Pituitary stalk interruption syndrome (PSIS) is a rare hypothalamic-pituitary disorder causing progressive anterior pituitary deficiency. Subtle early symptoms and unreliable sex hormone levels in prepubertal patients complicate diagnosis of anterior pituitary deficiency. This study aimed to investigate the association between serum prolactin (PRL) levels and anterior pituitary deficiency in PSIS patients, as well as its potential as a biomarker for complete anterior pituitary deficiency (CAPD). This retrospective study analyzed 155 patients with PSIS diagnosed and treated at the Chinese People’s Liberation Army General Hospital. We assessed the association between PRL levels and the severity of pituitary function deficits as well as testicular volume, and further evaluated its diagnostic value for CAPD. Among 155 patients with pituitary stalk interruption syndrome (89.03

This study aims to investigate the clinical characteristics of programmed cell death protein-1 (PD-1) or programmed cell death ligand-1 (PD-L1) inhibitors-induced pituitary injury (pituitary-irAE) by comparing with other pituitary diseases. We retrospectively reviewed clinical records of patients who were admitted for pituitary-irAE, idiopathic isolated ACTH deficiency (IIAD), and lymphocytic hypophysitis (LYH) from January 2015 to June 2024. Among 3689 patients treated with PD-1/PD-L1 inhibitors, 0.596% patients developed pituitary-irAE. The mean age of onset was 59.41 ± 10.69 years, with 13 patients (59.09%) being male. The median duration from symptom onset to confirmed diagnosis was 5.50 (2.00, 9.25) months. The clinical symptoms were similar between pituitary-irAE and IIAD, which mainly manifested as fatigue and appetite loss. Polydipsia/polyuria and amenorrhea/menstrual disorders were mainly found in patients with LYH. Central adrenal insufficiency was observed in all patients with pituitary-irAE, with cortisol concentrations typically falling below the detectable limit. Pituitary MRI appeared normal in 52.63% patients with pituitary-irAE. Furthermore, some patients with pituitary-irAE exhibited partial or complete functional recovery of the pituitary gland after hormone replacement therapy. The clinical manifestations observed in patients with pituitary-irAE are analogous to those seen in individuals with IIAD, yet they differ from the presentations of LYH.

Pituitary stalk interruption syndrome (PSIS) is an infrequently occurring congenital condition, and there exists a dearth of systematic investigative work focusing on the clinical features and long-term outcomes in adult patients. Individuals who have reached adulthood with PSIS are at an increased risk of developing metabolic disorders, including metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction associated fatty liver disease (MAFLD), which are also one of the main factors for the poor prognosis of these patients. An analysis was conducted on the clinical data of adult PSIS patients who visited the endocrinology department of the First Medical Center of the People’s Liberation Army General Hospital from January 2005 to August 2023. Patients were grouped based on their MAFLD and MS status, and the differences in clinical characteristics and risk factors between the groups were analyzed. Machine learning models were used to construct a prediction model for the occurrence of MAFLD in adult PSIS patients and to analyze high-risk predictors. Out of 136 PSIS adult patients, 93.3% were male. The prevalence of MAFLD was 55.5%, and MS was 22.3%. Patients with a history of growth hormone (GH) treatment were less likely to develop MAFLD (P = 0.032). MAFLD patients exhibited higher rates of hypertension, hyperuricemia, obesity, MS, and dyslipidemia. Multiple risk factors may contribute to MS, while no significant link was found between MS and hormone replacement. However, GH non-treatment may serve as the notable predictor of MAFLD in PSIS patients revealed by the Ridge regression model of machine learning model with the highest predictive performance of a mean area under the curve (AUC) of 0.82. The prevalence of MS and MAFLD is high among adult patients with PSIS. Multiple risk factors may contribute to these two diseases, and after constructing a predictive model, we found that MAFLD may be closely linked to the previous lack of GH treatment.

The 3D human pituitary organoid represents a promising laboratory model for investigating human pituitary diseases. Nonetheless, this technology is still in its nascent stage, with uncertainties regarding the cellular composition, intercellular interactions, and spatial distribution of the human pituitary organoids. To address these gaps, the culture conditions are systematically adjusted and the efficiency of induced pluripotent stem cells' (iPSCs') differentiation into pituitary organoids is successfully improved, achieving results comparable to or exceeding those of previous studies. Additionally, single-cell RNA-sequencing (scRNA-seq) and stereomics sequencing (Stereo-seq) are performed on the pituitary organoids for the first time, and unveil the diverse cell clusters, intricate intercellular interactions, and spatial information within the organoids. Furthermore, the SOX3 gene interference impedes the iPSCs' differentiation into pituitary organoids, thereby highlighting the potential of pituitary organoids as an ideal experimental model. Altogether, the research provides an optimized protocol for the human pituitary organoid culture and a valuable transcriptomic dataset for future explorations, laying the foundation for subsequent research in the field of pituitary organoids or pituitary diseases.

BackgroundPituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations across multiple systems. These include lifelong infertility, short stature, mental retardation, and potentially life-threatening pituitary crises if not promptly diagnosed and treated. Despite extensive research, the precise pathogenesis of PSIS remains unclear. Currently, there are two proposed theories regarding the pathogenic mechanisms: the genetic defect theory and the perinatal injury theory.MethodsWe systematically searched English databases (PubMed, Web of Science, Embase) and Chinese databases (CNKI, WanFang Med Online, Sinomed) up to February 24, 2023, to summarize studies on gene sequencing in PSIS patients. Enrichment analyses of reported mutated genes were subsequently performed using the Metascape platform.ResultsOur study included 37 articles. KEGG enrichment analysis revealed mutated genes were enriched in the Notch signaling pathway, Wnt signaling pathway, and Hedgehog signaling pathway. GO enrichment analysis demonstrated mutated genes were enriched in biological processes such as embryonic development, brain development, axon development and guidance, and development of other organs.ConclusionBased on our summary and analyses, we propose a new hypothesis: disruptions in normal embryonic development, partially stemming from the genetic background and/or specific gene mutations in individuals, may increase the likelihood of abnormal fetal deliveries, where different degrees of traction during delivery may lead to different levels of pituitary stalk interruption and posterior lobe ectopia. The clinical diversity observed in PSIS patients may result from a combination of genetic background, specific mutations, and variable degrees of traction during delivery.

The clinical data, laboratory test, and gene mutations were collected from a family with Liddle syndrome. Literatures on Liddle syndrome published in domestic and abroad since 1994 were reviewed and the types of gene mutations were summarized. The proband was diagnosed with hypertension at the age of 24. Laboratory test showed that serum potassium was 3.65 mmol/L, plasma renin was <0.5 mU/L, and plasma aldosterone was 1.5 ng/dL. Proband′s father was diagnosed with hypertension at the age of 34 with the serum potassium 3.34 mmol/L, plasma renin 3.72 mU/L, and plasma aldosterone 6.04 ng/dL. A nonsense mutation(1724G>A, p.Trp575*) in exon 13 of SCNN1G gene was detected in the proband and his father. In 288 cases from 107 families reported in the review of domestic and foreign literature, the incidence of hypertension, hypokalemia, and low renin/low aldosterone were 95.1%, 55.2%, and 49.6%, respectively. This case suggests that the clinical phenotype of Liddle syndrome is heterogeneous. Patients with early-onset hypertension, regardless of whether they are accompanied by hypokalemia, should be screened for renin-angiotensin-aldosterone and genetic testing related to Liddle syndrome should be further detected in patients with low plasma renin/aldosterone.

目的:探讨微小核糖核酸-122(MicroRNA-122,miR-122)、胰岛素抵抗指数(Insulin Resistance of Homeostasis Model Assessment,HOMA-IR)水平的表达与妊娠期糖尿病(Gestational Diabetes Mellitus,GDM)及妊娠结局的关系.方法:选取孕 24～32 周GDM孕妇 52 例作为观察组,口服葡萄糖耐量试验(Oral Glucose Tolerance Test,OGTT)正常的孕 24～32 周孕妇 45 例作为对照组,比较两组糖代谢指标、HOMA-IR水平及血清和胎盘中miR-122 水平;根据GDM患者妊娠结局(若出现流产、早产、巨大儿、死胎、死产、胎儿畸形、新生儿呼吸窘迫综合征及新生儿死亡等任一情况均归为不良结局组),将 52 例GDM患者分为结局良好组 34 例和不良结局组 18 例,比较两组上述指标;分析miR-122 水平与HOMA-IR的相关性.结果:两组年龄、分娩孕周、孕次、产次、孕前等一般资料比较,差异无统计学意义(P＞0.05);观察组空腹血糖、胰岛素水平、HOMA-IR及血清和胎盘miR-122 水平均高于对照组(P＜0.05).不良结局组HOMA-IR及血清和胎盘miR-122 表达水平均高于结局良好组(P＜0.05).经Pearson相关分析结果显示,GDM患者血清及胎盘 miR-122 水平均与 HOMA-IR 呈正相关(P＜0.05).结论:GDM 患者伴有明显的胰岛素抵抗,miR-122 在GDM患者体内呈高水平表达,且其高水平表达与胰岛素抵抗有关,并可影响妊娠结局,这可能是GMD临床诊断和治疗GMD的潜在靶点.

