The role of the immunoproteasome in cardiovascular disease.

The ubiquitinproteasome system (UPS) is the main mechanism responsible for the intracellular degradation of misfolded or damaged proteins. Under inflammatory conditions, the immunoproteasome, an isoform of the proteasome, can be induced, enhancing the antigen-presenting function of the UPS. Furthermore, the immunoproteasome also serves nonimmune functions, such as maintaining protein homeostasis and regulating signalling pathways, and is involved in the pathophysiological processes of various cardiovascular diseases (CVDs). This review aims to provide a comprehensive summary of the current research on the involvement of the immunoproteasome in cardiovascular diseases, with the ultimate goal of identifying novel strategies for the treatment of these conditions.

Apical papilla stem cell-derived exosomes regulate lipid metabolism and alleviate inflammation in the MCD-induced mouse NASH model.

Stem cells from the apical papilla(SCAPs) exhibit remarkable tissue repair capabilities, demonstrate anti-inflammatory and pro-angiogenic effects, positioning them as promising assets in the realm of regenerative medicine. Recently, the focus has shifted towards exosomes derived from stem cells, perceived as safer alternatives while retaining comparable physiological functions. This study delves into the therapeutic implications of exosomes derived from SCAPs in the methionine-choline-deficient (MCD) diet-induced mice non-alcoholic steatohepatitis (NASH) model. We extracted exosomes from SCAPs. During the last two weeks of the MCD diet, mice were intravenously administered SCAPs-derived exosomes at two distinct concentrations (50 µg/mouse and 100 µg/mouse) biweekly. Thorough examinations of physiological and biochemical indicators were performed to meticulously evaluate the impact of exosomes derived from SCAPs on the advancement of NASH in mice induced by MCD diet. This findings revealed significant reductions in body weight loss and liver damage induced by the MCD diet following exosomes treatment. Moreover, hepatic fat accumulation was notably alleviated. Mechanistically, the treatment with exosomes led to an upregulation of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) levels in the liver, enhancing hepatic fatty acid oxidation and transporter gene expression while inhibiting genes associated with fatty acid synthesis. Additionally, exosomes treatment increased the transcription levels of key liver mitochondrial marker proteins and the essential mitochondrial biogenesis factor. Furthermore, the levels of serum inflammatory factors and hepatic tissue inflammatory factor mRNA expression were significantly reduced, likely due to the anti-inflammatory phenotype induced by exosomes in macrophages. The above conclusion suggests that SCAPs-exosomes can improve NASH.

Effectiveness of Inactivated COVID-19 Vaccines Against Symptomatic, Pneumonia, and Severe Disease Caused by the Delta Variant: Real World Study and Evidence - China, 2021.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Effectiveness of China's 2 inactivated vaccines (BBIBP-CorV and CoronaVac) against pre-Delta severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants ranged from 47% to over 90%, depending on the clinical endpoint, and with greater effectiveness against more severe coronavirus disease 2019 (COVID-19). During an outbreak in Guangdong, inactivated vaccine effectiveness (VE) against the Delta variant was 70% for symptomatic infection and 100% for severe COVID-19. However, separate or combined VE estimates for the two inactivated vaccines against Delta are not available. WHAT IS ADDED BY THIS REPORT?: In an outbreak that started in a hospital, VEs of completed primary vaccination with inactivated COVID-19 vaccines against symptomatic COVID-19, COVID-19 pneumonia, and severe COVID-19 caused by the Delta variant were 51%, 61%, and 82%. Completed primary vaccination reduced the risk of progressing from mild to moderate or severe COVID-19 by 74%. VE estimates for BBIBP-CorV and CoronaVac or combined vaccination were similar, and partial vaccination was ineffective. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Completed primary vaccination with either of the 2 inactivated COVID-19 vaccines reduces risk of symptomatic COVID-19, COVID-19 pneumonia, and severe COVID-19 caused by the Delta variant. Completion of the completed primary vaccination with two doses is necessary for protection from Delta.

Epidemiological and clinical characteristics of 671 COVID-19 patients in Henan Province, China.

BACKGROUND: Despite many reports on the characteristics of coronavirus disease 2019 (COVID-19) in Wuhan, China, relatively little is known about the transmission features of COVID-19 outside Wuhan, especially at the provincial level. METHODS: We collected epidemiological, demographic, clinical, laboratory, radiological and occupation information, along with contact history, of 671 patients with laboratory-confirmed COVID-19 reported from January 23 to February 5, 2020, in Henan province, China. We described characteristics of these cases, compared the diagnostic accuracy and features of blood testing, computed tomography (CT) scans and X-rays, and analysed SARS-CoV-2 transmission sources and patients' occupations in Henan province. RESULTS: The mean age of patients in this case series was 43 years, 56.2% were male and 22.4% had coexisting medical disorders. The death rate was 0.3%. Fourteen patients did not show any symptoms. Lymphocyte percentage was associated with disease severity (χ2 = 6.71, P = 0.035) but had a large variation in each sample group. The mean time from illness onset to diagnosis was 5.6 days. A total of 330 patients had ever lived in or visited Wuhan, 150 had contact with confirmed cases, 323 had been to a hospital and 119 had been to a wet market. There were 33 patients who did not have a traceable transmission source, with 21.2% of these being farmers and 15.2% being workmen. CONCLUSIONS: Lymphocyte percentage was a sign of severe COVID-19 in general but was not a good diagnostic index. Longer time from illness onset to diagnosis was associated with higher COVID-19 severity, older age, higher likelihood of having coexisting cardiovascular diseases including hypertension, and being male. Farming was found to be a high-risk occupation in Henan province, China.

