Background:Primary aldosteronism (PA) subtypes exhibit significant sex-specific differences, particularly regarding cardiovascular risk and the metabolic syndrome. This study investigated these differences between subtypes and developed a machine learning model for subtype prediction. Design and Methods:This retrospective study analyzed clinical and imaging data from 276 PA patients, subtyped by adrenal venous sampling. Visceral and cardiac adipose deposition were quantified, least absolute shrinkage and selection operator (LASSO) regression identified optimal predictive parameters for model development. Results:Unilateral PA (UPA) presented with prominent hypertension and hypokalemia, whereas bilateral PA (BPA) showed more visceral fat deposition, with notable sex differences. (1) In males, the BPA group had a higher body mass index, abdominal fat, and larger epicardial adipose tissue (EAT) volume along with a greater E/e' ratio compared to UPA. (2) Across both subtypes, males demonstrated more abdominal fat than females. (3) In females, BPA had higher triglycerides, serum calcium than UPA. (4) In males, an XGBoost model using visceral fat area (VFA), serum potassium, systolic blood pressure, and plasma aldosterone concentration (PAC) achieved an AUC of 0.84±0.05. An XGBoost model in females based on serum potassium, lipid profile, PAC after saline infusion test, and CT nodule characteristics yielded an AUC of 0.75±0.02. Conclusion:PA subtypes exhibit prominent sex-specific cardiometabolic profiles. In males, BPA correlates with significantly greater ectopic fat deposition and elevated cardiovascular risks. Combining VFA with key biochemical markers demonstrates superior diagnostic efficacy for PA subtyping in the male group.

Background: Evidence supports the effectiveness and safety of open-source automated insulin delivery (AID) in patients with type 1 diabetes. However, evidence regarding the clinical application of open-source AID in perioperative patients with type 2 diabetes remains limited. Methods: This was an open-label, single-center, exploratory pilot randomized controlled trial (RCT) with parallel groups. Patients with diabetes (excluding type 1 diabetes mellitus) scheduled for elective surgery were randomly assigned to the closed-loop group (open-source hybrid closed-loop AID system) or the control group (conventional insulin pump). The primary outcome was the percentage of time in the target glucose range (TIR, 3.9-10.0 mmol/L). Other efficacy and safety outcomes were also compared between the groups. Results: A total of 49 participants were included and randomized to the closed-loop group (n = 25) or the control group (n = 24). Participants underwent abdominal, orthopedic, thoracic surgery, or neurosurgery during hospitalization. Patients in the closed-loop group had significantly higher TIR than patients in the control group (76.4 ± 14.1% vs. 61.2 ± 20.0%, p = 0.005). Compared with the control group, the closed-loop group also exhibited a 15.6 percentage point reduction in time above range (TAR, >10 mmol/L) without increasing time below range (TBR, <3.9 mmol/L). There were no episodes of severe hypoglycemia (<2.2 mmol/L) or diabetic ketoacidosis in either group. Conclusions: This study demonstrates that in patients with diabetes undergoing elective surgery, the open-source hybrid closed-loop AID system provides better glycemic control than conventional insulin pump therapy.

PURPOSE:Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare subtype of Cushing's syndrome, with some cases exhibiting a familial aggregation tendency. The heterogenous expression of CYP11B1 mRNA among multiple adrenal nodules in PBMAH had not been previously reported. This study aims to investigate the correlation between CYP11B1 mRNA expression and Hounsfield unit (Hu) density in computed tomography (CT) scans in a patient with ARMC5 mutated PBMAH. METHODS:A 47-year-old male came to our hospital for headache and hypertension. He was diagnosed as PBMAH later and received adrenalectomy. DNA sequencing was performed on the patient's peripheral blood, his relatives' peripheral blood, and the patient's adrenal tissues. Additionally, four different adrenal nodules from the patient were collected to explore the relationship between CYP11B1 mRNA expression and Hu density in CT scanning. RESULTS:A family with autosomal dominant inherited PBMAH was identified. Second generation sequencing of peripheral blood and Sanger sequencing of adrenal tissues identified a novel ARMC5 pathogenic variant, c.1865-2_1865-1del, which was also present in the patient's brother, sister and nephew. The patient's adrenal was enlarged diffusely but cushingoid feature was not severe. The adrenal imaging showed bilateral macronodules resembling adrenal tumors. Notably, the Hu values varied significantly among different nodules, and interestingly, the CYP11B1 mRNA expression was found to be parallel to the Hu values. CONCLUSIONS:We reported a family of PBMAH with novel ARMC5 pathogenic variant. The index patient exhibited heterogeneous adrenal nodules with distinct Hu values and CYP11B1 mRNA levels.

