Comprehensive safety profile evaluation of bivalirudin in Chinese ST-segment elevation myocardial infarction patients receiving percutaneous coronary intervention: a prospective, multicenter, intensive monitoring study.

BACKGROUND: This prospective, multi-center, intensive monitoring study aimed to systematically assess the occurrence of adverse events (AEs) and adverse drug reactions (ADRs), especially thrombocytopenia and bleeding, as well as their risk factors in Chinese ST-segment elevation myocardial infraction (STEMI) patients receiving bivalirudin as anticoagulant for percutaneous coronary intervention (PCI). METHODS: In total, 1244 STEMI patients undergoing PCI and receiving bivalirudin as anticoagulant were enrolled in the present study. Safety data were collected from hospital admission to 72 h after bivalirudin administration; in addition, patients were further followed up at the 30th day with safety data collected at that time. RESULTS: AEs, severe AEs, ADRs and severe ADRs were reported in 224 (18.0%), 15 (1.2%), 49 (3.9%) and 5 (0.4%) patients, respectively. Importantly, 4 (0.3%) patients were submitted to hospitalization and 6 (0.5%) patients died due to AEs, while 1 (0.1%) patient was submitted to hospitalization but no (0.0%) patient died due to ADRs. Meanwhile, thrombocytopenia and bleeding occurred in 24 (1.9%) and 21 (1.7%) patients, respectively. Further multivariate logistic analysis identified several important independent factors related to AEs, ADRs, thrombocytopenia or bleeding, which included history of cardiac surgery and renal function impairment, high CRUSADE risk stratification, elective operation and combination with glycoprotein IIb/IIIa inhibitors. Moreover, 4 multivariate models were constructed based on the above-mentioned factors, which all showed acceptable predictive value for AEs, ADRs, thrombocytopenia and bleeding, respectively. CONCLUSION: Bivalirudin is a well-tolerant anticoagulant in Chinese STEMI patients undergoing PCI procedure.

Time trends, associations and prevalence of blindness and vision loss due to glaucoma: an analysis of observational data from the Global Burden of Disease Study 2017.

OBJECTIVE: To estimate global prevalence of blindness and vision loss caused by glaucoma, and to evaluate the impact of socioeconomic factors on it. DESIGN: A population-based observational study. SETTING: The prevalence of blindness and vision loss due to glaucoma were obtained from the Global Burden of Disease Study 2017 database. The Human Development Index (HDI), inequality-adjusted HDI and other socioeconomic data were acquired from international open databases. MAIN OUTCOME MEASURES: The prevalence of blindness and vision loss due to glaucoma by age, gender, subregion and Socio-Demographic Index (SDI) levels. Multiple linear regression analysis was performed to explore the associations between the prevalence and socioeconomic indicators. RESULTS: The overall age-standardised prevalence of blindness and vision loss due to glaucoma worldwide was 81.5 per 100 000 in 1990 and 75.6 per 100 000 in 2017. In 2017, men had a higher age-standardised prevalence than women (6.07% vs 5.42%), and the worldwide prevalence increased with age, from 0.5 per 100 000 in the 45-49 year age group to 112.9 per 100 000 among those 70+. Eastern Mediterranean and African regions had the highest prevalence during the whole period, while the Americas region had the lowest prevalence. The prevalence was highest in low-SDI and low-income regions while lowest in high-SDI and high-income regions over the past 27 years. Multiple linear regression showed cataract surgery rate (ß=-0.01, p=0.009), refractive error prevalence (ß=-0.03, p=0.024) and expected years of schooling (ß= -8.33, p=0.035) were associated with lower prevalence, while gross national income per capita (ß=0.002, p<0.001) was associated with higher prevalence. CONCLUSIONS: Lower socioeconomic levels and worse access to eyecare services are associated with higher prevalence of glaucoma-related blindness and vision loss. These findings provide evidence for policy-makers that investments in these areas may reduce the burden of the leading cause of irreversible blindness.

