AIM To investigate the tissue distribution of brucine-loaded solid lipid nanoparticles in mice in vivo.METHODS Mice were intravenously injected with suspension of prepared brucine-loaded solid lipid nanoparticles and marked by fluorescein isothiocyanate (FITC).The in vivo tissue distribution of nanoparticles was analyzed by having the brucine contents in various tissues (heart,liver,spleen,lung,kidney and bone) determined by HPLC,after which fluorescence confocal laser endomicroscopy was used for further detection.RESULTS Brucine had its the highest (1.64) relative intake efficiency (Re) in mice liver,and the nanoparticles shared all over one value of targeting efficiencies (Te) in various tissues,manifesting a much stronger selectivity to liver than that of brucine solution.With the extension of time,the FITC-narked nanoparticles displayed a rich extracellular to intracellular distribution indicating a positive correlation.CONCLUSION Brucine's increased distribution in the liver tissue of mice due to its solid lipid nanoparticle form shows obvious for liver targeting.

Coffee administration has been shown to increase maximum voluntary contraction and muscular endurance. However, no study has addressed the association between daily consumption of coffee with muscular function. This cross sectional study aimed to investigate the association between frequency of coffee consumption (CC) in daily life and muscle strength among a population of working adult men. This cross sectional study included men (n = 516, mean age: 47.1) who participated in an annual health examination conducted in Sendai. The monthly frequency of coffee consumed was reported by a brief-type self-administered dietary history questionnaire. Leg extension power (LEP) was measured as an index of muscle strength. Subjects were divided into tertile levels according to CC. Analysis of covariance was used to examine the relation between the tertile levels of CC and LEP. After adjustment for potential confounders (including all lifestyle factors), the adjusted means (95% confidence interval) of LEP across the tertiles of CC were 17.4 (16.6 - 18.1) for the lowest tertile, 17.9 (17.4 - 18.5) for the mid tertile, and 18.9 (18.3 - 19.5) for the highest tertile (p for trend = 0.007). Higher frequency of monthly coffee consumption was associated with higher muscle strength.

Objective To explore the the characteristics of non-motor symptoms of essential tremor(ET).Methods Totally 50 ET patients and 45 age-gender-matched healthy volunteers,admitted in Department of Neurology,The Second Affiliated Hospital of Zhejiang University School of Medicine from May 2015 to April 2016,were included.Clinical data and tremor analyses under different postures were obtained.The non-motor symptoms were evaluated using the Pittsburgh Sleep Quality Index(PSQI),Hamilton anxiety scale(HAMA),Hamilton's Depression Scale(HAMD),and the MOS item short from health survey (SF-36).Cognitive functions were evaluated by the Minimental state examination(MMSE).Results ET group had lower MMSE total score of (25.81 ±2.75 vs.28.16 ± 1.71),increased rate of dyssomnia (62.0％ vs.15.6％) and higher PQSI score (6.42±2.71 vs.3.84±2.13)compared with the control group(all P＜0.05).Moreover,more patients in the ET group had moderate and severe anxiety(60.0 ％ vs.37.8 ％),moderate and severe depression (34.0％ vs.15.6％)than the control group(both P ＜ 0.05).Anxiety and depression had effects on physical and mental health and were also related to the quality of life.Conclusions Non-motor symptoms,such as mild cognitive deficits,depression,anxiety and dyssomnia are common in ET patients.Furthermore,depression and anxiety have negative effects on physical and mental health.

OBJECTIVE To investigate the effects of different doses of dexmedetomidine on intracranial pressure in patients undergoing gynecological laparoscopic surgery. METHODS Ninety patients undergoing selective gynecological laparoscopic surgery in trendelenburg position were divided into low-dose experimental group （group D 1），high-dose experimental group （group D 2） and control group （group C ）according to random number table ，with 30 cases in each group. Group D 1 and group D 2 received continuous intravenous infusion of dexmedetomidine 1.0 μ g/kg for 10 min for induction of anesthesia ，and then continued intravenous infusion at the rate of 0.4 μg（/ kg·h）and 0.6 μg（/ kg·h）respectively. Group C was continuously pumped with the constant volume of Sodium chloride injection. Three groups stopped pumping 30 minutes before the end of the operation. The heart rate（HR）and mean arterial pressure （MAP）were recorded when entering the room （T0），10 min after intravenous pump of dexmedetomidine（T1），10 min（T2），30 min（T3），60 min（T4）after pneumoperitoneum ，10 min after pneumoperitoneum was closed to restore the supine position （T5）. At the same time ，optic nerve sheath diameter （ONSD）in both eyes was measured by ultrasound，and the occurrence of intraoperative bradycardia and the use of atropine were recorded. RESULTS There was no statistical significance in ONSD ，HR or MAP among 3 groups at T 0（P＞0.05）. Compared with T 0，ONSD of 3 groups were decreased significantly at T 1（except for group C ）；ONSD of 3 groups were increased significantly at T 2-T5，while MAP and HR were all decreased significantly （P＜0.05）. HR of group D 2 was decreased significantly at T 1（P＜0.05）. Compared with group C ， ONSD and HR of group D 1 and D 2 were all decreased significantly at T 1-T5（P＜0.05）. Compared with group C ，the number of patients with bradycardia and those who used atropine in group D 1 and D 2 were increased significantly （P＜0.05）. CONCLUSIONS Continuous pumping of dexmedetomidine during gynecologic laparoscopic surgery can reduce the increase of intracranial pressure in patients ；compared with pumping rate of 0.6 μg（/ kg·h），the change of patient ’s HR tends to be more stable with a pumping rate of 0.4 μg（/ kg·h）.

