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 present the epidemiological characteristics of ≤28 days case fatality in both hemorrhagic stroke (HS) and ischemic stroke (IS) patients in national cardiovascular disease surveillance areas from 2015 to 2019.Methods:Data on all new patients with stroke and ≤28 days outcomes from 2015 to 2019 were from the China Registry of Cardiovascular Events, which was established in 2014, covering 100 counties (cities, districts) in 31 provinces in China. Poisson regression was used to analyze the annual trend of ≤28 days case fatality. The age-standardized case fatality was directly calculated based on all new stroke onset.Results:In total, 112 069 deaths in HS patients ≤28 days after the onset, as well as 94 373 in IS patients, were identified during the study period. In 2019, the ≤28 days case fatality rate in HS patients was 4.75 times that of IS patients (37.08% vs. 7.80%), as well as that 4.06 times in urban areas (30.13% vs. 7.43%) and 5.30 times in rural areas (42.63% vs. 8.05%), respectively. Thus, in rural areas, HS patients showed 41.49% higher ≤28 days case fatality rate than that in urban areas, as well as 8.34% higher in IS patients. Those ≤28 days case fatality in both stroke subtypes onset increased with age and reached the highest level in those aged 85 years and over. During the study period, HS and IS patients in each age group displayed significant decrease trend in ≤28 days case fatality rate (trend P<0.001). Compared with that in 2015, the age-standardized ≤28 days case-fatality in HS patients in 2019 decreased by 28.52%, which was more in urban areas (-34.27%) than that in rural areas (-23.19%). Meanwhile, IS patients experienced a 39.90% reduction in ≤28 days case fatality, which was much lower in urban areas (-31.62%) than in rural areas (-45.10%, all trend P<0.001). Conclusions:From 2015 to 2019, ≤28 days case fatality in both HS and IS patients decreased in China. Wide variations of ≤28 days case-fatality were evident in the level and trend in stroke subtype, age of patients, as well as urban and rural areas. More precise and comprehensive strategies for stroke prevention, treatment, and post-stroke management are urgently required in China.

Objective:To estimate the radiation dose to caregivers and the public from 177Lu- peptide receptor radionuclide therapy (PRRT) for pediatric neuroblastoma patients and determine the duration of contact restrictions, in order to provide a reference for relevant radiation protection measures. Methods:A retrospective study was conducted by collecting data from 18 pediatric neuroblastoma patients, aged between 3 and 13 (6.72±2.72), who received 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) treatment at the Nuclear Medicine Department of Shandong Cancer Hospital from June 2023 to July 2023. Absorbed dose rate in air at 0, 0.1, 0.5, 1 and 2 m from the patients was measured using a radiation-survey at 1, 4, 24, 48 and 96 h after administration. The whole-body region of interest was delined using HERMES software. Subsequently, curve regression fitting was performed using a biexponential function model. By incorporating hypothesized social contact durations, the effective doses received by family members and the public in contact with patients were estimated. Additionally, MIM software was used to outline the whole-body VOI to obtain the total volume of lesions, and the Pearson or Spearman correlation coefficient was employed to analyze the relationship between the absorbed dose rate in air and clinical indicators as well as the total volume of lesions. Results:The 177Lu-DOTATATE administration dose was (4 353.42±1 451.51) MBq. All patients were discharged from hospital 24 h after 177Lu-DOTATATE administration. At the time of discharge, patients had excreted (76.70±3.99)% of the administered activity, and the absorbed dose rate in air at 0.1, 1 and 2 m from the patients were (32.74±6.98), 3.68(3.01, 4.70) and (1.22±0.51) μSv/h, respectively. After being discharged, the radiation doses to caregivers from children aged 2-5 years and 5-13 years were (2.47±1.80) mSv and (0.88±0.47) mSv, respectively. The contact restriction duration was 2 d for nighttime sleeping with family members and 1 d for contact with other children. On the day of discharge, patients should limit their time on public transportation within 4 h and do not need to restrict private transportation. Conclusions:To ensure the effective dose kept within the safety limits stipulated by current regulations, it is necessary to implement contact restrictions for patients’ family members and the public. After implementing preventive measures, 177Lu-DOTATATE treatment is a safe radionuclide therapeutic option.

