A zebrafish model of diabetic nephropathy shows hyperglycemia, proteinuria and activation of the PI3K/Akt pathway.

Diabetic nephropathy (DN), as a complication of diabetes, is a substantial healthcare challenge owing to the high risk of morbidity and mortality involved. Although significant progress has been made in understanding the pathogenesis of DN, more efficient models are required to develop new therapeutics. Here, we created a DN model in zebrafish by crossing diabetic Tg(acta1:dnIGF1R-EGFP) and proteinuria-tracing Tg(l-fabp::VDBP-GFP) lines, named zMIR/VDBP. Overfed adult zMIR/VDBP fish developed severe hyperglycemia and proteinuria, which were not observed in wild-type zebrafish. Renal histopathology revealed human DN-like characteristics, such as glomerular basement membrane thickening, foot process effacement and glomerular sclerosis. Glomerular dysfunction was restored upon calorie restriction. RNA sequencing analysis demonstrated that DN zebrafish kidneys exhibited transcriptional patterns similar to those seen in human DN pathogenesis. Notably, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was activated, a phenomenon observed in the early phase of human DN. In addition, metformin improved hyperglycemia and proteinuria in DN zebrafish by modulating Akt phosphorylation. Our results indicate that zMIR/VDBP fish are suitable for elucidating the mechanisms underlying human DN and could be a powerful tool for therapeutic discovery.

Macrophage-induced integrin signaling promotes Schlemm's canal formation to prevent intraocular hypertension and glaucomatous optic neuropathy.

Schlemm's canal (SC) functions to maintain proper intraocular pressure (IOP) by draining aqueous humor and has emerged as a promising therapeutic target for glaucoma, the second-leading cause of irreversible blindness worldwide. However, our current understanding of the mechanisms governing SC development and functionality remains limited. Here, we show that vitronectin (VTN) produced by limbal macrophages promotes SC formation and prevents intraocular hypertension by activating integrin αvß3 signaling. Genetic inactivation of this signaling system inhibited the phosphorylation of AKT and FOXO1 and reduced ß-catenin activity and FOXC2 expression, thereby causing impaired Prox1 expression and deteriorated SC morphogenesis. This ultimately led to increased IOP and glaucomatous optic neuropathy. Intriguingly, we found that aged SC displayed downregulated integrin ß3 in association with dampened Prox1 expression. Conversely, FOXO1 inhibition rejuvenated the aged SC by inducing Prox1 expression and SC regrowth, highlighting a possible strategy by targeting VTN/integrin αvß3 signaling to improve SC functionality.

Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption.

BACKGROUND: Lymphatic vessels are responsible for tissue drainage, and their malfunction is associated with chronic diseases. Lymph uptake occurs via specialized open cell-cell junctions between capillary lymphatic endothelial cells (LECs), whereas closed junctions in collecting LECs prevent lymph leakage. LEC junctions are known to dynamically remodel in development and disease, but how lymphatic permeability is regulated remains poorly understood. METHODS: We used various genetically engineered mouse models in combination with cellular, biochemical, and molecular biology approaches to elucidate the signaling pathways regulating junction morphology and function in lymphatic capillaries. RESULTS: By studying the permeability of intestinal lacteal capillaries to lipoprotein particles known as chylomicrons, we show that ROCK (Rho-associated kinase)-dependent cytoskeletal contractility is a fundamental mechanism of LEC permeability regulation. We show that chylomicron-derived lipids trigger neonatal lacteal junction opening via ROCK-dependent contraction of junction-anchored stress fibers. LEC-specific ROCK deletion abolished junction opening and plasma lipid uptake. Chylomicrons additionally inhibited VEGF (vascular endothelial growth factor)-A signaling. We show that VEGF-A antagonizes LEC junction opening via VEGFR (VEGF receptor) 2 and VEGFR3-dependent PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) activation of the small GTPase RAC1 (Rac family small GTPase 1), thereby restricting RhoA (Ras homolog family member A)/ROCK-mediated cytoskeleton contraction. CONCLUSIONS: Our results reveal that antagonistic inputs into ROCK-dependent cytoskeleton contractions regulate the interconversion of lymphatic junctions in the intestine and in other tissues, providing a tunable mechanism to control the lymphatic barrier.

