Objective: To evaluate the intervention efficacy of integrated group social skills training on social ability in school age patients with high functioning ASD, so as to provide a reference for improving social skills in children with high functioning ASD. Methods: From January 2021 to December 2023, 62 children aged 7-12 with high functioning ASD who visited the Children s Psychiatry Outpatient Department of the Affiliated Kangning Hospital of Ningbo University were recruited, and were randomly divided into a training ( n =31) and a control group ( n =31) by a random number table method. The training group received a 20 week structured group social training program (mental interpretation courses and social courses), while the control group received only conventional treatment. Chinese version of Griffith Empathy Measure Parent Ratings (GEM-PR) and Social Response Scale (SRS) were used to assess the symptoms of social deficits before and after treatment. Emotional face recognition tasks and eye movement trajectories were used to test the characteristics of social visual attention in children with ASD. Group comparison was conducted using t-test and Mann-Whitney U test. Results: At baseline, there were no significant differences in GEM-PR score ( t = -1.20 to -0.81), SRS score ( t =-0.36-1.75), emotional face recognition accuracy and reaction time ( t =-0.58-1.85), and eye movement trajectory ( U/t =-1.63-0.29) between the two group ( P >0.05). After intervention, the total GEM-PR score and empathic cognitive factor score of training group [18.00(10.00，24.00)，9.00(8.00，13.00)] were significantly higher than those of the control group [12.00(-1.00，18.00)，2.00(-2.00，7.00)], and the total SRS score and social cognition, social perception, social communication, social motivation (73.23±14.20, 16.16±2.72, 6.58±2.50, 24.29±5.61, 9.52±3.73) were significantly lower than those of the control group (95.26±15.29, 19.90±2.84, 12.58±2.49,31.94±6.38, 13.74±4.81) ( U/t =-2.38, -4.59; -5.88, -5.29, -9.47, -5.01, -3.87, P <0.05). The overall correct rate of emotional face recognition and the correct rate of angry, fearful and neutral faces recognition in the training group [(81.55±6.62)%，(76.86±12.06)%，(79.61±12.42)%，(94.27±6.26)%] were significantly higher than the control group [(70.55±13.82)%，(62.82±18.77)%，(67.18±18.85)%，(79.60±20.05)%], and the average reaction time [(2 226.70±274.43)ms] was lower than the control group [(2 417.27±324.10)ms] (t=4.00, 3.50, 3.07, 3.89, -2.42, P<0.05). The time to first eye gaze [764.74 (748.64, 793.73) ms] in the training group was significantly lower than that in the control group [810.92 (782.86, 877.42) ms], and the proportion of moderatetohigh intensity attention area in the face [(37.37±1.27)%] was significantly higher than that in the control group [(30.34±1.23)%] (U/t=3.44, 8.89, P<0.05). Conclusion Integrated group social training can significantly improve the social communication and empathy ability of high functioning ASD children, increase active attention and recognition ability of faces, and improve mental development of children with ASD.

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Objective To explore the application of the Montreal cognitive assessment(MoCA)scale in the early postoperative cognitive function of patients with aneurysmal subarachnoid hemorrhage(aSAH).Methods The clinical data of 181 patients with aSAH hospitalized in Department of Neurosurgery,First Affiliated Hospital of Wenzhou Medical University from November 2021 to May 2022 were collected,and the scores of each dimension of the patients were evaluated using MoCA scale;Using gender,age,educational level,hypertension,responsible aneurysm diameter,Hunt-Hess grade,and surgical method as variables,the relationship between these factors and the scores of each dimension of the MoCA scale was studied.Logistic regression was used to analyze the influencing factors of low score dimensions and postoperative cognitive function.Results 61 cases(36.31％)had normal cognitive function(≥26 points).The results of multifactorial analysis of language dimensions showed that there was a statistically significant difference in the comparison of educational background,age,surgical method,Hunt-Hess grade,and the presence or absence of cognitive dysfunction(P<0.05);The results of multifactor analysis of delayed memory showed that there was a statistically significant difference in the occurrence of cognitive dysfunction among educational background,Hunt-Hess classification,alcoholism,family history of stroke,and surgical methods(P<0.05).Conclusion The incidence of early postoperative cognitive dysfunction in patients with aSAH is high;The scores of language and delayed memory were the lowest;Low cultural background,advanced age,craniotomy methods,and high Hunt-Hess scores are more likely to cause damage to language and delayed memory dimensions.

