Pharmacological interventions for the treatment of obstructive sleep apnea syndrome.

Obstructive Sleep Apnea Syndrome (OSAS) affects 13-33% of males and 6-9% of females globally and poses significant treatment challenges, including poor adherence to Continuous Positive Airway Pressure (CPAP) and residual excessive sleepiness (RES). This review aims to elucidate the emerging interest in pharmacological treatments for OSAS, focusing on recent advancements in this area. A thorough analysis of extensive clinical trials involving various drugs, including selective dopamine reuptake inhibitors, selective norepinephrine inhibitors, combined antimuscarinic agents, and orexin agonists, was conducted. These trials focused on ameliorating respiratory metrics and enhancing sleep quality in individuals affected by OSAS. The studied pharmacological agents showed potential in improving primary outcomes, notably the apnea-hypopnea index (AHI) and the Epworth sleepiness scale (ESS). These improvements suggest enhanced sleep quality and symptom management in OSAS patients. With a deeper understanding of OSAS, pharmacological interventions are emerging as a promising direction for its effective management. This review provides a comprehensive overview of the current state of drug research in OSAS, highlighting the potential of these treatments in addressing the disorder's complex challenges.

Deciphering the mechanism of Peptostreptococcus anaerobius-induced chemoresistance in colorectal cancer: the important roles of MDSC recruitment and EMT activation.

Peptostreptococcus anaerobius (P. anaerobius, PA) in intestinal flora of patients with colorectal cancer (CRC) are associated with poor prognosis. Studies have shown that P. anaerobius could promote colorectal carcinogenesis and progression, but whether P. anaerobius could induce chemoresistance of colorectal cancer has not been clarified. Here, both in vitro and in vivo experiments showed that P. anaerobius specifically colonized the CRC lesion and enhanced chemoresistance of colorectal cancer to oxaliplatin by recruiting myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment. Furthermore, this study revealed that it was the increased secretion of IL-23 by MDSCs that subsequently facilitated the epithelial-mesenchymal transition (EMT) of tumor cells to induce chemoresistance of CRC by activating the Stat3-EMT pathway. Our results highlight that targeting P. anaerobius might be a novel therapeutic strategy to overcome chemoresistance in the treatment of CRC.

Identification of a novel intermittent hypoxia-related prognostic lncRNA signature and the ceRNA of lncRNA GSEC/miR-873-3p/EGLN3 regulatory axis in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is still the most prevalent type of respiratory cancer. Intermittent hypoxia can increase the mortality and morbidity associated with lung cancer. Long non-coding RNAs (lncRNAs) are crucial in lung adenocarcinoma. However, the effects of intermittent hypoxia-related long non-coding RNAs (IHRLs) on lung adenocarcinoma are still unknown. Method: In the current research, eight IHRLs were selected to create a prognostic model. The risk score of the prognostic model was evaluated using multivariate and univariate analyses, and its accuracy and reliability were validated using a nomogram and ROC. Additionally, we investigated the relationships between IHRLs and the immune microenvironment. Result: Our analysis identified GSEC, AC099850.3, and AL391001.1 as risk lncRNAs, while AC010615.2, AC010654.1, AL513550.1, LINC00996, and LINC01150 were categorized as protective lncRNAs. We observed variances in the expression of seven immune cells and 15 immune-correlated pathways between the two risk groups. Furthermore, our results confirmed the ceRNA network associated with the intermittent hypoxia-related lncRNA GSEC/miR-873-3p/EGLN3 regulatory pathway. GSEC showed pronounced expression in lung adenocarcinoma tissues and specific cell lines, and its inhibition resulted in reduced proliferation and migration in A549 and PC9 cells. Intriguingly, GSEC manifested oncogenic properties by sponging miR-873-3p and demonstrated a tendency to modulate EGLN3 expression favorably. Conclusion: GSEC acts as an oncogenic lncRNA by interacting with miR-873-3p, modulating EGLN3 expression. This observation underscores the potential of GSEC as a diagnostic and therapeutic target for LUAD.

Pterostilbene in the treatment of inflammatory and oncological diseases.

