[TRAF4 promotes lung cancer development by activating tyrosine kinase of EGFR].

Objective: To explore the role of tumor necrosis factor receptor-associated factor 4 (TRAF4) in promoting the abnormal activation of epidermal growth factor receptor (EGFR) and its effect on lung cancer cell proliferation, migration and invasion. Methods: Tumor tissues from patients who underwent lung adenocarcinoma resection at The First Affiliated Hospital of Second Military Medical University, from January 2015 to May 2017 were collected, and the expressions of TRAF4 and Ki-67 in lung cancer tissues were detected by immunohistochemistry, the mRNA levels of Cyclin D and Vimentin were detected by real-time fluorescence quantitative PCR (qRT-PCR). The effect of TRAF4 on the tumor growth ability of lung cancer A549 cells was investigated by the xenograft model, the effect of TRAF4 or EGFR on the tumor proliferation ability was detected by using cell counting kit 8 (CCK8) and BrdU assay, and the migration and invasion abilities of tumor cells were detected by Transwell assay. Different structural domain deletion expression vectors of TRAF4 and EGFR were constructed to transfect cells, and the interaction mode of TRAF4 and EGFR was investigated by immunoprecipitation assay. Results: The expression of TRAF4 in non-small cell lung cancer (NSCLC) tissues was positively correlated with the expressions of Ki-67, cyclin D, and vimentin (r2: 0.438, 0.695, and 0.736, respectively, all P＜0.01). Immunohistochemical assay of tumor tissues from NSCLC patients showed that tissues with high expression of TRAF4 were also high in Ki-67. Patients with high TRAF4 expression (TRAF4 positivity >30%) had a shorter progression-free survival (PFS) time than that of patients with low TRAF4 expression (TRAF4 positivity ≤30%) (median PFS of 12 and 19 months, respectively; P=0.034). Traf4-/- cells had a weakened proliferative capacity than traf4+/+ cells and formed tumors with smaller size (P＜0.05). The expression level of Ki-67 in the tumor tissues formed by traf4-/- cells [(45.6±8.7)%] was lower than that in the tumor tissues formed by traf4+/+ cells [(62.3±10.3)%, P=0.015], the mRNA levels of cyclin D (1.01±0.15) and vimentin (1.01±0.12) in the traf4-/- cells were lower than those of the traf4+/+ cells (3.41±0.32 and 3.12±0.18, respectively, both P＜0.05).The western blot results showed that, with the elevated intracellular expression level of TRAF4, phosphorylation level of EGFR was significantly increased in both wild-type EGFR and activation mutant EGFR-expression cells. The capacities of proliferation, migration and invasion of A549 cells was weakened after EGFR knockdown (all P＜0.01). Immunoprecipitation experiments showed that TRAF4 binds to the peptide segment of the near-membrane region of EGFR through the TRAF structural domain, and the mutual binding between EGFR molecules was enhanced under TRAF4 overexpression conditions. Increasing TRAF4 expression promoted EGFR molecular phosphorylation and activation of downstream signaling. Conclusions: TRAF4 expression is elevated in NSCLC tissues and tumor cells, which promotes tumor proliferation, migration and invasion. TRAF4 directly binds to EGFR molecules, enhances its own phosphorylation and activates the downstream signaling pathway by promoting the interaction between EGFR molecules.

Thyroid Lobectomy for Low-Risk 1-4 CM Papillary Thyroid Cancer is not Associated with Increased Recurrence Rates in the Dutch Population with a Restricted Diagnostic Work-Up.

