Phenotype and genotype of patients with multiple endocrine neoplasia type 1 studied in Argentina / Fenotipo y genotipo de pacientes con neoplasia endocrina múltiple tipo 1 estudiados en Argentina

Abstract Introduction: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with an estimated prevalence of 2-10:100 000. The main locations of tumors are parathyroid glands (HPT), gas troenteropancreatic tract (GEPT), and anterior pituitary gland (PT). The aim of our investigation was to describe the phe notype and genotype of Argentinian patients with MEN1. Methods: A total of 68 index patients diagnosed with at least two of the three main tumors or one tumor and a relative with MEN1, and 84 first-degree relatives were studied. We sequenced the coding region (exons 2-10); the promoter, exon 1; and the flanking intronic regions of the MEN1 gene, following the Sanger method. We used MLPA in index patients without mutation. Results: Prevalence of tumors: HPT 87.5%, GEPT 49% (p< 0.001). No statistical differences in the prevalence of HPT vs. PT (68%). Prevalence of pathogenic variants: 90% in familial cases and 51% in sporadic cases. Of the different 36 pathogenic variants, 13 (36.2%) were frameshift micro-rearrangement, 8 (22.2%) were mis sense, 9 (25%) were nonsense, 3 (8.3%) were mutations in splicing sites, 2 (5.5%) were large deletions and, 1 in-frame micro-rearrangement. We found 7 novel pathogenic variants. Thirty-nine percent (n = 33) of first-degree relatives of 23 families were found to be mutation carriers. Conclusion: The phenotype and genotype of Argen tinian patients was similar to other MEN1 populations. A high frequency of PT and the identification of seven novel mutations are underscored.

Resumen Introducción: La neoplasia endocrina múltiple tipo 1 (NEM1) es una enfermedad hereditaria autosómica dominante con una prevalencia estimada de 2-10:100 000. Las localizaciones principales de los tumores son glándulas paratiroides (HPT), tracto gastroenteropan creático (TGEP) y glándula pituitaria (TP). El objetivo de nuestra investigación fue describir el fenotipo y genotipo de pacientes argentinos con NEM1. Métodos: Estudiamos 68 casos índices diagnostica dos por presentar al menos dos de los tres tumores principales, o un tumor y un pariente con NEM1, y 84 familiares de primer grado. Secuenciamos la región codificante (exones 2-10); el promotor, exón 1; y las re giones intrónicas flanqueantes del gen MEN1 siguiendo el método de Sanger. Utilizamos MLPA en pacientes índice sin mutación. Resultados: Prevalencia de tumores: HPT 87.5%, TGEP 49% (p < 0.001), sin diferencias estadísticas entre las prevalencias de HPT vs TP (68%). Prevalencia de variantes patogénicas: 90% en casos familiares y 51% en esporádi cos. Hallamos 36 variantes patogénicas, 7 (20%) fueron noveles. Fueron 13 (36.2%) microarreglos con cambio en el marco de lectura, 9 (25%) variantes sin sentido, 8 (22.2%) con cambio de sentido, 3 (8.3%) en sitio de unión de empalme, 2 (5.5%) grandes deleciones y 1 microarre glo sin cambio en el marco de lectura. El 39 % (n = 33) de los parientes de primer grado en 23 familias fueron portadores de mutaciones. Conclusión: El fenotipo y genotipo de los pacientes argentinos con NEM1 fue similar al de otras poblaciones. Destacamos una alta frecuencia de TP y de variaciones patogénicas noveles.

Metástasis hipofisarias: un desafío diagnóstico y terapéutico / Pituitary metastases: a diagnostic and therapeutic chal lenge

Resumen Introducción : La región selar es un sitio infrecuente de metástasis, encontrándose en el 1% de las cirugías hipofisarias. Los tumores primarios más habituales son mama y pulmón. En general son diagnosticadas en pa cientes con enfermedad avanzada, aunque pueden ser el debut de la enfermedad oncológica. Métodos : Análisis retrospectivo de las características clínicas, bioquímicas, radiológicas de pacientes con me tástasis selares o hipofisarias (MS) durante el periodo 2009-2020. Resultados : Se reportaron 18 casos de pacientes, 11 de ellos con confirmación histológica. La mediana de edad fue 53 años (rango: 35-75), 53% hombres. La loca lización del tumor primario fue: 8 pulmón, 6 mama, 1 carcinoma folicular de tiroides, 1 linfoma Hodgkin y 2 carcinomas renales de células claras. La media de tiem po entre el diagnóstico del tumor primario y la aparición de la MS -en los casos de presentación metacrónica- fue 108 meses (rango: 11-180). En 8 pacientes (44.4%), el diagnóstico de la neoplasia primaria se hizo a partir del hallazgo de la masa selar. Diabetes insípida, hipopitui tarismo, trastornos visuales, oftalmoplejía y cefalea se presentaron en el 78, 77, 61, 39 y 39%, respectivamente. Quince pacientes presentaron masas con extensión su pra/paraselar; y 3 lesión limitada a la hipófisis y tallo. Fueron operados 11/18 por vía transesfenoidal, para diagnóstico y/o descompresión. Fallecieron 17, con una mediana de sobrevida de 6 meses (1- 36). Discusión : La sospecha de MS debe estar presente ante una masa selar y supraselar con captación difusa del gadolinio, diabetes insípida, hipopituitarismo y/o disfunción visual, aun en pacientes sin antecedentes oncológicos.

