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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor of the digestive system which has a less than 1% 5-year survival rate. The pathogenesis of PDAC development is incompletely understood. Genetic predisposition, disease history of chronic pancreatitis and diabetes elevate the risk of PDAC while environmental and dietary factors including smoking, alcohol abuse, high fat/protein intake as well as air pollution exacerbate PDAC progression. BCAAs, consisting of leucine, isoleucine and valine are essential amino acids that are obtained from food and play versatile roles in carcinogenesis. Recent studies have demonstrated that BCAA metabolism affects PDAC development but the results are controversial. To explore the possible engagement of BCAA metabolism in PDAC, we took advantage of the GEO and TCGA database and discovered that BCAA uptake is closely related to PDAC development while BCAA catabolism is down-regulated in PDAC tissue. Besides, NOTCH and MYC are differentially involved in BCAA metabolism in tumor and muscle, and enhanced lipid synthesis is independent of BCAA catabolism. Altogether, we highlight BCAA uptake as a promising target for PDAC treatment.

Background and aim A novel coronavirus severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) caused pneumonia, Coronavirus Disease 2019 (COVID-19), broke out in Wuhan, China in December 2019, and spread all over the world. Patients with COVID-19 showed huge differences in the hospital stay, progression, and prognosis. As reported, the comorbidities may play an important role in COVID-19. Here, we aim to address the role of cardiovascular disease (CVD) in the progression and prognosis of COVID-19. Methods and results Eighty-three confirmed COVID-19 patients were divided into CVD (n = 42) and non-CVD (n = 41) group according to their medical history. Medical records including demographic data, medical history, clinical characteristics, laboratory examinations, chest computed tomography (CT), and treatment measures were collected, analyzed, and compared between the two groups. COVID-19 patients with CVD showed (1) more severe pathological changes in the lungs, (2) elevated injury-related enzymes including α-hydroxybutyrate dehydrogenase (HDBH), lactic dehydrogenase (LDH), γ-glutamyltransferase (GGT), creatine kinase (CK), and alanine aminotransferase (ALT), (3) significantly increased uncontrolled inflammation related markers, such as c-reactive protein (CRP), interleukin (IL)-6, serum ferritin, erythrocyte sedimentation rate (ESR), and serum amyloid A (SAA), (4) serious hypercoagulable status reflected by increased D-dimer and serum fibrinogen (FIB), and (5) higher mortality, compared to COVID-19 patients without CVD. Conclusions Our data indicated that CVD is a strong risk factor for rapid progression and bad prognosis of COVID-19. More intensive medical care should be applied to patients with CVD to prevent rapid deterioration of the disease.

In our previous studies, we found that extracellular vesicles in mesenchymal stem cells can alleviate ulcerative colitis. In view of the fact that extracellular vesicles have the same immunomodulatory effects as their maternal cells and considering the important role of Th17 cells in the pathogenesis of ulcerative colitis, we aimed to investigate whether extracellular vesicles from mesenchymal stem cells can affect the differentiation of Th17 cells in ulcerative colitis. Histone H3K27me3 can regulate the expression of Th17 cell-related genes. We focused on determining whether the effect of extracellular vesicles on Th17 cells in ulcerative colitis is related to H3K27me3. For our experiments, we used low, medium and high doses of extracellular vesicles from mesenchymal stem cells to interfere with TNBS-induced colitis in rats and then evaluated the alleviation of inflammation and observed the impact of the extracellular vesicles on the differentiation of Th17 cells in ulcerative colitis. In addition, we detected the levels of histone H3K27me3 and the expression of its upstream methyltransferase and demethylase in the colon tissues of each group. Our data showed that extracellular vesicles from bone marrow mesenchymal stem cells can inhibit the abnormal differentiation of Th17 cells in ulcerative colitis, and the content of histone H3K27me3 was also changed accordingly. Our study suggests that extracellular vesicles from mesenchymal stem cells could inhibit the differentiation of Th17 cells in ulcerative colitis by regulating H3K27me3. This study reveals that H3K27me3 is an important target for inflammatory immune diseases associated with abnormal Th17 cell differentiation and indicates that mesenchymal stem cell extracellular vesicles are promising agents for the treatment of ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by multi-factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that Celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and the mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR preforms the protective effect. We characterized the therapeutic effects and the potential mechanism of CSR in treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation approaches. CSR administration significantly ameliorated DSS-induced colitis, as evidenced by the recovery of body weight and colon length, decreased disease activity index (DAI) score, as well as decreased intestinal permeability. CSR down-regulated the secretion of proinflammatory cytokines, upregulated the anti-inflammatory mediators, and improved the balances of Treg/Th1 and Treg/Th17 to maintain colonic immune homeostasis. However, the protective effects of CSR disappeared when the antibiotic cocktail was applied to deplete the gut microbiota, and the gut microbiota-mediated effect was confirmed by FMT. Furthermore, CSR treatment increased the gut microbiota diversity and composition, and raised the metabolic productions of pyruvate and adenosine, which probably involve in gut microbiota mediated protective effect. In conclusion, CSR ameliorates colonic inflammation in a gut microbiota-dependent manner. The underlying protective mechanism is associated with the rectified Treg/Th1 and Treg/Th17 balance, and increased pyruvate and adenosine production. The study provided the solid evidence that CSR might be a promising therapeutic drug for UC.

Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder significantly decreasing patients’ lives of quality and placing huge economic burden on our society. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued. It is clinically important to assess these post-treatment therapeutic effects (PTTE), which prevent IBS from relapsing. To assess the PTTE in pinaverium treatment and obtain high-quality evidence to justify the use of PTTE for long-term IBS management, we performed this controlled, double blind study on patients with IBS who were randomized to pinaverium 50 mg (n = 132) or placebo (n = 132), three times daily, for 4 weeks, and were followed up for 57 weeks after the treatments. The primary endpoints were abdominal pain and stool consistency. The secondary endpoints were pain frequency and stool frequency. The tertiary endpoints were global overall symptom and adverse events. Three days after pinaverium was discontinued, endpoints rebounded only 23.2–42.8% (P P P’s > 0.05)], during which an average of 51.5–56.4% of patients (pool pinaverium and placebo data together) had IBS symptoms. These results provide clinical insights into efficient and cost-effective management of refractory IBS, and lend support to the IBS management that the selection of a therapy should consider both its effectiveness during treatment and its PTTE after the treatment.Trial registration number: NCT02330029 (16/08/2016).

Compound sophorae decoction (CSD), a traditional Chinese medicine (TCM) formula, has been voluminously used in China to deal with ulcerative colitis and gained significant therapeutic effect. Tremendous explorations have unraveled a contributory role of inflammatory bowel disease (IBD) like ulcerative colitis (UC) and Crohn’s disease (CD) at the onset of colorectal cancer, scilicet, and colitis-related cancer (CRC). In light of the anti-inflammatory properties of CSD in UC, we appraised its chemoprevention capacity and underlying mechanism in ulcerative colitis-related colorectal cancer (UCRCC), employing a model of azoxymethane (AOM) plus dextran sulfate sodium- (DSS-) induced colorectal cancer (CRC) in C57BL/6 mice. Rapturously, our results illuminated the ameliorative effect of CSD against UCRCC in mice portrayed by lesser polyps or adenomas, attenuated colonic xenograft tumor growth in company with the preferable well-being of mice in contrast to the Model Group. We examined significant downregulation of proinflammatory cytokines such as TNF-α, NF-κB, IL-6, STAT3, and IL-17 after exposure to CSD, with the concomitant repression of inflammation-associated proteins, including COX-2 and iNOS. Independent of this, treatment with CSD declined the proportion of T helper 17 cells (Th17) and protein level of matrix metallopeptidase 9 (MMP-9). Moreover, transmission electron microscopy (TEM) detected observably suppressed mitophagy in mice administered with CSD and that was paralleled by the pro-apoptotic effect as indicated by upregulating caspase-3 together with caspase-9 and deregulating B-cell lymphoma 2 (Bcl-2). In closing, these findings suggest CSD executes the UCRCC-inhibitory activity through counteracting inflammatory responses and rescuing detuning of apoptosis as well as neutralizing overactive mitophagy, concurring to build up an oncosuppressive microenvironment.

