Role of Proviral HIV-1 DNA Genotyping for People Living with HIV (PLWH) Who Had Low-Level Viremia While Receiving Antiretroviral Therapy.

Objective: To analyze the antiretroviral resistance in people living with HIV (PLWH) who developed low-level viremia (LLV) during antiretroviral therapy (ART) via sequencing of their HIV-1 proviral DNA and RNA and comparisons of their proviral DNA genotyping data with their past and synchronous RNA genotyping data. Patients and Methods: PLWH with LLV while receiving ART for 6 months or longer from January 2020 to September 2021 were included. HIV-1 proviral DNA and RNA were extracted from white-blood cells and concentrated plasma by ultracentrifugation, respectively, and HIV-1 pol gene fragments were amplified and sequenced. The concordance in the detection of resistance-associated mutations (RAMs) were examined between proviral DNA vs past RNA genotyping and proviral DNA vs synchronous RNA genotyping. Results: Of the 150 PLWH with LLV, 117 proviral DNA pol sequences detected in 105 PLWH were successfully amplified and RAMs were present in 27.6% and the rate of RAMs conferring low-level or greater resistance to antiretrovirals examined was 17.1%. Fifty-six and 57 PLWH had results of past and synchronous RNA genotyping, respectively, for comparisons with those of proviral DNA genotyping; and the concordance rates were 76.8% and 75.4%, respectively. However, proviral DNA genotyping lost than gained partial information on antiretroviral resistance compared with past or synchronous RNA genotyping. Conclusion: We found that the concordance between proviral DNA and past and synchronous RNA genotyping was moderate. Proviral DNA genotyping lost than gained more information on antiretroviral resistance compared with past or synchronous RNA genotyping. To optimize ART in PLWH with LLV, antiretroviral resistance profile should be interpreted in combination with proviral DNA and RNA genotyping and a comprehensive review of previous treatment history.

Integrated analysis reveals important differences in the gut and oropharyngeal microbiota between children with mild and severe hand, foot, and mouth disease.

Little is known about alternation and difference in gut microbiota between patients with mild and severe hand, foot, and mouth disease (HFMD). We investigated the differences in gut and oropharynx microbiota between mild and severe HFMD in young children and changes in bacterial profiles as the disease progresses from acute to convalescent phase. Forty-two patients with confirmed HFMD were studied, among which 32 had severe HFMD and 10 had mild HFMD. First rectal swabs were collected from all patients at an average of 2 days (acute phase) after the onset of symptoms, and second rectal swabs were collected from 8 severe patients at day 9 (convalescent phase) after the onset. Oropharyngeal swabs were obtained from 10 patients in the acute phase and 6 in the convalescent phase. 16S rRNA sequencing was performed for all 70 samples. Compared with mild HFMD, severe HFMD exhibited significantly decreased diversity and richness of gut microbiota. Gut microbiota bacterial profiles observed in the acute and convalescent phases resembled each other but differed from those in mild cases. Additionally, 50% of patients with severe HFMD in the acute phase harboured a dominant pathobiontic bacterial genus. However, none of the patients with mild HFMD had such bacteria. Similar bacterial compositions in oropharynx microbiota were detected between mild and severe cases. Our findings indicate that severe HFMD exhibits significantly impaired diversity of gut microbiota and frequent gut and oropharyngeal inflammation-inducing bacteria. However, the results should be interpreted with caution as the number of subjects was limited.

Psoas Muscle Index Can Be Used to Predict Long-Term Mortality in Young Male Patients With Acute-on-Chronic Liver Failure.

OBJECTIVE: The use of psoas muscle index (PMI) in acute-on-chronic liver failure (ACLF) has not been reported, and the aim of this study was to evaluate the predictive value of PMI for the prognosis of patients with ACLF. METHODS: In this study, male ACLF patients who underwent abdominal CT between 2015 and 2019 in our center were included to analyze the association between PMI and 1-year mortality in male ACLF patients, and subgroup analyses were performed according to age stratification (≤ 40 and >40 years). RESULTS: We included 116 male patients with confirmed ACLF, with a mean PMI of 5.98 ± 1.68 cm2/m2 and a 1-year mortality of 51.7% (60). Univariate COX regression analysis showed that PMI was a protective factor [hazard ratio (HR), 0.851, 95%CI: 0.734-0.987] for 1-year mortality in male patients with ACLF. Nevertheless, multivariate analysis did not find an independent relationship between PMI and 1-year mortality. Subgroup analysis by age found that adjusted for MELD score, PMI was independently associated with 1-year mortality in young (age ≤ 40 years) male patients with ACLF (HR 0.689, 95% CI: 0.496-0.958). While no effect of PMI on 1-year mortality in non-young (age > 40 years) male ACLF patients was found. Correlation analysis found that there was no significant correlation between PMI and age in young (age ≤ 40 years) male ACLF patients, but, PMI decreased with age (r = -0.246, P < 0.05) in non-young (age > 40 years) male ACLF patients. CONCLUSION: PMI was found to be associated with 1-year mortality in male ACLF patients, especially in patients younger than 40 years, PMI predict 1-year mortality independent of MELD score.

