Tumor microenvironment-mediated NIR-I-to-NIR-II transformation of Au self-assembly for theranostics.

The misdiagnosis of tumors due to insufficient penetration depth or signal interference and damage to normal tissues due to indiscriminate treatment are the biggest challenges in using photothermal agents for clinical translation. To overcome these limitations, a strategy of switching from the near-infrared (NIR)-I region to the NIR-II region was developed based on tumor microenvironment (TME)-mediated gold (Au) self-assembly. Using zeolitic imidazolate framework-8 (ZIF-8) metal-organic framework-coated gold nanorods (AuNRs@ZIF-8) as a model photothermal agent, we demonstrated that only a NIR-I photoacoustic imaging signal was observed in normal tissue because ZIF-8 could prevent the aggregation of AuNRs. However, when ZIF-8 dissociated in the TME, the AuNRs aggregated to activate NIR-II photoacoustic imaging and attenuate the NIR-I signal, thereby allowing an accurate diagnosis of tumors based on signal transformation. Notably, TME-activated NIR-II photothermal therapy could also inhibit tumor growth. Therefore, this TME-activated NIR-I-to-NIR-II switching strategy could improve the accuracy of deep-tumor diagnoses and avoid the injury caused by undifferentiated treatment. STATEMENT OF SIGNIFICANCE: Photothermal agents used for photoacoustic imaging and photothermal therapy have garnered great attention for tumor theranostics. However, always "turned on" near-infrared (NIR)-I laser (700-1000 nm)-responsive photothermal agents face issues of penetration depth and damage to normal tissues. In contrast, tumor microenvironment-activated NIR-II "smart" photothermal agents exhibit deeper penetration depth and tumor selectivity. Therefore, a NIR-I-to-NIR-II switching strategy was developed based on tumor microenvironment-mediated Au self-assembly. This work provides a new strategy for developing tumor microenvironment-activated NIR-II smart photothermal agents.

DLGAP1-AS2 promotes human colorectal cancer progression through trans-activation of Myc.

Substantial evidence suggests that non-coding RNA plays a vital role in human cancer, especially long non-coding RNA (lncRNA) with a length greater than 200nt. Herein, we found a lncRNA facilitating human colorectal cancer (CRC) progression. DLGAP1-AS2 was significantly increased in CRC tissues and cell lines. Knockdown of DLGAP1-AS2 inhibited CRC cell proliferation, migration, invasion in vitro, and tumor growth in vivo. The subcellular localization of DLGAP1-AS2 was translocated from the cytoplasm of normal cells to the nucleus of CRC cells due to reduced levels of N6-methyladenosine (m6A) modification. Further, through the screening of a series of signal pathways, we found that Myc pathway was involved in the effect of DLGAP1-AS2. Silencing of DLGAP1-AS2 markedly reduced Myc mRNA and protein levels. Blockade of Myc effectively abolished the enhanced aggressive behaviors of CRC cells caused by DLGAP1-AS2 overexpression. Mechanistically, DLGAP1-AS2 directly bound CTCF, a well-known transcriptional repressor of Myc, resulting in reduced binding of CTCF on Myc promoter and activating Myc transcription. The second hairpin structure of DLGAP1-AS2 was critical for the interaction between DLGAP1-AS2 and CTCF in the nucleus. Taken together, our study reveals the oncogenic regulatory axis of DLGAP1-AS2/CTCF/Myc in CRC, implying a promising targeted therapy for clinical application.

A New Aortic Arch Dissection Classification: The Fuwai Classification.

