Effect of intestinal microbiota transplantation on chronic hepatitis B virus infection associated liver disease.

Background: Research on the effects of intestinal microbiota transplantation (IMT) on chronic HBV infection (CHB) progression associated liver disease (HBV-CLD) and alterations in the microbiota post-IMT are quite limited for the moment. Methods: By integrating microbiome with metabolome analyses, we aimed to the function of IMT and the alterations of gut microbiota in patients with HBV-CLD. First, this study included 20 patients with HBV-CLD and ten healthy controls. Then, 16 patients with CHB were given IMT with donor feces (heterologous) via oral capsule. Fecal samples from CHB patients were obtained before and after IMT, as well as healthy controls, for 16S rDNA sequencing and untargeted metabolomics analysis. Results: The proalbuminemia were significantly increased after IMT, and the HBsAg and TBA showed a significant decrease after IMT in the HBV-CLD patients. There was statistical difference in the Chaol indexes between between CHB patients and healthy controls, suggesting a lower abundance of the gut microbiota in HBV-CLD patients. In addition, there was statistical difference in the Shannon and Simpson indexes between prior to IMT and post-IMT, indicating that the impaired abundance of the gut microbiota had been improved after IMT. The host-microbiota-metabolite interplay, amino acid metabolism, nicotinate and nicotinamide metabolism, starch and sucrose metabolism, steroid biosynthesis, and vitamins metabolism, were significantly lower in HBV-CLD patients than healthy controls. Conclusion: IMT may improve the therapeutic effects on patients HBV-CLD. Furthermore, IMT appears to improve amino acid metabolism by impaired abundance of the gut microbiota and therefore improve liver prealbumin synthesis.

Air pollutants and the risk of incident hepatobiliary diseases: A large prospective cohort study in the UK Biobank.

The association between air pollutants and hepatobiliary pancreatic diseases remains inconclusive. This study analyzed up to 247,091 participants of White European ancestry (aged 37 to 73 years at recruitment) from the UK Biobank, a large-scale prospective cohort with open access. An air pollution score was utilized to assess the combined effect of PM2.5, PM2.5-10, PM10, NO2, and NOX on total hepatobiliary pancreatic diseases, liver diseases, cholecyst diseases, and pancreatic diseases. Cox proportional hazard models were employed to evaluate the relationships between air pollutants and the incidence of these diseases. Restricted cubic spline regressions were used to examine the dose-response association between air pollutants and the risk of hepatobiliary pancreatic diseases. We identified 4865 cases of total hepatobiliary pancreatic diseases, over a median follow-up of 10.86 years. The air pollution scores were moderately associated with increased liver disease risk (HR = 1.009, 95 % CI: 1.004, 1.014), but not with cholecyst and pancreatic diseases. Among the individual air pollutants, PM2.5 (HR = 1.069, 95 % CI: 1.025, 1.115) and PM10 (HR = 1.036, 95 % CI: 1.011, 1.061) significantly increased liver disease risk. Males showed a higher risk of liver diseases with PM2.5 (HR = 1.075, 95 % CI: 1.015, 1.139). Additionally, individuals with overweight (HR = 1.125, 95 % CI: 1.052, 1.203), age ≥ 60 and ≤73 (HR = 1.098, 95 % CI: 1.028, 1.172), and alcohol intake ≥ 14 unit/week (HR = 1.078, 95 % CI: 1.006, 1.155) had a higher risk of developing liver diseases at high expose to PM2.5. This study suggests that prolonged exposure to ambient air pollutants may elevate the risk of liver diseases.

Life cycle assessment of plastic waste in Suzhou, China: Management strategies toward sustainable express delivery.