Chronic glucocorticoid therapy has serious side effects, including diabetes and fatty liver. However, the molecular mechanisms responsible for steroid-induced diabetes remain largely enigmatic. Here, we show that hepatic Kruppel-like factor 9 (Klf9) gene expression is induced by dexamethasone and fasting. The overexpression of Klf9 in primary hepatocytes strongly stimulated Pgc1a gene expression through direct binding to its promoter, thereby activating the gluconeogenic program. However, Klf9 mutation abolished the stimulatory effect of dexamethasone on cellular glucose output. Adenovirus-mediated overexpression of KLF9 in the mouse liver markedly increased blood glucose levels and impaired glucose tolerance. Conversely, both global Klf9-mutant mice and liver-specific Klf9-deleted mice displayed fasting hypoglycemia. Moreover, the knockdown of Klf9 in the liver in diabetic mouse models, including ob/ob and db/db mice, markedly lowered fasting blood glucose levels. Notably, hepatic Klf9 deficiency in mice alleviated hyperglycemia induced by chronic dexamethasone treatment. These results suggest a critical role for KLF9 in the regulation of hepatic glucose metabolism and identify hepatic induction of KLF9 as a mechanism underlying glucocorticoid therapy-induced diabetes.

Background: Disruption of intestinal barrier function and an imbalance in intestinal immunity are crucial for the occurrence and development of ulcerative colitis. Because of their important roles in regulating inflammation and immunity, exosomes (Exos) released from bone marrow mesenchymal stem cells (BMSCs) may be useful for treating ulcerative colitis. The EphB/EphrinB signaling pathway plays a crucial role in the inflammatory process and the development and function of immune cells, and can mediate long-distance intercellular communication through extracellular vesicles. This study was conducted to explore the effects of pre-modified BMSC-Exos expressing EphB2 (EphB2-Exos) on immunoregulation in vitro. Method: sWe transfected a lentivirus vector encoding EphB2 into BMSCs and isolated EphB2-Exos from the culture supernatant. Inflammation and oxidative damage in the human colon adenocarcinoma cell line (Caco-2) were induced by dextran sulfate sodium/hydrogen peroxide. In addition, spleen CD4+ T lymphocytes of rats were sorted in vitro. We conducted a series of experiments to explore the biological functions of EphB2-Exos. Results: EphB2-Exos were successfully isolated and were found to significantly protect the activity, proliferation, and migration of Caco-2 cells that were inhibited by dextran sulfate sodium. EphB2-Exos alleviated inflammation and apoptosis and increased the activity of antioxidant enzymes while inhibiting oxidative stress in Caco-2 cells. EphB2-Exos restored barrier function by inhibiting the RhoA/ROCK pathway and regulated the polarization of CD4+T cells. Conclusion: EphB2-Exos enhanced intestinal barrier function and regulated the immune balance by inhibiting the RhoA/ROCK pathway in vitro. These findings suggest that EphB2-Exos can be applied as a cell-free therapy for ulcerative colitis.

Background Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. Methods In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. Results CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. Conclusions These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.

Objective. We aimed to investigate the protective effect of s-nitrosoglutathione (SNG) pretreatment on acute kidney injury (AKI) in septic rats. Methods. We constructed a rat model of sepsis by cecal ligation and puncture and observed the survival of the rats. We obtained kidney and blood samples from rats, observed the pathological damage to the kidney tissues, and evaluated kidney function and the expression levels of inflammatory factors. We also detected the expression of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the kidneys by immunohistochemistry and evaluated the apoptosis of kidney tubular epithelial cells (KTEC) by TUNEL. Results. Pretreatment with SNG significantly reduced the mortality of septic rats, attenuated kidney pathological damage, and decreased the levels of serum creatinine, plasma neutrophil gelatinase-associated lipocalin, and plasma kidney injury molecule-1. Moreover, SNG pretreatment decreased the levels of TNF-α and IL-1β in serum and kidney and reduced the expressions of NO, iNOS, PGE2, and COX-2 in the kidneys. Furthermore, pretreatment with SNG significantly reduced the apoptotic rate of KTEC and decreased the levels of caspase-3 and Bax mRNA, but increased the level of Bcl-2 mRNA. Conclusion. Pretreatment with SNG has a protective effect on AKI in septic rats, and the specific mechanisms are related to inhibition of inflammation, oxidation, and apoptosis.

Inflammatory bowel disease (IBD) is an autoimmune disease characterized by unresolved colitis and epithelial injury. Intestinal microbiota and its interaction with immune system are critical etiologic factors. In response to gut virome and bacteria derived nucleic acid, interferon regulatory factors (IRFs) are activated to promote the production of cytokines, including type I interferons (IFN-Is), to help maintain intestinal homeostasis under both physiological and pathophysiological conditions. However, derailed IRF/IFN-I pathway other-wisely contributes to the progression of IBD with distinct IRF member exerting differential regulatory effect. Here, we summarize the recent advances regarding the role of IRF/IFN-I pathway in the development of IBD. We emphasize that IFN-I is a double-edged sword in IBD pathogenesis, as IFN-Is are protective in acute colitis while becoming pro-inflammatory during the chronic recovery phase. Besides, the functional outcome of IRFs is diverse and complex, which hinges on the cell types affected and the presence of other immune mediators. All in all, IRF/IFN-I pathway serves as a versatile regulator in IBD pathogenesis and holds the potential for therapeutic interventions.

