Progress of Basic and Clinical Research on Mucin-type O-Glycosylation and Colorectal Cancer / 胃肠病学

O⁃glycosylation is a common post⁃translational modification of mucins, widely present in both normal and tumor cells. In colorectal cancer (CRC) cells, there is a varying degree of dysregulation in O ⁃ glycosylation ⁃ related glycosyltransferases, molecular chaperones, and surface Tn antigen, sTn antigen, and T antigen. These dysregulations play a distinctive role in the occurrence and development of CRC, including invasion and metastasis, abnormal apoptosis and proliferation, immune escape, etc. They are extensively studied as novel tumor biomarkers and potential therapeutic targets. This article provides a comprehensive review of progress of research on mucin⁃type O⁃glycosylation and its relevance to the occurrence and development of CRC and its clinical application.

Parasitosis y antígenos TF, Tn y sTn / Parasitosis and TF, Tn and sTn antigens

Resumen Las investigaciones realizadas establecen una relación entre los epítopos T, Tn y sTn y las enfermedades parasitarias. Estos epítopos se expresan en un alto porcentaje de tumores epiteliales e inicialmente fueron relacionados con el síndrome T, caracterizado por trombocitopenia, leucopenia y anemia hemolítica. Se ha identificado la expresión de Tn en varios carcinomas, aunque los eventos asociados a su exposición en éstos parecen ser diferentes de los observados en el síndrome Tn. Diversos estudios comunicaron que estructuras asociadas a tumores, tales como los antígenos Tn y sialil-Tn, se expresan en algunos protozoarios y helmintos, y plantearon numerosos interrogantes a nivel de la interacción parásito-hospedador, de la glicobiología parasitaria y de las eventuales relaciones entre la biología de algunos parásitos y las células cancerígenas. Los hematíes son poliaglutinables cuando son aglutinados por casi todas las muestras de suero humano normal. Algunas formas de poliaglutinidad se deben a la exposición del determinante antigénico TF, mediante la eliminación del ácido N-acetilneuramínico, por la acción de neuraminidasas bacterianas o virales, aunque en los últimos años se ha comunicado el desenmascaramiento de este antígeno críptico eritrocitario por Ascaris lumbricoides y Trichinella spiralis. Debido a la importancia clínica de la activación T, se destaca la necesidad de estudiar la exposición del antígeno críptico TF en todos los parásitos cuyo hábitat sea la sangre, o bien en aquellos cuyos ciclos de vida comprendan una migración por el torrente circulatorio, pues su desenmascaramiento puede ocasionar autoaglutinación y/o hemólisis.

Abstract The investigations carried out establish a relationship between the T, Tn and sTn epitopes and the parasitic diseases. These epitopes are expressed in a high percentage of epithelial tumors, and they were initially related to the T syndrome, characterised by thrombocytopenia, leukopenia, and hemolytic anemia. The expression of Tn has been identified in several carcinomas, although the events associated with its exposure appears to be different from those observed in the Tn syndrome. Various studies report that tumor-associated structures such as Tn and sialyl-Tn antigens are expressed in some protozoa and helminths, raising numerous questions at the level of parasite-host interaction, parasitic glycobiology and eventual relationships between the biology of some parasites and cancer cells. Red cells are polyaglutinate when agglutinated by almost all normal human serum samples. Some forms of polyaglutinity are due to the exposure of the antigenic determinant TF, through the elimination of N-acetylneuraminic acid, by the action of bacterial or viral neuraminidases, although the unmasking of this erythrocyte cryptic antigen by Ascaris lumbricoides and Trichinella spiralis has been reported in recent years. Due to the clinical importance of T activation, the need to study the exposure of the cryptic TF antigen in all parasites whose habitats are blood or whose life cycles include migration through the circulatory stream is highlighted, since its unmasking can cause autoagglutination and/or hemolysis.

