Circ_UBAP2 exacerbates proliferation and metastasis of OS via targeting miR-665/miR-370-3p/HMGA1 axis.

Circ_UBAP2 is extensively engaged in regulating the development of various malignancies, containing osteosarcoma (OS). However, its biological significance and function are not fully understood. In this study, we found that circ_UBAP2 and HMGA1 levels were up-regulated, and miR-370-3p and miR-665 expressions were decreased in osteosarcoma tissues. Inhibition of circ_UBAP2 or HMGA1 expression in OS cells, cell viability, invasion and migration abilitities were notably hindered, and cell apoptosis abilities were increased. Bioinformatics analysis predicted that miR-665 and miR-370-3p were the downstream targets of circ_UBAP2, and the dual luciferase experiment demonstrated the correlation between them. In addition, inhibition of miR-665 and miR-370-3p expression could significantly reverse the impact of knocking down circ_UBAP2 on OS cells. HMGA1 was discovered to become the downstream target of both miR-665 and miR-370-3p. It was shown that over-expression of miR-665 or miR-370-3p notably stimulated the cell growth, invasion, and migration of osteosarcoma cells, while hindered cell apoptosis. Nevertheless, this effect could be reversed by concurrent over-expression of HMGA1. Our data strongly prove that circ_UBAP2 makes a vital impact on promoting the proliferation, invasion as well as migration of osteosarcoma cells via down-regulating the level of miR-665 and miR-370-3p, and later up-regulating the level of HMGA1. In conclusion, circ_UBAP2 is upregulated in osteosarcoma, and it competitively adsorbs miR-370-3p and miR-665, resulting in up-regulation of HMGA1, thus promoting OS development.

Quantum Simulation of Topological Zero Modes on a 41-Qubit Superconducting Processor.

Quantum simulation of different exotic topological phases of quantum matter on a noisy intermediate-scale quantum (NISQ) processor is attracting growing interest. Here, we develop a one-dimensional 43-qubit superconducting quantum processor, named Chuang-tzu, to simulate and characterize emergent topological states. By engineering diagonal Aubry-André-Harper (AAH) models, we experimentally demonstrate the Hofstadter butterfly energy spectrum. Using Floquet engineering, we verify the existence of the topological zero modes in the commensurate off-diagonal AAH models, which have never been experimentally realized before. Remarkably, the qubit number over 40 in our quantum processor is large enough to capture the substantial topological features of a quantum system from its complex band structure, including Dirac points, the energy gap's closing, the difference between even and odd number of sites, and the distinction between edge and bulk states. Our results establish a versatile hybrid quantum simulation approach to exploring quantum topological systems in the NISQ era.

Novel Cardioplegia Delivery in Patients with Severe Aortic Regurgitation.

During aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR), repeated delivery of cardioplegia into the coronary ostia using a routine infusion cannula may induce coronary ostial injury. This study aims to introduce a new no-touch delivery method with reduced time and similar or better outcomes. Preliminary results have shown that no-touch cardioplegia delivery method was a simple, safe, and effective approach for cardioplegia infusion during AVR in patients with severe AR.

Does the 45 mm Size Cutoff for Ascending Aortic Replacement Predict Better Early Outcomes in Bicuspid Aortic Valve?

BACKGROUND: The aim of this study is to test if the newly proposed 45 mm size criterion for ascending aortic replacement (AAR) in bicuspid aortic valve (BAV) patients undergoing aortic valve replacement (AVR) is predictive of improved early outcomes. METHODS: Data of 306 BAV patients with an aortic diameter of ≥45 mm undergoing AVR alone or with AAR were retrospectively analyzed. Patients were divided into groups of AVR + AAR (n = 220) and AVR only (n = 86) based on if surgery was performed according to the 45 mm criterion. End point was early adverse events, including 30-day and in-hospital mortality, cardiac events, acute renal failure, stroke, and reoperation for bleeding. Cox regression was used to assess if conformance to 45 mm criterion could predict fewer early adverse events. RESULTS: AVR + AAR group had significantly higher postoperative left ventricular ejection fraction (LVEF) (0.59 ± 0.09 vs. 0.55 ± 0.11, p = 0.006) and longer cardiopulmonary bypass (CPB) time (128 vs. 111 minutes, p = 0.002). Early adverse events occurred in 45 patients (14.7%), which was more prevalent in the AVR-only group (22.1% vs. 11.8%, p = 0.020). Conformance to the 45 mm criterion predicted lower rate of early adverse events (hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.28-0.98, p = 0.042). After adjustment for gender, age, AAo diameter, sinuses of Valsalva diameter, preoperative LVEF, Sievers subtypes, BAV valvulopathy, and CPB and cross-clamp times, conformance to the 45 mm size criterion still predicted lower incidence of early adverse events (HR: 0.37, 95% CI: 0.15-0.90, p = 0.028). CONCLUSIONS: This study shows that conformance to 45 mm size cutoff for preemptive AAR during aortic valve replacement in patients with BAV was not associated with increased risk for adverse events and may improve early surgical outcomes.

