Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

Tuberculosis, a global infectious disease caused by Mycobacterium tuberculosis infection, ranks among the top ten causes of human death. The BCG vaccine is currently the only tuberculosis vaccine in clinical use, but its effectiveness in protecting adults from tuberculosis remains uncertain. In recent years, protein subunit vaccines have garnered significant attention due to their well-defined composition, high safety profile, and ability to enhance the BCG vaccine′s effects. However, the protein antigens in subunit tuberculosis vaccines typically elicit weak immune responses, necessitating the use of adjuvants to boost their immunogenicity. This review focuses on exploring various types of adjuvants utilized in novel tuberculosis vaccine formulations, ranging from those undergoing clinical trials to those still in preclinical development. The review provides an objective assessment of the advantages, disadvantages, and suitability of different adjuvants, while also highlighting current challenges in adjuvant research and proposing future research directions.

Urinary tract infections (UTIs) are infectious diseases caused by uropathogenic bacteria, characterized clinically by high infection and recurrence rates, with uropathogenic Escherichia coli (UPEC) being the main causative agent. This bacterium possesses various virulence factors that enable it to adhere, colonize, invade, and cause disease in the bladder. This article reviews the pathogenic mechanisms of UPEC, focusing on its virulence factors, interactions with the host, and persistence in the body, aiming to expand our understanding of the processes involved in the occurrence and recurrence of UTIs.

Objective:To investigate the relationship between plasma fluoride content, daily calcium intake and blood cell parameters in children and adolescents.Methods:This study was based on the National Health and Nutrition Examination Survey (NHANES) database of the United States from 2013 to 2016, with 3 684 children and adolescents aged 6 - 19 as the research subjects. Information on plasma fluoride content, daily calcium intake and blood cell parameters from the database were collected. Non-linear relationships between plasma fluoride content, daily calcium intake and blood cell parameters were analyzed using restricted cubic splines. If there was a non-linear relationship, the optimal inflection point was calculated using threshold/saturation effect analysis method. Subsequently, multiple linear regression models were used to analyze the associations among the three, and the modification effect of daily calcium intake (binary classification, stratified by median daily calcium intake) on the association between plasma fluoride content and blood cell parameters was analyzed.Results:There was no non-linear relationship between plasma fluoride content and white blood cell count, hemoglobin content and platelet count ( Pnon-linear > 0.05), but there was a non-linear relationship between plasma fluoride content and erythrocyte count and hematocrit ( Pnon-linear < 0.001). After adjusting for confounding factors, the optimal inflection points of the effects of plasma fluoride content on erythrocyte count and hematocrit were 0.54 and 0.31 μmol/L, respectively. There was no non-linear relationship between daily calcium intake and blood cell parameters ( Pnon-linear > 0.05). After adjusting for confounding factors, for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.49 × 10 9/L ( P = 0.009). There was a saturation effect in the association between plasma fluoride content, erythrocyte count and hematocrit: when plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.46 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 6.29% for every 1 μmol/L increase ( P = 0.006). The above associations were not statistically significant when plasma fluoride content was higher than the optimal inflection points ( P > 0.05). After stratification according to the median daily calcium intake, in the low-calcium group (daily calcium intake < 0.87 g), for every 1 μmol/L increase in plasma fluoride content, the white blood cell count increased by 0.77 × 10 9/L ( P = 0.001). When plasma fluoride content was < 0.54 μmol/L, the erythrocyte count decreased by 0.41 × 10 12/L for every 1 μmol/L increase ( P = 0.002). When plasma fluoride content was ≥0.54 μmol/L, erythrocyte count decreased by 0.47 × 10 12/L for every 1 μmol/L increase ( P < 0.001). When the plasma fluoride content was < 0.31 μmol/L, the hematocrit decreased by 8.29% for every 1 μmol/L increase ( P = 0.011). The above associations were not statistically significant in the high-calcium group (daily calcium intake ≥0.87 g, P > 0.05). There was an interaction of daily calcium intake and plasma fluoride content on platelet count ( Pinteraction = 0.070), as demonstrated by an increase in platelet count of 12.68 × 10 9/L ( P = 0.013) in the low-calcium group and a decrease in platelet count of 9.05 × 10 9/L ( P = 0.035) in the high-calcium group for every 1 μmol/L increase in plasma fluoride content. Conclusions:The blood cell parameters of children and adolescents are closely related to plasma fluoride content, but not directly related to daily calcium intake. However, the correlation between plasma fluoride content and blood cell parameters varies among different calcium intake populations, and daily calcium intake can modify the association between plasma fluoride content and platelet count.

