Objective To establish a human luminal breast cancer stem cell(BCSC)model and investigate the inhibitory effects of astragaloside Ⅳ(AS-Ⅳ)on BCSC growth.Methods MCF-7 breast cancer cells were cultured in stem cell-specific medium to induce BCSC formation.The BCSCs were then divided into a blank control group and an AS-Ⅳ treatment group,both groups were given PBS or AS-Ⅳ treatment.Morphological changes were observed after intervention.The therapeutic efficacy of AS-Ⅳ was evaluated using 3D spheroid formation and cell viability assays.Transcriptomic profiling and gene expression analysis were performed to elucidate the underlying mechanisms.Results Compared with the MCF7 breast cancer cells,MCF7 breast cancer stem cell mammospheres exhibited accelerated growth(P＜0.01)and significantly increased expression of the stemness marker ALDH1A1(P＜0.01).Further comparison with the blank control group revealed that astragaloside Ⅳ(AS-Ⅳ)treatment significantly inhibited MCF7 breast cancer stem cell proliferation(P＜0.001)and slowed mammosphere growth(P＜0.01).Transcriptomic analysis demonstrated that differentially expressed genes(DEGs)induced by stem cell modeling and AS-Ⅳ intervention were enriched in the cellular senescence signaling pathway.AS-Ⅳ intervention substantially increased the number of SA-β-gal-positive cells(P＜0.01).RT-PCR analysis confirmed that AS-Ⅳsignificantly upregulated mRNA expression of IL-1α(P＜0.01),P21(P＜0.001),and P53(P＜0.05)in MCF7 breast cancer stem cells.Conclusion Astragaloside Ⅳ suppresses the growth of human luminal breast cancer stem cells by inducing cellular senescence.

Objective To investigate the risk factors and predictive value of mechanical ventilation withdrawal failure in patients with cardiogenic respiratory failure.Methods Eighty patients with cardiogenic respiratory failure who were treated in our Rugao Hospital of Traditional Chinese Medicine from January 2019 to July 2022 were enrolled in this study.They were divided into successful withdrawal group(n=67)and failed withdrawal group(n=13)according to the results of tracheal extubation.Clinical data and ultrasonic parameters were compared between the two groups.The influence factors of mechanical ventilation withdrawal were analyzed.Results The age,proportion of patients with hypertension,the levels of N-terminal precursor of B-type natriuretic peptide(NT-proBNP),procalcitonin(PCT),and C-reactive protein(CRP),acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,and systolic left atrial area(LAA)in the failed withdrawal group,were significantly higher than those in the successful withdrawal group(P<0.05).Logistic regression analysis showed that age,NT-proBNP,PCT,CRP,APACHE Ⅱ score and LAA were the influencing factors of mechanical ventilation withdrawal failure in patients with cardiogenic respiratory failure(P<0.05).The area under the ROC curve for predicting withdrawal failure was 0.834(95%CI:0.724-0.944,P<0.05),and the sensitivity and specificity were 84.60%and 68.40%,respectively.Conclusion The mechanical ventilation withdrawal is influenced by age,NT-proBNP,PCT,CRP,APACHE Ⅱ score and LAA in patients with cardiac respiratory failure.The construction of logistic regression model may help to predict the withdrawal failure.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objectives: . Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods: . We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results: . A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion . We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications. However, motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging. Herein, swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification. By decomposing urea into carbon dioxide and ammonia, the designed proteomotors are endowed with self-propulsive capability, which leads to improved internalization and enhanced penetration in vitro. As a glutamine synthetase inhibitor, the loaded l-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells, resulting in local ammonia amplification. After intravesical instillation, the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects. We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.

COVID-19 is an emerging infectious disease caused by SARS-CoV-2. After the infection of the virus, the host immune system is stimulated to produce multifarious specific antibodies to decrease or eliminate effects of the pathogen. Study of the specific antibodies dynamic characteristics in patients with COVID-19 is very important for the understanding and diagnosis of the disease, research and development of vaccine, and planning of prevention and control strategy. This paper reviews and summarizes the domestic and oversea research on dynamic characteristics of specific antibodies of COVID-19 patients, including the antibody producing, duration and level, and its possible influencing factors in order to improve the understanding of the immunological characteristics of COVID-19.

As the progress of population aging in China, the proportion of elderly population is increasing. Both chronic diseases and infectious diseases can threaten the health of the elderly. There are many kinds of infectious diseases, including vaccine preventable infectious diseases affecting the health of adults, such as influenza, pneumococcal diseases and herpes zoster. In addition, the newly emerged COVID-19 has caused a pandemic in the world, resulting the highest proportion of deaths occurred in the elderly and posing a serious threat to the health of the elderly. This paper mainly summarizes the prevention and control of vaccine preventable diseases and COVID-19 to which the elderly are susceptible, analyzes the infectious disease problems affecting the health of elderly population, and recommends countermeasures for the prevention and control of these diseases in elderly population.

