Lipoprotein(a) is associated with recurrent cardiovascular events in patients with coronary artery disease and prediabetes or diabetes.

PURPOSE: Elevated lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are both associated with adverse events in high-risk patients with established coronary artery disease (CAD). Currently, the association between Lp(a) levels and recurrent cardiovascular (CV) events (CVEs) remained undetermined in patients with different glucose status. Therefore, this study aimed to investigate the prognostic significance of Lp(a) levels for recurrent CVEs in high-risk CAD patients who suffered from first CVEs according to different glycemic metabolism. METHODS: We recruited 5257 consecutive patients with prior CVEs and followed up for recurrent CVEs, including CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. Patients were assigned to low, medium, and high groups according to Lp(a) levels and further stratified by glucose status. RESULTS: During a median 37-month follow-up, 225 (4.28%) recurrent CVEs occurred. High Lp(a) was independently associated with recurrent CVEs [adjusted Hazard Ratio (HR), 1.57; 95% confidence interval (CI) 1.12-2.19; P = 0.008]. When participants were classified according to Lp(a) levels and glycemic status, high Lp(a) levels were associated with an increased risk of recurrent CVEs in pre-DM (adjusted HR, 2.96; 95% CI 1.24-7.05; P = 0.014). Meanwhile, medium and high Lp(a) levels were both associated with an increased risk for recurrent CVEs in DM (adjusted HR, 3.09; 95% CI 1.30-7.34; P = 0.010 and adjusted HR, 3.13, 95% CI 1.30-7.53; P = 0.011, respectively). CONCLUSIONS: This study demonstrated that elevated Lp(a) levels were associated with an increased recurrent CVE risk in patients with CAD, particularly among those with pre-DM and DM, indicating that Lp(a) may provide incremental value in risk stratification in this population.

[Developments and challenges of liver transplantation in China].

With the vigorous promotion of organ donation after citizen death in China, increased utilization of marginal livers, and continuous expansion of hepatocellular carcinoma indications for liver transplantation, innovations in techniques such as auxiliary liver transplantation, pediatric liver transplantation laparoscopic liver transplantation, magnetic liver transplantation,and non-ischemic liver transplantation have significantly improved the number of liver transplantation surgery performed, patient survival rates, and graft survival rates in China, while complication rates have gradually decreased. As such,liver transplantation in China has now reached leading or advanced levels internationally. In the new development context,Chinese liver transplantation faces new opportunities and challenges for development. Evolutions in basic diseases of transplant recipients and tumor classifications of will further broaden the population eligible for transplantation and introduce new demands for liver transplantation procedures. Emerging technologies including artificial organs, xenotransplantation,and artificial intelligence are bringing prospects for advancing liver transplantation. Looking ahead, the progression of liver transplantation will go beyond prioritizing patient survival rates and graft survival rates alone, instead emphasizing improved quality of life for transplant recipients post-surgery to an even greater extent.

[Key issues related to clinical trials of xenotransplantation].

The development of xenotransplantation is expected to alleviate the supply and demand gap of donors' organs. Currently,gene-edited pigs are considered as ideal organ donor source for clinical xenotransplantation. Driven by relevant technologies,substantial progress have been achieved in preclinical studies of xenotransplantation,which creates good conditions for the opening of early clinical trials. Especially in recent two years,the foreign clinical research in this field has made a breakthrough. Here,the progress in xenotransplantation of clinical trials is briefly reviewed home and abroad,the key issues in clinical trials of xenotransplantation are discussed from the perspectives of gene editing of donor pigs,principles of whole-course management of subjects,ethics and social psychology issue. It is believed that under the background of multidisciplinary cross-fusion,xenotransplantation will be gradually transferred to clinical application in the future,and better benefit human beings.

[Benefits and risks of prolonged dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent in patients with stable coronary artery disease and diabetes].

