Objective:To evaluate the predictive value of age-adjusted Charlson comorbidity index (ACCI) for in-hospital mortality and 1-year mortality in patients with acute type A aortic dissection (ATAAD).Methods:This was a retrospective cohort study, and the clinical data of ATAAD patients admitted to Wuhan Union Hospital from January 1, 1999 to December 31, 2018 were collected for analysis. All the patients were confirmed by computed tomography angiography or magnetic resonance imaging of the aorta and the onset time was less than 14 days. Patients who survived at discharge were followed up to obtain 1-year survival information. The ACCI score was calculated for patients based on their comorbidities and age at admission, and they were divided into three groups of 0, 1 and ≥2 according to the ACCI score. The in-hospital mortality and 1-year mortality of the three groups were compared. Logistic regression analysis was applied to determine the independent predictors for in-hospital mortality and 1-year mortality.Results:Among 1 133 ATAAD patients, 383, 357 and 393 patients had ACCI score of 0, 1, and ≥2, respectively. The in-hospital mortality and 1-year mortality of patients with ACCI score ≥2 were significantly higher than those of patients with ACCI score of 0 (25.4% vs. 17.0%, 30.0% vs. 19.6%, both P<0.05). Multivariate Logistic regression analysis showed that ACCI score ≥2 was an independent risk factor for in-hospital mortality ( OR=1.670, 95% CI: 1.176-2.370, P=0.004) and 1-year mortality ( OR=1.762, 95% CI: 1.264-2.456, P<0.001). Age (per 10-year increase) and cerebrovascular diseases were independent risk factors for in-hospital mortality and 1-year mortality, while diabetes mellitus was a protective factor for in-hospital mortality. Conclusions:ACCI can predict the in-hospital mortality and 1-year mortality of ATAAD patients, and patients with ACCI score ≥2 have a poorer prognosis.

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3-MDM2-SLUG-SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.

Objective:To investigate the effects of two SNP sites of delta-like ligand protein-1 (DLL1) gene rs2738822 (C>T) and rs9459988 (T>G) and gene expression on bone marrow suppression after neoadjuvant chemotherapy for breast cancer.Methods:Breast cancer patients who received neoadjuvant chemotherapy were selected as study subjects, including 90 patients with severe bone marrow suppression and 72 patients with mild bone marrow suppression. Patient’s demographic characteristics and laboratory test indicators were collected. Two SNP sites of DLL1, rs2738822 and rs9459988, were genotyped by capillary electrophoresis and section analysis (SNaPshot) . The relative mRNA expression of DLL1 gene was detected by quantitative reverse polymerase chain reaction (QRT-PCR) method.Results:For The rs2738822 of DLL1 gene, the genotype distribution difference between severe and mild bone marrow suppression groups was statistically significant ( χ2=8.622, P=0.013) . Compared with CC genotype, CT and TT genotype carriers had a higher risk of severe bone marrow suppression, with an OR value of 2.746 (1.335-6.882) and 3.054 (1.282-8.143) , respectively. The dominant model results showed that TT OR CT carriers had a significantly higher risk of severe bone marrow suppression than THOSE with CC genotype [ OR=2.976 (1.231-4.963) ]. For rs9459988, there was no significant difference in genotype distribution between severe bone marrow suppression group and mild bone marrow suppression group ( χ2=2.149, P=0.342) . Results of the dominant model showed that TG or GG carriers had a significantly higher risk of severe bone marrow suppression than TT carriers, with an OR value of 2.046 (1.053-5.611) . The relative mRNA expression level of DLL1 gene was 1.15±0.23 in patients with severe bone marrow suppression, which was significantly lower than that in patients with mild bone marrow suppression (2.64±0.51) ( t=6.381, P<0.001) . For rs2738822, with the increase of T allele, the relative mRNA expression level of DLL1 gene decreased gradually ( P<0.05) . For rs9459988, the relative mRNA expression level of DLL1 gene in patients with mutant allele G was also significantly lower than that in wild-type CC carriers ( P<0.05) . Conclusion:Mutations of DLL1 genes rs2738822 and rs9459988 are related to the occurrence of severe bone marrow suppression after neoadjuvant chemotherapy for breast cancer, and can be used as a genetic marker to predict the degree of bone marrow suppression after neoadjuvant chemotherapy for breast cancer patients.

Pulmonary fibrosis (PF) is a chronic, progressive, fatal interstitial lung disease with limited available therapeutic strategies. We recently reported that the protein kinase glycogen synthase kinase-3

Vitamin D has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D [1,25(OH)D], the biologically active form of vitamin D, significantly attenuated monosodium glutamate (MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemic-euglycemic clamp. Moreover, 1,25(OH)D not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)D on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of in liver tissue, which was accompanied by increased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulin-targeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)D serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.

Objective To study the incidence and duration of residual dizziness after successful repositioning treatment in patients with benign paroxysmal positional vertigo(BPPV) and the clinical factors associated with the residual dizziness.Methods A total of 202 cases of confirmed BPPV patients,61 males and 141 females with the average age of 54.78± 13.71 years old,were followed up for 2 months after successful particle repositioning.The incidence and duration of residual dizziness were analyzed.The risk factors for residual dizziness were analyzed by logistic regression.Results A total of 202 cases of confirmed BPPV were included in this study,and 113 cases complained of residual dizziness.Over the time,residual dizziness disappeared gradually.The differences of the age,the duration of vertigo before treatment,recurrent,and underlying diseases between the two group were significant (P ＜0.05),while the side,the gender,the incubation period of BPPV,the duration time of BPPV,and the types of canals were not associated with the residual dizziness(P＞0.05).The logistic regression analysis showed that the duration of vertigo before treatment and the age were the risk factors for residual dizziness.Conclusion More than half of the patients included in this study complained of residual dizziness after particle repositioning,and the symptoms disappeared naturally.The duration of vertigo before treatment and the age were the risk factors for residual dizziness.

