Mismatch repair protein deficiency assessed by immunohistochemistry in sporadic colorectal carcinoma

Context: Globally, colorectal carcinoma (CRC) ranks the third most commonly diagnosed malignant disease, one of the leading causes of cancer deaths. Aims: To study the spectrum of clinicopathological characteristics of sporadic colorectal carcinoma and to assess mismatch repair gene deficiency by the expression pattern of the proteins assessed by immunohistochemistry. Setting and Design: Observational study conducted in a tertiary care hospital in West Bengal. Materials and Methods: Fifty-two surgically resected specimens of CRC received from January 2018 to May 2019 were studied for clinical, morphological, MSI status. Statistical Analysis Used: IBM SPSS 23. Results: A total of 50% of the cases belonged to younger and 50% to the older population, with male predominance being 53.8%. The most common histologic type was adenocarcinoma (88.5%). The majority was found to be well-differentiated carcinoma (50%). The majority cases were of the T3 stage accounting to 38.5%. A total of 24 out of 52 cases (46.15%) had an absent expression of at least one mismatch repair (MMR) protein. A significant correlation was found between the young age group and microsatellite instability (MSI) with a P value of 0.001. A significant association was found between MSI and tumor differentiation with P value of 0.018. A significant association was found between MSH6 and histological type with P value of 0.012. A significant association was found between MSI and tumor stage with P value of 0.032. Conclusions: This study shows a significantly higher number of sporadic colon cancers involving the young age group, and younger cases showed significant association with MSI. This alarming trend needs validation by studies involving larger populations and can be helpful prognostically as well as in formulating chemotherapeutic regimens.

BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer

Background & objectives: Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George’s Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. Methods: 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. Results: BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (?3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Interpretation & conclusions: Study results highlight the concept of “BRCAness” in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP- ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.

Sporadic Creutzfeldt-Jakob Disease With Slow Progression:Report of One Case / 中国医学科学院学报

Sporadic Creutzfeldt-Jakob disease(sCJD)is a prion-caused degenerative disease of the central nervous system,with the typical clinical manifestation of rapidly progressive dementia.The course of disease is less than 1 year in most patients and more than 2 years in only 2% to 3% patients.We reported a case of sCJD with expressive language disorder and slow progression in this paper.By summarizing the clinical manifestations and the electroencephalograhpy,MRI,and pathological features,we aimed to enrich the knowledge about the sCJD with slow progression.

Effect of human urinary kallidinogenase on cognitive function of SAMP8 mouse model and its mechanism / 中国药理学通报

Aim To study the effect of human urinary kallidinogenase(HUK)on the cognitive function of SAMP8 mouse model and its mechanism. Methods SAMP8 mice were divided intofive groups:SAMP8 group,treatment group(giving 8.75×10-3,1.75×10-2,3.5×10-2,7.0×10-2 HUK),and the SAMR1 vehicle group was used as blank control. Each group was performed Morris water maze to detect spatial cognition. Afterwards the group with the most obvious cognitive improvement(HUK group)was selected for the follow-up experiments. Immunohistochemical detection of ChAT expression in CA3 area was further verified by RtPCR. Western blot was used to detect the expression of PSD95,SYN,BDNF,and pCREB protein. The activity of MPO and the content of IL-1β and IL-18 were determined. Results The passing times in the SAMP8 group was less than that of the SAMR1 group(P<0.05). The passing times of treatment group increased compared with the SAMP8 group(P<0.05 or P<0.01),and the spatial probe time of the target quadrant was shorter(P<0.05 or P<0.01). We conducted follow-up experiments with group d(HUK group). The expression of ChAT positive cells in CA3 area of SAMP8 group was significantly lower than that of SAMR1 group; the expression of positive cells in HUK group significantly increased; RtPCR showed that ChAT expression in SAMP8 group was lower than that in SAMR1 group,and ChAT expression was significantly higher than that in SAMP8 group after HUK treatment. Compared with the SAMR1 group,the levels of IL-1β,IL-18 and MPO activity in the CA3 area of SAMP8 group significantly increased,and the protein expressions of PSD95,SYN,BNDF and pCREB decreased. After HUK treatment,the content of IL-1β,IL-18 and MPO activity decreased,and the expression of PSD95,SYN,BNDF and pCREB increased. Conclusions HUK can improve the spatial cognition of SAMP8 mice. The mechanism may be achieved by promoting the expression of ChAT in CA3 area,reducing the oxidative stress and increasing synapse-related proteins.