The explosive growth of China's express delivery industry has greatly increased plastic waste, with low-value plastics not effectively utilized, such as PE packaging bags, which are often not recycled and end up in landfills or incinerators, causing significant resource waste and severe plastic pollution. A gate -to- grave life cycle assessment was adopted to assess the impacts of express delivery plastic waste (EDPW) management models (S1, landfill; S2, incineration; S3, mechanical pelletization), with Suzhou, China as a case. Results showed that mechanical pelletization, was the most environmentally advantageous, exhibiting a comprehensive environmental impact potential of -215.54 Pt, significantly lower than that of landfill (S1, 78.45 Pt) and incineration (S2, -121.77 Pt). The analysis identified that the end-of-life disposal and sorting stages were the principal contributors to environmental impacts in all three models, with transportation and transfer stages of residual waste having minimal effects. In terms of all environmental impact categories, human carcinogenic toxicity (HTc) emerged as the most significant contributor in all three scenarios. Specifically, S1 exhibited the most detrimental effect on human health, while S2 and S3 showed positive environmental impacts. Based on these findings, it is recommended that the application and innovation in mechanical recycling technologies be enhanced, the promotion of the eco-friendly transformation of packaging materials be pursued, and a sustainable express delivery packaging recycling management system be established. These strategies are essential for achieving more eco-friendly management of EDPW, reducing its environmental pollution, and moving towards more sustainable express delivery management practices.

Enhancing Vibrio vulnificus infection diagnosis for negative culture patients with metagenomic next-generation sequencing.

Objective: To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) in Vibrio vulnificus (V. vulnificus) infection. Methods: A retrospective analysis of patients with V. vulnificus infection at the Fifth Affiliated Hospital of Sun Yat-Sen University from January 1, 2020 to April 23, 2023 was conducted. 14 enrolled patients were diagnosed by culture or mNGS. The corresponding medical records were reviewed, and the clinical data analyzed included demographics, epidemiology laboratory findings, physical examination, symptoms at presentation, antibiotic and surgical treatment, and outcome. Results: In this study, 78.6% (11/14) patients had a history of marine trauma (including fish stab, shrimp stab, crab splints and fish hook wounds), 7.1% (1/14) had eaten seafood, and the remaining 14.3% (2/14) had no definite cause. Isolation of V. vulnificus from clinical samples including blood, tissue, fester and secreta. 9 cases were positive for culture, 5 cases were detected synchronously by mNGS and got positive for V. vulnificus. 85.7% (12/14) cases accepted surgical treatment, with 1 patient suffering finger amputated. 14 enrolled patients received appropriate antibiotic therapy, and all of them had recovered and discharged. 9 strains V. vulnificus isolated in this study were sensitive to most beta-lactam antibiotics, aminoglycosides, quinolones, etc. Conclusion: Vibrio vulnificus infection is a common water-exposed disease in Zhuhai, which requires identification of a number of pathogens. Of severe infections with unknown pathogen, mNGS can be used simultaneously, and the potential to detect multiple pathogens is of great help in guiding treatment.

Weil's Disease in an HIV-Infected Patient: A Case Report and Literature Review.

Weil's disease, an icterohemorrhagic infection, is the most severe and fatal form of leptospirosis and is characterized by jaundice, renal dysfunction, and hemorrhagic predisposition. Weil's disease with HIV infection has rarely been reported. A 68-year-old male with HIV infection presented to our hospital with fever and dyspnea that progressed to severe hemoptysis and systemic multiple organ failure, necessitating a tracheal intubation ventilator. A diagnosis of Weil's disease was made after Leptospira interrogans was identified via metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF). After immediately receiving supportive therapy and targeted antimicrobial agents, the patient achieved complete recovery upon discharge. The co-infection of HIV infection and leptospirosis resulting in systemic multi-organ failure is rare, but awareness should be raised of the differential diagnosis. mNGS can help identify pathogens and facilitate the use of targeted and efficacious antimicrobial therapy in unusual clinical environments.

Appropriateness of Empirical Antibiotic Therapy in Hospitalized Patients with Bacterial Infection: A Retrospective Cohort Study.

