Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Objective:To explore the medication thinking and compatibility rules of TCM for the treatment of diabetic nephropathy (DN).Methods:Relevant journal literature of TCM for the treatment of DN was retrieved from CNKI, Wanfang Data, VIP, and CBM from January 1, 2000 to December 31, 2023, and a database was established through Excel 2016. Python 3.10 and the ancient and modern medical record cloud platform 2.3.5 were used to conduct Latent Dirichlet Allocation (LDA) topic modeling and association rule analysis to explore the thinking and compatibility rules of TCM prescriptions in the literature.Results:A total of 474 articles were included in the study, including 474 prescriptions, involving 260 kinds of Chinese materia medica, of which 40 kinds of Chinese materia medica with a frequency of ≥ 30, mainly Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Dioscoreae Rhizoma, Poria, and Corni Fructus, etc. The LDA topic model identified three groups of prescriptions, including four classic prescriptions: Liuwei Dihuang Pills, Taohong Siwu Decoction, Erzhi Pills, and Wuling Powder. The commonly used drug combinations extracted by association rules were: Rhizoma Alismatis - Poria, Cortex Moutan Radicis-Fructus Corni and Cortex Moutan Radicis - Rhizoma Dioscoreae.Conclusions:The main therapeutic principle of TCM in treating DN is to nourish the yin and tonify the kidney, supplemented by drugs that promoting blood circulation for removing blood stasis as well as promoting urination and draining dampness. In clinical application, modern doctors tend to use classic prescriptions such as Liuwei Dihuang Pills, Erzhi Pills, Taohong Siwu Decoction, and Wuling Powder as the basis, and modify them according to the specific conditions of patients. The LDA topic model can extract valuable prescription information from a large number of modern TCM literature, providing new perspectives and ideas for the study of clinical medication rules in TCM.

Objective:To investigate the correlation of the emm genotypes and virulence genes with the isolation sites of Group A Streptococcus (GAS). Methods:It was a retrospective study.The specimens were collected from children with impetigo in Beijing Children′s Hospital, Capital Medical University from 2006 to 2008 for GAS isolation and identification.A total of 24 GAS strains were isolated from 16 children with impetigo, among which 7 pairs of strains were isolated from the throat and skin of 7 children, and 1 pair of strains was isolated from the vulva and skin of one child, and the remaining 8 GAS strains were isolated from the skin pus samples of 8 children.Polymerase chain reaction was applied to detect the emm genotypes and 13 virulence genes ( speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa). The correlation of the emm genotypes and virulence genes with the isolation sites of GAS strains was analyzed. Results:In this study, four emm genotypes were detected, including emm1.0 (15/24), emm12.0 (4/24), emm22.0 (2/24) and emm160.0 (1/24), and one subtype emm12.19 (2/24) was detected as well.The carrying rates of 13 virulence genes speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa were 58.3%, 100%, 91.7%, 100%, 50.0%, 12.5%, 54.2%, 66.7%, 16.7%, 25.0%, 12.5%, 100% and 91.7%, respectively.All strains carried 5 to 11 virulence genes and they all carried speB, speF and smeZ.There were significant differences in the carrying rate of speA and speJ among the strains with different emm genotypes (all P<0.05). There was no significant difference in the distribution of virulence genes between skin isolates and pharyngeal isolates, including the 5 pairs of strains carrying the emm1.0 genotype (all P>0.05). Conclusions:The distribution of virulence gene of GAS in children with impetigo is significantly correlated with the emm genotype, rather than the isolation site.

Objective:To analyze the application effect of narrow elastic disposable tourniquet in liposuction reduction surgery for the lower extremity lymphedema,and to provide the basis for its clinical application.Methods:The retrospective analysis was conducted on the clinical data of 309 patients who underwent liposuction reduction surgery for the lower extremity lymphedema.The patients were divided into non-narrow elastic disposable tourniquet group(n=163)and narrow elastic disposable tourniquet group(n=146).The intraoperative blood loss,rates of allogenic blood transfusion,incidence of adverse reactions related to dilation fluid into blood,incidence of blood pressure fluctuations,and preoperative and postoperative 24 h levels of hemoglobin(Hb)and albumin(Alb)of the patients in two groups were compared.Results:Compared with non-narrow elastic disposable tourniquet group,the intraoperative blood loss,allogenic blood transfusion rate,and incidence of adverse reactions related to dilation fluid into blood of the patients in narrow elastic disposable tourniquet group were decreased(P<0.05),while the incidence of intraoperative blood pressure fluctuations was increased(P<0.05).Compared with non-narrow elastic disposable tourniquet group,the ΔHb level(preoperative Hb level-postoperative 24 h Hb level)and ΔAlb level(preoperative Alb level-postoperative 24 h Alb level)of the patients in narrow elastic disposable tourniquet group were decreased(P<0.05 or P<0.01).Conclusion:The application of narrow elastic disposable tourniquet in liposuction reduction surgery for the lower extremity lymphedema can effectively reduce the intraoperative bleeding and the need for allogenic transfusions,decrease the level of ΔAlb,and prevent the occurrence of adverse reactions related to dilation fluid into blood.However,attention should be given to the potential adverse reactions related to intraoperative circulatory fluctuations.

