Cellular and molecular insights into incomplete immune recovery in HIV/AIDS patients.

Highly active antiretroviral therapy (ART) can effectively inhibit virus replication and restore immune function in most people living with human immunodeficiency virus (HIV). However, an important proportion of patients fail to achieve a satisfactory increase in CD4+ T cell counts. This state is called incomplete immune reconstitution or immunological nonresponse (INR). Patients with INR have an increased risk of clinical progression and higher rates of mortality. Despite widespread attention to INR, the precise mechanisms remain unclear. In this review, we will discuss the alterations in the quantity and quality of CD4+ T as well as multiple immunocytes, changes in soluble molecules and cytokines, and their relationship with INR, aimed to provide cellular and molecular insights into incomplete immune reconstitution.

The Impact of Active Screening and Management on COVID-19 in Plateau Region of Sichuan, China.

Background: In December 2019, the cases of pneumonia of unknown etiology emerged in Wuhan, China, and rapidly spread throughout the country. The disease was later designated by the World Health Organization (WHO) as Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Few studies have assessed the clinical characteristics of COVID-19 and control strategies used to mitigate disease spread in high-altitude plateau regions of China. Study Objective: To assess the impact of real-world strategies to control COVID-19 spread in remote plateau regions. Methods: A retrospective study was performed to assess the epidemiology of COVID-19 and strategies used to control disease spread in the high-altitude plateau of Sichuan, China from 24 January 2020 to 19 March 2020. Results: COVID-19 spread and outbreaks in Sichuan were attributed to mass gatherings. A total of 70 patients and 20 asymptomatic individuals were found in the hypoxic plateau region of Sichuan. Twelve patients were admitted after the onset of symptoms, while 58 patients and 20 asymptomatic individuals were found by active screening. The symptomatic patients included those with uncomplicated illness (16/70, 22.9%), mild pneumonia (44/70, 62.9%), and severe pneumonia (10/70, 14.3%). Most patients in the study area showed relatively mild and atypical symptoms such as low or no fever and dyspnea. The incidence of severe pneumonia, fever, dyspnea, and interstitial abnormalities identified by chest CT were all significantly lower in screened patients than those admitted after symptom onset (P < 0.05). Severe pneumonia was noted in patients with chronic conditions like hypertension, diabetes etc. as compared to less severe pneumonia in healthy subjects (P <0.05). No patients died and all were eventually discharged. Conclusion: Mass gatherings increased risk of spread of SARS-CoV-2 responsible for COVID-19. Active screening and early management have collectively contributed to reduced incidence of severe pneumonia and satisfactory prognoses of infections with COVID-19 in this hypoxic plateau region.

Recent research and development of NDM-1 inhibitors.

Bacteria carrying New Delhi metallo-ß-lactamase-1 (New Delhi metallo-ß-lactamase, NDM-1) resistance gene is a new type of "superbug", which can hydrolyze almost all ß-lactam antibiotics, rapidly spread among the same species and even spread among different species. NDM-1 belongs to the class B1 broad-spectrum enzyme of ß-lactamase. The two positively charged zinc ions in the active center have electrostatic interaction with the hydroxyl ions in them to seize the hydrogen atom near the water molecule to form a bridging ring water molecule, which strengthens its nucleophilicity and attacks the carbonyl group on the lactam ring; thus, catalyzing the hydrolysis of ß-lactam antibiotics. Since NDM-1 has an open active site and unique electrostatic structure, it essentially provides a wider range of substrate specificity. Due to its flexible hydrolysis mechanism and more and more variants also aggravate the threat of drug-resistant bacteria infection, there is still no effective inhibitor in clinic, which is a serious threat to human health and public health safety. The electron-rich substituents of NDM-1 inhibitors coordinate with two positively charged zinc ions in the active center of the enzyme through ion-dipole interaction to produce NDM-1 inhibitory activity. In this review, the research progress of NDM-1 enzyme and its inhibitors in the past 5 years was reviewed. The crystal structure, active center structure, surrounding important amino acid residues, newly discovered inhibitors and their action mechanism are classified and summarized in detail, which can be used as a reference for the development of effective drugs against drug-resistant bacteria targeting NDM-1.