Objective:To summarize the clinical characteristics, reveal evolutionary patterns, and enhance the understanding of idiopathic isolated adrenocorticotripin(ACTH)deficiency(IIAD)by conducting a clinical analysis and follow-up.Methods:The clinical data of 12 patients with IIAD in our center were analyzed retrospectively, and the patients were further followed up to summarize the clinical characteristics of these patients.Results:Among 12 patients with IIAD, the ratio of male to female was 3∶1. The onset showed a bimodal trend, with 2 cases occurring below the age of 18(at 1 year and 11 years respectively), and 10 cases occurring in adults, with an average onset age of 59.4 years old. In adults, the main symptoms were chronic fatigue, anorexia, and weight loss, while pediatric patients exhibited hypoglycemia and seizures. Hyponatremia(50%)was a common biochemical abnormality. ACTH, cortisol, and 24 h urinary free cortisol were significantly lower in all patients, and the functions of other pituitary gland axes were normal. All patients were normal except 2 patients with pituitary MRI showing vacuolar sella turcica. The most common accompanying disease was Hashimoto thyroiditis. After glucocorticoid replacement therapy, all patients showed symptom improvement. The replacement doses include prednisone acetate at 2.5-7.5 mg/d or hydrocortisone at 12-20 mg/d. All the 8 patients were still alive with ongoing ACTH deficiency, without any decline in other pituitary axis functions or occurrence of other diseases.Conclusion:IIAD exhibits a bimodal onset pattern with a higher prevalence in males. Symptoms persist in a chronic and stable manner without remission. Prognosis is favorable with physiological dose of glucocorticoid replacement therapy.

目的 分析二氧化碳足浴在糖尿病下肢血管病变(DLEAD)辅助治疗中的应用效果.方法 80例DLEAD患者(均为2型糖尿病下肢血管病变)随机分为观察组和对照组各40例,两组均采用常规治疗(降糖、降压、调脂、抗血小板聚集等),观察组在此基础上给予二氧化碳足浴治疗,对照组则给予纯水足浴治疗,每次浸泡时间30 min,每周5次,共4周.比较两组疗效及治疗前后ABI、TBI、TcPO2、皮肤血流灌注量、足背动脉血管内径、足背动脉血流量和不良反应.结果 观察组终止研究3例,对照组终止研究3例.观察组显效18例、有效16例、无效3例、总有效率91.89％,对照组分别为12、12、13例和64.86％,两组总有效率比较,P<0.05.与同组治疗前比较,观察组左右侧ABI、TBI、TcPO2、皮肤血流灌注量及对照组左右侧TcPO2、皮肤血流灌注量增加(P均<0.05);与对照组比较,观察组治疗后左右侧ABI、TBI、TcPO2、皮肤血流灌注量增加(P均<0.05).与同组治疗前及对照组比较,观察组治疗后左右侧足背动脉血管内径、足背动脉血流量增加(P均<0.05).两组患者治疗过程中均未出现严重的不良反应,仅对照组有1例患者出现踝部皮肤变红现象,休息1 d后好转.结论 二氧化碳足浴在DLEAD辅助治疗中的应用效果较好,可以提高患者ABI、TBI,增加下肢血流量,改善微循环障碍,缓解缺血缺氧症状,并且安全性高.

目的:研究营养治疗在老年2型糖尿病患者中的作用.方法:选取2017年7月-2018年7月我院收活的老年2型糖尿病患者102例作为研究对象,随机将其分为观察组和对照组,两组均为51例.对对照组实施常规治疗方式,观察组进行营养治疗;比较两组治疗前后临床相关指标.结果:治疗前,两组血清甘油三酯(TG)、糖化血红蛋白(HbAlc)、餐后2h血糖(2h-PG)、空腹血糖(FPG)无显著差异,治疗后,观察组上述指标均优于对照组(P＜0.05).结论:营养治疗在老年2型糖尿病患者中具有显著疗效.

