The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture

BACKGROUND: The 2019 novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. METHODS: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. RESULTS: None of the 137 patients (61 males, 76 females, aged 20-83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. CONCLUSIONS: The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.

Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are a new type of glucose-lowering drug that can reduce blood glucose by inhibiting its reabsorption in proximal tubules and by promoting urinary glucose excretion. SGLT2i are widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). In recent studies, SGLT2i were found to not only reduce blood glucose but also protect the heart and kidney, which can significantly reduce cardiovascular events, delay the progression of renal failure, greatly improve the quality of life of patients, and reduce medical expenses for families and society. As adverse cardiac and renal events are the most common and serious complications of T2DM, it is very important to understand the cardio- and renoprotective mechanisms of SGLT2i. This article reviews the historical development, pharmacological mechanism, heart and kidney protection and safety of SGLT2i. The information presented provides a theoretical basis for the clinical prevention and treatment of diabetes and its complications and for the development of new glucose-lowering drugs.

m6A is the most common form of mRNA modification, and is dynamically regulated by the m6A RNA methylation regulators. However, little is known about m6A in gastric cancer. The aim of this work is to investigate the effects of m6A RNA methylation regulators in gastric cancer. Here, we found that most of the thirteen main m6A RNA methylation regulators are higher expressed in 375 patients with gastric cancer. We identified two subgroups of gastric cancer (cluster1 and 2) by applying consensus clustering to m6A RNA methylation regulators. Compared with the cluster1 subgroup, the cluster2 subgroup correlates with a poorer prognosis, and most of the thirteen main m6A RNA methylation regulators are higher expressed in cluster2. Moreover, the cancer-specific pathways are also significantly enriched in the cluster2 subgroup. This finding indicates that m6A RNA methylation regulators are closely associated with gastric cancer. Based on this finding, we derived a risk signature, using 3 m6A RNA methylation regulators(FTO, RBM15, ALKBH5), that is not only an independent prognostic marker but can also predict the clinicopathological features of gastric cancer. Moreover, FTO is higher expressed in high risk scores subtype in gastric cancer. Thus, this first finding provide us clues to understand epigenetic modification of RNA in gastric cancer.

Ferroptosis is a novel form of cell death that is closely associated with the formation of many tumors. Our study focused on the mechanism by which long noncoding RNAs (lncRNAs) regulate ferroptosis in gastric cancer (GC) peritoneal metastasis (PM). We utilized lncRNA sequencing and protein profiling analysis to identify ferroptosis-associated lncRNAs and proteins. qRT-PCR was used to analyze the expression of BDNF-AS and FBXW7 in GC tissues and adjacent normal tissues. Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and coimmunoprecipitation (co-IP) assays were performed to investigate the interaction between BDNF-AS and its downstream targets. Finally, the function of BDNF-AS was validated in vivo . We demonstrated that BDNF-AS was highly expressed in GC and PM tissues. High BDNF-AS expression was positively related to GC progression and poor prognosis. Functionally, BDNF-AS overexpression protected GC cells from ferroptosis and promoted the progression of GC and PM. Mechanistically, BDNF-AS could regulate FBXW7 expression by recruiting WDR5, thus affecting FBXW7 transcription, and FBXW7 regulated the protein expression of VDAC3 through ubiquitination. Conclusively, our research demonstrated that the BDNF-AS/WDR5/FBXW7 axis regulates ferroptosis in GC by affecting VDAC3 ubiquitination. BDNF-AS might be a biomarker for the evaluation of GC prognosis and the treatment of GC.

In this study we provide the first report of the characteristics, comorbidities,<br/>laboratory and x-ray findings, and clinical outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with pre-existing liver cirrhosis. The cause of death in most patients was respiratory failure rather than progression of liver disease. Lower numbers of blood lymphocytes and platelets, and higher bilirubin levels might represent indicators of poor outcome in this patient population.<br/><br/><br/><br/><br/><br/>