Pterostilbene (PTS), a naturally occurring analog of resveratrol (RSV), has garnered significant attention due to its potential therapeutic effects in treating inflammatory and oncological diseases. This comprehensive review elucidates the pharmacological properties, mechanisms of action, and therapeutic potential of PTS. Various studies indicate that PTS exhibits anti-inflammatory, antioxidant, and antitumour properties, potentially making it a promising candidate for clinical applications. Its influence on regulatory pathways like NF-κB and PI3K/Akt underscores its diverse strategies in addressing diseases. Additionally, PTS showcases a favorable pharmacokinetic profile with better oral bioavailability compared to other stilbenoids, thus enhancing its therapeutic potential. Given these findings, there is an increased interest in incorporating PTS into treatment regimens for inflammatory and cancer-related conditions. However, more extensive clinical trials are imperative to establish its safety and efficacy in diverse patient populations.

Association of Barrett's esophagus with obstructive sleep apnea syndrome: a bidirectional analysis of Mendelian randomization.

Background: Observational studies have reported associations between Barrett's esophagus (BE) and obstructive sleep apnea syndrome (OSAS), but the causal relationship remained unclear due to potential confounding biases. Our study aimed to elucidate this causal relationship by deploying a two-sample Mendelian randomization (MR) methodology. Methods: Instrumental variables (IVs) for Barrett's esophagus were obtained from a public database that comprised 13,358 cases and 43,071 controls. To investigate OSAS, we utilized summary statistics from a comprehensive genome-wide association study (GWAS) encompassing 38,998 cases of OSAS and 336,659 controls. Our MR analyses adopted multiple techniques, including inverse variance weighted (IVW), weighted median, weighted mode, MR-Egger, and simple mode. Results: The IVW analysis established a causal relationship between Barrett's esophagus and OSAS, with an odds ratio (OR) of 1.19 and a 95% confidence interval (CI) of 1.11-1.28 (p = 8.88E-07). Furthermore, OSAS was identified as a contributing factor to the onset of Barrett's esophagus, with an OR of 1.44 and a 95% CI of 1.33-1.57 (p = 7.74E-19). Notably, the MR-Egger intercept test found no evidence of directional pleiotropy (p > 0.05). Conclusion: This study identifies a potential association between BE and an increased occurrence of OSAS, as well as the reverse relationship. These insights could influence future screening protocols and prevention strategies for both conditions.

Presentation of Boerhaave's syndrome as an upper-esophageal perforation associated with a right-sided pleural effusion: A case report.

BACKGROUND: Spontaneous esophageal rupture or Boerhaave's syndrome is a rare and acute disease with a high incidence of misdiagnosis and mortality. Here, we aimed to explore the clinical characteristics, diagnosis, treatment, and prognosis of spontaneous esophageal rupture, and to analyze the causes of misdiagnosis during the treatment of spontaneous esophageal rupture. CASE SUMMARY: The clinical features of the patient with spontaneous esophageal rupture misdiagnosed earlier as pleural effusion were retrospectively analyzed and the reasons for misdiagnosis are discussed based on a current review of the literature. The patient was admitted to a local hospital due to shortness of breath accompanied by vomiting and abdominal distension for five hours. Based on the computed tomography (CT) scan analysis, clinically, right pleural effusion was diagnosed. However, the patient was unwilling to undergo right closed thoracic drainage. The patient also had intermittent fevers against infection, and during the course of treatment, he complained of chest pain, following which, he was transferred to our hospital. Grapefruit-like residue drainage fluid was observed. Re-examination of the chest CT scans suggested the presence of spontaneous perforation in the upper left esophagus. Therefore, the patient underwent an urgent esophageal hiatus repair. Unfortunately, the patient died of infection and respiratory failure due to progressive dyspnea after surgery. CONCLUSION: Spontaneous esophageal rupture is a rare disease associated with high fatality. The patients do not present typical clinical symptoms and the disease progresses rapidly. This case report highlights the importance of a dynamic review of chest CT scan, not only for the initial identification of segmental injury but also for prioritizing subsequent treatment strategies. Moreover, we have presented some clues for clinicians to recognize and diagnose spontaneous esophageal rupture at rare sites (upper-esophageal segment) through this case report of spontaneous esophageal rupture that caused the patient's death. We have also summarized the reasons for the misdiagnosis and lessons learned.