Genetic associations of anti-vascular endothelial growth factor therapy response in age-related macular degeneration: a systematic review and meta-analysis.

PURPOSE: To investigate the association of all reported common polymorphisms in anti-vascular endothelial growth factor (VEGF) therapy response and to identify potential clinically useful biomarkers for anti-VEGF therapy response in patients with age-related macular degeneration (AMD). METHODS: We searched the Embase, PubMed, Web of Science databases in English and the China National Knowledge Infrastructure, WanFang and VIP databases in Chinese for pharmacogenetics studies on anti-VEGF therapy response in AMD. Odds ratios with 95% confidence intervals were calculated using the random effects model. RESULTS: Among the 10 468 records yielded by the literature search, 33 articles that met the eligibility criteria were included in the meta-analysis. Nine single-nucleotide polymorphisms (SNP) in four genes were observed to be associated with the anti-VEGF therapy response in AMD patients. That is, rs1120063 in the HTRA1 gene; rs10490924 in the age-related maculopathy susceptibility (ARMS2) gene; rs1061170 in the complement factor H (CFH) gene; and rs323085 in the OR52B4 gene were associated with good anti-VEGF therapy responses, while rs800292, rs1410996 and rs1329428 in the CFH gene and rs4910623 and rs10158937 in the OR52B4 gene were associated with poor anti-VEGF therapy response in the AMD patients in our sample. CONCLUSION: In this study, nine SNPs of four genes were indicated to be significantly associated with the anti-VEGF therapy response in the samples: rs11200638 in the HTRA1 gene; rs10490924 in the ARMS2 gene; rs1061170, rs800292, rs1410996 and rs1329428 in the CFH gene; and rs323085, rs4910623 and rs10158937 in the OR52B4 gene. Further studies based on various ethnicities and large sample sizes are warranted to strengthen the evidence found in the present study.

IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin.

Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1.

Quantitative Analysis of a Weak Correlation between Complicated Data on the Basis of Principal Component Analysis.

The mining of weak correlation information between two data matrices with high complexity is a very challenging task. A new method named principal component analysis-based multiconfidence ellipse analysis (PCA/MCEA) was proposed in this study, which first applied a confidence ellipse to describe the difference and correlation of such information among different categories of objects/samples on the basis of PCA operation of a single targeted data. This helps to find the number of objects contained in the overlapping and nonoverlapping areas of ellipses obtained from PCA runs. Then, a quantitative evaluation index of correlation between data matrices was defined by comparing the PCA results of more than one data matrix. The similarity and difference between data matrices was further quantified through comprehensively analyzing the outcomes. Complicated data of tobacco agriculture were used as an example to illustrate the strategy of the proposed method, which includes rich features of climate, altitude, and chemical compositions of tobacco leaves. The number of objects of these data reached 171,516 with 14, 4, and 5 descriptors of climate, altitude, and chemicals, respectively. On the basis of the new method, the complex but weak relationship between these independent and dependent variables were interestingly studied. Three widely used but conventional methods were applied for comparison in this work. The results showed the power of the new method to discover the weak correlation between complicated data.

Comparison of a new anterior segment optical coherence tomography and Oculus Pentacam for measurement of anterior chamber depth and corneal thickness.

