Background/Aims: Systemic Inflammation (SI) is considered a key mechanism in disease progression and development of complications in decompensated liver cirrhosis. SI is mainly driven by portal hypertension and bacterial translocation. Transjugular intrahepatic portosystemic shunt (TIPS) insertion represents an effective treatment for portal hypertension. This study aims to investigate the impact of TIPS insertion on SI and bacterial translocation. Methods: We prospectively included 59 cirrhotic patients undergoing TIPS insertion. Blood samples were collected at TIPS insertion and follow-up (FU) 1, 3, 6, and 12 months thereafter. At all time points, we performed a comprehensive analysis of SI including 43 soluble inflammatory markers (SIMs), and surrogates of bacterial translocation (sCD14, sCD163). To investigate long-term kinetics of SI, C-reactive protein (CRP) and white blood cells (WBC) were retrospectively analyzed in a cohort of 177 patients up to 3 years after TIPS insertion. Results: At TIPS insertion, 30/43 SIMs, sCD14, and sCD163 measured significantly higher in cirrhotic patients compared to healthy controls. By FU6 25 SIMs and sCD14 measured at significantly lower levels compared to baseline. Interestingly, in patients with TIPS indication of refractory ascites, IL-6 decreased to levels documented in earlier stages of cirrhosis. In long-term follow-up, CRP levels significantly decreased after TIPS insertion, which translated into lower mortality in Cox regression analysis (HR 0.968, p=0.042). Notably, patients with residual ascites post-TIPS showed significantly higher CRP and IL-6 levels across all follow-ups compared to patients with resolved ascites. Conclusions Decreasing portal hypertension via TIPS insertion leads to a significant attenuation of SI and bacterial translocation over time.

Background/Aims: Systemic Inflammation (SI) is considered a key mechanism in disease progression and development of complications in decompensated liver cirrhosis. SI is mainly driven by portal hypertension and bacterial translocation. Transjugular intrahepatic portosystemic shunt (TIPS) insertion represents an effective treatment for portal hypertension. This study aims to investigate the impact of TIPS insertion on SI and bacterial translocation. Methods: We prospectively included 59 cirrhotic patients undergoing TIPS insertion. Blood samples were collected at TIPS insertion and follow-up (FU) 1, 3, 6, and 12 months thereafter. At all time points, we performed a comprehensive analysis of SI including 43 soluble inflammatory markers (SIMs), and surrogates of bacterial translocation (sCD14, sCD163). To investigate long-term kinetics of SI, C-reactive protein (CRP) and white blood cells (WBC) were retrospectively analyzed in a cohort of 177 patients up to 3 years after TIPS insertion. Results: At TIPS insertion, 30/43 SIMs, sCD14, and sCD163 measured significantly higher in cirrhotic patients compared to healthy controls. By FU6 25 SIMs and sCD14 measured at significantly lower levels compared to baseline. Interestingly, in patients with TIPS indication of refractory ascites, IL-6 decreased to levels documented in earlier stages of cirrhosis. In long-term follow-up, CRP levels significantly decreased after TIPS insertion, which translated into lower mortality in Cox regression analysis (HR 0.968, p=0.042). Notably, patients with residual ascites post-TIPS showed significantly higher CRP and IL-6 levels across all follow-ups compared to patients with resolved ascites. Conclusions Decreasing portal hypertension via TIPS insertion leads to a significant attenuation of SI and bacterial translocation over time.

Background/Aims: Systemic Inflammation (SI) is considered a key mechanism in disease progression and development of complications in decompensated liver cirrhosis. SI is mainly driven by portal hypertension and bacterial translocation. Transjugular intrahepatic portosystemic shunt (TIPS) insertion represents an effective treatment for portal hypertension. This study aims to investigate the impact of TIPS insertion on SI and bacterial translocation. Methods: We prospectively included 59 cirrhotic patients undergoing TIPS insertion. Blood samples were collected at TIPS insertion and follow-up (FU) 1, 3, 6, and 12 months thereafter. At all time points, we performed a comprehensive analysis of SI including 43 soluble inflammatory markers (SIMs), and surrogates of bacterial translocation (sCD14, sCD163). To investigate long-term kinetics of SI, C-reactive protein (CRP) and white blood cells (WBC) were retrospectively analyzed in a cohort of 177 patients up to 3 years after TIPS insertion. Results: At TIPS insertion, 30/43 SIMs, sCD14, and sCD163 measured significantly higher in cirrhotic patients compared to healthy controls. By FU6 25 SIMs and sCD14 measured at significantly lower levels compared to baseline. Interestingly, in patients with TIPS indication of refractory ascites, IL-6 decreased to levels documented in earlier stages of cirrhosis. In long-term follow-up, CRP levels significantly decreased after TIPS insertion, which translated into lower mortality in Cox regression analysis (HR 0.968, p=0.042). Notably, patients with residual ascites post-TIPS showed significantly higher CRP and IL-6 levels across all follow-ups compared to patients with resolved ascites. Conclusions Decreasing portal hypertension via TIPS insertion leads to a significant attenuation of SI and bacterial translocation over time.

