Association of blood groups/Rh and diabetes mellitus in Karachi city, Pakistan

Abstract The main purpose of this study was to find out a possible association between ABO blood groups or Rh and diabetes mellitus (DM) in the local population of eight (8) different towns of Karachi, Pakistan. For this purpose a survey was carried out in Karachi to have a practical observation of these towns during the period of 9 months from June 2019 to Feb. 2020. Out of eighteen (18) towns of Karachi, samples (N= 584) were collected from only eight (8) Towns of Karachi and gave a code-number to each town. Diabetic group sample was (n1=432) & pre-diabetes sample was (n2 =152). A standard Abbot Company Glucometer for Random Blood Sugar (RBS) and Fasting Blood Sugar (FBS) tests, standard blood anti sera were used for ABO/Rh blood type. Health assessment techniques were performed ethically by taking informed consent from all registered subjects. Finally data was analyzed by SPSS version 20.0. In our current study, the comparison of ABO blood groups frequencies between diabetic and pre-diabetic individuals were carried out. The percentage values of blood Group-B as given as: (32% in DM vs. 31% in pre-diabetics), followed by blood Group-O as: (18% in DM vs. 11% in pre-diabetics). Contrary to Group-B & O, blood Group-A and Group-AB were distribution percentage higher pre-diabetic as compared to DM patients, as given as: Group-A (32% in pre-diabetics vs. 26% in DM) & Group-AB (26% in pre-diabetics vs. 24% in diabetics patients). In addition, percentage distribution of Rh system was also calculated, in which Rh+ve Group was high and more common in DM patients as compared to pre-diabetics; numerically given as: Rh+ve Group (80% in DM vs. 72% in pre-diabetics). Different views and dimensions of the research topic were studied through literature support, some have found no any association and some established a positive association still some were not clear in making a solid conclusion. It is concluded that DM has a positive correlation with ABO blood groups, and people with Group-B have increased susceptibility to DM disease.

Resumo O objetivo principal deste estudo foi descobrir uma possível associação entre grupos sanguíneos ABO ou Rh e diabetes mellitus (DM) na população local de oito (8) diferentes cidades de Karachi, Paquistão. Para tanto, foi realizado um levantamento em Karachi para observação prática dessas cidades durante o período de 9 meses de junho de 2019 a fevereiro de 2020.De dezoito (18) cidades de Karachi, as amostras (N = 584) foram coletadas de apenas oito (8) cidades de Karachi e deram um número-código para cada cidade. A amostra do grupo de diabéticos foi (n1 = 432) e a amostra de pré-diabetes foi (n2 = 152). Um glicômetro padrão da Abbot Company para testes de açúcar no sangue aleatório (RBS) e açúcar no sangue em jejum (FBS), antissoros de sangue padrão foram usados para o tipo de sangue ABO / Rh. As técnicas de avaliação de saúde foram realizadas de forma ética, tomando o consentimento informado de todos os indivíduos registrados. Finalmente, os dados foram analisados pelo SPSS versão 20.0.No presente estudo, foi realizada a comparação das frequências dos grupos sanguíneos ABO entre diabéticos e pré-diabéticos. Os valores percentuais do sangue do Grupo-B são dados como: (32% em DM vs. 31% em pré-diabéticos), seguido pelo sangue do Grupo-O como: (18% em DM vs. 11% em pré-diabéticos). Ao contrário dos Grupos B e O, sangue do Grupo-A e Grupo-AB tiveram distribuição percentual maior de pré-diabéticos em comparação com pacientes com DM, dado como: Grupo-A (32% em pré-diabéticos vs. 26% em DM) e Grupo AB (26% em pré-diabéticos vs. 24% em pacientes diabéticos). Além disso, também foi calculada a distribuição percentual do sistema Rh, no qual o Grupo Rh + ve foi elevado e mais comum em pacientes com DM em comparação aos pré-diabéticos; dados numericamente como: Grupo Rh + ve (80% em DM vs. 72% em pré-diabéticos). Diferentes visões e dimensões do tema de pesquisa foram estudadas com o suporte da literatura, alguns não encontraram nenhuma associação e alguns estabeleceram uma associação positiva, embora alguns não estivessem claros em fazer uma conclusão sólida. Conclui-se que o DM tem correlação positiva com os grupos sanguíneos ABO, e as pessoas com o Grupo B têm maior suscetibilidade à doença DM.

Association of blood groups/Rh and diabetes mellitus in Karachi city, Pakistan / Associação de grupos sanguíneos/Rh e diabetes mellitus na cidade de Karchi, Paquistão