Paxlovid for hospitalized COVID-19 patients with chronic kidney disease.

BACKGROUND: COVID-19 causes significant mortality during the recent pandemic. Data regarding the effectiveness of Paxlovid on COVID-19 patients with chronic kidney disease (CKD, eGFR <90 ml/min) are limited. METHODS: A retrospective cohort study was performed on the clinical data of the hospitalized adult patients with confirmed COVID-19 infection collected at Renji Hospital from April 7, 2022 to June 21, 2022. The association of Paxlovid treatment with early (within 5 days post diagnosis) or late (5 days or later post diagnosis) initiation time with clinical outcomes was assessed by Cox proportional hazards regression model with time-dependent covariates. RESULT: 1279 of 2387 enrollees were included in the study. Patients with early initiation of Paxlovid had a lower all-cause death rate compared to those with late initiation or without Paxlovid treatment (P = 0.046). For the CKD patients with Charlson comorbidity index (CCI) > 7, the early initiation of Paxlovid was associated with a lower all-cause death rate compared to the later initiation or the lack of Paxlovid treatment (P = 0.041). Cox regression analyses revealed that eGFR (HR 4.21 [95%, CI 1.62-10.99]), Paxlovid treatment (0.32 [0.13-0.77]), CCI (4.32 [1.64-11.40]), ICU admission (2.65 [1.09-6.49]), hsCRP (3.88 [1.46-7.80]), chronic liver disease (4.02 [1.09-14.85]) were the independent risk factors for all-cause death for CKD patients after adjusting for demographics and biochemical indexes. CONCLUSIONS: All-cause death, invasive ventilation, and ICU admission were all significantly lowered by an early initiation of Paxlovid treatment in COVID-19 patients with severe CKD.

Targeting VEGF-A/VEGFR2 Y949 Signaling-Mediated Vascular Permeability Alleviates Hypoxic Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is associated with increased expression of VEGF-A (vascular endothelial growth factor A) and its receptor, VEGFR2 (vascular endothelial growth factor 2), but whether and how activation of VEGF-A signal participates in the pathogenesis of PH is unclear. METHODS: VEGF-A/VEGFR2 signal activation and VEGFR2 Y949-dependent vascular leak were investigated in lung samples from patients with PH and mice exposed to hypoxia. To study their mechanistic roles in hypoxic PH, we examined right ventricle systolic pressure, right ventricular hypertrophy, and pulmonary vasculopathy in mutant mice carrying knock-in of phenylalanine that replaced the tyrosine at residual 949 of VEGFR2 (Vefgr2Y949F) and mice with conditional endothelial deletion of Vegfr2 after chronic hypoxia exposure. RESULTS: We show that PH leads to excessive pulmonary vascular leak in both patients and hypoxic mice, and this is because of an overactivated VEGF-A/VEGFR2 Y949 signaling axis. In the context of hypoxic PH, activation of Yes1 and c-Src and subsequent VE-cadherin phosphorylation in endothelial cells are involved in VEGFR2 Y949-induced vascular permeability. Abolishing VEGFR2 Y949 signaling by Vefgr2Y949F point mutation was sufficient to prevent pulmonary vascular permeability and inhibit macrophage infiltration and Rac1 activation in smooth muscle cells under hypoxia exposure, thereby leading to alleviated PH manifestations, including muscularization of distal pulmonary arterioles, elevated right ventricle systolic pressure, and right ventricular hypertrophy. It is important that we found that VEGFR2 Y949 signaling in myeloid cells including macrophages was trivial and dispensable for hypoxia-induced vascular abnormalities and PH. In contrast with selective blockage of VEGFR2 Y949 signaling, disruption of the entire VEGFR2 signaling by conditional endothelial deletion of Vegfr2 promotes the development of PH. CONCLUSIONS: Our results support the notion that VEGF-A/VEGFR2 Y949-dependent vascular permeability is an important determinant in the pathogenesis of PH and might serve as an attractive therapeutic target pathway for this disease.