INTRODUCTION: The 2015 American Thyroid Association guidelines recommend to de-escalate treatment such as Thyroid lobectomy instead of total thyroidectomy for 1-4 cm papillary thyroid cancer (PTC). Dutch guidelines endorse restricted work-up for thyroid incidentalomas recommending only fine needle aspiration in case of a 'palpable thyroid nodule'. This diagnostic work-up algorithm may result in the identification of less indolent PTCs and may lead to a patient population with relatively more aggressive PTCs. This study aims to retrospectively analyze recurrence rates of low-risk 1-4 cm PTC in the Netherlands. METHODS: From the national cancer registry, patients with low-risk 1-4 cm PTC between 2005 and 2015 were included for analysis. Disease free survival (DFS) and overall survival were compared between patients who underwent TT ± RAI and TL without RAI. Post-hoc propensity score analysis was performed correcting for age, sex, T-stage, and N-stage. RESULTS: In total 901 patients were included, of which 711 (78.9%) were females, with a median follow-up of 7.7 years. TT was performed in 893 (94.8%) patients. Recurrence occurred in 23 (2.6%) patients. Multivariable analysis showed no significant correlation between extent of surgery and DFS (p = 0.978), or overall survival (p = 0.590). After propensity score matching, multivariable analysis showed no significant difference on extent of surgery and recurrence. CONCLUSION: Low-risk PTC patients with 1-4 cm tumor who underwent TL showed similar recurrence rates as those who underwent TT ± adjuvant RAI, which suggests that TL can be sufficient in treating low-risk 1-4 cm PTC, possibly reducing morbidity of these patients in the Netherlands.

High-effective biosynthesis of baccatin â ¢ by using the alternative acetyl substrate, N-acetyl-d-glucosamine.

AIMS: Paclitaxel is a type of broad-spectrum anticancer drug in short supply. The price of acetyl-CoA (17 709 677·4 USD mol-1 ), which is the acetyl group donor for the enzymatic synthesis of the intermediate, baccatin Ⅲ, is still the bottleneck of the mass production of paclitaxel. This study reports a novel acetyl group donor, which could substantially reduce the cost of production. METHODS AND RESULTS: In this study, a substrate spectrum with 14 kinds of representative acetyl-donor substitutes predicted by computer-aided methods was tested in a 10-deacetylbaccatin Ⅲ-10-O-acetyltransferase (DBAT) heterogeneous-expressed open-whole-cell catalytic system. The results of computer prediction and experimental analysis revealed the rule of the acetyl-donor compounds based on this substrate spectrum. N-acetyl-d-glucosamine (30·95 USD mol-1 , about 572 202-fold cheaper than acetyl-CoA) is selected as a suitable substitute under the rule. The yield when using N-acetyl-d-glucosamine as acetyl donor in open-whole-cell catalytic system was 2·13-fold of that when using acetyl-CoA. In the in vivo system, the yield increased 24·17%, which may indicate its cooperation with acetyl-CoA. CONCLUSION: The success of open-whole-cell synthesis and in vivo synthesis of baccatin Ⅲ by adding N-acetyl-d-glucosamine as acetyl substrate demonstrates that it is a useful substrate to improve the yield of baccatin Ⅲ. SIGNIFICANCE AND IMPACT OF THE STUDY: All these findings provided a potential acetyl-donor substitute for acetyl-CoA, as well as a low cost and efficient method of preparing paclitaxel through baccatin Ⅲ semi-synthesis.

[Electrocardiographic characteristics of idiopathic ventricular arrhythmias originating from the tricuspid annulus regions].

Object: To explore the electrocardiographic characteristics of ventricular arrhythmias (VAs) originating from tricuspid annulus region. Methods: Present study included 169 consecutive patients undergoing catheter ablation of VAs from tricuspid annulus origin in our department from August 2007 to September 2016. Based on the origin sites, the patients were divided into two subgroups, the free wall group (81 cases) and septal wall group (88 cases). Based on the location, patients in the free wall group were classified into anterolateral (22 cases), lateral (26 cases) and posterolateral (33 cases) subgroups. Patients in the septal group were classified into anteroseptal (10 cases), midseptal (71 cases) and posteroseptal (7 cases) subgroups. We analyzed the electrocardiographic features of these patients and in 87 patients with PVCs/VT originating from right ventricular outflow tract. Results: (1) A positive R wave inⅠ, aVL, V(5)-V(6) leads were found among most of patients, only few cases originating from tricuspid annulus anteroseptum group and tricuspid annulus anterolateral group demonstrated qr or qs pattern in aVL lead. 97.53% (79/81) patients demonstrated rS pattern in V(1)-V(3) leads with VAs originating from tricuspid annulus free wall, and 9/10 patients demonstrated rS pattern in V(1) lead with VAs originating from anteroseptum, and 97.44% (76/78) patients demonstrated QS pattern in V(1) lead with VAs originating from midseptum and posteroseptum. Precordial lead transition zone was on or behind V(3) for tricuspid annulus free wall group (96.3%, 78/81), but in front of V(3) for tricuspid annulus septum wall group (47.73%, 42/88) (P<0.01). The S wave's amplitude smaller than-1.81 mV in lead V(2) can be used as a cutoff value to identify if PVC/VT is originating from free wall or septum of TA. R wave in inferior wall leads was found among 98.85% (86/87) patients with PVCs/VT originating from right ventricular outflow tract. Conclusion: A positive R wave in Ⅰ, aVL, V(5)-V(6) leads was found among most of patients with idiopathic ventricular arrhythmias originating from the tricuspid annulus regions, but VAs originating from different portions of tricuspid annulus area have distinct electrocardiographic characteristics.

