Accidental conus medullaris injury following combined epidural and spinal anesthesia in a pregnant woman with unknown tethered cord syndrome

In most adults, the conus medullaris ends at around the inferior margin of the first lumbar （L1） vertebral body.However, location of terminus of the conus medullaris is variable and even extends more distally in patients with diseases such as tethered cord syndrome （TCS）. Here, we reported a conus medullaris injury following combined spinal and epidural anesthesia （CSEA） in a pregnant woman with unknown TCS.

C634Y mutation in RET-induced multiple endocrine neoplasia type 2A:A case report

BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.

MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

Molecular diagnostic approaches in detecting rearranged during transfection oncogene mutations in multiple endocrine neoplasia type 2

Different types of neuroendocrine cancer,including medullary thyroid cancer(MTC)and thyroid C-cell hyperplasia,are part of multiple endocrine neoplasia type 2(MEN2).A proto-oncogene mutation of the rearranged during transfection(RET)gene changes the way that receptor tyrosine kinases work.Multiple endocrine neoplasia,a pathological condition,involves these kinases.When the RET protooncogene changes,it can cause endocrine adenomas and hyperplasia to happen at the same time or one after the other.Pheochromocytoma,medullary thyroid carcinoma,and hyperparathyroidism,alone or in combination,are present in MEN2A patients.Some patients may also have skin lichen amyloidosis or Hirschsprung's disease.Patients with MEN2A often present with MTC.MTC is aggressive and has the worst prognosis,as most patients exhibit lymph node metastasis.MTC is one of the important causes of death in patients with MEN2A.RET mutation analysis aids in identifying MEN2A symptoms and monitoring levels of calcium,thyroid hormones,calcitonin,normetanephrine,fractionated metanephrines,and parathyroid hormone.The earlier diagnosis of MTC significantly improves survival and prompts better management of MEN2A.In this editorial,we will discuss the significance of molecular diagnostic approaches in detecting RET oncogene mutations in MEN2A.

甲状腺髓样癌术后多脏器转移1例

1临床资料患者,男,58岁,于32年前发现左侧颈部肿物就诊于当地医院,穿刺活检为甲状腺髓样癌(medullary thyroid carcinoma,MTC),遂在外院行甲状腺左侧叶切除并淋巴结清扫,术后给予甲状腺素片治疗并规律复查;于18年前发现右侧肾上腺转移,在外院行右侧肾上腺切除术,术后未给予抗肿瘤治疗,继续规律复查。

Clinical Factors Influencing the Neurological Recovery of Patients Operated for a Cervical Myelopathy at the Teaching Hospital of Bouake

Introduction: Cervical myelopathy is the most common myelopathy among people over 50 of age. Cervicosteoarthritis is the main etiology. The purpose of this work was to identify clinical factors that may influence neurological recovery in patients undergoing surgery for cervical myelopathy in our work setting. Materials and Methods: We performed a retrospective analytical study on patients operated on for cervical myelopathy at the teaching hospital of Bouake. The logistic regression model was used to identify the factors influencing post-operative neurological recovery. Results: 50 patients’ records have been enrolled in this study. The mean age of our patients was 53 years with extremes ranging from 25 to 78 years and 39 of our patients (62%) were male. The mean modified pre-operative JOA score was 11.62 versus 12.94 after the surgery. Age, sex, the number of levels operated on and the duration of the evolution of the signs showed no significant link with neurological recovery. Preoperative mild myelopathy (P = 0.0491) and post-operative functional rehabilitation (P = 0.0459) were identified as factors favouring neurological recovery after cervical myelopathy surgery. Conclusion: The good conducts of functional rehabilitation sessions as well as a mild myelopathy were the factors favouring neurological recovery.

