated and E-cadherin was up-regulated in IL-8 knockdown group compared with control group. On the other hand, N-cadherin, vimentin and ZEB2 were up-regulated and E-cadherin was down-regulated in IL-8 overexpression group compared with control group. This indicated IL-8 promotes EMT in breast cancer cells. Transwell assay showed that IL-8 increased the migration and invasiveness of tumor cells. Furthermore, we performed transient overexpression of miR-200 family after endogenous or exogenous IL-8 overexpression in MCF-7 cells, which showed that the miR-200 family could inhibit EMT induced by IL-8. IL-8 promoted EMT via downregulation of miR-200 family expression in breast cancer cells and increases tumor cell migration and invasion.

Aldosterone-producing adenomas (APA) is one of the causative factors of primary aldosteronism. Previous studies have suggested that there are somatic CTNNB1 mutations in APA, but the specific mechanism of CTNNB1 mutation in APA tumorigenesis and aldosterone secretion remains unclear. In the present study, human adrenocortical carcinoma cell line H295 R was used to establish stable CTNNB1 knockdown cell lines. Cell proliferation and aldosterone secretion of H295 R cells in response to angiotensin Ⅱ (Agn Ⅱ) were analyzed. We found that CTNNB1 knockdown reduced β-catenin expression and inhibited proliferation of H295 R cells. CTNNB1 knockdown inhibited Wnt/β-catenin signaling pathway and downregulated expression of downstream genes including axin 2, lymphoid enhancer binding factor 1 ( LEF1 ), and cyclin D1. In addition, CTNNB1 knockdown decreased responses of H295 R cells to Agn Ⅱ and decreased aldosterone secretion. Our findings suggest that CTNNB1 knockdown can inhibit H295 R cell proliferation and decrease aldosterone secretion in the responses of H295 R cells to Ang II through inhibiting Wnt/β-catenin signaling pathway, indicating that targeting Wnt/β-catenin signaling pathway may be an important approach to decrease aldosterone secretion in the treatment of aldoster-producing adenomas.

MicroRNAs (miRNAs) are emerging as critical mediators in tumors, including triple-negative breast cancer (TNBC). The role of miR-518a-3p in TNBC was investigated to identify potential therapeutic target. Data from KM Plotter database ( www.kmplot.com ) showed that high miR-518a-3p expression was significantly associated with overall survival of patients with TNBC ( p = 0.04). The expression of miR-518a-3p was dysregulated in TNBC cells. Functional assays revealed that over-expression of miR-518a-3p inhibited cell invasion and migration of TNBC. Additionally, miR-518a-3p could target TMEM2 (transmembrane protein 2), and decreased protein and mRNA expression of TMEM2 in TNBC cells. Knockdown of TMEM2 suppressed cell invasion and migration through inhibiting phospho (p)-JAK1 (Janus kinase 1) and p-STAT (signal transducer and activator of transcription protein) 1/2. Moreover, over-expression of TMEM2 counteracted the suppressive effect of miR-518a-3p on TNBC invasion and migration through promoting the levels of p-JAK1 and p-STAT1/2. In conclusion, miR-518a-3p negatively regulates the JAK/STAT pathway via targeting TMEM2 and suppresses invasion and migration in TNBC, suggesting that miR-518a-3p may be a potential therapeutic target in TNBC.

Objective: Long noncoding RNAs (lncRNAs) are potential biomarkers for cancers. Nevertheless, the ability of long noncoding RNA lung cancer-associated transcript 1 in patients with multiple myeloma remains unknown. The purpose of this current study was to figure out its function in multiple myeloma. Methods: Firstly, the expression of long noncoding RNA lung cancer-associated transcript 1 in cancer or normal tissues and serum from patients with multiple myeloma and normal donors was detected. Secondly, the expression of long noncoding RNA lung cancer-associated transcript 1 was overexpressed or silenced in U266 and H929 cells, respectively to detect changes of proliferation and apoptosis in multiple myeloma in vitro . Subsequently, the expression of transforming growth factor-β signaling pathway-related proteins was detected by western blot analysis. Finally, the effect of long noncoding RNA lung cancer-associated transcript 1 on the growth of multiple myeloma cells in vivo was evaluated by tumor xenograft in nude mice. Results: Long noncoding RNA lung cancer-associated transcript 1 was increased in cancer tissues and serum of patients with multiple myeloma as well as multiple myeloma cells, which was correlated with dismal prognosis of patients with multiple myeloma. Overexpression of long noncoding RNA lung cancer-associated transcript 1 promoted the activity of U266 and H929 cells, while inhibition of long noncoding RNA lung cancer-associated transcript 1 suppressed the activity of U266 and H929 cells. In addition, long noncoding RNA lung cancer-associated transcript 1 was found to promote activation of the transforming growth factor-β signaling pathway. Furthermore, long noncoding RNA lung cancer-associated transcript 1 knockdown restricted the growth of multiple myeloma cells in vivo . Conclusion: This study suggests that suppression of long noncoding RNA lung cancer-associated transcript 1 inhibits the activation of transforming growth factor-β signaling pathway, thereby inhibiting the growth of multiple myeloma cells.

