Objective:Through comprehensive analysis of symptoms and signs, biochemistry, imaging, and dynamic tests, to explore the diagnosis and differential diagnosis of thyrotropin-secreting pituitary adenoma(TSH adenoma) and syndrome of resistance to thyroid hormone(RTH).Methods:A retrospective analysis was conducted on clinical data from 14 patients who visited the First Affiliated Hospital of Zhengzhou University from July 2016 to September 2022, exhibiting elevated levels of free thyroxine(FT4) and free triiodothyronine(FT3) in the presence of increased TSH.Results:There were 7 cases of TSH adenoma and 7 cases of RTH, with the average age of diagnosis at 40.0 years and 26.6 years, respectively. Thirteen patients showed thyrotoxicosis or occasional palpitation, some with pituitary occupancy manifestations or abnormal growth and development; One patient presented with neck thickening. Sex hormone binding globulin was elevated in 3 cases of TSH adenoma. Pituitary magnetic resonance imaging showed that all 7 cases of TSH adenoma were macroadenomas and 1 case of RTH was microadenoma. The octreotide suppression test in 13 patients was inhibited, but there was a significant difference in the inhibition rate of 24 h/2 h TSH inhibition rate of TSH adenoma and RTH, ranging from 46.6% to 83.9% and 4.6% to 28.8% respectively. Six cases of RTH had thyroid hormone receptor β mutation.Conclusion:Syndrome of inappropriate secretion of thyrotropin is a rare condition, mainly including TSH adenoma and RTH. The diagnosis and differentiation of the two conditions require comprehensive assessment incorporating family history, symptoms and signs, laboratory tests, dynamic test, and genetic test. Among these, the 24 h/2 h TSH inhibition rate of octreotide suppression test can effectively distinguish TSH adenoma from RTH.

Objective:To investigate the mediating effect of inflammatory factors in the association between low density lipoprotein-cholesterol(LDL-C) and thyroid associated ophthalmopathy(TAO).Methods:This study was a prospective study, which icluded a total of 86 patients with Graves′ disease who attended the Department of Endocrinology of the First Affiliated Hospital of Zhengzhou University from January 2021 to June 2022. Among them, there were 56 patients with Graves′ disease accompanied by TAO, including 30 cases in the inactive group and 26 in the active group. Additionally, there were 30 cases having Graves′ disease alone. The relationship between LDL-C, inflammatory factors, and the onset and activity of TAO were analyzed using binary logistic regression. Mediation analysis was used to explore the mediating effect of inflammatory factors in the association between LDL-C and TAO onset and activity.Results:Interleukin(IL) -6 was a potential mediator that linking the association between LDL-C and TAO onset: LDL-C had a direct effect on TAO(Total effect value=0.274, 95% CI 0.161-0.386), while IL-6(mediated effect=0.067, 95% CI 0.011-0.123) and IL-17(mediated effect=0.042, 95% CI 0.007-0.077) partially mediated the effect of LDL-C on TAO, accounting for 24.45% and 15.33% of the total effect, respectively. IL-6 was a potential mediator of the association between LDL-C and TAO activity: LDL-C had a direct effect on TAO activity(Total effect value=0.320, 95% CI 0.204-0.435), and IL-6(mediated effect=0.103, 95% CI 0.021-0.185) partially mediated the effect of LDL-C on TAO activity, with a mediation effect of 32.19%. Conclusion:IL-6 plays a partiall mediating role in the association of LDL-C with TAO onset and activity.

Objective:To investigate the effects and potential mechanism of vitamin D supplementation on testicular function in aging rats induced by D-galactose.Methods:The aging rats were induced by D-galactose with subcutaneous injection. The animals were randomly divided into 6 groups: aging rats (DG), aging rats with low-dose vitamin D supplementation (LD), aging rats with high-dose vitamin D supplementation (HD), normal control rats(NC), normal rats with low-dose vitamin D supplementation(LN), normal rats with high-dose vitamin D supplementation (HN). The body weight, testicular weight, serum testosterone concentrations and sperm quality of the rats in each group were measured. The testis morphological changes were detected using light microscopy. The activity of superoxide dismutase (SOD) and level of malondialdehyde(MDA) were determined with spectrophotometer. The expression levels of Nrf2, GCLC, SOD2 and VDR in testis were detected by western blot.Results:At baseline, compared with NC group, testicular weight, serum testosterone level, SOD activity, Nrf2, GCLC and SOD2 expression levels were significantly decreased in DG group, while MDA level was significantly increased. After vitamin D supplementation, testicular weight, testosterone levels and SOD activity in both of HD and LD groups were significantly increased, while the MDA level was significantly decreased. The expression levels of Nrf2, GCLC, SOD2 and VDR were significantly increased.Conclusion:Vitamin D supplementation may enhance the testicular antioxidant capacity through activating Nrf2-ARE signaling pathway, and improve the testicular function in D-galactose-induced aging rats.

