Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25^th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.

The advancement of surgical techniques enables effective treatment for many patients with oral and maxillofacial tumors.How-ever,post-surgery problems such as chewing,swallowing and speech difficulty may arise due to the defects in speech organs and inade-quate compensatory function of tissue flap repair.Speech disorders,in particular,isolate patients by making it difficult for them to com-municate with others,not only impact their quality of life but also potentially lead to psychological problems and social interaction disor-ders.Although the decline in life quality and other related issues caused by speech dysfunction due to surgery and radiotherapy or chemo-therapy have been widely recognized,there is currently no standardized and universally applicable assessment method and standardized re-habilitation treatment management guideline or consensus for speech disorders following oral and maxillofacial tumor surgery at home and abroad.Based on previous clinical practice,combined with the characteristics of speech disorders in patients after oral and maxillofacial tumor surgery,the clinical experience of the experts in maxillofacial tumor surgery and rehabilitation and the relevant domestic and foreign literature,relevant experts organized discussions and modifications,reach a consensus on core content such as the assessment of speech disorders and the implementation plan for early rehabilitation treatment management,providing a reference for clinical practice,in order to improve patients'speech-related life quality and enhance the assessment and rehabilitation treatment techniques for speech disorders after oral and maxillofacial tumor surgery.

Objective To establish an expert consensus on in-hospital transfer safety management for patients undergoing invasive mechanical ventilation,providing guidance for clinical medical teams to conduct standardized transfers,reduce transfer risks,and ensure patient safety.Methods Through systematic searching,screening,evaluation,and summary of evidence related to in-hospital transfer safety management for patients on invasive mechanical ventilation,we extracted recommendations to form a preliminary draft of the expert consensus.From July to October 2024,totally 2 rounds of expert consultations,and 2 rounds of expert reviews were conducted,and the content was refined and finalized based on expert feedback.Results The final consensus encompasses 9 aspects,including transfer assessment and decision-making,pre-transfer preparation of medical staff,pre-transfer patient preparation,pre-transfer equipment preparation,pre-transfer medication preparation,monitoring and intervention during transfer,emergency events and management,transfer handover and documentation,and post-transfer management.Conclusion This consensus demonstrates strong practicality and operability,offering professional guidance for enhancing the safety of in-hospital transfers for patients on invasive mechanical ventilation.

Objective:To investigate the impact of different target sites, number of treatments, and age on setup errors in dual-isocenter radiotherapy for breast cancer, and to provide a basis for planning target volume (PTV) margin expansion.Methods:A retrospective analysis was conducted on data from 15 patients with left-sided breast cancer who underwent dual-isocenter breath-hold radiotherapy in the Department of Radiotherapy Oncology at the Second Hospital of Hebei Medical University from May 2021 to May 2023. Setup errors were acquired using a Varian TrueBeam STX linear accelerator. Patients were grouped by target site (supraclavicular/chest wall), treatment phase (early/late), and age (younger/older). Non-parametric tests were used to analyze differences in setup errors in : vertical (Vrt), longitudinal (Lng), lateral (Lat) directions, and pitch, roll, and rotation (Rtn) angles. The formula proposed by van Herk was applied to calculate PTV margins.Results:The Vrt direction setup error in the supraclavicular region (0.2 cm) was smaller than that in the chest wall region (0.26 cm), but errors and margin expansions in other directions were larger ( P<0.05 for Lng and Lat directions). No significant correlation was observed in Vrt direction errors between the two sites ( P=0.062), while significant correlations were found in the other directions and angles (all P<0.05). As treatment progressed, setup errors increased in the Vrt and Rtn directions for the supraclavicular region, and in the Vrt, Lng, Lat directions and Rtn angle for the chest wall region. Among these, only the increase in Lat direction error for the chest wall region was statistically significant ( P=0.028). The PTV margins in the late phase group (except for the Lat direction of the supraclavicular region) were greater than or equal to those in the early phase group. Elderly patients had significantly larger setup errors than younger patients in Vrt, Lng, and Lat directions for the supraclavicular region, as well as in Vrt and Lat directions for the chest wall region (all P<0.05). Conclusions:In dual-isocenter radiotherapy for breast cancer, the supraclavicular region requires larger PTV margins than the chest wall region, and elderly patients require greater margins overall. Mid-course rescanning is recommended. If cone-beam CT guidance cannot be ensured for every session, expansion of PTV margins should be considered for the supraclavicular region and elderly patients to reduce the risk of geographic miss.

