Olgotrelvir as a Single-Agent Treatment of Nonhospitalized Patients with Covid-19.

BACKGROUND: Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., Mpro) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events. RESULTS: The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log10 copies/ml in olgotrelvir-treated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported. CONCLUSIONS: Olgotrelvir as a single-agent treatment significantly improved symptom recovery. Adverse effects were not dose limiting. (Funded by Sorrento Therapeutics, a parent company of ACEA Therapeutics; ClinicalTrials.gov number, NCT05716425.).

Analysis of the immunological response to antiviral therapy in patients with different subtypes of HIV/AIDS: a retrospective cohort study.

OBJECTIVE: To evaluate the effectiveness of standardised antiretroviral therapy (ART) among different HIV subtypes in people living with HIV/AIDS (PLWHA), and to screen the best ART regimen for this patient population. DESIGN: A retrospective cohort study was performed, and PLWHA residing in Huzhou, China, between 2018 and 2020, were enrolled. SETTING AND PARTICIPANTS: Data from 625 patients, who were newly diagnosed with HIV/AIDS in the AIDS Prevention and Control Information System in Huzhou between 2018 and 2020, were reviewed. ANALYSIS AND OUTCOME MEASURES: Data regarding demographic characteristics and laboratory investigation results were collected. Immune system recovery was used to assess the effectiveness of ART, and an increased percentage of CD4+ T lymphocyte counts >30% after receiving ART for >1 year was determined as immunopositive. A multiple logistic regression model was used to comprehensively quantify the association between PLWHA immunological response status and virus subtype. In addition, the joint association between different subtypes and treatment regimens on immunological response status was investigated. RESULTS: Among 326 enrolled PLWHA with circulating recombinant forms (CRFs) CRF01_AE, CRF07_BC and other HIV/AIDS subtypes, the percentages of immunopositivity were 74.0%, 65.6% and 69.6%, respectively. According to multivariate logistic regression models, there was no difference in the immunological response between patients with CRF01_AE, CRF07_BC and other subtypes of HIV/AIDS who underwent ART (CRF07_BC: adjusted OR (aOR) (95% CI) = 0.8 (0.4 to 1.4); other subtypes: aOR (95% CI) = 1.2 (0.6 to 2.3)). There was no evidence of an obvious joint association between HIV subtypes and ART regimens on immunological response. CONCLUSIONS: Standardised ART was beneficial to all PLWHA, regardless of HIV subtypes, although it was more effective, to some extent, in PLWHA with CRF01_AE.

Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation.

Metabolic (dysfunction)-associated steatohepatitis (MASH) is the advanced stage of metabolic (dysfunction)-associated fatty liver disease (MAFLD) lacking approved clinical drugs. Adenosine A1 receptor (A1R), belonging to the G-protein-coupled receptors (GPCRs) superfamily, is mainly distributed in the central nervous system and major peripheral organs with wide-ranging physiological functions; however, the exact role of hepatic A1R in MAFLD remains unclear. Here, we report that liver-specific depletion of A1R aggravates while overexpression attenuates diet-induced metabolic-associated fatty liver (MAFL)/MASH in mice. Mechanistically, activation of hepatic A1R promotes the competitive binding of sterol-regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) to sequestosome 1 (SQSTM1), rather than protein kinase A (PKA) leading to SCAP degradation in lysosomes. Reduced SCAP hinders SREBP1c/2 maturation and thus suppresses de novo lipogenesis and inflammation. Higher hepatic A1R expression is observed in patients with MAFL/MASH and high-fat diet (HFD)-fed mice, which is supposed to be a physiologically adaptive response because A1R agonists attenuate MAFL/MASH in an A1R-dependent manner. These results highlight that hepatic A1R is a potential target for MAFL/MASH therapy.

Suppurative Meningitis Complicated with Arthritis Caused by Streptococcus Suis Infection: A Case Report.

