Physician Modified Fenestrated Endografts for Endovascular Aortic Arch Repair in Zone 0.

OBJECTIVE: This multicentre study aimed to assess the early and midterm outcomes of physician modified fenestrated endografts (PMEGs) for endovascular aortic arch repair in zone 0. METHODS: Between 2018 and 2022, a retrospective study was conducted in three centres of consecutive patients undergoing endovascular aortic arch repair in zone 0 with PMEGs. Endpoints included technical success, 30 day mortality rate, major adverse events, secondary interventions, stent stability, target vessel patency, and overall survival. RESULTS: A total of 54 patients (mean age 63 years; 45 males) with aortic arch pathology were included, comprising aortic dissections (n = 32; 59%) and aortic arch aneurysms (n = 22; 41%). Technical success was 98%. One patient died from stroke within 30 days. Major adverse events included stroke (n = 4; 7%), retrograde type A dissection (RTAD) (n = 3; 6%), and acute kidney injury (n = 2; 4%). During a median follow up of 12 months, there were two deaths (4%) of unknown cause at one month and 1.5 months, and no aortic related death. Type Ia, type Ic, and type IIIc endoleaks were observed in two (4%), three (6%), and two (4%) patients, respectively. No vessel stenosis was observed. Re-intervention was required in 10 patients (19%). Estimates of overall survival, freedom from secondary intervention, and freedom from target vessel instability at one year were 94.2% (standard error [SE] 3.3%), 81.8% (SE 6.0%), and 92.0% (SE 4.5%), respectively. CONCLUSION: This study has demonstrated the efficacy of PMEGs for zone 0 endovascular aortic arch repair, with acceptable technical success and mortality rates. Stroke, RTAD, and re-intervention rates remain a concern for endovascular therapy. A larger population and long term outcomes are required to assess the safety and durability of this technique as a beneficial choice for endovascular aortic arch repair in specialised centres.

[Identification and functional analysis of jasmonic acid signaling repressor McJAZ8 gene in Mentha canadensis].

Mentha canadensis, as a plant with medicinal and culinary uses, holds significant economic value. Jasmonic acid signaling repressor JAZ protein has a crucial role in regulating plant response to adversity stresses. The M. canadensis McJAZ8 gene is cloned and analyzed for protein characterization, protein interactions, and expression patterns, so as to provide genetic resources for molecular breeding of M. canadensis for stress tolerance. This experiment will analyze the protein structural characteristics, subcellular localization, protein interactions, and gene expression of McJAZ8 using bioinformatics, yeast two-hybrid(Y2H), transient expression in tobacco leaves, qRT-PCR, and other technologies. The results show that:(1)The full length of the McJAZ8 gene is 543 bp, encoding 180 amino acids. The McJAZ8 protein contains conserved TIFY and Jas domains and exhibits high homology with Arabidopsis thaliana AtJAZ1 and AtJAZ2.(2)The McJAZ8 protein is localized in the nucleus and cytoplasm.(3)The Y2H results show that McJAZ8 interacts with itself or McJAZ1/3/4/5 proteins to form homologous or heterologous dimers.(4)McJAZ8 is expressed in different tissue, with the highest expression level in young leaves. In terms of leaf sequence, McJAZ8 shows the highest expression level in the fourth leaf and the lowest expression level in the second leaf.(5) In leaves and roots, the expression of McJAZ8 is upregulated to varying degrees under methyl jasmonate(MeJA), drought, and NaCl treatments. The expression of McJAZ8 shows an initial upregulation followed by a downregulation pattern under CdCl_2 treatment. In leaves, the expression of McJAZ8 tends to gradually decrease under CuCl_2 treatment, while in roots, it initially decreases and then increases before decreasing again. In both leaves and roots, the expression of McJAZ8 is downregulated to varying degrees under AlCl_(3 )treatment. This study has enriched the research on jasmonic acid signaling repressor JAZ genes in M. canadensis and provided genetic resources for the molecular breeding of M. canadensis.

