miRNA-137-5p improves spatial memory and cognition in Alzheimer's mice by targeting ubiquitin-specific peptidase 30.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder causing progressive dementia. Research suggests that microRNAs (miRNAs) could serve as biomarkers and therapeutic targets for AD. Reduced levels of miR-137 have been observed in the brains of AD patients, but its specific role and downstream mechanisms remain unclear. This study sought to examine the therapeutic potential of miR-137-5p agomir in alleviating cognitive dysfunction induced in AD models and explore its potential mechanisms. METHODS: This study utilized bioinformatic analysis and a dual-luciferase reporter assay to investigate the relationship between miR-137-5p and ubiquitin-specific peptidase 30 (USP30). In vitro experiments were conducted using SH-SY5Y cells to assess the impact of miR-137-5p on Aß1-42 neurotoxicity. In vivo experiments on AD mice evaluated the effects of miR-137-5p on cognition, Aß1-42 deposition, Tau hyperphosphorylation, and neuronal apoptosis, as well as its influence on USP30 levels. RESULTS: It was discovered that miR-137-5p mimics efficiently counteract Aß1-42 neurotoxicity in SH-SY5Y cells, a protective effect that is negated by USP30 overexpression. In vivo experiments demonstrated that miR-137-5p enhances the cognition and mobility of AD mice, significantly reducing Aß1-42 deposition, Tau hyperphosphorylation, and neuronal apoptosis within the hippocampus and cortex regions. Mechanistically, miR-137-5p significantly suppresses USP30 levels in mice, though USP30 overexpression partially buffers against miR-137-5p-induced AD symptom improvement. CONCLUSION: Our study proposes that miR-137-5p, by instigating the downregulation of USP30, has the potential to act as a novel and promising therapeutic target for AD.

METTL3-mediated m6A RNA methylation induces the differentiation of lung resident mesenchymal stem cells into myofibroblasts via the miR-21/PTEN pathway.

BACKGROUND: The accumulation of myofibroblasts is the key pathological feature of pulmonary fibrosis (PF). Aberrant differentiation of lung-resident mesenchymal stem cells (LR-MSCs) has been identified as a critical source of myofibroblasts, but the molecular mechanisms underlying this process remain largely unknown. In recent years, N6-methyladenosine (m6A) RNA modification has been implicated in fibrosis development across diverse organs; however, its specific role in promoting the differentiation of LR-MSCs into myofibroblasts in PF is not well defined. METHODS: In this study, we examined the levels of m6A RNA methylation and the expression of its regulatory enzymes in both TGF-ß1-treated LR-MSCs and fibrotic mouse lung tissues. The downstream target genes of m6A and their related pathways were identified according to a literature review, bioinformatic analysis and experimental verification. We also assessed the expression levels of myofibroblast markers in treated LR-MSCs and confirmed the involvement of the above-described pathway in the aberrant differentiation direction of LR-MSCs under TGF-ß1 stimulation by overexpressing or knocking down key genes within the pathway. RESULTS: Our results revealed that METTL3-mediated m6A RNA methylation was significantly upregulated in both TGF-ß1-treated LR-MSCs and fibrotic mouse lung tissues. This process directly led to the aberrant differentiation of LR-MSCs into myofibroblasts by targeting the miR-21/PTEN pathway. Moreover, inhibition of METTL3 or miR-21 and overexpression of PTEN could rescue this abnormal differentiation. CONCLUSION: Our study demonstrated that m6A RNA methylation induced aberrant LR-MSC differentiation into myofibroblasts via the METTL3/miR-21/PTEN signaling pathway. We indicated a novel mechanism to promote PF progression. Targeting METTL3-mediated m6A RNA methylation and its downstream targets may present innovative therapeutic approaches for the prevention and treatment of PF.

Indicators and medical tests to identify lower limb swelling causes after total knee arthroplasty: a Delphi study with multidisciplinary experts.