Objective: To compare the efficacy and safety of prolonged dual antiplatelet therapy (DAPT>1 year) in patients with stable coronary artery disease (CAD) and diabetes who were event-free at 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) in a large and contemporary PCI registry. Methods: A total of 1 661 eligible patients were selected from the Fuwai PCI Registry, of which 1 193 received DAPT>1 year and 468 received DAPT ≤1 year. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding, MACCE was defined as a composite of all-cause death, myocardial infarction or stroke. Multivariate Cox regression analysis and inverse probability of treatment weighting (IPTW) Cox regression analysis were performed. Results: After a median follow-up of 2.5 years, patients who received DAPT>1 year were associated with lower risks of MACCE (1.4% vs. 3.2%; hazard ratio (HR) 0.412, 95% confidence interval (CI) 0.205-0.827) compared with DAPT ≤1 year, which was primarily caused by the lower all-cause mortality (0.1% vs. 2.6%; HR 0.031, 95%CI 0.004-0.236). Risks of cardiac death (0.1% vs. 1.5%; HR 0.051, 95%CI 0.006-0.416) and definite/probable ST (0.3% vs. 1.1%; HR 0.218, 95%CI 0.052-0.917) were also lower in patients received DAPT>1 year than those received DAPT ≤ 1 year. No difference was found between the two groups in terms of BARC type 2, 3, or 5 bleeding (5.3% vs. 4.1%; HR 1.088, 95%CI 0.650-1.821). Conclusions: In patients with stable CAD and diabetes who were event-free at 1 year after PCI with DES, prolonged DAPT (>1 year) provides a substantial reduction in ischemic cardiovascular events, including MACCE, all-cause mortality, cardiac mortality, and definite/probable ST, without increasing the clinically relevant bleeding risk compared with ≤ 1-year DAPT. Further well-designed, large-scale randomized trials are needed to verify the beneficial effect of prolonged DAPT in this population.

Selective interface transparency in graphene nanoribbon based molecular junctions.

A clear understanding of electrode-molecule interfaces is a prerequisite for the rational engineering of future generations of nanodevices that will rely on single-molecule coupling between components. With a model system, we reveal a peculiar dependence on interfaces in all graphene nanoribbon-based carbon molecular junctions. The effect can be classified into two types depending on the intrinsic feature of the embedded core graphene nanoflake (GNF). For metallic GNFs with |NA - NB| = 1, good/poor contact transparency occurs when the core device aligns with the center/edge of the electrode. The situation is reversed when a semiconducting GNF is the device, where NA = NB. These results may shed light on the design of real connecting components in graphene-based nanocircuits.

Combined Kidney Transplantation and Splenic Fossa Auxiliary Heterotopic Liver Transplantation in a Highly Sensitized Recipient: A Case Report.

BACKGROUND: Combined kidney and auxiliary orthotopic liver transplantation from the same donor is used to treat highly sensitized renal transplant recipients. Auxiliary liver can protect the transplanted kidney against hyperacute rejection. METHODS: In the current case, combined kidney and splenic fossa auxiliary heterotopic liver transplantation was performed from the same donor for a highly sensitized recipient without preoperative preconditioning. No postoperative hyperacute rejection occurred. RESULTS: Seven days after surgery, preexisting antibody levels rose and decreased after treatment; meanwhile, the function of transplanted kidney returned to normal. During 24 months of follow-up, the grafts showed good blood perfusion and functioned well. The levels of preexisting antibodies, donor-specific antibodies (DSA) and C1q-fixing human leukocyte antigen (C1q-HLA) antibodies, all decreased. CONCLUSIONS: Combined kidney and splenic fossa auxiliary heterotopic liver transplantation can be used in renal transplantation for highly sensitized recipients.

[Age-related differences in the clinical symptoms and triggering factors among Chinese patients with acute myocardial infarction].