Objective: The incidence of inappropriate and excessive empirical antibiotic therapy is unclear. The aim of this study was to determine the prevalence of different empirical antibiotic therapy prescriptions, related factors, and outcomes in hospitalized patients with bacterial infection. Methods: A retrospective cohort study was performed and patients with bacterial infection who were admitted between October 1, 2019, and September 30, 2020, were included. Multivariable analysis was performed by the logistic regression model. Results: A total of 536 (42.6%) of the 1257 included patients received inappropriate empirical antibiotic therapy (IEAT), and 368 (29.3%) patients received appropriate but unnecessarily broad-spectrum empirical antibiotic therapy (AUEAT). MDRO (adjusted OR 2.932 [95% CI 2.201~3.905]; p < 0.001) and fever on admission (adjusted OR 0.592 [95% CI 0.415~0.844]; p = 0.004) were correlates of IEAT; sepsis (adjusted OR 2.342 [95% CI 1.371~3.999]; p = 0.002), age (adjusted OR 1.019 [95% CI 1.008~1.030]; p < 0.001), MDRO (adjusted OR 0.664 [95% CI 0.469~0.941]; p = 0.021), and urinary tract infection (adjusted OR 0.352 [95% CI 0.203~0.611]; p < 0.001) were correlates of AUEAT. Patients who received AUEAT were more likely to have a poor prognosis (63 [17.8%] vs 101 [27.4%]; p = 0.002). Both IEAT (median [IQR], 24,971 [13,135-70,155] vs 31,489 [14,894-101,082] CNY; p = 0.007) and AUEAT (median [IQR], 24,971 [13,135-70,155] vs 30,960 [16,475-90,881] CNY; p = 0.002) increased hospital costs. 45.3% (570/1257) of patients were infected with MDRO and 62.9% of them received IEAT. Conclusion: Inappropriate and excessive empirical antibiotic use was widely prevalent among hospitalized patients. Either inappropriate or excessive use of antibiotics may increase the burden of healthcare costs, the latter of which may be associated with poor prognosis. Clinicians need to be more judicious in choosing antibiotic(s). The MDRO epidemic was severe, especially in patients who received IEAT. It is imperative to take effective measures to improve the current situation of antibiotic abuse and antimicrobial resistance.

Wogonin inhibits latent HIV-1 reactivation by downregulating histone crotonylation.

BACKGROUND: Wogonin, a flavone isolated from Scutellaria baicalensis Georgi, is a commonly used phytochemical with anti-inflammatory and antitumor properties. However, the antiviral activity of wogonin against human immunodeficiency virus type 1 (HIV-1) has not been reported. PURPOSE: The current study aimed to explore whether wogonin can suppress latent HIV-1 reactivation and the mechanism of wogonin in inhibiting proviral HIV-1 transcription. METHODS: We assessed the effects of wogonin on HIV-1 reactivation using flow cytometry, cytotoxicity assay, quantitative PCR (qPCR), viral quality assurance (VQA), and western blot analysis. RESULTS: Wogonin, a flavone isolated from S. baicalensis, significantly inhibited the reactivation of latent HIV-1 in cellular models and in primary CD4+ T cells from antiretroviral therapy (ART)-suppressed individuals ex vivo. Wogonin exhibited low cytotoxicity and long-lasting inhibition of HIV-1 transcription. Triptolide is a latency-promoting agent (LPA) that inhibits HIV-1 transcription and replication; wogonin had a stronger ability to inhibit HIV-1 latent reactivation than triptolide. Mechanistically, wogonin inhibited the reactivation of latent HIV-1 by inhibiting the expression of p300, a histone acetyltransferase, and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. CONCLUSION: Our study found that wogonin is a novel LPA that can inhibit HIV-1 transcription by HIV-1 epigenetic silencing, which could bear promising significance for future applications of HIV-1 functional cure.

Combined effects of light pollution and vegetation height on behavior and body weight in a nocturnal rodent.

