[Effect of oral administration of branched-chain amino acids supplementation on the mortality of patients with hepatocellular carcinoma: a meta-analysis].

Objective: To investigate the effect of oral administration of branched-chain amino acids (BCAA) supplementation on the mortality of patients with hepatocellular carcinoma (HCC) after treatment. Methods: Computer searching of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Biomedical Literature Database was conducted to search for clinical controlled trials and randomized controlled trials (RCTs) on the effect of oral administration of BCAA on the mortality of patients with HCC. The retrieval time limit was from the time of the establishment of each database to December 30, 2019. Two researchers independently screened the literature and extracted the data. Another researcher assessed the risk of bias in the included studies and then used RevMan 5.3 software for meta-analysis. Results: A total of 14 studies were included with 1 179 patients. The overall results showed that oral administration of BCAA had no significant effect on the mortality of HCC patients at 1 year after treatment (RR=0.85, 95%CI:0.68-1.06, P=0.16), while the mortalities of patients at 3 years (RR=0.73, 95%CI: 0.61-0.88, P=0.000 7) and 5 years (RR=0.57, 95%CI:0.34-0.96, P=0.03) after treatment were significantly lower than those of the control group. The subgroup analysis showed that for radiofrequency ablation (RFA) patients, there was no significant difference in 1-year mortality between the BCAA group and the control group (RR=0.96, 95%CI:0.14-6.5, P=0.97), while 3-year mortality was significantly reduced (RR=0.59, 95%CI:0.43-0.81, P=0.001); for hepatectomy patients, there was no significant differences in 1 -and 3-year mortality between the two groups (RR=0.90, 95%CI:0.44-1.88, P=0.79; RR=0.97, 95%CI:0.71-1.33, P=0.85, respectively). In addition, as for albumin levels, BCAA supplementation significantly increased albumin levels without considering the treatment of HCC (SD=0.45, 95%CI: 0.29-0.90; P=0.000 1), but had no significant effect on hepatectomy patients (SD=0, 95%CI: -0.41-0.41, P=0.99). Conclusion: BCAA supplementation might improve liver reserve function and long-term prognosis of HCC patients, which was related to the surgical method. Supplementing BCAA reduced the long-term mortality of RFA patients, but had no significant effect on hepatectomy patients.

[Comparison of efficacy between sorafenib and sunitinib as first-line therapy for metastatic renal cell carcinoma and analyze prognostic factors for survival].

Objective: To investigate the efficacy and drug related adverse reactions of sorafenib and sunitinib as first-line tyrosine-kinase inhibitors (TKIs) for patients with metastatic renal cell carcinoma (mRCC) and analyze the clinical prognostic factor for survival. Methods: The data of 271 patients with metastatic renal cell carcinoma who had complete clinicopathological data were retrospectively analyzed, including 174 cases in sorafenib group and 97 cases in sunitinib group, to access patients' overall survival (OS) and progression-free survival (PFS). Prognostic values of all characteristics were determined by using univariate and multivariate Cox regression models. Results: The objective response rates (ORR) of the sorafenib and sunitinib groups were 14.9% and 19.6%, respectively, and the disease control rates (DCR) were 85.1% and 88.6%, respectively. No significant difference was found between the sorafenib and sunitinib group in ORR (P=0.325) or DCR (P=0.408). The most common grade 3 to 4 adverse events in the sorafenib group were hand-foot syndrome (6.7%), diarrhea (2.3%), and rash (2.3%). The most common grade 3 to 4 adverse events in the sunitinib group were neutropenia (6.2%), hand-foot syndrome (6.2%), and thrombocytopenia (4.6%). During the follow-up, 97 cases death occurred and 81 cases disease progression occurred in sorafenib group. The median PFS was 12 months (95% CI: 9-15 months), and the median OS was 25 months (95% CI: 21-29 months) in sorafenib group. While 74 cases death occurred and 40 cases disease progression occurred in sunitinib group, the median PFS was 12 months (95% CI: 10-12 months) and the median OS was 23 months (95% CI: 20-32 months) in sunitinib group. No significant difference was found between the sorafenib and the sunitinib group in PFS (P=0.771) or OS (P=0.548). Multivariate analysis showed Fuhrman grades (HR=1.358, 95%CI: 1.004-1.835), number of metastatic sites (HR=1.550, 95%CI: 1.143-2.101) and MSKCC risk grade (Intermediate risk group: HR=1.621, 95%CI: 1.117-2.232; Poor risk group: HR=2.890, 95%CI: 1.942-4.298) were independent prognostic factors for PFS. Fuhrman grades (HR=2.135, 95%CI: 1.533-2.974), number of metastatic sites (HR=1.774, 95%CI: 1.279-2.461) and MSKCC risk grade (Intermediate risk group: HR=1.415, 95%CI: 1.002-1.998; Poor risk group: HR=3.161, 95%CI: 2.065-4.838) were independent prognostic factors for OS. Conclusions: The results of this study indicate that sorafenib and sunitinib are both effective as the first-line TKIs for mRCC patients and sorafenib has comparable efficacy to sunitinib. But they have differences in the incidence of adverse effects. Fuhrman grades, number of metastatic sites and MSKCC risk grade are independent prognostic factors for mRCC patients.