Background and aims Angiopoietin-like protein 8 (ANGPTL8), an important regulator of glucose and lipid metabolism, has recently been shown to be associated with renal function decline in patients with diabetic kidney disease (DKD). However, the underlying molecular mechanisms remain unclear. This study aimed to elucidate the novel role of ANGPTL8 in DKD progression. Methods The renal expression of ANGPTL8 was measured in patients and murine models with DKD. Proximal tubule-specific Angptl8 knockout mice were generated to elucidate the role of ANGPTL8 in the pathogenesis of DKD. In vitro, ANGPTL8 was inhibited in human proximal tubular epithelial cells (PTECs) under high glucose plus palmitic acid (HGPA) stress. ANGPTL8 interacting proteins were screened using the human proteome microarray and validated by complementary interaction assays. Functional validation employed the Akt2 small interfering RNA and the specific Akt2 inhibitor in vitro and proximal tubule-specific Akt2 knockout mice in vivo. Results ANGPTL8 expression was significantly increased in renal proximal tubules during DKD. Proximal tubule-specific Angptl8 knockout ameliorated tubular injury and reduced tubular inflammation and fibrosis in DKD mice. In vitro, ANGPTL8 inhibition protected human PTECs against HGPA-induced inflammation and epithelial-mesenchymal transition (EMT). Mechanistically, intracellular ANGPTL8 directly binds to and activates Akt2, triggering downstream NF-κB pathway activation and GSK3β inhibition. Akt2 inhibition abolished ANGPTL8's pathogenic effects in vitro and in vivo. Conclusions Our findings demonstrate for the first time that elevated tubular ANGPTL8 promotes tubular inflammation and fibrosis during DKD by interacting with Akt2, highlighting the ANGPTL8-Akt2 axis as a promising target to prevent DKD progression.

To investigate the potential mediating effect of remnant cholesterol (RC) in the associations between angiopoietin-like 8 (ANGPTL8) and the risk of all-cause, cardiovascular disease (CVD), and cancer death. This prospective observational study included 3278 individuals from China. Binary logistic regression and mediation analyses were conducted to investigate the mediating effect of RC in the associations between ANGPTL8 and all-cause, CVD, and cancer death. During up to 5-year follow-up, a total of 265 deaths (8.08

Previous studies have been limited by their inability to differentiate between the effects of insulin sensitivity and β-cell function on the risk of kidney function decline, cardiovascular disease (CVD), and all-cause mortality. To address this knowledge gap, we aimed to investigate whether the physiological subtypes based on homeostasis model assessment-2 (HOMA2) indices of β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) could be used to identify individuals with subsequently high or low of clinical outcome risk. This retrospective cohort study included 7,317 participants with a follow-up of up to 5 years. Based on HOMA2 indices, participants were categorized into four physiologic subtypes: the normal phenotype (high insulin sensitivity and high β-cell function), the insulinopenic phenotype (high insulin sensitivity and low β-cell function), the hyperinsulinaemic phenotype (low insulin sensitivity and high β-cell function), and the classical phenotype (low insulin sensitivity and low β-cell function). The outcomes included kidney function decline, CVD events (fatal and nonfatal), and all-cause mortality. Cox regression models were used to calculate hazard ratios (HRs) for outcomes, and spline models were used to examine the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes. A total of 1,488 (20.3

Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB −/− bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.