Objective To review our single institutional 10-year experience in complex chest wall reconstruction and identify a working algorithm based on our retrospective analysis.Methods A retrospective analysis of 87 patients who underwent chest wallreconstruction in our department from January 2005 to December 2015.Fifty female patients and 37 male patients who underwent the above procedure were reviewed retrospectively.The median age of the patients is 52.3 years (24-75years).Histologic diagnosis including squamous-cell carcinoma (n =10),soft tissue sarcoma(n =22),chondrosarcomas(n =13) and metastasis from breast cancer(n =42).Type of skeletal defect including partial ribs/sternum defects in 19 cases,soft tissue defects alone in 33 cases,complicated composite chest wall defects involving multiple layers(soft tissue,ribs/sternum,and intrathoracic organs) in 35 cases.Sole methylmethacrylate/polypropylene mesh was used for small sized rib defects in 26cases.Methylmethacrylate/polypropylene mesh sandwich prostheses was used in 28 cases with extensive skeletal reconstruction after partial sternectomy and rib resection.The chest wall defects were repaired with pedicled internal mammary artery perforator flap(3 cases),pedicled deep superior epigastric artery perforator flap(4 cases),pedicled pectoralis major flap(8 cases),free anterolateral thigh perforator flap(9 cases),free deep inferior epigastric artery perforator flap(17 cases),pedicled lateral thoracic flap(5 cases),pedicled latissimus dorsi flap(17 cases),pedicled rectus abdominis flap(15 cases),free deep inferior epigastric artery perforator flap combined with pedicled rectus abdominis flap (4 cases),pedicled bipaddled latissimus dorsi flap(5 cases).11 cases with extensive full-thickness defects of the chest wall,the skeletal reconstruction was achieved with prosthetic sandwich and then covered with the omental flap,further free flaps were harvested for skin and soft tissue repairing.Results 1 case with pedicled rectus abdominis flap partial necrosis was noted,free anterolateral thigh flap was used for repairmen after further revision.1 case with edicled bipaddled latissimus dorsi flap,necrosis of the distal 1/4 part of one paddle was noted,healed with dressing therapy,no secondary skin grafting was required.Postoperative venous congestion occurred in 2 cases with deep inferior epigastric artery flap transplantation,in which both skin flaps exhibited venous crisis within 24 h after surgery.The reexploration procedures were successful in both cases and the flaps survived totally.All other flaps survived.The mean follow-up was 31 months,ranged from 9 to 72 months.No tumour extirpation was noted,functional and appearance results were satisfied.Conclusion According to the size and location of chest wall defect,different pedicled and free flaps should be chosen to achieve optimal outcome.Free flaps are efficient for large complex chest defects reconstruction.

Objective To investigate the micrometastatic lesion of tumor stem cells in the axillary swollen lymph nodes of breast cancer patients and the influence of miR30a on its invasive ability ,and to explore the feasibility of miRNAs anti‐breast cancer treatment .Methods The tumor stem cell‐like breast cancer cells were separated from the axillary swollen lymph nodes in breast cancer patients and cultured .miR30a oligonucleotide fragment was synthesized and transfected into human primary generation breast cancer cells by using adenovirus ,meanwhile the breast cancer cell line MDA‐MB‐231 was taken as the experimental control and the transfection efficiency was assessed by the fluorescence microscopy .The changes of tumor cell proliferation and invasiveness before and after transfection were detected by the Transwell chamber in vitro invasion assay .Western blot was used to detect the ALDH1 ,Vimentin and N‐Cadherin protein expression .Results The Transwell chamber in vitro invasion assay showed that the pri‐mary generation breast cancer cell had more strong invasive ability than MDA‐MB‐231 cell line ,their invasion indexes were (75 .3 ± 3 .2)% and (58 .4 ± 2 .8)% respectively ,the difference was statistically significant (P<0 .05) ,and after transfecting miR30a ,the in vitro invasiveness ability in these two kinds of cells were significantly weakened and their invasion indexes were (21 .4 ± 1 .9)% and (28 .2 ± 2 .3)% respectively ,the difference compared with the control group showed the statistical significance (P<0 .05) .Conclu‐sion The ALDH expression in partial axillary hyperplasia and swollen lymph nodes in the patients with breast cancer is increased , and the tumor micrometastasis may exist ,which should be completely cleaned in operation .miR30a inhibits the expression and inva‐sive ability of tumor stem gene .

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disorder with high mortality. Accumulating evidence shows that toll-like receptor 2 (TLR2) plays a critical role in the regulation of wound-repairing process after tissue injury. We wondered if TLR2 signaling contributed to the pathogenesis of AAA and that targeting TLR2 would attenuate AAA development and progression. In this study, enhanced expression of TLR2 and its ligands were observed in human AAA tissue. Neutralization of TLR2 protected against AAA development and caused established AAA to regress in mouse models of AAA. In addition, TLR2-deficient mice also failed to develop AAA. The prophylactic and therapeutic effects of blocking TLR2 were accompanied by a significant resolution of inflammation and vascular remodeling, as indicated by the decreased expression or activity of MMP-2/9, α-SMA, inflammatory cytokines, and transcription factors NF-κB, AP-1 and STAT1/3 in AAA tissue. Mechanistically, blocking TLR2 decreased the expression and interaction of TLR2 and several endogenous ligands, which diminished chronic inflammation and vascular remodeling in the vascular tissue of AAA. Our studies indicate that the interactions between TLR2 and its endogenous ligands contribute to the pathogenesis of AAA and that targeting TLR2 offers great potential toward the development of therapeutic agents against AAA.