Frail older adults are predisposed to multiple comorbidities and adverse events. Recent interventional studies have shown that frailty can be improved and managed. In this study, effective ...individualized home-based exercise and nutrition interventions were developed for reducing frailty in older adults.
This study was a four-arm, single-blind, randomized controlled trial conducted between October 2015 and June 2017 at Miaoli General Hospital in Taiwan. Overall, 319 pre-frail or frail older adults were randomly assigned into one of the four study groups (control, exercise, nutrition, and exercise plus nutrition combination) and followed up during a 3-month intervention period and 3-month self-maintenance period. Improvement in frailty scores was the primary outcome. Secondary outcomes included improvements in physical performance and mental health. The measurements were performed at baseline, 1 month, 3 months, and 6 months.
At the 6-month measurement, the exercise (difference in frailty score change from baseline: - 0.23; 95% confidence interval CI: - 0.41, - 0.05; p = 0.012), nutrition (- 0.28; 95% CI: - 0.46, - 0.11; p = 0.002), and combination (- 0.34; 95% CI: - 0.52, - 0.16; p < 0.001) groups exhibited significantly greater improvements in the frailty scores than the control group. Significant improvements were also observed in several physical performance parameters in the exercise, nutrition, and combination groups, as well as in the 12-Item Short Form Health Survey mental component summary score for the nutrition group.
The designated home-based exercise and nutrition interventions can help pre-frail or frail older adults to improve their frailty score and physical performance.
Retrospectively registered at ClinicalTrials.gov (identifier: NCT03477097); registration date: March 26, 2018.
Kidney renal clear cell carcinoma (KIRC) is a prevalent type of urological malignancy. The present study aimed to predict biomarkers for KIRC.
We collected transcriptomic and clinical information for ...KIRC from The Cancer Genome Atlas and GSE22541 cohorts.
Unsupervised clustering of 35 epithelial-mesenchymal transformation (EMT)-related differentially expressed gene profiles divided samples into two clusters with distinct immune characteristics. Six genes (IL20RB, DDC, ANKRD36BP2, F2RL1, TEK, and AMN) were found to construct a prognostic risk model using multivariate Cox regression analysis. Kaplan-Meier analysis suggested the better prognosis of the KIRC patients in the low-risk group than that in the high-risk group. Immune infiltration analyses was conducted using xCell and single-sample gene set enrichment analysis, indicating that the risk score was associated with the immune microenvironment of the KIRC. Prognostic marker gene-targeted medications with high drug sensitivity were predicted in KIRC patients.
In summary, the present study identified IL20RB, DDC, ANKRD36BP2, F2RL1, TEK, and AMN as prognostic biomarkers, providing insight into immunotherapy and gene-targeted drugs of KIRC.
In this work, α-etherification of lignin in diol pretreatment was selectively enhanced at mild temperature for lignin isolation and subsequent valorisation. More than 90 % of lignin was removed from ...Eucalyptus at 120 °C in diol (ethylene glycol and 1,4-butanediol) pretreatment, resulting in >90 % cellulose conversion in 24 h at 7.5 FPU/g glucan cellulase loading. Subsequent catalytic transfer hydrogenolysis of the isolated lignins with Ru/C in ethanol gave 15 % monomer yield on native lignin basis, 5 times of that from the technical ethanol process (170 °C). HSQC NMR analysis revealed that diol pretreated lignin (120 °C) contained ∼23 % α-etherified β–O–4 interunit bonds, indicating that lignin degradation (i.e. cleavage of β–O–4 bonds) was suppressed via etherification by grafting a hydroxyl group at the α position of lignin. This finding was consistent with the isolated lignin (120 °C) had less number of phenolic OH and higher molecular weight via31P NMR and GPC analysis. 31P NMR analysis also revealed that diol isolated lignin contained more number of aliphatic OH than ethanol-isolated lignin, which increased lignin solubility and maintained the high yield (>80 %) of isolated lignin from Eucalyptus at 120 °C as expected. In summary, diol pretreatment of woody biomass can effectively isolate more lignin for hydrogenolysis to valued-added monomers without compromising the isolated yield of lignin and hydrolysis yield of remained cellulose.