This article reports a case of oligomenorrhea accompanied by acne over several years. The patient presented with hyperandrogenism and insulin resistance. The initial diagnosis considered polycystic ovary syndrome(PCOS) and was treated with oral medication for 2 months, with no significant improvement. Further ultrasound examination revealed a right ovarian heterogeneous mass (3.2 cm×3.0 cm). The patient underwent laparoscopic resection of the right ovarian lesion. Postoperative pathology revealed ovarian sex cord-stromal cell tumor, adult granulosa cell tumor(diffuse type). Testosterone levels decreased to the normal 3 days after the surgery, and menstruation resumed within 2 months. This article summarizes the presented case and reviews the relevant literature. For women with severe hyperandrogenism and masculinization, it is recommended to thoroughly assess the possibility of androgen-secreting tumors.

Background In this paper, we present a rare case of tumor-induced osteomalacia (TIO) and a literature review of this rare disease. Methods A case of TIO of the isolated sphenoid sinus was reported. Furthermore, the clinical features of TIO in the sphenoid sinus and other sinonasal sinuses were also reviewed and summarized. Results A 35-year-old man with muscle weakness and lower back pain came to the Department of Neurology. No obvious neurological disease was found; however, magnetic resonance imaging of the extremities accidentally showed a tumor in the axilla. Bone scintigraphy showed suspicious bone metastasis. Hypophosphatemia was neglected. Interestingly, 2-deoxy-2-[fluorine-18]fluoro- d -glucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) detected a tumor in the axilla and another in the sphenoid sinus, but only the tumor in the sphenoid sinus had somatostatin receptor (SSTR) expression in 68-gallium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid octreotate (Ga-68 DOTATATE) PET/CT. The sphenoid sinus tumor was proven to be a phosphaturic mesenchymal tumor (PMT), and the phosphate levels returned to normal after surgery. The literature review showed only 17 cases of TIOs that occurred in the sphenoid sinus, with an average age of 43.3 ± 13.7 years. Only three cases of TIOs in the sphenoid sinus did not invade the nasal cavity or other paranasal sinuses, which could be identified as isolated sphenoid sinus diseases. We compared the clinical features of sphenoid TIOs with those of non-sphenoid sinonasal TIOs, and it was found that the concentration of 1,25-dihydroxy vitamin D in the group with sphenoid TIOs was much higher than that in the group with non-sphenoid sinonasal TIOs. A total of 153 cases of TIOs in the sinonasal sinus were reviewed. The ethmoid sinus was found to be the major site (64.7%), followed by the nasal cavity (50.3%), maxillary sinus (19.0%), frontal sinus (16.4%), and sphenoid sinus (11.8%). There were 66 patients (43.1%) who showed tumors invading more than one sinus. Most of the tumors (69.3%) were diagnosed as PMTs by pathology, followed by hemangiopericytoma (14.3%). Immunostaining was beneficial in the differential diagnosis of these tumors; however, larger sample sizes are needed for better accuracy. Conclusion TIO in the sinonasal sinus, especially in the sphenoid sinus, is rare. Moreover, isolated sphenoid sinus disease can be easily misdiagnosed. When the clinical manifestation of osteomalacia is atypical, associating it with sphenoid sinus disease is even more difficult. Thus, TIO in the sphenoid sinus needs further exploration.