Abstract Introduction : Sellar metastases (SM) are rare mani festations of malignancy. Breast and lung cancer are the most common primary tumors. Most cases are di agnosed in patients with advanced malignant disease; however, symptoms of pituitary involvement can pre cede the diagnosis of the primary tumor. Methods : Retrospective analysis of symptoms at presentation, hormonal, radiological and histological findings, management, and outcome of patients with SM from 2009 to 2020. Results : Eighteen patients´cases were included, 11 with histological confirmation. Median (m) age was 53 years (range 35-75), 53% male. Primary malignant tu mors: 8 lungs, 6 breast, 1 follicular thyroid carcinoma, 1 Hodgkin lymphoma, and 2 clear cell renal carcinomas. The m time between the diagnosis of the primary neo plasm and the occurrence of the SM was 108 months (range: 11-180). In 8 patients the diagnosis of the primary neoplasm was made after the finding of the symptom atic sellar mass. Insipidus diabetes, adenohypophysis deficit, visual disorders, headache, and cranial nerve deficits were evident in 78, 77, 61, 39 and 39% of the cases, respectively. Fifteen patients harbored supra / parasellar masses, in three a lesion was limited to the pituitary gland, and stalk. Eleven out of 18 (61.1%) of the patients were operated on by the trans-sphenoidal approach, for diagnostic and / or decompressive pur poses. Eighteen died, with a median survival time of 6 months (1-36). Discussion : In the presence of a pituitary lesion with diffuse gadolinium uptake, associated with insipidus diabetes and / or visual disorder SM should be suspected even in patients without a history of oncological disease.

Pubertad precoz en niñas en un hospital de referencia

Introducción: La pubertad precoz se define como la aparición progresiva de signos puberales a una edad por debajo de 2,5 desviaciones estándar (DE) de la media para una población determinada. Se carece a nivel nacional de estudios epidemiológicos sobre esta afección. Objetivo: Determinar las características de la pubertad precoz para evaluar la edad de inicio de las características sexuales secundarias en una población de niñas menores de 8 años. Materiales y Métodos: El presente estudio es de tipo observacional, descriptivo, retrospectivo, de corte transversal. La población incluyó niñas menores de 8 años, que consultaron en un hospital de referencia, durante el periodo de enero de 2017 a diciembre de 2021. Como variables se analizó la edad al inicio de los síntomas, edad a la consulta, escolaridad, procedencia, motivo de consulta, signos y síntomas, cambios en edad ósea, respuesta positiva a la prueba con GnRH y asociación etiológica con cambios hallados en la RMN cerebral y ecografía pélvica; así como el abordaje terapéutico. Resultados: Ingresaron al estudio 48 pacientes de sexo femenino, menores de 8 años de edad. El inicio de los síntomas se presentó en promedio a los 5,4 +/- 2,27 años, siendo la edad de 6-7 años el 31,3% del total de pacientes. El diagnóstico predominante fue el de una pubertad precoz central y de las pruebas de estímulo con GnRH, el 68,8% resultaron positivas. Conclusión: La edad promedio de inicio del desarrollo puberal en este grupo de niñas fue 5 años, adelantado en relación a la literatura clásica, con etiología no conocida en la mayoría de los casos.

Introduction: Precocious puberty is defined as the progressive appearance of pubertal signs at an age below 2.5 standard deviations (SD) from the mean for a given population. There is a lack of epidemiological studies on this condition in our country. Objective: To determine the characteristics of precocious puberty and to evaluate the age of onset of secondary sexual characteristics in a population of girls under 8 years of age. Materials and Methods: This was an observational, descriptive, retrospective and cross-sectional study. Population: girls under 8 years of age, who consulted at a referral hospital from January 2017 to December 2021. The variables analyzed were age at the onset of symptoms, age at consultation, education, place of residence, reason for consultation, signs and symptoms, changes in bone age, positive response to the GnRH test and etiological association with changes found in brain MRI and pelvic ultrasound, as well as the therapeutic approach. Results: 48 female patients under 8 years of age entered the study. The onset of symptoms occurred on average at 5.4 +/- 2.27 years, in 31.3% of all patients at the age of 6-7 years. Predominant diagnosis was central precocious puberty and 68.8% of GnRH stimulus tests were positive. Conclusion: The average age of onset of pubertal development in this group of girls was 5 years, earlier than described in the literature, with unknown etiology in most cases.