OBJECTIVE: To analyze the age-related differences in the clinical symptoms and triggering factors among Chinese patients with acute myocardial infarction. METHODS: Acute myocardial infarction Patients (n=14 854) registered in the China Acute Myocardial Infarction Registry from January 2013 to March 2014 were included in this study. Patients were divided into 4 groups: <55 years old group (3 950 patients), 55-64 years old group (4 361 patients), 65-74 years old group ( 3 759 patients), and ≥75 years old group (2 784 patients). Demographic features, medical history, clinical presentation and triggering factors were obtained via electronic data capture system. RESULTS: (1)Persistent chest pain and sweat were the major typical symptoms 66.4%(9 863/14 854) and 63.8%(9 471/14 854)) in the whole cohort. Prevalence of persistent chest pain among four groups were 73.8%(2 915/3 950), 69.2%(3 016/4 361), 63.6%(2 394/3 759) and 55.2%(1 538/2 784), and radiating pain among four groups were 36.2%(1 428/3 950), 34.1%(1 487/4 361), 30.9%(1 160/3 759)and 25.9%(722/2 784), and sweat among four groups were 70.0%(2 765/3 950), 66.5%(2 898/4 361), 61.8%%(2 323/3 759)and 53.3%(1 485/2 784), and there were statistical significance for all above symptoms among groups (all P<0.001). (2)triggering factors before acute myocardial infarction could be found in 19.4%(2 879/14 854) of the patients. Prevalence of existed triggering factors among four groups were 23.8%(941/3 950), 21.0%(914/4 361), 16.6%(625/3 759) and 14.3%(399/2 784, P<0.001). Recent excessive unhealthy lifestyles among four groups were 20.8%(196/3 950), 11.9%(109/4 361), 10.1%(63/3 759) and 9.0%(36/2 784) among the 4 groups (P<0.001). CONCLUSIONS: Persistent chest pain and sweat are absent in nearly half of Chinese patients in ≥75 years old group. Triggering factors prior to acute myocardial infarction could be evidenced in about twenty percent patients, and which are more often in young patients. Clinical Trail Registry: National Institutes of Health，NCT018746.

Tailoring the transmission lineshape spectrum of zigzag graphene nanoribbon based heterojunctions via controlling their width and edge protrusions.

We report a first-principles analysis of electron transport through narrow zigzag graphene nanoribbon (up to 2.2 nm) based wedge-shaped heterojunctions. We show that the width difference between the electrode and the scattering region and the edge protrusion of heterojunctions can be tuned to endow the system's transmission spectrum with distinctive features. In particular, transport through junctions with a one sided protrusion in the scattering region is always dominated by a Breit-Wigner-type resonance right at the Fermi level, regardless of the large or small width difference. On the other hand, a junction with protrusions on both sides of the scattering region shows insulating behaviour near the Fermi level for a large width difference but weak transmission channels are formed at the core of the scattering region for a small width difference. When the protrusion is absent in the junction, transmission functions display rather complex structures: double peaks situating nearly symmetrically away from the Fermi level and a strongly asymmetric profile in the vicinity of the Fermi level are observed for large and small width differences, respectively. These results may shed light on the design of real connecting components in nanocircuits.

Connexin evolution ameliorates the risk of various cancers.

OBJECTIVE: Connexins can affect many cancers, but the relationship of many connexins is confused and the functions in cancers are unknown. MATERIALS AND METHODS: With conservative domains of connexins, the phylogenetic tree was constructed and all connexins could be divided into five groups (I, II, III, IV and V). The clock analysis showed that group V appeared earlier than group IV, which was earlier than group III, which was earlier than group I and II in the evolution. Group I involves in colorectal, lung, breast, pancreatic, gastric, colon, bladder and ovarian cancers. Group II affects bladder, breast, lung, gastric, colorectal, prostate, esophageal, renal, head and neck cancers. Group III affects bladder and breast cancer. The function of group IV and V has not been reported. RESULTS: When HT1376 bladder cancer cells were transfected with Cx31.9 (Group IV), the growth rate was inhibited by 17%. Inversely, when HT1376 cells were transfected with Cx31.9 RNAi, the growth rate was increased by 21%. For Cx23 (Group V), it could not affect the growth rate. CONCLUSIONS: The results suggested that ancient connexins did not involve in cancers. Recent connexins have developed the functions for inhibiting the progression of cancers in the evolution.

SU-E-T-309: Dosimetric Study and Clinical Implementation of an HDR Applicator of SAVI for Partial Breast Irradiation.