Breast cancer is a kind of common female cancers. Increasing evidence has exhibited that lncRNAs exert a crucial role in breast cancer. So far, the mechanism of lncRNAs in breast cancer is still not well established. In our current study, we focused on the biological role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in breast cancer. We observed that NEAT1 levels were significantly increased in human breast cancer cells including MCF-7, MDA-MB-453, MDA-MB-231, and SKBR3 cells compared to normal mammary epithelial cells MCF-10A while miR-448 was decreased. We found that downregulation of NEAT1 was able to inhibit the growth of breast cancer cells and miR-448 mimic exerted the similar function. Bioinformatics analysis and dual luciferase reporter assays confirmed the negative correlation between NEAT1 and miR-448 in vitro. In addition, ZEB1 was predicted as a novel mRNA target of miR-448. Overexpression of NEAT1 can induce breast cancer cell growth, migration, and invasion by inhibiting miR-448 and upregulating ZEB1. It was demonstrated that NEAT1 can increase ZEB1 levels while miR-448 mimic can repress ZEB1. It was speculated in our study that NEAT1 can serve as a competing endogenous lncRNA (ceRNA) to modulate ZEB1 by sponging miR-448 in breast cancer. To conclude, we uncovered that NEAT1 participated in breast cancer progression by regulating miR-448 and ZEB1. NEAT1 can be provided as a vital biomarker in breast cancer diagnosis and treatment therapy.

High-intensity focused ultrasound (HIFU) is being generally explored as a non-invasive therapeutic modality to treat solid tumors. However, the clinical use of HIFU for large and deep tumor-ablation applications such as hepatocellular carcinoma (HCC) is currently entangled with long treatment duration and high operating energy. This critical issue can be potentially resolved by the introduction of HIFU synergistic agents (SAs). Traditional SAs such as microbubbles and microparticles face the problem of large size, short cycle time, damage to mononuclear phagocytic system and unsatisfactory targeting efficiency. In this work, we have developed a facile and versatile nanoparticle-based HIFU synergistic cancer surgery enhanced by transarterial chemoembolization for high-efficiency HCC treatment based on elaborately designed Fe3O4-PFH/PLGA nanocapsules. Multifunctional Fe3O4-PFH/PLGA nanocapsules were administrated into tumor tissues via transarterial injection combined with Lipiodol to achieve high tumor accumulation because transarterial chemoembolization by Lipiodol could block the blood vessels. The high synergistic HIFU ablation effect was successfully achieved against HCC tumors based on the phase-transformation performance of the perfluorohexane (PFH) inner core in the composite nanocapsules, as systematically demonstrated in VX2 liver tumor xenograft in rabbits. Multifunctional Fe3O4-PFH/PLGA nanocapsules were also demonstrated as efficient contrast agents for ultrasound, magnetic resonance and photoacoustic tri-modality imagings, potentially applicable for imaging-guided HIFU synergistic surgery. Therefore, the elaborate integration of traditional transarterial chemoembolization with recently developed nanoparticle-enhanced HIFU cancer surgery could efficiently enhance the HCC cancer treatment outcome, initiating a new and efficient therapeutic protocol/modality for clinic cancer treatment.

Ovarian aging is a long-term and complex process associated with a decrease in follicular quantity and quality. The damaging effects of reactive oxygen species (ROS) in ovarian aging and ovarian aging-associated disorders have received relatively little attention. Thus, we assessed if the oxidative stress induced by long-term (defined by the Environmental Protection Agency as at least 30 days in duration) moderate ozone inhalation reduced ovarian reserves, decreased ovarian function and induced ovarian aging-associated disorders. The expression of oxidative stress markers and antioxidant enzymes was used to determine the degree of oxidative stress. Ultrastructural changes in ovarian cells were examined via electron microscopy. The ovarian reserve was assessed by measuring multiple parameters, such as the size of the primordial follicle pool and anti-Müllerian hormone (AMH) expression. The estrous cycle, hormone levels and fertility status were investigated to assess ovarian function. To investigate ovarian aging-associated disorders, we utilized bone density and cardiovascular ultrasonography in mice. The levels of oxidized metabolites, such as 8-hydroxy-2´-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE) and nitrotyrosine (NTY), significantly increased in ovarian cells in response to increased oxidative stress. The ultrastructural analysis indicated that lipid droplet formation and the proportion of mitochondria with damaged membranes in granulosa cells were markedly increased in ozone-exposed mice when compared with the control group. Ozone exposure did not change the size of the primordial follicle pool or anti-Müllerian hormone (AMH) expression. The estrogen concentration remained normal; however, progesterone and testosterone levels decreased. The mice exposed to ozone inhalation exhibited a substantial decrease in fertility and fecundity. No differences were revealed by the bone density or cardiovascular ultrasounds. These findings suggest that the decreased female reproductive function caused by long-term moderate oxidative damage may be due to a decrease in follicle quality and progesterone production.