Decoding pituitary tumors: a systematic analysis of diagnostic methods and treatment modalities

Pituitary tumors are growths that form in the gland these tumors are rare representing 10-15% of all brain tumors. They can disrupt the production of hormones, in the body leading to symptoms related to hormone imbalance. This review offers an overview of the methods used for diagnosing and treating tumors. It is worth noting that relying solely on references may restrict the scope and depth of discussions about tumors in this paper. Suggestions for research include exploring diagnostic tools like molecular imaging and liquid biopsy to enhance early detection and accurate assessment of these tumors. Additionally, more research is required to understand the long-term effects and quality of life outcomes for patients undergoing treatment options for tumors. In conclusion, significant progress has been made in diagnosing and treating tumors over time. Advances in imaging technologies such as diffusion-weighted imaging and magnetic resonance spectroscopy have enhanced precision and treatment strategies for these tumors. The discussion also covers the roles of surgery, radiation therapy and medical interventions, in managing tumor growth and hormonal imbalances further advancements, in research and innovation are crucial, for enhancing our knowledge and treatment of tumors ultimately bringing outcomes for both patients and healthcare professionals.

Hipertensión arterial secundaria a enfermedad de Cushing. Reporte de Caso / Hypertension secondary to Cushing´s Disease. Report of a clinical case

INTRODUCCIÓN: La Enfermedad de Cushing es una de las causas menos prevalentes de hipertensión arterial secundaria (HTA) (0,7 a 2,4 casos por millón de personas), sin embargo conlleva un aumento de la morbi-mortalidad que se relaciona con el tiempo de exposición al exceso de corticoides 6, lo cual representa un problema debido a que la inespecificidad de los síntomas y su baja prevalencia, llevan a un retraso diagnóstico de 2 a 4 años 6, generando un incremento del riesgo cardiovascular pese a una resolución completa de la enfermedad 6-9. Este artículo tiene como objetivo describir la presentación clínica de la Enfermedad de Cushing como causa de HTA secundaria. CASO CLÍNICO: Paciente femenina de 36 años con HTA de 7 años de evolución, a quien se identificó adenoma hipofisario productor de ACTH, con posterior exéresis transesfenoidal parcial, presentando enfermedad persistente, en quien se optó manejo farmacológico a base de inhibidor de la esteroidogénesis para control de la enfermedad. DISCUSIÓN: La HTA es un problema de salud pública considerado el principal factor de riesgo para discapacidad y muerte prematura 2, con las causas secundarias como responsables de gran afectación en la calidad de vida, tomando en cuenta que estas son potencialmente curables. El manejo de la enfermedad de Cushing (EC) es principalmente quirúrgico 6,13-14, pero en caso de enfermedad persistente existen alternativas para control de la enfermedad 6,15-16, siendo los fármacos inhibidores de la esteroidogénesis los más usados. CONCLUSIONES: La EC es una causa poco frecuente hipertensión arterial secundaria, pero implica un importante compromiso de la calidad de vida, al igual que otras etiologías secundarias, por lo que es fundamental tener en cuenta las características clínicas y bioquímicas que sugieran una etiología secundaria que lleven a un diagnóstico y tratamiento oportunos.

INTRODUCTION: Cushing's Disease is one of the least prevalent causes of secondary hypertension (0.7 to 2.4 cases per million people), however it entails an increase in morbidity and mortality that is related to the chronic exposure of corticosteroids 6, which represents a problem because the no specificity of the symptoms and their low prevalence lead to a diagnostic delay of 2 to 4 years 6, increasing the cardiovascular risk despite complete resolution of the disease 6 -9. The purpose of this article aims to describe the clinical presentation of Cushing Disease (CD) as a cause of secondary hypertension. CLINICAL CASE: 36-year-old female patient with hypertension of 7 years of evolution, in whom an ACTH-producing pituitary adenoma was identified, with subsequent partial transsphenoidal excision, presenting persistent disease, in whom pharmacological management based on a steroidogenesis inhibitor was chosen. for disease control. DISCUSSION: Hypertension is a public health problem, considered the main risk factor for disability and premature death 2, with secondary causes responsible for great impact on quality of life, considering that these are potentially curative. The management of CD is mainly surgical 6,13-14, but in cases of persistent disease there are alternatives to control the disease 6,15-16, with steroidogenesis inhibitor drugs being the most used. CONCLUSIONS: CD is a rare cause of secondary hypertension, but it implies a significant compromise in quality of life, like other secondary etiologies, so it is essential to consider the clinical and biochemical characteristics that suggest a secondary etiology, which can lead to timely diagnosis and treatment.

