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.

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.

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

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.

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.

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg^-1） groups， and a trimetazidine group （0.002 g·kg^-1）. By intragastric administration of vitamin D₃ and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

Objective To investigate the effects of cynomorium songaricum extract on cognitive dysfunction of Alzheimer disease (AD) model mice based on network pharmacology and animal experiments.Methods Network pharmacology was used to predict the related targets and signal pathways of the extract of cynomorium songaricum to improve AD.Senescence accelerated mice P8 (SAMP8) were selected as the model of AD.Based on the results of the preliminary experiment, 0.17 g/(kg·d) was selected as the optimal dosage for the extract of cynomorium son-garicum.The extract of cynomorium songaricum [0.17 g/(kg·d) , Donepezil hydrochloride [2.0 mg/(kg·d) ] and normal saline were given orally for 28 days according to the groups.Morris water maze evaluated the learning and cognitive function of animals.The number of neurons in cornu ammonis 1 (CA1) of hippocampus was observed by Nissl staining.The expression of recombinant Beclin 1(Beclin-1), Sequestosome 1 (p62), light chain 3 (LC-3) protein was detected by immunohistochemical method.The protein expression levels of phosphoinositide 3-ki-nase (PI3K), protein kinase B (AKT) and glycogen synthase kinase3β(GSK-3β) in the hippocampus of mice in each group were detected by Western blot.Results Based on the network pharmacology study, it was predicted that the biological mechanism of cynomorium songaricum to improve AD might be the regulation of autophagy, and the possible signaling pathway was PI3 K/AKT/GSK-3β.The results of animal experiments showed that the extract of cynomorium songaricum could improve the spatial memory learning ability of AD model mice, improve the dam-age of hippocampal neurons, significantly increase the number of neurons, and increase the expression levels of PI3K, p-AKT/AKT, p-GSK-3β/GSK-3β, Beclin-1 and LC3 in the hippocampus of mice.The expression level of p62 decreased.There was no significant difference between male and female mice during the experiment.Conclu-sion The extract may improve the cognitive dysfunction of male and female AD models by activating autophagy mediated by PI3K-AKT-GSK-3β signaling pathway, and there is no significant gender difference in the effect.

OBJECTIVE To estimate the quality markers of antioxidant activity for standard decoction of Schisandrae Chinensis Fructus.METHODS 15 batches of Schisandrae Chinensis Fructus standard decoctions were subjected to quality evaluation by ultra high-performance liquid chromatography(UPLC)based on single-marker(QAMS)method,before being summarized by chemometrics analysis.The antioxidant abilities of 15 batches of samples were determined by DPPH and ABTS methods,while gray correlation analy-sis(GRA)and the partial least squares regression(PLSR)methods were subsequently applied to investigating the relationship between the contents of 8 components and the antioxidant activity.Ultimately,molecule docking was utilized to explore the binding properties between candidate quality markers and the core targets of anti-oxidation,with the experimental verification being executed on the indi-vidual compound by in vitro anti-oxidation.RESULTS There was no remarkable difference between the results of QAMS and external standard method(ESM),with P valued greater than 0.05.And it was speculated that protocatechuic acid,gomisin A,schizantherin B and schisandrin B were the constituents of quality difference.Moreover,the 4 quality variation components were reckoned to be the al-ternative markers on antioxidant according to the results of GRA and PLSR.The molecule docking result also showed that 4 candidate quality markers presented good binding affinity with the antioxidant core targets.The antioxidant capacity was presumably originated from the collaborated effects by multi-components in the standard decoction of Schisandrae Chinensis Fructus.In the interim,protocate-chuic acid exhibited noteworthy antioxidant efficacy with dosage-depended manner in the results of single-compound verification,which was best conformed to the characteristics of quality markers and supposed to be the antioxidant quality marker for Schisandrae Chinensis Fructus standard decoction.CONCLUSION This research predicts the potential antioxidant substances on the basis of content deter-mination by UPLC and in vitro antioxidant assay,but also provides rational foundation for quality assessment on other preparations of Schisandrae Chinensis Fructus.

Purpose To explore the feasibility of the deep learning-based segmentation of extra-pelvic region and metastases in advanced prostate cancer based on metastasis reporting and data system for prostate cancer(MET-RADS-P).Materials and Methods Four datasets(68,91,57 and 263 patients with head,neck,chest and abdomen metastases,respectively)from Jan 2017 to Jan 2022 in Peking University First Hospital were retrospectively collected for the development of the classification model of scanning range and segmentation model of different regions and metastases according to the scanning sites(head,neck,chest and abdomen).In addition,90 patients with prostate cancer confirmed by pathology and underwent whole-body MRI were collected for external validation of the developed model.The manual annotation of the regions and metastases were used as the"reference standard"for the model evaluation.The evaluation indexes included dice similarity coefficient(DSC)and volumetric similarity(VS).Results In the external validation set,the classification accuracy of head,neck,chest and abdomen were 100%(90/90),98.89%(89/90),96.67%(87/90)and 94.44%(85/90),respectively.The range of DSC,VS values of the segmentation model for organs in different regions were(0.86±0.10)-(0.99±0.01),(0.89±0.10)-(0.99±0.01),respectively.The range of DSC,VS values of the segmentation model for metastases in different regions were(0.65±0.07)-(0.72±0.13),(0.74±0.04)-(0.82±0.13),respectively.Conclusion The 3D U-Net model based on deep learning may achieve the segmentation of extra-pelvic region and metastasis in advanced prostate cancer.

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.