Associations between hepatitis B infection and chronic kidney disease: 10-Year results from the U.S. National Inpatient Sample / Relaciones entre la infección por hepatitis B y la enfermedad renal crónica: resultados de 10 años de la muestra nacional de pacientes hospitalizados de EE. UU

INTRODUCTION: Viral hepatitis infection is associated with negative impacts on renal function that may lead to nephropathy. We investigated associations between chronic hepatitis B virus (HBV) infection and chronic kidney disease (CKD) and/or end-stage renal disease (ESRD) in a large, representative sample from a nationwide U.S. database. METHODS: This population-based, retrospective observational study extracted data from the U.S. Nationwide Inpatient Sample (NIS) database, including adults ≥18 years old admitted to U.S. hospitals between 2005 and 2014 with records of chronic HBV infection in medical history. The final analytic sample included 70,674 HBV-infected patients and 282,696 matched non-HBV controls. Study endpoints were prevalent CKD and ESRD. Associations between CKD/ESRD and HBV and patients' clinical characteristics were determined by logistic regression analysis. RESULTS: HBV infection was associated with slightly increased risk of prevalent CKD (OR: 1.06, 95% CI: 1.004-1.119) and an approximate 2-times risk of prevalent ESRD (OR: 1.98, 95% CI: 1.880-2.086). HBV infection in both genders was associated with slightly increased risk of CKD (males, OR: 1.09, 95% CI: 1.02-1.16; females, OR: 1.07, 95% CI: 0.98,1.17), and significantly associated with increased risk for CKD among non-diabetic patients (OR: 1.23, 95% CI: 1.15-1.32), white patients (OR: 1.14, 95% CI: 1.06-1.23) and Asian/Pacific Islanders (OR: 1.13, 95% CI: 0.98-1.30). CONCLUSIONS: Chronic HBV infection is associated with slightly increased risk for CKD and greater risk for ESRD in males and females, Whites and Asian/Pacific Islanders and non-diabetic patients

INTRODUCCIÓN: La infección por el virus de la hepatitis se asocia a impactos negativos en la función renal que pueden derivar en nefropatía. Investigamos las asociaciones entre la infección crónica por el virus de la hepatitis B (VHB) y la enfermedad renal crónica (ERC) y/o la enfermedad renal terminal (ERT) en una muestra de grandes dimensiones y representativa procedente de una base de datos nacional de los Estados Unidos. MÉTODOS: Este estudio observacional retrospectivo y poblacional extrajo datos de la base de datos de la muestra nacional de pacientes hospitalizados (Nationwide Inpatient Sample, NIS) de los EE. UU., que incluye adultos ≥18 años ingresados en hospitales de los EE. UU. entre 2005 y 2014 con registros de infección crónica por VHB en su historia médica. La muestra analítica final incluyó a 70.674 pacientes infectados por el VHB y a 282.696 controles emparejados no infectados por el VHB. Los criterios de valoración del estudio fueron la enfermedad renal crónica y la enfermedad renal terminal prevalentes. Las asociaciones entre la ERC o la ERT y el VHB y las características clínicas de los pacientes se determinaron mediante un análisis de regresión logística. RESULTADOS: La infección por VHB se asoció a un riesgo ligeramente mayor de prevalencia de enfermedad renal crónica (OR: 1,06; IC del 95%: 1,004-1,119) y un riesgo aproximadamente dos veces mayor de enfermedad renal terminal (OR: 1,98; IC del 95%: 1,880-2,086). La infección por VHB se asoció en ambos sexo a un riesgo ligeramente mayor de enfermedad renal crónica (hombres, OR: 1,09, IC del 95%: 1,02-1,16; mujeres, OR: 1,07, IC del 95%: 0,98-1,17), y se asoció significativamente a un mayor riesgo de enfermedad renal crónica entre los pacientes no diabéticos (OR: 1,23, IC del 95%: 1,15-1,32), pacientes blancos (OR: 1,14, IC del 95%: 1,06-1,23) y asiáticos o de las islas del Pacífico (OR: 1,13, IC del 95%: 0,98-1,30). CONCLUSIONES: La infección crónica por VHB se asocia a un riesgo ligeramente mayor de enfermedad renal crónica y a un mayor riesgo de enfermedad renal terminal en hombres y mujeres, blancos y asiáticos o de las islas del Pacífico y pacientes no diabéticos

