Anesthesia Management in Hereditary Pheochromocytoma and Paraganglioma:Updated Insights into Clinical Features and Perioperative Care

Approximately 40% of pheochromocytoma and paraganglioma(PPGL) cases are familial, typically presenting earlier with more complex symptoms. This paper synthesizes literature and guidelines to inform on clinical characteristics and perioperative care for PPGL. Pheochromocytoma in von Hippel-Lindau(VHL) disease exhibits heightened secretion activity without significant perioperative hemodynamic changes. Tumors in multiple endocrine neoplasia type 2(MEN2) have a stronger endocrine function, which may induce hemodynamic fluctuations during surgery. Therefore, pheochromocytoma screening is essential at all stages of MEN2. Neurofibromatosis type 1(NF1) often presents multisystem lesions and can result in difficult airway. Pheochromocytoma should be evaluated when NF1 patients present hypertension. Pheochromocytoma and paraganglioma type 5 may present multiple lesions of pheochromocytoma or paraganglioma. In summary, hereditary PPGLs may present with severe lesions in other systems, beyond tumor function. A multi-disciplinary team(MDT) approach is often invaluable in perioperative management.

Genetic Study on JS399-19 Resistance in Hyphal Fusion of Fusarium graminearum by Using Nitrate Nonutilizing Mutants as Genetic Markers

Twenty-two nitrate nonutilizing （nit） mutants were recovered from five wild-type isolates of Fusarium graminearum and fifty nit mutants were recovered from three JS399-19-resistant mutants of F. graminearum cultured on MMC medium. Some biological properties were compared between nit mutants and their parental isolates. The results showed that there were no significant differences in growth rate, cultural characters or pathogenicity between JS399-19-resistant nit mutants and their parental isolates. But the conidial production and the sexual reproduction ability changed to some extent. There was no cross resistance toward chlorate and JS399-19 in F. graminearum and the resistance could be stable through 20-time subcultures. Therefore, the nit could be used as a genetic marker for studying the genetics of JS399-19 resistance in E graminearum, which was used to study JS399-19 resistance transferability in hyphal fusion. Resistance in JS399-19 could not be transferred by hyphal fusion or could be transferred with low chance between two compatible isolates, which would delay the development of JS399-19 resistance in the field.

A Preliminary Study on Conservation Genetics of Endangered Vatica guangxiensis (Dipterocarpaceae)

运用 2 0个 10碱基随机引物 ,对中国龙脑香科 (Dipterocarpaceae)特有的珍稀濒危植物版纳青梅 (VaticaguangxiensisX .L .Mo)进行了RAPD多态性分析。 3个自然居群和 1个迁地保护居群 (分布于云南和广西 )共扩增出2 31个位点 ,多态位点所占比例 (PPB)为 5 3.6 8% ;观察等位基因数na =1.5 36 8,有效等位基因数ne =1.2 878,Nei基因多样性指数h为 0 .16 86 ,居群内的遗传多样性水平较低。基于AMOVA和POPGENE的结果均表明居群内的遗传变异大于居群间的遗传变异。居群内的遗传变异为 5 5 .0 9% ,居群间的变异为 44 .91% (AMOVA) ;基因分化系数Gst为 0 .3746 (POPGENE) ,表明居群间存在高水平的遗传分化。研究结果对该濒危植物的保护有重要意义。考虑到低水平的遗传多样性和高水平的居群分化 ,通过居群间种子和幼苗的交换来促进基因流是可行的保护方案。迁地保护居群 (ML)不具最高的遗传多样性 ,表明为了保护此濒危物种的全部遗传变异 。

Migraine as a sex-conditioned inherited disorder: evidences from China and the world