PURPOSE: To present clinical implementation and quality assurance for a new HDR applicator of Strut-Adjusted Volume Implant (SAVI) for partial breast irradiation and the higher-order DVH examined. METHODS: The SAVI applicator with multi-peripheral struts can be differentially loaded with the HDR source for a conformal dose distribution to the lumpectomy cavity. The treatment plan is evaluated by a dose volume histogram (DVH) as follows: V90 > 90%, V150 < 50 cc, and V200 < 20 cc. A higher-order DVH which may reflect radiation-induced toxicity, such as V300, was studied. The SAVI device status was verified by the 3D CT images and image fusion. Tissue invagination was investigated using an ion chamber and film with the cavity filled with air and water merged into a water phantom. RESULTS: Twenty-nine patients to date at Mercy Medical Center, Baltimore, Maryland were treated with SAVI device. The dosimetric data demonstrated the achievements of greater than 90% coverage for V90 at 96.8% and 94.1% for V95 while keeping a low V150 at 33.9 cc and V200 at 16.5 cc. V300 was found to be 2.7 cc in average. Potential uncertainties introduced by the SAVI applicator motion were a 3% variation in dose caused either by a 3-mm} translation or a rotation of 3 degree. CONCLUSIONS: Multiple catheters of the SAVI applicator allows for optimal and conformal dose distribution around a lumpectomy cavity while minimizing the dose to adjacent normal structures such as skin and ribcage. Multiple imaging techniques are capable to verify cavity variation, strut collapse or relative motion, and device shift. A nearly fully loaded dwell source position produced the discrepancy of less than 3% and allow for optimal and conformal dose distribution to a lumpectomy cavity. Advantages of the SAVI applicator have been shown in treating breast cancer with the shallower, elliptical, and asymmetric cavity.

Electron Transport Suppression from Tip-π State Interaction on Si(100)-2 × 1 Surfaces.

We investigate the electron transport between a scanning tunneling microscope tip and Si(100)-2 × 1 surfaces with four distinct configurations by performing calculations using density functional theory and the nonequilibrium Green's function method. Interestingly, we find that the conducting mechanism is altered when the tip-surface distance varies from large to small. At a distance larger than the critical value of 4.06 Å, the conductance is increased with a reduction in distance owing to the π state arising from the silicon dimers immediately under the tip; this in turn plays a key role in facilitating a large transmission probability. In contrast, when the tip is closer to the substrate, the conductance is substantially decreased because the π state is suppressed by the interaction with the tip, and its contribution in the tunneling channels is considerably reduced.

Diphenhydramine modulates cytokines and induces apoptosis in experimental acute pancreatitis.

In this study, we investigated the therapeutic potential of diphenhydramine (DPH), a H(1) receptor antagonist, on taurocholate-induced acute pancreatitis and the underlying mechanisms involved. Rats were randomly divided into sham-operated, model, DPH-treated, octreotide-treated and the DPH plus octreotide combination therapy groups (n = 30 per group). Animals were sacrificed 3, 6 and 24 h after modeling and drug administration (n = 10 per time point) and sera, pancreas and lungs were harvested for further studies. DPH and octreotide monotherapy relieved histopathological injuries in multiple organs when compared to the model group. Combination therapy (DPH + octreotide) demonstrated better therapeutic potential than monotherapy. Data indicated that combination therapy had a better ability to reduce average mortality rates in rats, decrease the number of inflammatory cells, attenuate necrosis, upregulate the levels of amylase, TNF-alpha and IL-8 and downregulate the levels of IL-10 in the serum. Moreover, enhanced expression of Bax in the pancreas and lung were recorded suggesting a pro-apoptotic mechanism involved in the therapeutic potential of DPH. Our study demonstrated the therapeutic potential of DPH in acute pancreatitis and suggested a novel strategy for clinical management of this disease.

Astrocytic activation in thoracic spinal cord contributes to persistent pain in rat model of chronic pancreatitis.