Quantitative risk analysis of the novel H7N9 virus in environments associated with H9 avian influenza virus, Zhejiang province, China.

H9 avian influenza virus played a key role during generation of the novel H7N9 virus. A surveillance programme was conducted to assess the H9 virus in relation to the risk of H7N9 virus contamination in the environment. Risk of H7N9 virus contamination in the presence of H9 virus was higher than without (adjusted odds ratio 4·49, 95% confidence interval 3·79-5·31). Adjusted odds ratios of the H7N9 virus associated with co-presence of H9 virus and interacting factors were 4·93 (rural vs. urban area), 46·80 (live poultry markets vs. other premises), 6·86 (Huzhou vs. Hangzhou prefecture), 40·67 (year 2015 vs. 2013), and 9·63 (sewage from cleaning poultry vs. poultry faeces). Regular surveillance on gene variability of H7N9 and H9 viruses should be conducted and extra measures are needed to reduce co-circulation of H7N9 and H9 viruses in the environment.

[The impacts of testosterone on insulin sensitivity and chronic low-grade].

Objectives: Insulin resistance (IR) is a common manifestation in patients with polycystic ovarian syndrome (PCOS). Both clinical observations and animal studies have demonstrated that IR could be induced by hyperandrogenemia, which is the charac-teristic of PCOS.Nevertheless, the mechanisms of IR in PCOS are still unclear especially at the molecular level.We conduct this study to ellucidate the effects of androgen on insulin sensitivity and chronic low-grade inflammation in adult C57BL/6 female mice. Methods: Eleven adult female C57BL/6 mice aged 8 weeks weredaily injected with testosterone (1.0 mg/100 g body weight)which dissolved in sesame oil (experimental group T) for 16 weeks.Ten control mice were injected with sesame oil only (group Con). The changes of body weight and body fat content were detected.Intraperitoneal glucose tolerance tests (IGTT) were performed at 0, 2, 3 and 16 weeks treatment, blood from tail vein was taken to detect levels of glucose.Intraperitoneal insulin tolerance tests (ITT) were performed at 16 weeks treatment.Both groups were sacrificed after16 weeks treatment, and phosphorylation of GSK3ßand InsR, two molecules of insulin signaling pathway, were detected by Western blot from adipose tissue.The phosphorylation of NF-κBp65, CD16/32, and CD206 were also detected in adipose tissues.ELISA was used totest the serum IL-6 and MCP-1. Results: (1) No obvious significance of body weight as well as body fat content was detected between both experimental groups (P>0.05); (2) 2 weeks treatment with testosterone induced the in-crease of fasting blood glucose and displayed obvious significance compared with group Con (P<0.05); (3) 3 weeks treatment with testosterone induced the increase of area under the curve (AUC) of the blood glucose following IGTT and displayed significance compared with group Con (P<0.05). And more obvious significance was detected at 16 weeks treat-ment (P<0.01); (4) 16 weeks treatment with testosterone induced the increase of AUC of the blood glucose following ITT(P<0.01); (5) the serum IL-6 and MCP-1 in testosterone treat-ment was higher than that in thecontrols (P<0.05). And 16 weeks treatment with testosterone decreased phosphorylation of GSK3ß and InsR in C57BL/6 adipose tissues (P<0.05), in-creased phosphorylation of NF-κBp65.Testosteroneenhanced the expression of CD206, and decreased the expression of CD16/32. Conclusions: Treatment with testosterone in adult fe-male mice can induce insulin resistance by blocking insulin signal transduction, without in-fluencing body weight and body fat content.Testosterone could activate the NF-κB to pro-mote the expression of IL-6 and MCP-1. And testosterone facilitated to promote macro-phage to M1-subtype transformation.