BACKGROUND: Lower limb swelling after total knee arthroplasty (TKA) hinders surgical effectiveness. The poor results of studies on swelling interventions are due to the lack of a classification of swelling causes through appropriate medical tests. A gold standard is missing. This study aimed to clarify the causes of TKA postoperative swelling and how to identify them through indicators and medical tests by consulting a wide range of experts from multiple disciplines. METHOD: The Delphi method was used. A first draft of the index was prepared based on a systematic search of the literature. A total of 11 experts from several disciplines were invited to evaluate the rationality of the indicators and suggest modifications. After two rounds of consultation, the experts reached a consensus, and the consultation was stopped. RESULTS: The response rate of the 11 experts was 100%, and the authoritative Cr was 0.896. Kendall's W values for opinion coordination of the two rounds of consultation were 0.262 and 0.226, respectively (P < 0.001). Among the final indicators, there were 4 primary indicators for swelling cause classification (inflammatory response, poor venous return, joint hematoma, muscle damage, and healing), 19 secondary and 19 tertiary indicators. CONCLUSION: The indications obtained by systematic literature review and multidisciplinary expert consultation are reliable and scientific. Multiple causes of lower extremity swelling after TKA were identified. Blood test indicators can reflect an inflammatory response, suggest poor venous return, and reflect muscle damage and healing progress. Ultrasound scans are needed to identify underlying thrombotic or valvular problems, joint hematomas, and muscle damage. These tests help clinicians and researchers determine the cause of swelling after TKA and take appropriate management.

Exploring expectations of Chinese patients for total knee arthroplasty: once the medicine is taken, the symptoms vanish.

BACKGROUND: Preoperative expectations of total knee arthroplasty (TKA) outcomes are important determinants of patient satisfaction. However, expectations of patients in different countries are affected by cultural background. The general goal of this study was to describe Chinese TKA patients' expectations. METHODS: Patients scheduled for TKA were recruited in a quantitative study(n = 198). The Hospital for Special Surgery Total Knee Replacement Expectations Survey Questionnaire was used for survey TKA patients' expectations. Descriptive phenomenological design was used for the qualitative research. Semi-structured interviews were conducted with 15 TKA patients. Colaizzi's method was used for interview data analysis. RESULTS: The mean expectation score of Chinese TKA patients was 89.17 points. The 4 highest score items were walk short distance, remove the need for walker, relieve pain and make knee or leg straight. The 2 lowest score items were employed for monetary reimbursement and sexual activity. Five main themes and 12 sub-themes emerged from the interview data, including multiple factors raised expectations, expectations of physical comfort, expect various activities back to normal, hope for a long joint lifespan, and expect a better mood. CONCLUSIONS: Chinese TKA patients reported a relatively high level of expectations, and differences across cultures result in different expectation points than other national populations, requiring adjustment of items when using assessment tools across cultures. Strategies for expectation management should be further developed. LEVEL OF EVIDENCE: Level IV.

Association between triglyceride-glucose index and carotid atherosclerosis in patients with psoriatic arthritis.

OBJECTIVE: To investigate the association of the triglyceride-glucose (TyG) index with atherosclerotic risk among patients with PsA. METHODS: This cross-sectional study included 165 consecutive PsA patients receiving carotid ultrasonography with integrated TyG index, calculated as ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. Logistic regression models were applied to analyse the association of TyG index as continuous variables and tertiles with carotid atherosclerosis and carotid artery plaque. Fully adjusted model included sex, age, smoking, BMI, comorbidities and psoriatic-related variables. RESULTS: Overall, PsA patients with carotid atherosclerosis had substantially higher TyG index than those without [8.82 (0.50) vs 8.54 (0.55), P = 0.002]. The frequency of carotid atherosclerosis was increased with increases in TyG index tertiles, showing 14.8%, 34.5%, 44.6% for tertile 1, 2 and 3, respectively (P = 0.003). Multivariate logistic analyses showed that each 1-unit increase in TyG index was significantly associated with prevalent carotid atherosclerosis [unadjusted odds ratio (OR) 2.65 (1.39-5.05); fully adjusted OR 2.69 (1.02-7.11)]. Compared with patients in tertile 1 of TyG index, the unadjusted and fully adjusted OR for occurrence of carotid atherosclerosis were 4.64 (1.85-11.60) and 5.10 (1.54-16.93) in patients in tertile 3. Similarly, higher prevalent carotid artery plaque was observed with increasing TyG index [unadjusted OR 3.11 (1.54-6.26); fully adjusted OR 3.61 (1.15-11.38)] or in tertile 3 vs tertile 1 [unadjusted OR 10.20 (2.83-36.82); fully adjusted OR 17.89 (2.88-111.11)]. Additionally, TyG index provided incremental predictive capacity beyond established risk factors, shown by an increase in discrimination ability (all P < 0.001). CONCLUSIONS: TyG index was positively correlated with the burden of atherosclerosis in PsA patients, independent of traditional cardiovascular risk factors and psoriatic-related factors. These findings suggest that TyG index may be a promising atherosclerotic marker for the PsA population.