AIM:To investigate the effect of fenofibrate(FF)on the heart of rats with high-altitude heart dis-ease-induced right ventricular hypertrophy(H-RVH),and to explore the mechanisms and associated signaling pathways.METHODS:A total of 36 six-week-old male SD rats were randomly divided into control,model(H-RVH),and FF inter-vention(H-RVH+FF)groups with 12 rats each.A rat model of H-RVH was established by single subcutaneous injection of Sugen 5416(20 mg/kg)and exposure to a hypoxic condition(5 000 m above sea level)for 21 d in all groups except the control group.The rats in H-RVH+FF group were given FF(60 mg·kg-1·d-1)through gavage,while those in control and model groups received equal volume of saline once daily for 21 d.Rat heart gross morphology was observed,and the heart volume and weight,right ventricular weight and other hypertrophy indexes were measured in each group at the end of the experiment.A right heart floating catheter was used for measuring pulmonary artery and right ventricular pressure.Cardi-ac function was checked through cardiac ultrasonography.The serum levels of atrial natriuretic peptide(ANP),N-termi-nal pro-brain natriuretic peptide(NT-proBNP),free fatty acids(FFA),and myocardial tissue glucose(Glu)in all groups of rats were detected.The protein expression of peroxisome proliferator-activated receptor α(PPARα),fatty acid binding protein 1(FABP1),carnitine palmitoyl transferase 1a(CPT1a),pyruvate dehydrogenase kinase(PDK),and pyruvate dehydrogenase(PDH)were detected through Western blot.RESULTS:(1)Compared with the control group,the H-RVH group showed a significant increase in heart morphology and weight and increases in heart weight/body weight(HW/BW),heart volume,right ventricular weight/heart weight(RVW/HW),and Fulton index(FI)(P<0.05).Cardiac mor-phology,volume,heart weight,and HW/BW significantly decreased in the fenofibrate intervention group compared with the H-RVH group(P<0.05).RVW/HW and FI also decreased.(2)The right heart float catheter test showed that the mean right ventricular pressure(mRVP)and mean pulmonary artery pressure(mPAP)significantly increased in the H-RVH group compared with the control group(P<0.01).The increases in mRVP and mPAP were reversed in rats in the fe-nofibrate intervention group compared with the H-RVH group.(3)Cardiac ultrasonography showed that compared with the control group,the H-RVH group had significantly increased right ventricular anterior wall(RVAW)and right ventricular posterior wall(RVPW)thickness(P<0.01),significantly decreased right ventricular end-diastolic diameter(RVEDD),and right ventricular end-diastolic length(RVEDL)(P<0.01).In addition,pulmonary artery acceleration time(PAAT)was reduced,ejection time(PAET)was prolonged,and PAAT/PAET ratio decreased(P<0.01).Compared with the H-RVH group,the fenofibrate intervention group showed significant decreases in RVAW and RVPW(P<0.05),increases in RVEDD and RVEDL,and an increase in PAAT/PAET ratio.(4)The kit assay showed that the levels of ANP and NT-Pro BNP in serum were significantly higher in the H-RVH group than in the control group(P<0.05),while the levels of both were lower in the fenofibrate intervention group.The levels of serum FFA and myocardial tissue Glu levels(P<0.05)were significantly higher in the H-RVH group than in the control group.The levels of serum FFA and myocardial tissue Glu level were significantly lower in the fenofibrate intervention group than in the H-RVH group(P<0.05).(5)Western blot results showed that the expression levels of PPARα,FABP1,CPT1a,and PDH in the myocardial tissues of rats in the H-RVH group were significantly reduced(P<0.01),whereas the expression level of PDK significantly increased relative to those of the control group(P<0.01).All the effects on the above indices in the H-RVH group can be significantly re-versed by fenofibrate intervention(P<0.05).CONCLUSION:Fenofibrate exerts a protective effect on the hearts of rats with right ventricular hypertrophy associated with high-altitude heart disease by activating PPARα/FABP1/CPT1a,en-hancing fatty acid oxidation,inhibiting PDK,and activating PDH to promote the aerobic oxidation of glucose.Hence,the medication can ameliorate glucose-lipid metabolism disorders.

