Comorbidity and frailty are prevalent clinical syndromes among the elderly population. The intricate interplay between them has profound implications for patients′ overall health and quality of life, rendering comorbidity and frailty as focal points in the research field of healthy aging. This review offers a detailed insight into the ongoing research concerning the shared physiological mechanisms and reciprocal influences of these syndromes, to provide reference for clinical practitioners in health care of the elderly.

Objective:To evaluate the effect of age factors on the pharmacodynamics of intranasal dexmedetomidine for sedation in the pediatric patients undergoing transthoracic echocardiography(TTE).Methods:American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ pediatric patients, aged 1-24 months, undergoing TTE from August 2019 to May 2022, were selected. This trial was performed in two parts. Part Ⅰ Pediatric patients were divided into 4 age groups: 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The initial dose of dexmedetomidine was 2.0 μg/kg in 0.1 μg/kg increment/decrement. The dose of dexmedetomidine was determined by using modified Dixon′s up-and-down method. The ED 50 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated by the Dexon-Massey method. Part Ⅱ One hundred patients were divided into 4 age groups ( n= 25 each): 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The 4 groups were further divided into 5 subgroups ( n=5 each) according to the dose of dexmedetomidine: 2.1 μg/kg subgroup, 2.2 μg/kg subgroup, 2.3 μg/kg subgroup, 2.4 μg/kg subgroup, and 2.5 μg/kg subgroup. Part Ⅰ and part Ⅱ trials were combined, and the ED 95 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated using the probit method. Results:A total of 220 pediatric patients were enrolled. There was no significant difference in ED 50 and ED 95 of dexmedetomidine intranasally administered for sedation among groups ( P>0.05). Conclusions:The pharmacodynamics of intranasal dexmedetomidine for sedation shows no significant difference in age in the pediatric patients aged 1-24 months undergoing TTE.