Resumo As investigações realizadas estabelecem uma relação entre os epítopos T, Tn e sTn e doenças parasitárias. Esses epítopos são expressos em alta porcentagem de tumores epiteliais e foram inicialmente relacionados à síndrome T, caracterizada por trombocitopenia, leucopenia e anemia hemolítica. A expressão de Tn foi identificada em vários carcinomas, embora os eventos associados à sua exposição neles pareçam ser diferentes dos observados na síndrome Tn. Vários estudos relatam que estruturas associadas a tumores, tais como antígenos Tn e sialil-Tn, são expressos em alguns protozoários e helmintos, levantando inúmeras questões no nível da interação parasita-hospedeiro, glicobiologia parasitária e eventuais relações entre a biologia de alguns parasitas e células cancerígenas. Os glóbulos vermelhos são poliaglutináveis quando são aglutinados por quase todas as amostras de soro humano normal. Algumas formas de poliaglutinidade são devidas à exposição do determinante antigênico TF, pela eliminação do ácido N-acetilneuramínico, pela ação de neuraminidases bacterianas ou virais, embora nos últimos anos tenha sido relatado o desmascaramento desse antígeno eritrocitário críptico por Ascaris lumbricoides e Trichinella spiralis. Devido à importância clínica da ativação T, destaca-se a necessidade de estudar a exposição do antígeno críptico TF em todos os parasitas cujo habitat seja o sangue ou naqueles cujos ciclos de vida incluam migração pela corrente circulatória, uma vez que seu desmascaramento pode causar autoaglutinação e/ou hemólise.

A STUDY OF THE CLINICAL, RADIOLOGICAL, CYTOLOGICAL AND HISTOPATHOLOGICAL CORRELATION OF SOLITARY THYROID NODULE

Background: Solitary thyroid lesions are a common presentation in the surgical OPD. The signi?cance of solitary nodule is its malignant potential. Thyroid nodule is an elusive clinical problem. Surgeons and Physicians are often required to make a diagnostic or management decision in its treatment. To study the Aim and Objectives: correlation between Clinical, Radiological, Cytological and Histopathological ?nding in patients who presented with “solitary thyroid nodule”. A prospective observational study, Ramakrishna Mission Materials and Methods:Study design: Study area: Seva Pratishthan Hospital, Kolkata, July 2019 to June 2022(3 years), 40 patients, Inclusion criteria: Study period: Sample size: Patients presenting with solitary thyroid nodule, Patients with multinodular goitre, patients with carcinoma Exclusion criteria: thyroid with distant metastasis, paediatric patients and those unwilling. Thorough history, clinical examination, Methodology: investigation (FNAC/USG/Isotope Scan, TSH), appropriate surgical intervention and HPE of excised specimen was done. Results: In our study of 40 cases, 28(70.0%) were colloid goiter, 7(17.5%) were papillary carcinoma, 2(5%) were follicular adenoma, 1(2.5%) was follicular carcinoma, 1(2.5%) was adenomatoid hyperplasia and 1(2.5%) was Hashimoto thyroiditis. 28(70%) cases underwent hemithyroidectomy, 11(27.5%) underwent total thyroidectomy and 1(2.5%) underwent hemithyroidectomy followed by revision total thyroidectomy. 2 cases of papillary carcinoma with enlarged neck nodes underwent total thyroidectomy with neck node dissection. Solitary nodule is most common in woman and in third Conclusion: and fourth decade of life, more common in the right lobe. USG and FNAC are common modalities of investigations with high speci?city and sensitivity. Isotope scan is only indicated to con?rm the toxic nodule. Malignancy reported in my study was 20%. Early diagnosis and prompt treatment will cure the disease since carcinoma thyroid is more curable amongst all cancers.