Enhancing α-etherification of lignin by diol pretreatment at mild temperature (120 °C) to isolate lignin for producing 5 times monomer yield of that from technical ethanol pretreatment (170 °C) by hydrogenolysis. Display omitted
•α-Etherification of lignin by diol pretreatment was selectively enhanced at 120 °C.•Removing 90 % lignin with near complete hydrolysis of cellulose was achieved.•Diol pretreated lignin contained ∼23 % α-etherified β-O-4 interunit linkages.•Lignin also had less number of phenolic OH and higher molecular weight.•Catalytic transfer hydrogenolysis of lignin gave 15 % monomer yield.
As a representative of acupuncture and nonpharmaceutical therapy, auricular acupuncture has been widely for the treatment of insomnia. Transcutaneous auricular vagus nerve stimulation (taVNS) is a ...combination of auricular point stimulation and vagus nerve stimulation. It can not only treat primary insomnia effectively, but also is noninvasive, painless, portable and economical. The medial prefrontal cortex (mPFC) is a core region of default mode network (DMN), which is important for maintenance of sleep. However, the mechanism of taVNS in alleviating primary insomnia (PI) remains to be clarified. In this study, we found that taVNS could not only effectively reduce the score of Pittsburgh Sleep Quality Index, but also decreased functional connection (FC) between the left mPFC and bilateral dorsal anterior cingulate gyrus as well as FC between the right mPFC and the occipital cortex in patients with PI. Furthermore, the decrease in FC was positively correlated with the decline of sleep index score. Therefore, we proposed that treatment with taVNS can improve sleep quality and prolong sleep duration in patients with PI by reducing FC within DMN, FC between DMN and salience network, as well as FC between DMN and the occipital cortex. This may be one of mechanisms of taVNS in treating PI.
摘要
耳针疗法作为针灸的代表，已作为一种非药物疗法被广泛用于失眠的治疗。经皮耳‐迷走神经刺激(taVNS)将中医耳穴刺激与迷走神经刺激术(VNS)相融合，不仅可有效治疗原发性失眠，且具有非侵入、无痛、便携、价廉等优势。内侧前额叶(mPFC)是默认网络的核心区域，对睡眠的维持非常重要。然而，taVNS治疗原发性失眠的作用机制仍待进一步阐明。本研究发现，taVNS不仅可有效降低PI患者的PSQI总分，还降低了PI患者左mPFC与双侧背侧前扣带回及右mPFC与枕叶皮层之间的功能连接。并且，这种功能连接的降低与患者睡眠指标评分的降低具有正相关。因此，taVNS可能是通过降低默认网络内部及其与突显网络、枕叶皮层之间的FC来改善PI患者的睡眠质量，延长睡眠维持时间，这可能是taVNS治疗PI脑效应机制之一。
Pancreatic ductal adenocarcinoma (PDAC), a subtype of pancreatic cancer, is a malignant tumor with unfavorable prognosis. Despite accumulating researches have made efforts on finding novel ...therapeutic methods for this disease, the underlying mechanism of long non-coding RNAs (lncRNAs) remains elusive. OIP5 antisense RNA 1 (OIP5-AS1) has been reported to play important role in the occurrence and development of multiple human cancers. This study was aimed at unveiling the regulatory role of OIP5-AS1 in PDAC.
RT-qPCR analysis revealed the OIP5-AS1 expression in PDAC tissues and adjacent normal ones. Kaplan-Meier method was applied to analyze the overall survival of patients with high or low level of OIP5-AS1. Gain- or loss-of function assays were performed to assess the effects of OIP5-AS1 knockdown on cell functions, including proliferation, migration and EMT process. Mechanism experiments, such as luciferase reporter and RNA pull-down assays proved the interaction between OIP5-AS1 and miR-429 as well as that between miR-429 and FOXD1.
OIP5-AS1 was up-regulated in PDAC tissues and cell lines, and high level of OIP5-AS1 indicated poor prognosis in PDAC patients. OIP5-AS1 knockdown hindered cell proliferation, migration and epithelial-mesenchymal transition (EMT) process, while overexpression of OIP5-AS1 caused the opposite results. OIP5-AS1 activated ERK pathway through up-regulating forkhead box D1 (FOXD1) expression by sponging miR-429. Furthermore, OIP5-AS1 facilitated cell growth in vivo.
