Tailoring the Growth and Morphology of Lithium Peroxide: Nickel Sulfide/Nickel Phosphate Nanotubes with Optimized Electronic Structure for Lithium-Oxygen Batteries.

Heterogeneous crystalline-amorphous structures, with tunable electronic structures and morphology, hold immense promise as catalysts for lithium-oxygen batteries (LOBs). Herein, a nanotube network constructed by crystalline nickel sulfide/amorphous nickel phosphate (NiS/NiPO) heterostructure is prepared on Ni foam through the sulfurization of the precursor generated hydrothermally. Used as cathodes, the NiS/NiPO nanotubes with optimized electronic structure can induce the deposition of the highly porous and interconnected structure of Li2 O2 with rich Li2 O2 -electrolyte interfaces. Abundant active sites can be created on NiS/NiPO through the charge redistribution for the uniform nucleation and growth of Li2 O2 . Moreover, nanotube networks endow cathodes with efficient transport channels and sufficient space for the accommodation of Li2 O2 . A high discharge capacity of 27 003.6 mAh g-1 and a low charge overpotential of 0.58 V at 1000 mAh g-1 can be achieved at 200 mA g-1 . This work provides valuable insight into the unique role of the electronic structure and morphology of catalysts in the formation mechanisms of Li2 O2 and the performances of LOBs.

Investigation of stretchable strain sensor based on CNT/AgNW applied in smart wearable devices.

Stretchable strain sensor, an important paradigm of wearable sensor which can be attached onto clothing or even human skin, is widely used in healthcare, human motion monitoring and human-machine interaction. Pattern-available and facile manufacturing process for strain sensor is pursued all the time. A carbon nanotube (CNT)/silver nanowire (AgNW)-based stretchable strain sensor fabricated by a facile process is reported here. The strain sensor exhibits a considerable Gauge factor of 6.7, long-term durability (>1000 stretching cycles), fast response and recovery (420 ms and 600 ms, respectively), hence the sensor can fulfill the measurement of finger movement. Accordingly, a smart glove comprising a sensor array and a flexible printed circuit board is assembled to detect the bending movement of five fingers simultaneously. Moreover, the glove is wireless and basically fully flexible, it can detect the finger bending of wearer and display the responses distinctly on an APP of a smart phone or a host computer. Our strain senor and smart glove will broaden the materials and applications of wearable sensors.

[SARS-CoV-2 damages male fertility: How and why].

The male reproductive system has a structural basis for being invaded by the SARS-CoV-2 virus. Existing evidence shows that SARS-CoV-2 can cause substantial damage to testicular tissues, pituitary-testicular axis hormone homeostasis, and production and quality of sperm in male patients. Local inflammation of the testis, cytokine storm and fever are considered to be the potential pathogenic factors for testis injury. COVID-19, as a rapidly spreading disease, requires close attention for its impact on the male reproductive system.

Serum Uric Acid is Associated with the Predicted Risk of Prevalent Cardiovascular Disease in a Community-dwelling Population without Diabetes.

OBJECTIVE: To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes. METHODS: We investigated the association between serum uric acid levels and the risk of prevalent cardiometabolic diseases, 10-year Framingham risk for coronary heart disease, and 10-year risk for atherosclerotic cardiovascular diseases (ASCVD) among 8,252 participants aged ⪖ 40 years without diabetes from Jiading district, Shanghai, China. RESULTS: Body mass index, waist circumference, blood glucose, glycated hemoglobin, blood pressure, and serum lipids increased progressively across the sex-specific quartiles of uric acid (all P trend < 0.05). Compared with individuals in the lowest quartile, those in the higher quartiles had a significantly higher prevalence of obesity, hypertension, and dyslipidemia (all P trend < 0.05). A fully adjusted logistic regression analysis revealed that individuals in the highest quartile had an increased risk of predicted cardiovascular disease compared with those in the lowest quartile of uric acid. The multivariate adjusted odds ratios (ORs) [95% confidence intervals (CIs)] for the highest quartiles for high Framingham risk were 3.00 (2.00-4.50) in men and 2.95 (1.08-8.43) in women. The multivariate adjusted ORs (95% CIs) for the highest quartile for high ASCVD risk were 1.93 (1.17-3.17) in men and 4.53 (2.57-7.98) in women. CONCLUSION: Serum uric acid level is associated with an increased risk of prevalent obesity, hypertension, dyslipidemia, 10-year Framingham risk for coronary heart disease, and 10-year risk for ASCVD among Chinese adults without diabetes.