Abstract The main purpose of this study was to find out a possible association between ABO blood groups or Rh and diabetes mellitus (DM) in the local population of eight (8) different towns of Karachi, Pakistan. For this purpose a survey was carried out in Karachi to have a practical observation of these towns during the period of 9 months from June 2019 to Feb. 2020. Out of eighteen (18) towns of Karachi, samples (N= 584) were collected from only eight (8) Towns of Karachi and gave a code-number to each town. Diabetic group sample was (n1=432) & pre-diabetes sample was (n2 =152). A standard Abbot Company Glucometer for Random Blood Sugar (RBS) and Fasting Blood Sugar (FBS) tests, standard blood anti sera were used for ABO/Rh blood type. Health assessment techniques were performed ethically by taking informed consent from all registered subjects. Finally data was analyzed by SPSS version 20.0. In our current study, the comparison of ABO blood groups frequencies between diabetic and pre-diabetic individuals were carried out. The percentage values of blood Group-B as given as: (32% in DM vs. 31% in pre-diabetics), followed by blood Group-O as: (18% in DM vs. 11% in pre-diabetics). Contrary to Group-"B" & "O", blood Group-A and Group-AB were distribution percentage higher pre-diabetic as compared to DM patients, as given as: Group-A (32% in pre-diabetics vs. 26% in DM) & Group-AB (26% in pre-diabetics vs. 24% in diabetic's patients). In addition, percentage distribution of Rh system was also calculated, in which Rh+ve Group was high and more common in DM patients as compared to pre-diabetics; numerically given as: Rh+ve Group (80% in DM vs. 72% in pre-diabetics). Different views and dimensions of the research topic were studied through literature support, some have found no any association and some established a positive association still some were not clear in making a solid conclusion. It is concluded that DM has a positive correlation with ABO blood groups, and people with Group-B have increased susceptibility to DM disease.

Resumo O objetivo principal deste estudo foi descobrir uma possível associação entre grupos sanguíneos ABO ou Rh e diabetes mellitus (DM) na população local de oito (8) diferentes cidades de Karachi, Paquistão. Para tanto, foi realizado um levantamento em Karachi para observação prática dessas cidades durante o período de 9 meses de junho de 2019 a fevereiro de 2020.De dezoito (18) cidades de Karachi, as amostras (N = 584) foram coletadas de apenas oito (8) cidades de Karachi e deram um número-código para cada cidade. A amostra do grupo de diabéticos foi (n1 = 432) e a amostra de pré-diabetes foi (n2 = 152). Um glicômetro padrão da Abbot Company para testes de açúcar no sangue aleatório (RBS) e açúcar no sangue em jejum (FBS), antissoros de sangue padrão foram usados ​​para o tipo de sangue ABO / Rh. As técnicas de avaliação de saúde foram realizadas de forma ética, tomando o consentimento informado de todos os indivíduos registrados. Finalmente, os dados foram analisados ​​pelo SPSS versão 20.0.No presente estudo, foi realizada a comparação das frequências dos grupos sanguíneos ABO entre diabéticos e pré-diabéticos. Os valores percentuais do sangue do Grupo-B são dados como: (32% em DM vs. 31% em pré-diabéticos), seguido pelo sangue do Grupo-O como: (18% em DM vs. 11% em pré-diabéticos). Ao contrário dos Grupos "B" e "O", sangue do Grupo-A e Grupo-AB tiveram distribuição percentual maior de pré-diabéticos em comparação com pacientes com DM, dado como: Grupo-A (32% em pré-diabéticos vs. 26% em DM) e Grupo AB (26% em pré-diabéticos vs. 24% em pacientes diabéticos). Além disso, também foi calculada a distribuição percentual do sistema Rh, no qual o Grupo Rh + ve foi elevado e mais comum em pacientes com DM em comparação aos pré-diabéticos; dados numericamente como: Grupo Rh + ve (80% em DM vs. 72% em pré-diabéticos). Diferentes visões e dimensões do tema de pesquisa foram estudadas com o suporte da literatura, alguns não encontraram nenhuma associação e alguns estabeleceram uma associação positiva, embora alguns não estivessem claros em fazer uma conclusão sólida. Conclui-se que o DM tem correlação positiva com os grupos sanguíneos ABO, e as pessoas com o Grupo B têm maior suscetibilidade à doença DM.

High-grade tumor budding is a risk factor for survival in patients with laryngeal squamous cell carcinoma

Abstract Objective: With the increasing incidence and mortality of laryngeal squamous cell carcinoma worldwide, researchers continue to search for novel prognostic factors and treatment methods for preventing early laryngeal squamous cell carcinoma from becoming advanced laryngeal squamous cell carcinoma. This study aims to determine if tumor budding is an independent risk factor associated with the survival of patients with laryngeal squamous cell carcinoma. Methods: 268 cases of laryngeal squamous cell carcinoma were studied, and tumor budding was analyzed for associations with clinicopathological features and clinical outcomes. Results: Tumor budding was divided into low-grade tumor budding (0-6/0.785mm2) and high-grade tumor budding (≥7/0.785 mm2) based on the results of the receiver operating characteristics curve analysis. Logistic regression analysis showed that smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were the risk factors for high-grade tumor budding (p < 0.05). In the low-grade tumor budding group, there was no statistic difference in survival between patients without tumor budding and those with 1 -6/0.785 mm2 tumor budding. Multivariate survival analysis showed high-grade tumor budding (p < 0.001) was independent prognostic factors for disease-free survival and overall survival in laryngeal squamous cell carcinoma. High-grade tumor budding was also an independent prognostic factor for disease-free survival (p = 0.037) and overall survival (p = 0.009) in T1-2N0 laryngeal squamous cell carcinoma. Conclusions: Smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were closely associated with high-grade tumor budding in laryngeal squamous cell carcinoma. High-grade tumor budding may be an adverse risk factor that affects not only the disease-free survival and overall survival of laryngeal squamous cell carcinoma patients but also the survival of T1-2N0 laryngeal squamous cell carcinoma patients. Level of Evidence: Level 4.

