Bo Shen

Following the adjustment of COVID-19 control policies in mainland China, particularly during the Omicron BA.5 and BF.7 waves, evaluating vaccine effectiveness in individuals aged ≥ 80 years is of critical importance. This retrospective study included 2,325 hospitalized patients aged 80 years and older from four hospitals between December 9, 2022, and January 27, 2023. We assessed the associations of vaccination dose, vaccination regimen, and the interval since the last vaccination with SARS-CoV-2 infection and mortality. Univariable and multivariable logistic regression analyses were performed to adjust for baseline imbalances across vaccination groups. An exploratory NAb analysis was conducted in 138 patients with paired serum samples at admission and discharge to evaluate immune responses associated with different vaccination strategies. In the unadjusted analyses, SARS-CoV-2 infection and mortality rates decreased with increasing vaccine doses. After adjustment for age, diabetes, and hyperlipidemia, receipt of 1, 2, and 3 vaccine doses was associated with lower odds of SARS-CoV-2 infection compared with no vaccination, with adjusted ORs of 0.644 (95% CI: 0.445-0.931, P = 0.019), 0.579 (95% CI: 0.407-0.823, P = 0.002), and 0.448 (95% CI: 0.332-0.607, P < 0.001), respectively. Three-dose vaccination was also associated with lower odds of mortality (OR = 0.563, 95% CI: 0.380-0.835, P = 0.004). In the regimen-based model, CoronaVac plus ZF2001 was associated with lower odds of infection (OR = 0.456, 95% CI: 0.235-0.885, P = 0.020) and mortality (OR = 0.410, 95% CI: 0.123-0.878, P = 0.047) after adjustment. In the exploratory NAb subgroup analysis, patients receiving CoronaVac plus ZF2001 showed higher NAb levels at both admission and discharge. During the Omicron BA.5/BF.7 wave, receipt of three COVID-19 vaccine doses was associated with lower risks of SARS-CoV-2 infection and mortality among hospitalized patients aged 80 years and older. The heterologous regimen of CoronaVac plus ZF2001 was associated with lower risks of infection and mortality and higher NAb levels. These findings support the potential value of optimized booster and heterologous vaccination strategies for improving COVID-19-related outcomes in this high-risk older population. N/A.

Background: Germline pathogenic variants (PVs) of succinate dehydrogenase subunit D ( SDHD ) are major genetic causes of pheochromocytomas and paragangliomas. Existing studies have reported inconsistent findings and lack a comprehensive synthesis regarding penetrance, multifocality and metastatic risk in carriers of SDHD PVs. Objective: To systematically assess age-specific penetrance (in all carriers) and the proportions of multifocality, metastatic disease and mortality among affected carriers, and explore potential genotype–phenotype associations through a systematic review and meta-analysis. Methods: Eligible observational studies were selected from PubMed, MEDLINE and EMBASE that reported age-specific penetrance (in all carriers) and the proportions of multifocality, metastatic disease and mortality among affected carriers (those with tumours). Additionally, data on specific SDHD variants associated with tumour multifocality or metastatic behaviour were collected. Following independent data extraction and quality assessment by two reviewers, these proportions were meta-analysed using random-effects models or fixed-effect model to generate pooled estimates with 95% CIs and prediction intervals. Results: Age-specific penetrance increased from 20% at 20 years of age (95% CI 16% to 25%) to 58% at 40 years (95% CI 48% to 67%) and 82% at 60 years (95% CI 75% to 90%). Among the affected SDHD PV carriers, the pooled proportions were 75% (95% CI 72% to 79%) for multifocal tumours, 3% (95% CI 2% to 4%) for metastatic disease and 1% (95% CI 1% to 2%) for mortality. Conclusion: SDHD PV carriers exhibit increasing age-specific penetrance, with a high proportion of patients having multifocal tumours but low proportions of metastatic disease and mortality, providing partial evidence for the need for lifelong monitoring of SDHD PV carriers. However, evidence linking specific variants to these phenotypes is limited and requires further investigation. PROSPERO registration number: CRD420251060752.