Circ_0026134 promotes NSCLC progression by the miR-3619-5p/CHAF1B axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Circular RNAs (circRNAs) have been implicated in the pathogenesis of NSCLC. In this study, we explored the molecular determinants underlying the oncogenic property of circ_0026134 in NSCLC. METHODS: The levels of circ_0026134, miR-3619-5p and chromatin assembly factor 1 subunit B axis (CHAF1B) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell colony formation, migration, invasion and apoptosis were detected by colony formation, Transwell, and flow cytometry assays, respectively. Direct relationships among circ_0026134, miR-3619-5p and CHAF1B were verified by dual-luciferase reporter assays. RESULTS: Our results showed that circ_0026134 was highly expressed in NSCLC tissues and cells. Reduced circ_0026134 expression or miR-3619-5p overexpression inhibited NSCLC cell colony formation, migration, invasion, glycolysis and promoted cell apoptosis in vitro. Moreover, circ_0026134 directly targeted miR-3619-5p, and circ_0026134 regulated CHAF1B expression through miR-3619-5p. CHAF1B was a downstream effector of circ_0026134 in affecting NSCLC cell functional behaviors in vitro. Additionally, circ_0026134 silencing weakened tumor growth in vivo. CONCLUSIONS: Our study identified a novel regulatory mechanism, the circ_0026134/miR-3619-5p/CHAF1B axis, for the oncogenic role of circ_0026134 in NSCLC, highlighting circ_00261345 inhibition as a potential therapeutic method against NSCLC.

Clinical characteristics of COVID-19 patients with asthma in Wuhan, China: a retrospective cohort study.

OBJECTIVE: Although it is reported that patients with coronavirus disease 2019 (COVID-19) disease who have comorbidities are at higher risk to suffer adverse clinical outcomes, there are inadequate evidence to clarify the association between COVID-19 and asthma. On this ground, this study aims to systematically analyze the clinical characteristics of COVID-19 patients with asthma. METHODS: In this single-center, retrospective and observational cohort study, 21 COVID-19 patients with asthma and 100 non-asthma COVID-19 patients were statistically matched by propensity score based on age, sex and comorbidities. Meanwhile, a collection and comparison concerning demographic indicators, clinical and laboratory examinations, treatments and outcomes were conducted between two groups to specify their differences. RESULTS: Statistically, the COVID-19 patients with asthma had a higher proportion of ICU admission (14.3% [3/21] vs. 2.1% [2/96] p = 0.040) than those who do not have. On top this, a higher level of inflammatory responses, such as interleukin 6, interleukin 8, procalcitonin, leukocytes, neutrophils and CD4+ T cells was presented in asthma patients. Moreover, the increase of organ damage indices like D-dimer, lactate dehydrogenase and high-sensitivity cardiac troponin I, were more pronounced in COVID-19 patients with asthma. CONCLUSIONS: Exacerbated inflammatory responses and multiple organ damages were triggered in COVID-19 patients with asthma, which highlights more intensive surveillance and supportive treatment.

Pachymic Acid Ameliorates Pulmonary Hypertension by Regulating Nrf2-Keap1-ARE Pathway.

OBJECTIVE: Pulmonary hypertension (PH) is a severe pulmonary vascular disease that eventually leads to right ventricular failure and death. The purpose of this study was to investigate the mechanism by which pachymic acid (PA) pretreatment affects PH and pulmonary vascular remodeling in rats. METHODS: PH was induced via hypoxia exposure and administration of PA (5 mg/kg per day) in male Sprague-Dawley rats. Hemodynamic parameters were measured using a right ventricular floating catheter and pulmonary vascular morphometry was measured by hematoxylin-eosin (HE), α-SMA and Masson staining. MTT assays and EdU staining were used to detect cell proliferation, and apoptosis was analyzed by TUNEL staining. Western blotting and immunohistochemistry were used to detect the expression of proteins related to the Nrf2-Keap1-ARE pathway. RESULTS: PA significantly alleviated hypoxic PH and reversed right ventricular hypertrophy and pulmonary vascular remodeling. In addition, PA effectively inhibited proliferation and promoted apoptosis in hypoxia-induced pulmonary artery smooth muscle cells (PASMCs). Moreover, PA pretreatment inhibited the expression of peroxy-related factor (MDA) and promoted the expression of antioxidant-related factors (GSH-PX and SOD). Furthermore, hypoxia inhibited the Nrf2-Keap1-ARE signaling pathway, while PA effectively activated this pathway. Most importantly, addition of the Nrf2 inhibitor ML385 reversed the inhibitory effects of PA on ROS generation, proliferation, and apoptosis tolerance in hypoxia-induced PASMCs. CONCLUSION: Our study suggests that PA may reverse PH by regulating the Nrf2-Keap1-ARE signaling pathway.