Objective:To compare the importance of 11 common influencing factors for fall and fall-induced injury reported previously in the elderly.Methods:The data were collected from the follow-up of the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2018. Binary logistic regression model and negative binomial regression model were used to test the significance of correlations between 11 factors and the incidence of fall and fall-induced injury during this period. The absolute value of the β^ was used to evaluate importance of 11 influencing factors. Results:This study included 9 279, 6 153, 4 142, 4 148, and 3 583 old persons. The cumulative incidence rates of fall in the 2 nd, 3 rd, 4 th, 5 th, and 7 th years were 19.4% (95% CI: 18.6%-20.2%), 22.1% (95% CI: 21.0%-23.1%), 31.9% (95% CI: 30.4%-33.3%), 35.1% (95% CI: 33.6%-36.5%), and 43.2% (95% CI: 41.6%-44.8%), respectively. The cumulative incidence rates of fall-induced injury were 8.4% (95% CI: 7.8%-8.9%), 9.4% (95% CI: 8.7%-10.1%), 15.1% (95% CI: 14.0%-16.2%), 16.2% (95% CI: 15.1%-17.3%), and 22.0% (95% CI: 20.6%-23.3%). The results of multivariate logistic regression and negative binomial regression analyses showed that in the 11 factors, only gender, history of fall, and depressive symptoms were identified as common risk factors for fall and fall-induced injury in the elderly in all the follow up visits (all P<0.05); the history of fall had the highest absolute value of β^ in all models, while gender ranked second except for the 5-year fall-induced injury model. Conclusions:Of the 11 influencing factors for fall and fall-induced injury reported by previous literature, only gender, history of falls, and depressive symptoms were identified as common risk factors for fall and fall-induced injury in the eldely in the 2 nd, 3 rd, 4 th, 5 th, and 7 th years follow-up visits. History of fall and gender were important influencing factors for fall and fall-induced injury in the elderly.

The universal health coverage agenda promotes population health and social equity and is a priority for the WHO and governments worldwide. This article outlines the basic concept, development, content, monitoring indicators, global progress, and challenges of the universal health coverage agenda. After over half a century of development, a global consensus has been reached on the definition and content of the universal health coverage agenda which emphasizes coverage proportion of the population, content of healthcare services, and economic protection measures. The implementation principle of the agenda for universal health coverage is to prioritize providing healthcare services of high health benefits and social value to the entire population under resource constraints. However, the healthcare service recommendations and evaluation frameworks proposed by the WHO and other international organizations tend to favor low-income countries, neglecting services related to injury prevention and mental health, and therefore may not be suitable for all countries. The development across various dimensions of the agenda for universal health coverage is uneven, with low-income countries lagging. Progress in the prevention and control of non-communicable diseases and injuries is delayed. Low-income groups and vulnerable populations are at a disadvantage in accessing services and economic protection. It is suggested that a globally applicable set of standards, methods, and processes be used to identify high-priority healthcare services. Countries should gradually expand the scope of healthcare services and population coverage based on their needs and capabilities. Additionally, efforts should be made to increase investment in healthcare system resources and international collaboration to promote the development and technological advancement of healthcare systems in low-income countries. Furthermore, it is also necessary to build a high-quality primary healthcare service system and strengthen protection for vulnerable groups.

Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

To explore the impact of an airway stepwise management strategy in the treatment of hospital acquired pneumonia (HAP) in the ultra elderly critically ill patients.