BACKGROUND AND OBJECTIVES

Among patients with macrovascular and microvascular disease, we investigated the association between sulodexide and cardiovascular (CV) outcomes and adverse events.

We conducted a meta-analysis of randomized control trials (RCTs) reporting CV outcomes and adverse events in patients with vascular disease receiving sulodexide for any indication versus control. The following outcomes were investigated: any CV event, myocardial infarction, CV death, bleeding events and gastrointestinal symptoms.

Twelve studies with a total of 8,436 patients were included. Sulodexide resulted in a significant reduction in CV events (OR 0.51 [95% confidence interval 0.41-0.73]; pCONCLUSION

Sulodexide has a beneficial effect among patients with macrovascular disease in terms of reducing the risk for MI, overall CV mortality and CV events. Larger RCTs are needed to corroborate these findings.

BACKGROUND:Previous studies have shown that the modified Tsuge suture method can be used to repair chicken tendon injuries.However,the lack of post-repair functional exercise leads to obvious tendon adhesions.Therefore,a functional exercise after tendon repair is very important. OBJECTIVE:To explore a scheme for passive functional exercise against tendon adhesion in a chicken model of flexor toe tendon rupture following repair using the modified Tsuge suture method. METHODS:A total of 100 Sanhuang chickens,10 months of age,were taken to make animal models of deep flexor tendon Ⅱ rupture of the third toe of the right foot.Animal models were randomized into five groups(n=20 per group):groups A,B,C and D were given plaster immobilization for 3 weeks after surgery,and were simultaneously given passive functional exercise 1,2,3,and 0 times a day for 3 weeks,respectively;group E had neither plaster immobilization nor passive functional exercise after surgery.The gross morphology of the chicken claw,the morphology of the tendon anastomosis end and the degree of peritendinous adhesion were observed.The slipping distance of the deep flexor tendon of the third toe,the flexion angles of all joints,the pathological morphology of the tendon at the anastomotic end and the hydroxyproline content were measured. RESULTS AND CONCLUSION:The tendon of group E was completely ruptured around 6 day after surgery and was removed from the experiment.The chicken claws in groups B and C had better grasping morphology,group D had almost no grasping morphology,and group A had worse grasping morphology than groups B and C.In groups B and C,the tendon anastomosis end was not obviously expanded,with the texture similar to that of normal tendon tissue.Compared with group C,tendon adhesion was relatively mild in group B.In group D,the tendon anastomosis end was obviously expanded,with the hard texture,obvious peritendinous scar and serious adhesion.Expansion at the tendon anastomosis end was more obvious than groups B and C but less severe than group D.The slipping distance and the related flexion angles of the deep flexor tendon of the third toe were better in groups B and C than groups A and D(P<0.05).The content of hydroxyproline in the tendon of chickens in group B was higher than those in groups A,C and D(P<0.05).Findings from hematoxylin-eosin and Sirius red staining showed that collagen fibers of the tendon in groups A,C and B were gradually arranged in a directional manner,where the number of bright red and thick type Ⅰ collagen fibers was gradually increased and the number of tiny green type Ⅲ collagen fibers was gradually decreased.In group E,collagen fibers of the tendon were poorly arranged in a directional manner and type Ⅰ and type Ⅲ collagen fibers were cross-distributed.To conclude,adequate passive functional exercises twice a day following repair with the modified Tsuge suture method could effectively alleviate tendon adhesion and reduce tendon rupture in the chicken model of deep flexor tendon rupture.

Objective: To investigate the clinicopathological features and differential diagnosis of olfactory carcinoma (OC). Methods: Twenty-one cases of sinonasal tumors, including those initially diagnosed as olfactory neuroblastoma (ONB) and those with uncertain diagnosis, were collected from the Department of Pathology, the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2016 to August 2022, among which 3 cases were reclassified as OC. The clinicopathological features were investigated, and the remaining 18 cases were used as control. Results: Of the three OC patients, 2 were male and 1 was female, with an average age of 57 years ranging from 35 to 74 years. Microscopically, the tumor cells were arranged in solid, nested or lobulated patterns with occasional palisading around the solid nests. The stroma was highly vascular with focal neurofibrillary areas. There were prominent rosettes or pseudorosettes formation. The tumor cells were mainly ovoid to spindly with scant to moderate amount of cytoplasm, one or several small nucleoli, and fine chromatin content. Brisk mitotic figures were seen. In all 3 cases of OC, there were scanty atypical glands and some were ciliated. Immunohistochemically, at least one epithelial marker and neuroendocrine marker were diffusely expressed in the tumor. Some of the tumor cells were positive for p40 and p63, and the sustentacular cells showed the expression of S-100 protein. All cases tested were negative for NUT, CD99 and desmin, with intact expression of SMARCA4 (BRG1) and SMARCB1 (INI-1). Ki-67 proliferation index varied from 20% to 80%. Follow-up after 16-18 months showed no mortality with tumor recurrence from 1 patient after 16 months. Conclusion: OC is a rare sinonasal tumor with neuroepithelial differentiation, its histomorphology is diverse, and the combination of immunohistochemical markers is essential for appropriate diagnosis.
Humans ; Male ; Female ; Middle Aged ; Paranasal Sinus Neoplasms/chemistry* ; Biomarkers, Tumor/metabolism* ; Carcinoma/chemistry* ; Diagnosis, Differential ; S100 Proteins ; DNA Helicases/metabolism* ; Nuclear Proteins/metabolism* ; Transcription Factors/metabolism*

