Management of cognitive frailty: A network meta-analysis of randomized controlled trials.

OBJECTIVES: We aimed to compare the effectiveness of interventions in cognitive function and frailty status and rank these interventions. METHODS: Data Sources-We searched PubMed, Embase, CINAHL, PsycINFO, Web of Science, Cochrane Library, Central Register of Controlled Trials (CENTRAL), CNKI, Wanfang, VIP and Google scholar. Data synthesis-The risk of bias was assessed using the Cochrane risk bias assessment tool. Statistical heterogeneity was assessed using the Chi-square test and quantified by I2 . The results were pooled using the standardized mean difference (SMD). The rank probability for each intervention was calculated using the surface under the cumulative ranking curve (SUCRA). Additionally, the quality of the evidence was evaluated using the GRADE approach. RESULTS: A total of 10 randomized controlled trials (RCTs) involving 1110 patients were included in our analysis. The network map of cognitive function comprised 9 RCTs with 1347 participants, examining eight different interventions. Nutritional support (SUCRA = 99.9%, SMD = 3.02, 95% CI: 2.53, 3.51) may be the most effective intervention to improve cognitive function. The network map of frailty (including 9 RCTs with 1017 participants and 9 interventions) suggested that multicomponent exercises (SUCRA = 96.4%, SMD = -5.10, 95% CI: -5.96, -4.23) tended to have a greater effect. CONCLUSIONS: Community-based multicomponent exercises have shown significant benefits for improving cognitive function and frailty status in older adults, with moderate certainty. For hospitalized older patients with Cognitive frailty (CF), current evidence suggests that nutritional support yields the most improvement. Additionally, aerobic exercise and dual-task training have proven effective in managing CF. Further studies are needed to validate these preliminary findings and exploring more accessible and effective physical and cognitive interventions to prevent CF in aging.

Effects of Ruxolitinib on Myeloproliferative Neoplasms via the Negative Regulators.

BACKGROUND: We evaluated the JAK2V617F mutation and p-JAK2, SOCS-1, SHP-1 expression in JAK2V617F positive myeloproliferative neoplasms (MPNs) patients and the role of JAK/STAT pathway in human erythroleukemia (HEL) cells, which had JAK2V617F mutation. METHODS: Protein expression of p-JAK2, SOCS-1, SHP-1 in bone marrow biopsies (BMBs) were detected by immunohistochemical staining methods. Cell apoptosis and cell cycle were detected by flow cytometry and Caspase 3/7 assay kits. RESULTS: 1. The p-JAK2, SOCS-1, and SHP-1 expressions were significantly different between JAK2V617F positive MPN and control patients (p < 0.01); 2. After being treated for 3 months, the p-JAK2, SOCS-1, and SHP-1 expressions were significantly different compared with newly diagnosed patients (p < 0.01). 3. HEL cell viabilities were significantly different after being treated with different concentrations of ruxolitinib. Ruxolitinib had a significant effect on the cell apoptosis, viability, and the protein activity of caspase-3 and -7 of HEL cells. 3. The mRNA and protein expressions of JAK2 and the protein expression of p-JAK2 were gradually decreased (p ＜ 0.01, p ＜ 0.05), while the mRNA and protein expressions of SOCS1 and SHP1 were gradually increased (all p ＜ 0.01).

ER/AR Multi-Conformational Docking Server: A Tool for Discovering and Studying Estrogen and Androgen Receptor Modulators.

The prediction of the estrogen receptor (ER) and androgen receptor (AR) activity of a compound is quite important to avoid the environmental exposures of endocrine-disrupting chemicals. The Estrogen and Androgen Receptor Database (EARDB, http://eardb.schanglab.org.cn/) provides a unique collection of reported ERα, ERß, or AR protein structures and known small molecule modulators. With the user-uploaded query molecules, molecular docking based on multi-conformations of a single target will be performed. Moreover, the 2D similarity search against known modulators is also provided. Molecules predicted with a low binding energy or high similarity to known ERα, ERß, or AR modulators may be potential endocrine-disrupting chemicals or new modulators. The server provides a tool to predict the endocrine activity for compounds of interests, benefiting for the ER and AR drug design and endocrine-disrupting chemical identification.

Zoledronic acid exerts antitumor effects in NB4 acute promyelocytic leukemia cells by inducing apoptosis and S phase arrest.