SIRT1/SREBPs-mediated regulation of lipid metabolism.

Sirtuins, also called silent information regulator 2, are enzymes that rely on nicotinamide adenine dinucleotide (NAD+) to function as histone deacetylases. Further investigation is warranted to explore the advantageous impacts of Sirtuin 1 (SIRT1), a constituent of the sirtuin group, on lipid metabolism, in addition to its well-researched involvement in extending lifespan. The regulation of gene expression has been extensively linked to SIRT1. Sterol regulatory element-binding protein (SREBP) is a substrate of SIRT1 that has attracted significant interest due to its role in multiple cellular processes including cell cycle regulation, DNA damage repair, and metabolic functions. Hence, the objective of this analysis was to investigate and elucidate the correlation between SIRT1 and SREBPs, as well as assess the contribution of SIRT1/SREBPs in mitigating lipid metabolism dysfunction. The objective of this research was to investigate whether SIRT1 and SREBPs could be utilized as viable targets for therapeutic intervention in managing complications associated with diabetes.

Ultrasonic Image Feature Analysis under Deep Learning Algorithm to Evaluate the Efficacy of Drug-Coated Balloon for Treatment of Arteriosclerotic Occlusion.

In order to explore the adoption of ultrasonic images under deep learning (DL) algorithm to evaluate the efficacy of drug-coated balloon (DCB) for treatment of arteriosclerotic occlusion, 56 patients who underwent DCB surgery of lower limb artery were selected and all the patients received the examinations of algorithmic ultrasound and digital subtraction angiography (DSA) before surgery. According to the examination methods, they were classified into algorithmic ultrasound group and DSA group. One to two months after DCB surgery, ultrasound examination was performed with the region-based faster convolutional neural network (faster R-CNN) target detection algorithm to check the therapeutic effect. The results showed that the image effect processed by the target detection algorithm based on DL was signally better than that of traditional ultrasonic processing algorithm in Dice, precision (Pre), and sensitivity, with significant difference (P < 0.05). Compared with DSA, algorithmic ultrasound showed better consistency between the two groups in the diagnosis of common femoral artery, superficial femoral artery, and popliteal artery stenosis, with statistical significance (P < 0.05). However, for the diagnosis of anterior tibial artery stenosis, the consistency between algorithmic ultrasound and DSA was general. The residual stenosis of each artery segment decreased obviously in postoperative review compared with that before surgery, and the difference was statistically significant (P < 0.05). Besides, both the pulsatility index (PI) and the blood flow velocity of the dorsalis pedis artery increased after surgery, compared with those before surgery, with significant differences (P < 0.05). To sum up, ultrasound based on DL target detection algorithm had good imaging effect and good consistency with DSA, which was of the clinical reference value. Additionally, DCB surgery was helpful to treat arteriosclerosis occlusion and improve limb blood supply, which had clinical adoption value.

GLI3 Promotes Invasion and Predicts Poor Prognosis in Colorectal Cancer.

PURPOSE: The epithelial-mesenchymal transition (EMT) is a key hallmark of cancer which promotes malignant progression, especially during the process of cancer invasion. A better understanding of EMT will help elucidate the molecular mechanism underlying colorectal cancer (CRC) metastasis and may provide new insights into the identification of potential biomarkers and therapeutic targets. METHODS: A series of bioinformatic approaches were combined and identify GLI3 as a potential key regulator in EMT. In vitro experiments were performed to knockdown GLI3 expression in two CRC cell lines and to reveal the oncogenic role of GLI3 in CRC. qRT-PCR and western blot were performed to show the influence of GLI3 in EMT and downstream pathways. The Kaplan-Meier analysis and log-rank test were used to evaluate the prognostic value of GLI3 in CRC patients. RESULTS: GLI3 was identified as a key regulator in coexpression and protein-protein interaction (PPI) networks involved in EMT. Bioinformatic analyses indicated that GLI3 had a high correlation with EMT markers in CRC. In vitro experiments showed that GLI3 knockdown attenuated the migratory and invasive capacities of CRC cells via influencing EMT property, especially by regulating phosphorylation of ERK signaling pathway. In addition, higher expression of GLI3 predicts worse prognosis in CRC patients. CONCLUSIONS: In summary, we presented the first evidence that GLI3 could promote the migratory and invasive capacities of CRC cells by regulating the EMT process. Our study might provide some useful clues to a better understanding of GLI3 in EMT during CRC progression.