Clinical features and survival analysis of 97 coronavirus disease 2019 (COVID-19) patients.

BACKGROUND: We aim to investigate the clinical characteristics and survival rate of coronavirus disease 2019 (COVID-19) patients. METHODS: Ninety-seven COVID-19 patients were enrolled. The laboratory results, lung imaging and medical treatment were compared. Patients were followed up after 1 year, and the Kaplan-Meier test was used for survival analysis. RESULTS: Compared with the non-severe group, the age of the severe group was older, and the proportion of concomitant diseases were higher. As fever was the primary clinical manifestation, dyspnea and anorexia were more common in severe patients. Lung imaging manifestations and laboratory indicators were worse in the severe group. Accordingly, the treatment of glucocorticoid, antibiotics, and advanced life support were in high proportion. Of the 97 patients with COVID-19, 4 severe patients died within one month during the 1-year follow-up, with the median survival time of 47.0 weeks (95% CI: 45.1-48.9). CONCLUSIONS: Severe cases of COVID-19 are characterized by advanced age, more concomitant diseases and complications, which lead to a decreased short-term survival rate. However, there were no deaths after one month, which implied a good prognosis if the risk period were passed smoothly.

Use of skeletal muscle index as a predictor of short-term mortality in patients with acute-on-chronic liver failure.

Sarcopenia is a well-recognized factor affecting the prognosis of chronic liver disease, but its impact on acute decompensation underlying chronic liver disease is unknown. This study evaluated the impact of sarcopenia on short-term mortality in patients with acute-on-chronic liver failure (ACLF). One hundred and seventy-one ACLF patients who underwent abdominal CT between 2015 and 2019 were retrospectively included in this study. Skeletal muscle index at the third lumbar vertebrae (L3-SMI) was used to diagnose sarcopenia.The ACLF patients in this study had a L3-SMI of 41.2 ± 8.3 cm2/m2 and sarcopenia was present in 95/171 (55.6%) patients. Body mass index (BMI), cirrhosis, and higher serum bilirubin were independently associated with sarcopenia. Following multivariate Cox regression analysis, cirrhosis (hazard ratio (HR) 2.758, 95%CI 1.323-5.750), serum bilirubin (HR 1.049, 95%CI 1.026-1.073), and international normalized ratio (INR) (HR 1.725, 95%CI 1.263-2.355) were associated with 3-month mortality (P < 0.05), whereas L3-SMI and sarcopenia were not. A subgroup analysis of the factors related to sarcopenia showed that sarcopenia was still not predictive of short-term outcome in ACLF patients. L3-SMI and sarcopenia are not associated with short-term mortality in patients with ACLF.

Duration of SARS-CoV-2 RNA shedding and factors associated with prolonged viral shedding in patients with COVID-19.

To investigate the factors associated with the duration of severe acute respiratory syndrome coronavirus 2 RNA shedding in patients with coronavirus disease 2019 (COVID-19). A retrospective cohort of COVID-19 patients admitted to a designated hospital in Beijing was analyzed to study the factors affecting the duration of viral shedding. The median duration of viral shedding was 11 days (IQR, 8-14.3 days) as measured from illness onset. Univariate regression analysis showed that disease severity, corticosteroid therapy, fever (temperature>38.5°C), and time from onset to hospitalization were associated with prolonged duration of viral shedding (P < .05). Multivariate regression analysis showed that fever (temperature>38.5°C) (OR, 5.1, 95%CI: 1.5-18.1), corticosteroid therapy (OR, 6.3, 95%CI: 1.5-27.8), and time from onset to hospitalization (OR, 1.8, 95%CI: 1.19-2.7) were associated with increased odds of prolonged duration of viral shedding. Corticosteroid treatment, fever (temperature>38.5°C), and longer time from onset to hospitalization were associated with prolonged viral shedding in COVID-19 patients.

Effect of Jinhua Qinggan granules on novel coronavirus pneumonia in patients.

