Cordycepin Alleviates Anterior Cruciate Ligament Transection (ACLT)-Induced Knee Osteoarthritis Through Regulating TGF-ß Activity and Autophagy.

INTRODUCTION: Osteoarthritis is the most prevalent articular disease in the elderly. We aimed to explore the role of cordycepin (COR) in the progression and development of osteoarthritis and its correlation with TGF-ß activity and autophagy. METHODS: Sprague Dawley rats were induced by anterior cruciate ligament transection (ACLT) to establish knee osteoarthritis model. To investigate the role of COR in knee osteoarthritis, rats were injected with 5, 10, and 20 mg/kg of COR before joint surgery. After surgery, paw withdrawal mechanical threshold (PWMT) was performed. HE staining and Alcian blue staining were carried out to detect cartilage damage. ELISA was used to detect the level of TGFß in the serum. Protein expression was analyzed by Western blotting. RESULTS: In this study, we found that the PWMT of rats with osteoarthritis induced by ACLT was decreased significantly, accompanied by obvious histological and cartilage damage. After different doses of COR treatment, the PWMT of osteoarthritis rats induced by ACLT was increased in a dose-dependent manner. In addition, compared with the control group, COR treatment also reversed the effect of ACLT on cartilage injury in rats. Furthermore, the level of TGF-ß in serum of ACLT rats was increased significantly, which may be related to the overexpression of TGF-ß R1. However, the increase of serum TGF-ß level in ACLT rats was reversed by COR treatment in a dose-dependent manner. It is worth noting that TGF-ß overexpression reduced the proportion of autophagy-related protein LC3-II/I, thus inhibiting autophagy. In order to further confirm the effect of TGF-ß on autophagy, TGF-ß was overexpressed or the autophagy inhibitor 3-MA was applied. The results showed that TGF-ß overexpression and 3-MA treatment reversed the effect of COR on autophagy. CONCLUSION: In summary, our findings declared that COR alleviated ACLT-induced osteoarthritis pain and cartilage damage by inhibiting TGF-ß activity and inducing autophagy in rat model with knee osteoarthritis.

Psycho-social and educational interventions for enhancing adherence to dialysis in adults with end-stage renal disease: A meta-analysis.

AIMS AND OBJECTIVES: To examine the influence of psycho-social and educational interventions on improving adherence to dialysis for patients with end-stage renal disease. BACKGROUND: Adherence to the complex regimen is poor, contributing to avoidable hospitalisation and morbidity. Psycho-social and educational interventions may be beneficial coping strategies. DESIGN: Systematic literature review and meta-analysis were conducted. METHODS: We conducted a systematic search of 8 databases from their inceptions to 16 January 2019 to identify relevant articles. Only randomised controlled trials (RCTs) were included in the analysis. The PRISMA checklist was used. RESULTS: A total of forty RCTs were included to evaluate the effect. The aggregated results of the studies showed that psycho-social and educational interventions elevated adherence rate in both peritoneal dialysis (PD) and haemodialysis (HD) patients. For physiological and biochemical indicators, meta-analysis revealed that significant post-treatment effects were evident for interdialytic weight gain (IDWG), IDWG/dry weight, serum potassium, phosphate, creatinine and blood urea nitrogen (BUN), except for albumin. In particular, subgroup analysis indicated that only the interventions carried out individually exerted significant combined effect for lowering IDWG. As for subjective measures, meta-analysis also revealed small but significant combined effects. CONCLUSIONS: The results of this meta-analysis suggest that psycho-social and educational interventions were associated with significant effects on adherence in patients receiving dialysis regimen. RELEVANCE TO CLINICAL PRACTICE: The analysis suggests that psycho-social and educational interventions should be considered as effective strategies for enhancing adherence to dialysis in adults with end-stage renal disease. The potential utility of these interventions should focus on how best to promote individually implementation in clinical practice.

Effects of non-pharmacological supportive care for hot flushes in breast cancer: a meta-analysis.