Aims: To investigate the associations between metabolic score for visceral fat (METS-VF) and clinical outcomes among populations with different glucose tolerance statuses.Methods: We analysed 6827 participants aged & GE; 40 years with different glucose tolerance statuses from a cohort study. The associations between METS-VF and cardiovascular disease (CVD) events and all-cause mortality were assessed using Cox regression, restricted cubic spline and receiver operating characteristic curves. Results: During a follow-up of 5.00 years, there were 338 CVD events and 307 subjects experienced all-cause death. The METS-VF quartile (Quartile 4 versus 1) was significantly related to CVD events [adjusted HRs and 95% CIs: 5.75 (2.67-12.42), 2.80 (1.76-4.48), and 3.31 (1.28-8.54) for subjects with normal glucose tolerance, prediabetes and diabetes, respectively] and all-cause mortality [adjusted HRs and 95% CIs: 2.80 (1.43-5.49), 4.15 (2.45-7.01), and 4.03 (1.72-9.42), respectively]. Restricted cubic spline suggested a dose-response asso-ciation of METS-VF with the risk of CVD events and all-cause mortality. The area under curve for CVD events and all-cause mortality was higher for METS-VF than for the other obesity and IR indexes in subjects with different glucose tolerance statuses. Conclusions: The METS-VF was associated with an increased risk of CVD events and all-cause mortality and could be used as a predictive index of the risk of CVD events and all-cause mortality among populations with different glucose tolerance statuses.

甲状腺激素抵抗综合征(resistance to the thyroid hormone,RTH)又称甲状腺激素不敏感综合征(thyroid hormone insensitivity syndrome,THIS),是由于甲状腺激素受体(thyroid hormone receptor,TR)基因突变,或甲状腺激素(thyroid hormone,TH)细胞膜转运缺陷(thyroid hormone cell membrane transport defect,THCMTD)、TH代谢缺陷(thyroid hormone metabolism defect,THMD)[1]、TR辅助调节因子的异常[2-3],导致垂体和/或外周组织对甲状腺激素的敏感性降低的一种罕见遗传病,患病率大约为1/40000[1],没有性别和种族差异,约85％具有家族遗传性,其中大多呈常染色体显性遗传,极少数呈常染色体隐性遗传,约15％为散发病例.

背景:糖尿病肾病已经成为终末期肾病的主要原因之一,但临床治疗效果仍然有限.近年来研究结果表明,间充质干细胞对糖尿病肾病具有一定的肾脏保护作用.目的:从糖尿病肾病的发病机制与一般治疗策略、间充质干细胞的特征和临床应用,以及间充质干细胞对糖尿病肾病的肾脏保护作用3个方面进行综述,阐述间充质干细胞治疗糖尿病肾病的研究进展.方法:以"mesenchymal stem cells,MSCs,diabetic nephropathy,diabetic kidney disease"为检索词检索PubMed数据库,筛选相关的研究性论文、综述和论著,并根据纳入标准和排除标准整理出62篇文献进行综述.结果 与结论:间充质干细胞在疾病治疗领域的研究已经广泛开展,但间充质干细胞治疗糖尿病肾病的临床试验开展较少,且临床疗效有限.动物实验证实间充质干细胞能够发挥肾脏保护作用并延缓糖尿病肾病进展,具体机制包括减少肾脏细胞凋亡、调节自噬、改善炎症反应、改善氧化应激和抑制纤维化等.

This study evaluated visual perceptual grouping in schizophrenia to test the hypothesis that the disorganization syndrome in schizophrenia is related to a deficit in cognitive coordination. Perceptual grouping was examined with three psychophysically well-controlled tasks in patients with disorganized schizophrenia (n=11), non-disorganized schizophrenia (n=24), psychotic disorders other than schizophrenia (n=31) and non-psychotic psychiatric disorders (n=35). These measures assessed processing of both concurrent and preceding stimulus context. Deficits in perceptual grouping were observed on all three tasks in disorganized schizophrenia patients. Dysfunctional perceptual grouping mechanisms produced both enhanced and impaired task performance suggesting that the pattern of performance observed was the result of a specific deficit in the grouping of stimulus elements. We interpret these data as further support for the hypothesis that the disorganization syndrome in schizophrenia reflects a widespread deficit in the cognitive coordination of contextually related stimuli, leading to dysfunctional grouping of stimulus features in vision, thought and language.