At a global scale, organisms are under threat due to various kinds of environmental changes, such as artificial light at night (ALAN), noise, climatic change and vegetation destruction. Usually, these changes co-vary in time and space and may take effect simultaneously. Although impacts of ALAN on biological processes have been well documented, our knowledge on the combined effects of ALAN and other environmental changes on animals remains limited. In this study, we conducted field experiments in semi-natural enclosures to explore the combined effects of ALAN and vegetation height on foraging behavior, vigilance, activity patterns and body weight in dwarf striped hamsters (Cricetulus barabensis), a nocturnal rodent widely distributed in East Asia. We find that ALAN and vegetation height affected different aspects of behavior. ALAN negatively affected search speed and positively affected handling speed, while vegetation height negatively affected giving-up density and positively affected body weight. ALAN and vegetation height also additively shaped total time spent in a food patch. No significant interactive effect of ALAN and vegetation height was detected. C. barabensis exposed to ALAN and short vegetation suffered a significant loss in body weight, and possessed a much narrower temporal niche (i.e. initiated activity later but became inactive earlier) than those under other combinations of treatments. The observed behavioral responses to ALAN and changes in vegetation height may bring fitness consequences, as well as further changes in structure and functioning of local ecosystems.

Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection.

Whether hypervariable region 1 (HVR1)-targeting antibodies elicited during natural hepatitis C virus (HCV) infection contribute to virus clearance and what is the mechanism underlying remain unclear. Here, we demonstrated that treatment of HCV-infected hepatoma Huh7.5 cells with the IgGs purified from 2 of 28 (7.1%) chronic hepatitis C (CHC) patients efficiently controlled the infection, for which genotype 1b HVR1 (1bHVR1)-binding antibody was critical. Moreover, we found that 1bHVR1 peptide was superior to 2aHVR1 in rabbit immunization to elicit antibodies neutralizing genotypes 1a, 2a, 3a, and 4a. The neutralization effect of 1bHVR1 IgG could be augmented by HH-1, an antibody constructed from CHC memory B cells but without binding to HVR1 peptide. Mechanistic studies showed that 1bHVR1 antisera and IgGs disrupted the interaction of E2-SR-B1 receptor. This study highlights the neutralizing activity of HVR1 antibody elicited by CHC patients and generated by HVR1-immunization against the established infections of multiple HCV genotypes.

Leukocyte Immunoglobulin-like Receptor A5 Deletion Aggravates the Pathogenesis of Pseudomonas aeruginosa Keratitis by Promoting Proinflammatory Cytokines.

PURPOSE: The purpose of this study was to assess the role of leukocyte immunoglobulin-like receptor A5 (LILRA5) in regulating bacterial infection and corneal inflammation. METHODS: The human corneal tissue microarray data set GSE58291 from Gene Expression Omnibus was downloaded. Then, the differentially expressed genes, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis, and the immune infiltration analysis were conducted. We constructed the Pseudomonas aeruginosa ( P. aeruginosa ) keratitis mice model using wild-type and LILRA5-deficient mice. The results of the bioinformatics analysis were verified by the cell in vitro and animal in vivo experiments. RESULTS: This study revealed that LILRA5 is substantially expressed in human keratitis and regulates the immune response negatively. Neutrophils were identified as the core fraction of immune cells in keratitis. After P. aeruginosa infection, neutrophils lacking LILRA5 induced elevated levels of proinflammatory cytokines and toll-like receptor 4. LILRA5 deficiency exacerbated the severity of the infection and the production of proinflammatory cytokines in mice. CONCLUSIONS: LILRA5 was discovered as an immunosuppressive regulator in P. aeruginosa keratitis, highlighting its significance in activated immune responses.