Aims: We describe a new aortic arch dissection (AcD) classification, which we have called the Fuwai classification. We then compare the clinical characteristics and long-term prognoses of different classifications. Methods: All AcD patients who underwent surgical procedures at Fuwai Hospital from 2010 to 2015 were included in the study. AcD procedures are divided into three types: Fuwai type Cp, Ct, and Cd. Type Cp is defined as the innominate artery or combined with the left carotid artery involved. Type Cd is defined as the left subclavian artery or combined with the left carotid artery involved. All other AcD surgeries are defined as type Ct. The Chi-square test was adopted for the pairwise comparison among the three types. Kaplan-Meier was used for the analysis of long-term survival and survival free of reoperation. Results: In total, 1,063 AcD patients were enrolled from 2010 to 2015: 54 patients were type Cp, 832 were type Ct, and 177 were type Cd. The highest operation proportion of Cp, Ct and Cd were partial arch replacement, total arch replacement, and TEVAR. The surgical mortality in type Ct was higher compared to type Cd (Ct vs. Cd = 9.38 vs. 1.69%, p < 0.01) and type Cp (Ct vs. Cp = 9.38 vs. 1.85%, p = 0.06). There was no difference in surgical mortality of type Cp and Cd (p = 0.93). There were no significant differences in the long-term survival rates (p = 0.38) and free of aorta-related re-operations (p = 0.19). Conclusion: The Fuwai classification is used to distinguish different AcDs. Different AcDs have different surgical mortality and use different operation methods, but they have similar long-term results.

Respiratory diseases are positively associated with PM2.5 concentrations in different areas of Taiwan.

The health effects associated with fine particulate matter (PM2.5) have attracted considerable public attention in recent decades. It has been verified that PM2.5 can damage the respiratory and cardiovascular systems and cause various diseases. While the association between diseases and PM2.5 has been widely studied, this work aims to analyze the association between PM2.5 and hospital visit rates for respiratory diseases in Taiwan. To this end, a disease mapping model that considers spatial effects is applied to estimate the association. The results show that there is a positive association between hospital visit rates and the PM2.5 concentrations in the Taiwanese population in 2012 after controlling for other variables, such as smoking rates and the number of hospitals in each region. This finding indicates that control of PM2.5 could decrease hospital visit rates for respiratory diseases in Taiwan.

Different treatment options for Takayasu arteritis patients with moderate-to-severe aortic regurgitation: long-term outcomes.

OBJECTIVES: To determine the prognosis of Takayasu arteritis (TA) patients with moderate-to-severe aortic regurgitation treated with surgical vs conservative treatment and to identify independent prognostic factors of long-term outcomes. METHODS: Between January 2002 and January 2017, 101 consecutive TA patients with moderate-to-severe aortic regurgitation treated with either surgical (n = 38) or conservative (n = 63) treatments were investigated in this retrospective observational case-control study. The primary end point was all-cause mortality, and the secondary end point comprised the combined end points of death, non-fatal stroke and cardiac events (non-fatal myocardial infarction and congestive heart failure). Propensity score matching was used to reduce the bias of baseline risk factors. RESULTS: The unadjusted all-cause 10-year mortality in the conservative group was increased compared with the surgical group (28.2% vs 7.4%; log-rank P = 0.036), and the combined end points showed the same trend (52.1% vs 25.3%; log-rank P = 0.005). After an adjustment of baseline risk factors, the conservative treatment was associated with reduced survival rates of both all-cause mortality [hazard ratio (HR): 8.243; 95% CI: 1.069, 63.552; P = 0.007] and combined end points (HR: 6.341; 95% CI: 1.469, 27.375; P = 0.002). Conservative treatment (HR: 3.838, 95% CI: 1.333, 11.053; P = 0.013) and left ventricular end-diastolic diameter (HR: 1.036, 95% CI: 1.001, 1.071; P = 0.042) were risk factors for increased combined end points. CONCLUSION: Surgical treatment improves the outcomes of patients with moderate-to-severe aortic regurgitation due to TA. The dilated left ventricle indicated a worse prognosis.

Different therapeutic modalities for aortic arch disease combined with Kommerell's diverticulum: single-center experience with nine cases.

