Single-cell RNA sequencing in tuberculosis: Application and future perspectives.

ABSTRACT: Tuberculosis (TB) has one of the highest mortality rates among infectious diseases worldwide. The immune response in the host after infection is proposed to contribute significantly to the progression of TB, but the specific mechanisms involved remain to be elucidated. Single-cell RNA sequencing (scRNA-seq) provides unbiased transcriptome sequencing of large quantities of individual cells, thereby defining biological comprehension of cellular heterogeneity and dynamic transcriptome state of cell populations in the field of immunology and is therefore increasingly applied to lung disease research. Here, we first briefly introduce the concept of scRNA-seq, followed by a summarization on the application of scRNA-seq to TB. Furthermore, we underscore the potential of scRNA-seq for clinical biomarker exploration, host-directed therapy, and precision therapy research in TB and discuss the bottlenecks that need to be overcome for the broad application of scRNA-seq to TB-related research.

PegIFN alpha-2a reduces relapse in HBeAg-negative patients after nucleo(s)tide analogue cessation: A randomized-controlled trial.

BACKGROUND & AIMS: Nucleo(s)tide analogue (NUC) cessation can lead to hepatitis B surface antigen (HBsAg) clearance but also a high rate of virological relapse. However, the effect of pegylated interferon alpha-2a (PegIFN-α-2a) on virological relapse after NUC cessation is unknown. Therefore, this study aimed to evaluate the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse up to week 96. METHODS: In this multicenter randomized-controlled clinical trial, 180 non-cirrhotic patients with HBeAg-negative chronic hepatitis B on continuous NUC therapy for ≥2.5 years, with HBV DNA levels <60 IU/ml, were randomized to discontinue NUC therapy (n = 90) or receive 48 weeks of PegIFN-α-2a treatment (n = 90). Patients were followed up for up to 96 weeks. The primary endpoint was the virological relapse rate up to week 96. RESULTS: Intention-to-treat analysis revealed patients in the interferon monotherapy group had significantly lower cumulative virological relapse rates than the NUC cessation group until week 96 (20.8% vs. 53.6%, p <0.0001). Consistently, a significantly lower proportion of patients in the interferon monotherapy group had virological relapse than those in the NUC cessation group at 48 weeks off treatment (17.8% vs. 36.7%, p = 0.007). The virological relapse rate positively correlated with HBsAg levels in the NUC cessation group. The interferon monotherapy group had a lower cumulative clinical relapse rate (7.8% vs. 20.9%, p = 0.008) and a higher HBsAg loss rate (21.5% vs. 9.0%, p = 0.03) than the NUC cessation group. CONCLUSIONS: Switching from NUC to PegIFN-α-2a treatment for 48 weeks significantly reduces virological relapse rates and leads to higher HBsAg loss rates than NUC treatment cessation alone in patients with HBeAg-negative chronic hepatitis B. IMPACT AND IMPLICATIONS: Nucleo(s)tide analogue (NUC) cessation can lead to HBsAg clearance but also a high rate of virological relapse, but an optimized scheme to reduce the virological relapse rate after NUC withdrawal is yet to be reported. This randomized-controlled trial investigated the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse up to week 96 in patients with HBeAg-negative chronic hepatitis B. The interferon monotherapy group had a significantly lower cumulative virological relapse rate (20.8% vs. 53.6%, p <0.0001) and higher HBsAg loss rate (21.5% vs. 9.0%, p = 0.03) than the NUC cessation group up to week 96. This provides an optimized strategy for NUC cessation in HBeAg-negative patients. TRIAL REGISTRATION NUMBER: NCT02594293.

Double-sided microstructured flexible iontronic pressure sensor with wide linear sensing range.