Epidemiological studies exploring the role of flavonoids intake in preventing type 2 diabetes mellitus (T2DM) showed inconsistent results. Therefore, we performed a meta-analysis of relevant studies to examine the relationship between flavonoids intake and risk of T2DM. We hypothesized that flavonoids intake may decrease the risk of developing T2DM.A systematical search in PubMed and Embase until September 2017 was performed to identify eligible prospective cohort studies. The summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effect models. Dose-response pattern between total flavonoids intake and T2DM risk was also estimated.Eight prospective studies were included with 312,015 participants, of whom 19,953 developed T2DM during the follow-up periods of 4 to 28 years. Compared with lower consumption, high intake of total flavonoids was associated with a decreased risk of T2DM (RR: 0.89, 95% CI: 0.82-0.96). Among flavonoid subclasses, inverse correlations with T2DM were achieved for intakes of anthocyanidins, flavan-3-ols, flavonols, and isoflavones. Dose-response meta-analysis indicated a curvilinear relationship between total flavonoids intake and incident T2DM (P for nonlinearity = .042), with a significant risk reduction at an intake of ≥550 mg/day. When assuming a linear pattern, the risk of T2DM was decreased by 5% for each 300-mg/day increment in total flavonoids intake (RR: 0.95, 95% CI: 0.93-0.97).Our study suggests that higher intakes of total flavonoids and subclasses (anthocyanidins, flavan-3-ols, flavonols, and isoflavones) are associated with lower risk of T2DM.

Curcumin, a major phytochemical in turmeric, inhibits the proliferation of many types of solid cancer cells by enhancing p53 expression. However, the long non-coding RNA H19 directly inhibits p53 activation and thus promotes gastric cancer progression. The aim of this study was to assess the role of H19 in curcumin-induced proliferative inhibition of gastric cancer. The gastric cancer cell line SGC-7901 was treated with curcumin at different concentrations and time points. The effect of curcumin on proliferation was assessed using cell counting kit-8 assays and flow cytometry with Ki67 staining. In addition, H19 expression was quantified by reverse transcription-quantitative polymerase chain reaction, and apoptosis was evaluated by flow cytometric detection of Annexin V and propidium iodide double staining. The protein expression of p53, B-cell lymphoma (Bcl)-2, Bcl-2-associated X protein (Bax) and c-Myc in curcumin-treated cells was detected by western blotting. The present study demonstrated that curcumin inhibited the proliferation of SGC7901 cells and suppressed H19 expression in a concentration-dependent manner, while p53 expression was enhanced. Ectopic expression of H19 in SGC7901 cells reversed curcumin-induced proliferative inhibition and downregulated p53 expression. Furthermore, while curcumin induced cell apoptosis and enhanced the expression ratio of Bax/Bcl-2, which are downstream molecules of p53, ectopic expression of H19 inhibited curcumin-induced cell apoptosis. In addition, curcumin decreased the expression of the c-Myc oncogene, and exogenous c-Myc protein reversed the curcumin-induced downregulation of H19 expression. These results suggested that curcumin inhibits the proliferation of gastric cancer cells by downregulating the c-Myc/H19 pathway. Therefore, curcumin may be considered a novel therapeutic strategy to inhibit gastric cancer cell growth.

Coronary artery disease (CAD) is the most common type of cardiovascular disease and becomes a leading cause of death worldwide. Aiming to uncover the underlying molecular features for different types of CAD, we classified 352 CAD cases into three subgroups based on gene expression profiles, which were retrieved from the Gene Expression Omnibus database. Also, these subgroups present different expression patterns and clinical characteristics. To uncover the transcriptomic differences between the subgroups, weighted gene co-expression analysis (WGCNA) was used and identified six subgroup-specific WGCNA modules. Characterization of the WCGNA modules revealed that lipid metabolism pathways, specifically upregulated in subgroup I, might be an indicator of increased severity. Moreover, subgroup II was considered as an early-stage of CAD because of normal-like gene expression patterns. In contrast, the mammalian target of rapamycin signaling pathway was significantly upregulated in subgroup III. Although subgroups II and III did not have a significant prognostic difference, their intrinsic biological characteristics were highly different, suggesting that the transcriptome classification may represent risk factors of both age and the intrinsic biological characteristics. In conclusion, the transcriptome classification of CAD cases revealed that cases from different subgroups may have their unique gene expression patterns, indicating that patients in each subgroup should receive more personalized treatment.