Oleic Acid Dissolves cGAS-DNA Phase Separation to Inhibit Immune Surveillance.

Phase separation (PS) is a fundamental principle in diverse life processes including immunosurveillance. Despite numerous studies on PS, little is known about its dissolution. Here, it is shown that oleic acid (OA) dissolves the cyclic GMP-AMP synthase (cGAS)-deoxyribonucleic acid (DNA) PS and inhibits immune surveillance of DNA. As solvent components control PS and metabolites are abundant cellular components, it is speculated that some metabolite(s) may dissolve PS. Metabolite-screening reveals that the cGAS-DNA condensates formed via PS are markedly dissolved by long-chain fatty acids, including OA. OA revokes intracellular cGAS-PS and DNA-induced activation. OA attenuates cGAS-mediated antiviral and anticancer immunosurveillance. These results link metabolism and immunity by dissolving PS, which may be targeted for therapeutic interventions.

Hemorrhage and necrosis of the liver caused by hepatic arteriovenous malformations in a fetus: A case report.

RATIONALE: Hepatic arteriovenous malformations (HAVMs) are a rare disorder reported in association with hereditary hemorrhagic telangiectasia (HHT), known as Rendu-Osler-Weber syndrome. HAVMs are usually detected in adulthood. PATIENT CONCERNS: A 29-year-old pregnant woman underwent a routine prenatal examination at 37 weeks of pregnancy. DIAGNOSIS AND INTERVENTIONS: There were fetal liver anomalies detected by prenatal ultrasonography and were managed. Furthermore, a hepatic mass was detected and was subsequently analyzed by fetal magnetic resonance imaging. There were no typical imaging findings in this case which was once misdiagnosed as a hepatoblastoma. OUTCOMES: Considering the massive hepatic lesion, labor induction was performed on a pregnant woman to avoid adverse maternal and fetal outcomes. Histopathological examination confirmed the diagnosis of HAVMs. Lesions detected by imaging were determined to be hemorrhagic and necrotic. LESSONS: Prenatal hepatic hemorrhage and necrosis due to an arteriovenous malformation are rare. The authors describe their observations and results.

Oncogenic lncRNA ZNFX1 antisense RNA 1 promotes osteosarcoma cells proliferation and metastasis by stabilizing serine and arginine­rich splicing factor 3.

Recent studies have demonstrated that lncRNAs play an important role in cancers, particularly osteosarcoma. ZFAS1 is a newly identified and characterized lncRNA linked to a variety of cancers. The role of ZFAS1 in osteosarcoma is mainly unknown. This study discovered that ZFAS1 was upregulated in osteosarcoma patient tissues, which correlates with elevated SRSF3 protein levels. Higher levels of ZFAS1 or SRSF3 were linked to a poor prognosis of osteosarcoma. ZFAS1 knockdown decreased SRSF3 protein levels but had a negligible effect on SRSF3 mRNA expression. Further research indicated that ZFAS1 could bind to the SRSF3 protein directly and prevent degrading. Functional studies revealed that ZFAS1 knockdown inhibited osteosarcoma cell proliferation as measured by the CCK-8 assay, colony formation assay, and Ki-67 immunofluorescence staining. Furthermore, ZFAS1 knockdown reduced the expression of PCNA, CDK1, CDK4, and CDK6, increasing p53 and p16. IT has also been observed that ZFAS1 knockdown inhibited osteosarcoma cell migration and invasion as measured by the wound healing assay and the trans-well assay with or without Matrigel.Furthermore, exogenous SRSF3 expression in ZFAS1-depleted osteosarcoma cells restored SRSF3 expression while simultaneously inhibiting cell proliferation and metastasis. Our findings show that ZFAS1 plays an essential role in osteosarcoma progression by stabilizing the SRSF3 protein. Our study provides novel insight into the role of ZFAS1 in osteosarcoma. ZFAS1 has the potential to be used as a prognostic biomarker as well as a therapeutic target in the treatment of osteosarcoma.

LncRNA BCYRN1 promotes cell migration and invasion of non-small cell lung cancer via the miR-30b-3p/ROCK1 axis.

