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Introduction The incidence of laryngeal tuberculosis has increased gradually in recent years. Laryngeal tuberculosis has strong infectivity and atypical clinical manifestations. Hence, establishing the early diagnosis of laryngeal tuberculosis is considered difficult, resulting in the high rate of misdiagnosis of laryngeal tuberculosis and increased rates of tuberculosis infection. Objective This study aimed to describe a case of laryngeal tuberculosis detected using the mycobacteria gene chips technology, facilitating the early diagnosis and the treatment of laryngeal tuberculosis. Case presentation A 27-year-old woman presented with a 7-day history of hoarseness, with a normal routine blood chemistry test and chest computed tomography results. Histological analysis of the vocal cord biopsy showed granulomatous inflammation and the negative acid-fast stain test. The mycobacteria gene chips method was used to directly examine the vocal cord tissue treated with homogenate, and the Mycobacterium tuberculosis was successfully identified. Thus, the early diagnosis of laryngeal tuberculosis and the drug sensitivity of rifampin and isoniazid were confirmed. The patient recovered after undergoing a 1-year standard anti-tuberculosis therapy. Conclusions Mycobacterial identification on homogenised biopsy using the mycobacteria gene chips method significantly facilitates the early diagnosis and the treatment of tuberculosis.

Serum lactate dehydrogenase (LDH) has been established as a prognostic indicator given its differential expression in COVID‐19 patients. However, the molecular mechanisms underneath remain poorly understood. In this study, 144 COVID‐19 patients were enrolled to monitor the clinical and laboratory parameters over 3 weeks. Serum LDH was shown elevated in the COVID‐19 patients on admission and declined throughout disease course, and its ability to classify patient severity outperformed other biochemical indicators. A threshold of 247 U/L serum LDH on admission was determined for severity prognosis. Next, we classified a subset of 14 patients into high‐ and low‐risk groups based on serum LDH expression and compared their quantitative serum proteomic and metabolomic differences. The results showed that COVID‐19 patients with high serum LDH exhibited differentially expressed blood coagulation and immune responses including acute inflammatory responses, platelet degranulation, complement cascade, as well as multiple different metabolic responses including lipid metabolism, protein ubiquitination and pyruvate fermentation. Specifically, activation of hypoxia responses was highlighted in patients with high LDH expressions. Taken together, our data showed that serum LDH levels are associated with COVID‐19 severity, and that elevated serum LDH might be consequences of hypoxia and tissue injuries induced by inflammation.

Ulcerative colitis (UC) is a disease characterized by inflammation and disruption of the intestinal epithelial barrier. Necroptosis plays a critical role in disease progression. Indole-3-carbinol (I3C), a natural dietary agonist of aryl hydrocarbon receptor (AHR), has shown alleviating effects on UC. However, its mechanisms of action have not been comprehensively elucidated. Therefore, we aimed at investigating the protective role of I3C in DSS-induced colitis mice models. I3C significantly ameliorated body weight loss, colon length shortening and colonic pathological damage in colitis mice, reduced disease activity index (DAI) and histological (HI) scores, as well as alleviated colonic necroptosis and inflammation. In vitro, I3C attenuated necroptosis and inflammation of colonoids and NCM460 cells. AHR, activated by I3C, inhibits activation of receptor-interacting protein kinase 1 (RIPK1) and the subsequent assembly of necrosome in a time-dependent manner, as well as suppressing NF-κB activation and decreasing TNF-α, IL-1β, IL-6 and IL-8 expression. Silencing of AHR aggravated necroptosis and inflammation of NCM460 cells, and did not be ameliorated by I3C. Furthermore, AHR activation induces the expression of inhibitor of apoptosis proteins (IAPs) and the ubiquitination of RIPK1. In conclusion, I3C exerts a protective effect in DSS-induced colitis mice models by alleviating the necroptosis and inflammation of IECs through activating AHR.