BACKGROUND: Accurate measurements of anterior chamber depth (ACD) and regional corneal thickness are especially important for the diagnosis and treatment of many ocular disease. This study aimed to evaluate the repeatability and reliability of a new swept source anterior segment optical coherence tomography (AS-OCT) and its agreement with Oculus Pentacam for measurements of ACD and corneal thickness (CT). METHODS: The central corneal thickness (CCT), superior corneal thickness (SCT), inferior corneal thickness (ICT), nasal corneal thickness (NCT), temporal corneal thickness (TCT) and ACD of the right eye from forty-nine adults aged 18 to 36 years (24.78±4.36 years old) were measured with Pentacam and AS-OCT (CASIA2). All subjects were measured twice with each device. The repeatability was determined using the coefficient of repeatability (COR), the relative COR and the limits of agreement (LOA). Bland-Altman plot was also used for evaluating the agreement between parameters from the two devices. RESULTS: For the repeatability of CASIA2, the COR of the two measurements of ACD, CCT, SCT, ICT, NCT and TCT was 0.31 mm, 18.58, 25.83, 28.32, 26.71 and 22.09 µm respectively. There were no statistically significant differences between the CT and ACD measurements by CASIA2 (P>0.05). For measurements with Pentacam and CASIA2, the COR of ACD, CCT, SCT, NCT, ICT and TCT was 0.294 mm, 13.10, 51.57, 48.06, 56.21 and 47.69 µm respectively. No significant differences were found between the values measured by CAISA2 and Pentacam for CT and ACD (P>0.05). The Bland-Altman analysis also suggested high consistency between measurements obtained by Pentacam and CASIA2. CONCLUSIONS: Our results suggest that Pentacam and CASIA2 have good agreement in CT and ACD measurements. The two devices can be considered interchangeable for these parameters' measurements in healthy subjects when monitoring corneal conditions or planning ocular surgery. However, subtle differences between CASIA2 and Pentacam should also be kept in mind for certain specific clinical or research purposes.

Characteristics and Risk Factors for Pupillary Capture of Intraocular Lens in Congenital Ectopia Lentis.

Importance: To analyze the characteristics and risk factors for pupillary capture (PC) of the intraocular lens (IOL) in congenital ectopia lentis (CEL) patients.Methods: Data of CEL patients who underwent lens extraction and intraocular implantation from 2013 to 2016 at Zhongshan Ophthalmic Center in China were collected. Best-corrected visual acuity (BCVA), axial length (AL), refractive status, corneal curvature, intraocular pressure (IOP), degree of lens dislocation, presence of strabismus, and methods of IOL fixation were recorded. Postoperative data were collected from the routine one-month postoperative follow-up. Patients with PC of IOL were characterized and risk factors for PC of IOL were analyzed using age-sex adjusted multiple logistic regression analysis.Results: Of the 89 included CEL subjects, 43.8% (39/89) of them suffered from PC after IOL implantation. There was no statistically significant difference in BCVA, AL, refractive status and IOP between the eyes which developed PC versus those which did not. Age-sex multiple logistic regression analysis shows that PC of IOL was associated with a more severe degree of lens dislocation and eyes with strabismus before surgery.Conclusions: Eyes with strabismus and more severe degrees of lens dislocation before surgery are risk factors for PC of IOL. When treating patients that present these risk factors, preoperative communication, and postoperative follow-up should be strengthened. Considering that PC of IOL has little effect on visual acuity, patients with slight PC of IOL can be exempt from surgical intervention.

Ginkgolide B ameliorates NLRP3 inflammasome activation after hypoxic-ischemic brain injury in the neonatal male rat.

INTRODUCTION: Perinatal hypoxic-ischemic (HI) insult is an important cause of brain injury in neonates. The development of novel treatment strategies for neonates with HI brain injury is urgently needed. Ginkgolide B (GB) is a main component of Ginkgo biloba extracts with a long history of use in traditional Chinese medicine. However, it is unknown whether GB could play a protective role in hypoxic stress in immature animals. METHODS: Using neonatal hypoxic-ischemic (HI) brain injury model of rat pups, neurological score, infarct size, and brain edema were evaluated after HI injury. The activation of microglia and the production of IL-1ß and IL-18 were detected by immunohistochemistry and ELISA, respectively. A priming signal (NF-κB P65) and an activation signal (Caspase-1) of NLRP3 inflammasome activation were detected by western blot analyses. RESULTS: GB administrated 30 min prior to ischemia induction can improve neurological disorder, reduce infarct volume and alleviate cerebral edema. Compared with the HI groups, GB inhibited the activation of microglia and decreased the production of IL-1ß and IL-18 in neocortex. Furthermore, GB reduced NLRP3 expression mainly in microglia, and significantly inhibited the expression of Caspase-1 and the nuclear translocation of NF-κB P65, preventing NLRP3 inflammasome activation. CONCLUSIONS: GB ameliorates hypoxic-ischemic brain injury in the neonatal male rat via inhibiting NLRP3 inflammasome activation.