Associations between hepatitis B infection and chronic kidney disease: 10-Year results from the U.S. National Inpatient Sample.

INTRODUCTION: Viral hepatitis infection is associated with negative impacts on renal function that may lead to nephropathy. We investigated associations between chronic hepatitis B virus (HBV) infection and chronic kidney disease (CKD) and/or end-stage renal disease (ESRD) in a large, representative sample from a nationwide U.S. METHODS: This population-based, retrospective observational study extracted data from the U.S. Nationwide Inpatient Sample (NIS) database, including adults ≥18 years old admitted to U.S. hospitals between 2005 and 2014 with records of chronic HBV infection in medical history. The final analytic sample included 70,674 HBV-infected patients and 282,696 matched non-HBV controls. Study endpoints were prevalent CKD and ESRD. Associations between CKD/ESRD and HBV and patients' clinical characteristics were determined by logistic regression analysis. RESULTS: HBV infection was associated with slightly increased risk of prevalent CKD (OR: 1.06, 95% CI: 1.004-1.119) and an approximate 2-times risk of prevalent ESRD (OR: 1.98, 95% CI: 1.880-2.086). HBV infection in both genders was associated with slightly increased risk of CKD (males, OR: 1.09, 95% CI: 1.02-1.16; females, OR: 1.07, 95% CI: 0.98,1.17), and significantly associated with increased risk for CKD among non-diabetic patients (OR: 1.23, 95% CI: 1.15-1.32), white patients (OR: 1.14, 95% CI: 1.06-1.23) and Asian/Pacific Islanders (OR: 1.13, 95% CI: 0.98-1.30). CONCLUSIONS: Chronic HBV infection is associated with slightly increased risk for CKD and greater risk for ESRD in males and females, Whites and Asian/Pacific Islanders and non-diabetic patients.

Epidemiological and clinical based study on four passages of COVID-19 patients: intervention at asymptomatic period contributes to early recovery.

BACKGROUND: With the worldwide spread of the 2019 novel coronavirus, scarce knowledge is available on the clinical features of more than two passages of patients. Further, in China, early intervention policy has been enacted since February. Whether early intervention contributes to swift recovery is still unknown. Hence, in this study, we focused on the patients from an isolated area, investigated the epidemiological and clinical characteristics of four serial passages of the virus. METHODS: From January 25 to February 29, 2020, all patient data on the SARS-CoV-2 passages in this isolated area were traced, and the patients were grouped according to the passaging of SARS-CoV-2. Clinical characteristics of patients, including laboratory, radiology, treatment and outcomes, were collected and analyzed. RESULTS: A total of 78 patients with four passages of virus transmission were included in this study. One patient transmitted SARS-CoV-2 to 8 patients (passage 2, P2), who next infected 23 patients (passage 3, P3), and then 46 patients (passage 4, P4). P2 received antiviral treatment when they had symptom, whereas P4 received antiviral treatment during their asymptomatic period. The incubation periods for P2, P3 and P4 patients were 7 days (IQR:2-12), 8 days (IQR:4-13) and 10 days (IQR:7-15), respectively. P2 patients showed lymphocytopenia (0.79 × 109/L), decreased lymphocyte percentages (12.15%), increased white blood cell count (6.51 × 109/L), increased total bilirubin levels (25% of P2 patients), increased C-reactive protein levels (100% of P2 patients) and abnormal liver function. By chest CT scans, all P2 patients (100%), 15 of P3 patients (65.22%) and 16 of P4 patients (34.78%) showed abnormality with typical feature of ground glass opacity. All of P2 patients (100%) received oxygen therapy, and in contrast, 19 of P4 patients (41.3%) received oxygen therapy. Further, significant decreased nucleic acid positive periods was found in P4 group (16 days, IQR: 10-23), compared with that of P2 group (22 days, IQR: 16-27). Moreover, the severity ratios were sharply decreased from 50% (P2 patients) to 4.35% (P4 patients), and the case fatality rate is zero. CONCLUSIONS: Judged from four passages of patients, early intervention contributes to the early recovery of COVID-19 patients.