[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.

[Lipopolysaccharide, TNFα, IL-6, dexamethasone, and insulin increase the expression of GPR54 in the MCF7 breasr cancer cell line].

OBJECTIVE: To investigate the effects of different concentrations of lipopolysaccharide (LPS), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), dexamethasone (Dex), and insulin on the mRNA and protein expressions of GPR54 in the MCF7 cell line in vitro. METHODS: MCF7 breasr cancer cells were cultured and treated with different concentrations of LPS (10 and 20 µg/ml), TNFα (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L). Those treated with culture fluid only served as controls. The mRNA and protein expressions of GPR54 were measured by real-time PCR and Western blot, respectively, after 6, 24, 48, and 72 hours of treatment. RESULTS: Compared with the blank con- trol, LPS (10 and 20 µg/ml), TNFα (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L) significantly increased the expressions of GPR54 mRNA (P < 0.05) and protein (P < 0.05). CONCLUSION: LPS, TNFα, IL-6, Dex, and insulin evidently increase the expression of GPR54 in the MCF7 cell line, indicating their influence on the function of gonads by regulating the GPR54 level.

Decreased plasma neuroactive amino acids and increased nitric oxide levels in melancholic major depressive disorder.

BACKGROUND: Amino acid neurotransmitters and nitric oxide (NO) are involved in the pathogenesis of major depressive disorder (MDD). Here we want to establish whether changes in their plasma levels may serve as biomarker for the melancholic subtype of this disorder. METHODS: Plasma levels of glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), and NO were determined in 27 medicine-naïve melancholic MDD patients and 30 matched controls. Seven of the MDD patients participated also in a follow-up study after 2 months' antidepressant treatment. The relationship between plasma and cerebral-spinal fluid (CSF) levels of these compounds was analyzed in an additional group of 10 non-depressed subjects. RESULTS: The plasma levels of Asp, Gly and GABA were significantly lower whereas the NO levels were significantly higher in melancholic MDD patients, also after 2 months of fluoxetine treatment. In the additional 10 non-depressed subjects, no significant correlation was observed between plasma and CSF levels of these compounds. CONCLUSION: These data give the first indication that decreased plasma levels of Asp, Gly and GABA and increased NO levels may serve as a clinical trait-marker for melancholic MDD. The specificity and selectivity of this putative trait-marker has to be investigated in follow-up studies.

Clinical manifestations and spermatogenesis outcomes in Chinese patients with congenital hypogonadotropic hypogonadism caused by inherited or de novo FGFR1 mutations.

Fibroblast growth factor receptor 1 ( FGFR1 ) mutations are associated with congenital hypogonadotropic hypogonadism (CHH) through inheritance or spontaneous occurrence. We detected FGFR1 mutations in a Chinese cohort of 210 CHH patients at Peking Union Medical College Hospital (Beijing, China) using next-generation and Sanger sequencing. We assessed missense variant pathogenicity using six bioinformatics tools and compared clinical features and treatment outcomes between inherited and de novo mutation groups. Among 19 patients with FGFR1 mutations, three were recurrent, and 16 were novel variants. Sixteen of the novel mutations were likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines, with the prevalent P366L variant. The majority of FGFR1 mutations was inherited (57.9%), with frameshift mutations exclusive to the de novo mutation group. The inherited mutation group had a lower incidence of cryptorchidism, short stature, and skeletal deformities. In the inherited mutation group, luteinizing hormone (LH) levels were 0.5 IU l -1 , follicle-stimulating hormone (FSH) levels were 1.0 IU l -1 , and testosterone levels were 1.3 nmol l -1 . In contrast, the de novo group had LH levels of 0.2 IU l -1 , FSH levels of 0.5 IU l -1 , and testosterone levels of 0.9 nmol l -1 , indicating milder hypothalamus-pituitary-gonadal axis (HPGA) functional deficiency in the inherited group. The inherited mutation group showed a tendency toward higher spermatogenesis rates. In conclusion, this study underscores the predominance of inherited FGFR1 mutations and their association with milder HPGA dysfunction compared to de novo mutations, contributing to our understanding of the genetic and clinical aspects of FGFR1 mutations.