BACKGROUND: Aortic arch disease with Kommerell's diverticulum is an uncommon but troublesome condition, and there are a variety of therapeutic modalities for treating this. We retrospectively analyzed cases who underwent open surgery to summarize different situations and approaches. METHODS: From November 2015 to January 2019, nine patients underwent operation for the mentioned disorder. Four patients with aortic dissection received total arch replacement. Two patients suffering from type B aortic dissection (TBAD) have accepted graft replacement from ascending aorta (aAO) to descending aorta. Two patients with true aneurysm and congenital malformation underwent graft bypass from aAO to descending aorta. One patient had graft replacement of descending aorta. RESULTS: There were nine (eight males and one female) patients with median age of 45 (from 14 to 54) years. The 30-day mortality was 11.1% (1 patient) due to refractory respiratory failure caused by compression of bronchus. One patient had complication of peripheral neuropathy and recovered eventually. Eight patients were followed-up for a median period of 20 [9-46] months. All patients were alive and had no long-term complications except one patient who received re-intervention due to delayed dilation of downstream aorta. CONCLUSIONS: Treatment for different arch lesions with Kommerell's diverticulum should follow corresponding indications. Open surgery is the preferred choice and detailed therapeutic strategy depends on the extension of aneurysm, classification and phase of dissection. Stenting might cause airway compression when right-sided arch and vascular ring exist.

Osthole inhibits proliferation of kainic acid­activated BV­2 cells by modulating the Notch signaling pathway.

Epilepsy is a syndrome involving chronic recurrent transient brain dysfunction. Activation and proliferation of microglia serve important roles in epilepsy pathogenesis and may be targets for treatment. Although osthole, an active constituent isolated from Cnidium monnieri (L.) Cusson, has been demonstrated to improve epilepsy in rats, its underlying mechanism remains to be elucidated. The present study investigated the effect of osthole on proliferation of kainic acid (KA)­activated BV­2 cells and explored the molecular mechanism by which it inhibited their proliferation. Using Cell Counting Kit­8, enzyme­linked immunosorbent assay, reverse transcription­quantitative PCR, western blot analysis and immunofluorescence staining, it was identified that following exposure of KA­activated BV­2 cells to 131.2 µM osthole for 24 h, cell proliferation and release of tumor necrosis factor α, interleukin 6 and nitric oxide synthase/induced nitric oxide synthase were significantly inhibited (P<0.05). Further experiments revealed that osthole significantly downregulated mRNA and protein levels of Notch signaling components in KA­activated BV­2 cells (P<0.05). Therefore, it was hypothesized that osthole inhibited the proliferation of microglia by modulating the Notch signaling pathway, which may be useful for the treatment of epilepsy and other neurodegenerative diseases characterized by Notch upregulation.

[Risk Factors for Acute Renal Failure after Thoracoabdominal Aortic Aneurysm Surgery].

Objective To investigate the risk factors associated with acute renal failure (ARF) after thoracoabdominal aortic aneurysm (TAAA) surgery. Methods A total of 156 patients underwent TAAA repair between January 2009 and December 2017. Renal failure was defined based on the Kidney Disease Improving Global Outcomes criteria. The patients were divided into ARF group and non-ARF group based on the presence/absence of postoperative ARF. The risk factors of ARF were analyzed by univariate analysis and multivariate logistic analysis. Results The subjects included 111 males and 45 females aged (40.4±10.9) years (range:19-65 years). The surgical reasons included aortic dissection (n=130,83.3%),aneurysm (n=22,14.1%),and pseudoaneurysm (n=4,2.6%). The degrees of repair included Crawford extent I in 6 patients (3.8%),extent Ⅱ in 128 patients (82.1%),extent Ⅲ in 20 patients (12.8%),and extent Ⅳ in 2 patients(1.3%). There were 3 patients presented with aortic rupture and 6 patients received emergent operations. Nine patients (5.8%) died within 30 days after surgery,and 8 patients (5.1%) suffered from permanent paraplegia. Thirty-six patients (23.1%) had ARF after surgery,and 18 of them needed dialysis. Multivariate logistic analysis showed that smoking (OR =2.637,95%CI=1.113-6.250,P=0.028),packed red blood cell usage in operation (≥6 U) (OR =5.508,95%CI=2.144-11.930,P=0.000),reoperation for bleeding (OR=3.529,95%CI=1.298-9.590,P=0.013) were independent risk factors for ARF after TAAA repair. Conclusion Smoking,packed red blood cell usage in operation (≥6 U),reoperation for bleeding are the independent risk factors of ARF after TAAA surgery.