Fibroscan improves the diagnosis sensitivity of liver fibrosis in patients with chronic hepatitis B.

The aim of the present study was to investigate the diagnostic accuracy of Fibroscan for liver fibrosis in patients with chronic hepatitis B (CHB) with alanine aminotransferase (ALT) levels <2 times the upper normal limit. A total of 263 consecutive patients with CHB and ALT levels <2 times the upper normal limit were enrolled in the present study. Liver biopsies and liver stiffness measurements (LSM) were conducted. Receiver operating characteristic (ROC) analysis was used to determine the predictive ability of LSM for the development of liver fibrosis in patients with stage S1, S2 and S3 liver fibrosis. Bivariate Spearman rank correlation analysis was performed in order to determine the association between liver stiffness value, which was measured by Fibroscan, and liver fibrosis stage, which was measured by liver biopsy. The liver stiffness value was found to be positively correlated with the liver fibrosis stage (r=0.522, P<0.001) and necroinflammatory activity (r=0.461, P<0.001), which was measured by liver biopsy. The optimal cut-off value in the patients with stage S1, S2 and S3 liver fibrosis was 5.5, 8.0 and 10.95 kPa, respectively. The area under the ROC curve for the prediction of the development of liver fibrosis in these patients was 0.696, 0.911 and 0.923, respectively. The threshold of the optimal cut-off value exhibited a high sensitivity and specificity. The results of the present study suggested that Fibroscan may improve the sensitivity of the diagnosis of liver fibrosis in patients with CHB and ALT levels <2 times the upper normal limit, and that this sensitivity may increase with the progression of liver fibrosis.

Hepatic actinomycosis: report of one case and analysis of 32 previously reported cases.

Hepatic actinomycosis is rare, with few published cases. There are no characteristic clinical manifestations, and computed tomography (CT) shows mainly low-density images, making clinical diagnosis difficult, and leading to frequent misdiagnosis as primary liver cancer, metastatic liver cancer or liver abscess. Diagnosis normally requires examination of both the aetiology and pathology. This article reports one male patient aged 55 who was hospitalized because of repeated upper abdominal pain for more than 2 mo. He exhibited no chills, fever or yellow staining of the skin and sclera, and examination revealed no positive signs. The routine blood results were: haemoglobin 110 g/L, normal numbers of leukocytes and neutral leukocytes, serum albumin 32 g/L, negative serum hepatitis B markers and hepatitis C antibodies, normal tumour markers (alpha-fetoprotein and carcinoembryonic antigen). An abdominal CT scan revealed an 11.2 cm × 5.8 cm × 7.4 cm mass with an unclear edge in the left liver lobe. The patient was diagnosed as having primary liver cancer, and left lobe resection was performed. The postoperative pathological examination found multifocal actinomycetes in the hepatic parenchyma, which was accompanied by chronic suppurative inflammation. A focal abscess had formed, and large doses of sodium penicillin were administered postoperatively as anti-infective therapy. This article also reviews 32 cases reported in the English literature, with the aim of determining the clinical features and treatment characteristics of this disease, and providing a reference for its diagnosis and treatment.