Serum lactate dehydrogenase (LDH) has been established as a prognostic indicator given its differential expression in COVID-19 patients. However, the molecular mechanisms underneath remain poorly understood. In this study, 144 COVID-19 patients were enrolled to monitor the clinical and laboratory parameters over three weeks. Serum lactate dehydrogenase (LDH) was shown elevated in the COVID-19 patients on admission and declined throughout disease course, and its ability to classify patient severity outperformed other biochemical indicators. A threshold of 247 U/L serum LDH on admission was determined for severity prognosis. Next, we classified a subset of 14 patients into high- and low-risk groups based on serum LDH expression and compared their quantitative serum proteomic and metabolomic differences. The results found COVID-19 patients with high serum LDH exhibited differentially expressed blood coagulation and immune responses including acute inflammatory responses, platelet degranulation, complement cascade, as well as multiple different metabolic responses including lipid metabolism, protein ubiquitination and pyruvate fermentation. Specifically, activation of hypoxia responses was highlighted in patients with high LDH expressions. Taken together, our data showed that serum LDH levels are associated COVID-19 severity, and that elevated serum LDH might be consequences of hypoxia and tissue injuries induced by inflammation.

In this issue of Diabetes Care , a comment letter by He and Li showed that obesity was consistently a significant risk factor for coronavirus disease 2019 (COVID-19) severity (1). Furthermore, they also reported 17 risk factors affecting the disease severity in 98 patients with COVID-19. Beyond the study findings themselves, this study is of interest in its use of four machine learning classification algorithms, although most of the predictors of COVID-19 severity have been reported recently (2). Similar predictors from different patient series identified by using different statistical methods might strengthen causal inference and shed light on …

Summary Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation., Graphical Abstract, Highlights • 93 proteins show differential expression in severe COVID-19 patient sera • 204 metabolites in COVID-19 patient sera correlate with disease severity • A model composed of 29 serum factors shows patient stratification potential • Pathway analysis highlights metabolic and immune dysregulation in COVID-19 patients, Proteomic and metabolomic analysis of COVID-19 sera identifies differentially expressed factors that correlate with disease severity and highlights dysregulation of multiple immune and metabolic components in clinically severe patients.

Hepatitis B virus (HBV) affects the malignant phenotype of hepatocellular carcinoma (HCC). The aim of the present study was to investigate the integration sites of HBV DNA and the expression of the zinc finger protein, zinc finger and BTB domain containing 20 (ZBTB20) in patients with hepatocellular carcinoma. Integration of the HBV gene was detected using a high‑throughput sequencing technique based on the HBV‑Alu‑PCR method. The expression of ZBTB20 was detected by western blotting. HBVX integration sites were detected in ~70% of the HCC tissue samples. HBV‑integrated subgene X detection suggested that 67% of the integrated specimens were inserted into the host X gene in a forward direction, 57% in a reverse direction, 24% in both forward and reverse directions, and 38% had two HBV integration sites. A total of 3,320 HBV integration sites were identified, including 1,397 in HCC tissues, 1,205 in paracancerous tissues and 718 in normal liver tissues. HBV integration fragments displayed enrichment in the 200‑800 bp region. Additionally, the results suggested that HBV was highly integrated into transmembrane phosphatase with tensin homology, long intergenic non‑protein coding RNA (LINC)00618, LOC101929241, ACTR3 pseudogene 5, LINC00999, LOC101928775, deleted in oesophageal cancer 1, LINC00824, EBF transcription factor 2 and ZBTB20 in tumour tissues. Furthermore, the expression of ZBTB20 was upregulated in HCC tissues compared with normal control liver tissues, and was associated with HBV integration frequency. The present study suggested that HBV DNA integrated into upregulated ZBTB20 in patients with hepatocellular carcinoma, which might promote the occurrence and development of HCC. Furthermore, the results of the present study may provide a theoretical basis for the diagnosis and treatment of HCC.