Expression of H2S in Gestational Diabetes Mellitus and Correlation Analysis with Inflammatory Markers IL-6 and TNF-α.

BACKGROUND: Gestational diabetes mellitus (GDM) is a severe threat to the health of both mother and child. The pathogenesis of GDM remains unclear, although much research has found that the levels of hydrogen sulfide (H2S) play an important role in complications of pregnancy. METHODS: We collected venous blood samples from parturient women and umbilical vein blood (UVB) and peripheral venous blood (PVB) samples one hour after childbirth in the control, GDM-, and GDM+ groups in order to determine the concentration of glucose and H2S in plasma; to measure levels of TNF-α, IL-1ß, IL-6, TGF-ß1, and ADP in parturient women and the UVB of newborns; and to find the correlation of H2S with regression. RESULTS: We found that, with the elevation of glucose, the level of H2S was decreased in GDM pregnant women and newborns and the concentrations of IL-6 and TNF-α were upregulated. With regression, IL-6 and TNF-α concentrations were positively correlated with the level of blood glucose and negatively correlated with H2S concentration. CONCLUSION: This study shows that downregulation of H2S participates in the pathogenesis of GDM and is of great significance in understanding the difference of H2S between normal and GDM pregnant women and newborns. This study suggests that IL-6 and TNF-α are correlated with gestational diabetes mellitus. The current study expands the knowledge base regarding H2S and provides new avenues for exploring further the pathogenesis of GDM.

Case Report: Complete Remission of C1q Nephropathy Treated With a Single Low-Dose Rituximab, a Reality or Coincidence?

C1q nephropathy is a glomerulopathy that is characterized by large amount of C1q deposits in the glomerular mesangium. It is a diagnosis of exclusion after ruling out systemic lupus erythematosus and membranoproliferative glomerulonephritis by systemic and serological examination. The pathogenesis of C1q nephropathy is unclear. In addition, there is very little generalizability in the treatment and prognosis for pediatric C1q nephropathy due to diversities in clinical manifestations and pathological types. Rituximab is a human/mouse chimeric monoclonal antibody against CD20, which is primarily used for treating lymphomas and, most recently, has been used to treat certain kidney diseases including C1q nephropathy. In this report, we used one quarter of the typical dose of rituximab for lymphoma treatment to achieve complete remission in a C1q nephropathy patient, significantly reducing deposition of immune complexes and glomerular damage. This case indicates that dosage reconsiderations may be necessary for rituximab in treatment of pediatric C1q nephropathy.

Surgical treatment for Kommerell's diverticulum associated with aortic dissection involving aortic arch.

OBJECTIVE: Kommerell diverticulum with aortic dissection involving aortic arch is a rare but troublesome condition. The purpose of this study is to summarize the experience and strategy of surgical treatment. METHOD: From November 2015 to January 2018, seven consecutive patients underwent surgical treatment in our institution. Three patients with acute type A aortic dissection and one patient with acute type B aortic dissection received total arch replacement and frozen elephant trunk (FET) implantation through median sternotomy. Three patients with chronic type B aortic dissection underwent total aortic arch and descending aorta replacement through median sternotomy and lateral thoracotomy. RESULT: There were seven male patients whose median age was 42.3 ± 11.7 (from 14 to 54) years old. There was no perioperative death in this study. One patient had postoperative critical illness polyneuropathy and required prolonged mechanical ventilation (485 hours) and recovered finally. Follow up was completed for all seven patients with a median follow-up time of 7 (3-46) months. One patient with type A dissection developed aneurysm of the descending aorta distal to the FET and received reintervention. No clinical events and abnormal computed tomography manifestations were found in the other seven patients. CONCLUSION: Total arch replacement and FET through single median incision is a reliable method for Kommerell diverticulum associated with acute dissection involving arch. For Kommerell diverticulum associated with chronic type A or B aortic dissection involving aortic arch, graft replacement by double or single incision is safe and appropriate.

miR-146a attenuates apoptosis and modulates autophagy by targeting TAF9b/P53 pathway in doxorubicin-induced cardiotoxicity.