Application of Hydrogen Peroxide Sensitive Fluorescen Nanoparticles in Atherosclerosis.

ROS plays an important role in the formation of atherosclerotic plaque, especially hydrogen peroxide, which can stimulate macrophages to express pro-inflammatory cytokines and chemokines to enhance the inflammatory activity of macrophages. Therefore, the development of drugs with sensitive release of hydrogen peroxide is safe and effective for the treatment of atherosclerosis The side chain hydroxyl groups of pHEMA were grafted with oxalylsimvastatin (SIM), fluoropolyethylene glycol (fpeg) and macrophage target molecule ISO-1 to prepare hydrogen peroxide sensitive fluorescent drug loaded nanomicelles (phema-simfpeg-iso-1). By using hydrogen peroxide sensitive and controlled-release drug, it can target macrophage, at the same time, improve the characteristics of traditional polyethylene glycol only as hydrophilic chain, and synthesize polyethylene glycol with fluorescence function, so that the polymer can have probe ability without modifying fluorescence substance, which is suitable for the diagnosis and treatment of atherosclerosis. The results show that the water-soluble nanoparticles show good biocompatibility and peroxide Hydrogen sensitivity and fluorescence ability provide new materials for the development of a nano system for the diagnosis and treatment of atherosclerosis.

NPY stimulates cholesterol synthesis acutely by activating the SREBP2-HMGCR pathway through the Y1 and Y5 receptors in murine hepatocytes.

AIMS: The development of non-alcoholic fatty liver disease (NAFLD) is partially attributed to disturbance in cholesterol metabolism and sympathetic overactivity. Excessive levels of the sympathetic neurotransmitter neuropeptide Y (NPY) positively correlated with both NAFLD and cholesterol accumulation. We wanted to determine, for the first time, whether NPY promotes cholesterol accumulation directly in hepatocytes and elucidate the underlying mechanism. MAIN METHODS: In vivo, NPY was injected through the hepatic portal vein into SD rats. One hour later, serum and liver tissues were collected. In vitro, BRL-3A hepatocytes were treated with NPY, and with Y1, Y2, Y5, receptor antagonists as well as with extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) antagonist, respectively. Cholesterol content was measured by coupled enzyme method. Precursor sterol-regulatory element binding protein 2 (pSREBP2), mature SREBP2 (mSREBP2), HMG-CoA reductase (HMGCR), ERK1/2, pERK1/2, cAMP-dependent protein kinase (PKA), and pPKA protein expression levels were examined by western blotting. KEY FINDINGS: In rats, intraportal vein injection of NPY activates pSREBP2, mSREBP2, and HMGCR protein expression, and induces hepatic cholesterol accumulation. In BRL-3A cells, we observed that NPY increases cholesterogenic protein expression and cholesterol synthesis through Y1 and Y5 receptors. This effect is mediated by the activation of the ERK1/2 signaling pathway. SIGNIFICANCE: We demonstrated, for the first time, that NPY can activate the cholesterogenic pathway and elucidated the underlying mechanism. Thus, NPY and NPY receptors might be new targets for the treatment of NAFLD and dyslipidemia.

Stage IA Patients With Pancreatic Ductal Adenocarcinoma Cannot Benefit From Chemotherapy: A Propensity Score Matching Study.