Molecular characteristics of Streptococcus suis type 2 from humans in Zhejiang Province / 中华传染病杂志

Objective:To determine the molecular characteristics of Streptococcus suis type 2 (SS2) in Zhejiang Province. Methods:Twenty-nine SS2 sporadic human isolates in Zhejiang Province from Januery 2005 to July 2021 were genotyped by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and minimum core genome (MCG) sequence typing.Results:Among 29 strains, 10 PFGE patterns and three main clusters were obtained by PFGE. Twenty-one (72.41%) of the strains were divided into two main branch groups and the remaining eight (27.59%) showed genetic diversity with the similarity ranging from 49.7% to 94.7%. Three sequence types were obtained from 29 strains by MLST, including ST7 (86.21%(25/29)), ST1 (10.34%(3/29)) and ST25 (3.45%(1/29)). In addition, three genotypes were obtained from 29 strains by MCG, including genotype E (41.38%(12/29)), genotype group 1 (55.17%(16/29)) and genotype group 4 (3.45%(1/29)).Conclusions:Two large clonal groups of highly pathogenic strains of SS2 have been prevalent in Zhejiang Province. A few strains display genetic diversity, indicating genetic variation may exist during transmission.

Rare Variants of Monogenic Cerebral Small Vessel Diseases -Related Genes: A Study in a Cohort of Patients with Cerebral Small Vessel Diseases / 罕见病研究

  Objective  This study aimed at describing the frequency of rare variants of monogenic cerebral small vessel diseases (CSVD) in a cohort of patients with CSVD, and to explore its clinical relevance.  Methods  This study included CSVD patients visiting the Neurology Department of Peking Union Medical College Hospital(PUMCH) from March 2017 to January 2022, collecting their demographic and clinical information and DNA samples for whole-exome sequencing. Descriptive analysis and statistical analysis were conducted exploring the differences between monogenic CSVD-related gene mutation carriers and noncarriers.  Results  A total of 292 patients were included, 51.03% of whom carried one or more rare variants of monogenic CSVD-related genes. The most common rare low-frequency variants were located in the NOTCH3 gene (70 patients, 23.97%), followed by HTRA1 and COL4A1/COL4A2 (22 patients, 7.53%) respectively. Among the subgroup of patients without a family history of stroke (n=176), the frequency of rare variants was as high as 47.16%. Compared with non-carriers, the carriers were diagnosed at a younger age (58.76±13.71 vs. 63.46±13.21, P=0.003). No difference was found in phenotypes among single-SNP carriers, multiple-SNPs carriers, and noncarriers.  Conclusions  The frequency of rare mutation of monogenic CSVD-related genes were relatively high in Chinese CSVD cohort. The most common rare variant was within the NOTCH3, followed by HTRA1 and COL4A1/COL4A2 genes. For CSVD patients of unknown causes, genetic screening should not be neglected even if there is not a family history of the disease.

Sporadic Creutzfeldt-Jakob disease / 中华神经科杂志

Sporadic Creutzfeldt-Jakob disease is a rare condition with a rapid disease course and a mortality rate of 100%. In clinical practice, it is difficult to diagnose, even if consistent conventional laboratory methodologies are used. This article will give a summary on the epidemiology, pathogenesis, clinical manifestations, auxiliary examination, diagnosis and differential diagnosis, management, and prognosis of sporadic Creutzfeldt-Jakob disease.

Carcinoma medular esporádico de tiroides / Sporadic Medullary Thyroid Carcinoma

Introducción: El carcinoma medular de tiroides, representa aproximadamente entre el 5 - 10 por ciento de todos los carcinomas tiroideos, aparece con más frecuencia entre los 25 y 60 años y en el sexo femenino. Se distinguen dos tipos: el esporádico (no hereditario) y el familiar (hereditario). La localización más frecuente es la unión del tercio superior de lóbulo tiroideo con el tercio medio, que es la zona de mayor concentración de células C. Objetivo: Presentar el caso de paciente masculino operado de carcinoma medular de tiroides, tipo esporádico, en la provincia de Cienfuegos. Caso clínico: Paciente masculino de 60 años de edad, piel blanca, que acudió a la consulta; refiere aumento de volumen del cuello acompañado de disfonía y disfagia a los alimentos sólidos. Al examen físico se constató la presencia del nódulo tiroideo. Se le realizó ultrasonido que corrobora la presencia de un nódulo en el lóbulo derecho del tiroides. La biopsia por aspiración con aguja fina informó el nódulo como sospechoso de malignidad. Se le realizó tiroidectomía total, informándose por la biopsia por parafina de la pieza como un carcinoma medular del tiroides. En la actualidad lleva 6 meses de operado con evolución favorable. Conclusiones: El carcinoma medular de tiroides constituye una entidad rara y agresiva más frecuente en los pacientes mayores de 45 años, cuyo tratamiento de elección es la cirugía(AU)