A report of a novel technique: The comprehensive fibular autograft with double metal locking plate fixation (cFALP) for refractory post-operative diaphyseal femur fracture non-union treatment.

INTRODUCTION: The refractory post-operative diaphyseal femur fracture (DFF) non-union is extremely difficult to treat and remains severe challenges for orthopedists. Although several traditional internal fixations and novel biomedical techniques have been used in managing this complication, its treatment is still fraught with severe challenges. PATIENTS AND METHODS: Starting from 1999, 5 patients after three previous internal fixation operations showing refractory DFF non-union underwent the comprehensive fibular autograft with double metal locking plates fixation (cFALP) surgery. The autogenous fibular was first harvested and non-evenly split into two halves in a longitudinal manner. After retracting all previous internal fixation(s), the larger half strut fibula was hammered into the femur canal while the smaller half was fragmented into small pieces and filled surrounding the DFF site. Two locking compression plate were fixed on the lateral and anterior (or antero-lateral) side of the femur, respectively. RESULTS: The follow-up ranged from 60 to 96 weeks. All cases (100%) achieved bony union without severe complications. The mean time to union was 36±14.7 weeks (range 24-60 weeks). CONCLUSION: The cFALP is a promising surgical modality for DFF non-union treatment. However, because fibular harvest may cause severe complications, the cFLAP should only be considered in refractory DFF non-union cases.

[Key aromatic amino acids of anti-hepatoma activity on Parasporin-2].

Nine mutants (P2M1-9) were obtained using PCR with 5-BU based on DNA template (P2Y) encoding the active region of Parasporin-2. Mutant proteins were purified after expressing in E. coli BL21 cells, followed by assayed against hepatoma cells and normal liver cells by MTT. They showed diverse anti-hepatoma activities, in which two mutant proteins, P2M1 and P2M8, exhibited high cytotoxicity against hepatoma cell lines SMMC7721 and Be17402, meanwhile leaving normal liver cells Chang-liver unaffected. Structural comparison among P2Y, P2M1 and P2M8 showed that the length of beta-sheet or beta-fold, and the amount of alpha helix greatly affected the anti-hepatoma activity of Parasporin-2. Results based on amino acid alignment, molecular docking between P2Y, P2M1 or P2M8 and receptor, and mimic mutation demonstrated that amino acid residues at the sites of 52, 56, 58 and 208 on P2Y, especially the aromatic amino acids such as Trp, Phe, and Tyr were involved in the interactions.

Treatment of ischial pressure sores with double adipofascial turnover flaps.

Despite a variety of flap reconstruction options, the ischium remains the most difficult pressure sore site to treat. This article describes the authors' successful surgical procedure for coverage of ischial ulcers using double adipofascial turnover flaps.After debridement, the adipofascial flaps are harvested both cephalad and caudal to the defect. The flaps are then turned over to cover the exposed bone in a manner so as to overlap the 2 flaps. The skin is then closed with sutures in 2 layers. A total of 15 patients with ischial sores were treated using this surgical procedure.The follow-up period ranged from 11 to 159 months, with a mean of 93.6 months. Overall, 86.7% of the flaps (13 of 15) healed primarily. One patient had a recurrent grade II ischial pressure sore again 11 months after the operation. The other 14 patients did not have a recurrence.Treatment of ischial pressure sores with adipofascial turnover flaps provides an easy, minimally invasive procedure, with preservation of future flap options, and a soft-tissue supply sufficient for covering the bony prominence and filling dead space. This technique is a reliable and safe reconstructive modality for the management of minor ischial pressure sores.