Comparison between the Medullary Indexes of Hairs from Apodemus orestes and A.draco,with Discussion about the Taxonomic Status of A.orestes

The taxonomic status of long-tailed field mouse (Apodemus orestes) is still uncertain up to now.Some scholars regarded it as a subspecies or a synonym of dragon field mouse (A.draco),while other scholars considered it a valid species.In the study,five specimens of adult long-tailed field mouse,dragon field mouse and Chevrier's field mouse (A.chevrieri) (as a contrast) were chosen respectively.After treated,with the eyepiece micrometer in the inverted microscope,we made measurements of the widths of hairs and medullas and then calculated the medullary indexes of straight guard hairs from around the mouth,head,back,abdomen and forelimb of each species.The results indicate that,viewing at each of the five parts and the mixture of the five parts,there are no significant differences between A.orestes and A.draco,Significant differences can be found between A.orestes & A.chevrieri and A.draco & A.chevrieri though.The standpoint that A.orestes was listed as a valid species is not supported by this study.

“心型”延髓内侧梗死2例报告

延髓内侧梗死（medial medullary infarction,MMI）最先由Spiller于1908年报道,临床非常少见,占椎基底动脉系统梗死的1%以下,而双侧MMI则更为罕见,首例由Davison于1937年报道。有文献报道86例延髓内侧梗死中,双侧MMI梗死仅12例[1]。双侧MMI主要表现为四肢瘫、延髓性麻痹、双侧深感觉障碍,重者出现呼吸衰竭。

Investigation of Calcitonin and Calcitonin Gene-related Peptide in 88 Cases of Medullary Thyroid Carcinoma

Objective： To investigate the changes of calcitonin （CT） and calcitonin gene-related peptide （CGRP） in patients with medullary thyroid carcinoma （MTC）. Methods： Fifty-eight cases of MTC were selected and the relationship between the CT levels and metastasis was investigated. The immunohistochemical method was used to detect the expression of CT and CGRP in the 58 samples of MTC tissues. The CT and CGRP in 30 newly diagnosed MTC inpatients were measured before operation and in the first few days after operation using a radioimmunoassy. Results： （1） The rate of residual tumor had a significant difference between the normal serum CT group one month after operation and the elevated group at the same period （P〈0.01）. （2） Immunohistochemical study revealed the positive rate of CT was about 98%, and that of the CGRP was 87.8%. （3） Part of the patients had an elevated CGRP levels while CT levels was normal. （4） The serum CT levels were decreased to a stable range one week after operation. Conclusion： CT is a useful index to evaluate the efficacy of surgical treatment. The measurement of serum CGRP is helpful in the diagnosis of MTC, especially for those whose preoperative CT levels are normal.

髓质海绵肾影像诊断(附1例报告)

髓质海绵肾(medullary sponge kidney,MSK)很少见,国内报道不多。

甲状腺髓样癌18例临床病理分析

甲状腺髓样癌（medullary thyroid carcinoma,MTC）是来自于甲状腺滤泡旁细胞（C细胞）的一种恶性肿瘤,又称C细胞癌,属APUD系统肿瘤。MTC是甲状腺较为少见的一种癌型,其发病、诊断和治疗都独具特点。本文现报道18例MTC,结合文献复习并探讨其临床病理特征、诊断、鉴别诊断与治疗,以提高对该肿瘤的认识,避免误诊。

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia(paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome(ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma(MTC).

A quantitative study on changes of the myelinated fibers in the cerebral cortex of cortical dysplasia rats

An animal model of cortical dysplasia was established through X-ray irradiation induced subcortical heterotopic nodules in rats. Transmission electron microscopy detection of the ultrastructure and the stereology examination showed that there was a significant decrease in cerebral white matter and hippocampal volume, the total volume, volume density, length density and total length of the myelinated fibers in the white matter of cortical dysplasia rats. Subcortical heterotopic nodules of the hippocampal CA1 region and synaptic number density in the CA3 region were reduced compared with normal rats. Our experimental findings indicate that erosed subcortical heterotopic nodules, decreased total length of myelinated nerve fibers and demyelination directly lead to a reduction of white matter volume.