Background: Streptococcus suis (S. suis) is a common gram-positive bacterium in pigs. Its natural infection sites are the upper respiratory tract (especially tonsils and nasal cavity), reproductive tract and digestive tract of pigs. It is a new emerging human and animal disease. A co-morbid pathogen that can cause serious infections in humans, including meningitis, sepsis, septic arthritis, and sometimes deafness. No cases have been reported in Huzhou City, Zhejiang Province, China. Case Presentation: A 50-year-old male patient who had Worked as a butcher in a slaughterhouse for 20 years. Admitted to the hospital due to abdominal pain, joint pain, fever, and headache.His condition rapidly worsened causing altered consciousness, drowsiness and developed hearing loss. S. suis induced pyogenic meningitis complicated by arthritis was suspected based on the results of biochemical and culture analysis of the cerebrospinal fluid, and metagenomic next-generation sequencing, The patient's symptoms significantly improved after treatment with antibiotics such as ceftriaxone, meropenem, and linezolid, as well as supportive therapies including steroids and hyperbaric oxygen therapy, and his hearing improved significantly.After about 2 years of follow-up, the hearing was significantly better than before, but hearing impairment still remained. Conclusion: Streptococcus suis is endemic in pork-consuming and pig-raising countries, but can occur throughout the world, especially among individuals with occupational exposure to pigs and/or pork, such as slaughterhouse workers, butchers, farmers, etc. Strengthen science education among key groups. This case was diagnosed as Streptococcus suis meningitis combined with arthritis. However, abdominal pain in the early stage of the disease is very rare and is easy to be misdiagnosed. It is necessary to identify whether it is complicated by peritonitis. For hearing loss caused by Streptococcus suis infection, the use of hyperbaric oxygen chamber treatment has obvious therapeutic effects.

Cytoplasmic expression of UTP23 promotes colorectal cancer progression.

UTP23 (UTP23 small subunit processome component) plays a pivotal role in the intricate processing and maturation of the small subunit of ribosomes within the nucleolus. In cases of nucleolar stress, such as those observed in certain tumor cells, the aberrant nucleolar organization and structure can lead to the translocation of nucleolar proteins into the nucleus or cytoplasm, consequently impacting the physiological processes of the tumor cells through non-ribosome-related functions. Our investigation revealed altered localization of UTP23 protein in colorectal cancer clinical tissue samples. Upon analyzing UTP23 expression and its correlation with patient prognosis in a cohort of 143 colorectal cancer patients, the result suggested that high cytoplasmic expression pattern of UTP23 was occured in early-stage metastasis-free colorectal cancer and was significantly associated with poor prognosis. Furthermore, we demonstrated that cytoplasmic expression of UTP23 significantly promoted the metastatic and invasive capabilities of colorectal cancer cells, which was not showed in the nucleollcalised UTP23. Intriguingly, mass spectrometry result suggested that KRT5 bind to UTP23 and showed a regulatory influence on UTP23 metastatic potential in colorectal cancer cells. Conclusively, our study demonstrated that the localization of UTP23 play a key role in colorectal cancer metastatic progression, which may serve as a novel prognostic indicator.

The Challenging Path to Diagnosing Extraintestinal Amoebiasis: A Case Report of an HIV-Infected Patient.

Background: Amoebiasis, an infectious disease caused by the parasitic protozoan E. histolytica, is easily misdiagnosed due to its declining incidence and atypical symptoms. Case Presentation: A 31-year-old male presented to the hospital with dyspnea and inability to lie flat. Imaging studies indicated a large amount of pleural effusion on the right side and multiple huge cysts in the liver. The patient underwent liver tumor resection surgery at another hospital due to suspected malignancy, but no evidence of relevant malignant tumors was found in the pathological examination. Subsequently, we performed metagenomic next-generation sequencing on the liver drainage fluid and obtained liver pathology slides from the hospital where the surgery was performed at that time. Both of them confirmed the diagnosis of amoebic infection. Empirical treatment with metronidazole was initiated before the diagnosis was confirmed, along with symptomatic treatments such as thoracic drainage and liver drainage. Eventually, the patient's condition improved and he was discharged smoothly. Conclusion: In order to avoid misdiagnosis of amoebiasis, thoroughly inquiring about the patient's medical history, shifting perspectives and continuing investigating are necessary when one diagnostic approach proves ineffective. Besides, interdisciplinary collaboration and persistent efforts are crucial for accurate diagnosis.