OIP5-AS1 exerted oncogenic function in PDAC cells through targeting miR-429/FOXD1/ERK pathway.
Inflammation, endothelial dysfunction, and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis (HD) patients. Physical exercise alleviates inflammation ...and increases bone density. Here, we investigated the effects of intradialytic aerobic cycling exercise on HD patients. Forty end-stage renal disease patients undergoing HD were randomly assigned to either an exercise or control group. The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up, 20 minutes of cycling at the desired workload, and a 5-minute cool down during 3 HD sessions per week for 3 months. Biochemical markers, inflammatory cytokines, nutritional status, the serum endothelial progenitor cell (EPC) count, bone mineral density, and functional capacity were analyzed. After 3 months of exercise, the patients in the exercise group showed significant improvements in serum albumin levels, the body mass index, inflammatory cytokine levels, and the number of cells positive for CD133, CD34, and kinase insert domain-conjugating receptor. Compared with the exercise group, the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs. The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program. Furthermore, the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program. Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition, bone mineral density, and exercise tolerance in HD patients.
Carbonic anhydrase IX (CAIX) protein has been correlated with progression and survival in patients with some tumors such as head and neck carcinoma. But renal cell carcinoma is an exception. The ...prognostic value of CAIX in RCC used to be associated with patients' survival according to published works. This study aimed to rectify the former conclusion.
This study was registered in PROSPERO (CRD42020160181). A literature search of the PubMed, Embase, Cochrane library and Web of Science databases was performed to retrieve original studies until April of 2022. Twenty-seven studies, including a total of 5462 patients with renal cell carcinoma, were reviewed. Standard meta-analysis methods were used to evaluate the prognostic impact of CAIX expression on patient prognosis. The hazard ratio and its 95% confidence interval were recorded for the relationship between CAIX expression and survival, and the data were analyzed using Stata 11.0. Then we verify the meta-analysis resort to bioinformatics (TCGA).
Our initial search resulted in 908 articles in total. From PubMed, Embase, Web of Science electronic and Cochrane library databases, 493, 318 and 97 potentially relevant articles were discovered, respectively. We took the analysis between CA9 and disease-specific survival (HR = 1.18, 95% CI: 0.82-1.70, I2 = 79.3%, P<0.05), a subgroup then was performed to enhance the result (HR = 1.63, 95%CI: 1.30-2.03, I2 = 26.3%, P = 0.228); overall survival was also parallel with the former (HR = 1.13, 95%CI: 0.82-1.56, I2 = 79.8%, P<0.05), then a subgroup also be performed (HR = 0.90, 95%CI:0.75-1.07, I2 = 23.1%, P = 0.246) to verify the result; the analysis between CAIX and progression-free survival got the similar result (HR = 1.73, 95%CI:0.97-3.09, I2 = 82.4%, P<0.05), we also verify the result by subgroup analysis (HR = 1.04, 95%CI:0.79-1.36, I2 = 0.0%, P = 0.465); at last the relationship between CAIX and recurrence-free survival got the same result, too (HR = 0.99, 95%CI: 0.95-1.02, I2 = 57.8%, P = 0.050), the subgroup's result was also parallel with the former (HR = 1.01, 95%CI: 0.91-1.03, I2 = 0.00%, P = 0.704). To validate our meta-analysis, we took a bioinformatic analysis based on TCGA database, survival curve between low and high CAIX expression in four endpoints (DSS, OS, PFI, DFI) have corresponding P value (DSS:P = 0.23, OS:P = 0.77, PFI:P = 0.25, DFI:P = 0.78).
CAIX expression in patients with RCC is an exception to predict tumor survival. Both low CAIX expression and high expression are not associated with survivals in RCC patients.
In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. Here, we aimed to elucidate the transitions of dialysis status in the unplanned first dialysis patients ...and determine factors associated with their outcomes. A total of 50,315 unplanned first dialysis patients aged more than 18 years were identified from the National Health Insurance Dataset in Taiwan between 2001 and 2012. All patients were followed for 5 years for the transitions in dialysis status, including robust (dialysis-free), sporadic dialysis, continued dialysis, and death. Furthermore, factors associated with the development of continued dialysis and death were examined by the Cox proportional hazard models. After 5 years after the first dialysis occurrence, there were 5.39% with robust status, 1.67% with sporadic dialysis, 8.45% with continued dialysis, and 84.48% with death. Notably, we have identified common risk factors for developing maintenance dialysis and deaths, including male gender, older age, diabetes, coronary heart disease, stroke, heart failure, sepsis, and surgery. There was an extremely high mortality rate among the first unplanned dialysis patients in Taiwan. Less than 10% of these patients underwent continued dialysis during the 5-year follow-up period. This study highlighted the urgent need for interventions to improve patient outcomes.
