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Introduction Elderly patients are at a high risk of postoperative delirium (POD), leading to increased postoperative morbidity and mortality. The use of dexmedetomidine and depth of anaesthesia may influence POD. This study aims to determine the effects of dexmedetomidine infusion versus normal saline placebo during light versus deep anaesthesia on POD among elderly patients undergoing major non-cardiac surgery.Methods and analysis This prospective, multicentre, randomised, controlled, factorial trial will be conducted at three tertiary hospitals in Jiangsu, China. We will recruit a total of 420 patients who are at least 60 years old and undergoing major non-cardiac surgery (thoracic, abdominal, urology, orthopaedic and spine surgery) under general anaesthesia. Patients will be randomised (1:1:1:1) to receive one of four anaesthesia regimens: (1) dexmedetomidine and light anaesthesia, (2) dexmedetomidine and deep anaesthesia, (3) placebo and light anaesthesia or (4) placebo and deep anaesthesia. Dexmedetomidine will be infused at 0.5 µg/kg/h throughout surgery, and intraoperative bispectral index target will be 55 for light anaesthesia and 40 for deep anaesthesia. The primary outcome is the occurrence of POD during the first 7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method two times per day. The secondary outcomes include days with POD, type of POD, pain scores at rest and on movement at 24 and 48 hours postoperatively, patient-controlled intravenous fentanyl consumption during 0–24 and 24–48 hours postoperatively, hypotension, bradycardia, postoperative nausea and vomiting, non-delirium complications, length of postoperative hospital stay, 30-day cognitive function and 30-day mortality. Data will be analysed on a modified intention-to-treat basis.Ethics and dissemination This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and each participating centre. The trial results will be published in a peer-reviewed journal.Trial registration Chinese Clinical Trial Registry (ChiCTR2300073271)

Abstract Pyroptosis may play an important role in the resistance of ovarian cancer (OC) to chemotherapy. However, the mechanism by which pyroptosis modulation can attenuate chemotherapy resistance has not been comprehensively studied in OC. Here, we demonstrated that RAS‐associated C3 botulinum toxin substrate 1 (RAC1) is highly expressed in OC and is negatively correlated with patient outcomes. Through cell function tests and in vivo tumor formation tests, we found that RAC1 can promote tumor growth by mediating paclitaxel (PTX) resistance. RAC1 can mediate OC progression by inhibiting pyroptosis, as evidenced by high‐throughput automated confocal imaging, the release of lactate dehydrogenase (LDH), the expression of the inflammatory cytokines IL‐1β/IL‐18 and the nucleotide oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome. Mechanically, RNA‐seq, gene set enrichment analysis (GSEA), coimmunoprecipitation (Co‐IP), mass spectrometry (MS), and ubiquitination tests further confirmed that RAC1 inhibits caspase‐1/gasdermin D (GSDMD)‐mediated canonical pyroptosis through the P21‐activated kinase 4 (PAK4)/mitogen‐activated protein kinase (MAPK) pathway, thereby promoting PTX resistance in OC cells. Finally, the whole molecular pathway was verified by the results of in vivo drug combination tests, clinical specimen detection and the prognosis. In summary, our results suggest that the combination of RAC1 inhibitors with PTX can reverse PTX resistance by inducing pyroptosis through the PAK4/MAPK pathway.

Abstract Crane usage is pervasive on construction sites, however, it is associated with a notably high accident rate. The analyzing of crane accident risks is essential for accident prevention, control, and ensuring the safety of lifting operations. Hence, significant emphasis should be placed on understanding the interaction among various risk factors. This paper proposes a quantitative coupling method for human, machine, management, and environmental risk factors in crane accidents, leveraging Bayesian networks (BN) and the N-K model. Firstly, text mining technology and fault tree analysis are employed to analyze the causes of crane accidents and categorize the associate risk factors. Secondly, the types of risk coupling resulting from human, machine, management, and environmental risk factors are defined. Thirdly, the BN model is developed based on the analysis of crane accident risksand its N-K model. Fourthly, the parameters of the risk coupling nodes in the developed BN are determined based on the calculation results of the N-K model. Finally, for the risk coupling types with high coupling values and the first-level node and second-level node, the failure probability is analyzed through posterior probability and sensitivity analysis. The results indicate that factors related to man and management significantly impact crane accidents and warrant enhanced attention. The interplay among multiple risk factors significantly influences the probability of crane accidents, necessitating careful attention.