Immune infiltration of tumors has been increasingly accepted as a prognostic factor in colon cancer. Here, we aim to develop a novel immune signature, based on estimated immune landscape from tumor transcriptomes, to predict the overall survival of patients with colon cancer. The compositions of 22 immune cell subtypes from three microarray datasets were characterized with the CIBERSORT deconvolution algorithm. A prognostic immunoscore (PIS) model for overall survival prediction was established by using least absolute shrinkage and selection operator (LASSO) penalized regression analysis. A total of 17 immune cell markers were screened out in the LASSO model and were then aggregated to generate the PIS. In the training cohort (n = 490), patients with high PIS exhibited a remarkably poorer overall survival than those with low PIS. Similar results were obtained in patients with different TNM stages and in patients receiving adjunctive chemotherapy or not. Multivariate Cox regression indicated that the PIS was an independent predictor for overall survival in colon cancer (hazard ratio: 2.734, 95% confidence interval: 2.052-3.643, p < .001). The prognostic capability of PIS was also confirmed in the testing cohort (n = 245) and the entire cohort (n = 735). As for biological implications, the PIS was significantly associated with some immune checkpoints, inflammatory factors, epithelial-mesenchymal transformation regulators, and many known signaling pathways in cancer. The results of our study provide a novel and promising immune signature for overall survival prediction of patients with colon cancer.

INTRODUCTION: It remains unclear whether marital status could affect the breast cancer-caused special survival (BCSS) of patients with breast cancer. Therefore, we sought to explore the influence of demographic and pathological factors on prognosis of patients with breast cancer. MATERIALS AND METHODS: We selected patients meeting the eligibility criteria from the Surveillance, Epidemiology, and End Results (SEER) cancer registry program. We assessed the effect of marital status on overall survival (OS) and BCSS using Kaplan-Meier curve and multivariate Cox proportional hazards regression. RESULTS: Compared with divorced/separated/widowed (DSW) patients, the married (AHR 0.7483, 95% CI: 0.729-0.7682, P < 0.001) and single patients had better BCSS (AHR 0.9096, 95% CI: 0.8796-0.9406, P < 0.001). Married patients kept better prognosis among all age subgroups, while the better BCSS of single patients occurred only in groups older than 35 years. As for race and hormone receptor status (HRs), the better BCSS of single patients was only observed in white race (AHR 0.881, 95% CI: 0.8457-0.9177, P < 0.001) and patients with ER+/PR + status (AHR 0.8844, 95% CI: 0.8393-0.932, P < 0.001). CONCLUSION: Our findings demonstrated that married and single patients with breast cancer had better prognosis than their DSW counterparts. Age, race, and HRs could affect the correlation between marital status and BCSS.

Current prognostic signatures need to be improved in identifying high-risk patients of gastric cancer (GC). Thus, we aimed to develop a reliable prognostic signature that could assess the prognosis risk in GC patients. Two microarray datasets of GSE662254 (n = 300, training set) and GSE15459 (n = 192, test set) were included into analysis. Prognostic genes were screened to construct prognosis-related gene pairs (PRGPs). Then, a penalized Cox proportional hazards regression model identified seven PRGPs, which constructed a prognostic signature and divided patients into high- and low-risk groups according to the signature score. High-risk patients showed a poorer prognosis than low-risk patients in both the training set (hazard ratios [HR]: 6.086, 95% confidence interval [CI]: 4.341-8.533) and test set (1.773 [1.107-2.840]). The PRGPs signature also achieved a higher predictive accuracy (concordance index [C-index]: 0.872, 95% CI: 0.846-0.897) than two existing molecular signatures (0.706 [0.667-0.744] for a 11-gene signature and 0.684 [0.642-0.726] for a 24-lncRNA signature) and TNM stage (0.764 [0.715-0.814]). In conclusion, our study identified a novel gene pairs signature in the prognosis of GC.