[Electrocardiogram characteristics of patients with ventricular arrhythmia originating from the distal great cardiac vein].

Objective: To explore the electrocardiographic characteristics of patients with idiopathic ventricular arrhythmias (VAs) originating from different portions of distal great cardiac veins (DGCV). Methods: The study included 49 patients underwent successful RFCA of premature ventricular complex(PVCs)/ventricular tachycardia(VT) from different portions of the DGCV in our department from July 2009 to March 2016. The surface 12-lead electrocardiogram (ECG) and intraventricular ablation mapping features were analyzed. Patients were divided into four groups according to the mapping and ablation results: DGCV1(10 patients), DGCV2 (13 patients), proximalanterior interventricular vein (PAIV, 17 patients)and extend distal great cardiac vein (EDGCV, 9 patients). We analyzed the similarities and differences between surface 12-lead ECG of patients with PVCs/VT from different portions of DGCV, and compared with random chosen 290 patients with PVCs/VT from ventricular outflow tract and adjacent structure. Results: A positive R wave in inferior leads, a negative QS morphology in lead aVL and aVR were found among all groups. The different characteristics of surface 12-lead ECG of VAs originating from DGCV were as follows: (1)EDGCV patients demonstrated a positive R or r wave on lead Ⅰ(6/9) while a negative rS or qr wave was evidenced in other three groups (39/40). (2)A positive R pattern on lead V(1), V(5)-V(6) (11/13) was presented in patients of DGCV2 group; R (without S or s) wave on V(1) (9/10), RS or Rs wave on V(5)-V(6) were found in DGCV1 group; RS or rS wave was seen on lead V(1), R(without S)wave in lead V(5)-V(6) (25/26) were found in EDGCV and PAIV group and the amplification of R wave in EDGCV was higher than V(1) of PAIV group.(3)Precordial lead transition zone was in front of V(1) for DGCV1 and DGCV2 groups (23/23), within V(1)-V(3) for EDGCV group, but on V(2) or within V(2)-V(3) for PAIV group.(4)Patients of DGCV1 and DGCV2 demonstrated a longer Pseudo delta wave time(PdW), intrinsicoid deflection time (IDT), significantly larger maximum deflection index (MDI) than those in PAIV and EDGCV groups (P<0.001). (5)The different characteristics of surface 12-lead ECG between VAs originating from DGCV and those from ventricular outflow tract and adjacent structure were as follows: ① The ECG features were similar between PVIA and LCC group, both demonstrated a rs wave on the lead Ⅰ, rS wave on V(1)-V(2) and R wave on V(5)-V(6); ②The ECG features were similar betweenEDGCV and RCC group, both presented with R or r wave on the lead Ⅰ, the QRS wave of precordial leads was similar as PAIV and LCC groups; ③A R wave on the lead V(1), V(5)-V(6) was found in group DGCV2, and ILCC; ④Similar to the group Endo-MAA, patients in DGCV1 group also demonstrated a R wave on the lead V(1) and a Rs wave on V(5)-V(6). Conclusion: A positive R wave in inferior leads, a negative QS morphology in lead aVL and aVR are seen in all patients, but different electrocardiographic characteristics of PVC/VT originating from the different portions of the DGCV are presented on lead Ⅰ and V(1)-V(6).