Cigarette smoking induces aberrant N6-methyladenosine of DAPK2 to promote non-small cell lung cancer progression by activating NF-κB pathway.

N6-methyladenosine (m6A) has recently emerged as an important regulatory mechanism for gene expression and aberrant m6A modification plays an important role in tumor progression. Emerging evidence has shown that aberrant m6A modification induced by cigarette smoking is involved in carcinogenesis, but whether cigarette smoking affects m6A modification and thus deteriorates to non-small cell lung cancer (NSCLC) is still unclear. Here, we identified a tumor suppressor gene-DAPK2 which was significantly associated with poor prognosis of NSCLC patients, especially in patients with a smoking history. Low levels of DAPK2 were detected in smokers and in NSCLC tissues. Cigarette smoking induced aberrant N6-methyladenosine modification of DAPK2, which resulted in decreased DAPK2 mRNA stability and expression of its mRNA and protein. This modification was mediated by the m6A "writer" METTL3 and the m6A "reader" YTHDF2. Mechanistically, we further demonstrated that DAPK2 functions as a tumor suppressor and downregulation of DAPK2 substantially enhances the proliferation and migration abilities in vitro and in vivo by activating NF-κB signaling pathway. Notably, the BAY 11-7085, a NF-κB signaling selective inhibitor, was shown to efficiently suppressed downregulation of DAPK2-induced oncogenic phenotypes of NSCLC cells. Our study reveals that cigarette smoking induces aberrant N6-methyladenosine of DAPK2 to promote NSCLC progression, which provides new insight into the mechanisms of NSCLC progression and a specific therapeutic target for NSCLC patients with a smoking history.

Long Noncoding RNA WDFY3-AS2 Represses the Progression of Esophageal Cancer through miR-18a/PTEN Axis.

BACKGROUND: Understanding the role of lncRNAs in the development of human malignancies is necessary for the targeted therapy of malignant tumors, including esophageal cancer (EC). Nevertheless, the specific role and regulatory mechanism of lncRNA WDFY3-AS2 in EC are still unclear. Here, we examined the functional role and regulatory mechanism of WDFY3-AS2 in EC. MATERIALS AND METHODS: RT-qPCR assay was applied to measure the expression of WDFY3-AS2 and miR-18a in EC samples and cells. The luciferase reporter and RIP assays were used to check the relationship between WDFY3-AS2, miR-18a, and PTEN. Counting Clock Kit-8 (CCK-8) assay was carried out to detect cell viability, and transwell assays were used for measuring cell migration and invasion. RESULTS: Underexpression of WDFY3-AS2 was found in EC specimens and cells, which predicted a poor prognosis of EC patients. Reexpression of WDFY3-AS2 repressed the progression of EC via inhibiting cell proliferation, migration, and invasion. Additionally, WDFY3-AS2 was negatively correlated with miR-18a and positively with PTEN. Furthermore, we discovered that the expression of PTEN decreased by miR-18a mimic was rescued by WDFY3-AS2 overexpression. CONCLUSIONS: WDFY3-AS2 modulates the expressional level of PTEN as a competitive endogenous RNA via sponging miR-18a in EC, which suggests that the WDFY3-AS2/miR-18a/PTEN pathway might be involved in the progression of EC.

Comparison of Immediate and Sequential Withdrawal of a Systemic Glucocorticoid in the Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Parallel-Controlled, Open-Label Study.

Patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) were treated with immediate or sequential withdrawal after 5 days of systemic glucocorticoids. The effects of the two withdrawal methods on the prognosis of patients were compared at 30, 90, 180, and 360 days after discharge. A multicenter, randomized, double-blind, parallel-controlled, open-label study was conducted in the respiratory department of tertiary hospitals in Central China. Patients met inclusion criteria for AECOPD and needed to use systemic glucocorticoids. They were randomly assigned to immediate and sequential withdrawal groups at a 1:1 ratio. The study was completed in August 2020 and is registered at the China Clinical Trials Registry (Chictr.org) (ChiCTR1800018894). According to general data and clinical characteristics, there were no statistically significant differences between the 329 patients in the immediate withdrawal group and the 310 patients in the sequential withdrawal group (P > 0.05). At the 30, 90, 180, and 360-days follow-up, the acute exacerbation frequency, rehospitalization rate, mortality, and intensive care unit (ICU) treatment rate were not significantly different between the immediate withdrawal group and sequential withdrawal group (P > 0.05). The modified Medical Research Council (mMRC) and COPD assessment test (CAT) scores were also not significantly different between the two groups. At the 180- and 360-day follow-up, forced expiratory volume in 1 s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups (P > 0.05). The time from discharge to first acute exacerbation was significantly lower in the immediate withdrawal group (46.12 days) than in sequential withdrawal group (49.02 days) (P < 0.05). The time of stay in the hospital for the first time after discharge was not significantly different between the two groups (P > 0.05). Adverse events were not significantly different between the immediate withdrawal group and sequential withdrawal group (P < 0.05). Subgroup analysis was performed according to age, degree of disease, and relevant indicators. At the 30-day follow-up, the acute exacerbation frequency of patients with advanced age, high global strategy for chronic obstructive lung disease (GOLD), and high fractional exhaled nitric oxide was significantly higher in the immediate withdrawal group than in the sequential withdrawal group (P < 0.05). In addition, according to receiver operating characteristic (ROC) curve analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly higher in patients with age > 63.5 years or GOLD > 3 in the immediate withdrawal group than in the sequential withdrawal group, suggesting that the short-term efficacy was poor.

Correlation between serum urea nitrogen, cystatin C, homocysteine, and chronic heart failure.

OBJECTIVE: To explore the correlation between uric acid (UA), cystatin C (Cys-C), homocysteine (Hcy), and chronic heart failure (CHF). METHODS: 45 patients with CHF were selected as the research group; 45 healthy people were selected as the control group. The levels of serum UA, Cys-C and Hcy were detected. RESULTS: The in The research group had much higher levels of serum UA, Cys-C and Hcy than the control group (all P<0.05). The levels of above indexes also increased with an increase in cardiac function classification. Patients with major adverse cardiovascular events (MACE) had much higher levels of serum UA, Cys-C, and Hcy than those without MACE in the research group (all P<0.05). In addition, the levels of these above indexes in the research group were all positively correlated with the left ventricular end diastolic diameter (LVEDD) (all P<0.05), and all negatively correlated with the f left ventricular ejection fraction (LVEF) (P<0.05). What is more, the levels of these above indexes in the research group were all positively correlated with New York Heart Association (NYHA) grade (all P<0.05). The diagnostic sensitivity of serum UA level, Cys-C level, and Hcy level in joint diagnosis of CHF patients was higher than that of any single index diagnosis (P<0.05), and the specificity of combined diagnosis was lower than that of single index diagnosis (P<0.05). CONCLUSION: The levels of serum UA, Cys-C, and Hcy in CHF patients may be used as reference indexes for clinical screening of early CHF patients and could provide a certain reference for clinical evaluation.

Dexmedetomidine Attenuates Lung Injury in Toxic Shock Rats by Inhibiting Inflammation and Autophagy.