Nutritional status in patients with active pulmonary tuberculosis and new nutritional risk screening model for active tuberculosis: a national, multicenter, cross-sectional study in China.

Background: Tuberculosis (TB) remains a significant challenge for public health and is closely associated with malnutrition; however, few studies have attempted to screen malnutrition among TB patients. The study aimed to evaluate the nutrition status and build a new nutritional screening model for active TB. Methods: A retrospective, multicenter, large cross-sectional study was conducted in China from 1 January 2020 to 31 December 2021. All included patients diagnosed with active pulmonary TB (PTB) were evaluated both by Nutrition Risk Screening 2002 (NRS 2002) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Univariate and multivariate analyses were conducted to screen the risk factors associated with malnutrition, and a new screening risk model, mainly for TB patients, was constructed. Results: A total of 14,941 cases meeting the inclusion criteria were entered into the final analysis. The malnutrition risk rate among PTB patients in China was 55.86% and 42.70%, according to the NRS 2002 and GLIM, respectively. The inconsistency rate between the two methods was 24.77%. A total of 11 clinical factors, including elderly, low body mass index (BMI), decreased lymphocyte cells, taking immunosuppressive agents, co-pleural TB, diabetes mellitus (DM), human immunodeficiency virus (HIV), severe pneumonia, decreased food intake within a week, weight loss and dialysis were identified as independent risk factors of malnutrition based on multivariate analyses. A new nutritional risk screening model was constructed for TB patients with a diagnostic sensitivity of 97.6% and specificity of 93.1%. Conclusions: Active TB patients have severe malnutrition status according to screening by the NRS 2002 and GLIM criteria. The new screening model is recommended for PTB patients as it is more closely tailored to the characteristics of TB.

Clinical features of Omicron variant infection in 445 patients with coronavirus 19 disease.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can mutate frequently and many new strains have emerged thus far. The clinical and epidemiological characteristics differ with each dominant strain. OBJECTIVES: Obtain an understanding of the clinical characteristics of patients infected with the Omicron variants of the SARS CoV-2. DESIGN: Retrospective cohort SETTINGS: Teaching hospital in China. PATIENTS AND METHODS: Data on sociodemography, signs/symptoms, hospital stay, viral shedding period, comorbidities, treatment options and final outcome were retrieved from hospital electronic medical record. We collected nasopharyngeal samples, laboratory data, and clinical data from patients admitted to the hospital with SARS CoV-2. MAIN OUTCOME MEASURES: Clinical characteristics of the patients infected with Omicron variant of SARS CoV-2. SAMPLE SIZE: 445 patients RESULTS: The median age was 43.0 years with a range from 2 to 75 years. Two-thirds of the participants were male and one-third were female. Almost half of the participants (51.9%) had no symptoms, whereas 48.1% had at least one symptom. Of symptomatic patients, 26.7% had mild symptoms and 21.3% had moderate symptoms. No patients were admitted with severe or critical symptoms. All patients discharged from the hospital after complete recovery without any serious complications or death. The most common symptom was cough followed by sore throat and fever. Less common symptoms were having sputum, stuffy nose, and muscle pain. Rare symptoms were weakness, headache, diarrhea, hemoptysis and nausea/vomiting. CONCLUSIONS: All patients had mild to moderate symptoms. Shortness of breath was not a common symptom among the study group. No patients needed invasive oxygen therapy in this cohort. LIMITATIONS: Single center and retrospective design. CONFLICT OF INTEREST: None.