Giant cystic parathyroid adenoma: two case reports and a literature review.

An uncommon cause of primary hyperparathyroidism is a cystic parathyroid adenoma. This paper describes two patients with hypercalcemia and right knee disease. Their serum calcium concentration was high, phosphorus concentration was low, and parathyroid hormone (PTH) concentration was high. Ultrasound and computed tomography scans of the neck indicated a cystic mass near the thyroid. Parathyroid scintigraphy showed no focal uptake in one patient and low tracer concentration in the cystic mass in the other patient. Following resection of the cystic masses, both were pathologically confirmed to be a cystic parathyroid adenoma with predominantly cystic degeneration. The calcium and PTH concentrations gradually decreased to the reference range. Both patients were stable at their last follow-up. The diagnosis of a functional cystic parathyroid adenoma is highly challenging because of the different clinical manifestations and negative result on parathyroid tracer scintigraphy. For patients with high serum calcium and PTH concentrations and a cystic mass in the neck, resection of the mass and subsequent postoperative pathological diagnosis is necessary even if the clinical diagnosis of a parathyroid adenoma cannot be confirmed preoperatively. Decreases in the PTH and serum calcium concentrations indicate successful resection of a functional parathyroid adenoma.

Blood Flow Regulates Glomerular Capillary Formation in Zebrafish Pronephros.

Background: The renal glomerulus is a tuft of capillaries in Bowman's capsule and functions as a blood-filtration unit in the kidney. The unique glomerular capillary tuft structure is relatively conserved through vertebrate species. However, the morphogenetic mechanism governing glomerular capillary tuft formation remains elusive. Methods: To clarify how glomerular capillaries develop, we analyzed glomerular capillary formation in the zebrafish pronephros by exploiting fluorescence-based bio-imaging technology. Results: During glomerular capillary formation in the zebrafish pronephros, endothelial cells initially sprouted from the dorsal aorta and formed the capillaries surrounding the bilateral glomerular primordia in response to podocyte progenitor-derived vascular endothelial growth factor-A. After formation, blood flow immediately occurred in the glomerular primordia-associated capillaries, while in the absence of blood flow, they were transformed into sheet-like structures enveloping the glomerular primordia. Subsequently, blood flow induced formation of Bowman's space at the lateral sides of the bilateral glomerular primordia. Concomitantly, podocyte progenitors enveloped their surrounding capillaries while moving toward and coalescing at the midline. These capillaries then underwent extensive expansion and remodeling to establish a functional glomerular capillary tuft. However, stopping blood flow inhibited the remodeling of bilateral glomerular primordia, which therefore remained unvascularized but covered by the vascular sheets. Conclusions: We delineated the morphogenetic processes governing glomerular capillary tuft formation in the zebrafish pronephros and demonstrated crucial roles of blood flow in its formation. Blood flow maintains tubular structures of the capillaries surrounding the glomerular primordia and promotes glomerular incorporation of these vessels by inducing the remodeling of glomerular primordia.

Diagnostic accuracy of vesical imaging-reporting and data system (VI-RADS) for the detection of muscle-invasive bladder cancer: a meta-analysis.