Background The bone marrow mesenchymal stem cell (BMSCs)-derived extracellular vesicles (EVs) open up a new avenue for ulcerative colitis (UC) treatment recently, but they are not selectively enriched in targeted tissues. EphB2, a cell-to-cell signaling receptor, is identified as a regulator for inflammatory response, immune homeostasis and cell migration. In this study, we investigated the therapeutic potential and underlying mechanism for EphB2 over-expressing BMSCs derived EVs (EphB2-EVs) in the treatment of UC. Methods BMSCs and EVs were obtained and characterized by a series of experiments. Lentivirus vector encoding EphB2 was transfected into BMSCs and verified by qRT-PCR. We analyzed the EphB2-EVs ability of colonic targeting in a DSS-induced colitis model by using confocal microscope and WB. The protective effect of EphB2-EVs in vivo was systematically evaluated by using a series of function experiments. Results We successfully constructed EphB2-overexpressing BMSCs derived EVs (EphB2-EVs). Overexpression of EphB2 significantly enhanced the homing of EVs to the damaged colon. In addition, EphB2-EVs were effective to attenuate inflammation in intestinal mucosa and restore the damaged colon tissue by inhibiting the release of proinflammatory cytokines and upregulating the anti-inflammatory mediators. EphB2-EVs effectively reduced the oxidative stress and repaired the intestinal mucosal barrier in the UC rats. Moreover, EphB2-EVs demonstrated a robust immunomodulatory effect to restore immune homeostasis via modulating Th17/Treg balance and restraining STAT3 activation. Conclusions Our results suggest that EphB2-EVs have high colonic targeting ability and could mitigate DSS-induced colitis via maintaining colonic immune homeostasis. These findings provide an effective therapeutic strategy for UC treatment in clinic.

Dental panoramic radiography (DPR) images have recently attracted increasing attention in osteoporosis analysis because of their inner correlation. Many approaches leverage machine learning techniques (e.g., deep convolutional neural networks (CNNs)) to study DPR images of a patient to provide initial analysis of osteoporosis, which demonstrates promising results and significantly reduces financial cost. However, these methods heavily rely on the trabecula landmarks of DPR images that requires a large amount of manual annotations by dentist, and thus are limited in practical application. Addressing this issue, we propose to automatically detect trabecular landmarks in DPR images. In specific, we first apply CNNs-based detector for trabecular landmark detection and analyze its limitations. Using CNNs-based detection as a baseline, we then introduce a statistic shape model (SSM) for trabecular landmark detection by taking advantage of spatial distribution prior of trabecular landmarks in DPR images and their structural relations. In experiment on 108 images, our solution outperforms CNNs-based detector. Moreover, compared to CNN-based detectors, our method avoids the needs of vast training samples, which is more practical in application.

BackgroundSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced Coronavirus Disease 2019 (COVID-19) has posed a global threat to public health. The immune system is crucial in defending and eliminating the virus and infected cells. However, immune dysregulation may result in the rapid progression of COVID-19. Here, we evaluated the subsets, phenotypic and functional characteristics of natural killer (NK) and T cells in patients with COVID-19 and their associations with disease severity.MethodsDemographic and clinical data of COVID-19 patients enrolled in Wuhan Union Hospital from February 25 to February 27, 2020, were collected and analyzed. The phenotypic and functional characteristics of NK cells and T cells subsets in circulating blood and serum levels of cytokines were analyzed via flow cytometry. Then the LASSO logistic regression model was employed to predict risk factors for the severity of COVID-19.ResultsThe counts and percentages of NK cells, CD4(+) T cells, CD8(+) T cells and NKT cells were significantly reduced in patients with severe symptoms. The cytotoxic CD3(-)CD56(dim)CD16(+) cell population significantly decreased, while the CD3(-)CD56(dim)CD16(-) part significantly increased in severe COVID-19 patients. More importantly, elevated expression of regulatory molecules, such as CD244 and programmed death-1 (PD-1), on NK cells and T cells, as well as decreased serum cytotoxic effector molecules including perforin and granzyme A, were detected in patients with COVID-19. The serum IL-6, IL-10, and TNF-alpha were significantly increased in severe patients. Moreover, the CD3(-)CD56(dim)CD16(-) cells were screened out as an influential factor in severe cases by LASSO logistic regression.ConclusionsThe functional exhaustion and other subset alteration of NK and T cells may contribute to the progression and improve the prognosis of COVID-19. Surveillance of lymphocyte subsets may in the future enable early screening for signs of critical illness and understanding the pathogenesis of this disease.