Objective:To analyze the infection status and epidemiological characteristics of respiratory pathogens in children with acute respiratory infections (ARI) at Xuzhou Children′s Hospital Affiliated to Xuzhou Medical University from 2023 to 2024.Methods:This study enrolled the patients (aged 0-17 years) who visited the outpatient or emergency department or were hospitalized at Xuzhou Children′s Hospital Affiliated to Xuzhou Medical University due to ARI from March 2023 to March 2024. Throat swab specimens of the patients were collected, and fluorescence quantitative PCR was used to detect influenza A virus (FluA), influenza B virus (FluB), respiratory syncytial virus (RSV), human rhinovirus (HRV), human adenovirus (HAdV), and Myocoplasima pneumonia ( Mp). These patients were divided into five groups by gender: <1, 1-2, 3-5, 6-11, 12-17 years. Chi-square test was used to perform statistical analysis on the detection rates of respiratory pathogens among patients of different genders and ages, and across distinct seasons. Results:A total of 46 379 children were enrolled and among them, 27 418 children tested positive for respiratory pathogens, with a positive rate of 59.12%. Among the positive cases, 5 177 (18.88%) were infected with more than one respiratory pathogen, with the co-infection of Mp and HRV being the most common type, followed by Mp and HAdV co-infection. The pathogens, ranked from the highest to the lowest detection rates, were Mp (20.74%, 9 620/46 379), RSV (12.76%, 5 920/46 379), HAdV (11.64%, 5 399/46 379), HRV (11.24%, 5 213/46 379), FluB (8.23%, 3 815/46 379), and FluA (6.80%, 3 154/46 379). There were statistically significant differences in the detection rates of RSV, HRV and Mp among children of different genders (χ 2=11.85, 15.23, 16.36; all P<0.001). The differences in the detection rates of the six pathogens among different age groups were statistically significant (all P<0.001), and the detection rates of FluA, FluB, HRV, HAdV and Mp in children aged 0-5 years showed an upward trend with age (all P<0.001). The highest detection rates of FluA, FluB, HRV and HAdV were in the 3-5 years group, while the highest detection rate of Mp was in the 6-11 years group, which was 40.15% (4 615/11 495). The detection rate of RSV showed a decreasing trend with age ( P<0.001), with the highest detection rate observed in the <1 year group (25.02%, 2 208/8 826). There were statistically significant differences in the detection rates of the six pathogens in different seasons (all P<0.001). Conclusions:The overall detection rate of respiratory pathogens in children with ARI in Xuzhou from 2023 to 2024 is high. Single-pathogen infection is the predominant pattern, and the most prevalent pathogen is Mp. There are gender differences in the detection rates of RSV, HRV, and Mp. The detection rate of RSV decreases with age, while the detection rates of FluA, FluB, HRV, HAdV, and Mp increase with age among children aged 0-5 years. The prevalence of FluA, FluB, RSV, HRV, HAdV, and Mp all exhibit seasonal patterns.

Restless legs syndrome （RLS） is a common neurological sensory-motor disorder， and the diagnosis of RLS mainly rely on the subjective clinical symptoms described by the patient， with a lack of specific auxiliary examinations or biomarkers. The diagnosis of this disease is still challenging for atypical cases. Various other diseases may have similar clinical symptoms as RLS， such as leg discomfort， leg pain and abnormal leg movement. This article summarizes the RLS mimics that might be confused with RLS symptoms， including the neurogenic， vascular， and musculoskeletal factors that might cause leg discomfort and pain， as well as the differential diagnosis of sleep-related movement disorders with symptoms overlapped with RLS， so as to help clinicians recognize RLS phenotype and provide a reference for the diagnosis of diseases that might be confused with RLS.

Objective: To evaluate the clinical value of combining low-dose energy spectrum CT with virtual un-enhanced(VUE) scanning and deep-learning image reconstruction(DLIR) in aortic CT angiography(CTA). Methods : In a prospective study, 94 patients scheduled for aortic CTA were randomized into two groups: a low-dose energy spectrum group and a standard 100 kVp enhancement group, with 47 patients in each. All patients initially underwent a true un-enhanced(TUE) scan at 120 kVp using adaptive statistical iterative reconstruction-V(ASIR-V) at 40% for image reconstruction. The low-dose group received enhanced scans using gemstone spectral imaging(GSI) mode with DLIR-H, producing 60 keV virtual monoenergetic images(VMIs) and VUE images. The standard group was scanned at 100 kVp, with images reconstructed using ASIR-V at 50%. Parameters were measured including CT values, noise(SD), signal-to-noise ratio(SNR), and contrast-to-noise ratio(CNR) for key vascular and muscular areas, alongside the effective radiation dose(ED). Two radiologists evaluated the image quality using a 5-point scale. Results : The low-dose group exhibited significantly higher SNR and CNR values in the ascending aorta, descending aorta, abdominal aorta, and common iliac artery compared to the standard group(P<0.05), with comparable subjective quality scores. The VUE images also demonstrated superior SNR values in the abdominal aorta, common iliac artery, and psoas major muscle, and CNR value in the ascending aorta compared to TUE images, with similar subjective quality. Importantly, the ED in the low-dose group was about 40% lower than that of the standard group. Conclusion Low-dose energy spectrum CT with DLIR in aortic CTA can significantly enhance SNR and CNR, while approximating the image quality of traditional TUE scans, thereby substantially reducing radiation exposure.