Background: The normal intestinal microbiota undergoes rapid and notable changes in patients in the intensive care unit (ICU) because of factors such as host physiological stress, changes in gastrointestinal function, and antibiotic exposure. Different specimen types are used for intestinal microbial analysis because of sampling difficulties. Therefore, this study conducted a meta-analysis to investigate changes in the intestinal microbiota of patients admitted to the ICU and whether using different specimen types affects microbiota analysis. Methods: A systematic review was conducted encompassing studies published in electronic databases up to May 1, 2024. We included 11 studies that compared the abundance and diversity of the gut microbiota between ICU patients and healthy cohorts (HC). A standardized mean difference (SMD) meta-analysis using random effects models was performed to quantify microbial differences, including an assessment of various sampling methods. Results: After ICU admission, the intestinal microbiota of patients differed significantly from that of the normal population, showing lower diversity and richness. A significant difference in beta diversity was also observed. Specifically, the relative abundances of Proteobacteria and Fusobacteria were elevated in ICU patients, while Firmicutes abundance was diminished. Crucially, the comparison of stool versus rectal swab specimens demonstrated no significant difference in the measured alpha diversity of the gut microbiota. Conclusion: The early intestinal microbiota of patients in the ICU differed from that of healthy individuals. A comprehensive understanding of the early changes in the intestinal microbiota of patients in the ICU can help formulate prevention and treatment strategies. Furthermore, using feces and swab samples for analysis did not significantly affect the diversity of the intestinal microecology. Therefore, rectal swabs may be an attractive method for sampling the gut microbiota and metabolome. Systematic review registration: PROSPERO Registration number is CRD42022385146 (Available from: https://www.crd.york.ac.uk/PROSPERO/view/CRD42022385146 ).

To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.

The prevalence of hyperuricemia (HUA) has been increasing among adolescents, yet the relationship between body composition and HUA remains underexplored. T

Background: Hyperuricemia (HUA) is closely associated with insulin resistance (IR). Retinol‐binding protein 4 (RBP4) plays a critical role in inducing IR. However, the combined effects of uric acid (UA) and RBP4 on IR remain unclear. This study aimed to identify the risk factors for IR in type 2 diabetes mellitus (T2DM) patients and to investigate the potential relationship between UA and RBP4 in this context. Methods: This study included 570 patients aged 18–60 years with T2DM who were treated at Taizhou Hospital in Zhejiang Province. Univariate and multivariate logistic regression analyses were performed to evaluate the associations of UA and RBP4 levels with IR risk in T2DM patients. Mediation analysis was conducted to assess the mediating role of RBP4 in the relationship between UA and homeostasis model assessment of insulin resistance (HOMA‐IR). Finally, ROC curve analysis was performed to examine the evaluation value of the model for IR in patients with T2DM. Results: RBP4 and UA levels were significantly correlated with HOMA‐IR ( p < 0.01). Mediation analysis revealed that RBP4 partially mediated the relationship between UA and IR ( p < 0.05, with the mediating effect accounting for 23.2%). Furthermore, both RBP4 and UA were identified as significant risk factors for IR in patients with T2DM ( p < 0.05). The risk of IR associated with HUA was greater when RBP4 ≥ 36.6 mg/L ( p < 0.001). The ROC analysis showed that compared with UA or RBP4 alone, the combination of RBP4 and UA was more effective in detecting IR and represented a superior assessment model (AUC = 0.788, p < 0.001). Conclusions: RBP4 played a partial mediating role between UA and IR. Both RBP4 and UA were risk factors for IR in T2DM patients. The combined use of these two indicators can better evaluate the risk of IR. Further research is needed to validate the reliability of using UA and RBP4 levels to evaluate IR.

To analyze the incidence, clinical characteristics, and mortality risk of acute kidney injury (AKI) in patients with preexisting chronic kidney disease (CK