Objective:To analyze the characteristics and changes in incidence and mortality of ischemic and hemorrhagic stroke among Chinese residents from 2015 to 2019.Methods:The incidence and mortality data of ischemic and hemorrhagic stroke from 2015 to 2019 were collected from the China Registry of Cardiovascular Events (China RACE), which was established in 2014 and covered 100 counties (cities and districts) in 31 provinces in China. The age-standardized incidence rate (ASIR) was calculated using the Seventh National Census data as the standard population. The ratio of the incidence rate of ischemic stroke to hemorrhagic stroke was calculated. The subtype-specific mortality-to-incidence ratio (M/I) was calculated by the ratio of the number of deaths to the reported incidence cases. The relative ratio (RR) of M/I for ischemic to hemorrhagic stroke was calculated. The Joinpoint model was used to analyze the annual percentage change (APC) and trend of the incidence rate of stroke.Results:From 2015 to 2019, a total of 1 354 614 new stroke cases were reported, including 1 077 244 (79.52%) ischemic stroke and 277 370 (20.48%) hemorrhagic stroke cases, respectively. A total of 248 620 stroke deaths were reported, including 119 819 (48.19%) ischemic stroke deaths and 128 801 (51.81%) hemorrhagic stroke deaths. The incidence ratio of ischemic/hemorrhagic stroke from 2015 to 2019 was 3.50∶1, 3.76∶1, 3.63∶1, 4.23∶1, and 4.35∶1, respectively. From 2015 to 2019, there was no statistically significant annual trend of ASIR of ischemic stroke in overall, urban and rural areas and males ( Ptrend>0.05), while there was a downward trend in females (APC=-1.02%, Ptrend=0.042). The incidence of hemorrhagic stroke in the whole population, rural areas, males and females showed a downward trend ( Ptrend<0.05). Patients aged 45-49 years had an upward trend in the incidence rate of ischemic stroke (APC=3.82%, Ptrend=0.011), while those aged 70-74 years (APC=-7.37%, Ptrend=0.034), 80-84 years (APC=-9.75%, Ptrend=0.001) and 85 years and over (APC=-11.22%, Ptrend=0.017) presented a downward trend in the incidence of hemorrhagic stroke. During the period, the overall relative ratio of M/I (RR) for ischemic to hemorrhagic stroke was 4.2∶1, which was lower in urban than in rural areas (3.8 vs. 4.3). The largest gap between urban and rural areas was in the 55-59 age group (6.8 vs. 9.3). Conclusion:The incidence and mortality of ischemic and hemorrhagic stroke among Chinese residents are severe from 2015 to 2019, and there are regional and population differences.

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 present the epidemiological characteristics of ≤28 days case fatality in both hemorrhagic stroke (HS) and ischemic stroke (IS) patients in national cardiovascular disease surveillance areas from 2015 to 2019.Methods:Data on all new patients with stroke and ≤28 days outcomes from 2015 to 2019 were from the China Registry of Cardiovascular Events, which was established in 2014, covering 100 counties (cities, districts) in 31 provinces in China. Poisson regression was used to analyze the annual trend of ≤28 days case fatality. The age-standardized case fatality was directly calculated based on all new stroke onset.Results:In total, 112 069 deaths in HS patients ≤28 days after the onset, as well as 94 373 in IS patients, were identified during the study period. In 2019, the ≤28 days case fatality rate in HS patients was 4.75 times that of IS patients (37.08% vs. 7.80%), as well as that 4.06 times in urban areas (30.13% vs. 7.43%) and 5.30 times in rural areas (42.63% vs. 8.05%), respectively. Thus, in rural areas, HS patients showed 41.49% higher ≤28 days case fatality rate than that in urban areas, as well as 8.34% higher in IS patients. Those ≤28 days case fatality in both stroke subtypes onset increased with age and reached the highest level in those aged 85 years and over. During the study period, HS and IS patients in each age group displayed significant decrease trend in ≤28 days case fatality rate (trend P<0.001). Compared with that in 2015, the age-standardized ≤28 days case-fatality in HS patients in 2019 decreased by 28.52%, which was more in urban areas (-34.27%) than that in rural areas (-23.19%). Meanwhile, IS patients experienced a 39.90% reduction in ≤28 days case fatality, which was much lower in urban areas (-31.62%) than in rural areas (-45.10%, all trend P<0.001). Conclusions:From 2015 to 2019, ≤28 days case fatality in both HS and IS patients decreased in China. Wide variations of ≤28 days case-fatality were evident in the level and trend in stroke subtype, age of patients, as well as urban and rural areas. More precise and comprehensive strategies for stroke prevention, treatment, and post-stroke management are urgently required in China.