PURPOSE: To assess the efficacy of non-pharmacological therapies for hot flushes (HFs) in women with breast cancer (BC). METHODS: Nine databases (MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), China Biology Medicine (CBM), and Wan Fang Database) were searched from their inceptions to October 2016. We also hand-searched reference lists of reviews and included articles, reviewed conference proceedings, and contacted experts. Finally, randomized controlled trials (RCTs) were aggregated to evaluate the therapeutic effect of acupuncture for HFs in women with BC. RESULTS: Sixteen trials were included in the meta-analysis. Significant combined effects of non-pharmacological therapies were observed in reducing frequency and severity of HFs after treatment (d = -0.57, P < 0.001). These effects were sustained, albeit reduced in part, during follow-up (d = -0.36, P < 0.001), with the exception of frequency (P = 0.41). Meta-analysis according to therapy types showed that for hypnosis, HFs scores instead of scores of HFs-related daily interference scale (HFRDIS) were significantly lowered at the post-treatment time point (d = -13.19, P < 0.001); for acupuncture, a small but significant effect on HFRDIS was found at the post-treatment time point (d = -3.34, P < 0.001). The effect was sustained during follow-up; however, no effect was evident for HFs frequency; for cognitive behavioral therapy (CBT), at the post-treatment time point, but not during follow-up, a small but significant effect was documented for HFs score (d = -0.88, P < 0.01). No serious adverse effect was reported in the included studies. CONCLUSIONS: Various types of non-pharmacological therapies were associated with significant effects on HFs in women with BC.

Effects of Acupuncture, Tuina, Tai Chi, Qigong, and Traditional Chinese Medicine Five-Element Music Therapy on Symptom Management and Quality of Life for Cancer Patients: A Meta-Analysis.

CONTEXT: Most cancer patients suffer from both the disease itself and symptoms induced by conventional treatment. Available literature on the clinical effects on cancer patients of acupuncture, Tuina, Tai Chi, Qigong, and Traditional Chinese Medicine Five-Element Music Therapy (TCM-FEMT) reports controversial results. OBJECTIVES: The primary objective of this meta-analysis was to evaluate the effect of acupuncture, Tuina, Tai Chi, Qigong, and TCM-FEMT on various symptoms and quality of life (QOL) in patients with cancer; risk of bias for the selected trials also was assessed. METHODS: Studies were identified by searching electronic databases (MEDLINE via both PubMed and Ovid, Cochrane Central, China National Knowledge Infrastructure, Chinese Scientific Journal Database, China Biology Medicine, and Wanfang Database). All randomized controlled trials (RCTs) using acupuncture, Tuina, Tai Chi, Qigong, or TCM-FEMT published before October 2, 2014, were selected, regardless of whether the article was published in Chinese or English. RESULTS: We identified 67 RCTs (5465 patients) that met our inclusion criteria to perform this meta-analysis. Analysis results showed that a significant combined effect was observed for QOL change in patients with terminal cancer in favor of acupuncture and Tuina (Cohen's d: 0.21-4.55, P < 0.05), whereas Tai Chi and Qigong had no effect on QOL of breast cancer survivors (P > 0.05). The meta-analysis also demonstrated that acupuncture produced small-to-large effects on adverse symptoms including pain, fatigue, sleep disturbance, and some gastrointestinal discomfort; however, no significant effect was found on the frequency of hot flashes (Cohen's d = -0.02; 95% CI = -1.49 to 1.45; P = 0.97; I(2) = 36%) and mood distress (P > 0.05). Tuina relieved gastrointestinal discomfort. TCM-FEMT lowered depression level. Tai Chi improved vital capacity of breast cancer patients. High risk of bias was present in 74.63% of the selected RCTs. Major sources of risk of bias were lack of blinding, allocation concealment, and incomplete outcome data. CONCLUSION: Taken together, although there are some clear limitations regarding the body of research reviewed in this study, a tentative conclusion can be reached that acupuncture, Tuina, Tai Chi, Qigong, or TCM-FEMT represent beneficial adjunctive therapies. Future study reporting in this field should be improved regarding both method and content of interventions and research methods.

Psycho-oncologic interventions to reduce distress in cancer patients: a meta-analysis of controlled clinical studies published in People's Republic of China.

