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Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To investigate the distribution of TCM syndromes and syndrome elements of irritable bowel syndrome(IBS);To provide reference for clinical TCM syndrome differentiation and treatment.Methods The patients with IBS who filled in the questionnaire were collected from 18 tertiary Chinese medicine hospitals in China from November 2019 to December 2022,including Xiyuan Hospital,China Academy of Chinese Medical Sciences,Guangdong Provincial Hospital of Traditional Chinese Medicine,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine.The contents of questionnaire included the patients'general condition,medical history(onset time,condition changes),Rome Ⅳ symptom diagnostic scale,somatic symptom cluster scale,quality of life scale,hospital anxiety and depression scale,TCM syndromes,etc.The methods of factor analysis and systematic clustering analysis were used,the factors of disease and syndrome were extracted,and the classification of TCM syndrome types was summarized.Results Totally 157 patients were included,87 were male and 70 were female.The age was from 18 to 74 years old.The longest course of disease was 30 years and the shortest was 3 months,with an average of(48.31±5.61)months.Anxiety score:was 3.66±0.30,depression score was 3.39±0.28.The most common TCM symptom was emotional distress(83.4%),followed by diarrhea(80.9%)and abdominal pain(72.6%).The results of factor analysis showed that rotation finally converged after 16 iterations,and 8 common factors and 33 variables were obtained,with a cumulative contribution rate of 60.016%.The sites of IBS were mainly distributed in liver,spleen,large intestine and stomach.The main syndrome factors were qi stagnation,phlegm,dampness,heat and yang deficiency.The results of clustering analysis of 8 common factors showed that the main TCM syndrome types were liver depression and qi stagnation syndrome,damp-heat internal accumulation syndrome,liver depression and spleen deficiency syndrome,and liver-stomach digression syndrome.The main TCM syndrome of diarrhea-predominant IBS was liver stagnation and spleen deficiency syndrome,and the main TCM syndrome of mixed type and constipation type was damp-heat accumulation syndrome.There were statistically significant differences in the distribution of TCM syndrome types in patients with different types(P<0.05).Conclusion The location of IBS is mainly in liver,spleen and large intestine,especially in liver.The TCM syndrome types are mainly liver depression and qi stagnation syndrome,damp-heat internal accumulation syndrome,liver depression and spleen deficiency syndrome.

The human gastrointestinal tract is the largest reservoir of bacteria in the body,inhabiting a very complex and active microbial community.Under normal circumstances,the interaction between the intestinal flora and the host maintains a dynamic balance.Spleen deficiency syndrome is a common classic syndrome type in TCM clinical practice.A large number of studies have shown that spleen deficiency syndrome is closely related to intestinal microorganisms,and the balance of intestinal flora is the basis for the normal functioning of the spleen's main transportation and transformation functions.Intestinal flora imbalance can lead to a series of manifestations of spleen deficiency.In addition,intestinal flora is an important medium for the metabolism of polysaccharide components and the effectiveness of traditional Chinese medicine for invigorating the spleen,and traditional Chinese medicine for invigorating the spleen can also play a therapeutic role by regulating the structure and quantity of intestinal flora.This article summarizes the relationship between intestinal flora and spleen deficiency syndrome in physiology,pathology,and the efficacy of traditional Chinese medicine for invigorating the spleen.Based on intestinal flora,the study of spleen deficiency syndrome aims to provide some thoughts and suggestions for revealing the connotation of spleen deficiency syndrome in traditional Chinese medicine.

Objective:To investigate the performance of medical students with different cognitive styles and temperament types in the flipped classroom of pediatrics.Methods:A total of 85 medical students of the class of 2018 in eight-year program who studied the course of Pediatrics 2 in West China Medical School, Sichuan University, were selected and received the flipped classroom teaching of pediatrics. The cognitive style figure test was used to investigate the cognitive style of students, and the temperament self-test questionnaire was used to investigate the temperament type of students. The methods such as the cluster analysis, the ANOVA analysis of variance, the Pearson correlation analysis, and the chi-square test were used to describe the distribution of flipped classroom scores and related differences between the students with different cognitive styles and temperament types.Results:There were four temperament types of these students, i.e., choleric and sanguine temperament, sanguine and phlegmatic temperament, melancholic temperament, and choleric temperament, accounting for 28.24%, 23.53%, 27.06%, and 21.18%, respectively. There were two cognitive styles of field independence and field dependence, accounting for 51.76% and 48.24%, respectively. There was a significant difference in flipped classroom scores between the students with different cognitive styles ( t=3.18, P<0.05), while there was no significant difference in such scores between the students with different temperament types ( F=0.38, P>0.05). The correlation analysis showed that the score of phlegmatic temperament was significantly negatively correlated with flipped classroom scores ( r=-0.283, P<0.05), and the score of cognitive test was significantly positively correlated with flipped classroom scores ( r=0.346, P<0.05). Conclusions:In the flipped classroom teaching of pediatrics, it is necessary to flexibly apply specific interaction and evaluation methods in students with different temperament types and cognitive styles and grasp the relationship between cooperative learning and independent learning. The design of different links of flipped classroom should be further improved.