Berberine Promotes Mouse Breast Cancer Metastasis to Lung via Inducing Epithelial–mesenchymal Transition / 肿瘤防治研究

Objective To study the effect and mechanism of berberine (BBR) on the lung metastasis of mouse breast cancer via epithelial-mesenchymal transition (EMT). Methods CCK-8 and Transwell migration assays were utilized to investigate the proliferation and migration properties of breast cancer 4T1 cells after BBR treatment.Mouse 4T1-Luc cells were injected into mice under the fourth mammary fat pad, and the mice were then randomly divided into the control and BBR groups.The mice in the BBR group received daily intraperitoneal injections of BBR working solution and those in the control group were continuously intraperitoneally injected with the same volume of the solvent used to dissolve BBR powder.Tumor metastasis in the lungs of living mice was detected by using an in vivo imaging system.After 42 days of administration, lung metastasis was measured via microscopy and HE staining.Western blot analysis was used to examine the effects of BBR on the expression of EMT-related proteins (Vimentin and Snail) as well as the activation of the Akt and ERK signaling pathways. Results BBR significantly promoted 4T1 cell migration (P < 0.05).In vivo experiments showed that the number of lung metastases in the BBR group had significantly increased compared with that in control group (P < 0.05) as observed under microcopy and histological staining.Compared with the control group, BBR upregulated the expression levels of Vimentin and Snail as well as the phosphorylated levels of p-Akt and p-ERK (P < 0.05). Conclusion BBR may promote EMT and lung metastasis of breast cancer 4T1 cells by activating the expression of proteins in the p-Akt and p-ERK pathways.

Possible mechanism of 191 measles attenuated live vaccine strains inhibiting the proliferation of triple negative breast cancer MDA-MB-231 cells based on proteomics technology / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：基于蛋白质组学技术探讨麻疹减毒活疫苗191株（MV-Hu191）在体内外对三阴性乳腺癌MDA-MB-231、4T1细胞的影响及其作用机制。方法：采用CCK-8法检测MV-Hu191对MDA-MB-231和4T1细胞增殖的影响；液相色谱-质谱联用技术分析MV-Hu191处理对MDA-MB-231细胞中蛋白质谱的影响，多重数据库筛选蛋白质谱中的典型差异蛋白质并进行GO、KEGG、亚细胞定位与功能注释。瘤内注射1×106 TCID50 MV-Hu191干预4T1细胞移植瘤模型小鼠，流式细胞术检测小鼠脾组织中T细胞亚群，ELISA法检测小鼠血清TNF-α和IL-6含量。结果：体外实验结果表明，MV-Hu191具有抑制MDA-MB-231和4T1细胞增殖的作用，差异均具有统计学意义（P<0.01）。蛋白质组学分析结果显示，MV-Hu191作用MDA-MB-231细胞后明显上调蛋白质有38个、下调有12个；差异表达的蛋白质主要参与细胞黏附、信号受体激活、细胞代谢、应激反应等生物学过程，22个差异蛋白质亚细胞定位位于细胞外，KEGG功能分类显示与免疫调节功能相关的差异蛋白质最多且均为上调蛋白，包括C4A、C8B、SERPINF2、A2M、SERPINC1、CTSB、SERPING1、C5；PPI预测发现免疫相关差异蛋白与CD4、CD8、TNF-α及IL-6相互关联。体内实验结果显示，MV-Hu191干预组小鼠脾组织中CD4+ T细胞数量略高于对照组，但差异无统计学意义（P>0.05），CD4+/CD8+ T细胞比值明显高于对照组（P<0.05），血清TNF-α和IL-6含量显著上升（均P<0.01）。结论：MV-Hu191显著抑制MDA-MB-231、4T1细胞增殖及拮抗4T1细胞荷瘤小鼠成瘤性，其机制可能是MV-Hu191通过激活免疫效应分子实现抗肿瘤作用。