PURPOSE: Vesical Imaging-Reporting and Data System (VI-RADS) was proposed and considered as a standardized reporting criterion for bladder magnetic resonance imaging (MRI). VI-RADS could suggest the likelihood of muscle invasion based on the multiparametric MRI (mp-MRI) findings which contain five-point scores. The current study is designed to comprehensively and systematically evaluate the diagnostic performance of VI-RADS (score 3 and 4) for predicting muscle invasion. METHODS: The Cochrane Library, Embase, and PubMed were searched comprehensively from inception to October 2021. RESULTS: Finally, 19 studies incorporating 2900 patients were enrolled. The pooled sensitivity and specificity of VI-RADS 3 for predicting muscle invasion were 0.92 (95%CI 0.89-0.94) and 0.82 (95%CI 0.76-0.87), respectively. The pooled sensitivity and specificity of VI-RADS 4 were 0.78 (95%CI 0.72-0.83) and 0.96 (95%CI 0.93-0.97), respectively. And the area under the curve (AUCs) of VI-RADS 3 and 4 were all 0.94 (95%CI 0.92-0.96). No significant publication biases were not observed for VI-RADS 3 (P = 0.74) and 4 (P = 0.57). CONCLUSION: The VI-RADS reveals a good diagnostic performance for predicting muscle invasive in bladder cancer, which also has good clinical utilities and applicability. And VI-RADS 3 and 4 as cutoff values provide similar overall diagnostic and could be selectively applied individually. Prospective studies with a large scale are further required to validate the accuracy of the VI-RADS score.

A novel heterozygous mutation of CHD7 gene in a Chinese patient with Kallmann syndrome: a case report.

BACKGROUND: Variants of chromodomain helicase DNA binding protein 7 (CHD7) gene are commonly associated with Kallmann syndrome (KS) and account for 5-6% of idiopathic hypogonadotropic hypogonadism (IHH) cases. Here we report a novel mutation of CHD7 gene in a patient with KS, which may contribute to the better understanding of KS. CASE PRESENTATION: A 29-year-old male patient with KS and a chief complaint of delayed puberty for 13 years (Tanner B Stage< 4) was admitted to the Department of Endocrinology of the First Affiliated Hospital of Zhejiang University (Hangzhou, China) in September 2019. Dual-energy X-ray absorptiometry (DEXA) showed low bone density in both lumbar spine (L1 ~ L5 mean Z-score - 3.0) and femoral neck (Z-score - 2.7). Dynamic contrast-enhanced magnetic resonance imaging (MRI) of pituitary and contrast-enhanced computed tomography (CT) showed no abnormal findings. Ophthalmological evaluation showed that his both eyes showed exotropia, and no sight loss was noted. Heterozygous c.1619G > T mutation of TCD7 gene (p.G4856V) was detected, whereas none of his family members had this mutation. Human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) were injected for three times/week to treat idiopathic hypogonadotropic hypogonadism (IHH). After several months of therapy, the patient's health condition improved. His testicles became larger, and his secondary sexual characteristics improved after treatment. CONCLUSION: Exploration of the novel splice-site mutation of CHD7 may further our current understanding of KS.

[Retracted] MicroRNA­145 inhibits migration and invasion via inhibition of fascin 1 protein expression in non­small­cell lung cancer cells.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell cell migration data shown in Fig. 4 were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 12: 6193­6198, 2015; DOI: 10.3892/mmr.2015.4163].

Prolonged podocyte depletion in larval zebrafish resembles mammalian focal and segmental glomerulosclerosis.

Focal and segmental glomerulosclerosis (FSGS) is a histological pattern frequently found in patients with nephrotic syndrome that often progress to end-stage kidney disease. The initial step in development of this histologically defined entity is injury and ultimately depletion of podocytes, highly arborized interdigitating cells on the glomerular capillaries with important function for the glomerular filtration barrier. Since there are still no causal therapeutic options, animal models are needed to develop new treatment strategies. Here, we present an FSGS-like model in zebrafish larvae, an eligible vertebrate model for kidney research. In a transgenic zebrafish strain, podocytes were depleted, and the glomerular response was investigated by histological and morphometrical analysis combined with immunofluorescence staining and ultrastructural analysis by transmission electron microscopy. By intravenous injection of fluorescent high-molecular weight dextran, we confirmed leakage of the size selective filtration barrier. Additionally, we observed severe podocyte foot process effacement of remaining podocytes, activation of proximal tubule-like parietal epithelial cells identified by ultrastructural cytomorphology, and expression of proximal tubule markers. These activated cells deposited extracellular matrix on the glomerular tuft which are all hallmarks of FSGS. Our findings indicate that glomerular response to podocyte depletion in larval zebrafish resembles human FSGS in several important characteristics. Therefore, this model will help to investigate the disease development and the effects of potential drugs in a living organism.