Introduction: Medullary thyroid carcinoma accounts for approximately 5-10 percent of all thyroid carcinomas. It appears more frequently at ages 25-60 years and in females. Two types are distinguished: sporadic (nonhereditary) and familial (hereditary). The most common location is the union of the upper third of the thyroid lobe to the middle third, the area with the highest concentration of C cells. Objective: To present the case of a male patient operated on for medullary thyroid carcinoma, of sporadic type, in the Cienfuegos Province. Clinical case: A 60-year-old male patient of white skin attended consultation. He reported an increase in neck volume accompanied by dysphonia and dysphagia for solid food. The physical examination revealed the presence of the thyroid nodule. Ultrasound was performed, which confirmed the presence of a nodule in the right lobe of the thyroid. Fine needle aspiration biopsy reported the nodule as suspicious for malignancy. A total thyroidectomy was performed, after which, paraffin biopsy of the specimen permitted to report a medullary carcinoma of the thyroid. At present, he has been operating for six months, with favorable evolution. Conclusions: Medullary thyroid carcinoma is a rare and aggressive entity, more frequent in patients over 45 years of age, whose treatment of choice is surgery(AU)

Identification of COL3A1 variants associated with sporadic thoracic aortic dissection: a case-control study / 医学前沿

Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10

Comparison of clinical characteristics between sporadic gastrinoma and multiple endocrine neoplasia type 1-related gastrinoma / 中华胃肠外科杂志

Objective: To compare clinical characteristics of sporadic gastrinoma and multiple endocrine neoplasia type 1 (MEN1)-related gastrinoma. Methods: A retrospective cohort study was conducted. Patients with clinical manifestations of Zollinger-Ellison syndrome, pathological diagnosis as neuroendocrine neoplasm (NEN) and complete clinical and follow-up data were enrolled. Patients with only high gastric acid secretion but without evidence of NEN, or with other concurrent non-NEN tumors were excluded. According to the above criteria, the clinicopathological data of 52 cases of gastrinoma diagnosed from April 2003 to December 2020 in the First Affiliated Hospital, Sun Yat-sen University, were collected. Patients who met the diagnostic criteria of gastrinoma and met one of the following conditions were diagnosed as MEN1-related gastrinoma: (1) the presence of pathogenic mutations in the MEN1 gene confirmed by genetic testing; (2) NENs involving two or more endocrine glands, namely, pituitary, parathyroid, thymic, pancreatic, and adrenal NENs; (3) NEN and at least one first-degree relatives diagnosed as MEN1. The remaining gastrinomas were defined as sporadic gastrinoma. Student's t test and chi-square test were used for statistical analysis. Clinicopathological characteristics, endoscopic findings, imaging characteristics, treatment, and prognosis of sporadic and MEN1-related gastrinoma were compared. Results: Among 52 patients with gastrinoma, 33 were sporadic gastrinoma and 19 were MEN1-related gastrinoma. The common symptoms of both sporadic and MEN1-related gastrinomas were diarrhea (24/33, 72.7%; 17/19, 89.5%) and abdominal pain (19/33, 57.6%; 9/19, 47.4%). Compared with sporadic gastrinoma, MEN1-related gastrinoma needed longer time for diagnosis [(7.4±4.9) years vs. (3.9±5.2) years, t=-2.355, P=0.022), were more likely multiple tumors [47.4% (9/19) vs. 15.2% (5/33), χ(2)=6.361, P=0.012], had smaller diameter [(1.7±1.0) cm vs. (3.1±1.8) cm, t=2.942, P=0.005), presented the lower tumor grade [G1: 83.3% (15/18) vs. 39.4% (13/33); G2: 11.1% (2/18) vs. 54.5% (18/33); G3: 5.6% (1/18) vs. 6.1% (2/33), Z=-2.766, P=0.006], were less likely to have serum gastrin which was 10 times higher than normal [11.8% (2/17) vs. 56.0% (14/33), χ(2)=8.396, P=0.004], had higher probability of complication with type 2 gastric neuroendocrine tumors (g-NET) [31.6% (6/19) vs. 3.0%(1/33), χ(2)=6.163, P=0.013], and had lower rate of liver metastasis [21.1% (4/19) vs. 51.5% (17/33), χ(2)=4.648, P=0.031). There was no obvious difference between sporadic gastrinomas and MEN1-related gastrinomas in endoscopic findings. Both types presented enlarged and swollen gastric mucosa under the stimulation of high gastric acid, and multiple ulcers in the stomach and duodenum could be seen. Gastrinoma with type 2 g-NET presented multiple polypoid raised lesions in the fundus and body of the stomach. (68)Ga-SSR-PET/CT scan had a 100% detection rate for both types while (18)F-FDG-PET/CT scan had a higher detection rate for sporadic gastrinoma compared with MEN1-related gastrinoma [57.9% (11/19) vs. 20.0% (3/15), χ(2)=4.970, P=0.026]. Among the patients with sporadic gastrinoma, 19 received surgical treatment, 1 underwent endoscopic submucosal dissection, 8 underwent transcatheter arterial embolization (TAE), and 5 underwent surgery combined with TAE. Among patients with MEN1-related gastrinoma, 13 received surgical treatment, and the other 6 received conservative treatment. The median follow-up of all the patients was 21.5 (1-129) months, and the 5-year survival rate was 88.4%. The 5-year survival rate of patients with sporadic and MEN1-related gastrinomas was 89.5% and 80.0% respectively (P=0.949). The 5-year survival rate of patients with and without liver metastasis was 76.2% vs. 100%, respectively (P=0.061). Conclusions: Compared with sporadic gastrinoma, MEN1-related gastrinoma has longer diagnosis delay, smaller tumor diameter, lower tumor grading, lower risk of liver metastasis, and is more likely to complicate with type 2 g-NET, while there is no difference in survival between the two tumor types.