Migraine is a complex and heterogeneous disorder. Although several genetic models has been proposed including autosomal-dominant/autosomal recessive, sex-linked, sex-limited, mitochondrial, and multi-gene, none of these models can well-explain the transmission of the disease. We hypothesied that migraine is a sex-conditioned inherited disorder （autosomal dominant in females and autosomal recessive in males）. This hypothesis is supported by the evidence such as the locations of genes associated with familial hemiplegic migraine, possibly ＂typical＂ migraine as well （dominantly on chromosome 19p, lq, and 2q）, male：female ratio of prevalence （1：2-1：4）, the mostly youth-onset, the provocation by the contraceptives, the induction by menstruation, and the self-limitation after menopause. Female sex-hormones appear to be the key contributor to a higher prevalence of migraine in female. Socio-environmental factors may also play an important role.

Comparison of Genetic Diversity Between Local Cultivated Aromatic and Non-aromatic Rice in Yunnan Province

[ Objective] The genetic diversity of the local cultivated aromatic rice and non-aromatic rice in Yunnan Province were compared to provide further genetic resources for breeding practice. [Method] Genetic diversity of 10 aromatic rice and 45 non-aromatic rice were analyzed by 64 SSR primers covered on 12 rice chromosomes. [ Result] Per locus 5.44 and 7.98 alleles in average were detected, ranging from 2 to 12 and from 2 to 17 in aromatic and non-aromatic rice, respectively. Average genetic multiplicity index（Hs） was 0.46 and 0.67 respectively. The average polymorphism information content （PIC） was 0.43 and 0.58 in aromatic and non-aromatic rice respectively. [ Conclusion] The results indicated that genetic diversity was higher in non-aromatic rice than in aromatic rice.

抗原刺激会增加基因翻译出错率

本刊讯 国立过敏与传染病研究所病毒病实验室、遗传性学系、生物与化学系、BenMay研究所．芝加哥大学医学院的科学家们在蛋白转录翻译的研究过程中发现了新的机制，相关成果文章Innate immune and chemically triggeredo xidative stress modifies translational fidelity公布在最新一期的Nature杂志上。

Family and twin studies in inflammatory bowel disease

Studies examining the inheritance of inflammatory bowel disease （IBD） within different family groups have been the basis for recent molecular advances in the genetics of IBD. The derived heritability in Crohn＇s disease （CD） is higher than in many other complex diseases. The risk of IBD is highest in first-degree relatives of a CD proband, but first-degree relatives of a proband suffering from ulcerative colitis （UC） and more distant relatives are also at increased risk. Disease concordance rates in IBD have been examined in multiplex families and in three large European twin studies.

POLYMORPHISM OF ANGIOTENSIN CONVERTING ENZYME GENE AND GENETIC SUSCEPTIBILITY TO ASTHMA WITH FAMILIAL AGGREGATION

Angiotensin converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness. Methods. A case control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho provocation and pulmonary function tests were performed in all asthmatics. Results. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P<0 05; odd ratio 4 98). Anhigher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67%vs 33%, P<0 05; odd ratio 3 8). Accordingly, the mean values of FEV 1% and FEV 1/FVC were higher in asthmatics carrying non DD alleles than patients with DD genotype (73 78% vs 56 56%, P<0 05; 79 19% vs 69 29%, P<0 05, respectively). Conclusion. These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.

Novel mechanisms in functional dyspepsia

Functional dyspepsia （FD） is a highly prevalent but heterogeneous disorder in which multiple pathogenetic mechanisms are involved. Although there are many studies that have investigated various pathophysiologic mechanisms, the underlying casual pathways associated with FD remain obscure. The currently proposed pathophysiologic mechanisms associated with FD include genetic susceptibility, delayed as well as accelerated gastric emptying, visceral hypersensitivity to acid or mechanical distention, impaired gastric accommodation, abnormal fundic phasic contractions, abnormal antroduodenal motility, acute and chronic infections, and psychosocial comorbidity. A greater understanding of the abnormalities underlying FD may lead to improved management. The aim of this editorial is to provide a critical overview of current pathophysiologic concepts in functional dyspepsia.