Clinical therapy of doxorubicin (DOX) is limited due to its cardiotoxicity. miR-146a was proved as a protective factor in many cardiovascular diseases, but its role in chronic DOX-induced cardiotoxicity is unclear. The objective of this study was to demonstrate the role of miR-146a in low-dose long-term DOX-induced cardiotoxicity. Experiments have shown that DOX intervention caused a dose-dependent and time-dependent cardiotoxicity involving the increased of apoptosis and dysregulation of autophagy. The cardiotoxicity was inhibited by overexpressed miR-146a and was more severe when miR-146a was downgraded. Further research proved that miR-146a targeted TATA-binding protein (TBP) associated factor 9b (TAF9b), a coactivator and stabilizer of P53, indirectly destroyed the stability of P53, thereby inhibiting apoptosis and improving autophagy in cardiomyocytes. Besides, miR-146a knockout mice were used for in vivo validation. In the DOX-induced model, miR-146a deficiency made it worse whether in cardiac function, cardiomyocyte apoptosis or basal level of autophagy, than wild-type. In conclusion, miR-146a partially reversed the DOX-induced cardiotoxicity by targeting TAF9b/P53 pathway to attenuate apoptosis and adjust autophagy levels.

Effects of Smoking Cessation with Nicotine Replacement Therapy on Vascular Endothelial Function, Arterial Stiffness, and Inflammation Response in Healthy Smokers.

The effects of nicotine replacement therapy (NRT)-aided smoking cessation on vascular function are not fully clarified. We investigated 100 healthy smokers who were motivated to quit and received NRT for a 3-month period. Vascular endothelial function (measured by reactive hyperemia-peripheral arterial tonometry [RH-PAT]), arterial stiffness (measured by augmentation index [AI] and brachial-ankle pulse wave velocity [baPWV]), and systemic inflammation markers (including serum soluble intercellular adhesion molecule-1 [sICAM-1] and interleukin-1ß [IL-1ß]) were assessed at baseline and 3 and 12 months of follow-up. After 3 months of intervention, endothelial function, arterial stiffness, and inflammatory markers significantly improved (RH-PAT increased, AI and baPWV decreased, sICAM-1 and IL-1ß decreased, all P < .05) for the participants who abstained from smoking completely, but for those who did not abstained completely, RH-PAT, AI, baPWV, and IL-1ß remained unchanged. At 12 months follow-up, endothelial function (RH-PAT), arterial stiffness (AI and baPWV), and inflammatory markers (sICAM-1 and IL-1ß) were further improved in participants who abstained from smoking (P < .001), while the above parameters deteriorated in continued smokers (P < .05). In conclusion, vascular dysfunction can be reversible after NRT-aided smoking cessation in healthy smokers and vascular function could be further damaged if they continue smoking.

Osthole inhibits proliferation and induces apoptosis in BV-2 microglia cells in kainic acid-induced epilepsy via modulating PI3K/AKt/mTOR signalling way.