Objective To explore the potential mechanism of Erchen decoction in the treatment of obese polycystic ovary syndrome and obese infertility, in order to provide theoretical basis for “treating different diseases with same method”. Methods The active ingredients and targets of Erchen decoction were obtained from TCMSP database, and the targets of obese polycystic ovary syndromes and obese infertility were obtained from GeneCard database. Active ingredient-target network was constructed by Cytoscape 3.7.1, and protein-protein interaction network and core target were obtained from STRING. GO and KEGG enrichment analysis were performed by Cytoscape 3.7.1 and online software. Results 125 ingredients and 218 targets of Erchen decoction were obtained. There were 2 783 target genes for obese infertility and 2 962 target genes for obese polycystic ovary syndrome. Erchen decoction has a total of 117 target genes in the treatment of obese infertility and obese polycystic ovary syndromes, which proves the principle of “treating different diseases with same method”. Potential active ingredients include quercetin, kaempferol, naringin, baicalin and formononetin. PPI showed that STAT3, JUN, AKT1, MAPK3, MAPK1, MAPK14, IL-6 and FOS were the core targets of “treating different diseases with same method”. Molecular docking results showed that quercetin, kaempferol, etc. had good binding ability with JUN. GO and KEGG enrichment analysis showed that AGE-RAGE signaling pathway, IL-17 signaling pathway and endocrine resistance might be the key pathways for the “treating different diseases with same method” of Erchen decoction. Conclusion Erchen decoction treating "different diseases with same method" involves same targets and same pathways, which can provide reference for future experimental research.

Background: Among the various glycemic indices in current use, glycemic variability has the greatest contribution in the development of microvascular and macrovascular complications in Type 2 Diabetes mellitus (T2DM). Most metrics that are currently used to measure glycemic variability are derived from continuous glucose monitoring (CGM) data. However, CGM is burdensome to the patient due to its relatively high cost as well as the need for multiple visits with the health care provider. With the use of serum 1,5-anhydroglucitol (1,5-AG) as a biomarker of glucose fluctuations, physicians and patients alike could have an easier surrogate measure of glycemic variability thus aiding in achieving target glucose control. This study aims to determine the diagnostic accuracy of 1,5-AG as compared to the glycemic variability metrics derived from CGM as a surrogate measure of glycemic variability among adult Filipinos with T2DM. Methods: Retrospective analysis of data of adult patients aged 20 years old and above diagnosed with T2DM referred for CGM at the Diabetes, Endocrine, Metabolic, and Nutrition Center of Cardinal Santos Medical Center from January 2017 to October 2021 who underwent serum 1,5-AG level determination within 2 weeks of CGM were collected. Diagnostic accuracy was obtained by computing the sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and Youden index. Pearson correlation coefficient was used to determine the correlation of 1,5-AG and the different metrics. Analysis of variance (ANOVA) was used to check for statistical significance with 99% confidence interval and a p < 0.05 considered as statistically significant. Results: This study involving 37 subjects showed a good diagnostic accuracy of serum 1,5-AG levels with the different measures of glycemic variability derived from CGM namely mean amplitude of glycemic excursion (MAGE), continuous overlapping net glycemic action at 1-hour intervals (CONGA-1), and mean of daily differences (MODD) with significant correlation among patients with HbA1c ≤ 7%. Subjects were on CGM for approximately 6 ± 1 day with statistically significant difference between the good and poor glucose control group (p<0.05). Determination of diagnostic accuracy between 1,5- AG and MAGE showed good accuracy (Sensitivity = 95.3%, Specificity = 100%, PPV = 100%, NPV = 75.43%, Diagnostic accuracy 96%, and a Youden Index of 92.3) with a statistically significant correlation among subjects with HbA1c level ≤ 7% (p=0.021). There is likewise good diagnostic accuracy between CONGA-1 and 1,5-AG level (Sensitivity = 99%, Specificity = 75.29%, PPV = 89.1%, NPV = 97%, Accuracy = 89.50% and Youden index of 58.41) with a statistically significant correlation among subjects with HbA1c ≤ 7% (p=0.038). Comparison with interday glycemic variability showed fair diagnostic accuracy between MODD and 1,5-AG (Sensitivity = 79.17%, Specificity = 78%, PPV = 97%, NPV = 32%, Accuracy = 76.89%, and Youden index of 49.07) and a statistically significant correlation among subjects with HbA1c ≤ 7% (p=0.009). Conclusion There is good diagnostic accuracy of serum 1,5-AG levels with the different measures of glycemic variability derived from CGM namely MAGE, CONGA-1, and MODD with significant correlation among patients with HbA1c ≤ 7%. Among diabetics with HbA1c ≤7%, 1,5-AG could be used as a surrogate measure of glycemic variability and excursions.
Diabetes Mellitus, Type 2

