Gitelman syndrome combined with diabetes mellitus: A case report and literature review.

RATIONALE: Gitelman syndrome (GS) is an uncommon autosomal recessive tubulopathy resulting from a functional deletion mutation in the SLC12A3 gene. Its onset is typically insidious and challenging to discern, and it is characterized by hypokalemia, metabolic alkalosis, and reduced urinary calcium excretion. There is limited literature on the diagnosis and management of GS in individuals with concomitant diabetes. PATIENT CONCERNS: A 36-year-old male patient with a longstanding history of diabetes exhibited suboptimal glycemic control. Additionally, he presented with concurrent findings of hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. DIAGNOSIS: Building upon the patient's clinical manifestations and extensive laboratory evaluations, we conducted thorough genetic testing, leading to the identification of a compound heterozygous mutation within the SLC12A3 gene. This definitive finding confirmed the diagnosis of GS. INTERVENTIONS: We have formulated a detailed medication regimen for patients, encompassing personalized selection of hypoglycemic medications and targeted electrolyte supplementation. OUTCOMES: Following 1 week of comprehensive therapeutic intervention, the patient's serum potassium level effectively normalized to 3.79 mmol/L, blood glucose parameters stabilized, and there was significant alleviation of clinical symptoms. LESSONS: GS has a hidden onset and requires early diagnosis and intervention based on patient related symptoms and laboratory indicators in clinical practice, and personalized medication plans need to be provided according to the specific situation of the patient.

Ursolic acid ameliorates Nthy-ori 3-1 cells injury induced by IL-1ß through limiting MALAT1/miR-206/PTGS1 ceRNA network and NF-κB signaling pathway.

RATIONALE: Ursolic acid (UA) has exhibited anti-inflammatory and anti-oxidative drug effects. OBJECTIVES: In the research, we assessed the effects of UA on Nthy-ori 3-1 cells stimulated by IL-1ß and attempted to elucidate the mechanisms underlying the effects. METHODS: Autoimmune thyroiditis (AIT) was simulated using Nthy-ori 3-1 cells by IL-1ß (10 µM) treatment. UA (20 µM) was applied to ameliorate the injury of Nthy-ori 3-1 cells. The target of UA was predicted by TCMSP, BATMAN, and GEO database. Targeted relationship between lncRNA MALAT1 and miR-206, as well as miR-206 and PTGS1, was predicted by bioinformatics software and identified by dual luciferase assays. Cytokines in the cell supernatant and the apoptosis of cells were detected by ELISAs and flow cytometry assays, respectively. Expression levels of NF-κB signaling pathway-related proteins were estimated by western blot. RESULTS: By enquiring TCMSP, BATMAN, and GEO database, PTGS1 was identified as a target of UA. Afterward, a ceRNA network among MALAT1, miR-206, and PTGS1 was constructed. The expression levels of MALAT1 and PTGS1 in AIT tissues were obviously enhanced. Moreover, the ceRNA network formed by MALAT1/miR-206/PTGS1 contributed to the damage of Nthy-ori 3-1 cells induced by IL-1ß. However, UA ameliorated the Nthy-ori 3-1 cells injury induced by IL-1ß through mediating the MALAT1/miR-206/PTGS1 ceRNA network and NF-κB signaling pathway. CONCLUSIONS: UA treatment significantly relieved the injury of Nthy-ori 3-1 cells via inhibiting the ceRNA mechanism of MALAT1/miR-206/PTGS1 and inflammatory pathways, insinuating that UA may be helpful for the treatment of AIT.

Clinical analysis of 249 cases of adrenal tumors in a Chinese hospital.