Background Since December 2019, novel coronavirus (SARS-CoV-2)-induced pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. COVID-19 patients demonstrated significantly different outcomes in clinic. We aimed to figure out whether obesity is a risk factor influencing the progression and prognosis of COVID-19. Methods 95 patients with COVID-19 were divided into obesity group and non-obesity group according to their body mass index (BMI). The demographic data, clinical characteristics, laboratory examination, and chest computed tomography (CT) were collected, analyzed and compared between two groups. Results Our data showed that COVID-19 patients with obesity had more underlying diseases and higher mortality rate compared to those without obesity. Furthermore, patients with obesity also demonstrated more severe pathological change in lung and higher blood lymphocytes, triglycerides, IL-6, CRP, cystatin C, alanine aminotransferase (ALT), erythrocyte sedimentation rate (ESR), which may greatly influence disease progression and poor prognosis of COVID-19. Conclusions It suggest that obesity contributes to clinical manifestations and may influence the progression and prognosis of COVID-19 and it is considered as a potential risk factor of the prognosis of COVID-19. Special medical care and appropriate intervention should be performed in obesity patients with COVID-19 during hospitalization and later clinical follow-up, especially for those with additional other comorbidities.

The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, has caused a pandemic worldwide. To investigate the immune responses after infection of SARS-CoV-2 in non-critical patients may help to better understand the disease progression. We collected 334 confirmed COVID-19 cases including 212 still in hospital with nucleic acid test positive on halfway for SARS-CoV-2 and 122 discharged from hospital, compared specific antibodies, immune cells, and cytokine changes between the hospitalized and discharged patients. The hospitalized patients had a longer illness time compared with discharged patients. Analysis of viral loads explained long-term or persistent infection of SARS-CoV-2, which existed with the median time of 18.5 days of the positive nucleic acid test. Serum analysis showed that the specific anti-N IgG antibody was positive in all detected patients after infection of two weeks. Neutrophils, Monocytes, NK cells, and CD4+ T cells significantly increased, while total lymphocytes and CD8+ T cells decreased from non-critical hospitalized patients after longer-term infection. Further analysis of the cytokines showed that IL-6, TNF-α, IFN-γ, IL-2, IL-4, and IL-10 from the hospitalized patients were significantly higher, indicating a potential of the increased CD4+ T cell differentiation., Highlights • Viral loads explained the long-term or persistent infection of SARS-CoV-2 in some non-critical and hospitalized patients. • After infection of two weeks, serum analysis showed that the specific anti-N IgG was positive in all detected patients. • Compared with the discharged patients, inpatients had different immune cells after longer-infection of SARS-CoV-2. • Compared with the discharged patients, hospitalized patients had an increase in some cytokines.

Background The outbreak of COVID‐19, caused by SARS‐CoV‐2, started in December 2019, Wuhan, China. We aimed to figure out the time‐point and duration of using antiviral drugs for receiving the maximal effects in patients with COVID‐19. Methods In this study, we enrolled 129 confirmed COVID‐19 mild to moderate patients who had been treated with antiviral drugs during their hospitalization in Wuhan Union Hospital China. The patients were divided into early antiviral treatment group and late antiviral treatment group. The demographic data, laboratory tests, the virus clearance time, chest computed tomography (CT) scans, etc. were extracted, calculated and compared between two groups. Results Our data showed that the median time from illness onset to initiation of antiviral treatment was 6 days in all patients. The group with early antiviral treatment demonstrated 7 days shorter in the virus clearance time when compared to the group with late antiviral treatment. After virus clearance, the group with early antiviral treatment showed milder illness than the group with late antiviral treatment. Conclusions Early antiviral treatment could effectively shorten the virus clearance time, and prevent the rapid progression of COVID‐19. Therefore, the COVID‐19 patients should receive combined therapies with antiviral treatment at early stage. This article is protected by copyright. All rights reserved.