Is new American Thyroid Association risk classification for hereditary medullary thyroid carcinoma applicable to Chinese patients? A single-center study

Objective: The American Thyroid Association (ATA) proposed a new risk classification for hereditary medullary thyroid carcinoma (MTC) in 2015. This study aimed to assess whether the new guidelines are suitable for the Chinese population, and reported our experience on prophylactic thyroidectomy. Methods: A total of 73 patients from 22 families were screened as rearranged during transfection (RET) mutation carriers from 2010 to 2016 in Cancer Hospital, Chinese Academy of Medical Science; the medical history for each patient was collected. Based on the initial treatment, we identified the risk factors for poor prognosis by univariate and multivariate logistic regression. Then, 4 RET mutation carriers were enrolled for prophylactic thyroidectomy, and their pathological data and follow-up outcomes were recorded. Results: In univariate and multivariate logistic regression analyses, age at initial surgery and risk classification were significant risk factors for stage III/IV hereditary MTC at initial diagnosis. The likelihood was increased by 11.6% per year of age at initial surgery [95% confidence interval (95% CI), 1.040-1.198; P=0.002). It was 7.888 times more likely to have III/IV stage disease for ATA highest risk patients, compared to ATA moderate risk individuals (95% CI, 1.607-38.717; P=0.003). Postoperative pathological results showed all 4 multiple endocrine neoplasia type 2A (MEN2A) patients had C-cell hyperplasia (CCH); multifocal malignancies were detected in 3 of them. All 4 patients were cured biochemically, and none developed permanent hypoparathyroidism. Conclusions: In Chinese individuals, hereditary MTC aggressiveness is in line with the new ATA risk classification. Germline RET gene mutation carriers should undergo prophylactic thyroidectomy according to basal serum calcitonin levels.

RANKL-RANK interaction in immune regulatory systems

The interaction between the receptor activator of NF-κB ligand(RANKL)and its receptor RANK plays a critical role in the development and function of diverse tissues.This review summarizes the studies regarding the functions of RANKL signaling in immune regulatory systems.Previous in vitro and in vivo studies have indicated that the RANKL signal promotes the survival of dendritic cells(DCs),thereby activating the immune response.In addition,RANKL signaling to DCs in the body surface barriers controls self-tolerance and oral-tolerance through regulatory T cell functions.In addition to regulating DC functions,the RANKL and RANK interaction is critical for the development and organization of several lymphoid organs.The RANKL signal initiates the formation of clusters of lymphoid tissue inducer cells,which is crucial for lymph node organogenesis.Moreover,the RANKL-RANK interaction controls the differentiation of M cells,specialized epithelial cells in mucosal tissues,that take up and transcytose antigen particles to control the immune response to pathogens or commensal bacterium.The development of epithelial cells localized in the thymic medulla(m TECs)is also regulated by the RANKL-RANK signal.Given that the unique property ofm TECs to express a wide variety of tissue-specific selfantigens is critical for the elimination of self-antigen reactive T cells in the thymus,the RANKL-RANK interaction contributes to the suppression of autoimmunity.Future studies on the roles of the RANKL-RANK system in immune regulatory functions would be informative for the development and application of inhibitors of RANKL signaling for disease treatment.

The genetic framework for development of nephrolithiasis

Over 1%-15% of the population worldwide is affected by nephrolithiasis,which remains the most common and costly disease that urologists manage today.Identification of atrisk individuals remains a theoretical and technological challenge.The search for monogenic causes of stone disease has been largely unfruitful and a technological challenge;however,several candidate genes have been implicated in the development of nephrolithiasis.In this review,we will review current data on the genetic inheritance of stone disease,as well as investigate the evolving role of genetic analysis and counseling in the management of nephrolithiasis.