Ayurvedic management of pituitary macroadenoma-a case report

Pituitary macroadenoma is an infrequently encountered clinical condition, characterized by a non-metastasizing neoplasm situated within the pituitary gland. This case report endeavours to elucidate the efficacy of ayurvedic interventions in achieving symptomatic resolution. A 44-year-old female patient, residing in Thrissur, diagnosed with features suggestive of pituitary macroadenoma, sought admission to Vaidyaratnam ayurveda college hospital for complaints of generalized pain, heaviness of head, impaired peripheral vision in the left eye, and amenorrhea persisting for approximately 7 months. The case was conclusively diagnosed as Pituitary Macroadenoma and meticulously addressed through therapeutic modalities including takradhara, nasyam, and thalapothichil. patient was already prescribed with Caberlin tablets at a dosage of 0.25 mg twice weekly, administered nocturnally. Following 21 days of treatment, notable improvement in the LBNQ-Pituitary score was observed from 60 to 21 accompanied by significant symptomatic alleviation. A specific treatment protocol for the management of pituitary macroadenoma is currently unavailable.

Studies on Serum T3, T4, TSH, Progesterone and Oestrogen in Cardiovascular Disease Patients

Aim: This research was done to ascertain if thyroid hormones and female sex hormones (progesterone and estrogen) play a role or are a risk factor in the development of cardiovascular diseases. Study Design: This is an observational study, specifically a case-control study. Place and Duration of Study: This study was conducted at Enugu State University Teaching Hospital for six months. Methodology: Blood samples were collected from 20 persons with cardiovascular disease. The sera from the study subjects were estimated for T3, T4, and TSH using the ELISA technique. The same parameters were estimated in 20 healthy individuals, and the results from both groups were analysed using SPSS version 21. Results: There were no significant differences in serum T3, T4 and TSH, Progesterone and Estradiol (p=0.236, p=0.834, p=0.412, p=0.995 and p=0.512, respectively) in cardiovascular disease patients compared with controls. There were no significant differences in serum T3, Progesterone, Estradiol and TSH (p=0.443, p=0.291, p=0.612 and p=0.550, respectively) in male cardiovascular disease patients compared to female cardiovascular disease patients. There was a significantly higher level of T4 (p=0.042) in male cardiovascular disease patients compared to female cardiovascular disease patients. A significant negative correlation of serum TSH with T4 (r=-0.759, p=0.000) in cardiovascular disease patients. There was no significant correlation of serum TSH with T3 (r=-0.131, p=0.560) in cardiovascular disease patients. There was a significant positive correlation of Serum Progesterone with Estradiol (r=0.815, p=0.000) in cardiovascular disease patients. Conclusion: T4, T3, and TSH serum levels may not be associated with the development of cardiovascular diseases in this environment. Also, serum progesterone may have a linear association with estradiol in cardiovascular disease patients.

The outcome of down-regulation+hormone replacement cycle endometrial preparation regimen in frozen-thawed embryo transfer in advanced age women / 重庆医学

Objective To analyze the effects of down-regulation+hormone replacement therapy(HRT)endometrial preparation regimen on the pregnancy outcomes of advanced age women(≥35 years old)undergoing frozen-thawed embryo transfer.Methods The clinical data of 329 patients with frozen-thawed em-bryo transfer in this hospital from June 2020 to June 2022 were analyzed retrospectively.Among them,149 pa-tients receiving gonadotropin-releasing hormone analogue(GnRHa)down-regulation+HRT endometrial preparation were included in the group A,and the other 180 patients with HRT endometrial preparation were included in the group B.The basic situation,endometrial transformation day situation and clinical outcome were compared between the two groups.The group A and group B were further divided into the two sub-groups according to age:group A1(35-＜40 years old,n=101),group A2(≥40 years old,n=48),group B1(35-＜40 years old,n=99)and group B2(≥40 years old,n=81).The effects of two endometrial prepara-tion regimens were compared among the different age groups.Results There were no significant differences in the age,infertility years,BMI,anti-Mullerian hormone level,as well as basal hormones levels such as estra-diol,progesterone,follicle-stimulating hormone,luteinizing hormone(LH),prolactin and testosterone between the two groups(P＞0.05).The levels of estradiol and LH on the endometrial transformation day in the group A were significantly lower than those in the group B(P＜0.05),the endometrial thickness,proportion of the patients with endometrial thickness ≥8 mm and proportion of the patients with type Ⅲ blood intima in the group A were significantly higher than those in the group B(P＜0.05).There was no significant difference in the number of transplanted embryos and the number of transplanted excellent embryos between the two groups(P＞0.05).The clinical pregnancy rate and embryo implantation rate in the group A were significantly higher than those in the group B(46.31％vs.35.56％;33.33％vs.25.18％,P＜0.05),and there was no significant difference in the early miscarriage rate between the two groups(P＞0.05).The further subgroup analysis showed that the clinical pregnancy rate and embryoimplantation rate in the group A2 were significant-ly higher than those in the group B2(35.42％vs.18.52％;21.43％vs.12.40％,P＜0.05),while there was no significant difference between the group A1 and group B1(P＞0.05).Conclusion The advanced age pa-tients undergoing frozen-thawed embryo transfer could select GnRHa down-regulation+HRT regimen to a-chieve better pregnancy outcomes,especially for those age ≥40 years old.