Importance: Since December 2019, a novel coronavirus (SARS-CoV-2) causing COVID-19 has spread across the world in a global pandemic. Tens of thousands of people were infected, several thousand patients died. However, key risk factors for predicting mortality remain unclear.Objective: To identify the key risk factors for COVID-19 mortality.Design, Setting, Participants: Retrospective, randomly selected eight family clusters consisting of 21 individual cases who had been confirmed positive for SARS-CoV-2 and admitted to the Wuhan Union Hospital, Wuhan, China, from February 6 to March 3 2020. This study aims to analyze the differences in mortal risk factors between fatal and non-fatal cases within each family.

Backgound To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID‐19). Methods A total of 174 consecutive patients confirmed with COVID‐19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. Results We found that COVID‐19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury‐related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation‐related biomarkers such as IL‐6, C‐reactive protein, serum ferritin and coagulation index, D‐dimer, were significantly higher (P

BackgroundIn December 2019, a novel coronavirus (SARS-CoV-2) caused infectious disease, termed COVID-19, outbroke in Wuhan, China. COVID-19 patients manifested as lung injury with complications in other organs, such as liver, heart, gastrointestinal tract, especially for severe cases. However, whether COVID-19 causes significant acute kidney injury (AKI) remained controversial.MethodsWe retrospectively analyzed the clinical characteristics, urine and blood routine tests and other laboratory parameters of hospitalized COVID-19 patients in Wuhan Union Hospital.Findings178 patients, admitted to Wuhan Union hospital from February 02 to February 29, 2020, were included in this study. No patient (0 [0%]) presented increased serum creatinine (Scr), and 5 (2.8%) patients showed increased blood urea nitrogen (BUN), indicating few cases with “kidney dysfunction”. However,for patients (83) with no history of kidney disease who received routine urine test upon hospitalization, 45 (54.2%) patients displayed abnormality in urinalysis, such as proteinuria, hematuria and leukocyturia, while none of the patients was recorded to have acute kidney injury (AKI) throughout the study. Meanwhile, the patients with abnormal urinalysis usually had worse disease progression reflecting by laboratory parameters presentations, including markers of liver injury, inflammation, and coagulation.ConclusionMany patients manifested by abnormal urinalysis on admission, including proteinuria or hematuria. Our results revealed that urinalysis is better in unveiling potential kidney impairment of COVID-19 patients than blood chemistry test and urinalysis could be used to reflect and predict the disease severity. We therefore recommend pay more attention in urinalysis and kidney impairment in COVID-19 patients.

An outbreak of pneumonia caused by a novel coronavirus (COVID-19) began in Wuhan, China in December 2019 and quickly spread throughout the country and world. An efficient and convenient method based on clinical characteristics was needed to evaluate the potential deterioration in patients. We aimed to develop a simple and practical risk scoring system to predict the severity of COVID-19 patients on admission. We retrospectively investigated the clinical information of confirmed COVID-19 patients from 10 February 2020 to 29 February 2020 in Wuhan Union Hospital. Predictors of severity were identified by univariate and multivariate logistic regression analysis. A total of 147 patients with confirmed SARS-CoV-2 infection were grouped into non-severe (94 patients) and severe (53 patients) groups. We found that an increased level of white blood cells (WBC), neutrophils, D-dimer, fibrinogen (FIB), IL-6, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), α-hydroxybutyrate dehydrogenase (HBDH), serum amyloid A (SAA) and a decreased level of lymphocytes were important risk factors associated with severity. Furthermore, three variables were used to formulate a clinical risk scoring system named COVID-19 index = 3 × D-dimer (µg/L) + 2 × lgESR (mm/hr) - 4 × lymphocyte (×109 /L) + 8. The area under the receiver operating characteristic (ROC) curve was 0.843 (95% CI, 0.771-0.914). We propose an effective scoring system to predict the severity of COVID-19 patients. This simple prediction model may provide healthcare workers with a practical method and could positively impact decision-making with regard to deteriorating patients.