Objectives:To present the epidemiological characteristics of stroke incidence and stroke-related mortality among the whole population in national cardiovascular disease surveillance areas from 2015 to 2019. Methods:Data of stroke incidence and stroke-related mortality from 2015 to 2019 were collected from the China Registry of Cardiovascular Events(China RACE),which was established in 2014,covering 100 counties(cities,districts)in 31 provinces in China.The Joinpoint model was used to analyze the annual percentage changes(APC)and trends of stroke incidence rate.The age-standardized incidence rate(ASIR)was calculated using the Seventh National Census data as the standard population.With annual reported stroke events and stroke-related deaths,the mortality to incidence ratio(M/I)were examined. Results:From 2015 to 2019,an increase of 9.41%(APC=2.12%,95%CI:1.43%-2.82%,Ptrend<0.01)resulted in the overall stroke crude incidence rate(CIR)of 468.48/100 000 in 2019 among the whole population,with relatively higher in male and in rural area.The more sharply elevating of CIR appeared in males(11.26%[APC=2.53%,95%CI:1.83%-3.24%,Ptrend<0.01])rather than in females(7.26%[APC=1.63%,95%CI:0.81%-2.46%,Ptrend<0.01]).Meanwhile,the general ASIR decreased 7.47%(APC=-1.72%,95%CI:-3.23%--0.20%,Ptrend<0.05),reaching 523.82/100 000 in 2019.The females generally showed significant descending trend(9.56%[APC=-2.27%,95%CI:-3.99%--0.52%,Ptrend<0.05]),as well as more reduction than that in the males(15.82%vs.11.40%)in urban area.The crude incidence rate of stroke increased with age.From 2015 to 2019,the CIR in 45-49 age group increased 12.48%(APC=3.18%,95%CI:1.67%-4.72%,Ptrend<0.01),compared with an reduction of 15.76%(APC=-4.39%,95%CI:-7.63%--1.04%,Ptrend<0.05)in 80-84 age group.Over the monitoring years,the overall M/I was 0.19,with an age-specific U-shaped distribution.The lowest of M/I(0.10)appeared in those aged 50-54 and 55-59,while the highest(0.45)detected in those aged 85 and over.The M/I of all age in urban areas were consistently lower than that in rural areas. Conclusions:Stroke incidence burden increased from 2015-2019 in the national surveillance areas in China,along with the unfavorable geographic diversity and age-specific divergence.Further efforts are required to improve health care covering all ages and regions in China to reduce the incidence of stroke and stroke-related mortality.