Advances in Noble Metal-Decorated Metal Oxide Nanomaterials for Chemiresistive Gas Sensors: Overview.

Highly sensitive gas sensors with remarkably low detection limits are attractive for diverse practical application fields including real-time environmental monitoring, exhaled breath diagnosis, and food freshness analysis. Among various chemiresistive sensing materials, noble metal-decorated semiconducting metal oxides (SMOs) have currently aroused extensive attention by virtue of the unique electronic and catalytic properties of noble metals. This review highlights the research progress on the designs and applications of different noble metal-decorated SMOs with diverse nanostructures (e.g., nanoparticles, nanowires, nanorods, nanosheets, nanoflowers, and microspheres) for high-performance gas sensors with higher response, faster response/recovery speed, lower operating temperature, and ultra-low detection limits. The key topics include Pt, Pd, Au, other noble metals (e.g., Ag, Ru, and Rh.), and bimetals-decorated SMOs containing ZnO, SnO2, WO3, other SMOs (e.g., In2O3, Fe2O3, and CuO), and heterostructured SMOs. In addition to conventional devices, the innovative applications like photo-assisted room temperature gas sensors and mechanically flexible smart wearable devices are also discussed. Moreover, the relevant mechanisms for the sensing performance improvement caused by noble metal decoration, including the electronic sensitization effect and the chemical sensitization effect, have also been summarized in detail. Finally, major challenges and future perspectives towards noble metal-decorated SMOs-based chemiresistive gas sensors are proposed.

Restraint stress induced anxiety and sleep in mice.

In humans and animals, exposure to changes in internal or external environments causes acute stress, which changes sleep and enhances neurochemical, neuroendocrine, and sympathetic activities. Repeated stress responses play an essential role in the pathogenesis of psychiatric diseases and sleep disorders. However, the underlying mechanism of sleep changes and anxiety disorders in response to acute stress is not well established. In the current study, the effects of restraint stress (RS) on anxiety and sleep-wake cycles in mice were investigated. We found that after RS, the mice showed anxiety-like behavior after RS manipulation and increased the amounts of both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in the dark period. The increase in sleep time was mainly due to the increased number of episodes of NREM and REM sleep during the dark period. In addition, the mice showed an elevation of the EEG power spectrum of both NREM and REM sleep 2 h after RS manipulation. There was a significant reduction in the EEG power spectrum of both NREM and REM sleep during the darkperiod in the RS condition. The expression of the c-Fos protein was significantly increased in the parabrachial nucleus, bed nucleus of the stria terminalis, central amygdala, and paraventricular hypothalamus by RS manipulation. Altogether, the findings from the present study indicated that neural circuits from the parabrachial nucleus might regulate anxiety and sleep responses to acute stress, and suggest a potential therapeutic target for RS induced anxiety and sleep alterations.

[Alterations of plasma aspartic acid, glycine and asparagine levels in patients with major depressive disorder].

OBJECTIVE: To evaluate the changes of plasma levels of the excitatory amino acid neurotransmitter aspartic acid (Asp), inhibitory neurotransmitter glycine (Gly) and asparagine (Asn) in patients with major depressive disorder (MDD). METHODS: Plasma samples were collected from 15 MDD patients (9 males and 6 females, aged 32-64 y) and 14 healthy subjects (7 males and 7 females, aged 30-65 y); and also collected from 7 MDD patients (5 males and 2 females) 2 months after antidepressant treatment. The plasma levels of amino acids were determined by high performance liquid chromatography with fluorescence detection method. RESULTS: Plasma Asp and Gly levels were significantly lower in MDD patients than those in controls (P<0.04). There were positive correlations between plasma levels of Gly and Asp, and between Gly and Asn (P<0.005) in the control group; while in MDD patients, a significant positive correlation was found only between plasma levels of Gly and of Asp (P<0.001). MDD patients did not show significant changes in plasma Asp, Asn and Gly levels after antidepressant treatment compared to those before treatment. CONCLUSION: The reduced plasma Asp and Gly levels may serve as a clinical biomarker for MDD.