The data of 10 patients with pituitary metastases were retrospectively analyzed, including tumor origin, clinical features, imaging characteristics, diagnosis and differential diagnosis, treatment and prognosis. The results showed that the average age of 10 patients at the time of consultation was 62.0 years. Nine metastases were originated from lung cancer and one from breast cancer. All patients started with central diabetes insipidus, and some of them accompanied with hypopituitarism, as well as occupancy manifestations such as headache, blurred vision, etc. MRI showed abnormalities in the pituitary stalk and posterior pituitary, four of which showed characteristic " dumbbell-shaped" changes. Three patients with epidermal growth factor receptor(EGFR)-mutated lung adenocarcinoma revealed improvement in both primary lesion and pituitary metastases after targeted therapy.

Objective:To summarize the clinical manifestations and molecular genetic characteristics of 5 families with maturity-onset diabetes mellitus of the young 2 (MODY2) caused by glucokinase (GCK) gene mutations.Methods:Clinical data and biochemical results of probands were collected. Peripheral blood samples of probands and first-degree family members were collected and whole exome gene was detected using second-generation sequencing. After comparing against the database, the suspected pathogenic sites were selected for Sanger sequencing verification.Results:All the 5 probands presented with mild fasting hyperglycemia, HbA 1C<7.5%, and no symptoms of thirst, polydipsia or polyuria. There were 6 mutants in 5 families, including M1: c.555delT (P.leu186CysFS Ter19) and M3: c. 263T>A (p.Met88Lys) which haven′t been reported before. During the follow-up, all probands received life-style intervention, except 2 pregnant women who should consider insulin treatment if necessary according to fetal genotypes. Conclusion:Among patients who meet the diagnostic criteria for MODY, MODY2 screening should be performed for children or pregnant women with mild hyperglycemia and family history. GCK gene detection is the gold standard for diagnosis, and accurate diagnosis will be conducive to the selection of appropriate treatment.

ObjectiveTo investigate the social support status and influencing factors of schizophrenics in remission in Northeast Sichuan， and to provide ideas for improving their social support. MethodsFrom May to September 2020， a total of 533 patients who met the diagnosis criteria of the International Classification of Diseases， tenth edition （ICD-10） for schizophrenics in remission at the mental health institutions in Guangyuan， Bazhong and Dazhou cities were selected for the survey， and patients were assessed by self-made demographic and clinical data inventory and Social Support Rating Scale （SSRS）. Then the social support status of schizophrenic in remission and influencing factors were analyzed， meantime， the impact of the second round reimbursement policy of medical insurance benefits on their social support was addressed particularly. Results①The SSRS total score， objective support， subjective support， and utilization of support scores of schizophrenics in remission were lower than those of the national norm （t=5.065~30.382， P<0.01）. ②Univariate analysis showed that SSRS score was relatively high among patients with female gender （t=-3.632）， retired status （F=5.951）， married status （F=5.951）， spouse as primary caregiver （F=23.841）， annual household income >5 000 yuan （F=15.892）， patient's economic income （t=4.083）， and outpatient or online follow-up （F=3.954）， with statistically significant differences （P<0.05 or 0.01）. ③The total and dimensional scores of SSRS in patients with access to the second round medical insurance reimbursement were significantly higher than those without （t=10.195~25.103， P<0.01）. ④Multiple linear regression analysis denoted that gender， work status， marital status， primary caregivers， annual family income， economic income， follow-up visits and the second round medical insurance reimbursement were the factors influencing social support status of schizophrenics in remission （β=0.201~2.115， P<0.05 or 0.01）. ConclusionThe social support of schizophrenics in remission in Northeast Sichuan is below the national average， furthermore， their social support levels are affected by the gender， work status， marital status， primary caregivers， annual family income， economic income， follow-up visits and the second round medical insurance reimbursement， and the second round medical insurance reimbursement may ameliorate the social support status of patients.

A 57-year-old man was admitted to hospital with diarrhea for 10 months and dizziness for 4 months. The patient had 1-2 liters watery stool per day, without pyogenic blood or abnormality in gastroenteroscopy examination. The level of hemoglobin and albumin was generally normal, and fasting test was positive. At the same time, he was accompanied with hyperalgesia of lower limbs and orthostatic hypotension. After the discussion of multiple disciplinary teams, the patient was diagnosed with amyloidosis by sural nerve biopsy, myocardial MRI, and the assays of urine immunoelectrophoresis and serum free light chain. Light chain amyloidosis was confirmed after excluded the diagnosis of familial amyloidosis. The patient was improved after courses of chemotherapy with melphalan and dexamethasone.