Background The number of patients with pneumonia stemming from the 2019 novel coronavirus (COVID-19) infection has increased rapidly. However, the clinical characteristics of discharged patients remain little known. Here, we attempt to describe the clinical characteristics and treatment experiences of discharged cases from Taizhou, China. Methods A total of 60 patients with COVID-19-infected pneumonia who were discharged from Taizhou Enze Medical Center (Group), from January 31, 2020, to February 16, 2020, were included in the analysis. The discharge criteria were based on the New Coronavirus Pneumonia Prevention and Control Program (Fifth Edition, China). Results Of the 60 patients, the median age was 41 years, and 58.3% were male. Only 13.3% of patients were identified as having severe novel coronavirus pneumonia. All patients received combined antiviral treatment on admission, including β-interferon, lopinavir/tonavir, Abidol and oseltamivir. All patients with severe conditions received gamma globulin and hormone therapy. No patients had endotracheal intubation or died. The median duration from symptom onset to hospitalization was 3 (range, 0-15) days. The median duration of COVID-19 shedding was 14 (range, 5-26) days, and the median duration of hospital stay was 15 (range, 7-23) days. Conclusions Early therapy and comprehensive therapy are key to the outcome for patients with COVID-19-infected pneumonia, especially for those with severe pneumonia. Trial registration number ChiCTR2000029866.

Background: On December 8, 2019, the first new coronavirus case was discovered in Wuhan, China, and an intensive outbreak incepted in the next month (about Janu

Background: New coronavirus pneumonia (COVID-19) outbreak and caused global human respiratory tract infections since 2019, however, the pattern of SARS-CoV-2 in

Several studies have suggested a role for the gut microbiome and cytokines in atherosclerosis development, but combined analyses of the changes of the gut microbiota and cytokines have not been explored previously.We treated ApoE-/- and wild-type mice with a high-fat diet for 12 weeks. The gut microbiome and cytokine composition were analyzed using 16S ribosomal DNA sequencing and RayBio Quantibody Arrays, respectively. GO and KEGG analysis were performed to rationalize the potential mechanisms involved in the process of atherosclerosis.Gut bacterial characteristics in ApoE-/- mice were clearly separated and 21 gut bacterial clades were detected by the LEfSe analysis showing significant differences during the development of atherosclerosis. The relative abundance of Verrucomicrobia, Bacteroidaceae, Bacteroides, and Akkermansia showed significant positive correlations with serum total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Additionally, the relative abundance of Ruminococcaceae was positive with the level of HDL and the abundance of Rikenellaceae showed a negative relationship with the level of TG and LDL. Thirteen differentially expressed proteins were identified with P-value0.05. CXCL5, FGF2, and E-Selectin were significantly negatively associated with Akkermansia and Verrucomicrobia. Additionally, CXCL5 was significantly negatively correlated with Bacteroides and Bacteroidaceae. Three "cellular component" subcategories, 24 ″molecular function" subcategories, 752 ″biological process" subcategories and 29 statistically remarkable KEGG pathway categories were identified.Gut microbiota changes of the mice having atherosclerosis and their relationship with the inflammatory status could be one of the major etiological mechanisms underlying atherosclerosis.

OBJECTIVE To systematically evaluate the efficacy of mycophenolate mofetil (MMF) compared with the standard treatment for autoimmune hepatitis. METHODS Medline (PubMed), Embase, and Cochrane Library databases were searched between 1966 and June 2018 for studies on prednisone and/or azathioprine/mycophenolate mofetil in autoimmune hepatitis. The keywords and descriptor terms used were 'hepatitis', 'autoimmunity', 'prednisone', 'prednisolone', 'azathioprine', and 'mycophenolate mofetil'. The Z test and Cochrane Q test were used in the statistical analysis. RESULTS Seven hundred and eighty-eight related articles were found; 779 studies were excluded after further review. Ultimately, seven studies (583 participants) were included. The remission rate of aminotransferase and immunoglobulin (Ig)-G levels with standard treatment was 33.33-86.67%, and the nonresponse rate was 15.15-66.67%. Although the remission rate of the aminotransferase level with prednisone and MMF was 55.17-88.89% and that of the IgG level was 61.16-88.89%, the nonresponse rate was 6.42-33.33%. Remission rates of the aminotransferase level (P