Abstract This study aims to explore changes in depression and pain for major depressive disorder (MDD) patients with somatic pain after repetitive transcranial magnetic stimulation (rTMS) using the event-related potentials (ERPs) technique. Eighty MDD patients with somatic pain were randomly assigned to drug therapy (DT) and combined therapy (CT) groups. CT group underwent intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) with 800 pulses and 1 Hz over the right DLPFC with 800 pulses, 5 times a week for 3 weeks. All patients were given sertraline at 50–100 mg per day. All subjects were evaluated at baseline and at weeks three and six of therapy using the Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Scale (HAMA), and Numerical Rating Scales (NRS), and the latency and amplitude of P300 and mismatch negativity (MMN) were measured. There were no significant differences in all indices between groups at baseline. At 3 weeks, HAMD subscale scores of Cognitive Impairment and NRS scores were significantly lower in the CT group than in the DT group. At 6 weeks, NRS and HAMD total scores in the CT group decreased significantly in the CT group compared with the DT group, especially for anxiety and pain, and the MMN and P300 latencies and P300 amplitude showed greater improvements. Our findings highlight that rTMS in combination with antidepressants is a rapid method of symptom improvement in patients with somatic pain with MDD and is helpful for cognitive impairment and anxiety.

Abstract Allergic rhinitis (AR) is a prevalent chronic inflammatory disease of the nasal mucosa primarily characterized by symptoms, such as nasal itching, sneezing, runny nose, and nasal congestion. It has a high recurrence rate and low cure rate, with a lack of effective drugs for treatment. The current approach to management focuses on symptom control. High mobility group box-1 (HMGB1) is a highly conserved non-histone protein widely present in the nucleus of eukaryotes. It is recognized as a proinflammatory agent, and recent studies have demonstrated its close association with AR. Here, we will elaborate the role and mechanism of HMGB1 in AR, so as to reveal the potential value of HMGB1 in the occurrence and development of AR, and provide a new target for clinical research on the treatment of AR.

Abstract The function of natural killer (NK) cells has previously been implicated in hematopoietic-related diseases. Killer immunoglobulin-like receptors (KIR) play an important role in NK cells after hematopoietic stem cell transplantation. To explore the immunogenetic predisposition of hematological-related diseases, herein, a multi-center retrospective study in China was conducted, analyzing and comparing 2519 patients with hematopathy (mainly, acute lymphoblastic leukemia, acute myeloid leukemia, aplastic anemia, and myelodysplastic syndrome) to 18,108 individuals without known pathology. Genotyping was performed by polymerase chain reaction with specific sequence primers (PCR-SSP). As a result, we discovered four genes including KIR2DL5 (OR: 0.74, 95% CI 0.59–0.93; Pc = 0.0405), 2DS1 (OR: 0.74, 95% CI 0.59–0.93; Pc = 0.0405), 2DS3 (OR: 0.58, 95% CI 0.41–0.81; Pc = 0.0180), and 3DS1 (OR: 0.74, 95% CI 0.58–0.94; Pc = 0.0405) to be protective factors that significantly reduce the risk of aplastic anemia. Our findings offer new approaches to immunotherapy for hematological-related diseases. As these therapies mature, they are promising to be used alone or in combination with current treatments to help to make blood disorders a manageable disease.

Abstract AlCrFeCoNiCu0.5 thin films were fabricated by cathodic arc deposition under different substrate biases. Detailed characterization of the chemistry and structure of the film, from the substrate interface to the film surface, was achieved by combining high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and atomic force microscopy. Computer simulations using the transport of ions in matter model were applied to understand the ion surface interactions that revealed the key mechanism of the film growth. The final compositions of the films are significantly different from that of the target used. A trend of elemental segregation, which was more pronounced with higher ion kinetic energy, was observed. The XPS results reveal the formation of $${\mathrm{Al}}_{2}{\mathrm{O}}_{3}$$ Al 2 O 3 and $${\mathrm{Cr}}_{2}{\mathrm{O}}_{3}$$ Cr 2 O 3 on the thin film surface. The grain size is shown to increase with the increasing of the ion kinetic energy. The growth of equiaxed grains contributed to the formation of a flat surface with a relatively low surface roughness as shown by atomic force microscopy.