Iontronic pressure sensors have garnered significant attention for their potential in wearable electronic devices. While simple microstructures can enhance sensor sensitivity, the majority of them predominantly amplify sensitivity at lower pressure ranges and fail to enhance sensitivity at higher pressure ranges, leading to nonlinearity. In the absence of linear sensitivity in a pressure sensor, users are unable to derive precise information from its output, necessitating further signal processing. Hence, crafting a linearity flexible pressure sensor through a straightforward approach remains a formidable task. Herein, a double-sided microstructured flexible iontronic pressure sensor is presented with wide linear sensing range. The ionic gel is made by 1-Ethyl-3-methylimidazolium bis(tri-fluoromethylsulfonyl)imide (EMIM:TFSI) into the matrix of poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP), which acts as active layer, featuring irregular microstructures (IMS) and pyramid microstructures (PMS) on both sides. Unlike previous complex methods, IMS and uniform PMS are easily and achieved through pattern transfer from a sandpaper mold and micro-pyramid template. The iontronic pressure sensor exhibits exceptional signal linearity with R2 values of 0.9975 and 0.9985, in the wide pressure range from 100 to 760 kPa and 760 kPa to 1000 kPa, respectively. This outstanding linearity and wide sensing range stem from a delicate balance between microstructure compression and mechanical alignment at the ionic gel interface. This study provides valuable insights into achieving linear responses by strategically designing microstructures in flexible pressure sensors, with potential applications in intelligent robots and health monitoring.

Proteomic and Cellular Characterization of Omicron Breakthrough Infections and a Third Homologous or Heterologous Boosting Vaccination in a Longitudinal Cohort.

The understanding of dynamic plasma proteome features in hybrid immunity and breakthrough infection is limited. A deeper understanding of the immune differences between heterologous and homologous immunization could assist in the future establishment of vaccination strategies. In this study, 40 participants who received a third dose of either a homologous BBIBP-CorV or a heterologous ZF2001 protein subunit vaccine following two doses of inactivated coronavirus disease 2019 vaccines and 12 patients with BA2.2 breakthrough infections were enrolled. Serum samples were collected at days 0, 28, and 180 following the boosting vaccination and breakthrough and then analyzed using neutralizing antibody tests and mass spectrometer-based proteomics. Mass cytometry of peripheral blood mononuclear cell samples was also performed in this cohort. The chemokine signaling pathway and humoral response markers (IgG2 and IgG3) associated with infection were found to be upregulated in breakthrough infections compared to vaccination-induced immunity. Elevated expression of IGKV, IGHV, IL-17 signaling, and the phagocytosis pathway, along with lower expression of FGL2, were correlated with higher antibody levels in the boosting vaccination groups. The MAPK signaling pathway and Fc gamma R-mediated phagocytosis were more enriched in the heterologous immunization groups than in the homologous immunization groups. Breakthrough infections can trigger more intensive inflammatory chemokine responses than vaccination. T-cell and innate immune activation have been shown to be closely related to enhanced antibody levels after vaccination and therefore might be potential targets for vaccine adjuvant design.

Clinical Characteristics, Treatment, and Prognosis of Osteoarticular Brucellosis: A Retrospective Real-World Study in Shenyang, China, 2014-2019.

