Search

Background Prolonged life expectancy is associated with increased prevalence of chronic diseases. The aim of this study was to determine the different disability trajectories for the top ten leading causes of death in Taiwan . Methods A total of 2,431 participants aged 50–96 in 1996 from the Taiwan longitudinal study on aging (TLSA) who died from 1996 to 2016 were analyzed. Integration of Cause of Death Data and TLSA helped sort out participants who had died from the ten leading causes of death. The level of physical disability was evaluated with the Activities of Daily Living Scale (ADLs), ranging from 0 to 6 points, in 1996, 1999, 2003, 2007, and 2011. A multilevel model was used to investigate the levels and rates of change in disability development before death. Results The outcome of the research showed that the earliest group to experience physical limitation was individuals living with diabetes. The groups with the highest ADL scores were participants with diabetes, cerebrovascular disease, and hypertension-related diseases. Most groups reach ADL scores ≥ 1 (mild-level) during 4–6 years before death except chronic hepatitis and cirrhosis and injury. Conclusions People who had died from the ten leading causes of death experienced different disability trajectories before death. The trajectory of the participants who had died from diabetes showed a unique pattern with the earliest occurrence and more severe deterioration in terms of development of disabilities. Disability trajectories provide a prediction of survival status for middle-aged and older adults associated with the ten leading causes of death.

Several studies have demonstrated increased postoperative mortality rates in patients on chronic hemodialysis compared with non-dialyzed patients. However, limited studies have examined factors that may contribute to postoperative mortality.In this retrospective cohort study, data were collected from 9,140 dialysis and 45,725 non-dialysis patients undergoing surgery between 2007 to 2009 from Taiwan's National Health Insurance Registry Database. Patient demographics, comorbidities, and anesthesia duration were used to compare 30-day postoperative mortality differences in dialysis patients.Dialysis patients undergoing first-time surgery were significantly older, more likely male, and possessed more comorbidities. Overall, dialysis patients had significantly higher all-cause postoperative mortality (odds ratio, 15.005; 95% confidence interval, 11.917-18.893). Gender (hazard ratio [HR], 0.762), age (HR, 1.012), longer duration of inhalation general anesthesia (HR, 1.113), and comorbidities of hypertension (HR, 0.759), diabetes (HR, 1.339), congestive heart failure (HR, 1.232), coronary artery disease (HR, 1.326), cerebral vascular accident (HR, 1.312), intracranial hemorrhage (HR, 6.765), gastrointestinal bleeding (HR, 1.396), and liver cirrhosis (HR, 2.027), independently increased postoperative mortality risk in dialysis patients. Of the comorbidities, intracranial hemorrhage posed the greatest risk.Patient demographics, anesthesia factors, and comorbidities help dialysis patients understand their postoperative mortality. These potential risk factors also inform anesthesiologists and surgeons weight perioperative conditions in dialysis patients before surgery.

Hyperthermia is one therapeutic tool for damaging and killing cancer cells, with minimal injury to normal tissues. However, its cytotoxic effects alone are insufficient for quantitative cancer cell death. To overcome this limitation, several studies have explored non-toxic enhancers for hyperthermia-induced cell death. Capsaicin may be applicable as a therapeutic tool against various types of cancer. In the present study, we employed nonivamide, a less-pungent capsaicin analogue, to investigate its possible enhancing effects on hyperthermia-induced apoptosis; moreover, we analyzed its molecular mechanism. Treatment of U937 cells at 44 °C for 15 min, combined with nonivamide 50 μM, revealed enhancement of apoptosis. Significant increases in reactive oxygen species generation, mitochondrial dysfunction, and cleaved caspase-3 were observed during the combined treatment; these were accompanied by an increase in pro-apoptotic Bcl-2 family proteins and a decrease in anti-apoptotic Bcl-2 proteins. In addition, significant increases in p-JNK and p-p38 were detected, following the combined treatment. In conclusion, nonivamide enhanced hyperthermia-induced apoptosis via a mitochondrial-caspase dependent pathway. The underlying mechanism may include elevation of intracellular reactive oxygen species, mitochondrial dysfunction, and increased activation of JNK and p38.