OBJECTIVE: This study was designed to evaluate the clinical and pathological characteristics of adrenal masses. METHODS: The clinical data of 249 cases of adrenal masses which were confirmed at operation and by pathology were analyzed. RESULTS: The series comprised 103 males and 146 females. Overall, females were more commonly represented than males, especially with Cushing's syndrome and typical pheochromocytoma (female:male ratio 3.3:1.9), however the prevalence of adrenal incidentalomas (AIs) in males and females was similar. In our series, 148 (59.4%) were symptomatic, of which 4 (2.7%) were malignant, and 101 (40.6%) were incidental, of which 20 (19.8%) were malignant. Hormonal work-up demonstrated that 30.3% of the AIs were functional. Of 109 adrenocortical adenomas, 47 were primary aldosteronism, 31 were Cushing's syndrome, 30 were AIs, and 1 was adrenal virilization. Of 72 benign pheochromocytomas, 51 were typical pheochromocytomas and 21 were AIs. Of 14 adrenal nodular hyperplasias, 6 were Cushing's syndrome and 8 were primary aldosteronism. Of the remaining 30 benign tumors, all presented as AIs. The diameter of malignant tumors (10.9 ± 5.6 cm) was significantly larger than that of benign tumors (4.5 ± 3.7 cm) (p < 0.001). CONCLUSION: This study shows a high rate of AIs in patients with adrenal masses selected for surgery. Hormone levels should be determined in symptomatic or incidental patients with adrenal masses. Imaging examination (CT and MRI) is the first method used to detect and localize adrenal masses. Tumor size is an important parameter of diagnosis and management of patients with adrenal masses, especially AIs.

Regulation of GSK-3 beta in the proliferation and apoptosis of human thyrocytes investigated using a GSK-3 beta-targeting RNAi adenovirus expression vector: involvement the Wnt/beta-catenin pathway.

Disorders in the proliferation and apoptosis of thyrocytes may induce goitre, adenoma and carcinoma in the thyroid. The Wnt/beta-catenin pathway has been demonstrated to be involved in the regulation of cell proliferation, differentiation and apoptosis in various cell lines. The regulatory mechanism on the proliferation and differentiation of thyrocytes is not well characterized. In the present study, a GSK-3beta-targeting RNA interference (RNAi) adenovirus vector was constructed and delivered to primary human thyrocytes. Results showed that the expression of beta-catenin protein in primary human thyrocytes was increased after GSK-3beta-targeting RNAi adenovirus infection, the proliferation of primary human thyrocytes was significantly stimulated using Bromodeoxyuridine (BrdU) assay, while cell apoptosis was slightly affected which was observed through flow cytometry. It is concluded that the Wnt/beta-catenin pathway plays a significant role in the regulation of the proliferation of primary human thyrocytes.

[Construction of GSK-3beta-targeting RNAi adenovirus vector and the influence of Wnt/beta-catenin pathway in proliferation of human thyrocytes].

OBJECTIVE: To construct RNAi recombinant adenoviral expressive vectors specific to glycogen synthase kinase-3beta (GSK-3beta) and to observe its gene knockdown effect on the expression of GSK-3beta, and to explore the effect of Wnt/beta-catenin pathway on the proliferation of human thyrocytes using the RNAi adenovirus vector. METHODS: An adenovirus plasmid that contained the RNAi cassette targeting the GSK-3beta gene was constructed by homologous recombination and cloning techniques, transfected into human embryo kidney (HEK) 293A cells to product adenovirus, and then was used to infect the HEK293A cells to amplify the adenoviral stock. Plaque forming assay was used to titer the adenoviral stock. Normal human thyrocytes fart from thyroid adenoma were obtained during resection of adenoma, cultured, and infected by the GSK-3beta specific RNAi adenovirus. The GSK-3beta gene silencing effect induced by the RNAi adenovirus was detected by Western blotting 0, 24, 48, 72, 120, and 144 hours later. BrdU method was used to detect the cell proliferation. Another HEK293A cells were divided into 3 groups: infected with recombinant adenovirus plasmid Ad-1457, infected with un-recombinant framework plasmid pAd-DEST, and un-infected. 72 hours later Western blotting was used to examine the level of beta-catenin. RESULTS: The GSK-3beta expression of the thyrocytes infected with the recombinant adenovirus plasmid Ad-1457 were significantly lower than those of the thyrocytes infected with Ad-DEST (all P<0.05). The expression of beta-catenin of the thyrocytes infected with Ad-DEST was significantly higher than those of the Ad-DEST group and un-infected group (both P<0.05). BrdU assay suggested that the proliferation rates 1, 3, 5, and 7 days after infection of the thyrocytes infected with Ad1457 plasmid were significantly higher than those of the thyrocytes infected with the plasmid pAd-DEST (all P<0.05). CONCLUSION: RNAi adenovirus is an important tool inhibiting the expression of target gene efficiently. The Wnt/beta-catenin pathway plays an important role in the regulation of proliferation of human thyrocytes.