OBJECTIVE: To explore the mechanisms whereby dexmedetomidine reversed lung injury in rats with toxic shock via inhibiting inflammation and autophagy. METHODS: Thirty-six specific pathogen-free male Sprague Dawley rats with were screened and randomly divided into three groups. Toxic shock was induced by intestinal leakage. The control group received no cecal ligation and the treatment group received dexmedetomidine hydrochloride. Lung tissue morphology was studied by hematoxylin-eosin staining. The expression levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The expression levels of beclin l and LC3 were measured, and the expression levels of apoptosis gene Bax and Bcl-2 were determined. The autophagosomes in lung cells were observed by transmission electron microscopy. Extracellular signal-regulated kinase (ERK) 1/2 expression was determined by Western blotting assays. RESULTS: The results showed that the W/D, total protein and myeloperoxidase (MPO) index in the toxic shock group were 5.45 ± 0.35, 3.21 ± 0.47 and 4.53 ± 0.36, respectively. The W/D (4.02 ± 0.67), total protein (2.01 ± 0.35) and MPO index (2.31 ± 0.59) were significantly lower in the dexmedetomidine group (p <0.05). Similarly, compared with the toxic shock group, the expression of p-ERK1/2 protein in the dexmedetomidine treatment group was significantly decreased (p <0.05). The expression levels of autophagy proteins beclin1 and LC3 in the dexmedetomidine treatment group were not significantly different from those of the control group (p >0.05). Transmission electron microscopy showed that the number of autophagic bodies in lung cells decreased. After induction with dexmedetomidine hydrochloride, the proapoptotic gene Bax was significantly downregulated in the cells. Bax expression levels in each group were 0.36 ± 0.12, 0.67 ± 0.06, and 0.32 ± 0.12, respectively. Compared with the control group, Bax expression in lung tissue significantly increased in the toxic shock group (p <0.05). CONCLUSION: Dexmedetomidine attenuates lung injury in toxic shock rats by inhibiting inflammation and autophagy.

Circ_SATB2 Attenuates the Anti-Tumor Role of Celastrol in Non-Small-Cell Lung Carcinoma Through Targeting miR-33a-5p/E2F7 Axis.

BACKGROUND: Celastrol (Cela) was a natural compound that exerted anti-tumor activity in many cancer cells. Nevertheless, the molecular mechanism behind the anti-tumor role of Cela in non-small-cell lung carcinoma (NSCLC) remains to be clarified. METHODS: Flow cytometry was used to analyze cell cycle progression and apoptosis. Colony formation assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were used to analyze cell proliferation. Cell migration and invasion abilities were assessed by transwell assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was implemented for the detection of RNA levels. Western blot assay was used for the determination of protein levels. Dual-luciferase reporter assay was conducted to confirm the interaction between microRNA-33a-5p (miR-33a-5p) and circular RNA SATB homeobox 2 (circ_SATB2) or E2F transcription factor 7 (E2F7). Xenograft tumor assay was conducted to test the roles of Cela and circ_SATB2 in NSCLC progression in vivo. RESULTS: Cela hampered the malignant behaviors of NSCLC cells. Cela down-regulated circ_SATB2 level in NSCLC cells. Cela stimulation-induced suppressive influence in NSCLC progression was alleviated by circ_SATB2 accumulation. E2F7 interference overturned circ_SATB2-mediated effects in Cela-stimulated NSCLC cells. MiR-33a-5p was a target of circ_SATB2, and E2F7 was verified as a target of miR-33a-5p. Circ_SATB2 attenuated Cela-mediated effects through targeting miR-33a-5p in NSCLC cells. Cela-mediated suppressive effect on tumor growth was partly attenuated by the overexpression of circ_SATB2 in vivo. CONCLUSION: Cela suppressed NSCLC development through regulating circ_SATB2/miR-33a-5p/E2F7 signaling cascade.

Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province.

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.

Long non-coding RNA JPX correlates with poor prognosis and tumor progression in non-small-cell lung cancer by interacting with miR-145-5p and CCND2.