The LINC01410/miR-122-5p/NDRG3 axis is involved in the proliferation and migration of osteosarcoma cells.

PURPOSE: It is generally accepted that long noncoding RNAs (lncRNAs) function as vital regulators of tumor development and progression. Long intergenic non-coding RNA 1410 (LINC01410) is a newly discovered lncRNA, and its role in osteosarcoma (OS) is yet to be determined. MATERIALS AND METHODS: The expression of LINC01410, microRNA-122-5p (miR-122-5p), and N-myc downstream-regulated gene 3 (NDRG3) in OS tissues was determined using reverse transcription-quantitative PCR. Interactions between LINC01410, miR-122-5p, and NDRG3 were predicted and verified using bioinformatics tools and luciferase assays. Cell proliferation, migration, and invasion were detected using cell counting Kit-8 and Transwell assays. RESULTS: LINC01410 was overexpressed in OS tissues. Furthermore, it was confirmed that LINC01410 facilitated OS cell proliferation and migration. Our studies also showed that LINC01410 binds to miR-122-5p, and miR-122-5p binds to NDRG3. Finally, we observed that LINC01410 knockdown inhibited the proliferation, invasion, and migration of OS cells. Knockdown of LINC01410 resulted in the upregulation of miR-122-5p and downregulation of NDRG3. CONCLUSION: Our results demonstrated that the LINC01410/miR-122-5p/NDRG3 axis is involved in the progression of OS.

Development and validation of a risk prediction score for patients with nasopharyngeal carcinoma.

BACKGROUND: We aimed to develop and validate a predictive model for the overall survival (OS) of patients with nasopharyngeal carcinoma (NPC). METHODS: Overall, 519 patients were retrospectively reviewed in this study. In addition, a random forest model was used to identify significant prognostic factors for OS among NPC patients. Then, calibration plot and concordance index (C-index) were utilized to evaluate the predictive accuracy of the nomogram model. RESULTS: We used a random forest model to select the three most important features, dNLR, HGB and EBV DNA, which were significantly associated with the OS of NPC patients. Furthermore, the C-index of our model for OS were 0.733 (95% CI 0.673 ~ 0.793) and 0.772 (95% CI 0.691 ~ 0.853) in the two cohorts, which was significantly higher than that of the TNM stage, treatment, and EBV DNA. Based on the model risk score, patients were divided into two groups, associated with low-risk and high-risk. Kaplan-Meier curves demonstrated that the two subgroups were significantly associated with OS in the primary cohort, as well as in the validation cohort. The nomogram for OS was established using the risk score, TNM stage and EBV DNA in the two cohorts. The nomogram achieved a higher C-index of 0.783 (95% CI 0.730 ~ 0.836) than that of the risk score model 0.733 (95% CI 0.673 ~ 0.793) in the primary cohort (P = 0.005). CONCLUSIONS: The established risk score model and nomogram resulted in more accurate prognostic prediction for individual patient with NPC.

Long noncoding RNA LINC01410 promotes tumorigenesis of osteosarcoma cells via miR-497-5p/HMGA2 axis.