Anemia is independently associated with mortality in people living with human immunodeficiency virus/acquired immune deficiency syndrome: A propensity score matching-based retrospective cohort study in China.

Although previous studies have suggested that hemoglobin is related to the health status of people living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) (PLWHA), the role of anemia in mortality remains unclear. This study aimed to comprehensively quantify the effect of anemia on the mortality risk of PLWHA. In this retrospective cohort study, we thoroughly estimated the effect of anemia on PLWHA mortality, using data collected from January 2005 to June 2022 in the Huzhou area, in 450 subjects extracted from the database of the China Disease Prevention and Control Information System and matched them using a propensity score matching approach to balance potential confounding bias. The potential exposure-response relationship between anemia, hemoglobin concentration, and the mortality of PLWHA was also carefully estimated. A series of subgroup analyses, including interaction analysis, was further conducted to validate the robustness of the effect of anemia on PLWHA death risk. Anemia was significantly associated with an elevated death risk in PLWHA, with an increase of 74% (adjusted hazard ratio [AHR]: 1.74; 95% confidence interval [CI]: 1.03-2.93; p = 0.038) in those with anemia after adjusting for potential confounders. PLWHA with moderate or severe anemia had a higher risk of death, with an 86% increase (AHR = 1.86; 95% CI: 1.01-3.42; p = 0.045). Meanwhile, the AHR tended to increase by 85% on average (AHR = 1.85, 95% CI: 1.37-2.50; p < 0.001) with a per standard deviation (SD) decrease in plasma hemoglobin. Consistent relationships between plasma hemoglobin and the risk of death were further observed in the results from multiple quantile regression models, restricted cubic spline regression models, and a series of subgroup analyses. Anemia is an independent risk factor for HIV/AIDS-related mortality. Our findings may provide new insights into the relevance of PLWHA administration to public health policy, which demonstrate that this low-cost and routinely measured marker (hemoglobin) can be a marker of poor prognosis even before the start of HAART.

Functionalized MOF-Derived Nanoporous Carbon as Compatible Nanofiller to Fabricate Defect-Free PDMS-Based Mixed Matrix Pervaporation Membranes.

Metal-organic framework (MOF)-based polydimethylsiloxane mixed matrix membranes applied for alcohol recovery with high permeability and selectivity are drawing more and more attention. However, the design and fabrication of high-quality and stable MOF-based mixed matrix membrane for pervaporation are still a big challenge. Herein, PDMS functionalized MOF-derived nanoporous carbon (P-ZNC) was first explored as compatible nanofiller to mutually blend with polydimethylsiloxane on PVDF substrate to fabricate defect-free mixed matrix membranes via dip-coating and thermal cross-linkng. Induced by UV illumination, hydrophobic modification of MOF-derived nanoporous carbon was successfully realized under mild conditions within one step, simplifying the operation step. By using this facile strategy, we can not only solve the existing problem of agglomeration, but also covalently cross-link MOF derivative with polymeric matrix and effectively eliminate the interface defect between polymer and nanoparticles without any extra steps. The method also gives a good level of generality for the synthesis of versatile stable nanoporous MOF-derived carbon-based mixed matrix membranes on various supports. The prepared PDMS/P-ZNC with commendable structures possessed excellent separation performance in low concentration n-butanol recovery and had a good balance between permeance, selectivity, and stability.

Determination of in vivo biological activities of Dodonaea viscosa flowers against CCL4 toxicity in albino mice with bioactive compound detection.