Concomitant autoimmune and genetic pancreatitis leads to severe inflammatory conditions

Chronic pancreatitis characterized by an early onset should be extensively investigated including the search for a mutation of the PRSS1, SPINK-1 or CFTR genes and potential features of autoimmune pancreatitis. We here describe a case of chronic pancreatitis with an onset at a very young age in which a mutation of the PRSS1 and several features of autoimmune pancreatitis were identified.

Identification of Rhodiola species by using RP-HPLC

An approach was established using RP-HPLC (reversed-phase high-performance liquid chromatography) to identify ten species of Rhodiola, R. coccinea A. Bor, R. junggarica C.Y. Yang et N.R. Cui spn., R. heterodonta A. Bor, R. linearifolia A. Bor, R. pamiro alaiucm A. Bor, R. kaschgarica A. Bor, R. litwinowii A. Bor, R. gelida schrenk, R. rosea L. and R. quadrifide Fisch et Mey collected from the Tianshan Mountains areas of China. Chromatograms of alcohol-soluble proteins, generated from these ten Rhodiola spp. were compared. Each chromatogram of alcohol-soluble proteins came from a single seed of one wild species only. The results showed that when using a Waters Delta Pak. C18, 5 μm particle size reversed phase column (150 mm×3.9 mm), a linear gradient of 22%?55% solvent B with a flow rate of 1 ml/min and a run time of 67 min, the chromatography gave optimum separation of Rhodiola alcohol-soluble proteins. Chromatogram of each species was different and could be used to identify those species. Cluster analysis of genetic similarity coefficients of 37% to 60% showed a medium degree of genetic diversity among the species in these eco-areas. Cluster analysis showed that the ten species of Rhodiola can be divided into four clusters and yielded the general and unique biochemical markers of these species. RP-HPLC was shown to be a rapid, repeatable and reliable method for Rhodiola species identification and analysis of genetic diversity.

Amelanotic malignant melanoma of the esophagus:Report of two cases with immunohistochemical and molecular genetic study of KIT and PDGFRA

The author reports herein two cases of amelanotic malignant melanoma of the esophagus. Case 1 is an 87-year-old woman who was admitted to our hospital because of nausea and vomiting. Endoscopic examination revealed an ulcerated tumor of the distal esophagus, and a biopsy was taken. The biopsy showed malignant polygonal and spindle cells. No melanin pigment was recognized. Immunohistochemically, the tumor cells were positive for melanosome （HMB45）, S100 protein, KIT and Platelet derived growth factor receptor-α （PDG- FRA）. The patient was treated by chemotherapy and radiation, but died of systemic metastasis 12 mo after the presentation. Case 2 is a 56-year-old man presenting with dysphagia. Endoscopic examination revealed a polypoid tumor in the middle esophagus, and a biopsy was obtained. The biopsy showed malignant spindle cells without melanin pigment. Immunohistochemically, the tumor cells were positively labeled for melanosome,S100 protein, KIT and PDGFRA. The patient refused operation, and was treated by palliative chemotherapy and radiation. He died of metastasis 7 mo aEer the admission. In both cases, molecular genetic analyses of gene （exons 9, 11, 13 and 17） and PDGFRA gene （exons 12 and 18） were performed by the PCR direct sequencing method, which showed no mutations of KIT and PDGFRA genes. This is the first report of esophageal malignant melanoma with an examination of the expression of KIT and PDGFRA and the mutational status of K/T and PDGFRA genes.

Genetic epidemiology of primary sclerosing cholangitis

The aetiology of primary sclerosing cholangitis (PSC) is not known. A more than 80-fold increased risk of PSC among first-degree relatives emphasizes the importance of genetic factors. Genetic associations within the human leukocyte antigen (HLA) complex on chromosome 6p21 were detected in PSC 25 years ago. Subsequent studies have substantiated beyond doubt that one or more genetic variants located within this genetic region are important. The true identities of these variants,however,remain to be identified. Several candidate genes at other chromosomal loci have also been investigated. However,according to strict criteria for what may be denominated a susceptibility gene in complex diseases,no such gene exists for PSC today. This review summarises present knowledge on the genetic susceptibility to PSC,as well as genetic associations with disease progression and clinical subsets of particular interest (inflammatory bowel disease and cholangiocarcinoma).