Curcumin is known to suppress the progression of colorectal cancer by inhibiting cancer cell proliferation. In this study, we explored the role of ferroptosis in the antiproliferative properties of curcumin. The effect of curcumin on ferroptosis In Vitro was evaluated in HCT-8 cells. Ferroptosis was first blocked by ferrostatin-1 (Fer-1) and the antiproliferative effect of curcumin was evaluated by determining the levels of ferroptotic markers, including glutathione (GSH), SLC7A11, GPX4, iron, malondialdehyde (MDA), and reactive oxygen species (ROS). An agonist and an inhibitor of PI3K were also used to verify the signaling pathway involved in the antiproliferative effects. Curcumin repressed HCT-8 cell proliferation in a dose-dependent manner. Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. In addition, curcumin promoted ferroptosis and reduced proliferation of HCT-8 cells by suppressing the PI3K/Akt/mTOR pathway, and these effects were antagonized by Fer-1. The effects of curcumin were antagonized by a PI3K agonist and reinforced by a PI3K inhibitor. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway. These results indicate its potential as a treatment against colorectal cancer.

Hepatocellular carcinoma (HCC) is the one of the most common malignancies worldwide and its prognosis is extremely poor. Tripartite motif (TRIM) proteins play crucial roles in cancer cell biology but the function of tripartite motif 26 (TRIM26) has not been investigated. We demonstrated that low expression level of TRIM26 in tumor samples was significantly correlated with worse prognosis in HCC patients. We also demonstrated its expression level was associated with several clinicopathologic features such as AFP level and T stage of HCC patients. Furthermore, we validated that TRIM26 was significantly downregulated in HCC tissue compared with normal liver tissue. To further clarify the functional role of TRIM26 in HCC, We confirmed that TRIM26 silencing can promote cancer cell proliferation, colony forming, migration and invasion in vitro with HCC cell lines HepG2 and Bel-7402. Then we utilized bioinformatic tool to predict gene influenced by TRIM26, showing TRIM26 could modulate gene sets about cancer cell metabolism. In conclusion, we proved that TRIM26 is a novel tumor suppressor modulating multiple metabolism-related pathways in HCC. To our best knowledge, this is the first study to investigate the function of TRIM26 in cancer biology. Our findings provide useful insight into the mechanism of HCC origin and progression. Moreover, TRIM26 may represent a novel therapeutic target for HCC.

Breast cancer adversely affects the health status of women; therefore, the prevention and treatment of breast cancer is of critical importance. Lycopene is known to possess several biological effects such as removal of free radicals, alleviation of biological oxidative injury, and inhibition of tumor growth. In this study, we aimed to illustrate the effect of lycopene on tumor cell proliferation and modulation of cancer progression as well as its possible underlying mechanisms in human breast carcinoma cell line MCF-7 in vitro. MCF-7 cells were treated with different lycopene concentrations for 24, 48, and 72 h. Light field microscopy was used to observe cell morphology. MTT assay was used to determine the effect of lycopene on MCF-7 proliferation. Flow cytometry was employed to evaluate cell apoptosis. Real-time quantitative polymerase chain reaction was performed to detect the expression of p53 and Bax. Under microscopic examination, the untreated MCF-7 cells appeared to have a diamond or polygonal shape. Lycopene treatment resulted in cell shrinkage and breakage, whose severity increased in a dose and duration dependent manner. In addition, reduced cell proliferation and increased apoptosis (P < 0.05) were observed using MTT assay and flow cytometry, respectively. Moreover, lycopene could also upregulate the expression of p53 and Bax mRNAs in MCF-7 cells. In conclusion, lycopene inhibits proliferation and facilitates apoptosis of MCF-7 cells in vitro, possibly by regulating the expression of p53 and Bax.