Multivariate correlation analysis of T1S and C7S / 中国骨伤

OBJECTIVE@#To determine whether C7 angles (C7 slope, C7S) could replace T1 angles (T1 slope, T1S) by correlation analysis of T1S and C7S.@*METHODS@#A total of 442 patients from July 2015 to July 2020 in outpatient and inpatient department were enrolled retrospectively, and 259 patients who could identify the upper endplate of T1 were screened out . Of them, there were 145 males and 114 females, aged from 20 to 83 years old with an average of (58.6±11.2) years, including 163 patients with cervical spine surgery and 96 non-surgical patients. Patients were stratified by sex, age, cervical kyphosis, cervical alignment imbalance, and cervical spine surgery. These 259 patients included 145 cases in the male group, 114 cases in the female group;76 cases in the youth group (<40 years old), 109 cases in the middle-aged group (40 to 60 years old), and 74 cases in the elderly group(>60 years old); 92 cases in the cervical kyphosis group, 167 cases in the non-kyphosis group;51 cases in the cervical sequence imbalance group, 208 cases in the non-imbalance group;163 cases in the cervical surgery group, 96 cases in the non-operation group. The correlations of C7S and T1S in various modalities groups were analyzed.@*RESULTS@#Of 442 patients, the recognition rate of upper endplate of T1 was 58.6%(259/442), and that of C7 was 90.7%. The mean T1S and C7S of the 259 patients were (24.5±8.0)° [(25.9±7.7)° in the male group and (23.7±6.9)° in the female group] and (20.8±7.3)° [(22.5±7.5)° in the male group and(19.7±5.8)° in the female group], respectively. The total correlation coefficient between C7S and T1S was r=0.89, R2=0.79, and the linear regression equation was T1S=0.91×C7S+4.35. In the above general information and the grouping of deformity factors, T1S was highly correlated with C7S(r value 0.85 to 0.92, P<0.05).@*CONCLUSION@#There is a high correlation between T1S and C7S in different factor groups. For cases where T1S cannot be measured, C7S can be used to provide guidance and reference for evaluating the sagittal balance of the spine, analyzing the condition, and formulating surgical plans.

Value of dynamic subtraction MRI in assessing HCC response to image-guided loco-regional therapy

Background: Hepatocellular carcinoma (HCC) is considered one of the foremost cancers worldwide. Although the hepatic resection of HCC has a high existence in the clinical scenarios, locoregional management is preferred owing to the preservation of hepatic parenchyma with lower morbidity and mortality. Dynamic contrast-enhanced MR with subtraction imaging improves the evaluation of managed HCC with easy detection of residual or recurrent viable lesions. Patients and methods: This study was designed in a retrospective pattern from December 2020 to December 2022. Forty patients were referred to our radiology department with solitary HCC, underwent therapeutic intervention, then underwent follow-up by dynamic MRI study. Results: Forty patients with solitary HCC were conducted during our study; all underwent locoregional therapy with follow-up by dynamic MRI with subtraction technique one month later. The subtraction image has a sensitivity of 100%, specificity of 100%, PPV of 100%, NPV of 100%, and 100% accuracy, compared to 90.91%, 77.78%, 83.33%, 87.5%, and 85% for conventional dynamic images, 45.45%, 100%, 100%, 60% and 70% for diffusion-weighted images. Analysis of those results exhibited a considerable additive value of the subtraction technique to the dynamic MRI to detect the response of HCC after management. Conclusions: Subtraction MRI is a pivotal tool to assess the interventional treatment of HCC, particularly in lesions having pre-contrast high signal intensity with distinguished radiologists' confidence

Effects of live attenuated measles vaccine Hu191 strain on epithelial mesenchymal transition,proliferation and migration of 4T1 breast cancer cells / 中国生物制品学杂志

@#Objective To investigate the effects of live attenuated measles vaccine Hu191 strain(MV-Hu191)on epithelial mesenchymal transition(EMT),proliferation and migration of 4T1 breast cancer cells.MethodsCCK-8 and clone formation assay were used to analyze the effect of MV-Hu191 on the proliferation of 4T1 cells;The effect of MV-Hu191 on 4T1cell migration was analyzed by cell scratch test;The expression of EMT pathway proteins(MMP-2,MMP-9,E-cadherin)in4T1 cells was detected by Western blot;4T1 tumor-bearing mouse model was established in female BALB/c mice. The model mice were divided into control group(PBS),MV-Hu191(1 × 106TCID50)group and paclitaxel group(15 mg/kg),with 10 mice in each group,and injected into tumor at the dosage of 100 μL every 2 d for 5 times. At 28 d after administration,the effects of MV-Hu191 on survival time,tumorigenicity and metastasis in vivo were observed;The pathological characteristics of lung tissue and tumor tissue were observed by HE staining under microscope;The expression of EMT pathway proteins(MMP-2,MMP-9 and E-cadherin)in tumor tissue was detected by immunohistochemical staining.Results The results of in vitro experiment showed that,compared with the control group,MV-Hu191 inhibited the proliferation and migration of 4T1 cells(F = 2. 811 and 13. 535,P = 0. 001 and 0. 002,respectively),down regulated the expression of MMP-2 and MMP-9(F = 45. 433 and 9. 744,P = 0. 011 and 0. 038,respectively),and up regulated the expression of Ecadherin(F = 7. 001,P = 0. 032);The results of in vivo experiment showed that MV-Hu191 significantly prolonged the survival time of tumor-bearing mice,and decreased the tumor quality(F = 8. 301,P = 0. 003)and the number of pulmonary nodules metastasis compared with the control group(F = 33. 792,P = 0. 000);MV-Hu191 treated tumor tissue gap was small,the cells were round,and the alveolar contour was clearly visible;The expression of MMP-2 and MMP-9 in MVHu191 treated tumor tissue decreased significantly(F = 6. 705 and 9. 047,P = 0. 028 and 0. 023,respectively),while the expression of E-cadherin increased significantly(F = 3. 468,P = 0. 039).ConclusionMV-Hu191 signi-ficantly inhibits the proliferation and migration of 4T1 breast cancer cells,antagonizes the tumorigenicity and lung meta-stasis of 4T1 tumorbearing mice,and prolongs the survival time of mice. The possible mechanism of MV-Hu191 against breast cancer is closely related to the regulation of EMT pathway protein expression.