目的 探讨服用达格列净对T2DM合并慢性心力衰竭(CHF)患者左心室舒张功能的影响.方法 选取2017年9月至2019年5月于我院内分泌科就诊、应用达格列净治疗、合并CHF的T2DM患者55例.收集患者基线及治疗6个月时的临床资料,比较治疗前后左心室舒张早期二尖瓣血流峰值速度(E)、二尖瓣环舒张早期运动峰值速度(e')、E/e'、左心房容积指数(LAVI)、左心室质量指数(LVMI)等变化.结果 符合入组条件并完成试验的患者共41例.达格列净治疗6个月后e'升高[(5.86 ± 1.26)vs(6.47 ± 1.45)cm/s,P＜0.05],E/e'、LAVI 、LVMI 降低[(11.39 ± 2.91)vs(10.38±2.16),(30.78±4.19)vs(29.00±4.57)ml/m2,(80.39±18.89)vs(76.75±19.22)g/m2,P＜0.05].结论 达格列净可改善T2DM合并CHF患者左心室舒张功能.

目的 观察贝前列素钠联合前列地尔对老年早期糖尿病肾病(DN)患者NOD样受体蛋白3(NLRP3)炎症小体表达的影响.方法 将老年DN患者142例按随机数字表法分为试验组71例及对照组71例.2组均接受降糖、优质低蛋白饮食和对症治疗.对照组给予前列地尔,每天10μg,静脉滴注,试验组前2周给予前列地尔,后2周给予贝前列素钠,每次40μg,每天3次,口服.2组均治疗4周.治疗前后,比较2组肾功能指标、氧化应激指标、NLRP3、凋亡相关斑点样蛋白(ASC)、胱天蛋白酶-1(Caspase-1)、白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18),并记录2组治疗期间药物不良反应发生情况.结果 治疗后,试验组和对照组NLRP3 mRNA分别为18.01±0.91,22.37±1.06,ASC mRNA分别为19.98±0.85,23.59±1.02,Caspase-1 mRNA分别为20.42±0.95,23.91±1.04,NLRP3蛋白分别为0.28±0.03,0.39±0.06,ASC蛋白分别为0.32±0.04,0.48±0.07,Caspase-1蛋白分别为0.30±0.05,0.41±0.08,差异均有统计学意义(均P<0.01).试验组和对照组的IL-18分别为(16.50±1.97)和(21.71±2.45)pg·mL-1,IL-1β分别为(7.59±2.33),和(12.37±3.24)pg·mL-1,超氧化物歧化酶(SOD)分别为(55.48±9.78),(46.20±7.36)U·mg-1,谷胱甘肽过氧化物酶(GSH-Px)分别为(169.29±18.40),(140.59±13.62)kU·L-1,丙二醛(MDA)分别为(6.90±1.40),(9.96±2.28)mmol·mg-1,尿蛋白排泄率(UAER)分别为(64.40±7.40),(91.59±9.48)mmol·L-1,血肌酸酐(Scr)分别为(91.90±8.09),(120.47±10.60)μmol·L-1,尿足细胞标志蛋白(PCX)分别为(1.47±0.28),(2.62±0.39)mg·mL-1,亮氨酸氨基肽酶(LAP)分别为(8.41±1.69),(11.61±2.48)mg·mL-1,差异均有统计学意义(均P<0.05).试验组和对照组的药物不良反应发生率分别为4.63％(4例/71例),11.27％(8例/71例),差异无统计学意义(P>0.05).结论 贝前列素钠联合前列地尔能够有效降低老年DN患者降低尿蛋白,改善肾功能,疗效显著,其机制与改善机体氧化应激状态、抑制NALP3炎症信号通路的活化及其介导的炎症反应密切相关.

目的 :了解OSAHS与甲状腺结节之间的相关性.方法 :选取成年患者184例,其中非OSAHS患者54例,OSAHS患者130例,收集多导睡眠图、甲状腺超声等资料.应用t检验、Logistic分析等方法分析两种疾病相关关系.结果:OSAHS组有较高的甲状腺结节发病率(P<0.05).年龄、BMI均为OSAHS合并甲状腺结节发生的影响因素.结论 :甲状腺结节为 OSAHS 发病的独立危险因素.

