[Association of Serum Vitamin D with Hand-grip Strength and Balance Ability: a Cross-sectional Study on Community-dwelling Women in Sichuan, China].

OBJECTIVE: To determine the relationship between serum levels of 25(OH)D and 1, 25(OH)2 D and the hand-grip strength and balance ability of women in Sichuan, China. METHODS: A cross-sectional study on a representative sample of 1 095 women aged 29-95 yr. in Sichuan Province was undertaken. Their hand-grip strength and balance ability were assessed using a hand-held dynamometer and the short physical performance battery (SPPB), respectively. The participants were divided into four groups according to the level of serum 25(OH)D: sufficient (>75 nmol/L), insufficient (51-75 nmol/L), deficiency (25-50 nmol/L), and serious deficiency (<25 nmol/L). General liner models were established to compare the differences of the four groups in balance ability. Logistic regression models were established to examine the associations of serum 25(OH)D and 1, 25(OH)2 D withhand-grip strength and physical performance. RESULTS: About 70.9% of the participants had vitamin D deficiency. Those with vitamin D insufficiency or deficiency were more likely to reside in a higher latitudinal area (P<0.001), spend less time in outdoor activities (P=0.013), and take less vitamin D supplements (P<0.001). Older women (≥65 years) had lower serum 25(OH)D (P=0.001) and were more likely to have ≤50 nmol/L 25(OH)D than their younger counterparts (74.6% vs. 68.9%, P=0.046). However, no significant age differences were found in serum 1, 25(OH)2 D. Serum levels of 25(OH)D and 1, 25(OH)2 D were not found to be associated with hand-grip strength and balance ability after adjusting for confounding factors. Hand-grip strength and balance ability decreased with age (OR=1.066, P<0.001; OR=1.111, P<0.001). Higher body mas was associated with higher hand-grip strength (OR=0.958, P<0.001). Higher serum albumin (OR=0.896, P=0.001) and longer walking time (OR=0.799, P=0.001) were associated with higher balance ability. CONCLUSION: Serum levels of 25(OH)D and 1, 25(OH)2D are not associated with hand-grip strength and balance ability.

Sex hormones affect acute and chronic stress responses in sexually dimorphic patterns: Consequences for depression models.

BACKGROUND: Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. METHOD: Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. RESULTS: Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. CONCLUSION: Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences.

Sexually Dimorphic Changes of Hypocretin (Orexin) in Depression.

BACKGROUND: Neurophysiological and behavioral processes regulated by hypocretin (orexin) are severely affected in depression. However, alterations in hypocretin have so far not been studied in the human brain. We explored the hypocretin system changes in the hypothalamus and cortex in depression from male and female subjects. METHODS: We quantified the differences between depression patients and well-matched controls, in terms of hypothalamic hypocretin-1 immunoreactivity (ir) and hypocretin receptors (Hcrtr-receptors)-mRNA in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex. In addition, we determined the alterations in the hypocretin system in a frequently used model for depression, the chronic unpredictable mild stress (CUMS) rat. RESULTS: i) Compared to control subjects, the amount of hypocretin-immunoreactivity (ir) was significantly increased in female but not in male depression patients; ii) hypothalamic hypocretin-ir showed a clear diurnal fluctuation, which was absent in depression; iii) male depressive patients who had committed suicide showed significantly increased ACC Hcrt-receptor-2-mRNA expression compared to male controls; and iv) female but not male CUMS rats showed a highly significant positive correlation between the mRNA levels of corticotropin-releasing hormone and prepro-hypocretin in the hypothalamus, and a significantly increased Hcrt-receptor-1-mRNA expression in the frontal cortex compared to female control rats. CONCLUSIONS: The clear sex-related change found in the hypothalamic hypocretin-1-ir in depression should be taken into account in the development of hypocretin-targeted therapeutic strategies.

Sex differences in the stress response in SD rats.

Sex differences play an important role in depression, the basis of which is an excessive stress response. We aimed at revealing the neurobiological sex differences in the same study in acute- and chronically-stressed rats. Female Sprague-Dawley (SD) rats were randomly divided into 6 groups: chronic unpredictable mild stress (CUMS), acute foot shock (FS) and controls, animals in all 3 groups were sacrificed in proestrus or diestrus. Male SD rats were randomly divided into 3 groups: CUMS, FS and controls. Comparisons were made of behavioral changes in CUMS and control rats, plasma levels of corticosterone (CORT), testosterone (T) and estradiol (E2), and of the hypothalamic mRNA-expression of stress-related molecules, i.e. estrogen receptor α and ß, androgen receptor, aromatase, mineralocorticoid receptor, glucocorticoid receptor, corticotropin-releasing hormone, arginine vasopressin and oxytocin. CUMS resulted in disordered estrus cycles, more behavioral and hypothalamic stress-related molecules changes and a stronger CORT response in female rats compared with male rats. Female rats also showed decreased E2 and T levels after FS and CUMS, while male FS rats showed increased E2 and male CUMS rats showed decreased T levels. Stress affects the behavioral, endocrine and the molecular response of the stress systems in the hypothalamus of SD rats in a clear sexual dimorphic way, which has parallels in human data on stress and depression.

Safety of Brucea javanica and cantharidin combined with chemotherapy for treatment of NSCLC patients.