OBJECTIVE: To evaluate the effectiveness and safety of Jinhua Qinggan granules in the treatment of patients with novel coronavirus pneumonia (COVID-19). METHODS: Eighty cases of COVID-19 diagnosed from January 24 to February 17, 2020 in Beijing YouAn Hospital Affiliated to Capital Medical University were retrospectively analyzed. All 80 patients received symptomatic and supportive treatment. Among them, 44 patients took Jinhua Qinggan granules (treatment group) within 24 h of admission, and the remaining 36 patients either did not take Jinhua Qinggan granules or took the granules for less than 2 d (control group). In this study, we compared the duration of viral nucleic acid detection and of pneumonia absorption improvement between the two groups. RESULTS: Among the 80 cases, 37 were male (46%) and 43 were female (54%) with age ranging from 15 to 86 years, with an average age of 51.19 years. The average duration of viral nucleic acid detection was (7 ± 4) d in the Jinhua Qinggan administration group and (10 ± 4) d for the control group (P = 0.010), following which, nucleic acid tests were negative. Of the two groups, 56.82% in the Jinhua Qinggan treatment group and 27.78% in the control group demonstrated negative nucleic acid tests within 7 d or less. The 7-day viral clearance rate was significantly higher in the Jinhua Qinggan group compared with the control group (P = 0.009). Furthermore, the pneumonia recovery time indicated by chest CT was (8 ± 4) d in the Jinhua Qinggan group, which was significantly shorter than the control group, at (10 ± 5) d (P = 0.021). No adverse reactions were found in the treatment group after taking this medicine. CONCLUSION: In patients with COVID-19, Jinhua Qinggan granules can effectively shorten the duration of nucleic acid detection and promote the absorption of pneumonia inflammatory exudate without obvious adverse reactions.

Clinical characteristics of Coronavirus Disease 2019 patients in Beijing, China.

The outbreak of Coronavirus Disease (COVID-19) in Wuhan have affected more than 250 countries and regions worldwide. However, most of the clinical studies have been focused on Wuhan, and little is known about the disease outside of Wuhan in China. In this retrospective cohort study, we report the early clinical features of 80 patients with COVID-19 admitted to the hospital in Beijing. The results show that 27 (33.8%) patients had severe illness. Six (7.5%) patients were admitted to the ICU, and 3 (3.8%) patients died. Forty-eight percent (39/80) of the patients had a history of living/traveling in Wuhan. Patients with severe- illness were significantly older (average age, 71 years old vs 44 years old) and had a high incidence of expectoration (59.3% vs 34.0%), shortness of breath (92.6% vs 9.4%), anorexia (51.9% vs 18.9%) and confusion(18.5% vs 0%) compared with nonsevere patients. The systolic blood pressure (median, 130 mmHg vs 120 mmHg) was higher and the oxygen saturation (median, 98.3% vs 92.0%) was significantly lower in severe patients than nonsevere patients. In addition, myoglobin (median, 56.0 ng/mL vs 35.0 ng/mL), troponin I (median, 0.02 pg/mL vs 0.01 pg/mL), C-reactive protein (median, 69.7 mg/L vs 12.9 mg/L) and neutrophils (median, 3.3×109/L vs 2.2×109/L) were significantly increased, while lymphocytes (median, 0.8×109/L vs 1.2×109/L), albumin (mean, 32.8 g/L vs 36.8 g/L) and the creatinine clearance rate (median, 91.2 vs 108.2 ml/min/1.73m2) were significantly decreased among severe patients. Our study revealed that older patients with high levels of C-reactive protein, myoglobin, troponin I, and neutrophil and high systolic blood pressure as well as low levels of lymphocytes, and albumin and a low creatinine clearance rate and oxygen saturation were more likely to have severe disease.

Spectrum of central nervous system disorders in hospitalized HIV/AIDS patients (2009-2011) at a major HIV/AIDS referral center in Beijing, China.