Objective:To estimate the radiation dose to caregivers and the public from 177Lu- peptide receptor radionuclide therapy (PRRT) for pediatric neuroblastoma patients and determine the duration of contact restrictions, in order to provide a reference for relevant radiation protection measures. Methods:A retrospective study was conducted by collecting data from 18 pediatric neuroblastoma patients, aged between 3 and 13 (6.72±2.72), who received 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) treatment at the Nuclear Medicine Department of Shandong Cancer Hospital from June 2023 to July 2023. Absorbed dose rate in air at 0, 0.1, 0.5, 1 and 2 m from the patients was measured using a radiation-survey at 1, 4, 24, 48 and 96 h after administration. The whole-body region of interest was delined using HERMES software. Subsequently, curve regression fitting was performed using a biexponential function model. By incorporating hypothesized social contact durations, the effective doses received by family members and the public in contact with patients were estimated. Additionally, MIM software was used to outline the whole-body VOI to obtain the total volume of lesions, and the Pearson or Spearman correlation coefficient was employed to analyze the relationship between the absorbed dose rate in air and clinical indicators as well as the total volume of lesions. Results:The 177Lu-DOTATATE administration dose was (4 353.42±1 451.51) MBq. All patients were discharged from hospital 24 h after 177Lu-DOTATATE administration. At the time of discharge, patients had excreted (76.70±3.99)% of the administered activity, and the absorbed dose rate in air at 0.1, 1 and 2 m from the patients were (32.74±6.98), 3.68(3.01, 4.70) and (1.22±0.51) μSv/h, respectively. After being discharged, the radiation doses to caregivers from children aged 2-5 years and 5-13 years were (2.47±1.80) mSv and (0.88±0.47) mSv, respectively. The contact restriction duration was 2 d for nighttime sleeping with family members and 1 d for contact with other children. On the day of discharge, patients should limit their time on public transportation within 4 h and do not need to restrict private transportation. Conclusions:To ensure the effective dose kept within the safety limits stipulated by current regulations, it is necessary to implement contact restrictions for patients’ family members and the public. After implementing preventive measures, 177Lu-DOTATATE treatment is a safe radionuclide therapeutic option.

Objective:To analyze the characteristics and changes in incidence and mortality of ischemic and hemorrhagic stroke among Chinese residents from 2015 to 2019.Methods:The incidence and mortality data of ischemic and hemorrhagic stroke from 2015 to 2019 were collected from the China Registry of Cardiovascular Events (China RACE), which was established in 2014 and covered 100 counties (cities and districts) in 31 provinces in China. The age-standardized incidence rate (ASIR) was calculated using the Seventh National Census data as the standard population. The ratio of the incidence rate of ischemic stroke to hemorrhagic stroke was calculated. The subtype-specific mortality-to-incidence ratio (M/I) was calculated by the ratio of the number of deaths to the reported incidence cases. The relative ratio (RR) of M/I for ischemic to hemorrhagic stroke was calculated. The Joinpoint model was used to analyze the annual percentage change (APC) and trend of the incidence rate of stroke.Results:From 2015 to 2019, a total of 1 354 614 new stroke cases were reported, including 1 077 244 (79.52%) ischemic stroke and 277 370 (20.48%) hemorrhagic stroke cases, respectively. A total of 248 620 stroke deaths were reported, including 119 819 (48.19%) ischemic stroke deaths and 128 801 (51.81%) hemorrhagic stroke deaths. The incidence ratio of ischemic/hemorrhagic stroke from 2015 to 2019 was 3.50∶1, 3.76∶1, 3.63∶1, 4.23∶1, and 4.35∶1, respectively. From 2015 to 2019, there was no statistically significant annual trend of ASIR of ischemic stroke in overall, urban and rural areas and males ( Ptrend>0.05), while there was a downward trend in females (APC=-1.02%, Ptrend=0.042). The incidence of hemorrhagic stroke in the whole population, rural areas, males and females showed a downward trend ( Ptrend<0.05). Patients aged 45-49 years had an upward trend in the incidence rate of ischemic stroke (APC=3.82%, Ptrend=0.011), while those aged 70-74 years (APC=-7.37%, Ptrend=0.034), 80-84 years (APC=-9.75%, Ptrend=0.001) and 85 years and over (APC=-11.22%, Ptrend=0.017) presented a downward trend in the incidence of hemorrhagic stroke. During the period, the overall relative ratio of M/I (RR) for ischemic to hemorrhagic stroke was 4.2∶1, which was lower in urban than in rural areas (3.8 vs. 4.3). The largest gap between urban and rural areas was in the 55-59 age group (6.8 vs. 9.3). Conclusion:The incidence and mortality of ischemic and hemorrhagic stroke among Chinese residents are severe from 2015 to 2019, and there are regional and population differences.

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.