BACKGROUND: Intervertebral disc degeneration (IDD) has a complicated and enigmatic pathogenic process. Accumulating evidence shows that long non-coding RNAs (LncRNAs) play a role in the pathogenesis of IDD. This study aimed to investigate the expression and role of the LncRNA HOTAIR in IDD pathogenesis. METHODS: Nucleus pulposus (NP) tissue samples from 10 patients with idiopathic scoliosis and 10 patients with lumbar disc herniation were collected. qRT-PCR was used to assess the expression of HOTAIR and ECM-related genes; western blotting was used to detect the expression of senescence biomarkers, apoptosis-related proteins, and Wnt/β-catenin pathway; flow cytometry was used to detect apoptosis; and the MTT assay was used to determine cell proliferation. Moreover, a classic needle-punctured rat tail model was used to investigate the role of HOTAIR in IDD in vivo. RESULTS: The results showed that the expression of HOTAIR significantly increased during IDD progression. The overexpression of HOTAIR was found to induce nucleus pulposus (NP) cell senescence, apoptosis, and extracellular matrix (ECM) degradation. HOTAIR silencing by RNA interference in NP cells prevented interleukin-1β-induced NP cell senescence, apoptosis, and ECM degradation. Furthermore, we found that the Wnt/β-catenin pathway played a role in regulating HOTAIR to induce these changes in NP cells. Moreover, HOTAIR inhibition in a rat model effectively attenuated IDD symptoms in vivo. CONCLUSIONS: Our findings confirmed that HOTAIR promoted NP cell senescence, apoptosis, and ECM degradation via the activation of the Wnt/β-catenin pathway, while silencing HOTAIR attenuated this degeneration process, indicating a potential therapeutic target against IDD.

Background: The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of remimazolam in clinical endoscopic procedure sedation. Methods: The authors searched the databases of PubMed, Embase, and Cochrane Library for studies published until January 2, 2021, that reported remimazolam sedation for endoscopic procedures. The sedative efficiency and the incidence of adverse events were assessed as outcomes. Cochrane Review Manager Software 5.3 was used to perform the statistical analyses. Results: Seven relevant studies involving a total of 1,996 patients were identified. We conducted a meta-analysis of the different controls used in the studies, that is, the placebo, midazolam, and propofol. The results demonstrated that remimazolam had a strong sedative effect, and its sedative efficiency was significantly higher than that of placebo [OR = 0.01, 95% CI: (0.00, 0.10), I 2 = 30%, p &amp;lt;0.00001]. The sedative efficiency of remimazolam was significantly higher than that of midazolam [OR = 0.12, 95% CI: (0.08, 0.21), I 2 = 0%, p &amp;lt; 0.00001] but lesser than that of propofol [OR = 12.22, 95% CI: (1.58, 94.47), I 2 = 0%, p = 0.02]. Regarding the adverse events, remimazolam is associated with a lower incidence of hypotension than placebo and midazolam. Similarly, remimazolam was associated with a lower incidence of hypotension and hypoxemia than propofol. Conclusions: Remimazolam is a safe and effective sedative for patients undergoing endoscopic procedures. The sedative efficiency of remimazolam was significantly higher than that of midazolam but slightly lower than that of propofol. However, the respiration and circulation inhibitory effects of remimazolam were weaker than those of midazolam and propofol.

Intervertebral disc degeneration (IDD) is a complex and chronic disease that involves disc cell senescence, death, and extracellular matrix (ECM) degradation. HOTAIR, a long non-coding RNA (lncRNA) is reportedly associated with autophagy, whereas autophagy is shown to promote IDD. However, how it affects nucleus pulposus (NP) cells, the primary component of intervertebral discs is still unclear. We hypothesized that HOTAIR promotes NP cell apoptosis and senescence through upregulating autophagy. Thus, silencing HOTAIR should inhibit autophagy and exert a therapeutic effect on IDD. Our in vitro experiments in human NP cells revealed that HOTAIR expression positively correlated with IDD grade, and overexpression enhanced autophagy. Autophagy inhibition via 3-methyladenine reversed HOTAIR stimulatory effects on apoptosis, senescence, and ECM catabolism, while the AMP-activated protein kinase (AMPK) inhibitor Compound C suppressed HOTAIR-induced autophagy through regulating AMPK/mTOR/ULK1 pathways. Our in vivo experiment then illustrated that silencing HOTAIR ameliorates IDD in rats. Collectively, we demonstrated that HOTAIR stimulates autophagy to promote NP cell apoptosis, senescence, and ECM catabolism. Therefore, silencing HOTAIR has the potential to become a treatment option for IDD.