Identification of Symptoms Prognostic of COVID-19 Severity: Multivariate Data Analysis of a Case Series in Henan Province.

BACKGROUND: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), has been declared a global pandemic. Identifying individuals whose infection can potentially become severe is critical to control the case fatality rate of COVID-19. However, knowledge of symptoms that are prognostic of COVID-19 severity is lacking. OBJECTIVE: The objective of our study was to identify symptoms prognostic of COVID-19 infection severity. METHODS: We analyzed documented symptoms, including fever, cough, fatigue, expectoration, sore throat, chest distress, headache, diarrhea, rhinorrhea, stuffed nose, nausea, vomiting, muscle or joint ache, shortness of breath, and their associations with disease severity using a case series, including 655 confirmed cases from January 23 to February 5, 2020 in Henan Province, China. We also analyzed the influence of individual characteristics, including age, gender, and comorbidities, on symptoms with prognostic value. RESULTS: Fatigue (95% CI 0.141 to 0.334, P<.001), expectoration (95% CI 0.107 to 0.305, P<.001) and stuffed nose (95% CI -0.499 to -0.082, P=.006) were identified as the prognostic symptoms of COVID-19 patients from the multivariate analysis. Fever occurred in 603/655 (92.1%) of the patients but was not associated with disease severity. Fatigue accounted for 184/655 (28.1%) of the patients and was linearly associated with infection severity with statistical significance. Expectoration occurred in 169/655 (25.8%) patients in the cohort and was the sole prognostic factor for patients with cardiovascular complications, including hypertension. Shortness of breath, chest distress, muscle or joint ache, and dry cough, which occurred in 33 (5%), 83 (12.7%), 78 (11.9%), and 276 (42.1%) of the 655 patients, respectively, were significantly enriched among patients classified as severe. Stuffed nose and nausea were associated with favorable disease severity, especially among male patients. More female than male patients were documented as having muscle or joint ache. Headache was most enriched in patents aged 15 to 39 years, followed by those aged 40 to 64 years, with statistical significance. CONCLUSIONS: Fatigue and expectoration are signs of severe COVID-19 infection. Shortness of breath, chest distress, muscle or joint ache, and dry cough are prevalent in severe patients. Expectoration is commonly present in older individuals and patients with cardiovascular disorders, including hypertension. Shortness of breath is prognostic of severe infection in male patients. Stuffed nose and nausea are favorable prognostic factors of severe infection, especially among male patients.

Seroprevalance of antibodies specific for severe fever with thrombocytopenia syndrome virus and the discovery of asymptomatic infections in Henan Province, China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging disease caused by SFTS virus (SFTSV), and the geographical distribution of SFTS has been increasing throughout China in recent years. To assess SFTSV-specific antibody seroprevalence, a cross-sectional study was conducted for healthy people in high SFTS endemic areas of Henan province in 2016. METHODS: This study used a stratified random sampling method to select 14 natural villages as the investigation sites. From April to May 2016, participants completed a questionnaire survey and serum samples were collected. All serum samples were subjected to ELISA to detect SFTSV-specific IgM and IgG. All IgM-positive samples were further tested by real-time RT-PCR, and isolation of virus from serum was attempted. Any participant who was IgM-positive was followed up with a month later to confirm health status. RESULTS: In total, 1463 healthy people participated in this study. The average seropositive rates for SFTSV-specific IgG and IgM were 10.46% (153/1463) and 0.82% (12/1463), respectively. IgM was detected in 12 individuals, and SFTSV RNA was detected in six of them. Virus was isolated from five of the six SFTSV RNA-positive individuals, and phylogenetic analyses revealed that all five isolates belonged to SFTSV group A. No IgM-positive participants exhibited any symptoms or other signs of illness at the one-month follow up. CONCLUSIONS: This study identified a relatively high incidence of SFTSV-specific antibody seropositivity in healthy people in Xinyang city. Moreover, our data provide the first evidence for asymptomatic SFTSV infections, which may have significant implications for SFTS outbreak control.

Avian Influenza A Viruses among Occupationally Exposed Populations, China, 2014-2016.