Survival advantage associated with multimodal therapy in women with node-positive (stage-IIIC) uterine papillary serous carcinoma: a National Cancer Database study.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer. Adjuvant chemotherapy (CT) has become standard care in treatment of women with advanced-stage UPSC, but the role of consolidative radiotherapy (RT) is unclear. This study aims to evaluate survival outcomes of multimodal therapy. DESIGN: Retrospective cohort study using a National Cancer Database (NCDB). SETTING: United States of America. SAMPLE: A total of 1816 women diagnosed with UPSC. METHODS: All women diagnosed with surgically staged FIGO (International Federation of Gynecology and Obstetrics) stage-IIIC UPSC were identified in the NCDB from January 1998 to December 2010. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate and multivariable analyses were performed to identify and control for prognostic factors. MAIN OUTCOME MEASURE: Overall survival. RESULTS: A total of 398 057 cases of uterine cancer were identified, 22 106 of which were UPSC. Of these women, 14 093 underwent lymph-node examination, 2902 (20.6%) were found to have stage-IIIC disease, and 1816 received chemotherapy. Younger age and higher number of total lymph nodes examined were independently predictive of receiving multimodality (CT + RT) therapy, compared with CT only. Median OS was 33.6 and 42.6 months, for the CT and CT + RT groups, respectively (P < 0.0005). Exploratory univariate analyses found age, comorbidity index, tumour size, and number of dissected and positive lymph nodes to be also associated with survival. Multivariable analysis controlling for the above found the use of consolidative radiotherapy to be independently predictive of improved OS, with a hazard ratio of 0.69 (95% confidence interval, 95% CI 0.56-0.84). CONCLUSIONS: Patients with stage-IIIC UPSC may benefit from multimodal treatment that includes adjuvant radiotherapy in addition to chemotherapy. TWEETABLE ABSTRACT: In this study of 1816 women with uterine papillary serous cancer, adjuvant radiotherapy increased survival.

[Effects and mechanism of testosterone on the production of inflammatory cytokines and glucose uptake in co-culture of RAW264.7 macrophage and 3T3-L1 adipocytes].

Objective: To investigate the effects of testosterone (T) on inflammatory cytokines (IL-6, MCP-1) production, insulin sensitivity of adipocyte and changes of macrophage phenotypes in indirect co-culture of RAW264.7 macrophages and 3T3-L1 adipocytes. Methods: 3T3-L1 preadipocytes were induced to mature in Transwell lower chamber, and then co-cultured with RAW264.7 macrophages in the upper chambers for 72 hours. Testosterone 10 µmol/L was added into indirect co-culture for 24 h. ELISA was used to testing IL-6, MCP-1 concentrations in supernatant. Western blot was used to detecting the phosphorylation of NF kappa B, ERK1/2, and theexpression of CD16/32 and CD206. Glucose transport was assessed by[3H]2-deoxy glucose uptake in adipocytes. Results: Testosterone enhanced inflammatory cytokines (IL-6, MCP-1) production in indirect co-culture of 3T3-L1 adipocytes and RAW264.7 macrophages, promoted the activation of ERK1/2 and nuclear factor kappa B p65, and inhibited glucose uptake in adipocytes. Testosterone facilitated the production of pro-inflammatory M1 macrophages. The above effects of testosterone can be completely reversed by PDTC, and can be partly reversed by PD98059 (70%-90%). Conclusion: NF kappa B and ERK1/2 could be the key proteins for testosterone to promote the production of inflammatory factors, to lead to insulin resistance, and to make macrophages differentiate to pro-inflammatory phenotypes in co-culture of RAW264.7 macrophages and 3T3-L1 adipocytes.

Prognosis and survival of 128 patients with severe avian influenza A(H7N9) infection in Zhejiang province, China.

No published studies have discussed details of the prognosis and survival of patients with severe avian influenza A(H7N9) infection. In this study we analysed 128 laboratory-confirmed cases of severe H7N9 infection in Zhejiang province, the most affected region during the H7N9 epidemic in mainland China. We found that an increase in patient age by 5 years was associated with a 1.41 [95% confidence interval (CI) 1.19-1.67] times odds ratio for fatality. In addition, the time interval between the first clinical visit after symptom onset and hospital admission was inversely associated with survival time since admission. Of the 47 patients who died of the disease, when the time interval between the first clinical visit and hospital admission increased by 1 day, the duration of survival was 0.78 times (95% CI 0.62-0.98) as long. Our results suggest that patients with severe influenza H7N9 infection at older ages were at a higher risk of fatality, and that a delay in hospital admission was associated with more rapid death. More studies are required to corroborate our major findings.

Epidemiology of human infections with avian influenza A(H7N9) virus in the two waves before and after October 2013 in Zhejiang province, China.