LINC01410 is a tumor promoter that is upregulated in some cancer types, such as osteosarcoma (OS). Nonetheless, its role in OS and the underlying molecular mechanism have not been fully understood. Hence, we sought to elucidate it. We performed reverse-transcription quantitative polymerase chain reaction for examining LINC01410, miR-497-5p and HMGA2 levels. Additionally, we carried out the cell counting kit-8 and Transwell assays for detecting cell proliferation and invasion/migration. Bioinformatics predicted that there was a miR-497-5p binding site in LINC01410 or HMGA2; meanwhile, miR-497-5p was found to interact with HMGA2 and LINC01410 through dual-luciferase reporter assay. LINC01410 and HMGA2 were high, and miR-497-5p showed low expression in OS tissues and cells. Cell function assay demonstrated that LINC01410 or HMGA2 knockdown or miR-497-5p overexpression obviously restrained OS proliferation, invasion, and migration. Oppositely, inhibiting miR-497-5p had the opposite effects. Functionally, miR-497-5p bound with LINC01410 3'-untranslated region and HMGA2 was found to be the miR-497-5p target gene. Lastly, LINC01410 enhanced OS cell growth, invasion, and migration via decreasing miR-497-5p expression, whereas increasing that of HMGA2. We have demonstrated that LINC01410 promoted OS development partly by miR-497-5p/HMGA2 signal transduction pathway and this provides a reference for studying the mechanism of LINC01410 in OS.

Is obstructive sleep apnoea associated with hypoxaemia and prolonged ICU stay after type A aortic dissection repair? A retrospective study in Chinese population.

BACKGROUND: Although obstructive sleep apnoea (OSA) is prevalent among patients with aortic dissection, its prognostic impact is not yet determined in patients undergoing major vascular surgery. We aimed to investigate the association of OSA with hypoxaemia and with prolonged intensive care unit (ICU) stay after type A aortic dissection (TAAD) repair. METHODS: This retrospective study continuously enrolled 83 patients who underwent TAAD repair from January 1 to December 31, 2018. OSA was diagnosed by sleep test and defined as an apnoea hypopnea index (AHI) of ≥ 15/h, while an AHI of > 30/h was defined severe OSA. Hypoxaemia was defined as an oxygenation index (OI) of < 200 mmHg. Prolonged ICU stay referred to an ICU stay of > 72 h. Receiver operating characteristic curve analysis was performed to evaluate the predictive value of postoperative OI for prolonged ICU stay. Multivariate logistic regression was performed to assess the association of OSA with hypoxaemia and prolonged ICU stay. RESULTS: A total of 41 (49.4%) patients were diagnosed with OSA using the sleep test. Hypoxaemia occurred postoperatively in 56 patients (67.5%). Postoperatively hypoxaemia developed mostly in patients with OSA (52.4% vs. 83.0%, p = 0.003), and particularly in those with severe OSA (52.4% vs. 90.5%, p = 0.003). The postoperative OI could fairly predict a prolonged ICU stay (area under the receiver-operating characteristic curve, 0.72; 95% confidence intervals [CI] 0.60-0.84; p = 0.002). Severe OSA was associated with both postoperative hypoxaemia (odds ratio [OR] 6.65; 95% CI 1.56-46.26, p = 0.008) and prolonged ICU stay (OR 5.58; 95% CI 1.54-20.24, p = 0.009). CONCLUSIONS: OSA was common in patients with TAAD. Severe OSA was associated with postoperative hypoxaemia and prolonged ICU stay following TAAD repair.

Identification of Blood miR-216a, miR-377 and Their Target Genes ANGPTL4, GAP-43 and Serum of PPARG as Biomarkers for Diabetic Peripheral Neuropathy of Type 2 Diabetes.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common and complex chronic complications of diabetes, but it is clinically lacking effective means for early diagnosis and early treatment. MicroRNA, in the occurrence and development of the disease, has an important regulatory role. Its role in diabetes has been reported more. However, specific research on microRNA in DPN is rare. METHODS: Based on the results of bioinformatics screening, miR-377 and miR-216a, their respective target molecules growth association protein 43 (GAP-43) and angiopoietin-like 4 protein (ANGPTL4), and related pathways peroxisome proliferator activated receptor gamma (PPARG) and chemerin were tested by RT-qPCR and ELISA in blood samples of DPN to analyze the correlation between these differentially expressed molecules and clinico-pathological factors of DPN. RESULTS: In this study, we found that miR-377, miR-216a, GAP-43, ANGPTL4, and PPARG were significantly differentially expressed genes for DPN. The correlation analysis showed that they were closely related to the clinical indicators of DPN suggesting that they may be involved in the development of DPN. In addition, receiver operating characteristic (ROC) curves generated for miR216a, miR377, ANGPTL4, GAP43, PPARG revealed that they can be used as new molecular diagnostic markers of DPN. CONCLUSIONS: miR-216a, miR-377, ANGPTL4, GAP-43, and PPARG could potentially be biomarkers of DPN.