Objective: The present study aimed to explore the correlation of protein kinase D 1 with prognosis in bortezomib-treated multiple myeloma patients and further investigate the effect of protein kinase D 1 knockdown on drug sensitivity to bortezomib in multiple myeloma cells. Methods: Totally, 104 de novo symptomatic multiple myeloma patients treated with bortezomib-based regimens and 30 healthy controls were recruited. Bone marrow mononuclear cells–derived plasma cells were collected from multiple myeloma patients before initial treatment and from healthy controls on the bone marrow donation, respectively, then protein kinase D 1 protein/messenger RNA expressions were detected by Western blot and reverse transcription quantitative polymerase chain reaction, respectively. The effect of protein kinase D 1 knockdown on drug sensitivity to bortezomib was detected by transfecting protein kinase D 1 knockdown plasmid and control plasmid into RPMI8226 and U266 cells. Results: Protein kinase D 1 protein/messenger RNA expressions were both upregulated in multiple myeloma patients compared with healthy controls and presented good value in differentiating multiple myeloma patients from healthy controls. Furthermore, protein kinase D 1 protein/messenger RNA expressions were both associated with high International Staging System stage and t (4; 14). Furthermore, both complete response rate and overall response rate were reduced in protein kinase D 1 high patients compared with protein kinase D 1 low patients; similarly, progression-free survival and overall survival were both decreased in protein kinase D 1 high patients compared with protein kinase D 1 low patients. In addition, in RPMI8226 and U266 multiple myeloma cells, protein kinase D 1 knockdown increased drug sensitivity to bortezomib. Conclusion: Protein kinase D 1 has the potential to predict poor treatment response and unfavorable survival of bortezomib-based treatment in multiple myeloma patients, and its knockdown enhanced drug sensitivity to bortezomib in multiple myeloma cells.

Background: Whether statins can reduce the incidence of cancers has been an interesting topic in recent years. This meta-analysis aimed to determine the relationship between statin treatment with the risk of hepatocellular carcinoma. Methods: Studies published up to July 2019 were screened from databases. The data from approved studies were pooled. Random-effects or fixed-effects model was used to calculate the relative risk with 95% CIs in the overall group and subgroups. Sensitivity and meta-regression analyses were performed, and publication bias was evaluated. Results: A total of 18 studies involving 1 611 596 patients were included in this meta-analysis. The overall result showed a significantly reduced risk of hepatocellular carcinoma (relative risk = 0.54, 95% CI: 0.42-0.66) in statin users. In comparison to the risk in nonstatin users, the risk of hepatocellular carcinoma was reduced in all subgroups. The dose of statins and their pharmacokinetics can partly explain the heterogeneity in the overall meta-analysis ( I 2 = 94.6%, P = .000). A dose-dependent effect of statin use for the reduced risk of hepatocellular carcinoma was found. Conclusions: Findings from this meta-analysis support that statin use can significantly reduce the incidence of hepatocellular carcinoma.

Gastric cancer is one of the most commonly occurring cancers worldwide. Investigation of long noncoding RNAs is of increasing interest, particularly in relation to their contribution to progression and prognosis of gastric cancers; however, insufficient studies been performed investigating the part of long noncoding RNAs play in gastric cancer carcinogenesis. Patterns of dysregulated long noncoding RNA and messenger RNA between mucosa gastric cancer and adjacent normal tissues were identified using long noncoding RNAs microarray analysis. Quantitative real-time polymerase chain reaction was conducted as a means to verify the obtained data. Both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were subsequently used to investigate the function of dysregulated long noncoding RNAs and messenger RNAs. Cis and trans action was used to predict the possible targets of long noncoding RNAs, and a coexpression network was created to simulate the complex intergenic interactions. Ninety-five dysregulated long noncoding RNAs and 123 messenger RNAs were identified, and quantitative real-time polymerase chain reaction was used to validate 6 filtered long noncoding RNAs. Gene Ontology and KEGG pathway analyses identified several remarkably biological processes and signaling pathways, including spliceosome, RNA transport, and ubiquitin-mediated proteolysis. The transcriptional factors MYC, GABPA, and E2F1 were found to play a central function in the long noncoding RNAs process, as indicated by the coexpression network. This study revealed the dysregulated long noncoding RNA profiles of mucosal gastric cancer. The results shed light on the biological function of long noncoding RNAs in gastric cancer pathogenesis. This provides useful information for exploring potential early screening biomarkers in gastric cancer.

