Evaluating the Effects of Omega-3 Polyunsaturated Fatty Acids on Inflammatory Bowel Disease via Circulating Metabolites: A Mediation Mendelian Randomization Study.

Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting. Additionally, little evidence exists regarding the effects of specific omega-3 components on IBD risk. We applied two-sample Mendelian randomization (MR) to disentangle the effects of omega-3 PUFAs (including total omega-3, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA)) on the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Our findings indicated that genetically predicted increased EPA concentrations were associated with decreased risk of IBD (odds ratio 0.78 (95% CI 0.63-0.98)). This effect was found to be mediated through lower levels of linoleic acid and histidine metabolites. However, we found limited evidence to support the effects of total omega-3, α-linolenic acid, and DHA on the risks of IBD. In the fatty acid desaturase 2 (FADS2) region, robust colocalization evidence was observed, suggesting the primary role of the FADS2 gene in mediating the effects of omega-3 PUFAs on IBD. Therefore, the present MR study highlights EPA as the predominant active component of omega-3 fatty acids in relation to decreased risk of IBD, potentially via its interaction with linoleic acid and histidine metabolites. Additionally, the FADS2 gene likely mediates the effects of omega-3 PUFAs on IBD risk.

Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study.

BACKGROUND: Observational studies and conventional Mendelian randomization (MR) studies showed inconclusive evidence to support the association between omega-3 fatty acids and type 2 diabetes. We aim to evaluate the causal effect of omega-3 fatty acids on type 2 diabetes mellitus (T2DM), and the distinct intermediate phenotypes linking the two. METHODS: Two-sample MR was performed using genetic instruments derived from a recent genome-wide association study (GWAS) of omega-3 fatty acids (N = 114,999) from UK Biobank and outcome data obtained from a large-scale T2DM GWAS (62,892 cases and 596,424 controls) in European ancestry. MR-Clust was applied to determine clustered genetic instruments of omega-3 fatty acids that influences T2DM. Two-step MR analysis was used to identify potential intermediate phenotypes (e.g. glycemic traits) that linking omega-3 fatty acids with T2DM. RESULTS: Univariate MR showed heterogenous effect of omega-3 fatty acids on T2DM. At least two pleiotropic effects between omega-3 fatty acids and T2DM were identified using MR-Clust. For cluster 1 with seven instruments, increasing omega-3 fatty acids reduced T2DM risk (OR: 0.52, 95%CI 0.45-0.59), and decreased HOMA-IR (ß = - 0.13, SE = 0.05, P = 0.02). On the contrary, MR analysis using 10 instruments in cluster 2 showed that increasing omega-3 fatty acids increased T2DM risk (OR:1.10; 95%CI 1.06-1.15), and decreased HOMA-B (ß = - 0.04, SE = 0.01, P = 4.52 × 10-5). Two-step MR indicated that increasing omega-3 fatty acid levels decreased T2DM risk via decreasing HOMA-IR in cluster 1, while increased T2DM risk via decreasing HOMA-B in cluster 2. CONCLUSIONS: This study provides evidence to support two distinct pleiotropic effects of omega-3 fatty acids on T2DM risk influenced by different gene clusters, which could be partially explained by distinct effects of omega-3 fatty acids on insulin resistance and beta cell dysfunction. The pleiotropic feature of omega-3 fatty acids variants and its complex relationships with T2DM need to be carefully considered in future genetic and clinical studies.

Poor Status of Vitamin D: A Survey of Area With Lowest Sunlight Radiation in Sichuan, China.

Objective: Vitamin D plays an important role in bone and mineral metabolism. Ultraviolet B (UVB) is the primary determinant for vitamin D synthesis. However, population-based data of vitamin D status was sparse in areas with sunlight deprivation in China. This study aimed to assess serum 25-hydroxyvitamin D [25(OH)D] levels among adult women in Sichuan basin with the lowest sunlight radiation in China, and the associations with sunlight exposure and age. Methods: In the context of the same ethnicity, similar latitude and lifestyle in sunlight-limited basin and sunlight-abundant plateau, 1,057 women in basin and 337 in plateau aged 29-95 years were included in this study, from November 2012 to February 2013. Daily sunlight exposure duration of previous month was obtained using questionnaires. Serum 25(OH)D was measured by enzyme-linked immunosorbent assay. Results: The prevalence of vitamin D severe deficiency [25(OH)D <30 nmol/L] and deficiency [30 ≤ 25(OH)D <50 nmol/L] was significantly higher in basin than plateau (21.85% vs. 10.09%, and 59.32% vs. 40.36%; P<0.0001). Women from basin exhibited lower serum 25(OH)D levels than those from plateau (40.66 ± 15.62 vs. 52.54 ± 19.94 nmol/L, P<0.0001). In basin, women more than 50 years old had higher 25(OH)D than younger counterparts, and 25(OH)D level of these groups was not associated with sunlight exposure duration. While in plateau, women younger than 60 years old had higher 25(OH)D than the older women. Furthermore, for those younger groups, women with long sunlight exposure (≥3 h daily) had higher 25(OH)D concentration than those with short sunlight exposure (<3 h daily). Serum PTH was negatively associated with 25(OH)D in basin, but not in plateau. Conclusions: Alarmingly high prevalence of vitamin D deficiency was observed in women in sunlight-deprived basin in Sichuan. Only the vitamin D status of younger women from plateau with adequate solar radiation could benefit from sunlight exposure. Vitamin D supplementation and vitamin D-fortified food should be encouraged to improve vitamin D status for women living in sunlight-limited areas, or with old age.

Bone mineral density and trabecular bone score in patients with 21-hydroxylase deficiency after glucocorticoid treatment.

