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.

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.

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.

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 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.

Upregulated microRNA-15b alleviates ovarian cancer through inhitbition of the PI3K/Akt pathway by targeting LPAR3.

Ovarian cancer characterizes as the fourth leading consequence of death associated with cancer for women. Accumulating evidence underscores the vital roles of microRNAs (miRNAs) in preventing ovarian cancer development. Besides, induction of the phosphatidylinositol-3 kinase/serine/threonine kinase (PI3K/Akt) pathway associated with the ovarian cancer cell migration and invasion. The study aims to examine the effects of miR-15b on the proliferation, apoptosis, and senescence of human ovarian cancer cells by binding to lysophosphatidic acid receptor 3 (LPAR3) with the involvement of the PI3K/Akt pathway. The positive expression of LPAR3 protein was detected by immunohistochemistry. Then the interaction between miR-15b and LPAR3 was examined. The possible role of miR-15b in ovarian cancer was explored using gain- and loss-of-function experiments. Subsequently, the functions of miR-15b on PI3K/Akt pathway, proliferation, migration, invasion, senescence and apoptosis of ovarian cancer cells were assessed. Furthermore, in vivo tumorigenicity assay in nude mice was performed. LPAR3 was overexpressed, whereas miR-15b was poorly expressed in ovarian cancer tissues. LPAR3 is a direct target of miR-15b. Restored miR-15b promoted Bax expression, apoptosis, and senescence, inhibited expression of LPAR3 and Bcl-2, the extent of PI3K and Akt phosphorylation, as well as ovarian cancer cell proliferation, migration, and invasion. Further, tumor growth was observed to be prevented by miR-15b overexpression. Collectively, our study demonstrates that miR-15b represses the proliferation and drives the senescence and apoptosis of ovarian cancer cells through the suppression of LPAR3 and the PI3K/Akt pathway, highlighting an antitumorigenic role of miR-15b.

Melatonin prevents chronic intermittent hypoxia-induced injury by inducing sirtuin 1-mediated autophagy in steatotic liver of mice.

BACKGROUND: Hepatic steatosis that occasionally results in nonalcoholic steatohepatitis (NASH) is related to obstructive sleep apnea (OSA). Many studies have shown that autophagy exerts protective effects on liver damage caused by various diseases and melatonin exhibits hepatoprotective properties. However, the mechanisms of liver injury induced by chronic intermittent hypoxia (CIH) and the effect of melatonin on the regulation of liver injury remain unclear. PURPOSE: This study was aimed to evaluate the role of CIH in steatohepatitis progression and the regulatory function of melatonin on fatty liver sensitivity to CIH injury, mainly focusing on autophagy signaling. METHODS: A high-fat diet (FD)-induced obesity mouse model was subjected to intermittent hypoxia/normoxia events for approximately 8 h per day using an autophagy agonist, rapamycin, or an inhibitor, 3-methyladenine (3-MA), and SRT1720, a sirtuin 1 (SIRT1) activator, or sirtinol, a SIRT1 inhibitor, with or without melatonin for a total of six successive weeks, followed by assessment of expression of autophagy-related genes and activity of serum aminotransferase as well as histological evaluation of tissue morphology. RESULTS: Neither FD nor CIH alone causes significant liver injury; however, the combination yielded higher serum aminotransferase activities and more severe histological changes, accompanied by a decrease in autophagy activity. Melatonin markedly inhibited FD/CIH-stimulated liver injury by enhancing autophagy. In contrast, SIRT1 inhibition resulted in a decrease in the expression of melatonin-induced autophagy-related genes as well as diminished its protective effects on FD/CIH-induced liver injury. CONCLUSION: These results suggest that melatonin could ameliorate FD/CIH-induced hepatocellular damage by activating SIRT1-mediated autophagy signaling.

Atorvastatin Attenuates Myocardial Hypertrophy Induced by Chronic Intermittent Hypoxia In Vitro Partly through miR-31/PKCε Pathway.

Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia (CIH). However, little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy, and whether specific hypertrophyrelated microRNAs are involved in the modulation. MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia. This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy. H9c2 cells were subjected to 8-h intermittent hypoxia per day in the presence or absence of atorvastatin for 5 days. The size of cardiomyocytes, and the expression of caspase 3 and miR-31 were determined by Western blotting and RT-PCR, respectively. MiR-31 mimic or Ro 31-8220, a specific inhibitor of protein kinase C epsilon (PKCε), was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes. PKCε in the cardiomyocytes with miR-31 upregulation or downregulation was detected using RT-PCR and Western blotting. The results showed that CIH induced obvious enlargement of cardiomyocytes, which was paralleled with increased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and slow/beta cardiac myosin heavy-chain (MYH7) mRNA levels. All these changes were reversed by the treatment with atorvastatin. Meanwhile, miR-31 was increased by CIH in vitro. Of note, the atorvastatin pretreatment significantly increased the mRNA and protein expression of PKCe and decreased that of miR-31. Moreover, overexpression of miR-31 abolished the anti-hypertrophic effect of atorvastatin on cardiomyocytes. Upregulation and downregulation of miR-31 respectively decreased and increased the mRNA and protein expression of PKCε. These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.