Objective:To study anti-tumor effect of Dunhuang medical prescription Dabupi Decoction on gastric cancer-bearing mice and effect of Dabupi Decoction combined with oxaliplatin on inflammatory immunity of gastric cancer-bearing mice based on IL-17/NF-κB signaling pathway.Methods:Mouse model of MFC gastric cancer subcutaneously bearing tumor was established and ran-domly divided into model group,oxaliplatin group,high,medium and low doses of Dabupi Decoction combined with oxaliplatin groups[21.58,10.79,5.40 g/(kg·d)],with 10 mice in each group,male and female cage rearing.Administration began after 8 days of inoculation and continued for 14 days;next day after the last administration,eyeball blood was taken,mice were killed,tumor tissues were taken and weighed,and tumor inhibition rate was calculated.ELISA was used to detect contents of IL-17 and IL-6 in mice serum,immunohistochemistry(IHC),RT-qPCR and Western blot were used to detect IL-17,IL-6,NF-κB and p-NF-κB mRNA and protein expressions in mice tumor tissues,respectively.Results:Tumor inhibition rates of oxaliplatin group,high,medium and low doses of Dabupi decoction combined with oxaliplatin groups were 33.02%,52.92%,46.33%and 39.52%,respectively,and tumor quality of each treatment group was significantly lower than that of model group(P<0.01).High,medium and low doses of Dabupi Decoction combined with oxaliplatin groups were higher than that of oxaliplatin group.Compared with model group,contents of IL-17 and IL-6 in serum and expressions of IL-17,IL-6,NF-κB p65 and pNF-κB p65 mRNA and protein in tumor tissues in each treatment group were significantly reduced(P<0.01,P<0.05).Compared with oxaliplatin group,levels of IL-17 and IL-6 in serum and expres-sions of IL-17,IL-6,NF-κB p65 and pNF-κB p65 mRNA and protein in tumor tissues in high and medium doses of Dabupi Decoction combined with oxaliplatin groups were significantly reduced(P<0.01,P<0.05).Conclusion:Dunhuang medical prescription Dabupi Decoction has a certain anti-tumor effect on MFC gastric cancer-bearing mice,which can regulate inflammatory immunity and inhibit occurrence and development of gastric cancer by inhibiting IL-17/NF-κB signaling pathway.

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. At present, the situation of tuberculosis control in China and even the world is severe. Bacillus Calmette-Guerin (BCG) vaccine is the only approved vaccine for tuberculosis, but its protective effect is limited. Hence, it is imperative to develop more effective tuberculosis vaccines. Currently, many new tuberculosis vaccine candidates are in clinical or preclinical trials. In this paper, to provide reference for the development of tuberculosis vaccines in China, the status of the research on vaccine candidates were reviewed and the progress in new tuberculosis vaccine strategies were summarized.

Objective:To retrieve, evaluate and summarize the best evidence of exercise reversal intervention in the elderly with cognitive frailty, and to provide evidence for guiding exercise in elderly patients.Methods:This study was a summary of evidence-based nursing evidence. Based on the PIPOST (P: Population; I: Intervention; P: Professional; O: Outcome; S: Setting; T: Type of evidence) mode, the evidence of exercise reversal intervention in the elderly with cognitive frailty in 25 relevant guideline network and association websites, Chinese and foreign language comprehensive databases such as PubMed, CINAHL, Web of Science, Embase, Chinese Biomedical Database, China National Knowledge Internet and others were searched, extracted and integrated. The retrieval time was from January 1, 2013 to February 14, 2022.Results:A total of 22 articles were included, including 3 guidelines, 2 expert consensuses, 1 clinical decision-making, 1 evidence summary, 9 Meta analysis, and 6 randomized controlled trials. Finally, 28 pieces of the best evidence including 7 dimensions were namely formulate principles,overall assessment, exercise mode, exercise intensity, exercise time and frequency, exercise management, health guidance.Conclusions:This study summarized the best evidence of exercise intervention in the elderly with cognitive frailty, which are systematic, comprehensive, rigorous, and reliable. It can provide references for healthcare administrators to dynamically evaluate patients′cognitive frailty status, formulate personalized exercise programs, and standardize exercise guidance for patients, so as to delay or even reverse cognitive frailty.