This study aimed to assess the clinical characteristics, treatment, and prognosis of osteoarticular brucellosis. We conducted a retrospective study enrolling brucellosis patients from the Sixth People's Hospital of Shenyang between September 2014 and June 2019. A total of 1917 participants were admitted during this period. After applying propensity score matching, we retrospectively analyzed 429 patients with osteoarthritis and 429 patients without osteoarthritis. The primary outcome was treatment completion. The secondary outcome was symptom disappearance and seroconversion. Brucellosis patients with osteoarthritis had longer treatment course (160 [134.3-185.7] vs. 120 [102.3-137.7] d, p = 0.008) than those without osteoarthritis. The most common involved site was lumbar vertebrae (290 [67.6%]) in brucellosis patients with osteoarthritis. Longer symptom duration (90 [83.0-97.0] vs. 42 [40.2-43.8], p < 0.001) along with no significant difference in seroconversion (180 [178.8-181.2] vs. 180 [135.1-224.9], p = 0.212) was observed in osteoarthritis patients with treatment course >90 d. Peripheral joint involvement (adjusted hazard ratio [95% confidence interval] 1.485 [1.103-1.999]; p = 0.009) had a shorter symptom duration compared with shaft joint involvement. No significant differences were observed in treatment therapy between doxycycline plus rifampin (DR) or plus cephalosporins (DRC) in treatment course (p = 0.190), symptom persistence (p = 0.294), and seroconversion (p = 0.086). Lumbar vertebra was the most commonly involved site. Even if all symptoms disappeared, Serum agglutination test potentially remained positive in some patients. Compared with peripheral arthritis, shaft arthritis was the high-risk factor for longer symptom duration. The therapeutic effects were similar between DR and DRC. In summary, our study provided important insights into the clinical characteristics, treatment, and outcomes of osteoarticular brucellosis. Clinical Trial Registration number: NCT04020536.

The Psychometric Properties of the Chinese version of the Interoceptive Awareness Questionnaire (IAQ) among PATIENTS WITH Cardiovascular Disease.

BACKGROUND: Interoceptive awareness (perception of body conditions and processes) and heart rate variability are connected physiologically in cardiovascular disease (CVD) patients. At present, there is no specific evaluation model for the perception of the physical state and processes of CVD patients in China. OBJECTIVES: The objective of this study is to examine the reliability and validity of the Chinese Interoceptive Awareness Questionnaire (C-IAQ) for Chinese CVD patients. METHODS: 160 CVD patients were recruited from a hospital in Hubei province using a convenient sampling method. A standard "forward-backward" translation method was applied to convert the C-IAQ into Mandarin. Split-half reliability and internal consistency were conducted by using reliability tests. Validity testing was conducted on the content, structure, and criterion-related validity. Criterion-related validity was assessed by using the Anxiety Sensitivity Index-III (ASI-III). RESULTS: The research results indicate that the dual factor structure of the original C-IAQ has 19 items, including attention to unpleasant sensations (9 items) and awareness of neutral body sensations (10 items). Moreover, C-IAQ is positively correlated with ASI-III (r = 0.48, P<0.01). The entire scale has a Cronbach's α value of 0.85 and split-half dependability of 0.77. CONCLUSION: The C-IAQ has favorable psychometric feature. Hence, it can be used to measure the interoceptive awareness of CVD patients.

Vaccination Shapes Within-Host SARS-CoV-2 Diversity of Omicron BA.2.2 Breakthrough Infection.

BACKGROUND: Low-frequency intrahost single-nucleotide variants of SARS-CoV-2 have been recognized as predictive indicators of selection. However, the impact of vaccination on the intrahost evolution of SARS-CoV-2 remains uncertain at present. METHODS: We investigated the genetic variation of SARS-CoV-2 in individuals who were unvaccinated, partially vaccinated, or fully vaccinated during Shanghai's Omicron BA.2.2 wave. We substantiated the connection between particular amino acid substitutions and immune-mediated selection through a pseudovirus neutralization assay or by cross-verification with the human leukocyte antigen-associated T-cell epitopes. RESULTS: In contrast to those with immunologic naivety or partial vaccination, participants who were fully vaccinated had intrahost variant spectra characterized by reduced diversity. Nevertheless, the distribution of mutations in the fully vaccinated group was enriched in the spike protein. The distribution of intrahost single-nucleotide variants in individuals who were immunocompetent did not demonstrate notable signs of positive selection, in contrast to the observed adaptation in 2 participants who were immunocompromised who had an extended period of viral shedding. CONCLUSIONS: In SARS-CoV-2 infections, vaccine-induced immunity was associated with decreased diversity of within-host variant spectra, with milder inflammatory pathophysiology. The enrichment of mutations in the spike protein gene indicates selection pressure exerted by vaccination on the evolution of SARS-CoV-2.