Abstract Background The diagnostic results of magnetic resonance imaging (MRI) are essential references for arthroscopy as an invasive procedure. A deviation between medical imaging diagnosis and arthroscopy results may cause irreversible damage to patients and lead to excessive medical treatment. To improve the accurate diagnosis of meniscus injury, it is urgent to develop auxiliary diagnosis algorithms to improve the accuracy of radiological diagnosis. Purpose This study aims to present a fully automatic 3D deep convolutional neural network (DCNN) for meniscus segmentation and detects arthroscopically proven meniscus tears. Materials and methods Our institution retrospectively included 533 patients with 546 knees who underwent knee magnetic resonance imaging (MRI) and knee arthroscopy. Sagittal proton density-weighted (PDW) images in MRI of 382 knees were regarded as a training set to train our 3D-Mask RCNN. The remaining data from 164 knees were used to validate the trained network as a test set. The masks were hand-drawn by an experienced radiologist, and the reference standard is arthroscopic surgical reports. The performance statistics included Dice accuracy, sensitivity, specificity, FROC, receiver operating characteristic (ROC) curve analysis, and bootstrap test statistics. The segmentation performance was compared with a 3D-Unet, and the detection performance was compared with radiological evaluation by two experienced musculoskeletal radiologists without knowledge of the arthroscopic surgical diagnosis. Results Our model produced strong Dice coefficients for sagittal PDW of 0.924, 0.95 sensitivity with 0.823 FPs/knee. 3D-Unet produced a Dice coefficient for sagittal PDW of 0.891, 0.95 sensitivity with 1.355 FPs/knee. The difference in the areas under 3D-Mask-RCNN FROC and 3D-Unet FROC was statistically significant (p = 0.0011) by bootstrap test. Our model detection performance achieved an area under the curve (AUC) value, accuracy, and sensitivity of 0.907, 0.924, 0.941, and 0.785, respectively. Based on the radiological evaluations, the AUC value, accuracy, sensitivity, and specificity were 0.834, 0.835, 0.889, and 0.754, respectively. The difference in the areas between 3D-Mask-RCNN ROC and radiological evaluation ROC was statistically significant (p = 0.0009) by bootstrap test. 3D Mask RCNN significantly outperformed the 3D-Unet and radiological evaluation demonstrated by these results. Conclusions 3D-Mask RCNN has demonstrated efficacy and precision for meniscus segmentation and tear detection in knee MRI, which can assist radiologists in improving the accuracy and efficiency of diagnosis. It can also provide effective diagnostic indicators for orthopedic surgeons before arthroscopic surgery and further promote precise treatment.

Introduction Optical coherence tomography (OCT) is a non-invasive approach for detecting changes in the retinal layers, which may also reflect changes in brain structure and function. As one of the leading causes of disability worldwide, depression has been associated with alteration of brain neuroplasticity. However, the role of OCT measurements in detecting depression remains unknown. This study aims to employ a systematic review and meta-analysis approach to explore ocular biomarkers measured by OCT for detecting depression.Methods and analysis We will search studies describing the relationship between OCT and depression across seven electronic databases, and retrieve articles published from database inception to date. We will also manually search grey literature and reference lists included in the retrieved studies. Two independent reviewers will screen studies, extract data and assess risk of bias. Target outcomes will include peripapillary retinal nerve fibre layer thickness, macular ganglion cell complex thickness and macular volume, as well as other related indicators. Next, we will conduct subgroup analysis and meta-regression to explore study heterogeneity, then perform sensitivity analysis to investigate the robustness of the synthesised results. Meta-analysis will be performed using Review Manager (V.5.4.1) and STATA (V.12.0), and the certainty of evidence will be graded according to the Grading of Recommendations Assessment, Development and Evaluation system.Ethics and dissemination Ethics approval is not necessary because the data used in this systematic review and meta-analysis will be extracted from published studies. Study results will be disseminated by publishing our findings in a peer-reviewed journal.