Influence of hormone therapy or C. foetida extract on breast tenderness in postmenopausal women.

OBJECTIVE: To evaluate the prevalence of breast tenderness in a population treated with menopausal hormone therapy (MHT) or Cimicifuga foetida extract. METHODS: A prospective, randomized, controlled trial was conducted. Ninety-six postmenopausal women were randomly assigned to three groups: group A, 1 mg estradiol valerate daily plus 4 mg medroxyprogesterone acetate (MPA), days 19-30; group B, 1 mg estradiol valerate daily plus 100 mg micronized progesterone (MP), days 19-30; group C, 100 mg C. foetida extract daily. Breast tenderness was evaluated daily for 12 months. RESULTS: Seventy-three patients completed the study. Group A had the highest prevalence of breast tenderness, while group C had the lowest. More than 50% of all participants reported no symptoms throughout the period. The participants in group A experienced a sharp increase in breast tenderness after treatment, but decreased after 1 month. No significant decline was found in the duration of pain in group B. The patients in group C reported no remarkable changes after 1 month. Compared to estrogen only, estrogen plus MPA/MP led to a higher incidence of prolonged breast symptoms. CONCLUSIONS: Compared to MHT groups, C. foetida extract had the lowest prevalence of breast tenderness. Most participants experienced mild or no symptoms.

Efficacy and safety evaluation of Cimicifuga foetida extract in menopausal women.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of long-term treatment with Cimicifuga foetida extract in menopausal women. METHODS: A prospective, randomized, controlled clinical trial was conducted. A total of 96 early postmenopausal women were randomly assigned to three groups: group A received 1 mg estradiol valerate daily plus 4 mg medroxyprogesterone acetate on days 19-30; group B received 1 mg estradiol valerate daily plus 100 mg micronized progesterone on days 19-30; group C received 100 mg C. foetida extract daily. The efficacy was evaluated. Safety parameters were recorded. RESULTS: A total of 81 patients completed the treatment and follow-up visit. The modified Kupperman Menopausal Index scores decreased after 3 months in all groups. No significant changes were observed in the liver, renal function and components of metabolic syndrome in group C (p > 0.05). There were no significant differences in the incidences of metabolic syndrome among the three groups (p > 0.05). After 24 months, the endometrial thickness increased significantly in group B (p = 0.014), but not in the C. foetida extract group (p > 0.05). CONCLUSIONS: C. foetida extract is safe and effective for the treatment of menopausal symptoms in postmenopausal women.

ß-Hydroxybutyric acid inhibits growth hormone-releasing hormone synthesis and secretion through the GPR109A/extracellular signal-regulated 1/2 signalling pathway in the hypothalamus.

ß-Hydroxybutyric acid (BHBA) has recently been shown to regulate hormone synthesis and secretion in the hypothalamus. However, little is known about the effects of BHBA-mediated hormone regulation or the detailed mechanisms by which BHBA regulates growth hormone-releasing hormone (GHRH) synthesis and secretion. In the present study, we examined the expression of the BHBA receptor GPR109A in primary hypothalamic cell cultures. We hypothesised that BHBA regulates GHRH via GPR109A and its downstream signals. Initial in vivo studies conducted in rats demonstrated that GHRH mRNA expression in the hypothalamus was strongly inversely correlated with BHBA levels in the cerebrospinal fluid during postnatal development (r = -0.89, P < 0.01). Furthermore, i.c.v. administration of BHBA acutely decreased GHRH mRNA expression in rats. Further in vitro studies revealed a decrease in GHRH synthesis and secretion in primary hypothalamic cells after treatment with BHBA; this effect was inhibited when hypothalamic cells were pretreated with pertussis toxin (PTX). BHBA had no effect on GHRH synthesis and secretion in GT1-7 cells, which do not exhibit cell surface expression of GPR109A. Furthermore, BHBA acutely decreased the transcription of the homeobox gene for Gsh-1 in the hypothalamus in both in vivo and in vitro, and this effect was also inhibited by PTX in vitro. In primary hypothalamic cells, BHBA activated the extracellular signal-regulated kinase (ERK)1/2, p38 and c-Jun N-terminal kinase mitogen-activated protein kinase (MAPK) kinases, as shown by western blot analysis. Moreover, inhibition of ERK1/2 with U0126 attenuated the BHBA-mediated reduction in Gsh-1 expression and GHRH synthesis and secretion. These results strongly suggest that BHBA directly regulates GHRH synthesis and secretion via the GPR109A/ERK1/2 MAPK pathway, and also that Gsh-1 is essential for this function.