The effect of growth hormone on invasion and migration of colon cancer cells / 重庆医学

Objective To explore the effects of growth hormone(GH)on the proliferation,cycle,inva-sion,and migration of colon cancer cells and its possible mechanism.Methods GH3 cells with growth hor-mone-type pituitary adenoma were cultured in vitro,and the secretion of growth hormone in the supernatant of GH3 cells was detected by ELISA.Colon cancer LoVo cells in logarithmic growth phase were randomly divid-ed into the control group and the experimental group.PBS was added to the control group,while high concen-trations of recombinant GH were added to the experimental group.The two groups of cells were cultured in vitro under the same conditions.CCK-8 method was used to detect the proliferation of the cells.Flow cytome-try was used to detect the cell cycle.Transwell assay was used to detect the effect of growth hormone on the invasion and migration of the cells.Western blot was used to detect the expressions levels of E-cadherin,N-cadherin,Vimentin,and Snail-1 proteins in the cells.Results The results of ELISA showed that GH3 cells could secrete a large amount of GH,and the concentration of GH in the supernatant was(1 208±9)ng/mL.GH promoted cell growth in a dose-dependent manner within a certain concentration range,and GH 200 ng/mL was the optimal intervention concentration for subsequent experiments.Compared with the control group,the cell cycle in the experimental group changed from G1 phase to S phase and G2 phase,the ratio of G1 phase cells decreased,and the ratio of S phase cells and G2 phase cells increased(P<0.05).Compared with the control group,the number of the cell invasion and migration increased in the experimental group(P<0.05),the expression levels of N-cadherin,Vimentin,and Snail-1 was up-regulated,while the expression level of E-cadherin was down-regulated(P<0.05).Conclusion High concentration of GH promotes the prolifera-tion,invasion and migration of colon cancer cells,and induces the transition of cell cycle from G1 to S and G2 phases.The mechanism may be related to the epithelial-mesenchymal transition(EMT)of colon cancer cells promoted by high concentration of GH.

Protective effect of LW-AFC against fear sensitization induced by traumatic stress / 军事医学

Objective To investigate the protective effects and underlying mechanisms of Liuwei Dihuang Glucoside(LW-AFC)against fear sensitization induced by traumatic stress.Methods Mice were divided into naive,control,stressed and LW-AFC administration groups.The LW-AFC treated group received LW-AFC(1.6 g/kg daily)via oral gavage for two weeks following exposure to traumatic stress.The non-associative memory dependent fear sensitization responses in mice subjected to trauma were investigated,including behavior in novel environments,social interaction,and observational fear tests.Z-score normalization method was employed to integrate and assess multiple behavioral variables such as travel distance,freezing time,and corner time,and comprehensively examined fear sensitization behaviors across the groups.Additionally,serum concentrations of adrenocorticotropic hormone,corticosterone,aldosterone,renin,angiotensin Ⅱ,and aldosterone were measured using ELISA.Results Compared to the control group,stressed mice exhibited significantly reduced travel distance(P<0.0001)and increased freezing time(P<0.0001)in the new context test.Integrated Z-scores indicated a significant increase in fear behavior among stressed mice during the new context test(P<0.0001).In the social interaction test,stressed mice demonstrated significantly reduced travel distance(P<0.0001),increased freezing time(P<0.0001),increased corner time(P<0.05),and higher integrated Z-scores(P<0.0001).In the observational fear test,stressed mice showed significantly reduced travel distance(P<0.05),increased freezing time(P<0.001),increased corner time(P<0.05),and higher integrated Z-scores(P<0.0001).Compared to the stressed group,mice in the LW-AFC treated group displayed trends toward improvement in travel distance,freezing time,corner time,and integrated Z-scores in the new context tests,albeit without statistical significance.In the social interaction test,the LW-AFC treated group exhibited a significant reduction in freezing time(P<0.05)and integrated Z-scores(P<0.05).In the observational fear test,the LW-AFC treated group showed a significant reduction in freezing time(P<0.05)and integrated Z-scores(P<0.01).Compared to the naive group,control and stressed groups exhibited an increased trend in renin and aldosterone levels after the fear sensitization test.Although there were no significant differences between stressed and control groups,renin and aldosterone levels significantly increased between stressed and naive groups(P<0.05,P<0.05).Following LW-AFC treatment,serum renin levels showed no significant change,while aldosterone levels significantly decreased(P<0.05).Conclusion Stressed mice exhibited significant fear sensitization behavior in new context,social interaction,and observational fear tests,possibly associated with partial activation of the renin-angiotensin-aldosterone system(RAAS)system.LW-AFC treatment significantly mitigated fear sensitization behavior of stressed mice in social interaction and observational fear test,potentially due to its regulatory effects on the RAAS system in mice subjected to traumatic stress.