Clinicopathological characteristics and prognosis of patients with sporadic multiple primary gastrointestinal stromal tumors / 中华胃肠外科杂志

Objective: To investigate the clinicopathological characteristics and prognosis of sporadic multiple primary gastrointestinal stromal tumor (GIST). Methods: A retrospective cohort study was conducted. Case inclusion criteria: (1) postoperative pathological diagnosis of GIST; (2) primary GIST with single lesion or sporadic multiple primary GIST (sporadic GIST was defined as primary GIST other than familial and syndrome-related GIST, and multiple primary GIST was defined as the number of primary GISTs in the same patient ≥ 2); (3) patients with complete clinicopathological data. Those with tumor recurrence or distant metastasis, and with other malignancies were excluded. Medical records of patients with primary GIST who underwent surgical resection in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2010 to December 2020 were collected. Patients were divided into sporadic multiple primary GIST group and single primary GIST group according to the number of primary GIST lesions. The clinicopathological data and prognosis of the two groups were observed and compared. Results: A total of 1200 patients with primary GIST were enrolled in this study, including 628 males (52.3%) and 572 females (47.7%), with a median onset age of 58 (19-93) years. Among them, 1165 cases (97.1%) were sporadic primary GIST with single lesion; 35 cases (2.9%) were sporadic multiple primary GIST. Among 35 cases of sporadic multiple primary GIST, 3 cases (8.6%) had acid reflux as the first symptom, which was higher than the single primary GIST group (22/1165, 1.9%) (χ(2)=7.437, P=0.006). There were no significant differences in other clinical characteristics between the two groups (all P>0.05). Patients in the sporadic multiple primary GIST group contained a total of 80 primary tumors. Compared with the single primary GIST group, the sporadic multiple primary GIST group had a higher proportion of tumors originating in the stomach [87.5% (70/80) vs. 59.1% (689/1165)], lower proportion of spindle cell in histology [85.0% (68/80) vs. 93.7% (1092/1165)], higher proportion of positive CD34 [97.5% (78/80) vs. 87.6% (1021/1165)], smaller maximum diameter [maximum diameter ≤2.0 cm: 61.2% (49/80) vs. 28.8% (335/1165)], lower mitotic rate [≤5/50 high-power fields (HPF): 93.8% (75/80) vs. 74.5% (868/1165)], lower risk of recurrence [60.0% (48/80) vs. 23.3% (271/1165)], and the differences were all statistically significant (all P<0.05). The 3-year recurrence-free survival rate in the sporadic multiple primary group and the single primary GIST group was 96.6% and 89.3% respectively (P=0.160), and the 3-year overall survival rate was 100.0% and 92.8%, respectively (P=0.088). Conclusions: The most common type of sporadic multiple primary GIST is multiple tumors originating in the stomach at the same time. Compared with primary GIST with single lesion, sporadic multiple primary GIST presents smaller maximum diameter and lower mitotic rate. The prognosis of patients between two groups is not significantly different.