Objectives:The present study aims to investigate the incidence and mortality feature of acute myocardial infarction(AMI)from 2015 to 2019 in China by utilizing national registry data. Methods:Data of AMI incidence and mortality in the surveillance area during 2015 to 2019 were abstracted from China Registry of Acute Cardiovascular Event(China RACE),which was established in 100 counties from 31 provincial regions in China.Incidence rate,age standardized incidence rate(ASIR)and mortality to incidence ratio(M/I)was estimated in AMI cases.A Joinpoint regression was executed and annual percent change(APC)was examined to identify trends in incidence. Results:From 2015 to 2019,a total of 257 686 acute myocardial infarction incidence and 149 169 deaths were registered.The annual incidence rate of AMI in 2019 was 82.76 per 100 000.Over the study period,the incidence rate of AMI increased by 6.05%for men(APC=1.30%,95%CI:0.56%to 2.02%)but decreased by 11.80%for women(APC=-3.10%,95%CI:-4.54%to-1.68%),resulting a steady trend for AMI crude incidence rate for the overall population.The overall ASIR of AMI declined by 16.59%(APC=-4.32%,95%CI:-5.32%to-3.34%)from 113.68 per 100 000 in 2015 to 94.82 per 100 000 in 2019.The ASIR of AMI declined by 11.04%(APC=-2.72%,95%CI:-3.78%to-1.67%)for men,23.96%(APC=-6.56%,95%CI:-8.57%to-4.58%)for women,12.57%(APC=-3.08%,95%CI:-6.01%to-0.08%)for the urban areas,and 19.24%(APC=-5.18%,95%CI:-10.19%to 0.03%)for rural areas respectively.The incidence rate of AMI increases gradually with age in both men and women.The incidence of AMI in urban men of 35-44 and 45-54 year age groups increased by 77.16%(APC=13.52%,95%CI:3.29%to 24.57%)and 26.36%(APC=5.71%,95%CI:-0.95%to 12.68%)over time.However,the incidence of AMI fell in the population above 65 year old,by 26.58%(APC=-6.68%,95%CI:-11.98%to-1.01%),19.85%(APC=-5.64%,95%CI:-11.57%to 0.65%)and 14.53%(APC=-4.44%,95%CI:-7.75%to-1.04%)in the 65-74 year age,75-84 year age and≥85year age groups respectively from 2015 to 2019.The mortality to incidence ratio of AMI was 0.58 over time,higher in women than in men,and higher in rural areas than in urban areas.The M/I ratio of AMI decreased from 0.62 in 2015 to 0.52 in 2019(APC=-4.28%,95%CI:-5.75%to-2.83%).There was a declined trends in M/I of AMI in urban residents of both male and female,and in the rural male residents(all P<0.05),while a steady trend in the rural female residents(P>0.05). Conclusions:The overall incidence of AMI remains steady during 2015 to 2019 in the national surveillance areas in China.Yet,downward trends in elder and female residents and increased trend in middle-aged urban males in AMI incidence are observed.The mortality of AMI in these period are age,sex and urban-rural dependent.Targeted mitigation strategies on AMI prevention and treatment need to be strengthened to reduce its incidence and mortality.

Objective To investigate the causal associations between components of metabolic syndrome(MetS)and endometrial carcinoma using Mendelian randomization(MR).Methods Data mining of the Genome-Wide Association Studies(GWAS)database was performed,with the exposure factors being MetS components(lipids,blood pressure,blood glucose,and obesity)and the outcome factor being endometrial carcinoma.MR analyses were performed with the help of regression models,including MR-Egger method,weighted median method,and inverse variance weighted(IVW)method,and the causal relationship between MetS components and endometrial carcinoma was evaluated by odds ratio(OR).Reverse MR analysis was performed for the MetS components found to have a causal relationship with endometrial carcinoma in the forward MR analysis.Results After applying Benjamini-Hochberg correction,IVW results showed a causal relationship between multiple MetS components(obesity,lipids,blood pressure,and blood glucose)and endometrial carcinoma.Specifically,the three components of obesity,including body mass index,overweight,and percentage of body fat,were causally associated with an increased risk of endometrial carcinoma(P＜0.001,OR＞1).In blood lipids,high cholesterol levels(P＜0.001,OR＜1),high triglyceride levels,and high phospholipid levels were causally associated with a reduced risk of endometrial carcinoma(P＜0.05,OR＜1).Regarding blood pressure,heart disease,atherosclerosis,and stroke were causally associated with a reduced risk of endometrial carcinoma(P＜0.05,OR＜1).Regarding blood glucose,low fasting insulin levels,type 1 diabetes mellitus,insulin resistance,and high glycated hemoglobin levels were causally associated with a reduced risk of endometrial carcinoma(P＜0.05,OR＜1),while type 2 diabetes mellitus and high fasting insulin levels were causally associated with an increased risk of endometrial carcinoma(P＜0.05,OR＞1).Reverse MR analysis did not produce any evidence for a reverse causality between the above positive MetS components and endometrial carcinoma.Conclusion The MR study suggests that obesity and type 2 diabetes mellitus are risk factors for endometrial carcinoma,while other MetS components,including hyperlipidemia,cardiovascular diseases,insulin resistance,and complications of diabetes mellitus,are protective factors for endometrial carcinoma.Further research is needed to clarify the association between MetS and endometrial carcinoma and to further explore the underlying mechanisms involved.

Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.