CONTEXT: Osthole is a natural coumarin compound most frequently extracted from plants of the Apiaceae family such as Cnidium monnieri (L.) Cusson, Angelica pubescens Maxin.f., and Peucedanum ostruthium (L.). Osthole is considered to have potential therapeutic applications for the treatment of diseases including epilepsy. However, the mechanism of osthole induced-apoptosis in BV-2 microglia cells is not yet clear. OBJECTIVE: To investigate the molecular mechanisms underlying the effect of osthole on PI3K/AKt/mTOR expression in kainic acid (KA)-activated BV-2 microglia cells. MATERIALS AND METHODS: Optimal culture concentration and time of osthole were investigated by MTT assay. The concentration of osthole was tested from 10 to 400 µM and the culture time was tested from 2 to 72 h. Ultrastructure difference among control, KA and osthole group was analyzed under transmission electron microscope. The mRNA expression of PI3K/AKt/mTOR was investigated using reverse transcription (RT)-PCR and the protein expression was investigated using western blotting and immunofluorescence assay. Apoptosis rate of BV-2 cells between each group was measured by flow cytometry. RESULTS: IC50 for cell viability of BV-2 cells by osthole was 157.7 µM. Treated with osthole (140 µM) for 24 h significantly increased the inhibition rate. Pretreatment with osthole inhibited the KA-induced PI3K/AKt/mTOR mRNA and protein expression. The results of flow cytometry analysis showed that the apoptotic rate of osthole group was obviously higher than KA group. CONCLUSIONS: Date showed that osthole may be useful in the treatment of epilepsy and other neurodegenerative diseases that are characterized by over expression of PI3K/Akt/mTOR.

The role of IDO, IL-10, and TGF-ß in the HCV-associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

Indoleamine-2,3-dioxygenase (IDO) is an enzyme that catalyzes tryptophan to kynurenine and studies have revealed that IDO play a vital role in regulation of liver immunity and inflammation activities. This study investigated the association between plasma IDO and disease severity and the possible marker role of IDO in the inflammatory process of hepatitis C. In this study, 80 individuals with HCV infection were retrospectively selected. Plasma levels of IDO, IL-10, and TGF-ß were assayed by ELISA. Clinical characteristics of patients, including the levels of ALT, AST, and total bilirubin (TBil) were collected from clinical databases. HCV-related liver cirrhosis (HC-Cirr) and HCV-related Hepatocellular carcinoma (HCV-HCC) had significantly high plasma levels of IDO compared to other patient groups and healthy controls. Plasma IL-10 level were significantly greater in all chronic liver disease groups and with respect to TGF-ß, the level was high in all the selected patients with HCV infection compare with controls. Moreover, HCV-HCC patients showed highest values for both IL-10 and TGF-ß, with significant difference compared with other groups. In addition, plasma IDO was positively correlated with TGF-ß among all patients with HCV infection (r = 0.4509, P < 0.0001), with IL-10 in CHC patients (r = 0.4787, P = 0.0047), with TBil in HCV-Cirr patients (r = 0.4671; P = 0.0093). High level of IDO and TGF-ß is associated with hepatocyte necrosis and intrahepatic inflammation, and may be used as an index of disease progression for patients with chronic HCV infection.

Prognostic value of Systemic immune-inflammation index in cancer: A meta-analysis.

Systemic immune-inflammation index (SII), on the basis of lymphocyte, neutrophil and platelet counts had been published to be a good prognostic factor in multiple cancers. Nevertheless, the prognostic value of SII in cancer patients remains inconsistent. Therefore, we carried out a meta-analysis to evaluate the prognostic value of SII in these patients with cancer. A total of 22 articles with 7657 patients enrolled in this meta-analysis. The combined result revealed that a high SII was evidently correlated with poor overall survival (OS) (HR=1.69, 95%CI=1.42-2.01, p<0.001), poor time to recurrent (TTR) (HR=1.87, p<0.001) , poor progress-free survival (PFS) (HR=1.61, p=0.012) ,poor cancer-specific survival (CSS) (HR=1.44, p=0.027) , poor relapse-free survival (RFS) (HR=1.66, p=0.025) and poor disease-free survival (DFS) (HR=2.70, p<0.001) in patients with cancers. Subgroup analysis indicated that SII over the cutoff value could predict worse overall survival in Hepatocellular carcinoma (p<0.001), Gastric cancer (p=0.005), Esophageal Squamous Cell Carcinoma (p=0.013), Urinary system cancer (p<0.001), Small cell lung cancer (p<0.001), Non-Small cell lung cancer (p<0.001) and Acral Melanoma (p<0.001). The largest effect size was observed in the Hepatocellular carcinoma (HR=2.11). In addition, these associations did not vary significantly by the cutoff value, sample size and ethnicity. Therefore, high SII may be a potential prognostic marker in patients with various cancers and associated with the poor overall outcomes.