OBJECTIVE: This study aimed to summarize the current result of controlled clinical studies published in China and analyzed the effect of psycho-oncologic interventions on distress of cancer patients. METHODS: Electronic searches were conducted in four databases. The study inclusion criteria were established on the basis of the PICOS (population, intervention, comparator, outcomes, and study design) framework. The main outcome measures were emotional distress, anxiety, and depression. Meta-analytic techniques were applied to analyze published data from the retrieved studies. RESULTS: A total of 207 controlled studies (involving 19,607 cancer patients) were included, among which 31 studies (3007 patients) were meta-analyzed. Pooled analysis showed large effects for psycho-oncologic interventions on anxiety (d = -8.71, p < 0.001) and depression (d = -8.12, p < 0.001). Health education combined with psychological support (d = -8.17, p = 0.04) or with relaxation training (d = -12.95, p < 0.001) significantly lowered the anxiety level in cancer patients. However, health education combined with relaxation training did not lower the depression levels (p > 0.05). Nurses were the primary health professionals (69.08%) responsible for delivering interventions. Meanwhile, none of the reports followed all the items of the consolidated standards of reporting trials checklist. Most studies suffered from some flaws concerning blinding, randomization procedures, participant follow-up, attrition, and so on. CONCLUSION: The findings pointed out that psycho-oncologic interventions significantly reduced distress in cancer patients of China; however, the quality of the randomized controlled trials was low. In the future, reports on controlled clinical studies should follow the consolidated standards of reporting trials statement and supply more comprehensive information.

Enhanced anticancer activity of gemcitabine coupling with conjugated linoleic acid against human breast cancer in vitro and in vivo.

Gemcitabine (GEM) is a nucleoside analog agent against a wide variety of tumors. To overcome its limitation of rapid metabolism in vivo that results in short circulation time and poor antitumor efficacy, a novel prodrug (CLA-GEM conjugate) has been developed through the covalent coupling of conjugated linoleic acid (CLA) to N(4)-amino group of GEM. The chemical structure of CLA-GEM conjugate was identified by NMR, FTIR and other methods. From in vitro tests, it was demonstrated that the linkage with CLA increased the plasma stability of GEM as well as the antitumor activity against human breast tumor cells (MCF-7). Importantly, it also altered the transport pattern of GEM across cell membrane (MCF-7 and MDA-MB-231), evidenced by the little effect of nucleoside transporter inhibitors (NBMPR and dipyridamole) on the IC(50) values of CLA-GEM, instead of the great effect on that of unmodified GEM. In vivo pharmacokinetic study showed that the CLA-GEM conjugate had a longer plasma half-life and a higher bioavailability compared to that of unmodified GEM. Significant stronger antitumor activity was observed in the nude mice xenografted MCF-7 breast tumor after treated with CLA-GEM than that of unmodified GEM, while no significant body weight loss was found in all treatments. In conclusion, the novel CLA-GEM conjugate prepared in this study would be a promising prodrug of gemcitabine for future clinical use.

[Detection of rearrangements of mixed lineage leukemia gene and its clinical significance].

To study the incidence, the types of fusion genes and the clinical significance of rearrangements of mixed lineage leukemia (MLL) gene in acute leukemia (AL), the rearrangements of MLL gene of 60 patients with AL were detected by fluorescence in situ hybridization (FISH) and 6 types of common fusion genes resulting from the rearrangements of MLL gene were detected by nested RT-PCR. The results showed that 7 out of 60 AL patients were found the rearrangements of MLL gene, the incidence of which was 11.67%. 2 out of 7 patients were diagnosed as AML-M(5), 5 patients were diagnosed as B-ALL. The fusion genes of the 2 AML-M(5) patients who had the rearrangements of MLL gene were MLL/AF(9). Among 5 B-ALL patients, 2 patients were confirmed to express MLL/ENL, 1 patient was confirmed to express MLL/AF(4), the other 2 patients did not express the fusion genes. It is concluded that FISH is a fast, specific and sensitive method to detect the rearrangements of MLL gene in AL patients and nested RT-PCR is a convenient and feasible method to detect the types of fusion genes resulting from the rearrangements of MLL gene. The detection of MLL gene rearrangement is of great importance in predicting prognosis and guiding therapy in AL.