To investigate the differences in serum tryptophan, lysine, and phenylalanine levels in breast cancer patients, the correlation between the three amino acids with the chemotherapy regimen, and their significance in the clinical diagnosis and treatment of breast cancer. Clinical data were collected from the Department of Breast Surgery at Yunnan Cancer Hospital, encompassing 216 cases from July to December 2020, including 91 healthy individuals, 38 with benign tumors, and 87 with cancer. Amino acid levels were measured using liquid chromatography-tandem mass spectrometry. Statistical analyses, such as the Kruskal-Wallis H-test and Wilcoxon test, were conducted to compare the levels of these amino acids across the healthy group, benign tumor group, and breast cancer group. The χ2 test and Fisher's exact probability method were employed to assess the relationship between amino acid levels and breast cancer stage, grade, and chemotherapy regimen. The results indicated that there were significant differences in serum lysine (H = 36.13, P .05) and phenylalanine (F = 1.466, P > .05) levels across different conventional chemotherapy regimens among the breast cancer cases studied. Serum lysine and phenylalanine levels might serve as potential biomarkers for breast cancer, and the choice of chemotherapy regimen is unlikely to impact significant changes in these amino acid levels.

Purpose Our study aimed to investigate the potential of radiomics with DCE-MRI for predicting Ki-67 expression in invasive ductal breast cancer. Method We conducted a retrospective study including 223 patients diagnosed with invasive ductal breast cancer. Radiomics features were extracted from DCE-MRI using 3D-Slicer software. Two Ki-67 expression cutoff values (20% and 29%) were examined. Patients were divided into training (70%) and test (30%) sets. The Elastic Net method selected relevant features, and five machine-learning models were established. Radiomics models were created from intratumoral, peritumoral, and combined regions. Performance was assessed using ROC curves, accuracy, sensitivity, and specificity. Result For a Ki-67 cutoff value of 20%, the combined model exhibited the highest performance, with area under the curve (AUC) values of 0.838 (95% confidence interval (CI): 0.774–0.897) for the training set and 0.863 (95% CI: 0.764–0.949) for the test set. The AUC values for the tumor model were 0.816 (95% CI: 0.745–0.880) and 0.830 (95% CI: 0.724–0.916), and for the peritumor model were 0.790 (95% CI: 0.711–0.857) and 0.808 (95% CI: 0.682–0.910). When the Ki-67 cutoff value was set at 29%, the combined model also demonstrated superior predictive ability in both training set (AUC: 0.796; 95% CI: 0.724–0.862) and the test set (AUC: 0.823; 95% CI: 0.723–0.911). The AUC values for the tumor model were 0.785 (95% CI: 0.708–0.861) and 0.784 (95% CI: 0.663–0.882), and for the peritumor model were 0.773 (95% CI: 0.690–0.844) and 0.729 (95% CI: 0.603–0.847). Conclusion Radiomics with DCE-MRI can predict Ki-67 expression in invasive ductal breast cancer. Integrating radiomics features from intratumoral and peritumoral regions yields a dependable prognostic model, facilitating pre-surgical detection and treatment decisions. This holds potential for commercial diagnostic tools.

The occurrence rate of frailty is high among patients with chronic diseases. However, the assessment of frailty among these patients is still far from being a routine part of clinical practice. The aim of this study is to develop a validated predictive model for assessing frailty risk in patients with chronic illnesses. This study recruited 543 patients with chronic diseases, and 237 were included in the development and validation of the predictive model. A total of 57 frailty related indicators were analyzed, encompassing sociodemographic variables, health status, physical measurements, nutritional assessment, physical activity levels, and blood biomarkers. There were 100 cases (42.2%) presenting frailty symptoms. Multivariate logistic regression analysis revealed that gender, age, chronic diseases, Mini Nutritional Assessment score, and Clinical Frailty Scale score were predictive factors for frailty in chronic disease patients. Utilizing these factors, a nomogram model demonstrated good consistency and accuracy. The AUC values for the predictive model and validation set were 0.946 and 0.945, respectively. Calibration curves, ROC, and DCA indicated the nomogram had favorable predictive performance. Altogether, the comprehensive nomogram developed here is a promising and convenient tool for assessing frailty risk in patients with chronic diseases, aiding clinical practitioners in screening high-risk populations.

Transporters of the solute carrier family 25 (SLC25) regulate the intracellular distribution and concentration of nucleotides, amino acids, dicarboxylates, and vitamins within the mitochondrial and cytoplasmic matrices. This mechanism involves changes in mitochondrial function, regulation of cellular metabolism, and the ability to provide energy. In this review, important members of the SLC25 family and their pathways affecting tumorigenesis and progression are elucidated, highlighting the diversity and complexity of these pathways. Furthermore, the significant potential of the members of SLC25 as both cancer therapeutic targets and biomarkers will be emphasized.