Intestinal barrier dysfunction is a hallmark of inflammatory bowel disease (IBD). MiR-155 is increased in colitis and downregulates expression of hypoxia-inducible factor 1α (HIF-1α). Here, we investigated the effects of miR-155 on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. We found that miR-155 antagomir treatment relieved weight loss and intestinal damage in IBD mouse models (P < 0.05). Furthermore, electron microscopy and immunofluorescence imaging showed that miR-155 increased intestinal barrier dysfunction and downregulated the expression of tight junction proteins in DSS-induced colitis. FG-4497, which upregulates HIF-1α expression, elicited protective effects on the intestinal barrier in DSS-induced colitis. Dual luciferase reporter assays also confirmed that miR-155 downregulated expression of HIF-1α. Finally, we discovered that HIF-1α levels were elevated by miR-155 antagomir treatment (P < 0.05) and that TFF-3 expression correlated positively with HIF-1α expression. These results suggest that miR-155 contributes to DSS-induced colitis by promoting intestinal barrier dysfunction and inhibiting the HIF-1α/TFF-3 axis.

Inflammatory bowel disease (IBD) has received much attention due to its increasing worldwide incidence and potential increased risk of colorectal cancer. The protective function of a Rho-associated protein kinase inhibitor (Y-27632) against 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced mouse colitis has been proven in previous studies, but the concrete therapeutic mechanism of Y-27632 is still not completely illuminated. This current research is intended for further investigation of the effect and mechanism of Y-27632 in a mouse model of acute experimental ulcerative colitis induced by dextran sulfate sodium (DSS). A total of 24 male BALB/c mice were randomly separated into the following three groups (n = 8 per group) and injected intraperitoneally with the corresponding reagents for 7 days: control group (PBS), DSS group (PBS), and Y-27632 group (PBS and Y-27632; 10 mg/kg). Our data indicated that Y-27632 could significantly improve the severity of colitis, as evidenced by the disease activity index (DAI) scores, histological damage, and colon length. Additionally, Y-27632 treatment significantly decreased CD68 and proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-17F (IL-17F), and interleukin-6 (IL-6). Furthermore, Y-27632 potently and pleiotropically suppressed nuclear factor-κB (NF-κB) and signal transduction and transcriptional activator 3 (STAT3) activation as well as the activity of prosurvival genes that are dependent on these transcription factors. In summary, the study demonstrates that Y-27632 exerts ameliorative effects on colonic inflammation mediated through dual inhibition of the NF-κB and IL-6/STAT3 pathways and thus is likely to function as a prospective novel treatment for human ulcerative colitis (UC).

Objective We aimed to assess the effects of physical activity (PA) on depression symptoms in patients with IgA nephropathy (IgAN). Methods We developed a 6-month personalized PA training program for patients with IgAN. At the beginning and after completion of the training intervention, patients’ cardiopulmonary function was assessed via a spiroergometric study. Prior to the start of and after the intervention, we administered the Beck Depression Inventory-II (BDI-II), Eysenck Personality Questionnaire (EPQ), Quality of Life Index (QLI), Life Satisfaction Index, and Short Form-36 (SF-36) to all participants. Scores of the QLI were used as the dependent variable. Results A total of 216 patients were included in our analysis. After completing the PA training program, cardiopulmonary function and depressive symptoms were significantly improved in patients with IgAN, as compared with baseline values. Multiple logistic regression analysis showed that regular PA; extended hemodialysis interval; decreased scores of the BDI-II, EPQ, and SF-36 Mental Component Scale; and increased SF-36 Physical Component Scale scores were independently associated with improved QLI. Conclusions Regular PA may improve cardiopulmonary function, depression symptoms, and health-related quality of life in patients with IgAN.

Background: Last winter, a new coronavirus-induced pneumonia, COVID-19, broke out in Wuhan, China, and spread rapidly throughout the country due to its high inf

Background: The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, caused global concern New cases of COVID-19 were gradually reduced unde