MicroRNA-374b inhibits cervical cancer cell proliferation and induces apoptosis through the p38/ERK signaling pathway by binding to JAM-2.

Cervical cancer (CC) remains a highly prevalent cancer and mortality globally among women globally. The aim of the present study was to assess the ability of miR-374b to regulate CC cells through JAM-2, whilst exploring whether the underlying mechanism and its relation to the p38/ERK signaling pathway. During the study, microRNA-374b (miR-374b) was observed to have been expressed at a low level among CC tissues. Hence, a series of miR-374b mimics, miR-374b inhibitors, siRNA against JAM-2, SB202190 (an inhibitor for p38), and PD98059 (an inhibitor for ERK) were introduced to treat CC Siha cells and normal cervical Ect1/E6E7 cells. MTT, flow cytometry, scratch test, and transwell assays were applied to determine cell viability, apoptosis, migration, and invasion. The inhibitory role of the p38/ERK signaling pathway was observed in the CC cells treated with miR-374b mimics or siRNA against JAM-2. miR-374b mimic exposure was found to reduce cell viability, migration, and invasion, but induce apoptosis. MiR-374b inhibitor exposure was observed to have induced effects on the CC cells in a contrary manner to those induced by that of the miR-374b mimics. The key findings of the study demonstrated that miR-374b significantly inhibits cell proliferation, migration, and invasion through the blockade of the p38/ERK signaling pathway activation, as well as negatively binding to JAM-2, highlighting its potential as a therapeutic target for CC.

Inhibition of microRNA-34a protects against propofol anesthesia-induced neurotoxicity and cognitive dysfunction via the MAPK/ERK signaling pathway.

AIM: To investigate the protective effect of microRNA-34a (miR-34a) on propofol-induced neurotoxicity and cognitive dysfunction. METHODS: After SH-SY5Y cells were treated with propofol to induce neurotoxicity, microRNA-34a mimics and inhibitors were transfected into the cells. The expression of apoptosis-related genes and the proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Sprague-Dawley (SD) rats received intraperitoneal injections of propofol, and were treated with microRNA-34a mimics and lentivirus-mediated microRNA-34a inhibitors. The Morris water maze (MWM) test was used to detect changes in motor function. RESULTS: Propofol anesthesia had an adverse effect on cell survival due to the increased expression of apoptosis-related genes such as cleaved caspase-3/8 and Bax, which was accompanied by reduced expression of ERK1/2, pERK1/2, and phosphorylated NF-kappaB p65 both in vivo and in vitro. Unexpectedly, microRNA-34a was upregulated after propofol treatment, and the inhibitors protected the SH-SY5Y cells from propofol-induced apoptosis. The microRNA-34a inhibitor suppressed the apoptosis-induced effects of propofol. This protection may have been partly diminished by PD98059, a MAPK kinase inhibitor. MicroRNA-34a inhibited or reverted the reduced expression of ERK1/2 and upregulated the expression of p-CREB significantly and specifically. Additionally, the microRNA inhibitors improved the learning and memory functions of animals suffering from neurologic impairment due to propofol treatment and reduced cell apoptosis in the hippocampus. CONCLUSION: microRNA-34a could improve anesthesia-induced cognitive dysfunction by suppressing cell apoptosis and recovering the expression of genes associated with the MAPK/ERK signaling pathway.

Losartan attenuates aortic endothelial apoptosis induced by chronic intermittent hypoxia partly via the phospholipase C pathway.

PURPOSE: Endoplasmic reticulum (ER) stress is known to play key roles in the development of endothelial cell apoptosis induced by chronic intermittent hypoxia (CIH), and the angiotensin II-phospholipase C-inositol-1,4,5-triphosphate (AngII-PLC-IP3) pathway has been demonstrated to induce ER stress. To explore whether the AngII-PLC-IP3 pathway is involved in the vascular damage induced by CIH, we examined whether the AngII-PLC-IP3 pathway is involved in ER stress induced by CIH and whether losartan, a selective angiotensin II type 1 receptor (AT1R) blocker, could suppress endothelial cell apoptosis induced by CIH. METHODS: Adult male Sprague Dawley rats were subjected to 8 h/day of intermittent hypoxia/normoxia, with or without losartan, a selective AT1R blocker, and/or U73122, a selective PLC inhibitor, for 8 weeks. Endothelial cell apoptosis, ER stress markers, and levels of PLC-γ1 and IP3R expression were determined. RESULTS: Losartan prevented increases in PLC-γ1 and IP3R protein levels and inhibited ER stress markers induced by CIH. Addition of U73122 reproduced all the protective effects of losartan. Losartan administration before CIH significantly ameliorated CIH-induced endothelial cell apoptosis. CONCLUSIONS: This study showed that the AngII-PLC-IP3 pathway is involved in ER stress induced by CIH and that pre-losartan administration ameliorates endothelial cell apoptosis following CIH partly via inhibition of the AngII-PLC-IP3 pathway and ER stress.