Management of acute type A aortic dissection during COVID-19 outbreak: Experience from Anzhen.

OBJECTIVES: We seek to report our management protocol and early outcomes of acute type A aortic dissection (ATAAD) repair during the early phase of coronavirus disease 2019 (COVID-19). METHODS: From January 23 to April 30, 2020, we performed ATAAD repair for 33 patients, including three with pregnancy-related TAADs. Confirmation of COVID-19 depended on the results of two nucleic acid tests and pulmonary computed tomography scan. Based on testing results and hemodynamic stability, patients were triaged to an isolated intensive care unit or negative pressure operating room for emergency surgery. RESULTS: Mean age 50.2 ± 13.3 years and 20 were male (60.1%) and 8 patients were febrile (>37.3°C; 24.2%) and 17 were lymphopenic (51.5%). No patient was excluded from COVID-19 infection preoperatively. Extensive aortic repair with total arch replacement (TAR) was performed in 24 (72.7%), and limited proximal repair in 9 patients (27.3%). Cardiopulmonary bypass and cross-clamp times averaged 177 ± 34 and 88 ± 20 min for TAR, and 150 ± 30 and 83 ± 18 min for hemiarch, respectively. The mean operation time was 410 ± 68.3 min. Operative mortality was 6.1% (2/33). Complications included reintubation in four (12.1%), acute kidney failure in two (6.1%), and cerebral infarction in one (3.0%). No paraplegia nor re-exploration for bleeding occurred. COVID-19 was excluded in 100% eventually. No nosocomial infection occurred. Nor did any patient/surgical staff develop fever or test positive during the study period. CONCLUSIONS: The results of this study show that our management protocol based on testing results and hemodynamic stability in patients with ATAAD during the COVID-19 pandemic was effective and achieved favorable early surgical outcomes.

Incidental para-ureteral aggressive angiomyxoma: a rare case report and literature review.

BACKGROUND: Aggressive angiomyxoma (AA) is a rare tumor that typically occurs in the pelvis and perineum, most commonly in women of reproductive age. However, no para-ureteral AA has been reported according to the literature. Case presentation We herein describe the first case of para-ureteral AA. A 62-year-old male presented to our institute in March 2017 with a para-ureteral mass that was 15 mm in diameter incidentally. No symptom was observed and laboratory analysis was unremarkable. Magnetic resonance and computed tomography imaging showed a non-enhancing mass abutting the left ureter without causing obstruction. Laparoscopic resection of the mass was performed without injury to the ureter. Pathologic and immunohistochemical results were consistent with AA. Till now, no recurrence was noticed. CONCLUSIONS: We reported a rare case of para-ureteral AA, along with a literature review. Early diagnosis, proper surgical plan and long-term close follow-up is recommended for its high risk of recurrence and malignant potential.

Predictors of Prolonged Mechanical Ventilation in Adults After Acute Type-A Aortic Dissection Repair.