ObjectivesHand, foot and mouth disease (HFMD) is a common infectious disease in children caused by intestinal virus and an important cause of child death. Early identification of critical HFMD and timely intervention are the key to reduce mortality. However, there is no available unified critical HFMD screening standard. This study aimed to explore the predictive evaluation of HFMD with critical illness scoring systems.MethodsA total of 31 patients with mild HFMD, 30 with severe HFMD, and 25 with critical HFMD were included. The platelet index in age-adapted sequential organ failure assessment score (SOFA) was re-assigned to constitute the SOFA for HFMD (H-SOFA). The results of age-adapted SOFA, quick SOFA (qSOFA), and pediatric logistic organ dysfunction score-2 (PELOD-2), pediatric multiple organ dysfunction score (P-MODS), pediatric critical illness score (PCIS), H-SOFA of the three groups were compared.ResultsSignificant differences in the following parameters were found between severe group and critical group: enterovirus 71 positive, heart rate, respiration, vomiting, cold sweat, moist rales, disturbance in consciousness, platelet, and blood glucose (PConclusionIncrease in platelet count was related to the severity of HFMD. Age-adapted SOFA, qSOFA, and PELOD-2, P-MODS, PCIS, H-SOFA had high predictive value on critical HFMD, with H-SOFA being the highest.

To investigate the effect of intermittent high glucose on oxygen-glucose deprivation/refurnish (OGD/R) neuronal survival.The primary cultured hippocampal neurons of mice were sub-cultured when the cell fusion reached about 80%. Cells in logarithmic growth phase were placed in a hypoxic incubator (37 centigrade, 5% COThe inverted phase contrast microscope showed that the cells in the normal glucose and oxygen control group were plump and refractive, and had obvious nucleus, clear processes and high cell activity. After 6 hours of hypoxia and hypoglycemia treatment, the cells were shrunk, refractive index was poor, the nucleus was unclear, the processes were not clear, and the cell activity was significantly lower than that of normal glucose and oxygen control group (A value: 0.34±0.06 vs. 1.09±0.06, P0.01), which indicated that the model of oxygen-glucose deprivation (OGD) was successfully prepared. After 72 hours of culture with different concentrations of glucose, the cells in the low-glucose control group were shrunk, the cell membrane was incomplete, the nucleus was unclear, and number of necrotic cells were more. In the constant high-glucose group, the refractive index of cells was poor, a large number of cells floated, and the nucleus was not obvious. In the intermittent high-glucose group, the cell morphology was normal, the refractive rate of cells was decreased slightly, and the necrotic cells were less. In the hypertonic control group, the cell status was close to that in the constant high-glucose group. Compared with the low-glucose control group or constant high-glucose group,the cell viability in the intermittent high-glucose group was significantly increased (A value: 2.04±0.15 vs. 0.64±0.18, 1.16±0.16, both P0.01), the apoptotic rate was significantly decreased [(59.60±2.55)% vs. (78.15±15.77)%, (95.60±0.14)%, both P0.05]. There was no significant difference in cell activity or apoptotic rate between the hypertonic control group and the constant high-glucose group [cell activity (A value): 1.07±0.07 vs. 1.16±0.16, apoptotic rate: (87.80±4.53)% vs. (95.60±0.14)%, both P0.05].Intermittent high glucose within a certain range had protective effect on OGD/R neuronal survival.

Background: Hemorrhagic Fever with Renal Syndrome (HFRS), caused by the hantavirus, is a natural infectious disease characterized by fever, hemorrhage and renal damage. China is the most severely endemic area for HFRS in the world. In recent years, critical scoring systems based on quantitative classification have become an important clinical tool for predicting and evaluating the prognosis of critical illness, and provide guidelines for clinical practice. Methods: The sample comprised 384 patients with HFRS treated in the Taizhou Hospital from January 2006 to February 2017. The patients were divided into the severe group and the mild group according to their clinical characteristics. By comparing the differences in clinical symptoms, signs and laboratory data between the two groups, the clinically relevant indicators of severe HFRS were explored. According to the previous studies, we incorporated the positive fecal occult blood test (FOBT) into the sepsis-related organ failure assessment (SOFA) tool and formulated a new scoring system specifically for HFRS, named H-SOFA. By comparing the simplified acute physiology score II (SAPS II), SOFA and H-SOFA scores of the two groups, their predictive values for the progression of HFRS were assessed. Results: Compared to the mild group, patients in the severe group had longer hospital stays; higher frequencies of nausea, vomiting, abdomen pain, signs of congestion and hemorrhage; and more pronounced impairment of liver and renal function. The levels of PLT, PCT, TB, and FOBT were positively correlated with the progression of HFRS (P

Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus.We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase-polymerase-chain-reaction assays, viral culturing, and sequence analyses.A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) viruses. Substitution Q226L (H3 numbering) at the 210-loop in the hemagglutinin (HA) gene was found in the A/Anhui/1/2013 and A/Shanghai/2/2013 virus but not in the A/Shanghai/1/2013 virus. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses. All three patients presented with fever, cough, and dyspnea. Two of the patients had a history of recent exposure to poultry. Chest radiography revealed diffuse opacities and consolidation. Complications included acute respiratory distress syndrome and multiorgan failure. All three patients died.Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).

Background The world’s first reported patient infected with avian influenza H7N9 was treated at the Fifth People’s Hospital of Shanghai. Shortly thereafter, several other cases emerged in the local area. Here, we describe the detailed epidemiological and clinical data of 6 cases of avian influenza H7N9. Methods and Findings We analyzed the epidemiologic and clinical data from clustered patients infected with H7N9 in the Minhang District of Shanghai during a 2-week period. Of the 6 patients, 2 were from a single family. In addition, 3 patients had a history of contact with poultry; however, all 6 patients lived in the proximity of 2 food markets where the H7N9 virus was detected in chickens and pigeons. The main symptoms were fever, cough, and hemoptysis. At onset, a decreased lymphocyte count and elevated creatine kinase, lactate dehydrogenase, procalcitonin, and C-reactive protein levels were observed. As the disease progressed, most patients developed dyspnea and hypoxemia. Imaging studies revealed lung consolidation and multiple ground-glass opacities in the early stage, rapidly extending bilaterally. All patients were treated with oseltamivir tablets beginning on days 3–8 after onset. The main complications were as follows: acute respiratory distress syndrome (ARDS; 83.3%), secondary bacterial infection (66.7%), pleural effusion (50%), left ventricular failure (33.3%), neuropsychiatric symptoms (33.3%), and rhabdomyolysis (16.7%). Of the 6 patients, 4 died of ARDS, with 2 patients recovering from the infection. Conclusions An outbreak of H7N9 infection occurred in the Minhang District of Shanghai that easily progressed to acute respiratory distress syndrome. Two cases showed family aggregation, which led us to identify the H7N9 virus and indicated that human transmission may be involved in the spread of this infection.

The aim of this study was to compare the efficacy of lamivudine or adefovir alone for 96 weeks versus initial treatment with the combination of lamivudine and adefovir for 12 to 24 weeks followed by adefovir alone. One hundred and fifty patients with HBeAg-positive chronic hepatitis B were randomized equally to lamivudine and adefovir diprivoxil combination therapy (LA), lamivudine alone (L), or adefovir dipivoxil alone (A) in a multicenter randomized clinical trial. In the LA group, the earliest time for lamivudine discontinuation was 12 weeks and adefovir monotherapy was continued until 96 weeks. Groups L and A received monotherapies for 96 weeks. At 12 weeks, the decrease in HBV DNA, percentage of patients with negative HBV DNA, and ALT normalization rate for the LA group were comparable to those of group L, but superior to those of group A. At 24 weeks, the rates of negative HBV DNA and HBeAg seroconversion of group LA were significantly higher than the monotherapy groups. This superiority was subsequently preserved during the maintenance phase with adefovir monotherapy. Starting at 48 weeks, the mean HBV DNA level of group L increased over the 24-week level. In contrast, the A group's rates of virological response, biochemical response, and HBeAg seroconversion continued to improve. At week 96, the percentage of patients with undetectable DNA and HBe seroconversion of LA group (100%, 51%) was higher than that of L (66%, 21%) and A group (49%, 33%), while no significant difference was observed between the L and A groups. During the course of therapy, no lamivudine- or adefovir-resistance mutations were discovered in the LA group. Rates of adverse reactions were comparable between the three groups. Combination therapy with lamivudine and adefovir for 12 to 24 weeks followed by adefovir monotherapy significantly improved antiviral efficacy and reduced drug resistance without compromising safety and tolerability compared to either drug alone in HBeAg-positive chronic hepatitis B.