患者,男,26岁,因"发现无精症4月余"遂于2018年10月26日入院.患者婚后一直未育,4个月前就诊于我院泌尿外科确诊为"无精症",遂于我科进一步诊治.既往史:患者出生时,外生殖器发育正常,8岁时出现第二性征发育,身高明显高于同龄人.成年后身高低于同龄人.家族史:家族成员发育正常,无不孕不育相关疾病史.体格检查:身高156 cm,体重67.5 kg,BMI27.74kg/m2,上部量75 cm,下部量81 cm.全身体毛分布正常,全身皮肤黏膜无色素沉着.左右睾丸长径分别为2.6 cm、2.5 cm,阴毛少许,分布于阴茎周围,阴茎长约5 cm,Tanner Ⅲ期.

患者男性，39岁。因"腰痛8个月"入院。8个月前患者出现腰痛，伴乏力、肩颈痛，偶有心悸，无头痛、头昏，无四肢疼痛，至本院门诊就诊，测血钙2.69~2.78 mmol/L(正常值2.15~2.50 mmol/L，下同)，门诊以"高钙血症"收住入院。自起病以来，患者精神、睡眠、饮食欠佳，大小便正常，体力下降、体重下降约5 kg。既往史：否认特殊病史，否认家族遗传病史，其父有高钙血症病史，无任何症状。体格检查：体温36.5℃，脉搏128次/min，呼吸20次/min，血压120/92 mmHg(1 mmHg＝0.133 kPa)，神志清楚，精神可，无关节畸形等，查体未见明显特殊。

甲状腺功能减退(简称甲减)能导致神经肌肉功能异常,即甲减肌病( HM) ,以"肌无力"为主诉的患者应筛查甲状腺功能.HM的发病率报道不一,为20％ ～80％.本文通过回顾性分析本院近15年的20例HM患者的临床资料,总结该病的临床特点,以期为临床诊疗提供指导,避免漏诊和误诊. 对象与方法 1.对象:2003年1 月～2018年8月于我院确诊的HM患者20例.HM诊断标准:甲减诊断明确,伴近端肌无力和(或)肌痛、肌酶升高,甲状腺素替代治疗有效.排除多发性肌炎、重症肌无力、其他内分泌肌病、感染性肌病或药物性肌病患者[1].

多发性内分泌腺瘤1型(multiple endocrine neoplasia typel,MEN1)为常染色体显性遗传性疾病,其典型特点是同时存在两种或两种以上内分泌腺体异常:最常见表现为甲状旁腺腺瘤、胰岛细胞瘤和(或)垂体肿瘤,部分不典型者可合并其他内分泌腺和非内分泌组织肿瘤.本文通过对多发性内分泌腺瘤1型、异位ACTH综合征(胸腺类癌)患者的诊治报道,以期提高临床医师对本病的认识,减少误诊漏诊,及时采取合理的检查明确诊断并提供及时的治疗方案,避免延误病情.