The present study aimed to investigate the association between insulin resistance (IR), nitric oxide (NO) production and myocardial apoptosis in a background of coexisting hypertension in a rodent animal model. A hypertensive rat model was established by feeding Wistar and spontaneously hypertensive rats (SHR) with a high sucrose/fat (HSF) diet for 12 weeks, in conjunction with isosorbide mononitrate (ISMN). Increased IR, NO content, apoptotic gene and protein expression, and morphological alterations within rat myocardium were evaluated. Following a total of 12 weeks of feeding with HSF and ISMN resulted in increased IR and NO content within the myocardial tissue of Wistar and SHR rats. HSF and ISMN activated myocardial apoptosis by downregulating the gene transcription and protein expression levels of the anti‑apoptotic B‑cell lymphoma 2 (Bcl‑2), and increasing the pro‑apoptotic Bcl‑2 associated X protein. Apoptosis was demonstrated by DNA fragmentation in terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labelling assay. In all experiments, the combination of HSF and ISMN was associated with more pronounced effects, indicating the possible synergistic effects. In addition, the correlation analysis in the Wistar rats fed with HSF only, revealed a positive association between NO production and IR. The results of the present study indicated that HSF and ISMN simultaneously increased IR, NO production and myocardial apoptosis in the hypertensive rat model, and may therefore contribute to investigations into the long‑term clinical use of ISMN in hypertensive patients.

目的 探讨二甲双胍对T2DM大鼠外周血及脂肪组织胎球蛋白A(FetA)的影响.方法 40只SD大鼠分为普食组(NC组)、T2DM组、二甲双胍治疗组(MET组)及胰岛素治疗组(INS组),每组各10只.高脂高糖饮食联合小剂量STZ建立T2DM大鼠模型,M ET组予二甲双胍灌胃,INS组皮下注射胰岛素使其血糖与MET组基本保持一致.16周龄时ELISA检测血清FetA浓度,Western blot法检测脂肪单磷酸腺苷激活蛋白激酶(AMPK)、核转录因子(NF-κB)及FetA的表达,RT-qPCR法检测脂肪NF-κB及FetA mRNA的表达.结果 T2DM组血清FetA较NC组升高[(11.26±1.76)vs(23.99±4.64)ng/ml,P<0.05],脂肪AMPK表达降低[(0.68±0.17)vs(0.11±0.03),P<0.05],NF-κB及其mRNA表达升高[(0.53±0.07)vs(0.86±0.14),(1.00±0.10)vs(2.42±0.47),P<0.05],FetA及其mRNA表达增多[(0.40±0.07)vs(0.66±0.11),(1.07±0.09)vs(1.98±0.27),P<0.05].与T2DM组比较,MET组血清FetA降低[(23.99±4.64)vs(17.37±3.25)ng/ml,P<0.05],脂肪AMPK表达升高[(0.11±0.03)vs(0.49±0.80),P<0.05],NF-κB及其mRNA表达减少[(0.86±0.14)vs(0.61±0.09),(2.42±0.47)vs(1.51±0.37),P<0.05],FetA及其mRNA表达降低[(0.66±0.11)vs(0.47±0.06),(1.98±0.27)vs(1.25±0.16),P<0.05].与T2DM组比较,INS组各指标变化差异无统计学意义(P>0.05).结论 二甲双胍降低T2DM大鼠外周血FetA的浓度,可能通过AMPK-NF-κB抑制脂肪组织FetA来表达.

Objective To evaluate the efficacy and safety of Shaofu Zhuyu Decoction in treatment of primarydysmenorrhea (PD) with cold-coagulation blood-stasis.Methods The related literatures till July,2015 in PubMed,Embase,Cochrane Librar,CNKI,CBM,Wanfang Database,and VIP Database were searched.The randomized controlled trials involving Shaofu Zhuyu Decoction for the treatment of PD were collected.According to Cochrane system evaluation method,study quality was evaluated and extracted the available information,and then performed Meta-analysis by Revman 5.2 software.Results Finally into 17 documents,involving 1591 patients,Meta-analysis showed that symptoms and signs of Shaofu Zhuyu Decoction improving PD with cold-coagulation blood-stasis were better than Ibuprofen Sustained Release Capsules,Yueyueshu Granules,Indometacin Tablets,and Indocin in the total efficiency.The long term efficacy and safety of Shaofu Zhuyu Decoction cannot be evaluated.Indomethacin subgroup had no statistical significance.Conclusions Effect of Shaofu Zhuyu Decoction is better than Ibuprofen Sustained Release Capsules,Yueyueshu Granules,Indometacin Tablets,and Indocin.Due to the quality of the included studies are not high and have a bias of risk.In the future,additional and high-quality studies on patients across the world might be required to validate the findings.