One of the most important symptoms in chronic pancreatitis (CP) is constant and recurrent abdominal pain. However, there is still no ideal explanation and treatment on it. Previous studies indicated that pain in CP shared many characteristics of neuropathic pain. As an important mechanism underlying neuropathic pain, astrocytic activation is probably involved in pain of CP. Based on the trinitrobenzene sulfonic acid (TNBS)-induce rat CP model, we performed pancreatic histology to assess the severity of CP with semiquantitative scores and tested the nociceptive behaviors following induction of CP. Glial fibrillary acidic protein (GFAP) expressions in the thoracic spinal cord were observed by immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, we injected intrathecally astrocytic specific inhibitor l-alpha-aminoadipate (LAA) and observed its effect on nociception induced by CP. Compared to the naive and sham group, TNBS produced long lasting pancreatitis, and persistent mechanical hypersensitivity in the abdomen that was evident 1 week after TNBS infusion and persisted up to 5 weeks. Compared with naive or sham operated rats, GFAP staining was significantly increased 5 weeks after CP induction. Real-time RT-PCR indicated that GFAP expression was significantly increased in TNBS treated rats compared to the sham group. TNBS-induced astrocytic activation was significantly attenuated by LAA, compared with the saline control. Treatment with LAA significantly, even though not completely, attenuated the allodynia. Our results provide for the first time that astrocytes may play a critical role in pain of CP. Some actions could be taken to prevent astrocytic activation to treat pain in CP patients.

Transplantation of embryonic small hepatocytes induces regeneration of injured liver in adult rat.

Small hepatocytes as hepatic stem cells or progenitors may be transplanted to treat several end-stage liver diseases. To identify the characteristics of epithelial cells enriched from fetal liver, we used immunocytochemistry and electron micrography. All cells in the colonies were immunocytochemically positive for alpha fetoprotein and cytokeratins (CK) 7, CK8, and CK18, which are markers of hepatic progenitor. Under transmission electron microscopy, we observed the cultured cells to show naive characteristics of stem cells and to be significantly distinct from mature hepatocytes. To identity whether these small hepatocytes were able to proliferate and differentiate into mature hepatocytes, we cultured them in vitro, and, through the portal vein, and transplanted elements whose membrane were stained with red fluorescence using PKH26 linker dye, into the livers of CCl(4)-treated rats that had been subjected to two-thirds partial hepatectomy. Significant liver regeneration was observed 30 days later in rats that did or did not receive the cells. The livers of hepatocytes recipients showed sharper edges and smoother surfaces than the control group. Diffused cells labeled with red fluorescence were observed in the portal area, with branch-like red fluorescence in regions near portal areas of some lobules, suggesting that these elements were involved in the repair of liver lobules and differentiation into mature hepatocytes. Our results revealed that small hepatocytes not only have characteristics of hepatic stem cells, but also may be a source of cellular transplantation to treat liver diseases.

Changes in the expression of endothelial-overexpressed lipopolysaccharide-associated factor 1 in grafts during acute rejection following liver transplantation in rats.

This study investigated changes in expression of endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1) in grafts following liver transplantation in rats. Thirty Lewis rats received liver transplants from Lewis rats (tolerance group); 30 received liver transplants from dark Agouti rats (acute rejection group). Changes in serum biochemical indexes (alanine aminotransferase and total bilirubin), graft histology and EOLA1 expression were measured on days 1, 3, 5, 7 and 10 post-operatively. Mean survival time was >100 days in the tolerance group and 16.2 +/- 1.4 days in the acute rejection group. Pathological evidence of acute rejection in grafts was seen after day 5 in the acute rejection group. Serum biochemical indexes were significantly higher in the acute rejection group than in the tolerance group from day 5 post-operatively, whereas EOLA1 expression in the liver graft was significantly higher in the tolerance group than in the acute rejection group. EOLA1 expression seems to be negatively correlated with severity of rejection after liver transplantation.

Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma.