Efficient identification of gene knockout mutant mediated by CRISPR/Cas9 by CELⅠ crude extracts / 生物工程学报

CRISPR/Cas9, emerged as an efficient and powerful gene editing technology, has become the mainstream genome editing technology. Constructing mutants using CRISPR/Cas9 system is of great significance to the functional study and breeding application of useful genes. As the basis of the technology, a method for identification of mutation with efficiency and lower cost is needed. In this report, we studied the factors influencing mutation detected by CEL Ⅰ crude extracts, such as the amount of protein, enzyme incubation time, PCR buffers. Under the optimized conditions, we can integrate the mutation detection steps into one-tube reaction. We used this system to examine the mutation types and frequency of rice stn1 mediated by CRISPR/Cas9. We also used this method to identify different mutation types including homozygous, heterozygous and bi-allelic mutations. The accuracy of this method reached 100% verified by sequencing. Altogether, our results showed that using CELⅠ crude extracts was an efficient and low cost method for identification of CRISPR/Cas9 mediated mutation.

Advances in Research on the Apathy of the Subthalamic Nucleus-deep Brain Stimulation / 现代生物医学进展

Parkinson's disease is characterized by progressive motor dysfunction owing to degeneration of dopaminergic neurons in the substantia nigra and other nuclei.Recently,the bilateral high frequency stimulation of the subthalamic nucleus deep brain stimula tion (STN-DBS) as the treatment of PD was famous with good curative effect.But postoperative apathy as its side-effect impact on the therapeutic effect and the quality of life of patients seriously,which drawn the attention of clinicians.In this article,we summarized the incidence,manifestation and treatment of postoperative apathy and tried to provide some ideas for clinicians.

An Open, Retrospective Study Of Comparison Of Fine Needle Aspiration Cytology (FNAC) And Histopathology Findings In 75 Cases Of Solitary Thyroid Nodule.

Background and objectives: Solitary thyroid nodule(STN} is a common clinical entity encountered in routine clinical practice.STN is defined as a single swelling involving either lobe of thyroid or isthmus of thyroid gland. Present study was undertaken to know distribution of lesion according to age and sex, and also to evaluate efficacy of FNAC in diagnosis of clinically obvious and palpable solitary thyroid nodule. Method: This study was done on 75cases operated in our hospital from May 2012 to May 2016. All patients included in the study were submitted to FNAC and ultrasonography. All patients were subjected to surgery and histopathology examination was obtained. Results: Out of 75 cases of thyroid lesions, 63 cases were benign (84%), 6 cases were malignant (8%) and 6 cases were suspicious(8%) on FNAC. On Histopathological examination, 60 cases were benign(80%) and 15 cases were malignant(20%). Conclusion: FNAC is a single best investigation for preoperative evaluation for STN to differentiate between benign and malignant nodules with 88% accuracy rate.[Doshi H NJIRM2016; 7(5):53-55]

The Expression and Clinical Significance of sTn in Endometrial Carcinoma / 天津医药

Objective To investigate the expression and clinical significance of tumor-associated carbohydrate anti-gen sTn in endometrium from patients with atypical hyperplasia of endometrium, endometrial carcinoma and benign the uter-ine lesion. And to analyze the association between sTn and the pathologic stage and grade of endometrial carcinoma. Meth-ods sTn was detected by immunohistochemistry in 193 patient samples, including 93 subjects with endometrial carcinoma, 50 subjects with atypical hyperplasia of endometrium and 50 subjects with benign uterine lesions. Results The positive sTn rate in endometrial carcinoma group was 73.1%,which was significantly different from that in atypical hyperplasia endo-metrium group (32%) and that in benign uterine lesion group (14%), (P＜0.017). sTn positive rate in patients with endometri-al carcinoma was 78.8%which is higher than that in patients with other diseases (P＜0.008 ). The positive rate of sTn in pa-tients with poorly differentiated endometrial carcinoma was significantly higher than that in patients with highly differentiat-ed endometrial carcinoma (P＜0.017). The positive rate of sTn in tissues of tumor infiltration with depth of more than half of myometrial was significantly higher than in tissues of tumor infiltration with depth of equal or less than half of myometrial (P＜0.05). But there was no significant difference in sTn positive rate between the endometrial carcinoma groups with and without lymph node metastasis (P>0.05). Conclusion sTn may play a role in the tumorigenesis and development of endo-metrial carcinoma.