Objective:To explore the current situation of motoric cognitive risk syndrome (MCR) in the community elderly in Taiyuan and analyze its influencing factors.Methods:From January to April 2021, convenience sampling was used to select 500 elderly people from 5 communities in Taiyuan as the research object. The elderly were investigated with the General Information Questionnaire, Mini-Mental State Examination (MMSE) , simplified Geriatric Depression Scale-15 (GDS-15) , Short-Form Mini Nutritional Assessment (MNA-SF) and Lubben Social Network Scale-6 (Lubben-6) , and 4-meter walk test.Results:A total of 500 questionnaires were distributed, and 492 valid questionnaires were recovered, with a valid recovery rate of 98.40%. The prevalence of MCR among 492 community elderly people in Taiyuan was 11.38% (56/492) . Univariate analysis showed that there were statistically significant differences in the incidence of MCR among the community elderly in Taiyuan with different age, education level, obesity, living alone, number of diseases, diabetes, coronary heart disease, stroke, number of medications, chronic pain, nutritional status, depression and social isolation ( P<0.05) . Logistic regression analysis showed that educational level, obesity, diabetes, chronic pain, nutritional status, depression, and social isolation were the influencing factors of MCR in the elderly in Taiyuan ( P<0.05) . Conclusions:The incidence of MCR among the elderly in Taiyuan is high. Individualized interventions should be formulated according to the influencing factors to prevent or delay the occurrence of MCR in the community elderly.

Background Indoor air pollution is an important risk factor affecting health of the respiratory system. Studies on indoor air pollution in China are mostly limited to the central and eastern regions, and there are few studies in the rural areas of northwest China. Objective To explore the influencing factors of lung ventilation function and its relationship with indoor air pollution in rural areas of Gansu Province based on a cross-sectional investigation. Methods A total of 399 subjects were selected from four villages in Baiyin and Yuzhong of Gansu Province. Questionnaires were used to collect demographic information, lifestyle, disease history, fuel use, and other information, and physical and functional tests were ordered such as height, weight, and lung function. The Indoor Air Pollution (IAP) exposure index was calculated based on smoking, fuel type, and weekly ventilation. IAP > 5 was defined as a high level of indoor air pollution. Lung function indexes included forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC, forced vital capacity as a percentage of predicted value (FVC%), and forced expiratory volume in the first second as a percentage of predicted value (FEV1%), which were used to determine pulmonary ventilation dysfunction. Logistic regression model was used to evaluate the relationship between indoor air pollution and pulmonary ventilation function, and subgroup analysis was further conducted according to home address and BMI , in order to identify the high-risk population of pulmonary ventilation dysfunction. Results The mean age of the subjects was (56.75±7.31) years old; 155 subjects (38.85%) had normal pulmonary ventilation function, and the other 244 subjects (61.14%) had impaired pulmonary ventilation function; about 89.97% of the subjects were exposed to high level of indoor air pollution (IAP > 5). We found that IAP > 5 (OR=2.327, 95%CI: 1.089-4.974) and use of bituminous coal as the main heating fuel in winter (OR=3.467, 95%CI: 1.197-10.037) increased the risk of pulmonary ventilation dysfunction after adjusting for age, BMI, residence, gender, smoking, drinking, and cardiovascular disease. The subgroup analysis results showed that no ventilation in the living room/bedroom (OR=3.460, 95%CI: 1.116-10.268) increased the risk of pulmonary ventilation dysfunction in Baiyin. Heating with coal stoves and Chinese Kang in the bedroom (OR=2.092, 95%CI: 1.030-4.247) and cooking in the bedroom in winter ( OR =2.954, 95% CI : 1.046-8.344) also increased the risk of pulmonary ventilation dysfunction in the residents with BMI≤24 kg·m⁻². IAP > 5 (OR=3.739, 95%CI: 1.147-12.182) was associated with a significantly increased risk of pulmonary ventilation dysfunction in the BMI > 24 kg·m⁻² subgroup. Conclusion The pulmonary ventilation function of rural residents in Gansu is poor, which is negatively correlated with indoor air pollution. Coal use, overweight, cooking in bedroom, and use of coal stoves and Chinese Kang for heating may increase the risk of pulmonary ventilation dysfunction, while room ventilation is a beneficial factor.