Mechanism of Electroacupuncture in Functional Dyspepsia Rats Based on Hypothalamic-Pituitary-Adrenal Axis / 世界科学技术-中医药现代化

Objective We aimed to explore the therapeutic mechanism of electroacupuncture at Yintang(EX-HN3),Neiguan(PC6)and Zusanli(ST36)on the Hypothalamic-Pituitary-Adrenal axis(HPA)of functional dyspepsia(FD)rats.Methods Forty SD rats were randomly divided into blank group,model group and EA group.The FD model was replicated by tail clamping,irregular diet,and filling the stomach with ice of Saline Solution.After modeling,the EA group received acupuncture treatment for 1 time day,30 minutes time,for 14 days.Recording the general state of the rat.Detection of locomotion and catatonia in rats by open field test.HE staining to observe the morphology and inflammation of gastric mucosa in rats.PCR detection of mRNA expression of 5-hydroxytryptamine3 receptor and corticotropin-releasing hormone in rat hypothalamus.Detection of corticotropin-releasing hormone receptor-2 and NOD-like receptor protein 6 inflammasome protein expression in rat duodenum by Western blotting.Alcian blue staining was used to detect the expression of rat duodenum goblet cells.Results Compared with the blank group,the general state,distance,speed,duodenum CRHR2 and NLRP6 proteins in the model group were significantly decreased(P<0.05),the hypothalamic 5-HT3R and CRH mRNA were significantly increased(P<0.05).Compared with the model group,the general state,distance,speed,expression of CRHR2,NLRP6 protein and goblet cells in the duodenum of rats in the EA group were significantly increased(P<0.05),the 5-HT3R and CRH mRNA in the hypothalamus were significantly decreased(P<0.05).In the model group,the connective tissue of the gastric mucosa was loosely arranged,the submucosa had mild edema,and there were some lymphocytes.The connective tissue of the gastric mucosa of the rats in the blank group and the electroacupuncture group was closely arranged,and there was no obvious proliferation of interstitial cells and no inflammatory cells.Conclusion EA can increase the expression of CRHR2,NLRP6 protein and goblet cells in the duodenum,and inhibit the expression of 5-HT3R and CRH in the hypothalamus.EA can improve gastrointestinal motility and locomotion,relieve anxiety,repair the mucosal barrier of the defective intestine,and restore the function of the Hypothalamic-Pituitary-Adrenal axis.

Risk factors of depression and anxiety in epilepsy patients and their relationship with quality of life / 实用医学杂志

Objective To explore the risk factors of depression and anxiety in adult patients with epilepsy and their relationship with quality of life.Methods From May 2022 to January 2023,patients diagnosed with epilepsy(aged≥18 years)in the department of neurology of our hospital were collected.General demographic data and disease-related information were recorded.Quality of life,depression and anxiety scales were measured in all patients.SPSS26.0 software was used for multiple linear regression analysis,multiple ordered Logistic regression analysis,rank sum test,Pearson correlation analysis,etc.Results Among the 111 patients,49.5%had depression and 43.2%had anxiety.Depression score and anxiety score were correlated with attack type,attack frequency,quality of life and right temporal lobe,and there was a significant negative correlation between life quality score and anxiety and depression score(P<0.01).Seizure frequency,seizure type and right temporal lobe were common risk factors for depression and anxiety in patients with epilepsy(P<0.05).Conclusion Epileptic depression and anxiety were affected by seizure frequency and seizure type,and this bad mood further affected the quality of life of patients.No clear link has been found between the lateralization of seizures and the presence of depression and anxiety states,and further research is needed.