An encounter with alobar holoprosencephaly: a case report

Alobar holopresencephaly is a rare embryonic condition where there is anomalous fusion of cerebral hemispheres. The key features include neurological impairment and facial dysmorphism like cyclopia, ocular hypertelorism with divided orbits and a proboscis. Obstetric ultrasound and foetal MRI are the diagnostic modalities. Majority of cases are sporadic in origin while a genetic association is also described. A small recurrence risk is noted in cases with sporadic origin. Early diagnosis and pregnancy termination are advisable for the condition since the survival rate is very low.

Mucinous Adenocarcinoma of the Colon in Uganda: A Case Report and Literature Review

Introduction:In Uganda, the Kampala Cancer Registry has reported a steady increase in the incidence of colorectal carcinoma(CRC) over the last few decades. The author reports a case of a 25 year old gentlemanpresenting with bowel obstruction and found to have mucinous adenocarcinoma of the colon. This is followed by a literature review of the clinical and pathological characteristics of young age sporadic colorectal carcinoma (YSCC) and hereditary nonpolyposis colorectal carcinoma (HNPCC).Presentation of Case:This patient presented with a family history of colorectal carcinoma (CRC) and with bowel obstruction. An emergency laparotomy involving a right hemicolectomy was carried out. The postoperative course of this patient was uneventful. Discussion:The typical histological features of mucinous adenocarcinoma of the colon were seen on the resected colon specimen. In addition this study reviews the literature regarding the clinical presentation, pathological characteristics, histology and prognosis of mucinous and medullary carcinoma of the colon.Conclusions:Mucinous adenocarcinoma happens to be the most common histological type of colorectal carcinoma in young adults. In Uganda, low risk young patients withsymptoms should be screened for colorectal lesions. A high index of suspicion should therefore be taken in the diagnosis of colorectal malignancy in these patients

Computed tomography imaging characteristics of clear cell papillary renal cell carcinoma

ABSTRACT Purpose: Clear cell papillary (CCP) renal cell carcinoma (RCC) is a new subtype of RCC that was formally recognized by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia in 2013. Subsequently, CCP RCC was added to the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. In this study, we retrospectively investigated the computed tomography (CT) findings of pathologically diagnosed CCP RCC. Materials and Methods: This study included 12 patients pathologically diagnosed with CCP RCC at our institution between 2015 and 2017. We reviewed the patient's CT data and analyzed the characteristics. Results: Nine solid masses and 3 cystic masses with a mean tumor size of 22.7±9.2mm were included. Solid masses exhibited slight hyper-density on unenhanced CT with a mean value of 34±6 Hounsfield units (HU), good enhancement in the corticomedullary phase with a mean of 195±34HU, and washout in the nephrogenic phase with a mean of 133±29HU. The walls of cystic masses enhanced gradually during the corticomedullary and nephrogenic phases. Solid and cystic masses were preoperatively diagnosed as clear cell RCC and cystic RCC, respectively. Conclusions: The CT imaging characteristics of CCP RCCs could be categorized into either the solid or cystic type. These masses were diagnosed radiologically as clear cell RCC and cystic RCC, respectively.

Diferencias atencionales y ejecutivas en jóvenes y adultos con consumo no patológico de sustancias / Attentional and executive differences in youth and adults with non-pathological substance use