OBJECTIVE: To assess the safety of Brucea javanica and Cantharidin combined with chemotherapy in treating patients with non-small-cell lung carcinoma. METHOD: A consecutive cohort of patients with NSCLC were divided into four groups: experimental group A treated with Brucea javanica injection combined with chemotherapy; experimental group B with Cantharidin injection combined with chemotherapy; experimental group C treated with Brucea javanica and Cantharidin injection combined with chemotherapy; and the control group receiving only chemotherapy. After more than two courses of treatment, safety, quality of life and side effects were evaluated. RESULTS: The incidences of myelosuppression in groups A, B and C were lower than that in Control group (p<0.05), but without significant differences among A, B and C. Adverse effects on the gastrointestinal tract also were lower than in controls (p<0.05) without variation amnog the combined treatment groups. CONCLUSIONS: Brucea javanica or Cantharidin combined with chemotherapy could in both cases improve quality of life in our cohort of NSCLC patients without any increase in toxicity. However, further clinical experiments should be conducted to evaluate the efficacy of Brucea javanica and Cantharidin combined with chemotherapy for patients with NSCLC.

Phase II study on Javanica oil emulsion injection (Yadanzi®) combined with chemotherapy in treating patients with advanced lung adenocarcinoma.

PURPOSE: To investigate the efficacy and safety of Javanica oil emulsion injection (Yadanzi®) combined with pemetrexed and platinum (PP) for treating patients with advanced lung cancer. PATIENTS AND METHODS: From June 2011 to June 2013, we recruited 58 patients with advanced lung cancer, and divided them into two groups. Twenty eight patients received Yadanzi® (from ZheJiang Jiuxu Pharmaceutical Co., Ltd.) together with PP chemotherapy (combined group), while the others were given only PP chemotherapy (control group). After two cycles of treatment, efficacy and safety of treatment were evaluated. RESULTS: The overall response rate [(CR+PR+SD)/(CR+PR+SD+PD)] of the combined group was higher than that of control group (89.7% vs. 86.2%, p>0.05). Regarding rate of life improvement, it was 82.8% in combined group, and 51.7% in the control group (p<0.05). In terms of side effects, leukopenia in combined group was less frequent than that in control group (p<0.05). More patients in the control group were found to suffer liver toxicity. CONCLUSIONS: Javanica oil emulsion injection combined with chemotherapy could be considered as a safe and effective regimen in treating patients with advanced lung adenocarcinoma. It can improve the quality of life and reduce the possibility of leukopenia. Further clinical trials with a large sample size should be conducted to confirm whether addition of Yadanzi® to chemotherapy could increase the response rate, reduce toxicity, enhance tolerability and improve quality of life for patients with advanced lung cancer.

Phase II study on safety and efficacy of Yadanzi® (Javanica oil emulsion injection) combined with chemotherapy for patients with gastric cancer.

OBJECTIVE: To investigate the efficacy and safety of Yadanzi® (Javanica oil emulsion injection) combined with chemotherapy for treatment of patients with advanced gastric cancer. METHODS: From January 2011 to December 2012, we recruited 75 patients with advanced gastric cancer, who received javanica oil emulsion injection together with chemotherapy. After two cycles of treatment, efficacy and safety of the combined therapies were evaluated. RESULTS: Overall response rate of 75 patients after treatment was 85.3% (CR+PR+SD). Treatment related side effects were recorded. No treatment related death occurred. CONCLUSIONS: Javanica oil emulsion injection combined with chemotherapy could be considered as a safe and effective regimen in treating patients with advanced gastric cancer. Further randomized clinical trials should be conducted to confirm whether the addition of Yadanzi® to chemotheraphy could be associated with reduced toxicity, enhanced tolerability and improved quality of life for patients with advanced gastric cancer.

Clinical safety and efficacy of Kanglaite® (Coix Seed Oil) injection combined with chemotherapy in treating patients with gastric cancer.

OBJECTIVE: To observe efficacy and side effects, as well as the impact on quality of life, of Kanglaite® (Coix Seed Oil) injections combined with chemotherapy in the treatment of advanced gastric cancer patiensts. METHOD: A consecutive cohort of 60 patients were divided into two groups:the experimental group receiving Kanglaite® Injection combined with chemotherapy and the control group with chemotherapy alone. After more than two courses of treatment, efficacy, quality of life and side effects were evaluated. RESULTS: The response rate and KPS score of experimental group were significantly improved as compared with those of the control group(P<0.05). In addition, gastrointestinal reactions and bone marrow suppression were significantly lower than in the control group(P<0.05). CONCLUSIONS: Kanglaite® Injection enhanced efficacy and reduced the side effects of chemotherapy, improving quality of life of gastric cancer patients; use of Kanglaite® injections deserves to be further investigated in randomized control clinical trails.

[Clinical values of triptorelin stimulating test in assessing hypothalamus-pituitary-gonad axis function in male patients with hypothalamus-pituitary-gonad axis disorders].

OBJECTIVE: To investigate the clinical values of luteinizing hormone-releasing hormone (LHRH) α (triptorelin) stimulating test in the differential diagnoses of hypothalamus-pituitary-gonad axis (HPGA) disorders. METHODS: A total of 229 male patients with various HPGA disorders were recruited for triptorelin stimulating test. And all patients were followed up for 12 - 48 months until a definite diagnosis was made. The values of triptorelin stimulating test in the differential diagnoses of HPGA disorders were assessed by examining the close relationship between LHmax and the final clinical diagnosis. RESULTS: (1) LH levels rose steady after an intramuscular injection of triptorelin 100 µg and the time of LHmax appeared at 45 - 60 min. (2) LHmax < 4 U/L indicated the function of HPGA was not activated. LHmax in the range of 4 - 12 U/L indicated the patients might have constitutional delayed puberty development. LHmax > 12 U/L indicated the fulfilled puberty development. CONCLUSION: Triptorelin stimulating test can precisely evaluate the functions of HPGA in various HPGA disorders and provide valuable information for the differential diagnoses in constitutional delayed puberty development, hypogonadotropic hypogonadism, central and peripheral precocious puberty disorders.