Neutralization against Omicron subvariants after BA.5/BF.7 breakthrough infection weakened as virus evolution and aging despite repeated prototype-based vaccination1.

BACKGROUND: Omicron had swept the mainland China between December 2022 and January 2023, while SARS-CoV-2 still continued to evolve. To fully prepare for the next wave, it's urgent to evaluate the humoral immune response post BA.5/BF.7 breakthrough infection against predominant sub-lineages among existing vaccination strategies and the elders. METHOD: This study enrolled a longitudinal young-adult cohort from 2/3-dose vaccination to 1 month after breakthrough infection, and an elder cohort at 1 month after breakthrough infection. Seral samples were collected and tested for humoral immune response to SARS-CoV-2 subvariants including WT, BA.2, BA.5, BF.7, BQ.1.1, CH.1.1, XBB.1.5. RESULTS: BA.5/BF.7 breakthrough infection induced higher neutralization activity than solely vaccination in all SARS-CoV-2 strains, while the latest Omicron subvariants, BQ.1.1, CH.1.1, XBB.1.5, exhibited the strongest neutralization evasion ability. There was a negative correlation between age and humoral immune response in WT, BA.5, BQ.1.1, and XBB.1.5. Compared to non-vaccination groups, breakthrough infection in two-dose vaccination groups had significantly higher neutralizing antibody against WT, BA.2, BA.5, BF.7 but not to BQ.1.1, CH.1.1, XBB.1.5 while booster dose against the prototype prior-breakthrough would not further significantly enhance individual's humoral responses against the latest Omicron subvariants. CONCLUSIONS: Newer variants manifest increasing immune evasion from neutralization and repeated prototype-based booster vaccines may not further enhance neutralizing antibody against emerging new variants. Older adults have lower levels of neutralizing antibody. Future vaccination strategies should aim to enhance effective neutralization to contemporary variants.

Validation of the Chinese version of the Perceived Stress Scale-10 integrating exploratory graph analysis and confirmatory factor analysis.

OBJECTIVE: The study aimed to initially assess the measurement properties of the 10-item simplified Chinese version of the Perceived Stress Scale (PSS-C-10) and as a first, assess a longitudinal measurement invariance (LMI). METHODS: A longitudinal survey was conducted with a convenient sample of healthcare students using the PSS-C-10. We assessed the PSS-C-10 mainly using composite analytical approaches, including exploratory graph analysis (EGA) and confirmatory factor analysis (CFA) to suggest the best-fit factor structure and assess measurement invariance. RESULTS: The EGA identified a two-factor structural solution with an accuracy of 98.6% at baseline and 100% at a 7-day follow-up. The CFA subsequently confirmed this structure, with a comparative fit index of 0.963 at baseline and 0.987 at follow-up, Tucker-Lewis index of 0.951 at baseline and 0.982 at follow-up, and root mean square error of approximation of 0.111 at baseline and 0.089 at follow-up. The LMI was supported by the goodness-of-fit indices, and their changes fell within the recommended cut-off range. Additionally, Cronbach's alpha (0.885 at baseline and 0.904 at follow-up), McDonald's omega (0.885 at baseline and 0.902 at follow-up), and an ICC value of 0.816 for 7 days demonstrated the robust reliability of the PSS-C-10. CONCLUSION: The PSS-C-10 exhibited a stable two-factor structure with promising LMI and measurement properties.

Epigenetic regulation of stem cells in lung cancer oncogenesis and therapy resistance.