Effects of astragalosides on cultured islets after cryopreservation in rats.

OBJECTIVE: To explore the effects of AST (astragalosides) on cultured rat islet yield, purity, and function after cryopreservation in rats. METHODS: Pancreatic islets were isolated from 30 Sprague-Dawley rats using the standard technique of collagenase P digestion and discontinuous Ficoll gradient purification. After thaw, the islets were randomly divided into AST group and control group (n=15). Next, the islet cells were cultured in AST-containing medium or standard medium for 7, 14, and 21 days after cryopreservation and thaw. The quantity, purity, and survival rate were calculated in the two groups before and after culture. Then the in vitro and in vivo function was observed in diabetic rats after islet transplantation. RESULTS: The quantity and purity of islets had no difference between the two groups before culture (P>.05) while the difference after culture was significantly (P<.05). The survival rate of islets was 48% in AST group and 32% in the control group 21 days after thaw (P<.05). After 3 days, there was significantly a higher simulation index in the AST group than in the control group (P<.05). There was a significant difference in blood glucose and insulin concentrations between the groups after 3 days (P<.05). CONCLUSION: AST can be added to the culture medium to reduce the loss of islet cryopreservation and be intravenously injected to improve culture islet function in vitro and prolong islet graft survival in diabetic rats.

Clinical application of Cordyceps sinensis on immunosuppressive therapy in renal transplantation.

OBJECTIVE: We sought to explore the adjunctive effects of Cordyceps sinensis (CS) in clinical renal transplantation. MATERIALS AND METHODS: Patients (n = 202) were divided randomly by lottery into a treatment (n = 93) and a control group (n = 109). Patients in the treatment group were treated with CS 1.0 g 3 times a day in addition to the immunosuppressive regimen given to the control group. We compared patient and graft survivals, incidence, time and severity of acute rejection episodes, chronic allograft nephropathy (CAN), hepatotoxicity and nephrotoxicity, biochemistry parameters including indicators of liver and kidney functions, fats, proteinuria, dosages, and whole blood concentrations of cyclosporine (CsA). RESULTS: Patient and graft survival rates, serum creatinine (SCr), and blood urea nitrogen (BUN) were not significantly different between the 2 groups (P > .05). Serum uric acid (UA) and 24-hour urinary total protein (24-hour UTP) were significantly lower in the treatment group than in the control group (P < .05). The incidences (11.83% vs 15.60%) and times to acute renal allograft rejection (23.48 +/- 7.22 vs 22.27 +/- 8.03 days posttransplantation) were not significantly different between the treated and control groups (P > .05). Patients receiving thymoglobulin antirejection therapy (3 cases) were fewer in the heated versus control group (13 cases; P = .014). The incidences of hepatotoxicity and nephrotoxicity in the treated group were 12.90% and 19.35%, significantly lower than 24.77% and 33.94% in the control group, respectively (P < .05). At 2 to 6 months posttransplantation, the CsA dosages in the treated group were significantly lower than those in the control group (P < .05). The whole blood trough CsA concentrations in the treated group were significantly lower than those in the control group at 3 to 6 months posttransplantation (P < .05). The decreasing trends of the 2 aforementioned parameters in the treatment group were approximately linear among treated subjects compared with approximately quadratic in the control group (P < .05). The incidence of CAN in the treated group was 7.53%, which was significantly lower than 18.35% in the control group (P = .024). The 24-hour UTP level in CAN patients within the treated group was significantly lower than the control group after transplantation (P = .045). The differences in total bilirubin, SCr, serum UA, and total cholesterol levels among otherwise normal patients in the treated group were significantly lower than those among the control group (P < .05). CONCLUSIONS: The use of CS may allow decreased dosages and concentrations of CsA causing fewer side effects without an increased risk of acute rejection. In addition, CS with reduced dose CsA may decrease proteinuria and retard CAN progression.

Tumor suppressor effect of follistatin-like 1 in ovarian and endometrial carcinogenesis: a differential expression and functional analysis.