Corneal confocal microscopy identifies structural small fibre abnormalities in an adolescent with type 1 diabetes and impaired awareness of hypoglycaemia / Journal of the ASEAN Federation of Endocrine Societies

@#Impaired awareness of hypoglycaemia (IAH) is present in around 25-40% of individuals with type 1 diabetes mellitus (T1DM). Herein, we present a case of an adolescent with T1DM and IAH who had worse corneal nerve parameters compared to a T1DM adolescent without IAH. Small fibre abnormalities detected by corneal confocal microscopy in an objective easy-to-perform non-invasive test might be a surrogate indicator of underlying autonomic dysfunction in T1DM and IAH.

Carcinosinumproduces phenotypic changes of 4T1 tumor cells in vitro

Considering that there are few published studies that specifically address the exclusive use of Carcinosinumin different potencies and, most of them focused on genotypic and clinical effects, the present study was proposed to identify possible phenotypic changes, including viability, expression of HER-2 and metastatic abilities, using 4T1 cells in vitroas a model. Carcinosinum was tested in different homeopathic potencies (12cH; 30cH; 200cH) mechanically prepared using sterile pure water. The time space between preparing the potencies and using them was 24 hours.The final dilutions were inserted into the culture medium in a volume equal to 10%, at the time of cell seeding. The same succussed vehicle used to prepare the drugs (70% ethanol) diluted 1:100 in sterile pure water was used as control. All treated cells were cultured in 25 mL flasks, with cell density of 5 x 105cells/mL. After 24 hours of treatment, cells were analyzed for apoptosis index using Annexin V kit and the Countess® system. The morphology of 4T1 cells was monitored by staining cell smears with hematoxylin-eosin and Giemsa methods. HER-2 expression was assessed by immunocytochemistry and metalloproteinase activity was assessed by zymography. The determination of the cytokine profile was performed using Cytometric Bead Array (CBA). The samples were evaluated in quadruplicate and the data were analyzed by one-way ANOVA. Carcinosinum30cH presented the highest apoptotic index and reduction of MMP-9-Pro expression; Carcinosinum200cH produced the highest positivity for HER-2 and no specific effect was seen after the treatment with Carcinosinum12cH. No change in cytokine expression was seen among treatments. We conclude that Carcinosinum30cH and 200cH can change phenotypic features important totumor development in vitro. The clinical meaning of these data deserves further investigation.

Effect of Intravesical Instillation Therapy on Cancer-specific Survival Rate of Stage T1 Non-muscle-invasive Bladder Transitional Cell Carcinoma Patients After Transurethral Resection / 肿瘤防治研究

Objective To investigate the effect of transurethral resection of bladder tumor (TURBT) with or without intravesical instillation therapy on cancer-specific-survival rate (CSS) of T1 stage non-muscle-invasive bladder transitional cell carcinoma (BTCC) patients. Methods The data of patients diagnosed with T1 stage non-muscle-invasive BTCC from 2010 to 2015 were obtained from the SEER database. The different dividing groups were based on TURBT with or without intravesical instillation therapy. A 1:1 PSM method was used to balance the differences in baseline data between each group. Herein, Kaplan-Meier methods were used to draw survival curves, and the difference between OS and CSS were compared by Log rank test. In addition, univariate and multivariate Cox regressionanalyses were used to explore the independent risk factors of CSS. Results The OS and CSS of patients in the TURBT combined with intravesical instillation therapy group were higher than those of the TURBT alone group (P < 0.05). TURBT combined with intravesical instillation therapy was a protective factor in prognosis with T1 stage non-muscle-invasive BTCC patients (HR=0.783, 95%CI: 0.650-0.942, P < 0.01). Conclusion TURBT combined with intravesical instillation therapy improves the CSS of patients with T1 stage non-muscle-invasive BTCC.

Avaliação dos níveis da citocina pró-inflamatória fator de necrose tumoral-α em pacientes com diabetes tipo 2 e sua relação com variações genéticas de enzimas antioxidantes e obesidade / Evaluation of proinflammatory cytokine tumor necrosis factor-α levels in obese vs nonobese patients with type 2 diabetes and their relationship to CAT C-262T polymorphism