OBJECTIVE: To describe the spectrum of central nervous system (CNS) disorders and the contribution of neurological immune reconstitution inflammatory syndrome (IRIS) in hospitalized HIV/AIDS patients in You'an Hospital, Beijing China. STUDY DESIGN & METHODS: A retrospective observational study conducted over a 24-month period in You'an Hospial, a public sector referral hospital in Beijing, China. This study enrolled HIV seropositive patients who were admitted for developing new or recurrent neurological and (or) psychiatric symptoms from September 2009 to August 2011. Medical records were reviewed, demographic and clinical data were collected. Patients with peripheral neuropathy and those in delirium were excluded from this study. RESULTS: Of the total 620 HIV/AIDS hospital admissions from September 2009 to August 2011, 60 patients (9.7%) were hospitalized for CNS complications. The diagnosis of HIV infection was made after hospital admission in 16 of the 60 patients (26.7%), and 34 of them (56.7%) were already on antiretroviral therapy (ART) at the point of admission. The median CD4 cell count in these subjects was 39 (21-133) cells/mm(3), and 93.3% (56/60) of these patients belonged to stage IV HIV disease according to World Health Organization (WHO) classification. The most frequent diagnosis in these subjects included cryptococcal meningitis (CM, n=13, 22%), cerebral toxoplasmosis (n=10, 17%), and CNS tuberculosis (n=7, 11.7%). The overall mortality was 13% (8/60) and the case-fatality rates were: cryptococcal meningitis 7.7% (1/13), cerebral toxoplasmosis 20% (2/10) and tuberculous meningitis 28.6% (2/7). Of the 34 patients who were on ART, paradoxical neurological IRIS (the conditions of their existing CNS disorders get paradoxically worse after ART because of an exuberant inflammatory response directed towards opportunistic pathogens) was diagnosed in 4 patients (11.8%), 2 of whom related to TB infection (out of 5 TB patients, 40%), and the other 2 related to CM (out of 8 patients, 25%). CONCLUSION: Opportunistic infections, such as cryptococcal meningitis, cerebral toxoplasmosis and CNS tuberculosis were the most frequent diagnosis of CNS disease in hospitalized HIV/AIDS patients in You'an Hospital, Beijing, China. About 10% patients on ART were diagnosed as neurological IRIS in such a group of patients.

Interleukin-8 is elevated in severe hand, foot, and mouth disease.

INTRODUCTION: Enterovirus 71 (EV71) infections can cause hand, foot, and mouth disease (HFMD), which is a potentially fatal illness in children. Epidemics of HFMD are seen every year globally and present an increasing threat to public health worldwide. METHODOLOGY: To identify potential severity markers for severe HFMD, laboratory findings and levels of eight serum cytokines in 143 EV71-infected patients in Beijing You'an Hospital were analyzed. Patients were grouped by disease severity: Mild (no severe complications) (n = 59), isolated isolated brainstem encephalitis (BE) (n = 47), isolated pulmonary edema (PE) (n = 12), and BE+PE (n = 25). RESULTS: IL-8 levels peaked at day one after admission and were found to be correlated to disease severity, maximal body temperature, and length of hospital stay. Among all tested cytokines, IL-8 was correlated to only IL-6 (p = 0.010). IL-6 and IL-10 were elevated in most patients (98.6% and 70.6%), but not correlated to disease severity (both p > 0.05). IFNγ was only negatively correlated to mild cases (p = 0.025). CONCLUSIONS: IL-8 was correlated to disease severity of HFMD. IL-6 and IL-10, although elevated in most HFMD patients, were not correlated to disease severity.

Comparison of the regulation of ß-catenin signaling by type I, type II and type III interferons in hepatocellular carcinoma cells.

BACKGROUND/OBJECTIVE: IFNs are a group of cytokines that possess potent antiviral and antitumor activities, while ß-catenin pathway is a proliferative pathway involved in carcinogenesis. Interaction between these two pathways has not been well elaborated in hepatocellular carcinoma (HCC). METHODS: HCC cell lines, HepG2 and Huh7, were used in this study. ß-catenin protein levels and corresponding signaling activities were observed by flow cytometry and luciferase assay, respectively. Cell proliferation was quantified by counting viable cells under microscope, and apoptosis by TUNEL assay. DKK1 and GSK3ß levels were determined by flow cytometry. Secreted DKK1 was tested by ELISA. FLUD, S3I and aDKK1 were used to inhibit STAT1, STAT3 and DKK1 activities, respectively. RESULTS: Our findings show that all three types of IFNs, IFNα, IFNγ and IFNλ, are capable of inhibiting ß-catenin signaling activity in HepG2 and Huh7 cells, where IFNγ was the strongest (p<0.05). They expressed suppression of cellular proliferation and induced apoptosis. IFNγ expressed greater induction ability when compared to IFNα and IFNλ (p<0.05). All tested IFNs could induce DKK1 activation but not GSK3ß in HepG2 and Huh7 cells. IFNs induced STAT1 and STAT3 activation but by using specific inhibitors, we found that only STAT3 is vital for IFN-induced DKK1 activation and apoptosis. In addition, DKK1 inhibitor blocked IFN-induced apoptosis. The pattern of STAT3 activation by different IFNs is found consistent with the levels of apoptosis with the corresponding IFNs (p<0.05). CONCLUSIONS: In hepatocellular carcinoma, all three types of IFNs are found to induce apoptosis by inhibiting ß-catenin signaling pathway via a STAT3- and DKK1-dependent pathway. This finding points to a cross-talk between different IFN types and ß-catenin signaling pathways which might be carrying a biological effect not only on HCC, but also on processes where the two pathways bridge.