The studies on infectiousness of person infected with SARS-CoV-2 at different stages of illness are an important basis for making effective prevention and control measures such as investigating the infectious source, determining the scope of close contacts and the timing of case isolation. This review discusses the infectiousness of cases infected with SARS-CoV-2 in the incubation period, symptomatic period and convalescent period by reviewing national and international literatures, technical and professional guidelines. Existing researches suggest that the infectious viruses could be isolated at the end of the incubation period as well as since illness onset, and viral load in upper respiratory tract swabs reached the peak on day 4-6 after illness onset and thereafter began to decline, implying the infectiousness was relatively strong at the end of incubation period and within one week after illness onset. Although there were a few cases who tested positive for SARS-CoV-2 after recovery, no evidence was found to indicate these cases can cause the transmission.

Objective:To analyze the incidence of acute respiratory infection (ARI) and related healthcare seeking behaviors in population in the period of COVID-19 epidemic in China.Methods:According to the province specific cumulative incidence rates of COVID-19 reported as of March 31, 2020, the low, medium and high-risk areas were classified. In these areas, a stratified two stage cluster random sampling method was used to select participants for face-to-face questionnaire surveys. Data on the incidence of ARI and related healthcare seeking behaviors in community residents during COVID-19 epidemic period were collected to calculate the attack rate of ARI and related healthcare seeking rate. Logistic regression method was used to explore the influencing factors for ARI incidence and healthcare seeking behavior.Results:A total of 34 857 community residents were surveyed, in whom 647 (1.9%) reported that they had ARI symptoms during the COVID-19 epidemic period, and 241 (37.2%) had healthcare seeking behaviors. In terms of the incidence of COVID-19-related ARI, in high-risk area, the risk of COVID-19-related ARI was 1.36 times (95% CI: 1.12-1.65) than that in low-risk area; among different age groups, the risk of COVID-19-related ARI in age groups 20-39 years, ≥60 years was 1.80 times (95% CI: 1.29-2.59) and 1.63 times (95% CI: 1.14-2.40) than that in age group 1-9 years; the risk of COVID-19-related ARI in people with underlying diseases was 1.53 times (95% CI: 1.23-1.89) than that in those without underlying diseases; the risk of COVID-19-related ARI in people with contacts with confirmed cases of COVID-19 and people with fever or respiratory symptoms was 1.53 times (95% CI: 1.01-2.27) and 6.60 times (95% CI: 5.05-8.53) than those in people without these contacts. The healthcare seeking rate in COVID-19-related ARI patients with exposures to those with fever or respiratory symptoms was 1.68 times (95% CI: 1.05-2.70) than that in such patients without the exposures. Conclusions:The attack rate of COVID-19-related ARI was affected by the local epidemic level of COVID-19, and in high-risk area, the attack rate of COVID-19-related ARI was also high. The healthcare seeking rate in patients with COVID-19-related ARI was low. Therefore, it is necessary to encourage the healthcare seeking in people with ARI in COVID-19 pandemic period.

Domestic and foreign literatures related to the persistence of SARS-CoV-2 and the re-positive cases infected with SARS-CoV-2 were reviewed, and the characteristics and infectivity of the re-positive cases were analyzed to provide scientific evidence for the improvement of case management and the development of measures to stop the spread of SARS-CoV-2. Existing studies have shown that re-positive rate of SARS-CoV-2 ranged from 2.4% to 19.8%, the median of interval between re-positive detection and discharge was 4-15 days. Following the second course of the disease, the anti-SARS-CoV-2 IgM, IgG and IgA positive rates of the cases were 11.11%-86.08%, 52.00%-100.00% and 61.54%-100.00% respectively, the total antibody and neutralizing antibody positive rates were 98.72% and 88.46%. The viral load of the re-positive cases was lower than that in the initial infection. At least 3 380 re-positive cases have been reported globally. SARS-CoV-2 strains were isolated from the samples of 3 re-positive cases (1 immunodeficiency case and 2 cases with abnormal pulmonary imaging). There were close contacts that were infected by an asymptomatic case taking immunosuppressive agents. In conclusion, the infectivity of re-positive cases infected with SARS-CoV-2 is generally very low. Rare re-positive cases infected with SARS-CoV-2 might cause further transmission. The management approach for the re-positive cases can be based on the assessment of the individual transmission risk according to the pathogen detection results.
Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Humans ; Immunoglobulin M ; SARS-CoV-2