Background Attention bias modification (ABM) , a newly emerging focus in emotion modification research, is a treatment to reduce individuals' attention bias toward negative stimuli to improve their abnormal cognition via repeated computer-based attention trainings toward neutral or positive stimuli. Recent studies about depression treated using ABM are increasing, but based on insufficient evidence with various efficacy assessment indicators. Objective To systematically assess the effect of ABM in patients with depression. Methods Databases including PubMed, The Cochrane Library, EMBase, CBM, CNKI, WanFang Data and VIP were searched from inception to December 31st, 2021 for randomized controlled trials (RCTs) regarding depressive patients treated by ABM (experimental group with computer-based ABM trainings) compared with placebo trainings under the same conditions (control group with no interventions or sham ABM trainings) . Primary outcome measures included Hamilton Rating Scale for Depression (HAMD/HRSD) , Beck Depression Inventory (BDI) and Center for Epidemiologic Studies Depression Scale (CES-D) . Secondary outcome measures included the State-Trait Anxiety Inventory (STAI-T) and Ruminative Responses Scale (RRS) . Two researchers independently performed literature enrollment, and extracted data, and evaluated the risk of bias using Risk of Bias 2 (RoB 2.0) tool. RevMan 5.4 and Stata 12.0 were used for Meta-analysis. Results Thirteen RCTs involving 968 patients were included, among which one had two trials. Risk of bias was low in seven RCTs, unclear in four, and high in two. Meta-analysis showed that the overall improvement of depression, anxiety and rumination in the experimental group was better than that in the control group (P0.05) . When the follow-up time was prolonged to at least two months, the mean BDI score was still similar in both groups (P>0.05) . Conclusion ABM treatment could improve depressive, anxiety symptom and rumination in patients with depression, but its long-term effect needs to be studied further.

Abstract MicroRNAs (miRNAs) are involved in lymphoma progression by regulating the tumor microenvironment. Serum miR130b is overexpressed in diffuse large B-cell lymphoma (DLBCL), inducing Th17 cell alterations. To further illustrate its biological significance and therapeutic rationale, miR130b was detected by quantitative real-time PCR in the serum samples of 532 newly diagnosed DLBCL patients. The mechanism of miR130b on lymphoma progression and the tumor microenvironment was investigated both in vitro and in vivo. Therapeutic targeting miR130b was also evaluated, including OX40 agonistic antibody and lipid nanoparticles (LNPs)-miR130b antagomir. The results showed that serum miR130b significantly correlated with tumor miR130b and serum interleukin-17, indicating lymphoma relapse and inferior survival of DLBCL patients. MiR130b overexpression altered tumor microenvironment signaling pathways and increased Th17 cell activity. As mechanism of action, miR130b downregulated tumor OX40L expression by directly targeting IFNAR1/p-STAT1 axis, recruiting Th17 cells via OX40/OX40L interaction, thereby promoting immunosuppressive function of Th17 cells. In co-culture systems of B-lymphoma cells with immune cells, miR130b inhibited lymphoma cell autophagy, which could be counteracted by OX40 agonistic antibody and LNPs-miR130b antagomir. In murine xenograft model established with subcutaneous injection of A20 cells, both OX40 agonistic antibody and LNPs-miR130b antagomir remarkably inhibited Th17 cells and retarded miR130b-overexpressing tumor growth. In conclusion, as an oncogenic biomarker of DLBCL, miR130b was related to lymphoma progression through modulating OX40/OX40L-mediated lymphoma cell interaction with Th17 cells, attributing to B-cell lymphoma sensitivity towards OX40 agonistic antibody. Targeting miR130b using LNPs-miR130b antagomir could also be a potential immunotherapeutic strategy in treating OX40-altered lymphoid malignancies.

Abstract A plethora of both acute and chronic conditions, including traumatic, degenerative, malignant, or congenital disorders, commonly induce bone disorders often associated with severe persisting pain and limited mobility. Over 1 million surgical procedures involving bone excision, bone grafting, and fracture repair are performed each year in the U.S. alone, resulting in immense levels of public health challenges and corresponding financial burdens. Unfortunately, the innate self‐healing capacity of bone is often inadequate for larger defects over a critical size. Moreover, as direct transplantation of committed osteoblasts is hindered by deficient cell availability, limited cell spreading, and poor survivability, an urgent need for novel cell sources for bone regeneration is concurrent. Thanks to the development in stem cell biology and cell reprogramming technology, many multipotent and pluripotent cells that manifest promising osteogenic potential are considered the regenerative remedy for bone defects. Considering these cells' investigation is still in its relative infancy, each of them offers their own particular challenges that must be conquered before the large‐scale clinical application.

Rich literature has examined the impact of the built environment on commuting distance. Linear models assume that the influence of the built environment is spatially homogeneous. However, given the spatial heterogeneity of urban space, conclusions might be different or even be contrary. The influence of the built environment might also be different by home and work locations. To explore the spatially heterogeneous effect of the built environment from both home-based and work-based perspectives, this study applied large-scale cellular cellphone data in Guangzhou, China. Commuting was measured by decay parameters of probabilistic distributions of commuting distances. Geographically weighted regression models were applied to examine the spatially heterogeneous effect, differentiated by home-based and work-based perspectives. Results confirmed that the impact of the built environment on commuting distance is spatially heterogeneous. The urban space is classified into clusters of central areas, inner suburbs, and outer suburbs. Results also revealed the double-edged effect of the built environment. Residential population, recreation facilities, and mixed development are residence-attractive factors that increase the home-based commuting distance and decrease the work-based commuting distance. Work population and transport facilities are work-attractive factors that decrease home-based commuting distance and increase work-based commuting distance. The results further provide evidence to support area-based policies in urban planning practice.