High-Performance PEO-Based All-Solid-State Battery Achieved by Li-Conducting High Entropy Oxides.

A rock-salt-structured Li-conducting high entropy oxide was prepared and utilized as an active filler in a polyethylene oxide (PEO)-based solid-state composite electrolyte. X-ray diffraction and high-resolution transmission electron microscopy were adopted to analyze the crystal structure of the high entropy oxide containing 20% of Li ions (HL20). The HL20 was crystallized in the Fm3̅m space group with Li+ ions located at the center of the MO6 octahedra. The ionic conductivity of the composite membrane at 30 °C reaches 3.44 × 10-5 S cm-1. The inflection point of activation energy of the membrane with HL20 decreases by 5 °C compared with that of the pure PEO membrane. In the galvanostatic plating/stripping test, the Li||Li symmetric batteries could be cycled at a current density of 200 µA cm-2 for over 1200 h with an overpotential of 140 mV. The Li||LiFePO4 full battery could be charged/discharged at 0.5 C for 100 circles with a high capacity retention rate of 91%. Excellent rate performance is also achieved at lower temperatures and higher rates, showing the superiority of HL20 as an active filler. This work sheds light on the development of high entropy oxide as a new type of fast ionic conductor, promoting the practical application of all-solid-state batteries at a lower temperature.

Neonatal myofibrillar myopathy type II associated with biallelic UNC-45B gene novel mutation and perinatal myasthenia as the core phenotype: A case report.

Myofibrillar myopathy (MFM) is characterized by phenotypic heterogeneity; decreased function of the myosin-directed chaperone, UNC-45B protein, leads to MFM II, which is characterized by slow progressive proximal myasthenia. Currently, only two studies have reported 11 cases worldwide. This study aimed to conduct genetic research and etiological analysis of a neonatal case of perinatal myasthenia who eventually died due to autonomic dyspnea. The case involved a newborn female admitted for weak cries and groaning. Physical examination revealed shallow and irregular spontaneous breathing, difficulty feeding, hip flexion and knee flexion in both lower limbs, hypotonia (level 1), less translation action, and inability to resist gravity. The child died at 23 days after birth. Gene testing, mutation analysis, and crystal structure analysis were conducted. Cell culture and plasmid construction were conducted, followed by western blot analysis. Pathological changes, including Z-line breakage, were observed in the muscle biopsies of different tissues. Gene testing showed that UNC-45B had a novel compound heterozygous mutation (c.2357T>A/p.Met786Lys, c.2591A>C/p.His864Pro), and in vitro functional experiments showed that the variants could lead to a decrease in protein expression. This study expands the UNC-45B mutation and phenotype spectrum by reporting an MFM II case in a Chinese patient for the first time.

[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.

[Clinical values of single or repeated triptorelin stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism and constitutional delayed puberty].

OBJECTIVE: To investigate the values of single or repeated luteinizing hormone (LH) releasing hormone analogue (triptorelin) stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism (IHH) and constitutional delayed puberty (CDP). METHODS: Male patients (n = 133) without puberty onset after the age of 14 were recruited for triptorelin stimulating test and were followed up for 24 - 48 months until the diagnosis were confirmed: 86 were IHH and the other 47 were CDP. Repeated triptorelin stimulating tests were conducted in 9 IHH patients and 13 CDP patients one year after the first stimulating tests with an attempt to evaluate the dynamic change of hypothalamus-pituitary-testis axis function. The relationship between the final diagnosis and the peak LH value (LH(max)), and the changes of repeated LH(max) were investigated. RESULTS: In the single triptorelin stimulating test, LH(max) was (1.9 +/- 1.2) U/L in IHH group, which was significantly lower than that in CDP group [(13.7 +/- 8.3) U/L] (P < 0.01); 75 IHH patients (87.2%) had a LH(max) lower than 4 U/L, while only 2 CDP patients (4.3%) had a LH(max) lower than 4 U/L. When LH(max) < 4U/L was used as a criteria for the diagnosis of IHH, the single triptorelin stimulating test had a sensitivity of 87.2%, a specificity of 95.7%, and a positive predictive value of 97.4%. The repeated triptorelin stimulating tests performed one year later showed that the LH(max) in the 9 IHH patients increased from (4.7 +/- 2.5) U/L to (5.1 +/- 3.3) U/L (P = 0.78), while that in the 13 CDP patients increased from (10.7 +/- 3.3) U/L to (24.5 +/- 5.7) U/L (P < 0.05). CONCLUSIONS: A single triptorelin stimulating test is highly effective in differentiating IHH from CDP. For some patients without definitive diagnosis, a repeated triptorelin stimulating test performed one year later may provide more valuable information on the dynamic change of the hypothalamus-pituitary-testis axis function.