Dodonaea viscosa L.Jacq. is an evergreen shrub and native to Asia, Africa, and Australia. It has been used as traditional medicine in different countries. The foremost objective of the current study was to discover the protective potential of D. viscosa flowers Methanol (DVM) and Chloroform (DVC) extracts against CCL4 induced toxicity in mice. This study was intended to identify phytochemicals through HPLC, GCMS, and FT-IR, as well as in vitro antioxidant and in vitro anti-tuberculosis activity. Our comprehensive findings indicate that Dodonaea viscosa is valuable and widespread herbal medicine through therapeutic potentials for curing various ailments. Dodonaeaviscosa flowersare found to have a protective effect against oxidative stress produced by CCL4 in the liver, kidney, and spleen. The intake of DV extracts restored the level of hepatic enzymes (ALP, AST ALT, and Direct bilirubin), hematological parameters (RBCs, WBCs, and Platelets), total protein, and liver antioxidant enzymes (SOD, GPx, and CAT) after a decline in levels by CCL4. Histopathological results discovered the defensive effect of 300 mg/kg of DVM extract against CCL4 induced damage, thus having an improved protective effect compared to DVC and control. As a result of metabolite screening, the total flavonoids and total phenolics were present in abundance. A phytochemical investigation by HPLC identified gallic acid, epicatechin, cumeric acid, flavonoids, while GCMS estimated oleic acid (Octadecenoic acid) (C18H34O2), Stearic acid (C18H36O2), Ricinoleic acid (C18H34O3), and Cedrol (C15H26O). DVM extract exhibited resistance against in vitro Mycobacterium tuberculosis strains. So this study proposed that the protective effect of DV against oxidative damage induced in the liver, kidney, and spleen can be correlated to the antioxidant compounds.

Global transmission dynamic of SIR model in the time of SARS-CoV-2.

This current work studies a new mathematical model for SARS-CoV-2. We show how immigration, protection, death rate, exposure, cure rate and interaction of infected people with healthy people affect the population. Our model is SIR model, which has three classes including susceptible, infected and recovered respectively. Here, we find the basic reproduction number and local stability through jacobean matrix. Lyapunvo function theory is used to calculate the global stability for the problem under investigation. Also a nonstandard finite difference sachem (NSFDS) is used to simulate the results.

Cross-sectional retrospective analysis of clinical characteristics of chronic hepatitis B patients with oral antiviral treatment in eastern China.

BACKGROUND: In China, more than 20 million patients with chronic hepatitis B need antiviral treatment. Side effects of antiviral treatment such as renal complications can be problematic, particularly in an aging population. METHODS: The data were retrospectively extracted from the hospital medical charts of five centers in eastern China from January 1 to December 31, 2018. RESULTS: A total of 8309 patients with CHB was enrolled in this study. The median age of the patients was 46 years. The prevalence of diabetes mellitus, hypertension, and hepatic cirrhosis was respectively 3.49%, 4.42%, and 23.72%. The prevalence of these comorbidities increased with age (P < 0.001). Of the patients with CHB, 5332 had complete renal function results. Among them, patients with an estimated glomerular filtration rate of < 60 mL/min/1.73m2 accounted for 4.14%, and those with proteinuria for 8.33%. According to the definition of chronic kidney disease, the proportion of patients with chronic kidney disease was 11.37%. The prevalence of chronic kidney disease increased with age (P < 0.001). In a multivariate analysis, age group [odds ratio (OR) = 2.387], diabetes mellitus (OR = 1.486), hypertension (OR = 2.557), hepatic cirrhosis (OR = 1.295), and a history of exposure to adefovir dipivoxil (OR = 1.644) were significantly associated with CKD (P < 0.05). Among patients with CKD, 17.66% (107/606) had a history of lamivudine exposure, and 34.65% (210/606) had a history of nucleotide analogue exposure CONCLUSION: The management of Chinese patients with CHB should take into consideration age, previous medication history, and renal impairment.

Seraprevir and sofosbuvir for treatment of chronic hepatitis C virus infection: A single-arm, open-label, phase 3 trial.

