Association of Frailty with recovery from disability among community-dwelling Chinese older adults: China health and retirement longitudinal study.

BACKGROUNDS: Little is known about the role of frailty in the recovery process of disability among older adults. We examined the association between frailty and recovery from activities of daily living (ADL) and instrumental ADL (IADL) disability among community-dwelling Chinese older adults. METHODS: Data were from the China Health and Retirement Longitudinal Study. Three waves were used. Participants ≥60 years, had frailty assessment at baseline, and had incident disability in ADL or IADL in 2013, and had disability assessment in 2015 were included. Recovery from ADL and IADL disability were used as outcome measure. Multivariable logistic regression was used to evaluate the potential association between frailty and recovery from ADL or IADL. RESULTS: We included 516 and 598 participants in the ADL and IADL analysis, respectively. In total, 237 participants recovered from ADL disability and 293 recovered from IADL disability. Nearly half of the non-frail persons recovered from ADL disability, while less than one-quarter of the frail persons had recovery. Over half of the non-frail persons had IADL disability recovery, while only 30% of the frail recovered. After adjustment, the odds of recovery from ADL disability were 59% (95% confidence interval [CI]: 1, 83%) lower among frail participants than those who were non-frail; the odds of recovery from IADL disability were 52% lower among frail persons than those who were non-frail and the association did not reach statistical significance. CONCLUSIONS: Frailty is an independent predictor of poor recovery from disability among nondisabled community-dwelling older adults in China.

Quantifying and Classifying Physical Resilience Among Older Adults: The Health, Aging, and Body Composition Study.

BACKGROUND: The concept of resilience has gained increasing attention in aging research; however, current literature lacks consensus on how to measure resilience. We constructed a novel resilience measure based on the degree of mismatch between persons' frailty level and disease burden and examined its predictive validity. We also sought to explore the physiological correlates of resilience. METHODS: Participants were 2,457 older adults from the Health, Aging, and Body Composition Study. We constructed the resilience measure as the residual taken from the linear model regressing frailty on age, sex, race/ethnicity, 14 diseases, self-reported health, and number of medications. Participants were classified into three groups-adapters, expected agers, and premature frailers-based on residuals (less than, within, or above one standard deviation of the mean). Validation outcomes included years of able life (YAL), years of healthy life (YHL), years of healthy and able life (YHAL), disability, hospitalization, and survival. RESULTS: The average YHAL was 5.1, 7.7, and 9.1 years among premature frailers, expected agers, and adapters, respectively. Compared with premature frailers and expected agers, adapters had significantly lower rates of disability, hospitalization, and mortality and higher proportion surviving to 90 years. The likelihood of surviving to 90 years was 20.4%, 30.6%, and 39.7% among premature frailers, expected agers, and adapters. CONCLUSIONS: We developed and validated a novel approach for quantifying and classifying physical resilience in a cohort of well-functioning white and black older adults. Persons with high physical resilience level had longer healthy life span and lower rates of adverse outcomes.

Incidence of frailty among community-dwelling older adults: a nationally representative profile in China.

BACKGROUND: Frailty is a clinically recognizable state of reduced resilience to stressors and increased vulnerability to adverse outcomes. The majority of studies have focused on the prevalence and risk factors of frailty, while the incidence of frailty has not been well documented, especially in less developed regions including China-a country that has the largest aging population in the world. We investigated the incidence of frailty among non-frail Chinese older adults by sociodemographic characteristics, disease burden, and geographic region. METHODS: Participants were 4939 adults aged ≥60 years from the China Health and Retirement Longitudinal Study, a cohort study of a nationally representative sample of middle-aged and older community-dwelling adults from 28 provinces in China. Frailty was assessed by an adapted version of the well-validated Fried's physical frailty phenotype, in which five criteria were included: weakness, slowness, exhaustion, physical inactivity, and shrinking. RESULTS: Over an average of 2.1 years of follow-up (10,514.2 person-years), the weighted incidence rate of frailty was 60.6 per 1000 person-years; the incidence rate was 28.8 and 86.6 per 1000 person-years for those who were initially robust and prefrail, respectively. Participants who were older and widowed, had lower education and household income, lived in rural areas, and had higher burden of chronic conditions had higher frailty incidence. Frailty incidence ranged from 44.8 per 1000 person-years in the Southeast to 93.0 per 1000 person-years in the Northwest. CONCLUSIONS: Incidence rate of frailty was 60.6 per 1000 person-years among community-living Chinese adults aged ≥ 60 years. Substantial sociodemographic and geographical disparities exist in frailty incidence.