Objective:To investigate the effect of miR-425-5p on glucagon-like peptide-1(GLP-1) secretion in intestinal L cells induced by lipopolysaccharide(LPS), and to explore its mechanism.Methods:GLUTag cells of intestinal L cell line were incubated with LPS to determine the levels of miR-425-5p and GLP-1. Cell viability was determined by MTT assay, and cell apoptosis was detected by flow cytometry. Quantitative real time-PCR and western blot were performed to determine the expressions of miR-425-5p, phosphatase and tensin homology(PTEN), proglucagon, and GLP-1. Activity of Wnt/β-catenin signaling pathway was determined by detecting TOP/FOP ratio. Interaction among miR-425-5p, PTEN, and β-catenin was analyzed using luciferase activity assay and chromatin immunoprecipitation(ChIP)assay.Results:In GLUTag cells, with the elevation of LPS concentration, the expression of miR-425-5p and the apoptosis rate were increased, while the level of active GLP-1 and the cell viability were decreased. MiR-425-5p was involved in the regulation of LPS on GLP-1 secretion and intestinal L cell viability. Inhibition of miR-425-5p reduced the mRNA expression of proglucagon and the TOP/FOP ratio, increased PTEN protein level, and inhibited cell viability. In LPS-treated GLUTag cells, miR-425-5p increased the level of β-catenin by targeting PTEN, and β-catenin acted as a cis-acting element to induce the transcription of proglucagon and promote the secretion of GLP-1.Conclusion:In LPS-induced intestinal L cells, miR-425-5p promotes the expression of GLP-1 by targeting PTEN to modulate β-catenin.

Objective:To explore the distribution of serum TRAb IgG subtypes in patients with thyroid-associated ophthalmopathy(TAO) at different stages and its value in assessing TAO activity.Methods:Forty-three patients with TAO, 30 patients with Graves′ disease (GD group), 19 patients with Hashimoto′s thyroiditis (HT group), and 50 healthy subjects (NC group)admitted to the First Affiliated Hospital of Zhengzhou University were collected from August 2018 to February 2019. According to the clinical activity score (CAS), the patients with TAO were further divided into the active period group (AP group, CAS≥3 points, 22 cases) and the inactive period group (IP group, CAS<3 points, 21 cases). The basic clinical data of subjects in each group were collected. The serum concentrations of FT 3, FT 4, TSH, thyroperoxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroid-stimulating hormone receptor antibody (TRAb) were detected by chemiluminescence immunoassay and the binding rate in percentage (B) of serum TRAb IgG and IgG subtypes were detected by ELISA. The positive rate in each group and relative content of positive samples were compared. Results:(1)Compared with HT group, the positive rates of IgG1 and IgG2 in TAO group and GD group were significantly decreased ( P<0.05). There was no significant difference in the relative content of positive TRAb IgG subtype among these disease groups ( P>0.05). (2)Compared with the IP group, IgG1(B) and the positive rates of IgG1 in the AP group were increased while IgG4(B) and the relative contents of IgG4 were reduced ( P<0.05). (3)IgG1(B)was positively correlated with TAO activity ( B=6.190, P=0.007), and higher IgG4(B)indicated more inclinations to the inactive period ( B=-16.390, P=0.052). (4) The area under the curve of receiver operating characteristic (ROC) for TAO developing into active period assessed by activity rate was 0.859 (95% CI 0.746-0.973, P<0.05). When the activity rate was 4.29, the Jordon index showed the largest, with sensitivity of 81.8% and specificity of 81.0%. Conclusions:Elevated levels of TRAb IgG1 in the patients with TAO indicate a tendency to active period, while elevated levels of TRAb IgG4 indicate a tendency to inactive period. The activity rate can provide a reference for assessing whether TAO is active or not.

Objective:To examine associations of sex hormone levels with bone turnover markers(BTMs) among men in the Northeast region of Henan Province.Methods:From December 2015 to March 2016, 707 male subjects were selected from a National Epidemiological Survey-2014(Thyroid Disorders, Iodine status and Diabetes, TIDE)research—Henan sub-center survey by using multistage stratified cluster random sampling. Fasting venous blood was collected to determine the levels of luteinizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E 2), testosterone(T), dehydroepiandrosterone-sulfate (DHEAS), androstenedione(AD), sex hormone binding globulin(SHBG), dihydrotestosterone(DHT), free testosterone(FT), osteocalcin(OC), pro-collagen type 1 N-terminal propeptide(PINP), C-terminal-cross-linking telopeptide of type 1 collagen(β-CTX), 25-hydroxyvitamin D [25(OH)D], and parathyroid hormone(PTH). Results:A total of 697 men with an average age of(46.6±15.9)years were included in the study. Pearson correlation analysis showed that age was positively associated with LH, FSH, T, and SHBG, while negatively associated with E 2, DHEAS, AD, FT, β-CTX, OC, and PINP, without significant correlation with DHT, 25(OH)D, and PTH. Pearson correlation analysis and linear regression analysis showed that E 2 was negatively associated with β-CTX; T was positively associated with OC, FSH was negatively associated with OC; LH, FSH, and SHBG were negatively associated with PINP; E 2, T, FT, DHT, and AD were positively associated with PINP. After adjusting for age and BMI, linear regression analysis showed that T was still significantly positively associated with OC and PINP, with 0.302 ng/ml and 0.015 ng/ml increasing for OC and PINP every 1 ng/ml increase in T; E 2 and DHT were positively associated with PINP, with 0.250 and 0.047 ng/ml increasing for PINP every 1 pg/ml increase in E 2 and DHT. Conclusions:Age is an important factor influencing sex hormones and BTMs. Serum levels of T, E 2, and DHT are associated with bone formation and bone absorption markers.