Melatonin, a safe endogenous hormone and a natural supplement, has recently been recognized to have antiproliferative effects and the ability to sensitize cells to other anticancer therapies. Phenylarsine oxide (PAO) has anticancer potential but it is considered as a toxic agent. In this study we combined melatonin to reduce the toxicity while securing the anti-cancer effects of PAO. Cell viability was determined by MTT assay, whereas cytotoxic assays were performed using an LDH cytotoxicity assay kit. Cell cycle analysis, Annexin V/PI staining, the mitochondrial membrane potential (MMP), mitochondrial calcium and reactive oxygen species (ROS) generation were analyzed using flow cytometry. Sytox stained cells were visualized by fluorescence microscopy and the expression of proteins was detected by western blotting. Melatonin increased the anticancer potential of PAO by decreasing the cell viability and increasing LDH release in various cancer cells. The mode of cell death was determined to be typical apoptosis, as evidenced by Annexin V/PI-stained cells, PARP cleavage, and caspase-3 activation, and with significant modulations in the expression of proapoptotic, antiapoptotic and cell cycle-related proteins. ROS generation played a critical role in induction of cell death by this combined treatment, which is validated by reversal of cytotoxicity upon cotreatment with NAC. Furthermore, the activation of MAPKs, especially JNK, contributed to the induction of cell death, accompanied by endoplasmic reticulum stress and autophagy, affirmed by the abrogation of cytotoxicity after JNK-IN-8 and TUDCA application. Melatonin showed promising potential as a chemotherapeutic agent in combination with PAO to achieve a better anticancer response.

Recent research suggests that melatonin (Mel), an endogenous hormone and natural supplement, possesses anti-proliferative effects and can sensitise cells to anti-cancer therapies. Although shikonin (SHK) also possesses potential anti-cancer properties, the poor solubility and severe systemic toxicity of this compound hinders its clinical usage. In this study, we combined Mel and SHK, a potentially promising chemotherapeutic drug combination, with the aim of reducing the toxicity of SHK and enhancing the overall anti-cancer effects. We demonstrate for the first time that Mel potentiates the cytotoxic effects of SHK on cancer cells by inducing oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway. Particularly, Mel-SHK treatment induced oxidative stress, increased mitochondrial calcium accumulation and reduced the mitochondrial membrane potential in various cancer cells, leading to apoptosis. This drug combination also promoted endoplasmic reticulum (ER) stress, leading to AKT dephosphorylation. In HeLa cells, Mel-SHK treatment reduced SIRT3/SOD2 expression and SOD2 activity, while SIRT3 overexpression dramatically reduced Mel-SHK-induced oxidative stress, ER stress, mitochondrial dysfunction and apoptosis. Hence, we propose the combination of Mel and SHK as a novel candidate chemotherapeutic regimen that targets the SIRT3/SOD2-AKT pathway in cancer., Highlights • Melatonin (Mel) greatly sensitises cancer cells to toxic effect of shikonin (SHK). • SIRT3/SOD2-AKT induced-excessive oxidative stress is the key node in Mel-SHK therapy. • ER stress and mitochondrial dysfunction is also associated in the cell death. • Mel-SHK is a novel candidate for advanced chemotherapeutic regimen.

Background/Aims: Hyperthermia is a widely used therapeutic tool for cancer therapy and a well-known inducer of apoptosis. Although the flavonoid compound baicalin (BCN) is a potent anticancer agent for several human carcinomas, it is less potent in the human U937 myelomonocytic leukemia cell line. To explore any enhancing effects of BCN on hyperthermia-induced apoptosis, this study investigated the combined effects and apoptotic mechanisms of hyperthermia and BCN in U937 cells. Methods: U937 cells were heat treated at 44ºC for 12 min with or without pre-treatment with BCN (10-50 µM) and then incubated for 6 h at 37 ºC with 5% CO2 and 95% air. Cell viability was analyzed by Trypan blue exclusion assay. Apoptosis was examined by DNA fragmentation, fluorescence microscopy and flow cytometry. Generation of mitochondrial trans-membrane potential (MMP), mitochondrial calcium, and reactive oxygen species (ROS) was also detected by flow cytometry. The expression of proteins related to apoptosis and signaling pathways was determined by western blotting. Results: Hyperthermia alone did not reduce cell viability or induce notable levels of apoptosis, but combined hyperthermia and BCN treatment markedly augmented apoptosis by upregulating proapoptotic proteins and suppressing antiapoptotic proteins, culminating in caspase-3 activation. Mitochondrial transmembrane potential was significantly decreased, and generation of reactive oxygen species (ROS) and suppression of antioxidant enzymes were marked. Furthermore, with the combined treatment, the phosphorylated forms of JNK and p38 showed increased expression, whereas AKT was dephosphorylated. JNK-IN-8 (a JNK inhibitor) and NAC (a ROS scavenger) abrogated the apoptotic effects of the combined treatment, significantly protecting the cells and indicating the involvement of high ROS generation and the MAPK pathway in the underlying molecular mechanism. Conclusion: This study provides compelling evidence that hyperthermia, in combination with BCN, is a promising therapeutic strategy for enhancement of apoptosis and suggest a promising therapeutic approach for cancer.