Long non-coding RNA brain cytoplasmic RNA 1 (LncRNA BCYRN1) has been proved to participate in the cancer cell metastasis process, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms involved in the BCYRN1-mediated function remain largely unknown. The qRT-PCR analysis was carried out to examine the relative expressions of BCYRN1, microRNA-30b-3p (miR-30b-3p), and Rho-associated coiled-coil protein kinase 1 (ROCK1). ROCK1 protein level was detected via western blot assay. The migrative and invasive abilities of H520 and A549 cells were evaluated via Transwell assay. The relationships between BCYRN1 and miR-30b-3p or ROCK1 and miR-30b-3p were examined by luciferase reporter assay. The expression levels of BCYRN1 and ROCK1 were upregulated in NSCLC tissues and cells, while miR-30b-3p was downregulated. Higher BCYRN1 expression indicated lymph node metastasis and advanced tumor-node-metastasis (TNM) stage of NSCLC patients. Loss of BCYRN1 suppressed cell migration and invasion. More importantly, miR-30b-3p possessed the binding sites with BCYRN1. Besides, BCYRN1 negatively regulated the expression level of miR-30b-3p. Meanwhile, ROCK1 was proven to be directly targeted by miR-30b-3p. In addition, the silencing of miR-30b-3p also weakened the effect of BCYRN1 knockdown on cell migration and invasion. In vivo, BCYRN1 silencing reduced the growth of A549 cells. LncRNA BCYRN1 was involved in the metastasis of NSCLC through modulating the miR-30b-3p/ROCK1 axis.

Quercetin promotes bone marrow mesenchymal stem cell proliferation and osteogenic differentiation through the H19/miR-625-5p axis to activate the Wnt/ß-catenin pathway.

BACKGROUND: Quercetin and H19 can promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, whether quercetin regulates H19 expression to promote osteogenic differentiation of BMSCs is unclear. METHODS: BMSC proliferation, matrix mineralization, and alkaline phosphatase (ALP) activity were assessed using the Cell Counting Kit-8, ALP assay kit, and alizarin red staining kit, respectively. Expression of H19, miR-625-5p, BMP-2, osteocalcin, and RUNX2 were measured by qRT-PCR; ß-catenin protein level was measured by western blotting. RESULTS: Quercetin promoted BMSC proliferation, enhanced ALP activity, and upregulated the expression of BMP-2, osteocalcin, and RUNX2 mRNAs, suggesting that it promoted osteogenic differentiation of BMSCs. Moreover, quercetin increased H19 expression, while the effect of quercetin on BMSCs was reversed by silencing H19 expression. Additionally, miR-625-5p, interacted with H19, was downregulated during quercetin-induced BMSC osteogenic differentiation, which negatively correlated with H19 expression. Silencing miR-625-5p expression promoted BMSC proliferation and osteogenic differentiation, whereas miR-625-5p overexpression weakened the effect of quercetin on BMSCs. Finally, quercetin treatment or downregulation of miR-625-5p expression increased ß-catenin protein level in BMSCs. Upregulation or downregulation of miR-625-5p or H19 expression, respectively, inhibited ß-catenin protein level in quercetin treated-BMSCs. CONCLUSION: H19 promotes, while miR-625-5p inhibits BMSC osteogenic differentiation. Quercetin activates the Wnt/ß-catenin pathway and promotes BMSC osteogenic differentiation via the H19/miR-625-5p axis.

[Mass spectrometry imaging technology and its application in breast cancer research].