Abstract Background This study aimed to establish and validate a nomogram for predicting brain metastasis in patients with bladder cancer (BCa) and assess various treatment modalities using a primary cohort comprising 234 patients with clinicopathologically-confirmed BCa from 2004 to 2015 in the National Cancer Database. Methods Machine learning method and Cox model were used for nomogram construction. For BCa patients with brain metastasis, surgery of the primary site, chemotherapy, radiation therapy, palliative care, brain confinement of metastatic sites, and the Charlson/Deyo Score were predictive features identified for building the nomogram. Results For the original 169 patients considered in the model, the areas under the receiver operating characteristic curve (AUC) were 0.823 (95% CI 0.758–0.889, P

Objective Aiming to investigate diabetic retinopathy (DR) risk factors and predictive models by machine learning using a large sample dataset.Design Retrospective study based on a large sample and a high dimensional database.Setting A Chinese central tertiary hospital in Beijing.Participants Information on 32 452 inpatients with type-2 diabetes mellitus (T2DM) were retrieved from the electronic medical record system from 1 January 2013 to 31 December 2017.Methods Sixty variables (including demography information, physical and laboratory measurements, system diseases and insulin treatments) were retained for baseline analysis. The optimal 17 variables were selected by recursive feature elimination. The prediction model was built based on XGBoost algorithm, and it was compared with three other popular machine learning techniques: logistic regression, random forest and support vector machine. In order to explain the results of XGBoost model more visually, the Shapley Additive exPlanation (SHAP) method was used.Results DR occurred in 2038 (6.28%) T2DM patients. The XGBoost model was identified as the best prediction model with the highest AUC (area under the curve value, 0.90) and showed that an HbA1c value greater than 8%, nephropathy, a serum creatinine value greater than 100 µmol/L, insulin treatment and diabetic lower extremity arterial disease were associated with an increased risk of DR. A patient’s age over 65 was associated with a decreased risk of DR.Conclusions With better comprehensive performance, XGBoost model had high reliability to assess risk indicators of DR. The most critical risk factors of DR and the cut-off of risk factors can be found by SHAP method to render the output of the XGBoost model clinically interpretable.

Objective: HLA-C*15:29 is a low-frequency allele in the human leukocyte antigen (HLA)-C locus. The aim of this study is to confirm the ethnicity of C*15:29 and to deduce a probable HLA haplotype in association with C*15:29 in Taiwanese population. Materials and Methods: A total of 12,534 healthy unrelated Taiwanese individuals were tested for HLA using a sequence-based typing method. The DNA material was subjected to HLA genotyping for the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci using a commercial polymerase chain reaction–sequencing-based typing kit as per the manufacturer's protocols. Results: The DNA sequence of C*15:29 is identical to C*15:02:01:01 in exons 1, 2, 3, 4, 5, and 6 except for residues 420 and 1034 where A and G of C*15:02:01:01 are substituted by C and A in C*15:29, respectively. The nucleotide substitutions introduce two amino acid replacements at residues 116 and 321 where leucine (L) and cysteine (C) of C*15:02:01:01 are replaced by phenylalanine (F) and tyrosine (Y) in C*15:29, respectively. A probable HLA haplotype associated with C*15:29 in Taiwanese was deduced as A*29:01-B*07:05-C*15:29-DRB1*10:01-DQB1*05:01. The frequency of C*15:29 is estimated at about 0.064%. Conclusion: Information on the ethnicity and distribution of C*15:29 and its deduced probable HLA haplotype is of value for HLA testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

Objective: HLA-B*40:247 is a low incidence allele in the HLA-B locus. The aim of this study is to confirm the ethnicity of B*40:247 and its deduced probable HLA- associated haplotype in Taiwanese individuals. Materials and Methods: A total of 2,329 unrelated Taiwanese individuals and 66,212 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. We confirmed the low incidence allele B*40:247 in Taiwanese. Polymerase chain reaction was performed to amplify exons 2, 3 and 4 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions with the *BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols. Results: The DNA sequence of B*40:247 is identical to B*40:01:01 in exons 2, 3 and 4 except for residue 853, where G of B*40:01:01 is changed to A in B*40:247 (codon 261, GTA->ATA). The nucleotide replacement causes a one amino acid change at codon 261 where V (valine) of B*40:01:01 is replaced by I (isoleucine) in B*40:247. We deduced the probable HLA haplotype associated with B*40:247 in Taiwanese to be HLA-A*24:02-B*40:247-C*03:04-DRB1*16:02. Conclusion: Information on the ethnicity and distribution of B*40:247 and its deduced probable HLA haplotype in association with the low incidence allele is of value for HLA testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