Purpose: Adjuvant chemotherapy following resection is recommended by clinical practice guidelines for all patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to evaluate the efficacy of adjuvant chemotherapy among the staging groups of the American Joint Committee on Cancer (AJCC) for PDAC. Patients and Methods: This retrospective cohort analysis was performed by the Surveillance Epidemiology and End Results (SEER) (2004-2015) database and multi-institutional dataset (2010-2018). Baseline clinicopathologic characteristics of PDAC patients, including age, gender, ethnicity, marital status, education level, county income level, county unemployed rate, insurance status, grade, stage, chemotherapy, and radiotherapy, were collected. Overall survival (OS) was analyzed using the Kaplan-Meier method. The SEER and multi-institutional data were adjusted with 1:1 ratio propensity score matching (PSM). Results: In total, 6,274 and 1,361 PDAC patients were included from the SEER database and multi-institutional dataset, respectively. Regardless of the count of resected lymph nodes, adjuvant chemotherapy prolonged the long-term OS time for stage IB, IIA, IIB, and III patients in both SEER and multi-institutional cohorts. Nevertheless, adjuvant chemotherapy did not provide additional clinical benefits even after a PSM adjustment for stage IA patients in both SEER and multi-institutional cohorts. Conclusion: Adjuvant chemotherapy improved the long-term survival of stage IB, IIA, IIB, and III PDAC patients; however, it demonstrated no survival benefit in stage IA PDAC patients. Thus, adjuvant chemotherapy should not be recommended for stage IA PDAC patients. These would significantly reduce the economic burden of society and improve the life quality of stage IA PDAC patients.

Changes in Serum Nesfatin-1 After Laparoscopic Sleeve Gastrectomy are Associated with Improvements in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a serious and widespread disease worldwide. Bariatric surgery is one of the treatments for NAFLD. Nesfatin-1 is located in the brain, periphery and plasma. We studied the relationship between nesfatin-1 changes after laparoscopic sleeve gastrectomy (LSG) and NAFLD remission. METHODS: A total of 29 patients participated in the study, which collected clinical information on the patients and indicators of liver function, hepatic steatosis score and nesfatin-1 level before and after LSG. RESULTS: The average BMI of the patients before surgery was 42.63±8.91 kg/m2, and the average BMI was 28.54±5.63 kg/m2 one year after surgery (p < 0.05). One year after LSG, the total weight loss percentage (TWL%) was 32.11±7.10%. The mean value of nesfatin-1 before surgery was 3.04±0.81 ng/mL, and the mean value of nesfatin-1 was 5.52±1.55 ng/mL at one year after surgery (p < 0.05). The average preoperative hepatic steatosis index (HSI) score of the patients was 52.55±9.17, and the average postoperative HSI score was 38.84±5.82 (p < 0.05). Before LSG (p < 0.05, r= -0.81) and 1 year after surgery (p < 0.05, r = -0.58), HSI and nesfatin-1 were significantly negatively correlated. Percentage of increased nesfatin-1 and percentage of decreased HSI showed positive correlation after LSG. CONCLUSION: There was a negative correlation between HSI and nesfatin-1 before and after LSG, which may suggest that nesfatin-1 plays a role in NAFLD.

ZW10 Binding Factor (ZWINT), a Direct Target of Mir-204, Predicts Poor Survival and Promotes Proliferation in Breast Cancer.

BACKGROUND ZW10 binding factor (ZWINT) has been reported to be upregulated in various human cancers and predict worse survival. However, the expression profile, clinical significance, and biological role of ZWINT remains unclear in breast cancer. MATERIAL AND METHODS In this study, we investigated messenger RNA (mRNA) and protein expression levels of ZWINT in breast cancer tissues, and the prognostic value of ZWINT protein expression was validated in a cohort of breast cancer patients using immunohistochemistry analysis. Then, different bioinformatic analyses were combined to explore the potential cancer-related hallmark underlying ZWINT in breast cancer, and a series of experiments in vitro were performed to reveal the oncogenic role of ZWINT in breast cancer. RESULTS Significant upregulation of ZWINT was observed in breast cancer tissues compared to normal and para-tumor tissues and upregulation of ZWINT predicts poor prognosis in breast cancer patients. Additionally, ZWINT could promote breast cancer proliferation via cell cycle regulation, especially by influencing the expression of some critical cell cycle regulators involved in G1 phase and G1/S transition. Finally, miR-204 was identified as a tumor suppressor microRNA which directly targets a specific site in 3'-UTR of ZWINT. CONCLUSIONS Overall, our results indicated that miR-204/ZWINT/cell cycle process might play an important role in breast cancer progression.