Introdução: Diabetes tipo 2 (DM2) é um distúrbio multifatorial caracterizado pelo aumento dos níveis de radicais livres. Tanto o estresse oxidativo quanto a obesidade contribuem para um estado inflamatório da doença, principalmente pelo aumento da citocina TNF-α. Sabendo-se que a genética individual pode contribuir para o estresse oxidativo, o estudo avaliou o impacto das variações genéticas de enzimas antioxidantes C262T no gene CAT e polimorfismos nulos dos genes GSTM1 e GSTT1 nos níveis de TNF-α, assim como, avaliou se as variantes genéticas atuariam sinergicamente com a obesidade aumentando os níveis da citocina em diabéticos da Grande Vitória/ES, Brasil.Métodos: O polimorfismo no gene CAT foi avaliado pela técnica PCR/RFLP e nos genes GSTM1 e GSTT1 por PCR multiplex, em 56 pacientes, sendo 28 obesos e 28 não obesos. Níveis de TNF-α foram medidos pela técnica de ELISA sanduíche.Resultados: Frequências das variantes nulas de GSTM1 e GSTT1 foram 44,6% e 17,9%, respectivamente. As frequências genotípicas C262T-CAT foram 73,2%, 25% e 1,8% para homozigoto normal, heterozigoto e homozigoto polimórfico, respectivamente. Não houve associação entre genótipos polimórficos e aumento dos níveis de TNF-α, assim como, não foi demonstrado aumento significante da citocina quando avaliado o sinergismo entre obesidade e genética individual do paciente.Conclusão: Níveis de TNF-α não se elevam em diabéticos tipo 2 na presença dos polimorfismos nos genes CAT, GSTM1 e GSTT1, e a obesidade não atua no aumento dessa citocina na população estudada, separadamente ou em conjunto com a genética individual de variantes nos genes CAT, GSTM1 e GSTT1.

Introduction: Type 2 diabetes is a multifactorial disorder characterized by increased levels of free radicals. Both oxidative stress and obesity contribute to an inflammatory state of the disease, mainly by increasing the levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α). Considering that personal genetics may contribute to oxidative stress, this study assessed the impact of CAT C-262T polymorphism and GSTM1 and GSTT1 null polymorphisms on TNF-α levels in patients with type 2. diabetes. The study also evaluated whether the genetic variants act synergistically with obesity to increase TNF-α levels in patients with diabetes from Grande Vitória, Brazil.Methods: Fifty-six patients were included, of whom 28 were obese and 28 were nonobese. The CAT gene polymorphism was assessed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, whereas GSTM1 and GSTT1 polymorphisms were assessed using multiplex PCR. TNF-α levels were measured using the sandwich ELISA technique.Results: Frequencies of GSTM1 and GSTT1 null polymorphisms were 44.6% and 17.9%, respectively. The genotype frequencies of CATC-262T polymorphism were 73.2%, 25.0%, and 1.8% for normal homozygote, heterozygote, and polymorphic homozygote, respectively. Polymorphic genotypes were not associated with increased TNF-α levels, and there was no significant increase in TNF-α levels when evaluating the synergism between obesity and personal genetics.Conclusion: The presence of CAT, GSTM1, and GSTT1 gene polymorphisms was not associated with increased TNF-α levels in patients with type 2 diabetes. Obesity alone or combined with personal genetics of CAT, GSTM1, and GSTT1gene polymorphisms did not promote increased TNF-α levels in the study population.

Glycaemic changes among children and adolescents with Type 1 Diabetes Mellitus before and during Ramadan fasting using continuous glucose monitoring / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#This study described and compared glycaemic changes with the use of the following Continuous Glucose Monitoring (CGM) metrics: time in range, time in hyperglycaemia and time in hypoglycaemia from retrospective CGM data among children and adolescents with Type 1 Diabetes Mellitus (T1DM), before and during Ramadan to better understand the impact of fasting during this season. @*Methodology@#This study was conducted in 2 tertiary centres: Hospital Putrajaya (HPJ) and Hospital Universiti Sains Malaysia (HUSM) from February to May 2020. Muslim T1DM patients between ages 8 to18 who intended to fast during Ramadan were given Ramadan-focused education. CGM iPro2® (Medtronic) was used before and during Ramadan, complemented by finger-prick glucose monitoring or self-monitoring of blood glucose (SMBG). @*Results@#Of the 32 patients, only 24 (12 female) were analysed. Mean age was 13.6 ± 3.1 years old, mean HbAlc was 9.6 ± 1.9% and mean duration of illness was 5.4 ± 3.4 years. Majority (91.7%) were on multiple dose injections (MDI) while only 8.3% were on continuous subcutaneous insulin infusion (CSII). All fasted in Ramadan without acute complications. Retrospective CGM analysis revealed similar results in time in range (TIR), time in hyperglycaemia and time in hypoglycaemia before and during Ramadan, indicating no increased hypoglycaemic or hyperglycaemic events related to fasting. Glycaemic variability before Ramadan as measured by the LBGI, HBGI and MAG, were similar to values during Ramadan.@*Conclusion@#Ramadan fasting among T1DM children and adolescents, by itself, is not associated with short-term glycaemic deterioration. T1DM youths can fast safely in Ramadan with the provision of focused education and regular SMBG.