OBJECTIVES: Prolonged mechanical ventilation (PMV) after surgical repair of acute type-A aortic dissection (ATAAD) is associated with an increased risk for mortality and morbidity. The goal of this study was to evaluate the influence of PMV on early and late outcomes and to identify the risk factors for PMV after ATAAD repair. DESIGN, SETTING, AND PARTICIPANTS: This study was a retrospective analysis of prospectively collected data, which resulted from a prior clinical trial. Clinical outcomes were analyzed in 121 patients with ATAAD (mean age 46.6 ± 10.4; 93 men) who underwent total arch replacement combined with a frozen elephant trunk implantation at a mean of 3.6 days from onset. Multivariate analysis was used to identify risk factors for PMV after surgery. MEASUREMENTS AND MAIN RESULTS: The primary endpoint of this study was the occurrence of PMV after ATAAD surgery. The secondary end-points were risk factors for PMV, in-hospital mortality, and 1-year survival. Thirty-five (28.9%) patients required PMV. The PMV group demonstrated a longer ventilation time and length of intensive care unit stay (129 ± 79 h and 167 ± 119 h v 19 ± 10 h and 32 ± 23 h, respectively, p < 0.001). Postoperative mortality was 6.6% (8 of 121), including 6 (17.2%) in the PMV and 2 (2.3%) in the non-PMV groups (p = 0.003). PMV was associated with increased in-hospital mortality (odds ratio 6.4; 95% confidence interval 1.1-36.0; p = 0.036). Follow-up was complete in 88.6% (98 of 113) of patients at a mean of 26 months (1-39 mo). Survival at 1 year was significantly lower in the PMV group compared with the non-PMV group (77.1% v 95.3%, p = 0.002). Risk factors for PMV were the level of serum lactate (mmol/L) at the end of surgery (odds ratio 1.189; 95% confidence interval 1.026-1.377; p = 0.021) and a lower preoperative platelet count (109/L) (odds ratio 0.918; 95% confidence interval 0.847-0.994; p = 0.034). CONCLUSION: In this study, the occurrence of PMV was 28.9% in patients with ATAAD. A lower preoperative platelet count and a higher serum lactate level after ATAAD surgery were risk factors for PMV. Identification of risk factors may be helpful for preventing PMV and improving outcomes after surgical repair of ATAAD.

Twenty-five year outcomes following composite graft aortic root replacement.

BACKGROUND: Operative choices for aortic root disease include traditional root replacement with a composite valved graft as well as various valve-sparing and root repair procedures. OBJECTIVES: To report our experience with traditional composite graft aortic root replacement by a single surgeon over a 25-year period in 449 patients, focusing on long-term survival and freedom from late reoperation and adverse events. METHODS: The coronary button technique was used in all patients. Mean age was 56.1 ± 14.0 years (range 14-87) with 83% males (373/449). Valve prosthesis was mechanical in 343 (76%) and bioprosthetic in 106 (24%). A modified Cabrol procedure (Dacron coronary graft) was employed in 10% (45/449) and concomitant coronary artery bypass graft in 10.9% (49/449). There were 15.8% (71/449) urgent/emergent and 8.2% (37/449) redo procedures. Survival follow-up was 100%. Mean follow-up was 7.0 ± 5.1 years (range 0.1-24.8). RESULTS: Operative mortality occurred in 14 patients (3.1%) and was 2.2% (9/418) in non-dissection and 1.9% (7/361) in elective first-time operations. Stroke and re-exploration for bleeding occurred in nine (2.0%) and 20 (4.5%) patients, respectively. Major late events included bleeding in 2.5% (11/435) and thromboembolism in 1.1% (5/435). At 5, 10, and 20 years, freedom from major events and reoperations on the root were 97.8, 95.4, and 94.39%, and 99.0, 99.0, and 97.9%, respectively. Survival in patients aged <60 years was 92.0, 90.1, and 79.8% at five, 10, and 20 years versus 88.4, 67.9, and 42.6% in patients aged ≥60 years (p = 0.001). Compared with age- and gender-matched controls, survival was not significantly different (p = 0.20). CONCLUSIONS: Composite graft aortic root replacement is associated with low operative risk, excellent long-term survival, and low incidence of reoperation and late events.

Hybrid Operation for Descending Aortic Pathologies Involving Distal Aortic Arch.

Background A combined endovascular and debranching hybrid procedure was performed for descending aortic pathologies involving the distal aortic arch. We reviewed our results of this procedure to summarize clinical experiences. Methods From April 2009 to April 2013, 36 patients (21 males and 15 females) underwent the hybrid operation. Hospital stay and complications were closely monitored after operation. Follow-up CT scan was performed at postoperative 3 months and 12 months. Results The hospital stay ranged from 7 to 25 (15.1 ± 5.0) days. The mean age at operation was 67.6 ± 4.8 years (range: 60-79 years). In-hospital mortality and stroke rates were 2.8% (1/36) and 2.8% (1/36). At a mean follow-up of 22 months (4-52 months), the mortality was 0% (0/35). All remaining 35 patients returned to normal life. During the follow-up period, one patient required secondary endovascular reintervention for a type 1 distal endovascular leak. Conclusion Hybrid repair for descending aortic pathologies involving the distal arch proves to be effective and safe at midterm follow-up with acceptable surgical risks and satisfactory results.