Emerging studies have shown that the aberrant expression and function of long non-coding RNAs (lncRNAs) are involved in carcinogenesis and the development of various cancers. The long noncoding RNA JPX (lncRNA JPX) on the X chromosome is an activator of X-inactive-specific transcript (XIST) and is a molecular switch for X-chromosome inactivation. However, the exact mechanism by which JPX acts in non-small-cell lung cancer (NSCLC) is not well studied. Here, through integrating clinical data and a series of functional experiments, we found that lncRNA JPX expression is significantly upregulated in NSCLC tissues compared with that in paired adjacent normal tissues from two independent datasets and significantly associated with a poor survival and other malignant phenotypes (tumor stage, tumor volume) of NSCLC. Furthermore, we elucidated that JPX functions as an oncogene in NSCLC-promoting cell proliferation and cell migration by affecting cell-cycle progression. Mechanistically, JPX upregulates cyclin D2 (CCND2) expression in a competing endogenous RNA mechanism by interacting with miR-145-5p, thus provoking the development and progression of NSCLC. These findings reveal the mechanism of X-chromosome lncRNA JPX and its core regulatory circuitry JPX/miR-145-5p/CCND2 in the development and progression of NSCLC, which bring us closer to an understanding of the molecular drivers of NSCLC.

Long Intervening Noncoding 00467 RNA Contributes to Tumorigenesis by Acting as a Competing Endogenous RNA against miR-107 in Cervical Cancer Cells.

The functional roles of individual large intervening noncoding RNAs in carcinogenesis and progression of cervical cancer have been uncovered in previous studies. In this study, we aimed to identify the role of long intervening noncoding 00467 (LINC00467) in epithelial-mesenchymal transition (EMT), invasion and migration of cervical cancer cells by regulating miR-107 and kinesin family member 23 (KIF23). Microarray analyses were used to detect cervical cancer-related differentially expressed genes, followed by determination of LINC00467, miR-107, and KIF23 levels and subcellular location of LINC00467. Cervical cancer cells were treated with a series of siRNA and mimics to measure the regulatory role of LINC00467, miR-107, and KIF23 in EMT, cell invasion, migration and proliferation, and tumorigenic ability in vivo and in vitro. LINC00467 and KIF23 were highly expressed, whereas miR-107 was poorly expressed, in cervical cancer. LINC00467 was found to be primarily located in the cytoplasm and function as a competing endogenous RNA against miR-107 to suppress KIF23. Cell proliferation, migration, invasion, and EMT in vitro were inhibited as a result of lentiviral-mediated LINC00467 knockdown and miR-107 overexpression in cervical cancer. In addition, LINC00467 silencing or miR-107 up-regulation repressed tumorigenic ability in xenograft tumor-bearing nude mice in cervical cancer in vivo. LINC00467 silencing or miR-107 up-regulation may serve as novel potential strategies for the treatment of cervical cancer.

Long noncoding RNA LINC00958 regulates cell sensitivity to radiotherapy through RRM2 by binding to microRNA-5095 in cervical cancer.

Long noncoding RNAs (lncRNAs) have been implicated in the regulation of resistance to radiotherapy in cervical cancer, which is a type of gynecological disease with high mortality in women around the world. Hence, our purpose is to delineate the involvement of LINC00958 in regulating cell sensitivity to radiotherapy in cervical cancer. LINC00958 expression in cervical cancer was assayed, followed by verification of the relationship among LINC00958, microRNA-5095 (miR-5095) and ribonucleotide reductase subunit M2 (RRM2). Hela cells were transduced with up-/downregulation of miR-5095 or RRM2, or LINC00958 silencing, respectively, and then treated with or without a 6 Gy dose of X-ray irradiation. Then the cell proliferation, apoptosis, survival fraction rate, as well as sensitivity to radiotherapy, were assessed. Finally, xenograft tumor in nude mice was established by transplanting Hela cells transfected with sh-LINC00958 and irradiated with 6 Gy of X-ray. High expression of LINC00958 was revealed in The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis, as well as in radiation-resistant patients, which was associated with lower sensitivity to radiotherapy in cervical cancer. Moreover, cervical cancer patients with higher LINC00958 expression exhibited a shorter overall survival according to Kaplan-Meier analysis. In addition, LINC00958 could regulate the expression of RRM2 by competing for miR-5095. A combination of radiotherapy with LINC00958 silencing, RRM2 downregulation or miR-5095 overexpression was found to inhibit cervical cancer cell proliferation and tumor growth, while promoting cell apoptosis both in vitro and in vivo. Collectively, our results suggest that LINC00958 could regulate RRM2 by competing to miR-5095, which regulates cell sensitivity to radiotherapy in cervical cancer.