Objective:To observe the clinical characteristics of steroid-induced ocular hypertension (SIOH) in patients with uveitis, and explore the relationship between its clinical phenotype and gene polymorphism.Methods:A retrospective case-control study. From July 2019 to December 2020, 576 patients with uveitis who were treated with glucocorticoid eye drops in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 175 confirmed glucocorticoid responders (SRs) and 401 glucocorticoid non-responders (NRs). Seventy cases of SRs (age ≥18 years) using 1 % prednisone acetate eye drops were selected as the experiment group and 64 cases of NRs were selected as the control group. The polymorphism of rs2523864 and rs3873352 of human leukocyte antigen complex group ( HCG) 22 gene were detected by Sanger sequencing. To observe the clinical characteristics of SIOH after the use of glucocorticoid eye drops, and the correlation between rs2523864 and rs3873352 and the occurrence of SIOH. Differences among groups were compared with the Chi-square test or Fisher's exact test. The correlation between the occurrence of SIOH and the range of intraocular pressure increases after glucocorticoid use and the rs2523864 and rs3873352 loci were compared using the odds ratio ( OR) and its 95% confidence interval ( CI). Results:SIOH occurred in 175 (30.4%, 175/576) of 576 patients. Among them, there were 96 males (54.9%, 96/175) and 79 females (45.1%, 79/175); the average age was 33.64±17.40 years. Steroid high responders (HRs) and steroid moderate responders (MRs) were 58 (33.1%, 58/175) and 117 (66.9%, 117/175) cases. The medication time for the increase in intraocular pressure in MRs that was 33 (19, 56) days, and in HRs that was 28 (14, 36) days, the difference of which was significant ( Z=-1.999, P=0.046). No differences were found in daily doses of ocular hypertension induced by 1% prednisone acetate eye drops between MRs which was 4.24 (3.46, 4.66) drops/day and HRs that was 4.32 (3.84, 5.36) drops/day ( Z=-1.676, P=0.094). The genotype and allele frequency distribution of the rs3873352 locus in the case group and HRs group were significantly different from those in the control group ( P<0.05). The intraocular pressure with rs3873352 GG genotype after the medication was higher than that with GC and CC genotype ( Z=2.855, 2.628; P=0.013, 0.026), whereas there was no significant difference between different genotypes of rs2523864 ( Z=3.580, P>0.05). Genetic model analysis revealed the risk of SIOH in rs3873352 G allele carriers (GG+GC) was 2.048 times that of non-G allele carriers ( OR=2.048, 95% CI: 1.027-4.081, P=0.041). The genotype and allele frequency of rs2523864 locus showed no significant difference between different group ( P>0.05). Conclusions:After the use of glucocorticoid eye drops, HRs have an earlier increase in intraocular pressure than MRs. HCG22-rs3873352 gene polymorphism is related to the occurrence of SIOH, GG genotype increases the risk of SIOH, and G allele is a risk gene for SIOH.

Objective:To describe the status and influencing factors of nurse-related empowerment perception in inpatients with chronic diseases.Methods:Totally 586 inpatients with chronic diseases from 6 class A hospitals in Shanghai from November 2019 to September 2020 were investigated by the Chinese version of Patient Perception of Patient-empowering Nurses Behaviors (PPPNBS), Self-Efficacy of Chronic Diseases (SECD6), Nurse-patient Trust Scale (NPTS), Chinese version of Chronic Illness Resource Survey (CV-CIRS) and a general information questionnaire which was designed by researchers.Results:The total score of PPPNBS was (134.98 ± 59.60) points, and the average score for each item was (6.14 ± 2.71) points. The total score of SECD6 was (38.81 ± 9.28) points. The total score of NPTS was (141.94 ± 11.42) points, and the total score of CV-CIRS was (57.90 ± 15.24) points, which were positively correlated with empowerment perception through Pearson correlation analysis. Multiple Linear Regression showed that the degree of education, the number of forms and compliance of health education, the times of admission, participation intention in medical decision-making, the dimension of Symptom Management in Self-efficacy, three dimensions of consistency, respect, and confidence in knowledge and technology in Nurse-Patient Trust degree and four dimensions of medical staff support, organization support, family and friends support, media and government support in Chronic Illness Resource were influencing factors of patients ′ empowerment perception (adjusted R 2 value was 0.636, F value was 79.441, P<0.01). Conclusions:Compared with the foreign level, the perception of nurses ′ empowerment of inpatients with chronic diseases is at a lower level, and self-efficacy, nurse-patient trust and chronic disease resource support are all at a medium level, which still need to be improved. Nurses should allow them to participate in their treatment, improve the control of life and reduce their anxiety.