Introduction : Preimplantation genetic diagnosis/screening (PGD/PGS) can effectively detect chromosomal abnormalities in an embryo but only if an embryo is available. However, not all couples can obtain an embryo that is available for testing. The purpose of this study was to identify factors which might affect the formation of PGD/PGS embryos to predict the possibility of obtaining embryos that could be detected. Material and methods : In a retrospective study, we included all couples who underwent PGD/PGS at our center from January 2015 to December 2016. We compared these patients according to the non-blastocyst group and the blastocyst group. Results : There were 302 couples who had blastocysts in their first PGD/PGS cycle. Fifty-seven couples had no blastocysts in their PGD/PGS cycles: 43 couples had no blastocysts in one cycle; 10 in two cycles; 4 in three cycles. The non-blastocyst group was older than the blastocyst group (32.37 vs. 30.69, p = 0.048). Anti-mullerian hormone (ng/ml) in the non-blastocyst group was significantly lower than in the blastocyst group (4.80 ±3.67 vs. 3.07 ±2.30, p = 0.00). Women whose chromosome were aneuploid (47, XXX or 45, X) had a similar AMH level compared with others, but the number of retrieved oocytes was much lower; the normal karyotype was 14.25 and aneuploidy was 5.40 (p = 0.01) in women < 30 years old. There was the same condition in women aged 30–38 years (14.60 vs. 3.44, p < 0.001). Male’s different chromosome karyotype had no influence on double pronuclear number or the rate of blastocyst formation. Presence of endometriosis, polycystic ovary syndrome and tubal factor showed no difference between the blastocyst and non-blastocyst group. Nor did oligospermia and asthenospermia. Conclusions : Elderly women, those with lower AMH and women with 47, XXX or 45, X have fewer ova, leading to the possibility of no blastocyst. These couples should be fully informed and weigh the advantages and disadvantages before undergoing PGD/PGS.

Objective: Human leukocyte antigen (HLA)-DRB1*15:140 is a low-frequency allele in the HLA-DRB1 locus. The aim of this study is to confirm the ethnicity of DRB1*15:140 and to deduce a probable HLA-DRB1*15:140-associated HLA haplotype in Taiwanese individuals. Materials and Methods: A total of 1815 healthy unrelated Taiwanese individuals and 14,562 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exons 1 and 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions with the BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols. Results: The DNA sequence of HLA-DRB1*15:140 is identical to DRB1*15:02:01:01 in exons 1 and 2, except at residue 91 of DRB1*15:02:01:01 where a G in DRB1*15:02:01:01 is replaced by an A in DRB1*15:140 (codon 2; GAC->AAC). The nucleotide substitution in exon 1 introduces a one amino acid substitution at residue 2 where an aspartic acid (D) in DRB1*15:02:01:01 is replaced by an asparagine (N) in DRB1*15:140. We deduced the probable HLA haplotype associated with DRB1*15:140 in Taiwanese to be HLA-A*33:03-B*58:01-DRB1*15:140. Conclusion: Information on the ethnicity and distribution of DRB1*15:140 and its deduced probable HLA haplotype in association with the low-incidence allele is of value for HLA-testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