Epigenetics plays an important role in regulating stem cell signaling, as well as in the oncogenesis of lung cancer and therapeutic resistance. Determining how to employ these regulatory mechanisms to treat cancer is an intriguing medical challenge. Lung cancer is caused by signals that cause aberrant differentiation of stem cells or progenitor cells. The different pathological subtypes of lung cancer are determined by the cells of origin. Additionally, emerging studies have demonstrated that the occurrence of cancer treatment resistance is connected to the hijacking of normal stem cell capability by lung cancer stem cells, especially in the processes of drug transport, DNA damage repair, and niche protection. In this review, we summarize the principles of the epigenetic regulation of stem cell signaling in relation to the emergence of lung cancer and resistance to therapy. Furthermore, several investigations have shown that the tumor immune microenvironment in lung cancer affects these regulatory pathways. And ongoing experiments on epigenetics-related therapeutic strategies provide new insight for the treatment of lung cancer in the future.

Visualizing in situ viral replication across the natural history of chronic HBV infection.

BACKGROUND AND AIMS: Chronic HBV infection evolves through different phases. Interactions between viral replication and the host immune response in the liver underlie the pathogenesis of this disease. The aim of this study was to directly visualize the HBV replication intermediates at a single-cell resolution inscribed on morphological changes corresponding to disease activity. METHODS: A set of archived formalin-fixed paraffin-embedded liver needle biopsies from treatment-naïve patients were collected and categorized into phases according to the American Association for the Study of the Liver Diseases (AASLD) guidelines. HBV RNA and DNA were detected using in situ hybridization assays. RESULTS: The hepatocytes were ubiquitously infected in subjects with immune tolerance, and their percentage was gradually decreased in immune-active and inactive chronic hepatitis B phases. HBV-infected hepatocytes were prone to localize close to fibrous septa. The subcellular distribution of signals was able to distinguish hepatocytes with productive infection from those harboring HBV integrants and transcriptionally inactive covalently closed circular DNAs. A smaller number of hepatocytes with productive infection and more harboring transcriptionally inactive covalently closed circular DNA or HBV integrants became apparent in the inactive chronic hepatitis B phase. CONCLUSION: An atlas of in situ characteristics of viral-host interactions for each phase is described, which sheds light on the nature of viral replication and disease pathogenesis among the phases of chronic HBV infection.

Establishment of Bactrian Camel Induced Pluripotent Stem Cells and Prediction of Their Unique Pluripotency Genes.

Induced pluripotent stem cells (iPSCs) can differentiate into all types of cells and can be used in livestock for research on biological development, genetic breeding, and in vitro genetic resource conservation. The Bactrian camel is a large domestic animal that inhabits extreme environments and holds value in the treatment of various diseases and the development of the local economy. Therefore, we transferred four mouse genes (Oct4, Sox2, Klf4, and c-Myc) into Bactrian camel fetal fibroblasts (BCFFs) using retroviruses with a large host range to obtain Bactrian camel induced pluripotent stem cells (bciPSCs). They were comprehensively identified based on cell morphology, pluripotency gene and marker expression, chromosome number, transcriptome sequencing, and differentiation potential. The results showed the pluripotency of bciPSCs. However, unlike stem cells of other species, late formation of stem cell clones was observed; moreover, the immunofluorescence of SSEA1, SSEA3, and SSEA4 were positive, and teratoma formation took four months. These findings may be related to the extremely long gestation period and species specificity of Bactrian camels. By mining RNA sequence data, 85 potential unique pluripotent genes of Bactrian camels were predicted, which could be used as candidate genes for the production of bciPSC in the future. Among them, ASF1B, DTL, CDCA5, PROM1, CYTL1, NUP210, Epha3, and SYT13 are more attractive. In conclusion, we generated bciPSCs for the first time and obtained their transcriptome information, expanding the iPSC genetic information database and exploring the applicability of iPSCs in livestock. Our results can provide an experimental basis for Bactrian camel ESC establishment, developmental research, and genetic resource conservation.

Evidence of Residual Ongoing Viral Replication in Chronic Hepatitis B Patients Successfully Treated With Nucleos(t)ide Analogues.