Integrated DNA-based/biochemical screening for early diagnosis of multiple endocrine neoplasia type 2A (MEN2A)

Multiple endocrine neoplasia type 2A （MEN2A）, a subtype of MEN2, is characterized by medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism. A Han Chinese pedigree with MEN2A was investigated following confirmation of the proband＇s diagnosis by pathological findings and DNA/biochemical screening. DNA samples from 4 other family members were collected and exon 5, 8, 10, 11, 13, 16 and 18 of the RET proto-oncogene were sequenced and then analyzed. A missense mutation of TGG （Trp） to TGC （Cys） at codon 634 （the classic MEN2A mutation） in exon 11 of the RET gene was detected in 3 family members, including the proband. Sequencing data were compared with the human gene mutation database. Elevated serum calcitonin level was detected initially; medullary thyroid carcinoma was revealed in the 3 cases and adrenal pheochromocytoma was also found in the proband. Elective operations were successfully performed on the adrenal and thyroid glands because of pheochromocytoma and medullary thyroid carcinoma. Our case study confirms that integrated DNA-based/biochemical screening is crucial for early diagnosis of MEN2A and is helpful in the screening of their relatives. In addition, DNA-based screening may occasionally uncover a previously unknown RET sequence.

Do you want to participate in a clinical study as a healthy control?-Risk or benefit?

A healthy woman volunteered to participate as "healthy control" in a study.An increased level of procalcitonin(PCT) was detected and remained elevated on follow-up measurements.As calcitonin levels were elevated as well,thyroid ultrasound was performed which revealed nodes in both thyroid lobes,one of them showing metabolic activity in positron emission tomography-computed tomography scan.To exclude a malignant thyroid cancer despite the negative findings in a fine needle aspiration the patient underwent thyroidectomy and a medullary thyroid carcinoma(MTC) was detected in the right lobe.MTC is a rare endocrine tumor with a poor prognosis once having spread,therefore early detection remains a priority for the outcome.Screening parameter is serum calcitonin,in absence of infection the pro-hormone PCT can be used as a screening parameter as well with high sensitivity.

THE MORPHOLOGICAL MEASURE OF THE TIBIAL MEDULLARY CAVITY AND ITS SIGNIFICANCE

Objective To provide morphological reference for the designing of the intramedullary nail fixation which suitable for Chinese by investigating the morphological characteristics of tibial medullary cavity. Methods The morphological parameters of the 113 normal adult tibiale were measured on the X-ray photographs with the image analysis software. Results The total lengths of tibial medullary cavities were 299.49±11.03 mm(male) and 274.60± 6.77 mm(female), and the lengths of the narrow part were 66.36±3.90 mm(male) and 51.57±3.92mm(female). The end-points of narrow part were about 29.9 mm(male) and 26.09 mm(female)below the midpoints of medullary cavities. The radians of the longitudinal axes of medullary cavities were 2.53±1.27°(male) and 2.57±1.16°(female). The proximal opening K were 9.47±2.71(male) and 8.59±2.46(female). The distal opening K were 8.21± 2.93(male)and 7.65±2.87(female). Conclusion The morphology of tibial medullary cavity, the characteristic variety of radian and the opening K were very important references for designing the Chinese intramedullary nail fixation.

Clinical and functional comparison of endoprosthetic replacement with intramedullary nailing for treating proximal femur metastasis

Objective： To evaluate the clinical and functional outcomes of modular endoprosthetic replacement （EPR） compared to proximal femur intramedullary nailing （IMN） for the treatment of proximal femur metastases. Methods： We retrospectively studied the records of patients with proximal femur metastatic lesions treated with surgical stabilization between January 2007 and December 2014 in terms of operation time, blood loss, postoperative score, soreness, Karnofsky performance score （KPS） and survival time. Results： There were 34 patients treated with surgical stabilization. The mean follow-up period was 12.1~8.6 months （range： 10-47 months）. Thirteen were treated with EPR and 21 were stabilized with IMN （20 males, 14 females; mean age： 68.7 years）. The median survival time was 11.0 months for both groups （P=0.147）. The operation time, blood loss and Harris score of IMN group were lower than those of EPR group （P=0.001, P=0.001, P=0.002, respectively）. Conclusions： Both EPR and IMN for treating proximal femur metastasis achieved effective clinical outcomes. Therefore, the suitable surgical methods depended on the general conditions and medical requirements of patients, as well as the technical advantages of the doctor.