Lipid analysis of coronary atherosclerotic plaques and the mechanism of restenosis after coronary endarterectomy / 中华胸心血管外科杂志

Objective:To analyze the lipid composition of coronary atherosclerotic plaques and explore the mechanism of its influence on the medium and long-term efficacy of coronary endarterectomy(CE).Methods:From January 2018 to December 2019, a total of 50 patients with diffuse coronary artery disease(DCAD)and hyperlipidemia in Beijing Anzhen Hospital were enrolled to undergo coronary artery bypass grafting combined with anterior descending CE. After the informed consent was signed before the operation, the coronary endarterectomy plaque tissue and blood plasma samples were taken during the operation. Patients were further examined by coronary atherosclerosis T1-weighted characterization(CATCH) and power domain non-orthogonal multiple access(NOMA)postoperatively to analyze middle and long-term coronary restenosis risks. They were divided into high-risk group(restenosis rate >25%, study group) and matched low-risk group(control group). Lipid and molecular biological analysis were performed in the two groups to detect the tissue and cytochrome P450 3A4 enzyme(CYP3A4) content of plaque samples.Results:8 patients were enrolled in each group. The lipid analysis showed that and tissue samples from patients in the study group had a significantly higher level of 4α- Hydroxycholesterol(4α-OHC)as compared to the control group(0.050 μmol/g vs. 0.016 μmol/g, P<0.05). Further, 12 months after the operation, CATCH results showed that the patency rate of the control group was better than that of the study group[coronary artery stenosis rate(9.01±1.9)% vs.(22. 31±2.3)%, P<0.05]. Comparison of CYP3A4 content showed that: the CYP3A4 in blood plasma for the study group was higher than that in the control group[immediate(0.88±0.05)ng/ml vs.(0. 45±0.03) ng/ml and(2. 08± 0.40) ng/ml vs.(1. 58± 0.16)ng/ml, P<0.05]. Conclusion:High expression of 4 α- OHC may accelerate atherosclerosis(AS) after CE and cause restenosis in the middle and long term; It was also confirmed that 4 α- OHC is a biomarker of CYP3A4, which suggests for further investigation of the mechanism of progression after CE.

A hybrid bacterium with tumor-associated macrophage polarization for enhanced photothermal-immunotherapy

Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages (TAMs) and increasing the immunogenicity of tumors via immunogenic cell death (ICD) have been emerging as promising anticancer immunotherapy strategies. However, the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging. To overcome these dilemmas, a hybrid bacterium with tumor targeting and penetration, TAM polarization, and photothermal conversion capabilities is developed for improving antitumor immunotherapy in vivo. The hybrid bacteria (B.b@QDs) are prepared by loading Ag2S quantum dots (QDs) on the Bifidobacterium bifidum (B.b) through electrostatic interactions. The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues, enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment. It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photothermal effect of the QDs, resulting in an enhanced immune effect. This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.

Immunomodulatory effect of adriamycin in mouse 4T1 model of breast cancer / 生物工程学报

To explore the immunomodulatory effect of adriamycin on 4T1 breast cancer. We used a tandem mass tag-based quantitative proteomic method to detect differential proteins in breast cancer tissues, and multiple bioinformatics databases to analyze the differentially expressed proteins in the proteome. Also, we used enzyme-linked immunosorbent assay to detect the effects of adriamycin on helper T cells 1 and 2 in breast cancer tissues, and flow cytometry to detect CD4+ T cells, CD8+ T cells and regulatory T cells. We discovered the immunomodulatory targets of adriamycin in differential proteins. In total 170 differential proteins were significantly up-regulated, whereas 58 were markedly down-regulated. In addition, 73 proteins were involved in immune regulation. Kyoto encyclopedia of genes and genomes enriched important protein pathways related to cytokines and factor receptors, interleukin 17 pathway and cancer transcriptional regulatory pathways. These pathways and important differential proteins related to immunomodulatory functions were ultimately regulated by adriamycin on CD4+ T cells, CD8+ T cells and regulatory T cells, thereby affecting the prognosis of breast cancer. Moreover, adriamycin significantly increased interleukin 2, CD4+ T and CD8+ T (P<0.01) and markedly reduced regulatory T cells (P<0.05). The function of adriamycin against triple-negative breast cancer was closely related to the immunoregulation process of the differential proteins Ighm, Igkc, S100A8, S100A9 and Tmsb4x. Adriamycin could regulate the content of helper T cells 1 cytokines, CD4+ T and CD8+ T lymphocytes in breast cancer and reduce the number of regulatory T cells to produce immunomodulatory effects.

Reactive oxygen species and senescence modulatory effects of rice bran extract on 4T1 and NIH-3T3 cells co-treatment with doxorubicin

Objective:To determine the effect of rice bran extract (RBE) in combination with doxorubicin on 4T1 triple-negative breast cancer cells and NIH-3T3 cells. Methods:RBE was obtained by maceration with n-hexane. The phytochemical profile of RBE was observed using high-performance liquid chromatography. Cytotoxic effect of RBE was evaluated through MTT assay. In addition, flow cytometry was used for cell cycle and apoptosis analysis. Cellular senescence was observed using SA-β-Gal assay and intracellular reactive oxygen species (ROS) levels were evaluated using DCFDA staining. The pro-oxidant property of RBE was also evaluated through 1-chloro-2,4-dinitrobenzene spectrophotometry and molecular docking. Results:RBE was obtained with a yield of 18.42％ w/w and contained tocotrienols as the major compound. RBE exerted no cytotoxic effect on 4T1 and NIH-3T3 cells. However, RBE in combination with doxorubicin decreased 4T1 cell viability synergistically (combination index<0.9) and induced apoptosis and senescence on 4T1 cells. RBE significantly decreased senescence in doxorubicin-treated NIH-3T3 cells. Additionally, RBE did not increase ROS levels in doxorubicin-treated 4T1 cells. Meanwhile, the combination of RBE and doxorubicin reduced ROS levels in NIH-3T3 cells. RBE significantly reduced glutathione-S-transferase activity and alpha-tocotrienol interacted with glutathione-S-transferase in the glutathione binding site. Conclusions:Rice bran may be used as a co-chemotherapeutic agent to improve the therapeutic effectiveness of doxorubicin while protecting against the cellular senescence effects of doxorubicin on healthy cells.