BACKGROUND: Chronic hepatitis B is usually treated with nucleos(t)ide analogues (NAs). However, a cure is rarely achieved, even with years of treatment. Here, we investigated whether viral replication is completely halted and how long covalently closed circular DNA (cccDNA) persists in patients successfully treated with NAs. METHODS: A series of longitudinal serum samples and a collection of cross-sectional liver biopsies were obtained from patients successfully treated with NAs. Viral variants in serum HBV RNA were enumerated by deep sequencing. Viral replication intermediates in hepatocytes were directly visualized by in situ hybridization. The apparent half-life of each cccDNA was estimated. RESULTS: Three of 6 successfully treated patients demonstrated clear evidence of a small proportion of virus evolution, although the overwhelming proportion of variants were identical or possessed a similar degree of divergence through time. The apparent half-life of variants was estimated to be from approximately 7.42 weeks to infinite. Hepatocytes remained positive for cytoplasmic nucleocapsids-associated relaxed circular DNA in 4 of 7 liver needle biopsies. CONCLUSIONS: We conclude that even after prolonged treatment, a small proportion of the cccDNA reservoir is constantly replenished by continued low-level HBV replication, whereas a large proportion of the cccDNA reservoir persists over time.

Cellular basis of enhanced humoral immunity to SARS-CoV-2 upon homologous or heterologous booster vaccination analyzed by single-cell immune profiling.

SARS-CoV-2 vaccine booster dose can induce a robust humoral immune response, however, its cellular mechanisms remain elusive. Here, we investigated the durability of antibody responses and single-cell immune profiles following booster dose immunization, longitudinally over 6 months, in recipients of a homologous BBIBP-CorV/BBIBP-CorV or a heterologous BBIBP-CorV/ZF2001 regimen. The production of neutralizing antibodies was dramatically enhanced by both booster regimens, and the antibodies could last at least six months. The heterologous booster induced a faster and more robust plasmablast response, characterized by activation of plasma cells than the homologous booster. The response was attributed to recall of memory B cells and the de novo activation of B cells. Expanded B cell clones upon booster dose vaccination could persist for months, and their B cell receptors displayed accumulated mutations. The production of antibody was positively correlated with antigen presentation by conventional dendritic cells (cDCs), which provides support for B cell maturation through activation and development of follicular helper T (Tfh) cells. The proper activation of cDC/Tfh/B cells was likely fueled by active energy metabolism, and glutaminolysis might also play a general role in promoting humoral immunity. Our study unveils the cellular mechanisms of booster-induced memory/adaptive humoral immunity and suggests potential strategies to optimize vaccine efficacy and durability in future iterations.

Emerging Role of Noncoding RNAs in EGFR TKI-Resistant Lung Cancer.

Lung cancer accounts for the majority of malignancy-related mortalities worldwide. The introduction of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment and significantly improved the overall survival (OS) of lung cancer. Nevertheless, almost all EGFR-mutant patients invariably acquire TKI resistance. Accumulating evidence has indicated that noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), have a central role in the tumorigenesis and progression of lung cancer by regulating crucial signaling pathways, providing a new approach for exploring the underlying mechanisms of EGFR-TKI resistance. Therefore, this review comprehensively describes the dysregulation of ncRNAs in EGFR TKI-resistant lung cancer and its underlying mechanisms. We also underscore the clinical application of ncRNAs as prognostic, predictive and therapeutic biomarkers for EGFR TKI-resistant lung cancer. Furthermore, the barriers that need to be overcome to translate the basic findings of ncRNAs into clinical practice are discussed.

CircRNAs in lung cancer- role and clinical application.

Lung cancer holds the highest mortality rate among malignancies worldwide. Nevertheless, the potential molecular mechanisms of its tumorigenesis and evolution remain obscure. Circular RNAs (circRNAs), a broad category of covalently closed molecules, follow a malignancy-restricted expression pattern. Leading-edge studies have demonstrated the clinical application prospects of circRNAs in lung cancer. Herein, this review elucidates the biogenesis, biological functions, and pathophysiology of circRNAs. Furthermore, we underscore the forefront of the diagnostic, prognostic, and therapeutic potential of circRNAs in lung cancer as well as discuss the bottleneck that needs to be overcome to translate the basic advances of circRNAs into clinical practice.