Las funciones ejecutivas y la atención se muestran comprometidas en la dependencia crónica al alcohol y al abuso de sustancias en adultos. Los efectos del consumo ocasional sobre el funcionamiento ejecutivo no se encuentran extensamente valorados y reportados. Se evaluaron 45 jóvenes y adultos universitarios, sin antecedentes de consumo problemático ni antecedentes psiquiátricos, con inventarios para valorar sintomatología disejecutiva (DEX e ISP); y cuestionarios para relevar los problemas derivados del consumo de alcohol (AUDIT) y marihuana (MSI-X). Los examinados con mayor puntaje en el MSI-X muestran índices mayores índices de problemas motivacionales y problemas de control emocional en el ISP, así como mayor índice de desorganización/apatía y puntaje total del DEX. Los examinados con mayor puntaje en el AUDIT presentan mayores índices de desorganización/apatía y del puntaje total en el DEX, así como mayor índice de problemas de control ejecutivo y puntaje total del ISP. El consumo no problemático de alcohol y marihuana podría dar lugar a diferencias ejecutivas y atencionales en jóvenes y adultos(AU)

Executive functions and attention were altered in chronic alcohol dependence and substance abuse in adults. The effects of sporadic consumption on executive functioning are not widely valued or reported. Were evaluated 45 young and adults with university studies, with no history of problematic consumption or psychiatric history, with inventories to assess disejecutive symptoms (DEX and ISP); and questionnaires to assess the problems derived from the consumption of alcohol (AUDIT) and marijuana (MSI-X). The participants with higher score in the MSI-X show higher indices of emotional control problems and in the total ISP score, as well as higher rate of disorganization / apathy and total DEX score. The participants with higher score in the AUDIT show higher rates of executive control problems and total ISP score, as well as higher rate of disorganization / apathy and total DEX score. The non-problematic consumption of alcohol and marijuana could lead to executive and attentional differences in young people and adults(AU)

rs12904 polymorphism in the 3'-untranslated region of ephrin A1 ligand and the risk of sporadic colorectal cancer in the Iranian population

Background: Colorectal cancer (CRC) is rated as the second cause of cancer death. Genetic determinants are considered as driving forces in the development of sporadic CRC. Single-nucleotide polymorphisms (SNPs), due to their abundance in the human genome with collectively huge effect on cellular signaling pathways, are attributed as the main genetic factor in disease susceptibility including cancers. MicroRNAs are contributing to posttranslational gene regulation. They exert their regulatory function by binding to their specific recognition sequences located at 3'-untranslated region (UTR) of mRNAs. In the present study, we have elucidated the role of rs12904, a naturally occurring SNP, in the recognition site of miR200c in the 3'UTR of ephrin A1 ligand gene, in the development of sporadic CRC in the Iranian population. Materials and Methods: A case–control study using 152 CRC patients and 160 noncancerous counterparts was conducted to determine the rs12904 genotypes using polymerase chain reaction–restriction fragment length polymorphism method. Results: The results revealed no significant association between the rs12904 and sporadic CRC (odds ratio = 0.97, 95% confidence interval = 0.70–1.34). The frequency of genotypes and also alleles of the mentioned polymorphism were not significantly different between case and control groups (P = 0.765 and P = 0.847, respectively). Conclusion: The results suggest that this polymorphism probably has not a crucial role in the Iranian CRC risk and is not an important potential risk factor in molecular diagnostics of mentioned disease among the Iranian population.

Idiopathic inflammatory myopathy / 中华神经科杂志

Idiopathic inflammatory myopathies (IIM) are a group of acquired immune myopathy,which mainly include polymyositis,dermatomyositis,amyopathic dermatomyositis,sporadic inclusion body myosistis (sIBM) and immune-mediated necrotizing myopathy,as well as some special types of antisynthetase syndrome,anti-signal recognition particle antibody positive necrotizing myopathy (NM),anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody positive NM.The diagnosis of these different types of IIM mainly depends on clinical manifestations,antibody detection and muscle pathological techniques.Different types of IIM have different clinical manifestations,or overlapping manifestations.This article systematically describes the evolution of IIM types,the main antibodies to myositis,the pathological characteristics of muscles,the manifestations of various types and the treatment of myositis.In addition to sIBM,patients with most of the other types of IIM have good outcomes by early diagnosis,timely,correct and adequate drug treatment.