Subtalamotomía por radiofrecuencia: aspectos técnico-quirúrgicos / Radiofrequency subtalamotomy: technical-surgical aspects

Objetivo: Describir la técnica estereotáxica de subtalamotomía por radiofrecuencia utilizando microrregistro intraoperatoriocon semimicroelectrodo.Descripción: Se detalla la técnica efectuada sobre 51 subtalamotomías desde el año 2011, en pacientes con diagnósticode Enfermedad de Parkinson (EP) refractaria al tratamiento. La técnica quirúrgica consta de tres etapas: adquisición de lasimágenes estereotácticas, localización anatómo-funcional de blanco quirúrgico y lesión por radiofrecuencia de la regiónsensitivo-motora del núcleo. Se describe el método utilizado para la exploración de la somatotopía del NST que permite laposterior lesión, confiriendo seguridad y efectividad al procedimiento.Conclusión: La subtalamotomía constituye una técnica segura y efectiva realizada en grupos entrenados con los recursostécnicos necesarios, para el tratamiento de la EP refractario, constituyendo una alternativa adaptable a nuestro medio conel objetivo mejorar la calidad de vida.

Purpose: To describe the stereotaxic subthalamotomy technique with radiofrequency using intraoperative micro-recordingwith semimicroelectrodes.Description: We depict the surgical technique used in 51 lesions affecting the STN in cases of advanced Parkinson'sdisease from 2011. This technique consists of three stages: acquisition of stereotactic images, anatomofunctionallocalization of surgical target, and lesioning by means of radiofrequency of the subthalamic nucleus (STN). We also describethe method for the somatotopic exploration of the STN in its posterior part and its lesionConclusion: Subthalamotomy might be considered a safe surgical technique for the treatment of advanced Parkinson'sdisease symptoms. When performed by experienced surgical teams, it can result in a valid option for this group of patients.

Electrode Position and the Clinical Outcome after Bilateral Subthalamic Nucleus Stimulation

We compared the surgical outcome with electrode positions after bilateral subthalamic nucleus (STN) stimulation surgery for Parkinson's disease. Fifty-seven patients treated with bilateral STN stimulations were included in this study. Electrode positions were determined in the fused images of preoperative MRI and postoperative CT taken at six months after surgery. The patients were divided into three groups: group I, both electrodes in the STN; group II, only one electrode in the STN; group III, neither electrode in the STN. Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr stage, and activities of daily living scores significantly improved at 6 and 12 months after STN stimulation in both group I and II. The off-time UPDRS III speech subscore significantly improved (1.6 +/- 0.7 at baseline vs 1.3 +/- 0.8 at 6 and 12 months, P < 0.01) with least L-dopa equivalent daily dose (LEDD) (844.6 +/- 364.1 mg/day at baseline; 279.4 +/- 274.6 mg/day at 6 months; and 276.0 +/- 301.6 mg/day at 12 months, P < 0.001) at 6 and 12 months after STN deep brain stimulation (DBS) in the group I. Our findings suggest that the better symptom relief including speech with a reduced LEDD is expected in the patients whose electrodes are accurately positioned in both STN.

Alterations of the Mucin Glycoprotein Expression and Their Relationship with the Pathologic Prognostic Factors in Gastric Carcinoma