Racial differences in Urinary Bladder Cancer in the United States.

Urinary bladder cancer (UBC) has a high incidence rates in many southern and eastern European countries, in parts of Africa and the Middle East, and in North America. It exhibits a wide variety of histological types that goes from less aggressive to rapid-growing ones. In order to compare the different presentations, etiologies, and prognoses among racial groups, including NHW (non-Hispanic white), HW (Hispanic white), blacks, and API (Asian and Pacific Islander), we analyzed the UBC patients diagnosed between 1973 and 2014 using SEER (Surveillance, Epidemiology, and End Results) database. Patient characteristics, age-adjusted incidence rates, and survival were compared across races. There are significant racial differences in patients' characteristics, including gender, marital status, age at diagnosis, treatment strategies, grade, stage, survival time, and so on. Overall, non-Hispanic whites have the highest incidence rate, followed by blacks, Hispanic whites, and APIs. In the analysis of survival, significant racial differences exist when stratified by gender, age group, histological type, stage, location and treatment strategies. Racial differences exist among UBC patients in the United States in terms of characteristics, incidence, and survival. Future studies may collect and analyze more data for comprehensive description and interpretation of the racial differences.

Single Stage Hybrid Repair for DeBakey Type I Aortic Dissection in High Risk Patients.

OBJECTIVES: To evaluate the efficacy of the less invasive hybrid zone 0 (Z0) total aortic arch repair (HAR, ascending repair + complete debranching + thoracic endovascular aortic repair [TEVAR]) without deep hypothermic circulatory arrest in management of DeBakey type I aortic dissection (IAD). The adverse outcome was defined as a single composite endpoint comprising peri-operative mortality, permanent neurological deficit, and renal failure necessitating haemodialysis at discharge. METHODS: A retrospective review of prospectively collected data was conducted of 120 consecutive patients (mean EuroSCORE = 11.6%) with IAD undergoing HAR (urgent/emergency, n = 97, 80.8%) involving reconstruction of the ascending aorta (zone 0) and total arch exclusion with TEVAR during a 7.5 year period. Multivariable analysis of 27 potential pre-operative and intra-operative risk factors was performed to examine the early composite endpoint and short and long-term overall mortality. RESULTS: The total early (30 day or in hospital) mortality was 9.2% (n = 11). The incidence of the composite endpoint was 11.7% (n = 14). On multivariable analysis, malperfusion syndromes were predictors of the composite endpoint (odds ratio [OR], 4.789; 95% CI 1.362-16.896; p = .015), and previous cerebrovascular accident (OR, 13.74; 95% CI 2.330-81.039; p = .004) and myocardial ischaemia time (OR, 1.038; 95% CI 1.015-1.061; p = .001) predicted short and long-term overall mortality. The overall survival was 84.7% during a median follow up of 3.4 years. Freedom from late aortic adverse events was 93.1% at 5 years, including secondary aortic intervention and endoleak. The maximum diameters of the true lumen increased significantly in stented thoracic (14.4 ± 6.5 mm to 29.7 ± 5.3 mm, p < .001), lower thoracic (14.2 ± 6 mm to 21.6 ± 7.2 mm, p < .001) and abdominal (11.7 ± 4.8 mm to 17.4 ± 4.1 mm, p < .001) aorta. Complete thrombosis of the peri-stent false lumen was achieved in 88.2% of CT scans (82/93) performed a mean of 12 ± 17 months (median 5 months; 25-75% quartile, 2-12 months) post-operatively. CONCLUSIONS: IAD was treated safely and durably by Z0 HAR, and peri-operative mortality and morbidity were not substantially higher despite the older age and high risk of patients.