The aim of this study was to investigate the antitumor effect of zoledronic acid (ZOL) in the NB4 human acute promyelocytic leukemia (APL) cell line and explore the potential mechanism of action of this compound. NB4 cells were exposed to various concentrations (0-200µM) of ZOL. Cell viability was measured by MTS assay. The extent of cell apoptosis and distribution of cells in the different phases of the cell cycle were analyzed with flow cytometry. The expression of apoptosis- and cell cycle-related proteins was assayed by Western blot. The combined effect of ZOL and arsenic trioxide (ATO) on the proliferation of NB4 cells was also determined. The results of this study indicate that ZOL inhibits cell proliferation in a time- and dose-dependent fashion and also induces apoptosis and S phase arrest in a dose-dependent manner. The Western blot analysis confirmed the induction of apoptosis and S phase arrest, revealing that the pro-apoptosis proteins Bax, Puma and activated caspase-9 were upregulated and the anti-apoptosis proteins Bcl-2 and Bcl-xL were downregulated. ZOL at a concentration of 50µM synergized with 0.5µM ATO on the growth inhibition of NB4 cells. Taken together, our data indicate that ZOL exerts a potent antitumor effect on NB4 cells by inducing apoptosis and cell cycle arrest, and that ZOL can synergize with the traditional chemotherapy drug ATO.

[Effects of activating and inhibiting Wnt/ß-catenin signaling pathway on murine model of eutopic endometrium and endometriosis].

OBJECTIVE: To employ the classical Wnt/ß-catenin signaling pathway interference to explore the effects on the functional changes of eutopic endometrium stromal cells and the differences between endometriosis in a murine model. METHODS: Two out of three mouse groups received an injection of either Wnt/ß-catenin signaling pathway activator or blocker. Later the endometrial tissue samples were obtained to develop endometrial stromal cell cultures for the detection of cell invasion ability via Boyden chamber invasion assay and Western blot (WB). Then the methods of WB and Immunohistochemical staining (IHC) were used to examine the factors of eutopic endometrium. And an endometriosis model was established to investigate the factors of signaling pathway via quantitative polymerase chain reaction (QPCR) and IHC. RESULTS: According to WB test, the level of ß-catenin, GSK-3ß and APC in the activation group were significantly higher than in the inhibition group (P < 0.01). In Boyden chamber invasion assay, the number of cells on membranes in the trial group was significantly higher than the control group [(113 ± 12) vs (64 ± 13)]. The expressions of VEGF and MMP-9 in the endometrial stromal cells culture from Boyden chamber assay analyzed via WB were ranked from highest to lowest respectively as activation group (vs control group was 35.6% and 27.4% higher), control group and inhibition group (vs control group was 12.3% and 30.4% lower). Furthermore, the endometrial E-cadherin and VEGF examined via IHC respectively showed a positive expression in inhibitor group and strong positive expression in activation group. QPCR showed the level of Wnt3, Wnt7, GSK3ß, Lef and E-cadherin in the activation group was higher than those in the inhibition group (P < 0.05). CONCLUSION: The intervention of WNT signaling pathway in vivo cause the changes of eutopic endometrial invasion and adhesion function, and further affect the development of endometriosis. Wnt/ß-catenin signaling pathway may promote the eutopic endometrial cell proliferation and improve the ability of eutopic endometrial implantation, invasion, metastasis and angiogenesis.

[A clinical study on the efficacy of HBeAg-positive chronic hepatitis B patients treated with adefovir dipivoxil for 4 years].

OBJECTIVE: To observe the efficacy and safety on the efficacy of HBeAg-positive chronic Hepatitis B patients treated with adefovir dipivoxil for 4 years. METHODS: Ninety-five patients with HBeAg-positive chronic hepatitis B were treated with adefovir dipivoxil 10 mg per day orally. The patients were observed before and after treatment for their serum levels of ALT and HBV DNA, the new increasing rates of serum ALT normalization, HBV DNA clearances, HBeAg loss, HBeAg seroconversion and adverse drug events. RESULTS: At 4 years on study, the rates of ALT normalization, HBV DNA clearances, HBeAg loss, HBeAg seroconversion and HBV DNA rebound were 89.5%, 63.2%, 47.4%, 41.1% and 8.0%, respectively. No drug related to renal function impairment was found during the treatment, eight patients had adverse drug events but all were mild. CONCLUSION: Adefovir dipivoxil could effectively inhibit HBV replication, normalize ALT and enhance transformation from HBeAg to HBeAb for cases with naive and treated-first patients. The efficacy were increased with prolongation of the treatment period. It is safe and has a good tolerance.