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*

Objective: To investigate the policies and coverage of influenza vaccine during the influenza epidemic seasons of 2020-2021 and 2021-2022 in China. Methods: The national influenza vaccination policy and vaccination rate were investigated in counties and districts and described in the two epidemic seasons. Results: In the epidemic seasons of 2020-2021 and 2021-2022, the vaccination coverage of influenza in China was 3.16% and 2.47%, respectively. The free vaccination policy had the highest vaccination coverage (51.75% and 38.32%), followed by the medical insurance reimbursement policy (9.74% and 7.36%). During the epidemic season of 2021-2022, the number of counties and districts implementing the free vaccination policy in China decreased 61 compared with the previous year, but the number of people covered increased by 51.29%. However, the vaccination coverage of the vast population decreased significantly, with the medical staff (75.69% and 40.15% for two epidemic seasons), preschool children (58.86% and 26.15%), and the elderly (45.71% and 32.94%). During the epidemic season of 2021-2022, the number of counties and districts implementing the medical insurance reimbursement policy increased by 6 compared with the previous year, and the number of people covered increased by 11.12%, but the vaccination coverage decreased. Conclusion: The influenza vaccination rate in China is low, and the implementation of cost preferential policy can greatly improve the influenza vaccination rate.
Child, Preschool ; Humans ; Aged ; Influenza, Human/prevention & control* ; Seasons ; Influenza Vaccines ; Vaccination ; China/epidemiology* ; Policy

Objective:To understand the current situation of female cancer survivors′ self-advocacy and analyze its influencing factors.Methods:Convenience sampling was used. From August to November 2021, 243 female cancer survivors from 10 tertiary A hospitals in Jiangsu Province were selected as the research objects. The general information questionnaire and the Female Self-Advocacy in Cancer Survivorship (FSACS)were used for the survey. Multiple stepwise linear regression was used to analyze the influencing factors of female cancer survivors′ self-advocacy rights.Results:The self-advocacy score of this group of female cancer survivors was (82.42±10.42); the results of multiple stepwise linear regression analysis showed that education level was an influencing factor for female cancer survivors′self-advocacy ( P<0.05), but age, marital status, number of children, work status, family monthly income, reimbursement method, illness time, disease diagnosis, and disease stage had nothing to do with female cancer survivors′ self-advocacy( P>0.05). Conclusions:Female cancer survivors′ self-advocacy is affected by their educational level.It is recommended that medical staff pay attention to patients with low education level, provide personalized guidance according to their conditions, and encourage them to actively obtain external information, seek effective communication and external support, so as to improve Self-advocacy ability.

Objective:To explore the prognostic utility of LifePort perfusion parameters plus perfusate biomarkers for predicting delayed graft function(DGF)and recovery time during deceased donor kidney transplantation(KT).Methods:From January 1, 2019 to August 31, 2019, retrospective analysis was performed for clinical data of 113 KT recipients. Based upon whether or not DGF occurred within 3 months, they were divided into two groups of DGF group(20 cases)and non-DGF (93 cases). Two groups were compared using LifePort perfusion parameters, biomarker concentrations, incidence of DGF and kidney recovery time. Statistical analysis was performed.Results:The incidence of DGF was 17.7%(20/113); Multivariate Logistic regression results indicated that terminal resistance(OR 1.879, 95% CI 1.145~3.56)and glutathione S-transferase(GST)(OR 1.62, 95% CI 1.23~2.46)were independent risk factors for DGF; Cox hazard model revealed that terminal resistance was a risk factor for recovery time of renal function(HR=0.823, 95% CI 0.735~0.981). The model combining terminal resistance and GST(AUC=0.888, 95% CI 0.842~0.933)significantly improved the predictive efficacy for DGF as compared with using terminal resistance(AUC=0.756, 95% CI 0.693~0.818)or GST alone(AUC=0.729, 95% CI 0.591~0.806).Conclusions:Combining LifePort perfusion parameters and fluid biomarkers can improve the predictive utility of DGF.

BACKGROUND: Delayed graft function (DGF) is the main cause of renal function failure after kidney transplantation. This study aims at investigating the value of hypothermic machine perfusion (HMP) parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor (DD) kidney transplantation. METHODS: HMP parameters, perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1, 2019 to August 31, 2019 in the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis. RESULTS: In this study, the DGF incidence was 17.7% (20/113); The multivariate logistic regression results showed that terminal resistance (OR: 1.879, 95% CI 1.145-3.56) and glutathione S-transferase (GST)(OR = 1.62, 95% CI 1.23-2.46) were risk factors for DGF; The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time (HR = 0.823, 95% CI 0.735-0.981). The model combining terminal resistance and GST (AUC = 0.888, 95% CI: 0.842-0.933) significantly improved the DGF predictability compared with the use of terminal resistance (AUC = 0.756, 95% CI 0.693-0.818) or GST alone (AUC = 0.729, 95% CI 0.591-0.806). CONCLUSION According to the factors analyzed in this study, the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.
Biomarkers ; Delayed Graft Function ; Graft Survival ; Humans ; Kidney/physiology* ; Kidney Transplantation/adverse effects* ; Organ Preservation ; Perfusion ; Retrospective Studies ; Tissue Donors