Functional variants of autophagy-related genes are associated with the development of hepatocellular carcinoma.

AIMS: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and accounts for substantial morbidity and mortality. Autophagy plays an essential role in the development and progression of HCC. This study aims to evaluate whether genetic variants in autophagy-related genes (ATGs) affect the development of HCC. MATERIALS AND METHODS: We conducted a case-control study with 986 HCC cases and 1000 healthy controls to analyze 14 functional variants of five ATGs (ATG3, ATG5, ATG10, ATG12 and ATG16L1) among a Chinese population. KEY FINDINGS: We found ATG5 rs17067724 (G vs A: OR = 0.80; 95% CI = 0.65-0.98; P = 0.031), ATG10 rs1864183 (G vs A: OR = 1.29; 95% CI = 1.07-1.57; P = 0.009), ATG10 rs10514231 (C vs T: OR = 1.41; 95% CI = 1.15-1.73; P = 0.001), ATG12 rs26537 (C vs T: OR = 1.16; 95% CI = 1.02-1.33; P = 0.030), and ATG16L1 rs4663402 (T vs A: OR = 1.28; 95% CI = 1.01-1.63; P = 0.044) were significantly associated with HCC risk. Specifically, ATG10 rs10514231 kept significant association even adjusted for Bonferroni correction (P = 0.001 × 14 = 0.014). Bioinformatics analyses showed that allele C of ATG10 rs10514231 was significantly correlated with higher expression of ATG10 gene in both HCC tissues and normal liver tissues. Dual-luciferase reporter assay presented that cell lines transfected with vectors containing the risk allele C of rs10514231 showed higher relative luciferase activity compared to that containing the allele T. SIGNIFICANCE: These results suggested that ATG10 rs10514231 might contribute to an allele-specific effect on the expression of host gene ATG10 and explain a fraction of HCC genetic susceptibility. Our study would benefit the construction of early warning model, early prevention, screening, even therapeutic target of HCC.

Status of the Field of Bariatric Surgery: a National Survey of China in 2018.

BACKGROUND: Due to the slow development of bariatric surgery in mainland China, we aimed to provide fact-based status reports and recommendations for the development of bariatric surgery in mainland China by investigating the basic context, social environment, and perioperative treatment options of surgeons who perform bariatric surgery. STUDY DESIGN: A questionnaire was prepared based on a literature review, consultations with experts and current issues. The three-part questionnaire was sent to medical professionals in the field of bariatric surgery. The results were gathered, and analysis was performed after collecting the data. RESULTS: In total, 98.5% of respondents were employed at public grade 3 class A hospitals, 70.8% were chief physicians and professors, 53.2% were trained at other institutions before their first bariatric surgery, 65.0% were previously engaged in gastrointestinal surgery, 76.9% were currently engaged in multiple fields of general surgery, 39.5% believed that low self-acceptance was the primary obstacle, 39.0% regarded news media networks as the most valued publicity platform, 48.0% accepted patients less than 16 years old, and 46.0% accepted patients greater than 65 years old. Additionally, 84.6% of respondents addressed comorbidities, 73.4% developed exercise guidance for patients, 81.6% believed that the total hospitalization cost was greater than 50,000 (CNY), 41.5% chose oral purgative for bowel preparation, 40.0% allowed patients to resume oral intake of liquids on the first day after surgery, and 70.7% routinely placed an abdominal drainage tube. CONCLUSION: Bariatric surgery has great potential in mainland China, but many inconsistencies exist. This field is still in its infancy, and much work is needed.