Isolated Langerhans cell histiocytosis in the hypothalamic-pituitary region: a case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease that mainly affects children, but this disease is significantly rarer in patients who are older than 15 years. In this disease, any organ can be involved. The skeleton, skin and lung are commonly affected, and isolated hypothalamic-pituitary (HP) involvement is relatively rare. Here we report a 17-year-old adolescent with isolated HP-LCH of enlarged pituitary stalk presented with central diabetes insipidus (CDI). CASE PRESENTATION: A 17-year-old male adolescent with polydipsia and polyuria accompanied with elevated serum sodium level and low urine osmolality for 3 weeks was referred to our hospital. After admission, hormonal evaluation showed that his growth hormone (GH) was slightly elevated, and serum osmolality and glucose were normal. The fluid deprivation-vasopressin test demonstrated CDI. Imaging examination showed an obvious thickening of the pituitary stalk. Lymphocytic hypophysitis, sarcoidosis and granulation tissue lesions were suspected. After oral 1-deamino-8-Darginine vasopressin (DDAVP) and prednisone were administered for 2 months, symptoms were relieved, and he discontinued taking the drugs by himself. On reexamination, imaging revealed changes in the size and shape of the pituitary stalk, with thickened nodules. Then, a diagnostic biopsy of the pituitary stalk lesion was performed. Immunohistochemistry confirmed the definitive diagnosis of LCH. The clinical symptoms subsided with oral hormone replacements. CONCLUSION: CDI is a rare symptom in children and adolescents. Most of the causes are idiopathic, while others are caused by central nervous system (CNS) disorders. Meanwhile, lymphocytic hypophysitis, germinoma, LCH and other CNS disorders can all present as thickening of the pituitary stalk, diffuse enlargement of the pituitary gland, and weakening of high signal intensity in the neurohypophysis on magnetic resonance imaging (MRI). The differential diagnosis among these diseases depends on immunohistochemistry evidence.

A rare case of pure testosterone-secreting adrenal adenoma in a postmenopausal elderly woman.

BACKGROUND: Hyperandrogenemia is more common in puberty and reproductive age, but relatively rare in postmenopausal women. Postmenopausal virilization may result from androgen-producing tumors. Androgen-secreting adrenal tumors are rare in clinical practice and are diagnosed as adrenocortical carcinoma, most of which can co-secrete androgen and cortisol. Highly elevated serum testosterone level with normal adrenal androgens such as dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS) and androstenedione is usually regarded as ovary origin. Here we describe an unusual case of a postmenopausal woman with markedly elevated serum testosterone level, while DHEAS, androstenedione, 17-hydroxyprogesterone and cortisol were within the normal range. CASE PRESENTATION: A 67-year-old postmenopausal woman with hirsutism in the upper lip and armpit, accompanied by clitoromegaly for 5 months. Hormonal evaluation showed markedly elevated serum testosterone level (714.8 ng/ml), whereas DHEAS, androstenedione, 17-hydroxyprogesterone, and cortisol were within the normal range. Imaging examination showed a mass of 1.5 cm in diameter in the left adrenal gland and normal appearance of both ovaries. PET-CT indicated that it was a case of benign adrenal adenoma and excluded ovarian abnormalities and other ectopic tumors. Thus, a pure testosterone-secreting adrenal tumor was suspected and then adrenalectomy was performed. Histology and immunohistochemistry furtherly confirmed the benign adrenocortical adenoma with immunohistochemistry positive for inhibin α, melan A, ß-captenin, SYN (focal), Ki-67(< 3%), and negative for chromogranin (CgA), cytokeratin (CK), S-100, P53. After surgery, the level of testosterone returned to normal range and the clinical symptoms also subsided. CONCLUSIONS: Pure testosterone-secreting adrenal adenomas are extremely rare, but it can induce severe hyperandrogenism and virilization. The source identification of hyperandrogenemia only based on the levels of testosterone, DHEAS and androstenedione is limited. It is important to evaluate not only ovaries but also adrenals in all women with virilization particularly during menopause, even their androstenedione, DHEA and DHEAS level are normal.

Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure.

Background For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure.Methods We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure. We performed genome-wide linkage analysis, sequencing, and expression studies in kidney biopsy specimens and renal cells along with knockout mouse studies and evaluations of mitochondrial morphology and function. Structural studies examined the effects of recognized mutations.Results The renal disease in these patients resulted from monoallelic mutations in the gene encoding glycine amidinotransferase (GATM), a renal proximal tubular enzyme in the creatine biosynthetic pathway that is otherwise associated with a recessive disorder of creatine deficiency. In silico analysis showed that the particular GATM mutations, identified in 28 members of the five families, create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells. GATM aggregates-containing mitochondria were elongated and associated with increased ROS production, activation of the NLRP3 inflammasome, enhanced expression of the profibrotic cytokine IL-18, and increased cell death.Conclusions In this novel genetic disorder, fully penetrant heterozygous missense mutations in GATM trigger intramitochondrial fibrillary deposition of GATM and lead to elongated and abnormal mitochondria. We speculate that this renal proximal tubular mitochondrial pathology initiates a response from the inflammasome, with subsequent development of kidney fibrosis.

An ovarian Leydig cell tumor of ultrasound negative in a postmenopausal woman with hirsutism and hyperandrogenism: A case report.

RATIONALE: The incidence of severe hyperandrogenism associated with masculinity in women is very low. While rare and difficult to diagnose, androgen secreting tumors should be suspected in women with hyperandrogenism and hirsutism, especially in the postmenopausal population. Herein we present one case of ovarian Leydig cell tumor (LCT) with markedly elevated serum testosterone levels and frank hirsutism. PATIENT CONCERNS: A 60-year-old woman, presented with increased hair growth and androgenic alopecia and the hormonal laboratory examination showed that she had elevated serum testosterone level and normal dehydroepiandrosterone sulfate (DHEAS), androstenedione, 17- hydroxyprogesterone, cortisol and thyroid stimulating hormone (TSH). DIAGNOSES: The diagnosis of possible testosterone secreting tumor was performed when pelvic computed tomography (CT) and magnetic resonance image (MRI) showed a right adnexal mass of 15mm×16mm indicative of sex cord- stromal tumors. INTERVENTIONS: The patient received laparoscopic total abdominal hysterectomy and bilateral salpingo-oophorectomy. OUTCOMES: After operation, testosterone got back to the normal level and clinical symptoms subsided. LESSONS: It is common that postmenopausal androgen excess is a state of relative or absolute androgen excess originating from the adrenal gland and/or ovaries. In either case, doctors need to assess such patients and exclude relatively rare potential causes of tumors. Any woman who has hirsutism or frank evidence of markedly increased testosterone should exclude this kind of possibility of androgen producing tumors. It is possible to determine the origin of androgen hypersecretion with the severity of symptoms, the extent of androgen excess, and the relevant imaging studies. Since LCT are rare ovarian sex-cord stromal tumors, it can be beneficial for diagnosis with careful research of patient history of the defeminization followed by virilization, and a CT and MRI image.

Oncogenic Role of THOR, a Conserved Cancer/Testis Long Non-coding RNA.