Endometrial and ovarian cancers are the most common and the most lethal gynecologic malignancies worldwide, respectively. By performing differential expression analysis using annealing control primer-based reverse transcription (RT)-polymerase chain reaction (PCR) on pooled complementary DNA (cDNA) from 45 endometrial and 36 ovarian cancers and their non-tumor samples, reduced expression of the follistatin-like 1 (FSTL1) was identified. Downregulation of FSTL1 was further confirmed on individual samples and cell lines by quantitative real-time RT-PCR and western blotting. For in vitro functional study, full-length cDNA of FSTL1 was cloned and transiently transfected into the ovarian cancer cell line Ovca420 and endometrial cancer cell line AN3CA. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cell count demonstrated significantly slower proliferation rate. By terminal uridine deoxynucleotidyl transferase dUTP nick end labeling and flow cytometric analysis, higher apoptotic activity and a remarkable increase in sub-G(1) cell population were observed in transfected cells, suggesting that FSTL1 induced apoptosis in cancer cells. Subsequent messenger RNA and protein expression analysis on downstream apoptotic molecules revealed upregulation and/or activation of FAS, FASLG, TRADD, Caspase-3, Caspase-7 and PARP by FSTL1 transfection, suggesting that FSTL1-induced apoptosis may be initiated mainly by FAS/FASLG death receptor-ligand binding. Cell migration and invasion assays demonstrated a remarkably lower cell migration and invasion capability in FSTL1-transfected cells in relation to downregulation of matrix metallopeptidase-2. Our findings suggested that a tumor suppressor role of FSTL1 may be important in ovarian and endometrial carcinogenesis.

The therapeutic effects of Sheng Jing Zhong Zi Tang in treating male infertility.

Eight-seven cases of male infertility due to spermatopathy were treated with Sheng Jing Zhong Zi Tang (SJZZT [symbol: see text]) for 1-3 courses. The total effective rate was 95.40% (83/87). 56.32% (49/87) of their spouses got pregnant and the semen quality was markedly improved (P < 0.01). The results showed that the decoction could dual-directionally regulate the levels of follicle-stimulating hormone (FSH), prolan B luteinizing hormone (LH), testosterone (T), and cortisol (C).

Selenium supplementation of children in a selenium-deficient area in China: blood selenium levels and glutathione peroxidase activities.

Keshan disease is a cardiomyopathy restricted to the endemic areas of China and seen in residents having an extremely low selenium (Se) status. Prophylactic administration of sodium selenite has been shown to decrease significantly the incidence of acute and subacute cases. The aim offthe study was to assess the relative bioavailability of selenite versus organic Se-yeast in a Se-deficient area in China with a randomized double-blind double-dummy design. Healthy children (n=30) between 14 and 16 yr of age were randomized into three equal groups receiving either 200 microg/d selenite Se or 200 microg/d Se-yeast or placebo for 12 wk. Blood was drawn at baseline, 4, 8, and 12 wk and 4 wk postsupplementation. The plasma Se concentration (mean +/- SD) was 0.16+/-0.03 micromol/L at baseline. Selenite and Se-yeast supplementation increased plasma Se to plateau values, 1.0+/-0.2 and 1.3+/-0.2 micromol/L, respectively. In red cells, Se-yeast increased the selenium level sixfold and selenite threefold compared to placebo. The relative bioavailability of Se-yeast versus selenite measured as glutathione peroxidase (GSHPx) activity was similar in plasma, red blood cells, and platelets. GSHPx activity reached maximal levels in plasma and platelets of 300% and 200%, respectively, after 8 wk compared to the placebo group, but continued to increase in red cells for 16 wk. Our study showed that although both forms of Se were equally effective in raising GSHPx activity, Se-yeast provided a longer lasting body pool of Se. Se-yeast may be a better alternative to selenite in the prophylaxis of Keshan disease with respect to building up of body stores.

Further investigation on the role of selenium deficiency in the aetiology and pathogenesis of Keshan disease.

Selenium supplements were not able to restore the ultrastructural changes in the myocardium of latent Keshan disease patients taken by using cardiac catheter endomyocardial biopsy. Observations on the changes of selenium status and the incidence of Keshan disease showed that new latent and naturally-occurring chronic cases were found in the endemic area even after selenium levels had been elevated in the residents to the levels typical in the non-endemic area. These results indicate that although selenium deficiency might be a primary pathogenetic geogen in the occurrence of Keshan disease, it is rather a conditional predisposing factor than a specific or initiative aetiologic factor for the occurrence of Keshan disease. Selenium supplementation could apparently alleviate the higher platelet responsiveness of residents in the endemic area, which might contribute to eliminating the basis for the occurrence of the multifocal perivascular necroses in myocardium of acute and subacute Keshan disease.