To determine the seroprevalence and seroconversion of avian influenza virus (AIV) antibodies in poultry workers, we conducted a seroepidemiologic study in 7 areas of China during December 2014-April 2016. We used viral isolation and reverse transcription PCR to detect AIVs in specimens from live poultry markets. We analyzed 2,124 serum samples obtained from 1,407 poultry workers by using hemagglutination inhibition and microneutralization assays. We noted seroprevalence of AIV antibodies for subtypes H9N2, H7N9, H6N1, H5N1-SC29, H5N6, H5N1-SH199, and H6N6. In serum from participants with longitudinal samples, we noted seroconversion, with >4-fold rise in titers, for H9N2, H7N9, H6N1, H5N1-SC29, H6N6, H5N6, and H5N1-SH199 subtypes. We found no evidence of H10N8 subtype. The distribution of AIV antibodies provided evidence of asymptomatic infection. We found that AIV antibody prevalence in live poultry markets correlated with increased risk for H7N9 and H9N2 infection among poultry workers.

Prevalence of severe fever with thrombocytopenia syndrome virus in animals in Henan Province, China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV). SFTSV has been found in humans, ticks and animals, and SFTS has high mortality and increasing prevalence in East Asia. In the study, the samples (heart, liver, lung, kidney, spleen, brain tissue and serum) were collected from 374 domestic animals and 241 wild animals in Pingqiao District and Xinxian County of Xinyang in Henan Province, China. 275 (44.72%, 275/615) animals were positive for anti-SFTSV antibodies, the anti-SFTSV antibodies positive ratios of domestic and wild animals were 43.58% (163/374) and 46.47% (112/241), respectively. There was no significant difference in domestic and wild animals, but significant differences were detected among different species of animals (χ2 = 112.59, P < 0.0001). Among 615 animals, 105 (17.07%, 105/615) animals were positive for SFTSV RNA, and only one SFTSV strain was isolated from heart tissue of a yellow weasel. The phylogenetic analysis shows that the sequence from animals belonged to the same group with viral sequences obtained from humans. The animals maybe play a reservoir host in maintaining the life cycle of SFTSV in nature.

Continued reassortment of avian H6 influenza viruses from Southern China, 2014-2016.

H6 subtype avian influenza virus (AIV) was prevalent in poultry and could sporadically infect humans. Here, a total of 196 novel H6 AIVs isolated from poultry in eight provinces of China from 2014 to 2016 were phylogenetically characterized. Our analysis revealed that they could be divided into two clades in the Asian H6 HA lineage, A/wild duck/Shantou/2853/2003(H6N2) (ST2853-like) (85.7%) and A/duck/Shantou/339/2000(H6N2) (ST339-like) (14.3%), in which ST2853-like strains predominate. These novel strains belonged to the H6N6 (n = 165, 84.2%), H6N2 (n = 30, 15.3%), and H6N3 (n = 1, 0.51%) subtypes, which could be classified into 36 genotypes including 12 novel genotypes described in this study. In particular, several strains possessed the V190 and S228 mutations in HA (H3 numbering), which is critical for human receptor binding and identical to the human-derived strain A/Taiwan/2/2013(H6N1). Furthermore, 10.3% of the H6N6 isolates possessed the N6-∆11b (59-69) deletion. In summary, we describe phylogenetic and molecular characterizations of H6 AIVs in southern China and highlight the constant prevalence of H6 AIVs in poultry as well as adaptation to mammalian hosts.

Identification of tumor-associated antigens by using SEREX in hepatocellular carcinoma.

AIM: To identify biomarkers for diagnosis and prognosis of hepatocellular carcinoma (HCC). METHODS: Screening the HCC cDNA library with HCC patients sera. Isolated proteins were used as antigens to detect antibodies from patients with HCC and control sera. RESULTS: Eighty-one positive clones were identified. The frequencies of autoantibody against five HCC-associated antigens were higher in HCC than that in chronic hepatitis and normal human sera. The sensitivity and specificity of KRT23, AHSG and FTL antigens combination tests up to 98.2% in joint test and 90.0% in series test separately. CONCLUSIONS: HCC associate antigens identified from this study supply candidate markers of diagnosis, combined detection and immunotherapy of HCC.

[A case-control family study of gastric cancer in Henan province].

OBJECTIVE: To explore the risk factors of gastric cancer in the rural area of Henan province. METHODS: Three hundred and twenty-five families with gastric cancer and 325 control families (1010 persons in each group) were selected among the rural residents in 4 counties of Henan province. Totally 2020 people were surveyed and assessed using population-based case-control family study. RESULTS: Gastric cancer was related to stomach upset, irregular dietary, hobby for salty taste, residual food, and history of mental stimulus. CONCLUSION: Stomach upset, irregular dietary, hobby for salty taste, residual food, and history of mental stimulus are the risk factors of gastric cancer.