Recent developments in nanomedicine for melanoma treatment.

Melanoma is a most aggressive skin cancer with limited therapeutic options and its incidence is increasing rapidly in recent years. The discovery and application of new targeted therapy agents have shown significant benefits. However, adverse side-effects and resistance to chemotherapy remain formidable challenges in the clinical treatment of malignant melanoma. Nanotherapeutics offers an important prospect of overcoming these drawbacks. The anti-tumoral applications of nanomedicine are varied, including those in chemotherapy, RNA interference, photothermal therapy, and photodynamic therapy. Furthermore, nanomedicine allows delivery of the effector structures into the tumor site via passive or active targeting, thereby allowing increased therapeutic specificity and reduced side effects. In this review, we summarize the latest developments in the application of nanocarrier-mediated targeted drug delivery to melanoma and nanomedicine-related clinical trials in melanoma treatment. We also discuss existing problems and opportunities for future developments, providing direction and new thoughts for further studies.

Standardization of the manufacturing procedure for Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine.

ETHNOPHARMACOLOGICAL RELEVANCE: Pinelliae Rhizoma (PR), the dried tuber of Pinellia ternata (Thunb.) Breit., is a traditional Chinese medicinal herb. It is commonly used for treating cancer, cough and phlegm. To treat cancer, Chinese medicine practitioners often use raw PR; while to treat cough and phlegm, they usually use Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRZA, raw PR processed with ginger juice and alumen as adjuvant materials). Currently, the producing protocol of PRZA varies greatly among different places in China. This study aims to standardize the manufacturing procedure for PRZA. We also evaluated the impact of processing on the bioactivities and chemical profile of raw PR. MATERIALS AND METHODS: We used the orthogonal design to optimize the manufacturing procedure of PRZA at bench scale, and validated the optimized procedure in pilot-scale production. The MTT assay was used to compare the cytotoxicities of raw PR and PRZA in hepatocellular carcinoma HepG2 cells. Animal models (ammonia liquor-induced cough model and phenol red secretion model) were used to compare the antitussive and expectorant effects of raw PR and PRZA, respectively. The chemical profiles of raw PR and PRZA samples were compared using a newly developed ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method. RESULTS: The standardized manufacturing procedure for PRZA is as follows: soak raw PR in water until the center of the cut surface is devoid of a dry core, after that, boil the herb in water (for each 100kg raw PR, 12.5kg alumen and 25L freshly squeezed ginger juice are added) for 6h, and then take out and dry them. The cytotoxicity of PRZA was less potent than that of raw PR. Intragastric administration of raw PR or PRZA demonstrated antitussive and expectorant effects in mice. These effects of PRZA were more potent than that of raw PR at the dose of 3g/kg. By comparing the chemical profiles, we found that six peaks were lower, while nine other peaks were higher in PRZA than in raw PR. Six compounds corresponding to six individual changed peaks were tentatively identified by matching with empirical molecular formulae and mass fragments. CONCLUSION: The manufacturing procedure for PRZA was standardized. This protocol can be used for PRZA industrial production. The bioactivity assay results of raw PR and PRZA (produced using the standardized protocol) support the common practice for the clinical applications of these two decoction pieces. Moreover, raw PR and PRZA showed different chemical profiles. Further studies are warranted to establish the relationship between the alteration of chemical profiles and the changes of medicinal properties caused by processing.

Metabolomics reveals the mechanisms for the cardiotoxicity of Pinelliae Rhizoma and the toxicity-reducing effect of processing.

Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR. Rat serum metabolites were analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data highlighted the biological pathways and network functions involved in raw PR-induced toxicities and the toxicity-reducing effect of processing, which were verified by molecular approaches. Results showed that raw PR caused cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling and activation of the TGF-ß pathway contributed to raw PR-induced cardiotoxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on the mechanisms of raw PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This study provides scientific justifications for the traditional processing theory of PR, and should help in optimizing the processing protocol and clinical combinational application of PR.