OBJECTIVE: Patients with 21-hydroxylase deficiency (21-OHD) are at risk of reduced bone mineral density (BMD) and fracture due to long-term glucocorticoid treatment. Trabecular bone score (TBS) is complementary to conventional BMD as a marker for bone quality in patients with glucocorticoid-induced osteoporosis. The purpose of this study is to evaluate the BMD and TBS in a cohort of patients with 21-OHD and analyse factors related to TBS. DESIGN: An observational study. PATIENTS: A total of 46 21-OHD adult patients treated with glucocorticoid for over 10 years who visited Peking Union Medical College Hospital between 2015 and 2019 were recruited. Eight male patients included in this study were all under 50 years old, and 38 female patients were all premenopausal. MEASUREMENTS: Diagnosis was confirmed by multiplex ligation-dependent probe amplification combined with sequencing. Data were collected on physical characteristics, serum hormones and glucocorticoid treatment. Skeletal quality was evaluated by BMD and TBS, and factors related to TBS were analysed. RESULTS: Among the 46 patients, 2 (4.3%) had low BMD (Z-score ≤ -2), while 11 (23.9%) patients had low TBS (degraded or partially degraded microarchitecture). The proportion of bone abnormality evaluated by TBS was higher than that by BMD (p < .001). Patients with lower TBS had significantly higher daily hydrocortisone dosage (p = .009 for males; p = .019 for females). TBS value was negatively correlated with daily hydrocortisone dosage (r = -.317, p = .026), and positively correlated with BMI in female patients (r = .345, p = .034). And there was a negative correlation between TBS value and the current age in male patients (r = -.741, p = .036). The distribution of genotypes (p = 1.000 for male; p = .567 for female) or phenotypes (p = .486 for male; p = .075 for female) had no statistical difference in patients with normal or abnormal TBS. CONCLUSIONS: Approximately 24% of patients with 21-OHD had abnormal microarchitecture of their bone in our study, and TBS score was negatively correlated with daily glucocorticoid dosage in patients. TBS may be used alongside conventional BMD as a complementary marker for bone evaluation in 21-OHD patients.

Comparison of antidiabetic effects of saponins and polysaccharides from Momordica charantia L. in STZ-induced type 2 diabetic mice.

Saponins as small organic molecules and polysaccharides as biomacromolecules are the main bioactive substances of Momordica charantia L. (M. charantia) with anti-hyperglycemic activities. This study was aimed to fully compare the antidiabetic effects and the potential mechanism of saponins (SMC) and polysaccharides (PMC) from M. charantia in STZ-induced type 2 diabetic mice with high-fat diet. Three dosages of SMC (L-SMC: 20 mg/kg, M-SMC: 40 mg/kg, H-SMC: 80 mg/kg) have a certain of therapeutic effect on type 2 diabetic mice, and M-SMC (40 mg/kg) is the optimal dosage for the prevention and treatment of diabetes. The results showed that oral administration of SMC, especially M-SMC (40 mg/kg) compared to PMC (500 mg/kg), could significantly restore the body weight, reduce fasting blood glucose levels, ameliorate insulin resistance and increase the proportion of hepatic phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK)/total protein. The above results proved that hypoglycemic mechanism of SMC might involve in the AMPK/NF-κB signal pathway by activating AMPK phosphorylation and regulating the energy metabolism of the body. However, oral administration of PMC could significant improve the antioxidant capacity by increasing the level of SOD and decreasing the level of MDA, and alleviate the STZ-induced organ tissues (kidney and pancreas), which proved that the hypoglycemic mechanism of PMC might by repairing the pancreatic ß cells damaged by STZ.

[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.

Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.

Context: The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. Objective: To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Design: Prospective, self-controlled, 3-month clinical trial. Settings: University endocrine clinic. Patients: Men with hypogonadotropic hypogonadism caused by CCPHD. Intervention: Pulsatile GnRH was administered subcutaneously for 3 months. Main outcome measures: Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. Results: A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. Conclusions: This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice.

[Effects of lipopolysaccharide and dexamethasone on the expression of Kisspeptin/GPR54 in mouse hypothalamus].

OBJECTIVE: To evaluate the effects of lipopolysaccharide (LPS) and dexamethasone on function of hypothalamus-pituitary-testis axis and to explore the possible underlying mechanisms. METHODS: LPS (100 µg/kg), dexamethasone (DEX, 1 mg/kg) and phosphate buffer saline (PBS) were injected subcutaneously into castrated mice (n=5 in each group) for 4 weeks. The expression of Kisspeptin and its receptor GPR54 in hypothalamus were measured by immunohistochemistry, and plasma luteinizing hormone (LH) were measured by chemiluminescence immunoassay. RESULTS: After LPS and DEX were administered for 4 weeks, the LH level in LPS group and DEX group was (1.79±0.74) U/L and (2.19±0.60) U/L, respectively, which were lower than PBS group (4.87±1.25) U/L (all P<0.01). In LPS group, after treatment, the kisspeptin immunohistochemistry index in hypothalamus was 4.2±1.1, which was lower than the control group (10.2±1.6, P<0.05). The GPR54 immunohistochemistry index in hypothalamus was 3.6±0.5, which was lower than PBS group (6.2±1.8, P<0.05). In DEX group, the expressions of kisspeptin and GPR 54 in hypothalamus did not change after treatment. CONCLUSIONS: LPS may downregulate function of hypothalamus-pituitary-testis axis through Kisspeptin/GPR54 system. Dexamethasone could suppress function of gonadal axis as well, while the underlying mechanism is still unclear.

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.