Background/Objective Because galectin-3 has been proposed to regulate obesity and insulin resistance in mice, we hypothesized that circulating galectin-3 levels are associated with presence of gestational diabetes mellitus (GDM), progesterone, and insulin resistance. Methods Circulating galectin-3 levels were measured using an enzyme-linked immunosorbent assay (ELISA) in women with GDM (n = 137) and their controls (n = 81). Associations of galectin-3 and progesterone with GDM and insulin resistance were evaluated using regression models. Results Circulating galectin-3 levels were increased in the individuals with GDM (P < .001) and associated significantly with progesterone (r = 0.42,P < .001), gestational age at sampling (r = 0.23,P < .001), current body mass index (BMI; r = 0.17,P= .02), estrogen (r = 0.15,P < .03), fasting glucose (r = 0.41,P < .001), fasting insulin (r = 0.39,P < .001), and homeostasis model assessment of insulin resistance (HOMA-IR; r = 0.44,P < .001). After adjustment for potential confounders, including current BMI, subjects in the highest tertile of galectin-3 levels were more likely to have GDM (odds ratio 4.71, 95% confidence interval 2.01-11.06) as compared with the lowest tertile. The association between circulating galectin-3 levels and GDM remained significant after adjusting for progesterone, but significantly attenuated after adjustment with HOMA-IR. Furthermore, the multiple linear regression analyses after adjustment for confounders showed an independent association between galectin-3 levels and HOMA-IR (beta = .41,P < .001), suggesting that association of circulating gelactin-3 levels with GDM might be mediated via insulin resistance. Progesterone demonstrated the expected associations with galectin-3, GDM, and HOMA-IR. Conclusions Circulating galectin-3 levels are associated with GDM possibly through increased insulin resistance. The association of galectin-3 with progesterone highlights a potential role of progesterone in its interaction with galectin-3.

Primary thyroid lymphoma (PTL) is an exceptionally rare and highly aggressive potentially curable malignant disease. We report three typical cases of PTL referred to our hospital. All three cases had long history of Hashimoto’s thyroiditis, and presented with progressively enlarging neck mass. The first two cases were confirmed by surgical biopsy to be diffuse large B cell lymphoma, and received radiotherapy combined with chemotherapy, or received only chemotherapy. The third case was confirmed by core needle biopsy to be mucosa-associated lymphoid tissue lymphoma, and received radiotherapy. In summary, confirmation of PTL diagnosis is essential for further clinical decisions. Core biopsy should be one of the most important methods to make the diagnosis of PTL, while the use of fine needle aspiration cytology alone is still limited in diagnosing PTL.

Background: ANGPTL8, an important regulator of glucose and lipid metabolism, is increased in diabetes and associated with insulin resistance. However, the role of ANGPTL8 in diabetes outcomes remains unclear. The study aimed to investigate circulating levels of ANGPTL8 in participants with and without diabetes and its potential association with death and cardiovascular and renal outcomes in a 5-year cohort study.Methods: Propensity-matched cohorts of subjects with and without diabetes from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A longitudinal (REACTION) study was generated on the basis of age, sex and body mass index at baseline. The primary outcome was death from any cause. The secondary outcome was a composite of new-onset major adverse cardiovascular events, hospitalization for heart failure and renal dysfunction (eGFR < 60/min/1.73 m2).Results: We identified 769 matched pairs of patients from the diabetes group and the control group. Serum ANGPTL8 levels were elevated in patients with diabetes compared to subjects in the control group (618.82 318.08 vs. 581.20 299.54, p = 0.03). Furthermore, increasing quartiles of ANGPTL8 were associated with increased all-cause mortality in both the control and diabetes groups (all p values < 0.05). Binary logistic regression analysis showed that elevated ANGPTL8 levels were associated with greater risk ratios (RRs) of death (RR in quartile 4 vs quartile 1, 3.47; 95% CI 1.30 – 9.29) and renal dysfunction (RR in quartile 4 vs quartile 1, 10.50; 95% CI 1.32 – 83.60) only in diabetic patients. Multivariable-adjusted restricted cubic spline analyses suggested a significant linear relationship between ANGPTL8 and all-cause mortality in diabetic patients (p for nonlinear trend = 0.99, p for linear trend = 0.01) but not in the controls (p for nonlinear trend = 0.26, p for linear trend = 0.80). According to the ROC curves, the QMortality and QFrailty scores, combined with ANGPTL8, showed better performance in predicting death, especially in diabetic patients.Conclusion: Serum ANGPTL8 levels were associated with an increased risk for all-cause mortality and renal dysfunction in subjects with diabetes. Furthermore, ANGPTL8 had good performance in predicting all-cause mortality in diabetic patients, which may contribute to the early detection of individuals with diabetes at high risk.