Growth hormone cocktail improves hepatopulmonary syndrome secondary to hypopituitarism: A case report.

BACKGROUND: Metabolic associated fatty liver disease frequently occurs in patients with hypopituitarism and growth hormone (GH) deficiency. Some patients may develop to hepatopulmonary syndrome (HPS). HPS has a poor prognosis and liver transplantation is regarded as the only approach to cure it. CASE SUMMARY: A 29-year-old man presented with progressive dyspnea for 1 mo. At the age of 10 years, he was diagnosed with panhypopituitarism associated with pituitary stalk interruption syndrome. Levothyroxine and hydrocortisone were given since then. To achieve ideal height, he received GH treatment for 5 years. The patient had an oxygen saturation of 78% and a partial pressure of arterial oxygen of 37 mmHg with an alveolar-arterial oxygen gradient of 70.2 mmHg. Abdominal ultrasonography showed liver cirrhosis and an enlarged spleen. Perfusion lung scan demonstrated intrapulmonary arteriovenous right-to-left shunt. HPS (very severe) was our primary consideration. His hormonal evaluation revealed GH deficiency and hypogonadotropic hypogonadism when thyroid hormone, cortisol, and desmopressin were administrated. After adding with long-acting recombinant human GH and testosterone for 14 mo, his liver function and hypoxemia were improved and his progressive liver fibrosis was stabilized. He was off the waiting list of liver transplantation. CONCLUSION: Clinicians should screen HPS patients' anterior pituitary function as early as possible and treat them primarily with GH cocktail accordingly.

Prevalence of gene mutations in a Chinese 46,XY disorders of sex development cohort detected by targeted next-generation sequencing.

46,XY disorders of sex development (DSD) is characterized by incomplete masculinization genitalia, with gonadal dysplasia and with/without the presence of Müllerian structures. At least 30 genes related to 46,XY DSD have been found. However, the clinical phenotypes of patients with different gene mutations overlap, and accurate diagnosis relies on gene sequencing technology. Therefore, this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted next-generation sequencing (NGS) technology. Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital (Beijing, China). A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD. The incidence of these rare variants was approximately 69.0% (60/87). Twenty-five novel variants and 29 reported variants were identified. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance. The overall diagnostic rate was about 42.5% based on the pathogenic and likely pathogenic variants. Androgen receptor (AR), steroid 5-alpha-reductase 2 (SRD5A2) and nuclear receptor subfamily 5 Group A member 1 (NR5A1) gene variants were identified in 21, 13 and 13 patients, respectively. The incidence of these three gene variants was about 78.3% (47/60) in patients with rare variants. It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR, SRD5A2, and NR5A1 genes were the most common pathogenic genes in our cohort.

Efficacy and safety of pulsatile gonadotropin-releasing hormone therapy in patients with congenital hypogonadotropic hypogonadism: a multicentre clinical study.

BACKGROUND: Pulsatile gonadotropin-releasing hormone (GnRH) therapy may restore function of the hypothalamus-pituitary-gonad axis and induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism (CHH). The study sought to test the reliability of a newly developed Innopump® hormone pump, and to confirm the efficacy and safety of pulsatile GnRH therapy (by Innopump® hormone pump) in CHH patients. METHODS: From November 2017 to November 2018, 28 male patients with CHH were treated with pulsatile GnRH at Peking Union Medical College Hospital, Beijing Chaoyang Hospital, and Shandong Provincial Hospital. A prospective, self-controlled, 7-day clinical trial was conducted. The primary outcome measures were the efficacy and safety of pulsatile GnRH therapy (which was administered via the Innopump® hormone pump). The secondary outcome measures included total serum testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels. RESULTS: All of the patients participated the clinical study. For 7 days, a dosage prescribed by doctors was accurately administered by the Innopump® hormone pump, and recorded by the pump. During the treatment, LH and FSH levels gradually increased to 2.66±1.74 and 5.05±3.03 IU/L, respectively. Upper respiratory tract infection in 1 patient and slight nausea in another patient were reported, which were confirmed to be unrelated to the pulsatile GnRH therapy. CONCLUSIONS: The Innopump® hormone pump was found to be reliable in drug administration, and to have an accurate alarming system. It effectively and safely treated patients with CHH. Pulsatile GnRH therapy may produce a physiological pattern of GnRH secretion, and re-establish pituitary-gonad axis function by increasing gonadotropin levels.