BACKGROUND AND AIM: This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of seraprevir, an hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic HCV infection without cirrhosis. METHODS: Treatment-naive or interferon-experienced adult patients without cirrhosis were treated with a universal, combinational regimen of seraprevir 100 mg, twice daily and sofosbuvir 400 mg, once daily, for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response at week 12 after treatment (SVR12). RESULTS: Overall, 205 patients with genotype 1 HCV infection without cirrhosis were enrolled from 23 sites, 202 of whom completed the full treatment and post-treatment course and 3 discontinued follow-up. In total, 27 patients (13.2%) were interferon experienced. SVR12 was achieved by 201 out of 205 (98.0% [95% CI, 95.1%, 99.5%]) patients, 100.0% of patients with genotype 1a, and 98.0% of genotype 1b. In the other exploratory study, SVR 12 was achieved by 100% patients with genotype 2 (n = 21), genotype 3 (n = 7), and genotype 6 (n = 8). The majority of adverse events were mild to moderate and transient and did not require a specific medical intervention. CONCLUSIONS: The all-oral, ribavirin-free regimen of seraprevir and sofosbuvir is an effective and well-tolerated treatment option for Chinese patients mono-infected with HCV, including those with a history of interferon treatment.

Preparation of Amino-Functional UiO-66/PIMs Mixed Matrix Membranes with [bmim][Tf2N] as Regulator for Enhanced Gas Separation.

Development of mixed matrix membranes (MMMs) with excellent permeance and selectivity applied for gas separation has been the focus of world attention. However, preparation of high-quality MMMs still remains a big challenge due to the lack of enough interfacial interaction. Herein, ionic liquid (IL)-modified UiO-66-NH2 filler was first incorporated into microporous organic polymer material (PIM-1) to prepare dense and defect-free mixed matrix membranes via a coating modification and priming technique. IL [bmim][Tf2N] not only improves the hydrophobicity of UiO-66-NH2 and facilitates better dispersion of UiO-66-NH2 nanoparticles into PIM-1 matrix, but also promotes the affinity between MOFs and polymer, sharply reducing interface non-selective defects of MMMs. By using this strategy, we can not only facilely synthesize high-quality MMMs ignoring non-selective interfacial voids, but also structurally regulate MOF nanoparticles in the polymer substrate and greatly improve interface compatibility and stability of MMMs. The method also gives suitable level of generality for fabrication of versatile defect-free MMMs based on different combination of MOFs and PIMs. The prepared UiO-66-NH2@IL/PIM-1 membrane exhibited outstanding gas separation behavior with large CO2 permeation of 8283.4 Barrer and high CO2/N2 selectivity of 22.5.

Identification of the association of CD28+ CD244+ Tc17/IFN-γ cells with chronic hepatitis C virus infection.

CD8+ T cells play multiple and complex immunological roles including antiviral, regulatory, and exhaustive effects in hepatitis C virus (HCV) infected patients. Some CD8+ T-cell subsets were confirmed to be closely related to HCV infection such as TCM , TEM , TEM RA, Tc17, and CD8+ Treg. Herein, we report a new subset of interleukin (IL)-17/interferon (IFN)-γ producing CD8+ T (Tc17/IFN-γ) cells that markedly correlate with CD28+ CD244+ cells, IL-17 levels, and HCV RNA in HCV patients. During early treatment with peg-IFN-a2a plus ribavirin, the imbalance of these Tc17/IFN-γ cells could be partially restored, together with normalized serum alanine aminotransferase but not aspartate transaminase. Also, we analyzed the dynamic change of the percentage of this T cells subset in patients with different outcome after 4-week course of treatment with peg-IFN-a2a plus ribavirin and found that the percentage of CD8+ CD28+ CD244+ T cells significantly decreased in recovered patients but not in nonrecovered patients. In vitro, CD28+ CD244+ T cells were the only CD8+ T-cell group that secreted both IL-17 and IFN-γ in this axis and blockade with anti-CD244 antibodies significantly reduced cytokine production. Taken together, this study demonstrates that the frequency and regulatory functions of CD28+ CD244+ Tc17/IFN-γ cells may play an important role in persistent HCV infection.