Objective: Human leukocyte antigen (HLA) DRB1*04:36 is a low-frequency HLA-DRB1 allele. The aim here is to report the ethnicity of DRB1*04:36 and its associated HLA haplotypes among Taiwanese individuals. Materials and Methods: A sequence-based typing method was employed to confirm this low incidence allele. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready Reaction kits and the manufacturer's protocols. One group of unrelated blood donors used in this study consists of randomized individuals with Taiwanese ethnicity who participate in the Tzu Chi Bone Marrow Donor Registry and the other group are randomized unrelated individuals from mainland China. The family members in the family part of the study are volunteer blood donors. Results: In exon 2, the DNA sequence of DRB1*04:36 is identical to DRB1*04:03:01 except for a nucleotide segment from residue 286 to residue 308. The nucleotide segment from residue 286 to residue 308, incidentally, is identical to that of DRB1*11:01:01:01. These observations suggest that DRB1*04:36 may have been derived through a gene recombination event involving DRB1*04:03:01 and DRB1*11:01:01:01. Our family study indicated that the HLA haplotype in association with DRB1*04:36 can be deduced to be A*24:02-B*39:01-DRB1*04:36. A randomized population study using Taiwanese suggests that additional DRB1*04:36 associated HLA haplotypes seem to exist. Conclusion: The information on the ethnicity of the DRB1**04:36 allele, and the deduced probable HLA haplotypes associated with the low incidence DRB1*04:36 allele that we report here, is of value to HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplantation donor search coordinators to aid the creation of strategy for finding compatible donors who are part of unrelated bone marrow donor registries when a patient carries this uncommon HLA allele.

Objective: HLA-A*11:256Q and HLA-A*02:621 are two low-frequency HLA-A alleles. The aim here is to report the ethnicity of A*11:256Q and A*02:621 and associated human leukocyte antigen (HLA) haplotypes among Taiwanese individuals. Materials and Methods: HLA data from randomized Taiwanese registered in the Tzu Chi Stem Cells Centre and China Shanghai Tissuebank Diagnostics were analyzed. HLA typing of the donors was carried out using a sequence-based typing method to confirm the two low-incidence alleles. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready Reaction kits and the manufacturer's protocols. Exon 1 and exons 4-8 of the A*11:256Q allele were also sequenced and analyzed. Results: The Taiwanese ethnicity for both A*11:256Q and A*02:621 alleles was confirmed in this study. Further, the DNA sequence of A* 11:256Q was confirmed to be identical to A*11:02:01from exon 1 to exon 8 except for the residues from 409 to 417 where a segment of nine nucleotides (TACCGGCAG) is deleted in A*11:256Q. The HLA haplotype associated with A*11:256Q was deduced as A*11:256Q-B*27-DRB1*12. In exons 2 and 3, the DNA sequence of A*02:621 is identical to A*02:01:01:01 except at residue 169 where T of A*02:01:01:01 is replaced by C in A*02:621 (at codon 33; TTC->CTC). The HLA haplotype in association with A*02:621 was deduced as A*02:621-B*15:18-DRB1*12:02. Conclusion: The information on the ethnicity of the A*11:256Q and A*02:621 alleles and the deduced probable HLA haplotypes associated with the two low-incidence alleles reported here are valuable to HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplantation donor search coordinators to aid in finding compatible donors in unrelated bone marrow donor registries when a patient carries these uncommon HLA alleles.

Background. Cardiotrophin-1 (CT-1), a member of the IL-6 superfamily, is elevated in the serum of patients with ischemic and valvular heart disease. In this study, we hypothesized that CT-1 induces endothelial cell angiogenesis and that the ADMA/DDAH pathway plays an important role in the process. Methods. pEGFP-N1-CTF1-GFP and pEGFP-N1 were constructed and used to transiently transfect to HUVECs, mediated by LipofectamineTM 2000. After transfection, the expression of CT-1 was examined by qRT-PCR and western blotting. Endothelial cell proliferation assay was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) method. Migration assay was performed using transwell, tube formation test was examined on Matrigel, eNOSmRNA expression was assayed by qRT-PCR, DDAH I, DDAHII and VEGF expression were detected by western blotting, the level of ADMA and the activity of DDAH were measured by High Performance Liquid Chromatography, NOS activity and the concentration of NO were assayed by L-[3H] citrulline production from L-[3H]arginine. Results: Overexpression of CT-1, increased endothelial cell proliferation, migration and formation of blood vessels, upregulated the expression of eNOSmRNA, DDAHI, DDAHII and VEGF, elevated the activity of DDAH and NOS, decreased the level of ADMA and promoted NO synthesis. In contrast, ADMA partially inhibited the effects of CT-1 induction. Conclusions: Overexpression of CT-1 increases cell proliferation, migration and formation of blood vessels. This result also suggests that CT-1 may regulate angiogenesis through the ADMA/DDAH pathway.