Progress of the COVID-19: Persistence, Effectiveness, and Immune Escape of the Neutralizing Antibody in Convalescent Serum.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a new coronavirus causing Coronavirus Disease 2019 (COVID-19), is a major topic of global human health concern. The Delta and Omicron variants have caused alarming responses worldwide due to their high transmission rates and a number of mutations. During a one-year follow-up (from June 2020 to June 2021), we included 114 patients with SARS-CoV-2 infection to study the long-term dynamics and the correlative factors of neutralizing antibodies (NAbs) in convalescent patients. The blood samples were collected at two detection time points (at 6 and 12 months after discharge). We evaluated the NAbs response of discharged patients by performing a micro-neutralization assay using a SARS-CoV-2 wild type. In addition, a total of 62 serum samples from discharged COVID-19 patients with Alpha, Beta, Delta, and Omicron variants of infection were enrolled to perform cross-neutralization tests using the original SARS-CoV-2 strain and VOCs variants (including Alpha, Beta, Gamma, Delta, and Omicron variants) and to assess the ability of NAbs against the SARS-CoV-2 variants. NAbs seroconversion occurred in 91.46% of patients (n = 82) in the first timepoint and in 89.29% of patients (n = 84) in the second detection point, and three kinds of NAbs kinetics curves were perceived. The NAbs levels in young patients had higher values than those in elder patients. The kinetics of disease duration was accompanied by an opposite trend in NAbs levels. Despite a declining NAbs response, NAbs activity was still detectable in a substantial proportion of recovered patients one year after discharge. Compared to the wild strain, the Omicron strain could lead to a 23.44-, 3.42-, 8.03-, and 2.57-fold reduction in neutralization capacity in "SAlpha", "SBeta", "SDelta", and "SOmicron", respectively, and the NAbs levels against the Omicron strain were significantly lower than those of the Beta and Delta variants. Remarkably, the NAbs activity of convalescent serum with Omicron strain infection was most obviously detectable against six SARS-CoV-2 strains in our study. The role of the vaccination history in NAbs levels further confirmed the previous study that reported vaccine-induced NAbs as the convincing protection mechanism against SARS-CoV-2. In conclusion, our findings highlighted the dynamics of the long-term immune responses after the disappearance of symptoms and revealed that NAbs levels varied among all types of convalescent patients with COVID-19 and that NAbs remained detectable for one year, which is reassuring in terms of protection against reinfection. Moreover, a moderate correlation between the duration of disease and Nabs titers was observed, whereas age was negatively correlated with Nabs titers. On the other hand, compared with other VOCs, the Omicron variant was able to escape the defenses of the immune system more significantly, and the convalescent serum infected with the Omicron variant played a critical part in protection against different SARS-CoV-2 variants. Recovery serum from individuals vaccinated with inactivated vaccine preceding infection with the Omicron strain had a high efficacy against the original strain and the VOCs variants, whereas the convalescent serum of persons vaccinated by inactivated vaccine prior to infection with the Delta variant was only potent against the wild-type strain.

Trace Analysis of Emerging Virus: An Ultrasensitive ECL-Scan Imaging System for Viral Infectious Disease.

Emerging infectious diseases have brought a huge impact on human society in recent years. The outbreak of Zika virus (ZIKV) in the Americas resulted in a large number of babies born with microcephaly. More seriously, the Coronavirus Disease 2019 (COVID-19) was globally spread and caused immeasurable damages. Thus, the monitoring of highly pathogenic viruses is important to prevent and control emerging infectious diseases. Herein, a dendritic polymer probe-amplified ECL-scan imaging system was constructed to realize trace analysis of viral emerging infectious diseases. A dendritic polymer probe was employed as the efficient signal emitter component that could generate an amplified ECL signal on the integrated chip, and the signal was detected by a single-photon level charge coupled device-based ECL-scan imaging system. With this strategy, the ZIKV in a complex system of blood, urine, and saliva was detected. The results indicated that a high sensitivity of 50 copies and superior specificity were achieved. Furthermore, this strategy realized highly sensitive detection (10 copies) of the S and N protein gene sequence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov2) and spiked pseudovirus samples. Thus, the dendritic polymer probe-amplified ECL-scan imaging system suitably met the strict clinical requirements for trace analysis of an emerging virus, and thus has the potential to serve as a paradigm for monitoring emerging infectious diseases.