Background: In December 2019, a novel coronavirus (SARS-CoV-2) caused infectious disease, termed COVID-19, outbroke in Wuhan, China. COVID-19 patients manifested as lung injury with complications in other organs, such as liver, heart, gastrointestinal tract, especially for severe cases. However, whether COVID-19 causes significant acute kidney injury (AKI) remained controversial. Methods: We retrospectively analyzed the clinical characteristics, urine and blood routine tests and other laboratory parameters of hospitalized COVID-19 patients in Wuhan Union Hospital. Findings: 178 patients, admitted to Wuhan Union hospital from February 02 to February 29, 2020, were included in this study. No patient (0 [0%]) presented increased serum creatinine (Scr), and 5 (2.8%) patients showed increased blood urea nitrogen (BUN), indicating few cases with “kidney dysfunction”. However，for patients (83) with no history of kidney disease who received routine urine test upon hospitalization, 45 (54.2%) patients displayed abnormality in urinalysis, such as proteinuria, hematuria and leukocyturia, while none of the patients was recorded to have acute kidney injury (AKI) throughout the study. Meanwhile, the patients with abnormal urinalysis usually had worse disease progression reflecting by laboratory parameters presentations, including markers of liver injury, inflammation, and coagulation. Interpretation: Many patients manifested by abnormal urinalysis on admission, including proteinuria or hematuria. Our results revealed that urinalysis is better in unveiling potential kidney impairment of COVID-19 patients than blood chemistry test and urinalysis could be used to reflect and predict the disease severity. We therefore recommend pay more attention in urinalysis and kidney impairment in COVID-19 patients. Funding Statement: This study was funded by the grants from the project of Thousand Youth Talents for D.H.; and from the China National Natural Science Foundation (Nos. 31770983 and 81974249 to D.H., No. 81601747 to S.L.). Declaration of Interests: The authors have no conflicts of interest. Ethics Approval Statement: This study was approved by the Institutional Ethics Board of Wuhan Union Hospital of Tongji Medical College, Huazhong University of Science and Technology (No. Union Hospital-0093). Written informed consent was waived by the Ethics Commission of the designated hospital for the emerging infectious diseases.

To examine the efficacy and safety ofpersonalized tongxie formulas; to decrease type II errors to minimum.Patients were randomized (1:1:1) into three groups given tongxie, placebo, or pinaverium 3 times daily for 4 weeks. Patients in the tongxie group were treated with personalized formulas based on TCM differential diagnosis, i.e., basic type of IBS, IBS due to liver depression and qi stagnation, excess heat in the liver, deficient spleen function, deficient kidney function, and others (groups 1-6). Primary endpoints were significantly greater reductions in abdominal pain and Bristol stool score. Secondary endpoints were reductions in pain and stool frequencies and abdominal discomfort and its frequency.There were significantly more patients whose stool consistencies were improved than pains were relieved in the entire population (p0.001), but there was no significantly difference in subpopulation group 3 (p0.05). There were significantly more patients whose stool frequencies were reduced than pain frequencies were reduced in the entire population (p0.001), but there were no significantly difference in the subpopulation Groups 1, 3, 4, and 6 (p0.05). Multiple active ingredients and their mechanisms of actions to relieve IBS symptoms were identified.The outcomes in subpopulations may be different from those of the entire population, indicating that personalized formulas are important to achieve optimal outcomes; the active ingredients and innovative mechanisms identified in this study can be the candidates for developing new IBS drugs, and used to manage IBS, respectively.NCT01641224 (www.ClinicalTrials.gov).

Our study was to explore the potential role of miRNA-200b in modulating tumorigenesis in the model of ulcerative colitis-related colorectal cancer (UCRCC) and, further, to decipher the underlying mechanisms associated with this effect. In this study, we examined a greater number of polyps or adenomas, a higher grade of epithelial dysplasia accompanied with a decrease in survival ratio in azoxymethane (AOM)/dextran sulfate sodium (DSS) model mice compared to mice treated with over-expressed miRNA-200b. Surprisingly, enforced miRNA-200b expression significantly suppressed AOM/DSS-induced up-regulation of oncologic markers including β-catenin and CD133. Independent of this, treatment with miRNA-200b obviously attenuated inflammatory responses, as indicated by down-regulating tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and blockade of AKT2-mediated NF-κB/IL-6/STAT3 signaling pathway. Furthermore, a simultaneous shift in epithelial-mesenchymal transition (EMT) markers such as E-cadherin and N-cadherin were observed to be increased and decreased, respectively. Coupled with the associated influence of over-expressed miRNA-200b were change in colorectal cell morphology shown by Transmission electron microscope (TEM) and a decrease in expression of rho-kinase2 (ROCK2) together with AKT2 phosphorylation (p-AKT2). Moreover, mice which were transfected with negative control of miRNA-200b possessed results that were in line with that obtained from AOM/DSS model mice. Additionally, we demonstrated that the 3'untranslated region (UTR) of AKT2 was a direct target of miRNA-200b through bioinformatics analysis and dual-luciferase assay. Collectively, these findings suggest that miRNA-200b's contribution to tumor-suppressing program was correlated with EMT and inflammatory responses in a AKT2-dependent manner.