Introduction Acute diarrhea is one of the most frequent illnesses in children and causes hospital attendance in developing countries. This systematic review and meta-analysis aimed to assess the beneficial effect and safety of acupoint herbal patching (AHP) at Shenque (CV8) as an adjunctive therapy for acute diarrhea in children. Methods We searched for published or registered randomized clinical trials (RCTs) in seven databases (from their inception to September 30, 2016) and three clinical trial registries that compared combined therapy of AHP applied at Shenque together with conventional treatments to conventional treatments alone. Data extraction and risk of bias assessment were conducted by two independent reviewers. Stata 12.0 was used for statistical analyses. Results 21 eligible studies involving 3560 children with acute diarrhea were included. All of the RCTs were generally of poor methodological quality. Compared with conventional treatments which included symptomatic treatment (fluid supplementation, nutritional management, adsorbents, probiotics, etc.) and anti-infection therapy (antibiotics or antiviral drugs), AHP at Shenque as adjuvant therapy reduced mean duration of diarrhea (MD = −36.49 h, 95% confidence interval −47.50 to −25.49) and decreased the risk of treatment failure (RR = 0.21, 95% confidence interval 0.17 to 0.27) at 72 h after treatment began without any reports of serious adverse events. Conclusions AHP applied at Shenque (CV8) as an adjunct therapy seemed to be a therapeutic choice in the management of diarrhea in children. However, a robust conclusion could not be drawn. Future clinical trials should be designed more rigorously.

ObjectiveTo observe the protection effect of rhTPO and granulocyte colony stimulating factor (G-CSF) on brain nerve after hypoxic ischemic brain damage (HIBD) in neonatal rats, exploring new ways for the laboratory basis of treatment for hypoxic ischemic encephalopathy, and provide for possible.MethodsA total of 120 newborn SD rats aging 7 d were randomly divided into control group, model group, TPO group and G-CSF group, using the method of blockingleft carotid artery to establish HIBD model. The left carotid artery was only seperated rather than blocked in the control group; after modeling, saline injection, rhTPO treatment and G-CSF treatment were adopted in the model group, TPO group and G-CSF group respectively. Then 10 rats of 4 groups were executed at Day 3, 7, 14 after modeling, brain tissue was extracted to observe the brain damage; Immunohistochemical method was used to observe the histopathological changes of brain tissue and changes of nest protein (nestin) expression.ResultsInjured brain mass of model group, TPO group and G-CSF group were significantly higher than that of control group at corresponding time point (P

BACKGROUND: The safety and health benefits of Tai Chi mind-body exercise has been documented in a large number of clinical studies focused on specific diseases and health conditions. The objective of this systematic review is to more comprehensively summarize the evidence base of clinical studies of Tai Chi for healthcare. METHODS AND FINDINGS: We searched for all types of clinical studies on Tai chi in PubMed, the Cochrane Library and four major Chinese electronic databases from their inception to July 2013. Data were analyzed using SPSS17.0 software. A total of 507 studies published between 1958 and 2013 were identified, including 43 (8.3%) systematic reviews of clinical studies, 255 (50.3%) randomized clinical trials, 90 (17.8%) non-randomized controlled clinical studies, 115 (22.7%) case series and 4 (0.8%) case reports. The top 10 diseases/conditions was hypertension, diabetes, osteoarthritis, osteoporosis or osteopenia, breast cancer, heart failure, chronic obstructive pulmonary disease, coronary heart disease, schizophrenia, and depression. Many healthy participants practiced Tai Chi for the purpose of health promotion or preservation. Yang style Tai Chi was the most popular, and Tai Chi was frequently practiced two to three 1-hour sessions per week for 12 weeks. Tai Chi was used alone in more than half of the studies (58.6%), while in other studies Tai Chi was applied in combination with other therapies including medications, health education and other physical therapies. The majority of studies (94.1%) reported positive effects of Tai Chi, 5.1% studies reported uncertain effects and 0.8% studies reported negative effects. No serious adverse events related to Tai Chi were reported. CONCLUSIONS: The quantity and evidence base of clinical studies on Tai Chi is substantial. However, there is a wide variation in Tai Chi intervention studied and the reporting of Tai Chi intervention needs to be improved. Further well-designed and reported studies are recommended to confirm the effects of Tai Chi for the frequently reported diseases/conditions.