Association between Polymorphism of the BRCA2 Gene rs206115 Loci and Sporadic Breast Cancer / 中国医科大学学报

Objective To analyze the correlation between polymorphism of the BRCA2 gene rs206115 loci and sporadic breast cancer in Inner Mongolia. Methods We enrolled patients from the Affiliated Hospital of Inner Mongolia Medical University from December 2015 to December 2016 who underwent breast surgery and were confirmed by pathology, resulting in a total of 101 cases of primary sporadic breast cancer (case group) and benign breast diseases (control group). DNA was extracted from blood samples and analyzed using polymerase chain reaction (PCR) and direct sequencing methods for determining the BRCA2 gene rs206115 loci polymorphism. SPSS 17.0 was used for statistical analysis. Results In this experiment, regardless of whether the patients were Han or Mongolian, the rs206115 loci could be detected in 3 kinds of genotypes:AA, AG, and GG. The BRCA2 gene rs206115 locus gene polymorphism was not significantly different between the case and control groups (χ2=3.490, P = 0.175). The A allele frequency of the BRCA2 gene rs206115 loci in the case group was significantly increased compared to the control group (χ2=4.259, P = 0.039). Conclusion The A allele of rs206115 may be one of the susceptibility alleles in sporadic breast cancer in Mongolian and Han populations.

Impaired Nucleoporins Are Present in Sporadic Amyotrophic Lateral Sclerosis Motor Neurons that Exhibit Mislocalization of the 43-kDa TAR DNA-Binding Protein

BACKGROUND AND PURPOSE: Disruption of nucleoporins has been reported in the motor neurons of patients with sporadic amyotrophic lateral sclerosis (sALS). However, the precise changes in the morphology of nucleoporins associated with the pathology of the 43-kDa TAR DNA-binding protein (TDP-43) in the disease process remain unknown. We investigated the expression of nucleoporins that constitute the nuclear pore complex (NPC) in spinal motor neurons that exhibit sALS in relation to TDP-43 pathology, which is a reliable neuropathological hallmark of sALS. METHODS: Paraffin-embedded sections of the lumbar spinal cord were obtained for immunofluorescence analysis from seven control subjects and six sALS patients. Anti-TDP-43 antibody, anti-nucleoporin p62 (NUP62) antibody, and anti-karyopherin beta 1 (KPNB1) antibody were applied as primary antibodies, and then visualized using appropriate secondary antibodies. The sections were then examined under a fluorescence microscope. RESULTS: NUP62 and KPNB1 immunoreactivity appeared as a smooth round rim bordering the nuclear margin in normal spinal motor neurons that exhibited nuclear TDP-43 immunoreactivity. sALS spinal motor neurons with apparent TDP-43 mislocalization demonstrated irregular, disrupted nuclear staining for NUP62 or KPNB1. Some atrophic sALS spinal motor neurons with TDP-43 mislocalization presented no NUP62 immunoreactivity. CONCLUSIONS: Our findings suggest a close relationship between NPC alterations and TDP-43 pathology in the degenerative process of the motor neurons of sALS patients.

Expression and clinical significance of DNA mismatch repair proteins in sporadic colorectal carcinoma / 上海交通大学学报（医学版）

Objective: To investigate the expressions of mismatch repair (MMR) proteins, i.e. MLH1 (mutL homolog 1), MSH2 (mutS homolog 2), MSH6 (mutS homolog 6) and PMS2 (postmeiotic segregation increased 2) in sporadic colorectal carcinoma (SCRC) and their correlation with clinicopathological characteristics. Methods: Cancer tissue samples of the SCRC patients who underwent radical resection of colorectal cancer at Tongren Hospital, Shanghai Jiao Tong University School of Medicine from April 2014 to August 2018 were collected. MLH1, MSH2, MSH6, PMS2 and p53 proteins in colorectal cancer tissue samples from 209 patients who met the criteria were detected by immunohistochemistry, and 67 samples were detected by real-time PCR for KRAS oncogene mutation. Results: In 209 cases of cancer tissues, MLH1, MSH2, MSH6 and PMS2 deficiency rates were 17.2% (36/209), 2.4% (5/209), 12.9% (27/209), and 16.7% (35/209), respectively. The total deficiency rate of MMR system proteins was 30.1% (63/209), which was higher in the patients under 55 years old, with tumor at the right colon, with tumor bigger than 6 cm or with mucinous adenocarcinoma (all P<0.05). MLH1 deficiency rate of the patients with p53 mutation was significantly higher than that of unmutated patients (P=0.012); MLH1 deficiency rate of the patients with KRAS mutation was significantly lower than that of unmutant patients (P=0.044). There was no significant difference in the positive expression rates of MLH1 and PMS2 in these SCRC patients (P=1.000). Conclusion: MMR systemic protein deletion may be associated with patient age, tumor location, tumor size, and histopathological typing; MLH1 protein deletion may be associated with mutations of p53 and KRAS genes.