Large-scale transcriptome sequencing efforts have vastly expanded the catalog of long non-coding RNAs (lncRNAs) with varying evolutionary conservation, lineage expression, and cancer specificity. Here, we functionally characterize a novel ultraconserved lncRNA, THOR (ENSG00000226856), which exhibits expression exclusively in testis and a broad range of human cancers. THOR knockdown and overexpression in multiple cell lines and animal models alters cell or tumor growth supporting an oncogenic role. We discovered a conserved interaction of THOR with IGF2BP1 and show that THOR contributes to the mRNA stabilization activities of IGF2BP1. Notably, transgenic THOR knockout produced fertilization defects in zebrafish and also conferred a resistance to melanoma onset. Likewise, ectopic expression of human THOR in zebrafish accelerated the onset of melanoma. THOR represents a novel class of functionally important cancer/testis lncRNAs whose structure and function have undergone positive evolutionary selection.

[Immunomodulatory effects of human amniotic versus bone marrow-derived mesenchymal stem cells on peripheral blood T lymphocytes in vitro].

OBJECTIVE: To compare the immunomodulatory effects of human amniotic mesenchymal stem cell (hAMSCs) and human bone marrow mesenchymal stem cells (hBMSCs) on peripheral blood T lymphocytes in an in vitro co-culture system. METHODS: hAMSCs and hBMSCs isolated using enzymatic digestion and Ficoll-Hypaque density gradient centrifugation, respectively, were culture-expanded in vitro to obtain the 4th-generation cells. The two MSCs were co-cultured separately with human peripheral blood mononuclear cells stimulated with phytohemagglutinin (PHA-PBMSC) to investigate the changes in T lymphocyte subsets using flow cytomety and the production of interleukin-2 (IL-2) and IL-10 by the T lymphocytes using enzyme-linked immunosorbent assay (ELISA). RESULTS: Co-culture with either hAMSCs or hBMSCs significantly increased the proportions of Treg, Th2 and Tc2 and decreased Th1 and Tc1 cell subsets in the PBMCs as compared with the PBMCs cultured alone (P<0.05), and the changes in the PBMCs were similar between the two co-culture systems (P>0.05). In both of the two co-culture systems, IL-2 production by the lymphocytes was significantly lowered (P<0.05) and IL-10 production was significantly increased (P<0.05) as compared with their levels in the PBMCs cultured alone; no significant difference was found in IL-2 or IL-10 levels between the two co-culture systems (P>0.05). CONCLUSION: The MSCs derived from human amnion and bone marrow have similar immunomodulatory effects on the T lymphocytes, suggesting the possibility of using hAMSCs in the treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

A case report of mediastinal ectopic parathyroid adenoma presented as parathyroid crisis localized by SPECT/CT.

INTRODUCTION: Parathyroid crisis due to ectopic parathyroid adenomas can pose diagnostic and management challenges, since it is quite rare in clinical practice. CLINICAL FINDINGS/PATIENT CONCERNS: A 67-year-old Chinese male presented as a parathyroid crisis due to an ectopic mediastinal parathyroid adenoma with his serum calcium and PTH markedly increased in short time. An ultrasonography and computed tomography (CT) scan of the neck did not reveal any parathyroid adenoma. Thoracic CT detected a contrast-enhanced mass in the mediastinum. Although the ectopic location is difficult to appreciate on anterior planar technetium-99m-sestamibi scintigraphy views but has been accurately localized with single photon-emission computed tomography/computed tomography. After fluid resuscitation, loop diuretic, and calcitonin treatment, a thoracoscope surgery was performed. The histopathology of the mediastinal nodule was consistent with a parathyroid adenoma. Hypocalcemia due to hungry bone syndrome occurred after surgery and was resolved quickly with large-dose calcium and calcitriol supplementation. He is asymptomatic and has normal serum calcium and PTH levels on regular follow-up. DIAGNOSES: The ultrasonography, CT, sestamibi, and single photon-emission computed tomography/computed tomography provide limited sensitivity in the detecting ectopic parathyroid adenomas alone. The combination of these techniques has incremental value in localizing ectopic parathyroid adenomas over either technique alone. CONCLUSION: Any parathyroid crisis without parathyroid adenoma in the neck should alert physicians to search for ectopic locations through combination of imaging techniques.