Epidemiological and clinical studies have clearly established the link between low-density lipoprotein cholesterol (LDL-C) and atherosclerosis-related cardiovascular consequences. Although it has ...been a common practice for physicians to prescribe lipid-lowering therapy for patients with dyslipidemia, the achievement rate is still not satisfied in Taiwan. Therefore, the determinants for achieving the LDL-C target needed to be clarified for better healthcare of the patients with dyslipidemia.
This registry-type prospective observational study enrolled the patients with cardiovascular diseases (coronary artery disease (CAD) and cerebrovascular disease (CVD)) from 18 medical centers across Taiwan, and clinically followed them for five years. At every clinical visit, vital signs, clinical endpoints, adverse events, concurrent medications and laboratory specimens were obtained as thoroughly as possible. The lipid profile (total cholesterol, high-density lipoprotein cholesterol, LDL-C, triglyceride), liver enzymes, and creatinine phosphokinase were evaluated at baseline, and every year thereafter. The cross sectional observational data was analyzed for this report.
Among the 3,486 registered patients, 54% had their LDL-C < 100 mg/dL. By univariate analysis, the patients achieving the LDL-C target were associated with older age, more male sex, taller height, lower blood pressure, more under lipid-lowering therapy, more smoking cessation, more history of CAD, DM, physical activity, but less history of CVD. The multivariate analysis showed statin therapy was the most significant independent determinant for achieving the treatment target, followed by age, history of CAD, diabetes, blood pressure, and sex. However, most patients were on regimens of very-low to low equipotent doses of statins.
Although the lipid treatment guideline adherence is improving in recent years, only 54% of the patients with cardiovascular diseases have achieved their LDL-C target in Taiwan, and the most significant determinant for this was statin therapy.
Growing evidence shows that the preoperative lymphocyte-related systemic inflammatory biomarkers are associated with the prognosis of patients with upper tract urothelial carcinoma (UTUC). These ...markers include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). However, these findings are inconsistent, and the prognostic significance of these biomarkers is unclear. Moreover, the currently available prognostic indicators do not precisely predict the outcome of UTUC patients. This motivated us to investigate the prognostic values of NLR, PLR, and MLR in UTUC patients treated with radical nephroureterectomy (RNU).
We prospectively registered this in PROSPERO (CRD42020186531). We performed a comprehensive literature search of the PubMed, Web of Science, EMBASE, and Cochrane Library databases to identify the eligible studies evaluating the prognostic values of preoperative NLR, PLR, and MLR. Hazard ratios with 95% confidence intervals of overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), recurrence-free survival (RFS), metastasis-free survival (MFS), and progression-free survival (PFS) were extracted from the multivariate analyses and analyzed with fixed or random effects models when applicable. Heterogeneity among the studies was evaluated using Cochran's Q test and I
statistic. Sensitivity and subgroup analyses were conducted to explore the origin of heterogeneity. The Newcastle-Ottawa Scale (NOS) was applied to assess the quality of each enrolled study. Publication bias was determined using funnel plots together with Egger's tests. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of the evidence.
Overall, we included 10,339 UTUC patients from twenty-five retrospective studies. The results indicated that elevated preoperative NLR, PLR, and MLR were significantly associated with worse OS, CSS, DFS/RFS/MFS, and PFS in the UTUC patients undergoing RNU. Furthermore, the results of sensitivity and subgroup analyses demonstrated the rationality and reliability of the results.
The present meta-analysis demonstrated a significant association between elevated preoperative NLR, PLR, and MLR and poor prognosis in patients with surgically treated UTUC. Hence, lymphocyte-related systemic inflammatory biomarkers, in conjunction with clinicopathological factors, molecular markers, and other prognostic indicators, could be helpful to determine the primary treatment strategies and to design individualized follow-up plans for UTUC patients.
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