Objective To investigate the relationship between circular RNA homeodomain interacting protein ki-nase 3 (circHIPK3) and the activation of rat microglia (RM) cells.Methods In vitro, RM cells were cultured and randomized into normal and oxygen-glucose deprivation/reperfusion (OGD/R) groups, and the expression lev-el of circHIPK3 in each group was detected by RT-qPCR.The circHIPK3 lentiviral vector with puromycin resist-ance was constructed, and the overexpression (OE) group and negative control (NC) group were set up.The opti-mal multiplicity of infection (MOI) for RM cells was determined based on fluorescence expression, and puromycin was used to screen RM cells stably expressing circHIPK3 .The cells of OE and NC groups were treated with OGD/R, and the expression levels of ionized calcium binding adaptor molecule 1 (Iba-1) and eukaryotic tumor necrosis factor receptor superfamily (CD40) were detected by Western blot.The circHIPK3 translational protein potential was analyzed by the circRNAdb database, while the potential binding microRNAs on circHIPK3 were predicted by circBank and Starbase databases.Results OGD/R down-regulated circHIPK3 in RM cells (P <0.0001).The sequencing results were accurate and the lentiviral vector of circHIPK3 was constructed successfully.The optimal MOI of RM cells was 80 , puromycin at a concentration of 2μg/ml was used to screen RM cell lines stably express-ing circHIPK3 .RT-qPCR results showed that the expression level of circHIPK3 was significantly higher in the OE group compared with the NC group (P<0.01) .Western blot results revealed that the expression levels of Iba-1 and CD40 in the OE group were markedly lower than those in the NC group (P<0.05) .Protein translation analy-sis showed that circHIPK3 encoded a polypeptide of 404 amino acids with two internal ribosome entry sites (IRES) and an open reading frame (ORF) .Database analysis uncovered that circHIPK3 could target eight specific miR-Nas, namely hsa-miR-3529-5p, hsa-miR-379-5p, hsa-miR-506-3p, hsa-miR-33, hsa-miR-450b-5p, hsa-miR-551b-3p, hsa-miR-193, and hsa-miR-508-3p.Conclusion The overexpression of circHIPK3 effectively suppres-ses OGD/R-induced activation of RM cells.It has the potential to encode peptides and may act as a miRNA sponge.These findings provide a foundation for further study of circHIPK3 functions.

Objective To investigate the correlation between the expression levels of serum calcitonin gene related peptide(CGRP),macrophage clearance receptor 1(Msr1)and pulmonary function and blood gas inde-xes in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods A to-tal of 114 patients with chronic obstructive pulmonary disease(COPD)who visited the hospital from June 2019 to June 2021 were selected as study subjects,including 47 patients with AECOPD as AECOPD group and 67 patients with stable condition as COPD stable group.The gender,body mass index(BMI),age,smoking history,white blood cell count(WBC),pulmonary function index[ratio of forced expiratory volume in the first second to forced vital capacity(FEV1/FVC),and percentage of forced expiratory volume in the first sec-ond to predicted value(FEV1％pred)],blood gas indexes[arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2)]and other basic data of patients were collected,114 healthy volun-teers who were examined in the hospital at the same time were selected as the control group.The levels of ser-um CGRP and Msr1 were detected by enzyme-linked immuno sorbent assay(ELISA).The correlation be-tween the expression levels of CGRP and Msr1 in serum of patients with AECOPD and lung function and blood gas indexes was analyzed.The diagnostic value of CGRP and Msr1 expression levels in AECOPD was analyzed by receiver operating characteristic(ROC)curve.Multivariate Logistic regression was used to ana-lyze the influencing factors of AECOPD.Results The proportion of smoking history,WBC and PaCO2 levels in AECOPD group were higher than those in stable COPD group and control group,PaO2,FEV1/FVC and FEV1％pred levels were lower in stable COPD group and control group,and the differences were statistically significant(P＜0.05).The levels of serum CGRP and Msr1 in the control group,stable COPD group and AE-COPD group increased in turn,the differences were statistically significant(P＜0.05).Serum CGRP and Msr1 expression levels in AECOPD patients were positively correlated with smoking history,WBC and PaCO2(P＜0.05),and negatively correlated with PaO2,FEV1/FVC,FEV1％pred(P＜0.05).The area under the curve(AUC)of the combination of CGRP and Msr1 in the diagnosis of AECOPD was 0.927(95％CI:0.863-0.967),which was greatly higher than that of single detection of CGRP and Msr1(Z combination vs.cGRP=2.417,P=0.016;Z combination vs.Msr1=2.3 84,P=0.017).Smoking history,CGRP and Msr1 were risk factors for AECOPD in COPD patients(P＜0.05),FEV1/FVC and FEV1％pred were protective factors(P＜0.05).Conclusion CGRP and Msr1 are highly expressed in the serum of patients with AECOPD.Both of them are closely related to the lung function and blood gas indexes of patients,and have certain value in clinical diagno-sis of AECOPD.