Objective:To conduct a meta-analysis to analyze the efficacy and adverse reactions of fractionated high dose rate brachytherapy (HDR-BT) as monotherapy for localized prostate cancer.Methods:Relevant databases were searched to collect the clinical trials on HDR-BT as monotherapy in patients with localized prostate cancer. Included studies were limited to full-text publications of fractionated HDR-BT as monotherapy with a median follow-up of at least 5 years, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis.Results:According to the inclusion and exclusion criteria, a total of 11 clinical trials involving 2 683 patients with prostate cancer were included in this meta-analysis. The results of the meta-analysis showed that 5-year biochemical recurrence-free survival (bRFS) rate and overall survival (OS) rate were 94% (95% CI: 93% - 96%) and 96% (95% CI: 94% - 98%), respectively. Long-term (≥5 years) cancer-specific survival (CSS) rate and distant metastasis-free survival (DMFS) rate were 99% (95% CI: 98% - 100%) and 98% (95% CI: 98% - 99%), respectively. Long-term (≥5 years) late grade ≥3 grade gastrointestinal and genitourinary adverse reactions rates were 2% (95% CI: 1% - 3%) and 9% (95% CI: 6% - 13%), respectively. Conclusions:Fractionated HDR-BT as monotherapy is an effective treatment for patients with localized prostate cancer. Its long-term efficacy is encouraging, and the treatment is well tolerated and safe.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Objective:To investigate the effect of nano lead oxide (nano-PbO) exposure on learning and memory as well as spatial exploration ability in the mice, and the role of leukocyte infiltration of brain tissue in neurobehavioral damage caused by nano-PbO exposure.Methods:A total of 60 male SPF grade Kunming mice were divided into control group, low-dose nano-PbO group, medium-dose nano-PbO group and high-dose nano-PbO group according to body mass matching method, with 15 mice in each group.Mice in low, medium and high dose groups of nano-PbO were intraperitoneally injected with 5 mg·kg -1, 10 mg·kg -1, 20 mg·kg -1 nano-PbO, respectively. And mice in the control group were intraperitoneally injected with the same volume of 0.9% normal saline.The frequency of intervention was once a day for 28 days.Morris water maze test and open field test were used to detect the ability of learning and memory and spatial exploration of mice. Western blot was used to detect the protein expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in hippocampus of mice, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) in mouse microvessels and lymphocyte function-associated antigen-1 (LAF-1) in mouse blood leukocyte. The proportion of leukocytes in mouse brain was detected by flow cytometry. All statistical analyses were performed by SPSS 20.0. Morris water maze data were analyzed by repeated measures ANOVA, the other data among multiple groups were compared by one-way ANOVA, and Tukey's test was used for further pairwise comparison.Pearson correlation analysis was performed to evaluate the correlation between neurobehavioral indexes and the proportion of white blood cells, TNF-α and IL-1β in brain tissue. Results:Morris water maze results showed that the escape latency of the four groups of mice had a significant interaction between group and time( F=3.21, P<0.05). The escape latencies of mice in middle and high dose groups of nano-PbO were higher than that in the control group (both P<0.05), and the numbers of crossing the platform of the two groups were lower than that in the control group (both P<0.05). The results of open field test showed that there was a statistically significant difference in the residence time of the mice in the four groups ( F=119.10, P<0.01). The total standing times of mice in the middle group and high dose group of nano-PbO were lower than that in the control group (both P<0.01). The results of Western blot showed that the levels of TNF-α and IL-1β in hippocampus tissue of mice were significant differences among the four groups ( F=7.21, 9.89, both P<0.05). The levels of TNF-α and IL-1β in the hippocampus of mice in the high-dose nano-PbO group were higher than those in the control group (TNF-α: (0.35±0.10), (1.03±0.30), P<0.05; IL-1β: (0.32±0.10), (0.50±0.15), P<0.05). The results of flow cytometry analysis showed that the proportions of leukocytes in the brain tissue of mice in the low, medium and high dose groups of nano-PbO were (9.99±1.09)%, (13.03±0.94)% and (16.51±3.89)%, respectively. Among them, the proportions of leukocytes in the middle and high dose groups of nano-PbO were significantly higher than that in the control group((8.13±1.29)%) (both P<0.05). The results of correlation analysis showed that the proportion of leukocytes, levels of TNF-α, IL-1β protein of hippocampus in the medium, high dose groups of nano-PbO were negatively correlated with the behavioral indexes ( r=-0.815, -0.744, -0.578, all P<0.01; r=-0.771, -0.836, -0.704, all P<0.05; r=-0.823, -0.876, -0.695, all P<0.05). The results of Western blot showed that the levels of ICAM-1 and VCAM-1 in cerebral microvessels of mice in the four groups were significantly different ( F=5.51, 16.19, both P<0.05). The levels of ICAM-1 and VCAM-1 in the middle and high dose groups of nano-PbO were higher than those in the control group(ICAM-1: (1.07±0.16), (1.21±0.35), (0.59±0.19), all P<0.05; VCAM-1: (0.68±0.12), (1.92±0.23), (0.23±0.05), both P<0.05). In addition, there was a significant difference in the level of LFA-1 protein in blood leukocytes of mice in the four groups ( F=41.80, P<0.05). The levels of LFA-1 in the middle and high dose groups of nano-PbO were higher than that in the control group((0.33±0.06), (0.89±0.23), (0.05±0.01), both P<0.05). Conclusion:The nano-PbO exposure can lead to cognitive impairment and increased inflammatory factors in the hippocampus of mice, which may be related to the increase of ICAM-1 and VCAM-1 in vascular endothelial cells, which promotes leukocyte infiltration into brain tissue.

Objective:To investigate the relationship between caspase activation and recruitment domain 8 ( CARD8) gene rs2043211 polymorphism and the age of onset for large artery atherosclerosis (LAA) stroke in Chinese Han population. Methods:Based on Nanjing Stroke Registry Program, patients with LAA stroke from January 2010 to December 2014 were included retrospectively and genotyped. Grouping according to different genetic models, the age distribution among different genotypes were compared, and Kaplan-Meier curve was used to compare the age-related cumulative non-onset frequency of the patients with different genotypes.Results:A total of 738 patients were admitted and 717 (97.15%) were successfully genotyped and included in the study. There were no significant differences in age, sex, body mass index, hypertension, diabetes, hyperlipidemia, smoking and drinking history among the genotype groups. Patients with T allele had earlier onset under codominant model (AA genotype: 61.68 years, 95% confidence interval [ CI] 59.92-63.45 years; AT genotype: 60.51 years, 95% CI 59.41-61.60 years; TT genotype: 60.44 years, 95% CI 58.96-61.92 years). Kaplan-Meier curve analysis showed that there was a significant difference in the age-related cumulative non-onset frequency between patients with different genotypes (log-rank test, P=0.041). Similar results in the female was observed in the stratified analysis (log-rank test, P=0.001). Conclusions:T allele of CARD8 rs2043211 is associated with the early age of onset of large artery atherosclerosis stroke in Chinese Han population, especially in female patients.