Aminoguanidine reverses cognitive deficits and activation of cAMP/CREB/BDNF pathway in mouse hippocampus after traumatic brain injury (TBI).

PRIMARY OBJECTIVE: We aim to study the effects of chronic aminoguanidine (AG) administration on learning and memory impairment after TBI and explore the potential mechanism involved in this process. RESEARCH DESIGN: Male C57BL/6J mice were divided into 6 groups: Control, TBI + Veh, TBI+ AG (50, 100, 200 and 400 mg/kg, i.p.). METHODS AND PROCEDURES: Then, we measured cyclicadenosine 3', 5'-monophosphate (cAMP) content, phosphorylated form of cAMP-response element binding protein (p-CREB) level, iNOS, brain-derived neurotrophic factor (BDNF) and postsynaptic density-93/95 (PSD-93/95) expression in hippocampus. The learning and memory abilities were assessed using Morris water maze and step-down test. MAIN OUTCOMES AND RESULTS: The results demonstrate that TBI induced down-regulation of BDNF, loss of PSD-93/95, learning and memory deficits with down-regulation of cAMP content and p-CREB/CREB ratio. Administration of AG (200 and 400 mg/kg) reversed TBI induced down-regulation of BDNF and PSD-93/95, up-regulated the cAMP content and p-CREB/CREB ratio, which resulted in improvement of learning and memory ability. CONCLUSIONS: We suspect that AG (200 and 400 mg/kg) might reverse TBI-induced selective loss of postsynaptic proteins and learning and memory deficits with the activation of cAMP/CREB/BDNF signalling pathway.

Upregulation of CDCA5 promotes gastric cancer malignant progression via influencing cyclin E1.

The cell division cycle associated 5(CDCA5) was reported to be associated with progression of several human cancers, however, its clinical significance and biological role still remain unknown in gastric cancer(GC). By analyzing The Cancer Genome Atlas(TCGA), we found CDCA5 was significantly upregulated in GC tissues compared to adjacent normal tissues. Tissue microarray(TMA) indicated upregulation of CDCA5 was significantly correlated with more advanced clinicopathological features, and acts as an independent risk factor for worse overall survival(OS) in GC patients. Moreover, silence of CDCA5 suppresses proliferation of GC cells by inducing G1-phase arrest via downregulating Cyclin E1(CCNE1). Our results demonstrate upregulation of CDCA5 promotes GC malignant progression, which may offer a potential prognostic and therapeutic strategy.

Prognostic significance of distal subtotal gastrectomy with standard D2 and extended D2 lymphadenectomy for locally advanced gastric cancer.

This study was conducted to investigate prognosis and survival of patients undergoing distal subtotal gastrectomy with D2 and D2+ lymphadenectomy for patients with locally advanced gastric cancer. Overall survival rates of 416 patients with locally advanced gastric cancer were compared between D2 and D2+ lymphadenectomy. Univariate analysis and multivariate analysis was used to identify significant prognostic factors correlated with LN metastasis and prognosis. Univariate analysis identified tumor size, lymphatic vessel invasion, pT stage, pN stage, TNM stage, locoregional recurrence, and distant recurrence, to significantly correlate with prognosis; Tumor size, LVI, and pT stage were identified as independent factors correlating with LN metastasis. Multivariate analysis demonstrated that tumor size, pT stage, pN stage, locoregional recurrence, and distant recurrence were independent prognostic factors; Tumor size and pT stage were independent prognostic factors predicting LN metastasis. When comparing 5-year survival rates of patients who underwent D2 and D2+ lymphadenectomy, as stratified by pT stage and pN stage, a significant difference was found in pN3 patients, but not for pT2-4 and pN0-2 patients, or the patient cohort as a whole. In conclusion, D2 lymphadenectomy for patients with locally advanced gastric cancer undergoing distal subtotal gastrectomy was recommended, especially in eastern Asia.