Efficacy of surgical management for esophageal squamous cell carcinoma in pathological stage T1b / 中国胸心血管外科临床杂志

@#Objective    To investigate the prognostic survival status and influence factors for surgical treatment of esophageal squamous cell carcinoma (ESCC) in pathological stage T1b (pT1b). Methods    The patients with ESCC in pT1b undergoing Ivor-Lewis or McKeown esophagectomy in Lanzhou University Second Hospital from 2012 to 2015 were collected, including 78 males (78.3%) and 17 females (21.7%) with an average age of 61.4±7.4 years. Results    The most common postoperative complications were pneumonia (15.8%), anastomotic leakage (12.6%) and arrhythmia (8.4%). Ninety-three (97.9%) patients underwent R0 resection, with an average number of lymph node dissections of 14.4±5.6. The rate of lymph node metastasis was 22.1%, and the incidence of lymph vessel invasion was 13.7%. The median follow-up time was 60.4 months, during which 25 patients died and 27 patients relapsed. The overall survival rate at 3 years was 86.3%, and at 5 years was 72.7%. Multivariate Cox regression analysis showed that lymph node metastasis (P=0.012, HR=2.60, 95%CI 1.23-5.50) and lympovascular invasion (P=0.014, HR=2.73, 95%CI 1.22-6.09) were independent risk factors for overall survival of pT1b ESCC. Conclusion    Esophagectomy via right chest approach combined with two-fields lymphadenectomy is safe and feasible for patients with pT1b ESCC. The progress of pT1b ESCC with lymph node metastasis or lymphovascular invasion is relatively poor.

Prognostic analysis of pT1b esophageal squamous cell carcinoma after open or minimally invasive esophagectomy / 中国胸心血管外科临床杂志

@#Objective    To compare the short-term and long-term effects of minimally invasive esophagectomy (MIE) and traditional open esophagectomy (OE) in patients with stage T1b esophageal squamous cell carcinoma (ESCC). Methods    We retrospectively analyzed the clinical pathology data of 162 patients undergoing thoracic surgery at Northern Jiangsu People's Hospital from 2015 to 2018 whose pathological diagnosis was stage pT1b ESCC. According to the surgical approach, they were divided into MIE group and OE group. There were 55 males and 21 females in the OE group, with an average age of 63.3±5.6 years, and 60 males and 26 females in the MIE group, with an average age of 64.7±6.1 years. The preoperative, intraoperative and postoperative data of the two groups were compared and followed up. Survival data were compared using Kaplan-Meier and log-rank tests between the two groups, and Cox proportional hazard regression models were used to analyze prognostic factors. Results    Compared with the OE group, the intraoperative bleeding volume of the MIE group was less (119.8±70.0 mL vs. 210.5±136.2 mL, P<0.001), and the lymph nodes dissected during the operation were more (19.1±7.4 vs. 13.8±5.9, P<0.001), the rate of postoperative pulmonary infections was lower (9.3% vs. 21.1%, P=0.036), but the operation time was longer (240.0±52.4 min vs. 179.5±35.7 min, P<0.001). Twenty-one patients had lymph node metastasis, and the lymph node metastasis rate was 13.0%. At the end of the follow-up, 19 patients died, and the overall survival (OS) at 1 year, 3 years, and 5 years after operation were 97.5%, 88.8% and 82.9%, respectively; 31 patients had recurrence and metastasis, and the disease-free survival (DFS) rate at 1 year, 3 years, and 5 years after operation was 95.1%, 80.9% and 75.6%. There was no significant difference in OS and DFS between the two groups. Multivariate Cox regression analysis of OS found that lymph node metastasis, anastomotic fistula and chylothorax were independent risk factors for OS. Multivariate Cox regression analysis of DFS found that lymph node metastasis, anastomotic fistula, chylothorax, and vascular cancer thrombus were independent risk factors for OS. Conclusion    MIE can achieve the same long-term effects as OE, with less intraoperative bleeding, more lymph nodes dissected, and lower incidence of postoperative pulmonary infections, but it takes longer operation time.

Cardiac Magnetic Resonance in the Assessment of Chagas Disease and its Complications

Abstract The well-known occurrence of Chagas disease in endemic areas has become a worldwide problem, and cardiac magnetic resonance allows the early detection of cardiac involvement and complications of this disease. Cardiac magnetic resonance is a useful tool in all phases of Chagas disease, and new promising techniques using T1 mapping and extracellular volume measurements are able to detect cardiac involvement even earlier than conventional techniques.