Cognition is very important in our daily life. However, amblyopia has abnormal visual cognition. Physiological changes of the brain during processes of cognition could be reflected with ERPs. So the purpose of this study was to investigate the speed and the capacity of resource allocation in visual cognitive processing in orientation discrimination task during monocular and binocular viewing conditions of amblyopia and normal control as well as the corresponding eyes of the two groups with ERPs. We also sought to investigate whether the speed and the capacity of resource allocation in visual cognitive processing vary with target stimuli at different spatial frequencies (3, 6 and 9 cpd) in amblyopia and normal control as well as between the corresponding eyes of the two groups. Fifteen mild to moderate anisometropic amblyopes and ten normal controls were recruited. Three-stimulus oddball paradigms of three different spatial frequency orientation discrimination tasks were used in monocular and binocular conditions in amblyopes and normal controls to elicit event-related potentials (ERPs). Accuracy (ACC), reaction time (RT), the latency of novelty P300 and P3b, and the amplitude of novelty P300 and P3b were measured. Results showed that RT was longer in the amblyopic eye than in both eyes of amblyopia and non-dominant eye in control. Novelty P300 amplitude was largest in the amblyopic eye, followed by the fellow eye, and smallest in both eyes of amblyopia. Novelty P300 amplitude was larger in the amblyopic eye than non-dominant eye and was larger in fellow eye than dominant eye. P3b latency was longer in the amblyopic eye than in the fellow eye, both eyes of amblyopia and non-dominant eye of control. P3b latency was not associated with RT in amblyopia. Neural responses of the amblyopic eye are abnormal at the middle and late stages of cognitive processing, indicating that the amblyopic eye needs to spend more time or integrate more resources to process the same visual task. Fellow eye and both eyes in amblyopia are slightly different from the dominant eye and both eyes in normal control at the middle and late stages of cognitive processing. Meanwhile, abnormal extents of amblyopic eye do not vary with three different spatial frequencies used in our study.

Cystic fibrosis patients frequently develop chronic rhinosinusitis as a result of their propensity to form inspissated mucus and impairment of mucociliary clearance. They exhibit variable symptom burden even in the setting of positive radiographic and endoscopic findings. Current evidence suggests a positive effect of managing sinonasal disease on pulmonary health. Topical antimicrobial and mucolytic therapies are frequently required to manage the disease with surgery reserved for refractory cases. Endoscopic sinus surgery has been demonstrated to be safe and efficacious in controlling symptoms of chronic rhinosinusitis in patients with comorbid cystic fibrosis. However, the impact of surgery on pulmonary health remains an active area of investigation. In addition, a growing body of research has suggested a more extended surgical approach creating large sinonasal cavities with gravity-dependent drainage pathways, followed by adjuvant medical therapies, as an ideal strategy to optimally control disease and prevent pulmonary exacerbations. In this manuscript, we provide an up-to-date review of current evidence in the surgical management of chronic rhinosinusitis in cystic fibrosis patients.

Chronic rhinosinusitis (CRS) is nearly ubiquitous in patients with cystic fibrosis (CF). CF CRS is a challenging entity to define, diagnose, and treat, as patients often have severe refractory sinus disease in addition to complex medical comorbidities. The purpose of this article is to review the literature on the medical management of CF CRS and determine how to best identify, diagnose, and manage CF CRS. Ultimately, the treatment of these patients requires a multi-disciplinary approach involving the pulmonologist and otolaryngologist.

Pigs provide outstanding models of human genetic diseases due to their striking similarities with human anatomy, physiology and genetics. Although transgenic pigs have been produced using genetically modified somatic cells and nuclear transfer (SCNT), the cloning efficiency was extremely low. Here, we report an improved method to produce diploid cloned embryos from porcine induced pluripotent stem cells (piPSCs), which were synchronized to the G2/M stage using a double blocking method with aphidicolin and nocodazole. The efficiency of this synchronization method on our piPSC lines was first tested. Then, we modified our traditional SCNT protocol to find a workable protocol. In particular, the removal of a 6DMAP treatment post-activation enhanced the extrusion rate of pseudo-second-polar bodies (p2PB) (81.3% vs. 15.8%, based on peak time, 4hpa). Moreover, an immediate activation method yielded significantly more blastocysts than delayed activation (31.3% vs. 16.0%, based on fused embryos). The immunofluorescent results confirmed the effect of the 6DMAP treatment removal, showing remarkable p2PB extrusion during a series of nuclear transfer procedures. The reconstructed embryos from metaphase piPSCs with our modified protocol demonstrated normal morphology at 2-cell, 4-cell and blastocyst stages and a high rate of normal karyotype. This study demonstrated a new and efficient way to produce viable cloned embryos from piPSCs when synchronized to the G2/M phase of the cell cycle, which may lead to opportunities to produce cloned pigs from piPSCs more efficiently.