Culture,identification,and differentiation of rabbit pituitary stem cells / 中国组织工程研究

BACKGROUND:The pituitary gland is an important endocrine organ in the body.Certain diseases can cause damage to the pituitary gland,such as pituitary adenoma and abnormal hormone secretion.Pituitary stem cells,due to their self-renewal and multi-directional differentiation potential,are expected to become a new therapeutic approach for repairing damaged pituitary glands. OBJECTIVE:To isolate and culture pituitary stem cells using the suspension cell ball culture method and identify their proliferation and differentiation ability. METHODS:Pituitary stem cells were isolated and cultured from the pituitary gland of newborn New Zealand white rabbits using the suspension cell ball culture method,and their morphological characteristics were observed.Immunofluorescence cytochemistry was used to detect the expression of pituitary stem cell markers SOX2 and Nestin.EdU labeling method was utilized to detect the proliferative ability of pituitary stem cells.After adherent and induced differentiation,the hormone levels in the culture medium were detected by ELISA. RESULTS AND CONCLUSION:Pituitary stem cell spheres could be successfully isolated by the suspension cell ball culture method,with strong proliferative ability.Positive expression of stem cell-specific markers SOX2 and Nestin was found in the cultured cells.After induction and differentiation,adrenocorticotropic hormone,thyroid hormone,growth hormone,luteinizing hormone,follicle-stimulating hormone,and prolactin levels significantly increased in the medium(P<0.001),with strong differentiation ability.

A case of pituitary crisis caused by cadonilimab treatment of advanced gastric cancer / 药物流行病学杂志

A 75-year-old female patient with gastric cancer received cadonilimab(500 mg,iv,d1)combined with albumin-bound paclitaxel(300 mg,iv,d2)and tegafur,gimeracil and oteracil potassium(40 mg,po,bid,d2-15)and 21 days was a cycle.Admission examination at the end of 4 cycles of treatment,laboratory tests showed adrenocorticotropic hormone＜1.00 pg,mL-1,cortisol 0.42 μg·dL-1 and serum sodium 131 mmol·L-1.Immune checkpoint inhibitor-related hypophysitis was diagnosed,and pituitary crisis was developed on the 4th day.The diagnosis of hypophysitis concurrent with pituitary crisis was considered to be related to cadonilimab.High-dose glucocorticoids replacement and symptomatic treatment such as rehydration to maintain electrolyte imbalance were given.On the 9th day after admission,the patient was basically in remission.The administration of cadonilimab may cause pituitary crisis,which is relatively rare in clinical practice.This case reminds that the possibility of hypophysitis when patients emerge with the symptom of fatigue and anorexia along with hyponatremia.Assessment of endocrine gland function,correct diagnosis and proper therapy are of significant clinical value to improve the patients'prognosis.

Syndrome of inappropriate secretion of thyrotropin: Differential diagnosis / 中华内分泌代谢杂志

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.

A Case Report of Marfan Syndrome with Pituitary Tumor Which Could be Misdiagnosed as Gigantism / 罕见病研究

Marfan syndrome (MFS) is an autosomal dominant disorder that is prone to fibrodysplasia, lens dislocation and rapid height growth, which needs to be distinguished from gigantism. This article reports a 14-year-old patient with MFS who had a typical binocular lens subluxation in both eyes, with visual impairment and rapid height growth. MRI with contrast to the pituitary suggested a pituitary microadenoma, but growth hormone and insulin-like growth factor 1 were in the normal range, thus excluding gigantism or acromegaly. Non-functional pituitary adenoma was considered. MFS patients need long-term follow-up and multidisciplinary collaboration, and attention should be paid to cardiovascular system monitoring and genetic testing, which can be helpful for the diagnosis and treatment of patients and risk prevention and control.