We compared the epidemiological and clinical features of avian influenza A(H7N9) virus infections in the population in Zhejiang province, China, between March and April 2013 (first wave) and October 2013 and February 2014 (second wave). No statistical difference was found for age, sex, occupation, presence of underlying conditions, exposure history, white blood cell count, lymphocyte percentage and illness timeline and duration (all P > 0.05). The virus spread to 30 new counties compared to the first wave. The case-fatality rate was 22% in the first wave and 42% in the second (P = 0.023). Of those infected, 66% in the first wave and 62% in the second wave had underlying conditions. The proportion of those exposed to live poultry markets were 80% and 66%, respectively. We recommend permanent closure of live poultry markets and reformation of poultry supply and sales.

Seroprevalence of severe fever with thrombocytopenia syndrome virus in southeastern China and analysis of risk factors.

Severe fever with thrombocytopenia syndrome virus (SFTSV) has been prevalent for some time in China and it was first identified in 2010. However, the seroprevalence of SFTSV in the general population in southeastern China and risk factors associated with the infection are currently unclear. Blood samples were collected from seven counties across Zhejiang province and tested for the presence of SFTSV-specific IgG antibodies by ELISA. A total of 1380 blood samples were collected of which 5·51% were seropositive for SFTSV with seroprevalence varying significantly between sites. Seroprevalence of SFTSV in people who were family members of the patient, lived in the same village as the patient, or lived in a different village than the patient varied significantly. There was significant difference in seroprevalence between participants who bred domestic animals and participants who did not. Domestic animals are probably potential reservoir hosts and contact with domestic animals may be a transmission route of SFTSV.

Role of valence fluctuations in the superconductivity of Ce122 compounds.

Pressure dependence of the Ce valence in CeCu(2)Ge(2) has been measured up to 24 GPa at 300 K and to 17 GPa at 18-20 K using x-ray absorption spectroscopy in the partial fluorescence yield. A smooth increase of the Ce valence with pressure is observed across the two superconducting (SC) regions without any noticeable irregularity. The chemical pressure dependence of the Ce valence was also measured in Ce(Cu(1-x)Ni(x))(2)Si(2) at 20 K. A very weak, monotonic increase of the valence with x was observed, without any significant change in the two SC regions. Within experimental uncertainties, our results show no evidence for the valence transition with an abrupt change in the valence state near the SC II region, challenging the valence-fluctuation mediated superconductivity model in these compounds at high pressure and low temperature.

[A rapidly enlarging neck mass]. / Een snelgroeiende zwelling in de hals.

The differential diagnosis of a rapidly enlarging neck mass consists of many different benign ((haemorrhagic) cyst) and malignant (anaplastic thyroid cancer (ATC) and lymphoma) causes. ATC is a rare disease with a median survival of 6 months. As early diagnosis and management are key for fast-growing cancers, in our centre we have implemented a dedicated short-stay in-hospital fast-track diagnostic work-up for patients with a rapid growing mass in the neck. The goal of this track is to have a fast diagnostic and therapeutic plan for this disease. Based on three clinical cases we discuss our experience with this fast-track diagnostic work-up for rapidly growing mass in the neck and illustrate the additional value in this clinical entity.

Resumption of menstruation and pituitary response to gonadotropin-releasing hormone in functional hypothalamic amenorrhea subjects undertaking estrogen replacement therapy.

BACKGROUND: Functional hypothalamic amenorrhea (FHA) refers to a functional menstrual disorder with various causes and presentations. Recovery of menstrual cyclicity is common in long-term follow-up but the affecting factors remain unknown. AIM: To explore factors affecting the menstrual resumption and to evaluate the pituitary response to gonadotropin-releasing hormone (GnRH) in FHA. MATERIALS AND METHODS: Thirty cases with FHA were recruited. All subjects were put on continuous 1 mg/day estradiol valerate orally and followed up monthly. Recovery was defined as the occurrence of at least three consecutive regular cycles. Responder referred to those who recovered within two years of therapy. Gonadotropin response to the 50 µg GnRH challenge was tested every three months. RESULTS: Nineteen (63.3%) subjects recovered with a mean time to recovery of 26.8 months. Time to recovery was negatively correlated with body mass index (BMI) before and by amenorrhea. Twentyone cases had undertaken therapy for more than two years and 10 of them recovered. BMI before and by amenorrhea were negatively correlated with the recovery. Significant increase of serum luteinizing hormone (LH) and LH response to GnRH were noted after recovery. CONCLUSIONS: Menstrual resumption was common in FHA undertaking estrogen replacement therapy (ERT). The likelihood of recovery was affected by their BMI before and by amenorrhea but not by the weight gain during therapy. Low serum LH and attenuated LH response to GnRH were the main features of pituitary deficiency in FHA. The menstrual resumption in FHA was accompanied by the recovery of serum LH and the LH response to GnRH.