Objective:The research analyzed the current situation and trend of health science and technology innovation in China, developed the national health and health science and technology innovation index to estimate the development of health science and technology innovation in China.Methods:The research discussed the connotation and scope of National Health Science and technology innovation, designed the national health science and technology innovation index, and developed the evaluation index system that covered various aspects including innovation resources, innovation output, innovation environment.Results:The total index and sub-index of national health science and technology innovation index from 2011 to 2017 were calculated. Suppose the base number of 2011 was 100, the value of national health science and technology innovation index in 2017 was 201.73.Conclusions:By using multi-level indicators, the indicators that reflect the basic characteristics of scientific and technological innovation can be transformed into the overall indicators that comprehensively reflect the level of scientific and technological innovation, which can be used to monitor the overall development of health scientific and technological innovation and the situation of each innovation stage.

Objective To investigate the current status analysis the risk factors of medical adhesive related skin injury(MARSI) in neonates in NICU, in order to provide guidance in prevention and nursing of the skin injury. Methods Convenience sampling five NICU in Shenyang, prospective investigate the incidence of MARSI of neonates during the NICU stay, and analysis the incidence , injury type distribution and risk factors. Results The incidence of MARSI in neonates in NICU was 12.8%(53/413);the major injury type of MARSI was epidermal stripping(47.2%,25/53)and skin tear(35.8%,19/53) in mechanical injury;Logistic analysis showed that the independent risk factors of MARSI were the use of stomach tube, dehydrate skin and blue light therapy (χ2=5.953, 9.806 and 7.568, P<0.05). Conclusions MARSI is frequency interrupted in neonates during the NICU stay, correct selection of medical adhesive products, application of suitable paste and remove skills are helpful to reduce the incidence of MARSI in neonates during the NICU stay.

The paper puts forward the method for evaluation on the scientific influence of institution based on PageRank algorithm,configures the initial weight of each institution based on the problems of dividing equally the webpage weight number in the classical PageRank algorithm and cited frequency of the application chapter,constructs the network matrix cited by institution through the citation situation of medical SCI papers published by partial colleges and universities in 2015,respectively calculates the PageRank values of institution when self-citation is excluded or included,and conducts comparative analysis on the sequence of cited frequency indicators of the institution as well as H index.This method can be used to evaluate scientific influence of institution from two dimensions of quality and quantity.

Objective To investigate the predictive value of neutrophil to lymphocyte ratio (NLR) in peripheral blood for the outcomes in patients with acute intracerebral hemorrhage.Methods Consecutive inpatients with intracerebral hemorrhage diagnosed with the head CT were entolled.The modified Rankin Scale (mRS) was used to evaluate the functional outcomes at 90 d,0-2 wvas defined as good outcome,3-6 were defined as poor outcome,and 6 was defined as death.Univariate analysis was used to compare the demographic characteristics,baseline data,imaging,and laboratory findings between the groups.Multivariate logistic regression analysis was used to determine the independent correlation between NLR and the outcomes,and receiver operating characteristics (ROC) analysis was performed to assess the predictive value of NLR for the outcomes.Results A total of 205 patients with acute intracerebral hemorrhage were enrolled in the study,107 (52.2％) had poor outcome and 57 (27.8％) died.There were significant differences in age (P=0.038),Glasgow Coma Scale (GCS) scores (P=0.001),National Institutes of Health Stroke Scale (NIHSS) scores (P =0.001),neutrophil count (P =0.005),lymphocyte count (P =0.002),NLR (P =0.001),fasting blood glucose (P =0.012),hypersensitivity C-reactive protein (P=0.002),hematoma volume (P =0.005),and proportion of bleeding into the ventricles (P =0.002) between the poor outcome group and the good outcome group.There were significant differences in age (P =0.002),previous stroke (P =0.018),GCS scores (P =0.001),NIHSS scores (P =0.001),neutrophil count (P=0.008),lymphocyte count (P=0.001),NLR (P=0.001),fasting blood glucose (P=0.016),hematoma volume (P=0.001),and proportion of bleeding into ventricle (P=0.002) between the death group and the survival group.Multivariate logistic regression analysis showed that NLR was an independent predictive factor for poor outcome (odds ratio [OR] 2.405,95％ confidence interval [CI] 1.613-3.587;P=0.001) and death (OR 2.268,95％ CI 1.532-3.358;P =0.001) after adjusting for confounders.The ROC curve analysis showed that NLR had a higher predictive value for poor outcome at 90 d (area under the ROC curve 0.703,95％ CI 0.632-0.774;P ＜ 0.001).When the cutoff value was 2.3,the sensitivity and specificity were 61.7％ and 72.4％,respectively.NLR also had a predictive value for death within 90 d (area under the ROC curve 0.706,95％ CI 0.629-0.786;P =0.003).When the cutoff value was 2.2,the sensitivity and specificity were 63.2％ and 72.6％,respectively.Conclusion NLR may have certain predict value for outcomes in patients with acute intracerebral hemorrhage.