Alterations of the mucin-type glycoproteins may contribute to changes in cancer cell growth regulation, immune regulation, and cellular adhesion, which in turn may influence the invasive and metastatic capabilities of the cancer. Many of the cancer-associated antigens such as mucin antigens have been identified recently and alterations in the glycosylation of the mucins have been described in the cancer. Immunohistochemical studies of 3 antigens associated with alteration of the mucin glycoprotein (MUC1, MUC2, STn) were done to evaluate their relationship with known pathologic prognostic factors and their usefulness in assessment of the progression of gastric carcinoma in 127 gastric carcinoma tissues. The MUC1 was detected in 57 (44.9%), MUC2 in 76 (59.8%) and STn antigen in 77 (60.6%) out of 127 cases of gastric carcinomas. The expression rate of MUC1 was significantly correlated with depth of tumor invasion, lymph node and distant metastases, and advanced tumor stage (p=0.001). The expression rate of MUC2 was not significantly correlated with pathologic findings and known prognostic factors. The STn antigen was significantly associated with incidence of lymph node metastasis (p=0.02). The coexpression of both MUC1 and MUC2 or MUC1 and STn was more frequent in tumors with deep invasion, lymph node metastasis and advanced tumor stage than one or none expression (p<0.05). These results suggest that the alterations of expression of the mucin proteins, especially MUC1 and carbohydrate antigen (STn) are associated with poor biological behavior of the gastric carcinoma.

Evaluation of new ovarian cancer markers, STN, CA 546 and CA 72-4 in Thai patients.

Ovarian cancer is the most fatal gynaecologic malignance. At present, there is no sensitive test to detect early stages of the disease. In our study of 32 ovarian cancer patients admitted in Siriraj Hospital, 3 new tumor makers, STN, CA 546 and CA 72-4 were selected to evaluate for their sensitivity as compared with CA 125 Kit. The best positive rate for non-mucinous type of ovarian cancer was 82% obtained from the CA 125 test while the result for mucinous type was 67% obtained from a combined test of CA 125 and STN. As a requirement for early diagnosis, tests using CA 125 or CA 72-4 showed best sensitivity of 33% in early stages of non-mucinous, while CA 546 test revealed the highest result of 33% for mucinous type. Thus, the combination of new tumor marker assay of STN, CA 546, CA 72-4 together with CA 125 would increase sensitivity in detecting ovarian cancer especially for the mucinous type which is more common in Thailand.

A study of succiny trialanine p-nitroanilide hydrolytic activity in workers exposed to organic solvents / 예방의학회지

To measure the serum succinyl trialanine p-nitroanilide hydrolytic activity as new index of liver function in workers exposed to organic solvents, this study conducted 114 workers in department of shoe-making of shoes factories. The results obtained from this study were as follows: 1. The mean values of serum GOT, GPT, gamma GT in whole workers were 22+/-12.32, 20+/-9.65, 28+/-21.35IU/l, respectively and the mean value of serum STN hydrolytic activity was 0.08 0.05. 2. The serum STN hydrolytic activity was significantly higher for male(p<0.05) and there was no difference among the groups of age. 3. There was no difference in the groups by working hours but significant difference in persons who worked over 3 years or were exposed to toluene over 100ppm(p<0.05). 4. The correlation of the exposed dose of toluene and serum GOT, GPT, gamma GT and serum STN hydrolytic activity were statistically significant(r=0.027-0.518). 5. The exposed dose of toluene was most explainable variable and statistically significant among the factors affecting serum STN hydrolytic activity(p<0.05).

CONSTRUCTION OF SALMONELLA STN-DEFICENT MUTANTS AND DETECTION OF THEIR VIRULENCE / 解放军医学杂志

The plasmids of recombinant suicide vector containing the truncated stn gene and the deleted stn gene were constructed. The Salmonella stn-deficient mutant was prepared by homologous recombination between the mutant stn gene in the recombinant suicide vector and the wild-type gene in the chromosome of S. Typhimurium 2000. The detection of biological activity of stn gene production in those mutants indicated that Salmonella stn-deficient mutants evoked significantly less fluid secretion in mouse intestinal loops compared to that seen with wild-type Salmonella. Upon oral challenge of mice, the fifty percent lethal dose of the Salmonella stn-deficient mutants was greater than that for the wild-type bacteria. Those studies showed that the stn gene is very important factor in the pathogenesis of salmonellosis.