OBJECTIVE To analyze the cost-effectiveness of abemaciclib， palbociclib and ribociclib combined with aromatase inhibitors （AI） in first-line treatment of hormone receptor-positive （HR+） advanced breast cancer from the perspective of Chinese medical system. METHODS The 20-year disease course of the patients was simulated by the partitioned survival model， and the simulation period was determined to be 4 weeks， the model output was the total cost and quality-adjusted life year （QALY）， the cost and effect were discounted at a discount rate of 5%. A network meta-analysis was constructed by systematically searching relevant clinical trials to obtain the efficacy parameters of abemaciclib， palbociclib and ribociclib combined with AI. Survival fitting and extrapolation were performed based on the survival curve of the placebo group in MONALEESA-2 trial. Cost-effectiveness was assessed by incremental cost-effectiveness ratio （ICER） and incremental net monetary benefit （INMB）， with a willingness-to-pay threshold of 3 times China’s per capita gross domestic product （GDP） in 2023； one-way sensitivity analysis and probability sensitivity analysis were used to detect the influence of parameters on the results and the robustness of the incremental analysis results. RESULTS In the 20-year simulation， compared with palbociclib+AI scheme， the ICER of ribociclib+AI scheme was 58 558.38 yuan/QALY and the INMB was 62 988.20 yuan. Compared with ribociclib+AI scheme， the ICER of abemaciclib+AI scheme was 264 928.34 yuan/QALY and the INMB was 344.84 yuan. One-way sensitivity analysis showed that the incremental analysis results of abemaciclib+AI scheme compared to ribociclib+AI scheme were not robust. Probabilistic sensitivity analysis confirmed that the probability of ribociclib+AI scheme becoming the most economical was the highest when the threshold was 1-3 times China’s per capita GDP in 2023. CONCLUSIONS Ribociclib+AI scheme is more likely to be the most economical first-line treatment than abemaciclib+AI scheme and palbociclib+AI scheme in Chinese patients with HR+ advanced breast cancer when threshold is 1-3 times China’s per capita GDP in 2023.

BACKGROUND: Changes in thyroid hormone levels are commonly recognized characters among the elderly, which were reported to potentially influence incident frailty. Therefore, we examined the cross-sectional associations of thyroid hormones (THs) with frailty as well as the five components characterizing frailty (fatigue, resistance, ambulation, number of illnesses, and loss of weight) among the oldest-old. METHODS: Four hundred and eighty-seven community-dwelling oldest-old from a local community in Haidian District, Beijing, participated in our recruitment campaign between April 2019 and May 2020. The primary outcomes were a definitive diagnosis of frailty according to the FRAIL scale (Fatigue, Resistance, Ambulation, Illnesses, Loss of weight) and a positive score for each frailty subdomain. Demographic information (age, sex, marital status, and educational status), comorbidities, and details on the participants' lifestyles were recorded. Serum THs including free triiodothyronin (fT3), triiodothyronine (T3), free thyroxine (fT4), and thyroxine (T4) and thyroid stimulating hormone (TSH) levels were also measured at the beginning of our study. Logistic regressions were conducted to screen for potential risk factors for frailty and its subdomains. RESULTS: Among the total 487 subjects at enrollment, 60 (12.23%) of them were diagnosed with subclinical hypothyroidism and 110 (22.59%) of the total population scored positive for frailty. Logistic regression analyses adjusted for all potential confounders, showed that frailty was significantly associated with the serum TSH concentration (odds ratio [OR]: 1.06), fT3 concentration (OR: 0.54), and subclinical hypothyroidism score (OR: 2.18). The association between fT4 and frailty was absent in our observational study. The fT3/fT4 ratio characterizing peripheral hormone conversion was also tested to be correlated with frailty. CONCLUSION Subclinical hypothyroidism, higher TSH level, lower fT3 level, and decreased fT3/fT4 ratio were all associated with frailty assessed by the FRAIL scale among the community-dwelling oldest-old, suggesting a relevant role of thyroid function in aging. Future longitudinal studies are warranted to determine the casual relationship between thyroid dysfunction and frailty in the oldest-old.
Humans ; Aged, 80 and over ; Aged ; Thyroxine ; Cross-Sectional Studies ; Thyrotropin ; Frailty ; Independent Living ; Triiodothyronine ; Thyroid Function Tests ; Thyroid Hormones ; Hypothyroidism ; Fatigue