[摘 要] 目的：探讨甲基转移酶样因子3（METTL3）在食管鳞状细胞癌（ESCC）组织和细胞中的表达水平及其对ESCC细胞糖酵解和增殖能力的影响和潜在的分子机制。方法：基于TCGA数据库分析METTL3在ESCC细胞中的表达及可能的富集通路。收集2021年1月至2021年6月间在北川医学院附属医院外科手术切除的34例ESCC组织及相应癌旁组织，采用免疫组化法验证ESCC组织中METTL3的表达。采用CCK-8法和平板克隆形成实验检测干扰METTL3后ESCC细胞增殖能力的变化，利用比色法检测干扰METTL3后ESCC细胞总RNA中m6A的表达水平，采用甲基化RNA免疫沉淀定量PCR（MeRIP-qPCR）检测METTL3对葡萄糖转运蛋白4（GLUT4）基因mRNA的m6A修饰水平的影响，采用WB和qPCR等技术探索METTL3参与ESCC细胞糖酵解的生物学机制。结果：METTL3在ESCC组织以及细胞中均呈高表达（均P<0.001）。干扰METTL3表达后，ESCC细胞的增殖能力明显减弱、细胞内总RNA的m6A修饰水平显著降低（均P<0.001）。此外，干扰METTL3可显著抑制KYSE150和TE-1细胞中GLUT4基因mRNA的m6A修饰水平（均P<0.01），并通过下调GLUT4的表达抑制葡萄糖的摄取以及乳酸的释放（均P<0.01），最终下调mTORC1通路活性并抑制ESCC细胞的增殖；在干扰METTL3的ESCC细胞同时联合运用mTORC1通路抑制剂显示有协同的抗癌作用。结论：METTL3介导的m6A修饰通过调控GLUT4-mTORC1信号轴影响ESCC细胞的糖酵解及增殖。

PURPOSE: This research examined road traffic injury mortality and morbidity disparities across of country development status, and discussed the possibility of reducing country disparities by various actions to accelerate the pace of achieving Sustainable Development Goals target 3.6 - to halve the number of global deaths and injuries from road traffic accidents by 2020. METHODS: Data for road traffic mortality, morbidity, and socio-demographic index (SDI) were extracted by country from the estimates of the Global Burden of Disease study, and the implementation of the three types of national actions (legislation, prioritized vehicle safety standards, and trauma-related post-crash care service) were extracted from the Global Status Report on Road Safety by World Health Organization. We fitted joinpoint regression analysis to identify and quantify the significant rate changes from 2011 to 2017. RESULTS: Age-adjusted road traffic mortality decreased substantially for all the five SDI categories from 2011 to 2017 (by 7.52%-16.08%). Age-adjusted road traffic mortality decreased significantly as SDI increased in the study time period, while age-adjusted morbidity generally increased as SDI increased. Subgroup analysis by road user yielded similar results, but with two major differences during the study period of 2011 to 2017: (1) pedestrians in the high SDI countries experienced the lowest mortality (1.68-1.90 per 100,000 population) and morbidity (110.45-112.72 per 100,000 population for incidence and 487.48-491.24 per 100,000 population for prevalence), and (2) motor vehicle occupants in the high SDI countries had the lowest mortality (4.07-4.50 per 100,000 population) but the highest morbidity (428.74-467.78 per 100,000 population for incidence and 1025.70-1116.60 per 100,000 population for prevalence). Implementation of the three types of national actions remained nearly unchanged in all five SDI categories from 2011 to 2017 and was consistently stronger in the higher SDI countries than in the lower SDI countries. Lower income nations comprise the heaviest burden of global road traffic injuries and deaths. CONCLUSION Global road traffic deaths would decrease substantially if the large mortality disparities across country development status were reduced through full implementation of proven national actions including legislation and law enforcement, prioritized vehicle safety standards and trauma-related post-crash care services.