The incidence of breast cancer, one of the most common malignancies affecting women, is increasing significantly worldwide. Given the rapid development of medical technology, early and effective diagnostic methods should be able to improve the survival rate and quality of life of patients suffering from disease. However, although existing treatment options, including chemotherapy and endocrine therapies, have greatly improved the survival of patients, disease recurrence in the long term remains a challenge. Because breast cancer is a heterogeneous and complex disease, which includes several subtypes with different responses to treatment, the continual acquisition of spatial information on related biomolecules is important for accurate tracking of the tumor heterogeneity and microenvironment. At present, prognostic and predictive biomarkers, such as human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), Ki-67, progesterone receptor (PR), and programmed death-ligand 1 (PD-L1), are validated for use in the decision-making over breast cancer therapies. Mass spectrometry imaging (MSI) is a useful technique for acquiring molecular information about biological tissues, including qualitative, quantitative, and spatial distribution information, because it is based on the ion mass-to-charge ratio of the biomolecules and avoids the need for their labeling and staining. MSI can also acquire molecular information on drugs and their metabolites, as well as that on molecules related to endogenous metabolism, such as lipids, peptides, and proteins. Of the various ion sources available for MSI, the most popular are matrix-assisted laser desorption ionization, secondary ion mass spectrometry, and desorption electrospray ionization, and modifications or derivatives of these sources are still emerging. MSI-based techniques provide new ideas and directions for the molecular typing of tumors, as well as knowledge on the metabolism of related antitumor drugs. The process of MSI analysis generally involves tissue acquisition, section preparation, mass spectrometry ionization, map acquisition, and data analysis, with the most crucial step being sample handling to preserve the original chemical and location information of the analytes. The sample preparation steps are sample collection, storage, and slicing, tissue pretreatment, and matrix spraying. This review focuses mainly on the preparation of biological specimens for MSI analysis and the recent progress made in breast cancer research with this technology. With regard to sample preparation, four aspects are discussed: small-molecule samples, macromolecular samples, paraffin-embedded samples, and matrix spraying methods. To solve the difficulties associated with small-molecule sample processing, including the low extraction efficiency for certain lipids and matrix interference in the low-molecular-weight region, the addition of a cationic reagent to the extractant, the use of a new matrix, and tissue derivatization have been used. In the review of macromolecular sample processing, several different washing protocols are summarized. With regard to paraffin-embedded samples, the solutions to several common problems are reviewed. Additionally, the application of MSI to three models associated with breast cancer research is discussed, viz. cell models, animal models, and clinical tumor samples. For these models, MSI technology is used to evaluate the penetration and metabolism of antitumor agents in breast cancer, which can better reflect the malignant transformation of cells and changes in the microenvironment. With regard to lipid molecules, the use of MSI to study differences in their spatial distribution may provide a better understanding of the relationship between lipid metabolism and cancer. This review also provides important information for accurate molecular typing and drug screening in cancer research. Analytically, the tissue preparation method, tissue storage conditions, instrumentation choice, and experimental parameters have all been associated with variability in the imaging and mass-spectral qualities of MSI, thereby affecting the performance of the method. Large-scale studies using diverse sample cohorts are therefore needed to properly evaluate the robustness of MSI molecular markers and workflows for the clinical diagnosis and characterization of breast cancer variants. Our review provides strong evidence that MSI is a reliable, highly reproducible, and rapid technique for the diagnosis of breast cancer biopsies and may be useful in clinical application.

The effect of gemcitabine combined with AMD3100 applying to cholangiocarcinoma RBE cell lines to CXCR4/CXCL12 axis.

PURPOSE: To evaluate the effect of AMD3100 treatment to cholangiocarcinoma by analyzing the relationship between them, and provide experimental evidence for whether AMD3100 can become a clinical treatment drug for cholangiocarcinoma. MATERIALS AND METHODS: Cholangiocarcinoma RBE cell lines were used in this study. MTT cell proliferation test was used for evaluating the effect of gemcitabine and AMD3100 to cell. CXCR4, N-cadherin, VEGF-C and MMP-9 were detect by RT-PCR and western. Transwell was used for evaluating the invasion effect. RESULTS: We demonstrated that as the concentration of gemcitabine increasing from 0.33, 3.33 to 33.33 uM, the cell survival rate was 76.65%, 71.40%, 52.25%, respectively. RT-PCR and Western blot that gemcitabine could affect the expression of CXCR4 protein and the level of mRNA transcription in a dose-dependent manner. N-cadherin VEGF-C, MMP-9 mRNA transcription level showed a significant upward trend in gemcitabine group. In Transwell test, the number of cells in the gemcitabine group was significantly higher than that in the no-medication group (p < .05), the AMD3100 group and the combination group of gemcitabine and AMD3100, the difference between the no-medication group and the AMD3100 monotherapy group was not significant, and the combination group was between them. CONCLUSIONS: This study showed that gemcitabine significantly inhibited the growth of cholangiocarcinoma RBE cells in a dose-dependent manner, and gemcitabine can affect the expression of CXCR4, N-cadherin, VEGF-C, MMP-9 protein and mRNA. Cell invasion and metastasis-related factors decreased after AMD3100 combined with gemcitabine.

miR-493 by regulating of c-Jun targets Wnt5a/PD-L1-inducing esophageal cancer cell development.