Whole-Genome Sequencing Reveals the High Nosocomial Transmission and Antimicrobial Resistance of Clostridioides difficile in a Single Center in China, a Four-Year Retrospective Study.

Clostridioides difficile, which causes life-threatening diarrheal disease, presents an urgent threat to health care systems. In this study, we present a retrospective genomic and epidemiological analysis of C. difficile in a large teaching hospital. First, we collected 894 nonduplicate fecal samples from patients during a whole year to elucidate the C. difficile molecular epidemiology. We then presented a detailed description of the population structure of C. difficile based on 270 isolates separated between 2015 and 2020 and clarified the genetic and phenotypic features by MIC and whole-genome sequencing. We observed a high carriage rate (19.4%, 173/894) of C. difficile among patients in this hospital. The population structure of C. difficile was diverse with a total of 36 distinct STs assigned. In total, 64.8% (175/270) of the isolates were toxigenic, including four CDT-positive (C. difficile transferase) isolates, and 50.4% (135/268) of the isolates were multidrug-resistant. Statistically, the rates of resistance to erythromycin, moxifloxacin, and rifaximin were higher for nontoxigenic isolates. Although no vancomycin-resistant isolates were detected, the MIC for vancomycin was higher for toxigenic isolates (P < 0.01). The in-hospital transmission was observed, with 43.8% (110/251) of isolates being genetically linked to a prior case. However, no strong correlation was detected between the genetic linkage and epidemiological linkage. Asymptomatic colonized patients play the same role in nosocomial transmission as infected patients, raising the issue of routine screening of C. difficile on admission. This work provides an in-depth description of C. difficile in a hospital setting and paves the way for better surveillance and effective prevention of related diseases in China. IMPORTANCE Clostridioides difficile infections (CDI) are the leading cause of healthcare-associated diarrhea and are known to be resistant to multiple antibiotics. In the past decade, C. difficile has emerged rapidly and has spread globally, causing great concern among American and European countries. However, research on CDI remains limited in China. Here, we characterized the comprehensive spectrum of C. difficile by whole-genome sequencing (WGS) in a Chinese hospital, showing a high detection rate among patients, diverse genome characteristics, a high level of antibiotic resistance, and an unknown nosocomial transmission risk of C. difficile. During the study period, two C. difficile transferase (CDT)-positive isolates belonging to a new multilocus sequence type (ST820) were detected, which have caused serious clinical symptoms. This work describes C. difficile integrally and provides new insight into C. difficile surveillance based on WGS in China.

Dolutegravir plus lamivudine versus efavirenz plus tenofovir disoproxil fumarate and lamivudine in antiretroviral-naive adults with HIV-1 infection.

BACKGROUND: Concerns regarding potential toxicity and drug-drug interactions during long-term treatment with three-drug active antiretroviral therapy (ART) regimens have been attracting increasing attention. We aimed to evaluate the efficacy and safety of dolutegravir (DTG) plus lamivudine (3TC) in ART-naive adults in China. METHODS: This prospective observational cohort study enrolled HIV-naive inpatients treated with DTG + 3TC (2DR arm) or efavirenz (EFV) plus tenofovir disoproxil fumarate (TDF) and 3TC (3DR arm). There were no limits on baseline viral load. Inflammatory biomarkers were also investigated in the 2DR arm. RESULTS: Between September 2019 and January 2020, 27 patients treated with DTG + 3TC and 28 patients treated with EFV + TDF + 3TC were enrolled in the study. At week 12, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 81.5% (22/27) compared with 53.6% (15/28) in the 3DR arm (p < 0.01). At week 24, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 100% (26/26) compared with 83.3% (20/24) in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 12 were 125.46 cells/µL in the 2DR arm and 41.20 cells/µL in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 24 were 209.68 cells/µL in the 2DR arm and 73.28 cells/µL in the 3DR arm (p < 0.05). CONCLUSIONS: DTG + 3TC achieved virologic suppression more rapidly than EFV + TDF + 3TC after 12 and 24 weeks. DTG + 3TC could represent an optimal regimen for advanced patients. Clinical Trial Registration ChiCTR1900027640 (22/November/2019).