Aorta-Iliac Bypass in Thoracoabdominal Aortic Aneurysm Repair in Young Chinese Patients.

BACKGROUND: Many surgical methods of thoracoabdominal aortic aneurysm repair (TAAAR) have been introduced over the past several decades, with varying degrees of success. We developed an aorta-iliac bypass technique to treat thoracoabdominal aortic aneurysm (TAAA) in young Chinese patients. The aim of this study is to evaluate the results of this technique intraoperatively and postoperatively. METHODS: From June 2014 to March 2015, 28 patients underwent TAAAR using aorta-iliac bypass technique. A four-branched tetrafurcate graft was used. Two branches of the graft are sutured to bilateral common iliac arteries in an end-to-side fashion. The trunk of the graft was sutured to the proximal descending aorta in an end-to-end fashion. Then aorta-iliac bypass was established, and the lower extremities, viscera organ and spinal cord (SC) obtained perfusion from proximal descending aorta via the bypass graft. The thoracic and abdominal aorta were clamped in a staged fashion. The patent segmental arteries (SAs), and visceral arteries (coeliac trunk, superior mesenteric arteries, and renal arteries) were reattached sequentially. Evoked potential (EP) monitoring was adopted to assess the SC ischaemia throughout the procedure. The postoperative outcomes and follow-up results of this technique were evaluated. RESULTS: There was no in-hospital mortality. Complications included acute kidney dysfunction and pulmonary haemorrhage in one case (3.6%) each. The SAs were reattached in all cases. The EP wave disappeared after proximal descending aorta was clamped, and gradually recovered after the patent SAs reattached. The median follow-up after operation was eight months (range, 1-10 months). There was no delayed neurologic deficit or late death. CONCLUSIONS: Thoracoabdominal aortic aneurysm repair using aorta-iliac bypass may be a simple and safe choice for young Chinese patients with thoracoabdominal aortic aneurysms.

Is Previous Cardiac Surgery a Risk Factor for Short and Mid-term Mortality Following Total Aortic Arch Replacement in Patients with Stanford Type A Aortic Dissection?

BACKGROUND: The aim of this study was to evaluate if the previous cardiac surgery (PCS) is the risk factor for short- and mid-term mortality following total aortic arch replacement in patients with Stanford type A aortic dissection. METHODS: Between February 2009 and February 2012, a total of 384 patients who suffered Stanford type A aortic dissection involving aortic arch underwent total aortic arch replacement with frozen elephant trunk. Of these patients, 36 patients had PCS. Logistic regression was used to identify if the previous cardiac surgery was the risk factor for in-hospital mortality. Propensity score-matching (1:1 match) was used to yield patients from the primary surgery group who matched PCS group with respect to pre-operative clinical characteristics and post-operative complications. Survival analysis and differences between the two groups were performed by the Kaplan-Meier estimate and the log-rank test. RESULTS: The overall in-hospital mortality was 8%. Logistic multiple regression identified that cardiopulmonary bypass time≥ 300minutes (OR=12.05, p<0.001) and surgical period from symptom onset shorter than one week (OR=2.43, p=0.04) were final risk factors for in-hospital mortality and PCS was not the final risk factor. Of 36 patients with PCS, three patients died in the hospital and 33 patients were discharged from the hospital. Of these 33 patients, 32 patients matched primary surgery group successfully. During the follow-up period, two patients died in PCS group, one patient died in primary surgery group. The mean follow-up time was 35.38±14.12 months. The five-year survival was 96% for the primary surgery group. Previous cardiac surgery group five-year survival was 73%. Five-year survival was not significantly different between the two groups (p=0.84 log-rank test). CONCLUSIONS: PCS is not the risk factor for short- and mid-term mortality following total aortic arch replacement in patients with Stanford type A aortic dissection.

[Effect of Banxia Qinlian Decoction on Th17/IL-17 Immune Inflammatory Way of Sjögren's Syndrome NOD Model Mice].