BACKGROUND: Esophageal cancer is one of the most common cancers across the globe; the 5-year survival of esophageal cancer patients is still low. MicroRNA (miRNA) dysregulation has been implicated in cancer development, and the miRNAs play a pivotal role in esophageal cancer pathogenesis. It is urgently needed to find out how miRNA dysregulation was involved in esophageal cancer (EC) development. METHODS: Through experiments in vivo and in vitro, we explored potential signaling pathways, miR-493/Wnt5A/c-JUN loop, in EC. Their mechanistic roles in EC cell proliferation, migration, and invasion were investigated through multiple validation steps in EC9706 and TE13 cell lines and EC specimens. RESULTS: Overexpression of miR-493 attenuates esophageal cancer cell proliferation, migration, and invasion in vivo and in vitro. Moreover, miR-493 downregulation is an unfavorable factor in EC and negatively correlated with Wnt5A. The existence of miR-493 is also an important attribute of metabolism. Based on mechanism analyses, we show that miR-493 inhibits the activity of c-JUN and p-PI3K/p-AKT with enhanced p21 and directly regulates Wnt5A expression and function, whereas c-JUN binds the promoter region of miR-493 and suppressed the expression of miR-493, forming a negative feedback loop. CONCLUSIONS: The miR-493/Wnt5A/c-JUN loop is a molecular feedback loop that refers to the development of esophageal cancer cells and a potential target for the treatment of esophageal cancer.

Circular RNA CircCDYL Regulates Proliferation and Apoptosis in Non-Small Cell Lung Cancer Cells by Sponging miR-185-5p and Upregulating TNRC6A.

AIM: A series of research reveal that circular RNA (circRNA) plays a vital role in regulating the development of tumor cells. In this research, we would explore the role and mechanism of circCDYL in non-small cell lung cancer (NSCLC). METHODS: RT-PCR was performed to detect the expression of circCDYL in NSCLC tissues, plasma, and cell lines. The tumor cell proliferation ability was evaluated by clone formation assay, and cell cycle determination. Flow cytometry was used to detect apoptosis in NSCLC cell lines. Western blot and RT-PCR were used to assess the expression of proteins and genes. Luciferase assay was performed to confirm the relationship of circRNA-miRNA-mRNA. RESULTS: The decreased level of circCDYL was observed in NSCLC patients' tissues and plasma, which was also downregulated in NSCLC cell lines. Forced expression of circCDYL inhibited cell viability, proliferation and induced apoptosis in A549 cells. Luciferase assay verified that circCDYL could bind with miR-185-5p and confirmed that TNRC6A was a downstream target of miR-185-5p. Overexpression of miR-185-5p or silencing of TNRC6A could inhibit the anti-tumor effect of circCDYL in A549 cells via regulating the ERK1/2 signal. CONCLUSION: Here, we revealed that circCDYL inhibited proliferation and induced apoptosis in NSCLC cell lines via regulating ERK1/2 signal, and the mechanism of this progression may target miR-185-5p/TNRC6A, which provided a theoretical basis for clinical therapy.

Predictors of health-related quality of life in Chinese patients receiving treatment for neovascular age-related macular degeneration: a prospective longitudinal study.

BACKGROUND: Age-related macular degeneration (AMD) is currently the leading cause of irreversible visual impairment in developed countries and seriously affects the health-related quality of life (HRQoL) of patients. However, the majority of the research in this area employs cross-sectional design; longitudinal research investigating changes in HRQoL and influencing factors is limited. The aim of this study was to use a longitudinal study design to investigate descriptive trends in HRQoL and their predictive factors in Chinese AMD patients receiving treatment with vascular endothelial growth factor inhibitors (anti-VEGF) at baseline and follow-ups. METHODS: In a sample of 142 AMD patients from the outpatient clinic of the Southwest Eye Hospital, a tertiary major hospital in the southwest of China, each patient completed a self-administered questionnaire assessing demographics, clinical features, HRQoL, depression, anxiety, coping style, social support, and self-efficacy at baseline and at 1-, 3-, 6-, and 12-month follow-up appointments. RESULTS: The total score of HRQoL fluctuated, with the highest score at the 6-month follow-up and the lowest score at baseline. Multivariable linear regression showed the predictors of HRQoL are best-corrected visual acuity (BCVA), income level, depression, and visual acuity (VA) of the treated eye at baseline; BCVA, income, and depression at the 1-month follow-up; duration, area of residence, gender, VA of the treated eye, BCVA, income, anxiety, social support, self-efficacy, and depression at the 3-month follow-up; gender, BCVA, income, anxiety, social support, self-efficacy, depression, negative coping, and positive coping at the 6-month follow-up; and BCVA, social support, self-efficacy, and depression at the 12-month follow-up. CONCLUSIONS: The HRQoL and its predictive factors in Chinese AMD patients receiving anti-VEGF treatment fluctuated over time. It is suggested that medical staff should get more information when planning precise care for improving patients' HRQoL.