The Antitumor Effect of Xihuang Pill on Treg Cells Decreased in Tumor Microenvironment of 4T1 Breast Tumor-Bearing Mice by PI3K/AKT~AP-1 Signaling Pathway.

To study the antitumor effect of Xihuang pill (XHP) on the number of Treg cells in the tumor microenvironment of 4T1 breast tumor-bearing mice by PI3K/AKT/AP-1 pathway, a mouse model was established. Flow cytometry (FCM) and immunohistochemistry (IHC) were used to detect the number of Treg cells in the tumor microenvironment; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect the apoptosis of Treg cells in tumor microenvironment. Quantitative real-time PCR (RT-qPCR) was used to detect the mRNA expression of PI3K, AKT, and AP-1 in Treg cells in tumor microenvironment; immunofluorescence (IF) and Western Blot (WB) were used to detect the protein expression of PI3K, AKT, and AP-1 in Treg cells in tumor microenvironment. Compared with the naive control group, the tumor weight in XHP groups decreased significantly (P < 0.05); FCM and IHC results showed that the number of Treg cells in the tumor microenvironment decreased with the dose of XHP groups (P < 0.05); TUNEL staining showed that the number of Treg cells in tumor microenvironment increased with the dose of XHP groups (P < 0.05); RT-qPCR results showed that the mRNA expression of PI3K and AKT in Treg cells decreased with the dose of XHP groups, while RNA expression of AP-1 increased with the dose of XHP groups (P < 0.05); IF and WB results showed that the protein expression of PI3K and AKT in Treg cells decreased with the dose of XHP groups and the protein expression of AP-1 increased with the dose of XHP groups (P < 0.05). The results suggested that XHP decreased the number of Treg cells via inhibiting PI3K and AKT expression and upregulating AP-1 expression in Treg cells and then promoting the apoptosis of Treg cells. Thus, XHP could improve the immunosuppressive state of tumor microenvironment and reverse the immune escape to inhibit tumor growth.

Transcatheter arterial chemoembolization (TACE) combined with γ-knife compared to TACE or γ-knife alone for hepatocellular carcinoma.

To compare the clinical efficacies and adverse reactions between transcatheter arterial chemoembolization (TACE), γ-ray 3-dimensional fractionated stereotactic conformal radiotherapy (FSCR), and TACE combined with FSCR for primary hepatocellular carcinoma.The study was approved by the Institutional Review Board, and informed consent was waived due to the retrospective study design. About 121 patients met the inclusion criteria and were included in this study, from March 2008 to January 2010, in the Second Xiangya Hospital. Forty-six patients underwent TACE alone, 36 patients underwent γ-knife alone, and 39 were treated by γ-knife combined with TACE. Short-term effects, overall survival rates, adverse reactions, and survival times were compared between the 3 treatment groups.Short-term effects were observed in 41.3% of the TACE group, 33.3% of the γ-knife group, and 64.1% of the TACE combined γ-knife group (P = .020). Overall survival rates at 6,12, 18, and 24 months were 50%, 34.8%, 28.3%, and 21.7% for the TACE group, 36.1%, 30.6%, 16.7%, and 11.1% for γ-knife group, and 84.6%, 71.8%, 61.5%, and 30.8% for TACE combined γ-knife group, respectively. The differences in the overall survival rates at 6, 12, and 18 months between the 3 groups were statistically significant (P = 0), but the overall survival rates at 24 months in the 3 groups were not significantly different (P = .117). The median survival time was 7 months for the TACE group, 3 months for the γ-knife group, and 20 months for the TACE combined γ-knife group (P = 0). There were statistically significant differences (P = .010) of leukopenia between the 3 groups, and no statistically significant differences of (P > .05) thrombocytopenia, anemia, nausea, vomiting, and liver function lesions.TACE combined with γ-knife for primary hepatocellular carcinoma is superior to TACE or γ-knife alone in short-term and long-term effects. This procedure is a mild, safe, and effective treatment for primary hepatocellular carcinoma.