Pradefovir Treatment in Patients With Chronic Hepatitis B: Week 24 Results From a Multicenter, Double-Blind, Randomized, Noninferiority, Phase 2 Trial.

BACKGROUND: Pradefovir is a liver-targeted prodrug of adefovir, a nucleoside/nucleotide analogue with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30, 45, 60, or 75 mg) versus tenofovir disoproxil fumarate (TDF; 300 mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study. METHODS: Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible. RESULTS: A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were hepatitis B e antigen (HBeAg) positive, and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/mL, with pradefovir doses of 30-, 45-, 60-, and 75-mg, respectively, compared with 5.12 log10 IU/mL with TDF. However, HBeAg loss was attained by more participants who received 45-, 60-, or 75-mg pradefovir than by those receiving TDF (12%, 6%, and 9% vs 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30- and 45-mg groups, and serum phosphate levels were comparable among all groups. Most adverse events (AEs) were mild (grade 1). No treatment-related severe AEs were reported. Overall, AEs and laboratory abnormalities were comparable to those in the TDF group. CONCLUSIONS: Pradefovir and TDF exhibited comparable reductions in HBV DNA levels. All treatments were safe and well tolerated. CLINICAL TRIALS REGISTRATION: NCT00230503 and China Drug Trials CTR2018042.

Pathogen Metagenomics Reveals Distinct Lung Microbiota Signatures Between Bacteriologically Confirmed and Negative Tuberculosis Patients.

Understanding the dynamics of lung microbiota in tuberculosis patients, especially those who cannot be confirmed bacteriologically in clinical practice, is imperative for accurate diagnosis and effective treatment. This study aims to characterize the distinct lung microbial features between bacteriologically confirmed and negative tuberculosis patients to understand the influence of microbiota on tuberculosis patients. We collected specimens of bronchoalveolar lavage fluid from 123 tuberculosis patients. Samples were subjected to metagenomic next-generation sequencing to reveal the lung microbial signatures. By combining conventional bacterial detection and metagenomic sequencing, 101/123 (82%) tuberculosis patients were bacteriologically confirmed. In addition to Mycobacterium tuberculosis, Staphylococcus aureus, Kluyveromyces lactis, and Pyricularia pennisetigena were also enriched in the bacteriological confirmation group. In contrast, Haemophilus parainfluenzae was enriched in the bacteriologically negative group. Besides, microbial interaction exhibits a different state between bacteriologically confirmed and negative tuberculosis patients. Mycobacterium tuberculosis was confirmed correlated with clinical characteristics such as albumin and chest cavities. Our study comprehensively demonstrates the correlation between unique features of lung microbial dynamics and the clinical characteristics of tuberculosis patients, suggesting the importance of studying the pulmonary microbiome in tuberculosis disease and providing new insights for future precision diagnosis and treatment.

The epidemic of Q fever in 2018 to 2019 in Zhuhai city of China determined by metagenomic next-generation sequencing.

Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018-2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China.

Antibody Responses and the Effects of Clinical Drugs in COVID-19 Patients.