Treatment Efficacy of Chuang Ling Ye, a Traditional Chinese Herbal Medicine Compound, on Idiopathic Granulomatous Mastitis: A Randomized Controlled Trial.

OBJECTIVE: To explore whether Chuang Ling Ye (CLY), a traditional Chinese herbal medicine compound, could improve the treatment of idiopathic granulomatous mastitis (IGM) via decreasing inflammatory response. METHODS: Herein, 40 patients with IGM who had wounds requiring dressing change were enrolled and randomly divided into two groups: the CLY group and the control group. The size of the neoplasm and pain score of patients were followed-up for 4 weeks. Local tissues were taken during dressing change and examined by commercial enzyme-linked immunosorbent assay (ELISA) kits. The levels of inflammatory markers, including interleukin-1ß (IL-1ß), IL-2, IL-6, interferon gamma (IFN-γ), and tumor necrosis factor-α (TNF-α) were measured. RESULTS: After treatment, the size of the neoplasm in the CLY group was significantly smaller than that in the control group (14.28 cm ± 8.96 cm vs. 21.14 cm ± 0.12 cm, P=0.038), and the pain scores were markedly reduced (P=0.004). Besides, CLY downregulated the expression levels of IL-1ß, IFN-γ, and TNF-α. CONCLUSION: External use of CLY could reduce the neoplasm of IGM by inhibiting local inflammation. This trial is registered with ChiCTR1800017744.

Clinical outcome of open surgery versus laparoscopic surgery for cirrhotic hepatocellular carcinoma patients: a meta-analysis.

BACKGROUND AND AIM: Open surgery remains the major approach to treat hepatocellular carcinoma, and laparoscopy-assisted liver resection has been recommended as a superior treatment. However, the efficacy of laparoscopic surgery versus open surgery for cirrhotic patients is under debate. Therefore, the aim of this meta-analysis was to compare the clinical outcomes of laparoscopic and open resection of hepatocellular carcinoma in patients with cirrhosis. METHODS: Electronic databases were searched for eligible literature updated on November 2018. After rigorous review of quality, the data were extracted from eligible trials. All the data were pooled with the corresponding 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were quantitatively evaluated. RESULTS: Fourteen trials met the inclusion criteria. According to the pooled result of surgery duration, laparoscopic surgery was associated with significantly shorter hospital stay [STD mean difference (SMD) = -0.61, 95% confidence interval -0.89 to -0.32; P < 0.0001], lower intraoperative blood loss (SMD = -0.56, 95% confidence interval -0.99 to -0.12; P = 0.01), fewer complications (odds ratio = 0.38, 95% confidence interval 0.28 to 0.52; P < 0.00001) and lower transfusion rate (odds ratio = 0.58, 95% confidence interval 0.36-0.93; P = 0.02). Nevertheless, there was no remarkable difference in operative time (SMD = 0.17, 95% confidence interval -0.25 to -0.59; P = 0.42) between the two groups. The pooled analysis of overall survival showed that laparoscopic surgery did not achieve benefit compared with open surgery (P = 0.02). Moreover, the pooled results of three subgroups indicated that laparoscopic surgery was associated with significantly better disease-free survival (P < 0.05). CONCLUSION: The current analysis indicates that laparoscopic liver resection for hepatocellular carcinoma improved intraoperative and disease-free survival, with similar overall survival compared to the open procedure. Laparoscopic surgery may serve as a safe and feasible alternative for selected hepatocellular carcinoma patients with cirrhosis.

Exosomal lncRNA ZFAS1 regulates esophageal squamous cell carcinoma cell proliferation, invasion, migration and apoptosis via microRNA-124/STAT3 axis.

BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) are of great importance in development of different types of tumors, while the function of lncRNA ZFAS1 is rarely discussed in esophageal squamous cell carcinoma (ESCC). Therefore, we performed this study to explore the expression of exosomal lncRNA ZFAS1 and its molecular mechanism on ESCC progression. METHODS: Expression of ZFAS1 and miR-124 in ESCC tissues was detected. LncRNA ZFAS1 was silenced to detect its function in the biological functions of ESCC cells. A stable donor and recipient culture model was established. Eca109 cells transfected with overexpressed and low expressed ZFAS1 plasmid and miR-124 inhibitor labeled by Cy3 were the donor cells, and then co-cultured with recipient cells to observe the transmission of Cy3-ZFAS1 between donor cells and recipient cells. The changes of cell proliferation, apoptosis, invasion, and migration in recipient cells were detected. The in vivo experiment was conducted for verifying the in vitro results. RESULTS: LncRNA ZFAS1 was upregulated and miR-124 was down-regulated in ESCC tissues. Silencing of ZFAS1 contributed to suppressed proliferation, migration, invasion and tumor growth in vitro and induced apoptosis of ESCC cells. LncRNA ZFAS1 was considered to be a competing endogenous RNA to regulate miR-124, thereby elevating STAT3 expression. Exosomes shuttled ZFAS1 stimulated proliferation, migration and invasion of ESCC cells and restricted their apoptosis with increased STAT3 and declined miR-124. Furthermore, in vivo experiment suggested that elevated ZFAS1-exo promoted tumor growth in nude mice. CONCLUSION: This study highlights that exosomal ZFAS1 promotes the proliferation, migration and invasion of ESCC cells and inhibits their apoptosis by upregulating STAT3 and downregulating miR-124, thereby resulting in the development of tumorigenesis of ESCC.

Effects of Astragaloside IV on treatment of breast cancer cells execute possibly through regulation of Nrf2 via PI3K/AKT/mTOR signaling pathway.

Traditional Chinese medicine (TCM) has from ancient times been applied in China for the treatment of breast cancer with its own unique theoretical system. Sanhuang decoction composed of astragalus membranaceus, prepared rhubarb, and rhizoma curcumae longae has traditionally been used for antioxidant stress, inflammatory reaction, and angiogenesis. However, the role and mechanism of Sanhuang decoction in breast cancer remains unknown. The present study demonstrated the antitumor activity of Sanhuang decoction against breast cancer xenografts in nude mice. Notably, Sanhuang decoction promoted severe necrosis and induced cell death. In addition, Sanhuang decoction obviously regulated the inflammation and oxidative stress. Despite these, Sanhuang decoction could increase the expression of Nrf2. Moreover, si-Nrf2 exhibited the opposite effects compared with the Sanhuang decoction treatment group and reversed the antibreast cancer role of Sanhuang decoction. Further, Sanhuang decoction remarkably suppressed the expression of PI3K/AKT/mTOR signaling pathway. Taken together, Sanhuang decoction was firstly evaluated to possess potent antibreast cancer effect in vivo through regulation of inflammation and oxidative stress accomplished by up-regulation of Nrf2 via PI3K/AKT/mTOR signaling pathway and Sanhuang decoction might be a powerful candidate formula for antibreast cancer.

miR­381 functions as a tumor suppressor by targeting ETS1 in pancreatic cancer.

Increasing evidence shows that microRNA (miR)­381 is involved in the carcinogenesis and biologic progression of various types of cancer in humans. However, its potential biologic role and mechanism in pancreatic cancer remain to be elucidated. In the present study, the expression and functional role of miR­381 in pancreatic cancer were investigated. It was found that miR­381 was significantly downregulated in pancreatic cancer tissues and cell lines. The biological functions of miR­381 were examined by measuring cell proliferation, migration, invasion and apoptosis in vitro and in vivo. The miR­381 target gene and signaling pathway were identified by luciferase activity assay and western blot assay. In vitro experiments confirmed that the enforced expression of miR­381 markedly suppressed cell proliferation, migration and invasion, and induced apoptosis in pancreatic cancer cells. By contrast, silencing the expression of miR­381 had the opposite effect. In addition, miR­381 inhibited xenograft tumor growth in vivo. Furthermore, ETS1 was identified as a direct target of miR­381, and western blot analysis showed that miR­381 negatively modulated the expression of ETS1. It was also demonstrated that miR­381 serves a key role in pancreatic cancer cells through regulating the phosphoinositide 3­kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. In conclusion, the data obtained suggested that miR­381 mediated cell proliferation, migration and invasion by targeting ETS1, partly through PI3K/AKT/mTOR signaling pathway. These results provide novel insights into understanding the potential effects and molecular mechanism of miR­381 on pancreatic cancer. miR­381 may serve as a novel potential marker for pancreatic cancer treatment in the future.