[Influence of sleep fragmentation in infancy and toddler period on emotional and behavioral problem at the age of 6 years: a birth cohort study].

Objective: To investigate the influence of sleep fragmentation in infancy and toddler period on emotional and behavioral problems at the age of 6 years. Methods: Using a prospective cohort design, 262 children were extracted from mother-child birth cohort recruited from May 2012 to July 2013 in Renji Hospital, School of Medicine, Shanghai Jiao Tong University. Children's sleep and physical activities were assessed using actigraphy at 6, 12, 18, 24, and 36 months of age, from which the sleep fragmentation index (FI) at each follow-up point was calculated. Children's emotional and behavioral problems at 6 years of age were assessed using the strengths and difficulties questionnaire. Group-based trajectory model was applied to determine sleep FI in infancy and toddler period trajectory groups with Bayesian information criteria being used to determine the best fitting model. Children's emotional and behavioral problems between groups were examined with independent t test and linear regression models, etc. Results: A total of 177 children, with 91 boys and 86 girls, were included in the final analysis and were divided into 2 groups: high FI group (n=30) and low FI group (n=147). Compared with children in the low FI group, those in the high FI group presents with higher total difficulties score and higher hyperactivity or inattention score ((11.0±4.9) vs. (8.9±4.1), (4.9±2.7) vs. (3.7±2.3) scores, t=2.17, 2.23, both P<0.05, respectively), with the differences remaining significant after adjusting for covariates (t=2.08, 2.09, both P<0.05 respectively). Conclusion: High sleep fragmentation in infancy and toddler period is associated with more emotional and behavioral problems, especially hyperactivity or inattention problems, at 6 years of age.

Association between Iodized Salt Intake and Cognitive Function in Older Adults in China.

OBJECTIVES: To investigate the association between iodized salt intake and cognitive function in older adults. DESIGN: A cross-sectional study. SETTINGS: Individuals from the Zhejiang Major Public Health Surveillance Program (ZPHS). PARTICIPANTS: Data of 10,217 participants (including 4,680 coastal residents and 5,537 inland residents) aged ≥ 60 years were analyzed. MEASUREMENTS: Salt intake was evaluated using a questionnaire, and participants were stratified into the following three groups: iodized salt, non-iodized salt, and mixed salt. Cognitive function was assessed through the Mini-Mental State Examination and defined using education-specific cut-off points. Logistic regression models controlling for an extensive range of potential confounders were generated to examine the association between salt intake and cognitive function among all participants. RESULTS: Data from 10,217 participants with a 16.1% prevalence of cognitive impairment were analyzed. Compared with non-iodized salt intake, consumption of iodized salt was inversely associated with cognitive impairment (odds ratio [OR], 0.410; 95% confidence interval [CI], 0.351-0.480; P < 0.001) in all participants after multivariable adjustment. An association between iodized salt intake and cognitive impairment was observed in coastal (OR, 0.441; 95% CI, 0.340-0.572; P < 0.001) and inland residents (OR, 0.569; 95% CI, 0.439-0.738; P < 0.001). Despite the insufficient sample size, the results for individuals consuming mixed salt suggested an inverse association between mixed salt intake and cognitive impairment among coastal residents (OR, 0.598; 95% CI, 0.405-0.885; P = 0.010) after multivariable adjustment. CONCLUSION: Our results indicate that iodized salt intake may reduce the risk of cognitive impairment in older adults living in coastal or inland areas, and the protective effect of iodized salt intake is greater in coastal areas than in inland areas.