Relationship between oral diseases and depression / 口腔疾病防治

@#Oral health is an integral component of overall well-being, with the oral cavity serving as a channel for external communication and expression of emotions such as stress and pessimism. Oral diseases can intensify feelings of depression, whereas depression can worsen oral health conditions. As a crucial part of the human microbiome, an imbalance in oral microbiota can release oral pathogenic microbes, which, through pathways including the circulation, nervous, and immune systems, can reach the brain and significantly affect the central nervous system. This can lead to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, further intensifying the development of depression. Similarly, an imbalance in oral microbiota in individuals with depression can intensify the occurrence of oral diseases. The relationship between depression and oral diseases is not isolated but rather a complex interplay in which they mutually influence and act as causative factors. To elucidate the causal relationship between oral diseases and depression and devise strategies for the prevention and treatment of both conditions, we explore the interaction mechanisms between oral diseases and depression from the perspective of oral microbiota. The occurrence of dental caries, periapical periodontitis, and periodontal diseases is closely associated with the excessive proliferation of specific bacteria in the oral cavity, such as Streptococcus mutans, Porphyromonas gingivalis, and Fusobacterium nucleatum. These bacteria can directly invade the brain through the compromised blood-brain barrier, activating pro-inflammatory cytokines and worsening depressive symptoms. Inflammatory conditions and ulcers in the oral mucosa are caused by various factors, including infection and immune abnormalities. Because of compromised immune function in individuals with depression, these inflammatory responses are often more severe and difficult to control. Malocclusion, trigeminal neuralgia, and temporomandibular joint disorders increase the risk of depression because of psychological stress and changes in the immune system. We also outline the diagnostic and therapeutic considerations for oral diseases in patients with depression, emphasizing the importance of early intervention for disease management. Future research will explore the therapeutic potential of oral microbiota in individuals with depression, with the aim to improve symptoms and treatment outcomes by adjusting oral microbiota, thus providing novel avenues for the prevention and treatment of depression.

Changes of macular retinal structure and microcirculation in patients with pituitary adenoma observed by optical coherence tomography and optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the changes of macular retinal structure and microcirculation in patients with pituitary adenoma(PA)by optical coherence tomography(OCT)and optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 40 PA patients treated at the department of neurosurgery, Affiliated Hospital of Guangdong Medical University from September 2021 to March 2023 were included as PA group, and 42 age- and gender-matched healthy volunteers were selected as normal control group. All patients underwent visual field, OCT and OCTA examinations, and the correlation of ocular parameters in PA patients was analyzed.RESULTS:The vessel density(VD)of each retinal layer in the macular area of the PA group was lower than that of the normal control group, and the superficial vascular complex(SVC)-VD in the macular area was positively correlated with the thickness of the macular ganglion cell complex(mGCC)(except the nasal side of the inner ring and the lower part of the outer ring; P&#x0026;#x003C;0.05). The thickness of mGCC in each quadrant of the macular area and the thickness of the circumpapillary retinal nerve fiber layer(CP-RNFL)in each quadrant were negatively correlated with the mean defect(MD)value of the visual field(P&#x0026;#x003C;0.05), and the area of the foveal avascular zone(FAZ)was positively correlated with the MD value(P&#x0026;#x003C;0.05).CONCLUSION:The combination of OCT and OCTA can fully understand the microscopic changes of retinal structure and microcirculation function in PA patients, which is of great value in evaluating the preoperative visual function of PA patients.

Syndromes and Mechanisms of Depression Induced by Second Hit in Mice / 中国实验方剂学杂志

ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.

Expression and Clinical Significance of Insulin-like Growth Factor-1 in Pituitary Adenomas / 医学研究杂志

Objective To analyze the expression of insulin-like growth factor-1(IGF-1)in the serum of patients with pituitary adenomas and compare them according to different standards,investigating the expression of IGF-1 in pituitary adenoma and its clinical significance.Methods A total of 156 cases of pituitary adenomas admitted to the Second Affiliated Hospital of Kunming Medical Univer-sity from January 2019 to June 2021 were selected as the experimental group,and a total of 22healthy subjects during the same period were selected as the control group.To determinate the IGF-1 level by magnetic particle chemical luminescence immunoassay.The tumor di-ameter was obtained by combining the diameter measured on magnetic resonance imaging(MRI)with the diameter of postoperative tumor pathological specimen.The experimental group were divided into groups according to different clinical characteristics,and to compare the differences in IGF-1 levels between each subgroup and the control group.Results The levels of IGF-1 in patients with somatotroph adenoma,dual hormone and multihormone adenoma were higher than those in the control group and other types,and the differences were statistically significant(P＜0.05);the level of IGF-1 in giant adenoma patients was higher than those in the control group and other types,and the difference was statistically significant(P＜0.05);the level of IGF-1 in patients with invasive pituitary adenoma was higher than that in non-invasive patients and controls,and the difference was statistically significant(P＜0.05);Logistic regression a-nalysis showed that IGF-1 level and tumor diameter were risk factors for invasiveness of pituitary adenomas,the higher the IGF-1 level and the larger the tumor diameter,the higher the invasiveness risk;the level of IGF-1 in patients with pituitary adenoma within one month after surgery was significantly lower than that before surgery,and the difference was statistically significant(P＜0.05).Conclu-sion IGF-1 has a certain value in the diagnosis of different functional types of pituitary adenomas and the early invasiveness judgment of pituitary adenomas,and is expected to be used as a reliable indicator for postoperative follow-up.