The coronavirus disease 2019 (COVID-19) emerged around December 2019 and have become a global epidemic disease currently. Specific antibodies against SAS-COV-2 could be detected in COVID-19 patients' serum or plasma, but the clinical values of these antibodies as well as the effects of clinical drugs on humoral responses have not been fully demonstrated. In this study, 112 plasma samples were collected from 36 patients diagnosed with laboratory-confirmed COVID-19 in the Fifth Affiliated Hospital of Sun Yat-sen University. The IgG and IgM antibodies against receptor binding domain (RBD) and spike protein subunit 1 (S1) of SAS-COV-2 were detected by ELISA. We found that COVID-19 patients generated specific antibodies against SARS-CoV-2 after infection, and the levels of anti-RBD IgG within 2 to 3 weeks from onset were negatively associated with the time of positive-to-negative conversion of SARS-CoV-2 nucleic acid. Patients with severe symptoms had higher levels of anti-RBD IgG in 2 to 3 weeks from onset. The use of chloroquine did not significantly influence the patients' antibody titer but reduced C-reaction protein (CRP) level. Using anti-viral drugs (lopinavir/ritonavir or arbidol) reduced antibody titer and peripheral lymphocyte count. While glucocorticoid therapy developed lower levels of peripheral lymphocyte count and higher levels of CRP, lactate dehydrogenase (LDH), α-Hydroxybutyrate dehydrogenase(α-HBDH), total bilirubin (TBIL), direct bilirubin (DBIL). From these results, we suggested that the anti-RBD IgG may provide an early protection of host humoral responses against SAS-COV-2 infection within 2 to 3 weeks from onset, and clinical treatment with different drugs displayed distinct roles in humoral and inflammatory responses.

A predictive score for progression of COVID-19 in hospitalized persons: a cohort study.

Accurate prediction of the risk of progression of coronavirus disease (COVID-19) is needed at the time of hospitalization. Logistic regression analyses are used to interrogate clinical and laboratory co-variates from every hospital admission from an area of 2 million people with sporadic cases. From a total of 98 subjects, 3 were severe COVID-19 on admission. From the remaining subjects, 24 developed severe/critical symptoms. The predictive model includes four co-variates: age (>60 years; odds ratio [OR] = 12 [2.3, 62]); blood oxygen saturation (<97%; OR = 10.4 [2.04, 53]); C-reactive protein (>5.75 mg/L; OR = 9.3 [1.5, 58]); and prothrombin time (>12.3 s; OR = 6.7 [1.1, 41]). Cutoff value is two factors, and the sensitivity and specificity are 96% and 78% respectively. The area under the receiver-operator characteristic curve is 0.937. This model is suitable in predicting which unselected newly hospitalized persons are at-risk to develop severe/critical COVID-19.

Association between Nonalcoholic Fatty Liver Disease and Bone Mineral Density in HIV-Infected Patients Receiving Long-term TDF-Based Antiretroviral Therapy.

BACKGROUND: Tenofovir (TDF) has a detrimental effect on bone mineral density (BMD), while nonalcoholic fatty liver disease (NAFLD) is associated with a lower BMD. OBJECTIVE: To help understand the mutual effects of NAFLD and TDF on BMD, this study was designed to explore the potential association between NAFLD and BMD in HIV-infected patients receiving long-term TDF-based antiretroviral therapy (ART). METHODS: A total of 89 HIV-infected patients who received TDF-based ART for more than three years were enrolled in this cross-sectional study. We measured BMD using an ultrasonic bone density apparatus, and liver ultrasonography was performed to determine the severity of the fatty liver. The association of NAFLD with BMD was examined using multiple logistic regression analyses. RESULTS: Patients with NAFLD showed a worse BMD status than those without NAFLD. The incidence rates of osteopenia (42.86% versus 25.93%) and osteoporosis (17.14% versus 3.70%) were significantly higher in HIV-infected patients with NAFLD than in those without NAFLD. After multivariate adjustment, the odds ratio (OR) for patients with NAFLD exhibiting a worse BMD status compared with those without NAFLD was 4.49 (95% confidence interval [CI] 1.42, 14.15). CONCLUSION: Based on our results, NAFLD was significantly associated with a worse BMD status, including osteopenia and osteoporosis, in HIV patients after receiving long-term TDF-based ART. Furthermore, we may want to avoid using TDF for ART in HIV-infected patients with NAFLD.