Prevalence of Hepatitis C Virus Infection in a Surgical Population of Southeast China: A Large-Scale Multicenter Study.

Background: Chronic HCV infection affects 80 million people globally and may progress to advanced liver disease. The present study aims to investigate the present epidemiology of HCV infection in a southeastern Chinese surgical patient cohort. Methods: Blood samples obtained from 78,484 surgical patients from 18 different city and county hospitals were enrolled. The incidence of serum HCV antibody positivity, HCV RNA load, and HCV genotyping, as well as demographics and relevant clinical history, were investigated. Data were stratified using the multistage cluster random sampling method and further analyzed using the SPSS-20 package. Results: HCV antibody positivity was detected in 0.15% of the population (95% confidence interval (CI): 0.12%-0.18%). Genotype 1b (55.74%) was the dominant type. The HCV infection peaked in the age groups of 16-20, 41-50, and 61-65 years, and it was higher in males than in females (0.19% vs. 0.13%, P < 0.05). The geographical distribution of infection rates differed: 0.19% (95% CI: 0.14%-0.24%), 0.18% (95% CI: 0.13%-0.23%), and 0.06% (95% CI: 0.03-0.09%) in plain areas, islands, and valley regions, respectively. Patients with transfusion history and urban residence were associated with high HCV RNA levels (adjusted odds ratio = 11.24 and 6.20, P < 0.05). Conclusion: The prevalence of HCV infection in this cohort from southeast China was 0.17%, which is lower than the reported 0.43% infection rate in China in 2006. This result can be (partially) explained by the improvement of blood donor screening and the successful campaign for the use of disposable syringes and needles.

Constitutively expressed MHC class Ib molecules regulate macrophage M2b polarization and sepsis severity in irradiated mice.

Macrophages can change their physiology in response to microenvironmental signals. This differentiation into classically activated M1 or alternatively activated M2 macrophages is known as polarization. In this study, we isolated bone marrow-derived macrophages from ß2m-deficient (deficient in both MHC class Ia and Ib) and Kb Db -deficient (deficient only in MHC class Ia) mice and found that ß2m-deficient macrophages showed a significantly lower M2b polarization efficiency. In addition, the absence of constitutive MHC class Ib expression decreased the stability of the Notch-1 intracellular domain. Finally, we found that ß2m-deficient mice exposed to irradiation showed reduced bacterial translocation and sepsis severity. Overall, our study demonstrates that MHC class Ib molecules are essential for M2b macrophage polarization and suggests that MHC class Ib molecules play an important role during infection-induced innate immunity.

Identification of IL-10-secreting CD8+CD28-PD-1+ regulatory T cells associated with chronic hepatitis C virus infection.

CD8+CD28- regulatory T cells (Tregs) play important roles in chronic viral infections. Programmed death 1 (PD-1) is highly expressed on hepatitis C virus (HCV)-specific CTLs. However, little is known regarding the role of CD8+CD28-PD1+ T cells in hepatitis C. Herein, we found that the frequency of CD8+CD28-PD1+, but not CD8+CD28-PD1- T cells, correlated with markers of chronic hepatitis C virus (HCV) infection and the response to treatment. Our results showed that CD8+CD28-PD1+ T cells were significantly elevated in chronic HCV-infected patients and there was a distinct correlation between the frequency of CD8+CD28-PD1+ T cells and serum levels of HCV RNA. During a 48-week course of treatment with peg-IFN-a2a plus ribavirin, dynamic changes in the frequencies of CD8+CD28-PD1+ T cells were observed, associated with the virologic response. IL-10 secretion may explain the suppressive function of CD8+CD28-PD1+ T cells in chronic HCV-infected patients. Overall, our study demonstrates that PD-1 is an important marker of CD8+CD28- Tregs in chronic HCV infection. Thus, the frequency and regulatory function of CD8+CD28-PD1+ T cells play vital roles in HCV infection and the response to treatment.