[A report of familial male-limited precocious puberty caused by a germ-line heterozygous mutation (M398T) in luteinizing hormone receptor gene].

OBJECTIVE: To clarify the possible gene mutations in luteinizing hormone(LH) receptor gene in a boy with LH independent precocious puberty and probe the mechanism the of diseases caused by LH receptor activating mutations. METHODS: (1) Describe the clinical manifestations and laboratory data in a 5-year-old boy with LH independent precocious puberty. (2) Peripheral leukocytes were collected from the proband, his parents and other 20 normal puberty developed males. PCR and direct DNA sequence of 11 exons in LH receptors gene were conducted. RESULTS: (1) The proband was diagnosed to have LH independent precocious puberty according to the clinical symptoms and the laboratory tests. (2) A germ-line heterozygous point mutation in the 11 exon of LH receptor gene was found in the proband and his mother: c1193 T-->C leading to amino acid change with M398T, which causes consecutively an activation of the LH receptor. (3) Other nucleotide changes in the proband and other normal males include c935 A-->G (N312S) and c1065 -->C (same sense mutation). CONCLUSIONS: (1) A germ-line heterozygous point mutation in the LH receptor gene with M398T leads to consecutively activation of the LH receptor and LH independent precocious puberty. (2) The same point mutation does not have any influence on the puberty development, menstruation and productive functions of the proband's mother. (3) The LH receptor gene has possible polymorphism in the Han ethnic population.

[Clinical features of 9 patients with X-linked adrenal hypoplasia congenita caused by DAX1/NR0B1 gene mutations].

OBJECTIVE: To study the clinical features of 9 patients with X-linked adrenal hypoplasia congenita (AHC) by gene sequencing so as to provide diagnostic rationales. METHODS: The patients were 9 cases of X-linked AHC treated at our hospital from July 2007 to June 2009. The clinical manifestations were analyzed. The blood biochemistry tests and the hormone examinations including luteinizing hormone-releasing hormone (LHRH) stimulation tests and human chorionic gonadotropin (HCG) stimulation tests were conducted to evaluate the functions of gonads. And CT scans of adrenal glands and gene tests of DAX1/NR0B1 were performed. RESULTS: Nine AHC patients from 8 families were studied. All patients had DAX1/NR0B1 gene mutations. The main clinical features were: (1) some patients (3 families) had a family history of X-linked recessive inheritance; (2) the ages of onset were all below 10 years old (from 2 month after birth to 9 years old) and ages of being treated at our hospital were from 15 to 34 years old; (3) all patients had adrenocortical hypofunctions, but clinical situations were different, most of them had pigmentation (n = 9), nausea and vomiting (n = 8), hypotension (n = 6), Addisonian crisis (n = 4). Others were debility, hypoglycemia and cold susceptibility. Laboratory tests indicated that all patients had hyponatremia at the onset and higher blood adrenocorticotropic hormone level, lower blood 17-hydroxyprogesterone level compared to normal controls; (4) none of the patients had puberty and there was no responses to LHRH stimulation tests, 3 of them had normal responses to HCG stimulation tests; (5) small bilateral adrenal glands were displayed on CT scans. CONCLUSIONS: The main clinical features of X-linked AHC are adrenocortical hypofunction and hypogonadotropic hypogonadism. But the phenotypes vary greatly in different patients. So male children with adrenal cortical hypofunction should be suspected of X-linked AHC and DAX1/NR0B1 gene tests should be performed. The sexual development of the patients also should be followed up.