BACKGROUND: Although the primitive haematopoietic and neuronal stem cell marker CD133 is known to be present in cancer stem cells (CSCs) in hepatocellular carcinoma (HCC), the postresection prognostic impact of CD133 in HCC patients remains limited. METHODS: Sixty-three resected specimens were collected from HCC patients. The expression of CD133 protein was analysed by immunohistochemistry and the association of CD133 expression with clinicopathological characteristics, tumour recurrence and survival of the patients was evaluated. RESULTS: Immunohistochemical analysis of 63 HCC tissue specimens revealed that CD133 positive tumour cells were frequently present in HCC. Increased CD133 immunostaining was found in 26 specimens (41.3%). Increased CD133 expression levels were correlated with increased tumour grade, advanced disease stage, and elevated serum alpha-fetoprotein levels. Kaplan-Meier analysis indicated that patients with increased CD133 levels had shorter overall survival and higher recurrence rates compared with patients with low CD133 expression. Multivariate analyses revealed that increased CD133 expression was an independent prognostic factor for survival and tumour recurrence in patients with HCC. CONCLUSIONS: These findings suggest that reactivated CD133 positive cells are frequently present in HCC. Additionally, increased CD133 expression corresponds with higher stage tumours in HCC, thus indicating a poor prognosis for patients. These data support the CSC hypothesis.

EPR study of ZnS: Mn2+ nanocrystals in Pyrex glasses.

ZnS: Mn2+ nanocrystals embedded in Pyrex glasses were spectrally studied using EPR and photoluminescence techniques. Photoluminescence (PL) and excitation (PLE) spectra revealed that manganese impurities can be classified as two types of luminescent centers, i.e., occupying substitutional sites (Mn2+)sub or interstitial sites (Mn2+)int. Three types of manganese sites of (Mn2+)sub, (Mn2+)int, and Mn clusters were identified by the EPR spectra. An increase of the g1 factor and hyperfine structure (HFS) constant with decreasing sizes of nanocrystals was observed. The increase was attributed to a hybridization of the s-p state of ZnS and the d state of manganese ions enhanced by quantum confinement effects or surface states.

The Na+/H+ exchange inhibitor: a new therapeutic approach for hepatic ischemia injury in rats.

BACKGROUND: Na+/H+ exchanger (NHE) is one of the major mechanisms for restoring pH after ischemia-induced intracellular acidosis. However, activation of NHE during ischemia and reperfusion (I/R) is also involved in the paradoxical induction of cell injury. This study was designed to evaluate the effects of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), an NHE inhibitor, on hepatic I/R injury. METHODS: Partial hepatic ischemia was induced in male Wistar rats by cross-clamping the hepatic arterial and portal venous branches to the left lateral and median lobes of the liver for 120 minutes. The caudate and right lateral lobes were removed immediately after reperfusion. The concentrations of serum enzymes and ATP levels and energy charge in the live tissue were examined after 1-hour reperfusion. RESULT: EIPA afforded considerable protection against I/R injury, as demonstrated by decreased transaminase release and reduced histologic hepatocyte damage and increased energy charge. The 7-day survival rate was significantly improved from 15.4% to 55.6% (P <.05). CONCLUSIONS: This study shows for the first time that NHE may play an important role in the hepatic I/R injury and that EIPA should be considered as a new therapeutic approach to prevent hepatic I/R injury.

[Thyroidectomy and injury of recurrent laryngeal nerve].

OBJECTIVE: To study factors related to recurrent laryngeal nerve (RLN) paralysis, a major complication of thyroidectomy. METHOD: Retrospective study of outcome of patient's medical records in Xijing Hospital and Tumor Hospital of Liaoning Province. Records of 1,563 patients who underwent thyroidectomy by departments of general surgery, ENT and head & neck surgery at these two hospitals were reviewed for RLN paralysis. MAIN OUTCOME MEASURES: RLN injury was analyzed in relation to types of surgery, RLN identification, and histopathology. RESULT: The incidence of RLN paralysis was 7.8%, and significantly related to the histopathologic findings of malignancy (P < 0.01). The positive identification and prevention of RLN would not be in either permanent RLN paralysis or temporary RLN paralysis, and the types of surgery were not found to be significant factors in both paralysis. CONCLUSION: RLNs should be identified to avoid iatrogenic injury and subsequent paralysis, and meticulous surgical technique should be applied in patients whose results of biopsy suggested malignancy.