Safety and immunogenicity of COVID-19 vaccination in patients with hepatocellular carcinoma (CHESS-NMCID 2101): A multicenter prospective study.

Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccinations in hepatocellular carcinoma (HCC) patients are limited. In this multicenter prospective study, HCC patients received two doses of inactivated whole-virion COVID-19 vaccines. The safety and neutralizing antibody were monitored. Totally, 74 patients were enrolled from 10 centers in China, and 37 (50.0%), 25 (33.8%), and 12 (16.2%) received the CoronaVac, BBIBP-CorV, and WIBP-CorV, respectively. The vaccines were well tolerated, where pain at the injection site (6.8% [5/74]) and anorexia (2.7% [2/74]) were the most frequent local and systemic adverse events. The median level of neutralizing antibody was 13.5 (interquartile range [IQR]: 6.9-23.2) AU/ml at 45 (IQR: 19-72) days after the second dose of vaccinations, and 60.8% (45/74) of patients had positive neutralizing antibody. Additionally, lower γ-glutamyl transpeptidase level was related to positive neutralizing antibody (odds ratio = 1.022 [1.003-1.049], p = 0.049). In conclusion, this study found that inactivated COVID-19 vaccinations are safe and the immunogenicity is acceptable or hyporesponsive in patients with HCC. Given that the potential benefits may outweigh the risks and the continuing emergences of novel severe acute respiratory syndrome coronavirus 2 variants, we suggest HCC patients to be vaccinated against COVID-19. Future validation studies are warranted.

Natural History of and Dynamic Changes in Clinical Manifestation, Serology, and Treatment of Brucellosis, China.

Serum agglutination test plus exposure history were used to diagnose most cases of human brucellosis in 2 China provinces. After appropriate treatment, 13.3% of acute brucellosis cases progressed to chronic disease; arthritis was an early predictor. Seropositivity can persist after symptoms disappear, which might cause physicians to subjectively extend therapeutic regimens.

Safety and immunogenicity of SARS-CoV-2 vaccines in Chinese patients with cirrhosis: a prospective multicenter study.

BACKGROUND: Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with compensated (C-cirrhosis) and decompensated cirrhosis (D-cirrhosis) are limited. METHODS: In this prospective multicenter study, adult participants with C-cirrhosis and D-cirrhosis were enrolled and received two doses of inactivated whole-virion COVID-19 vaccines. Adverse events were recorded within 14 days after any dose of vaccination, and serum samples of enrolled patients were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Risk factors for negative neutralizing antibody were analyzed. RESULTS: In total, 553 patients were enrolled from 15 centers in China, including 388 and 165 patients with C-cirrhosis and D-cirrhosis. The vaccines were well tolerated, most adverse reactions were mild and transient, and injection site pain (23/388 [5.9%] vs 9/165 [5.5%]) and fatigue (5/388 [1.3%] vs 3/165 [1.8%]) were the most frequently local and systemic adverse events in both the C-cirrhosis and D-cirrhosis groups. Overall, 4.4% (16/363) and 0.3% (1/363) of patients were reported Grades 2 and 3 alanine aminotransferase (ALT) elevations (defined as ALT > 2 upper limit of normal [ULN] but ≤ 5 ULN, and ALT > 5 ULN, respectively). The positive rates of COVID-19 neutralizing antibodies were 71.6% (278/388) and 66.1% (109/165) in C-cirrhosis and D-cirrhosis groups. Notably, Child-Pugh score of B and C levels was an independent risk factor of negative neutralizing antibody. CONCLUSIONS: Inactivated COVID-19 vaccinations are safe with acceptable immunogenicity in cirrhotic patients, and Child-Pugh score of B and C levels is associated with hyporesponsive to COVID-19 vaccination.