OBJECTIVE: To explore the molecular mechanism of exocrine immune inflammatory injury of Sjögren's Syndrome and the intervention of Banxia Qinlian Decoction (BQD). METHODS: Totally 18 female NOD mice were randomly divided into the model group, the positive drug group, and the BQD group, 6 in each group. Six female BALB/c mice were recruited as a blank control group. Mice in the blank control group and the model group were gavaged with deionized water at the daily dose of 0.1 mL/10 g body weight. Tripterygium Tablet was administered by gastrogavage to mice in the positive group at the daily dose of 10 mg/kg. BQD was administered by gastrogavage to mice in the BQD group at the daily dose of 60 g crude drugs/kg. After 12 weeks of medication, mice were sacrificed. Their eyeballs were excised and blood collected. Tissues of bilateral parotids and submandibular glands were kept. mRNA transcriptional levels of IL-17, IL-6, type 3 muscarinic acetylcholine receptors (M3R), aquaporin protein-5 (AQP5) were detected by RT-PCR. Expression levels of M3R and AQP5 protein were detected by Western blot. Protein expression levels of IL-17 and IL-6 were detected by ELISA. RESULTS: Compared with the normal group, mRNA transcriptional levels and protein expression levels of IL-17, IL-6, M3R, and AQP5 were significantly up-regulated in the model group (P < 0.01). Compared with the model group, mRNA transcriptional levels and protein expression levels of IL-17, IL-6, M3R, and AQP5 were significantly down-regulated in the positive drug group and the BQD group with statistical difference (P < 0.01, P < 0.05). Compared with the BQD group, mRNA-transcriptional levels of IL-17, IL-6, and M3R, as well as M3R and AQP5 protein expression levels were significantly down-regulated in the positive drug group (all P < 0.01). CONCLUSION: The molecular mechanism of BQD in inhibiting SS exocrine neurotoxic injury might be possibly related to regulating Th17/IL-17 immune inflammatory way.

Investigation of a novel biomarker, neuropilin-1, and its application for poor prognosis in acute myeloid leukemia patients.

According to the previous studies, numerous biomarkers impact on the prognosis of acute myeloid leukemia (AML) and the prediction for AML had been improved tremendously in the past decades. However, accurate risk-stratification at diagnosis or prognosis remained difficult. In order to further investigate the prognosis evaluation biomarker, the transcription or expression of neuropilin-1 (NRP-1) in 87 AML patients and 32 non-malignant controls were examined. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot were used to detect the NRP-1 expression. Clinical data were collected and analyzed for the 87 AML patients. The results indicated that high NRP-1 expression discriminated the complete remission (CR) rate of AML patients (22.12 % vs. 68.04 % for AML, P < 0.01). De novo AML patients tended to express higher NRP-1 proteins than relapsed AML patients. The overall survival (OS) and relapse-free survival (RFS) rate of the high NRP-1 expression patients decreased significantly compared with the low NRP-1 expression patients (P < 0.001). NRP-1 was revealed to be an independent risk factor for OS in AML (P = 0.003). In conclusion, NRP-1 could predict the shorter OS and RFS rate, and also related with the CR response in AML. Therefore, NRP-1 may act as a more aggressive and promising predictor for the poor prognosis of AML.

Identification and surgical repair of familial thoracic aortic aneurysm and dissection caused by TGFBR1 mutation.

BACKGROUND: This study aimed at exploring the causative gene and summarizing the clinical characteristics in a Chinese thoracic aortic aneurysm and dissection (TAAD) family. METHODS: Family members were examined for features of syndromic genetic diseases by clinician and geneticist. Genomic DNA was extracted from 2 distantly related members with definite TAAD for exome sequencing. RESULTS: A pathogenic mutation (rs111426349, c.1459C >T) of transforming growth factor ß receptor 1 (TGFBR1) was confirmed, which result in the amino acid substitution p.R487W. Fourteen TGFBR1 mutation carriers were detected among 39 tested members in this family. The average age at diagnosis of aortic root dilatation or aneurysm was 23.2 ± 12.6 years (range 3-37 years). Early onset of aortic root dilatation was significant in this family without reported phenotypes. The David procedure was performed prophylactically in 3 carriers of this family. CONCLUSIONS: Familial TAAD caused by TGFBR1 mutation (c.1459C >T) was confirmed in a large Chinese Han ethnic family using exome sequencing. Aggressively prophylactic David procedure may be not necessary at a smaller aortic size in familial TAAD patients with TGFBR1 mutation and further observation is warranted.