Cytogenetic and Clinical Analysis of 340 Chinese Patients with Primary Amenorrhea

Objective To analyze the relationship between karyotypes and clinic features of patients with primary amenorrhea.Methods G banding was done for 340 patients with primary amenorrhea to facilitate individual chromosome identification,and if specific staining for certain portions of the chromosome was necessary,C banding was used.The clinical data were recorded by physical examination and ultrasound scanning.Results Karyotype analysis of the 340 patients revealed that 180(52.94%) patients had normal female karyotypes and 160(47.06%) patients had abnormal karyotypes.The abnormal karyotypes included abnormal X chromosome(150 patients),mosaic X-Y chromosome(4 patients),abnormal autosome(5 patients),and X-autosome translocation(1 patient).The main clinical manifestations in patients with primary amenorrhea were primordial or absent uterus(95.9%),invisible secondary sex features(68.8%),little or absent ovary(62.6%),and short stature(30.0%).The incidence of short stature in patients with X chromosome aberration(46%,69/150) was significangly higher that in patients with 46,XX(9.44%,17/180) as well as 46,XY(6.67%,3/45;χ2=146.25,P=0.000).All primary amenorrhea patients with deletion or break-point at Xp11.1-11.4 were short statures.Conclusions One of the main reasons of primary amenorrhea is choromosome abnormality,especially heterosome abnormality.It implies the need to routinely screen chromosomal anomalies for such patients.There might be relationship between Xp11.1-11.4 integrity and height improvement.

Etiology for Degenerative Disc Disease

Degenerative disc disease is a multifaceted progressive irreversible condition and an inevitable part of aging,which has been found to be a contributing factor for low back pain and might cause radiculopathy,myelopathy,spinal stenosis,degenerative spondylolisthesis,and herniations.Its etiology is complex and multifactorial.Although genetics influence more dominant,the occupational and mechanical influences still persist as a major risk factor.This review emphasizes up-to-date knowledge regarding etiology of disc degeneration with special consideration on occupational,lifestyle factors,and genetic polymorphisms.

Charaterization of Citrus Hybrid ＂Huangguogan＂ through the Combination of Morphological and Molecular Markers

Huangguogan, an obvious Citrus hybrid, is suitable for transportation and export and ripens in March or April. Because of late season, it may playa significant role in fruit market. However, its origin is still unconfirmed. The aim of this study was to clarify the possible parentage of Huangguogan via the combination of morphological and molecular markers including simple sequence repeat （SSR） and chloroplast simple sequence repeat （cpSSR）. Analysis of morphological traits including leaf stalk length, phylliform index and fruit shape index indicated that Huangguogan had similarities in morphology with Sweet orange. The SSR Cluster Analysis showed that Huangguogan was clustered together with Hongju tangerine and revealed -80% genetic similarity. They illustrated a close genetic distance between Huangguogan and Hongju tangerine. In addition, the bands of2 polymorphic cpSSR were identical in Huangguoggan and Sweet orange. Consequently, it is likely that its female parentage was the sweet orange （Citrus sinensis （L.） Osbeck） and its male parentage was the tangerine （Citrus reticulata Blanco）.

Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families:Implications for genetic testing

AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplifi cation (MLPA). RESULTS: Eighteen germline mutations (50%) were identifi ed, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the defi nite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam Ⅰ/Ⅱ criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family.CONCLUSION: Our study describes for the f irst time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population.

Genetic and molecular changes in ovarian cancer

Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications.However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.

Human biochemical genetics: an insight into inborn errors of metabolism

Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.