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Exploring efficient photoactive material presents an intriguing opportunity to enhance the analytical performance of photoelectrochemical (PEC) sensor in the environmental analysis. In this work, a sandwich-structured multi-interface Co 9 S 8 @ZnIn 2 S 4 /CdSe QDs dual Z-Scheme heterojunction, derived from metal-organic framework (MOF), was synthesized as a sensing platform for chlorpyrifos detection, by integrating with enzyme-induced in situ insoluble precipitates strategy. The meticulously designed Co 9 S 8 @ZnIn 2 S 4 /CdSe QDs exhibited enhanced charge separation efficiency and was proved to be a highly effective sensing platform for the immobilization of biomolecules, attributing to the intrinsic dual Z-Scheme heterojunction and the distinctive hollow structure. The proposed PEC sensing platform combined with enzyme-induced in situ precipitate signal amplification strategy achieved superior performance for sensing of chlorpyrifos (CPF), showing in wide linear range (1.0 pg mL -1 -100 ng mL -1 ), with a limit of detection (0.6 pg mL -1 ), excellent selectivity, and stability. This work offers valuable insights for the design of novel advanced photoactive materials aimed at detecting environmental pollutants with low level concentration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As an important prognostic indicator in breast cancer, human epithelial growth factor receptor-2 (HER-2) is of importance for assessing prognosis of breast cancer patients, whose accurate and facile analysis are imperative in clinical diagnosis and treatment. Herein, photoactive Z-scheme UiO-66/CdIn 2 S 4 heterojunction was constructed by a hydrothermal method, whose optical property and photoactivity were critically investigated by a range of techniques, combined by elucidating the interfacial charge transfer mechanism. Meanwhile, PtPdCu nanoflowers (NFs) were fabricated by a simple aqueous wet-chemical method, whose peroxidase (POD)-mimicking catalytic activity was scrutinized by representative tetramethylbenzidine (TMB) oxidation in H 2 O 2 system. Taken together, the UiO-66/CdIn 2 S 4 based photoelectrochemical (PEC) aptasensor was established for quantitative analysis of HER-2, where the detection signals were further magnified through catalytic precipitation reaction towards 4-chloro-1-naphthol (4-CN) oxidation (assisted by the PtPdCu NFs nanozyme). The PEC aptasensor presented a broader linear range within 0.1 pg mL -1 -0.1 μg mL -1 and a lower limit of detection of 0.07 pg mL -1 . This work developed a new PEC aptasensor for ultrasensitive determination of HER-2, holding substantial promise for clinical diagnostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor ( EGFR )-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration., Methods: We initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402). The eighth arm assessed the efficacy and safety of AZD3759 in untreated EGFR -mutated NSCLC with CNS metastases. The primary objective was the objective response rate (ORR). Simon's minimax two-stage design was used to calculate the sample size. Dose optimal selection was performed using 200- and 300-mg bid cohorts., Findings: Between Oct 18, 2018 and Sep 14, 2020, 30 patients received AZD3759 at 200 mg (n = 15) or 300 mg (n = 15) bid. At data cutoff (Dec 31, 2022), median follow-up was 35.4 months. The primary endpoint was reached, with a confirmed ORR of 70% (21/30) (200 mg, 80%; 300 mg, 60%). The median progression-free survival was 12.9 months (200 mg, 15.8 months; 300 mg, 10.7 months). Grade 3 or 4 treatment-related adverse events occurred in 73% (22/30) of the patients (200 mg: 60%; 300 mg: 87%). 59% (10/17) of the patients developed a T790M mutation at disease progression. The median overall survival was 33.7 months, and 34.1 months and 25.3 months in patient treated with or without osimertinib in a later-line setting, respectively., Interpretation: AZD3759 showed promising efficacy and tolerable safety as a first-line therapy in EGFR -mutated NSCLC with CNS metastases. The 200-mg bid cohort had better clinical outcomes. Sequential use of AZD3759 and third-generation EGFR-TKIs represents a new option., Funding: Chinese Thoracic Oncology Group (CTONG)., Competing Interests: Prof. Yi-Long Wu reports grants and personal fees from AstraZeneca, BMS, Pfizer; and personal fees from Boehringer Ingelheim, Eli Lilly, Hengrui, MSD, Sanofi, Roche, outside the submitted work. Prof. Qing Zhou reports honoraria from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi. Prof. Wen-Zhao Zhong reports speech honoraria from AstraZeneca, Roche, Eli Lilly and Pfizer. Dr. Chong-Rui Xu reports grants from Hengrui Pharmaceutical and Pfizer. The other authors have no competing interests to declare., (© 2023 The Author(s).)

A split-type photoelectrochemical (PEC) sensor was designed for the detection of profenofos (PFF) depending on the magnetic-assisted exciton-plasmon interactions (EPI) between the semiconductor substrate and Au NPs. The core-shell Bi 2 S 3 nanorods@MoS 2 nanosheets (Bi 2 S 3 NRs@MoS 2 NSs) heterostructure nanomaterial with fascinating performance was synthesized and used as the photovoltaic conversion substrate and signal molecules absorption platform. The PEC sensor is operated by co-incubating with the released Au NPs-cDNA from the surface of magnetic beads, originating from the target-triggered DNA double-stranded structure opening event. Due to the strong EPI effects, the photocurrent of Bi 2 S 3 NRs@MoS 2 NSs decreased and varied with the PFF concentrations. The proposed PEC sensor exhibited outstanding analytical performances, including a wide linear range (1.0 pg mL -1 ~1.0 μg mL -1 ), low detection limitation (0.23 pg mL -1 , at 3 σ/m), excellent specificity, high stability, and applicability. Overall, this work provides a new signal strategy for PEC biosensors and extends its application in environmental analysis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

To explore targeted treatment options in patients with non-small-cell lung cancer (NSCLC) with rare genetic mutations in the context of a patient-centric clinical trial, we initiated, in parallel, a phase 2 adaptive umbrella trial consisting of a criteria-fulfilled (CF) cohort and a compassionate use (CU) cohort under expanded eligibility criteria, and a prospective real-world study (RWS). Here, we present efficacy and safety data from 48 patients with treatment-naive, advanced HER2-mutant NSCLC treated with the pan-HER receptor tyrosine kinase inhibitor pyrotinib (CF and CU cohorts) or physician's therapy of choice (RWS cohort). In the phase 2 trial CF cohort (n = 28), the primary endpoint was reached with an objective response rate of 35.7% after pyrotinib treatment. Secondary endpoints included disease control rate (89.3%), median progression-free survival (PFS) (7.3 months), median overall survival (OS) (14.3 months) and toxicity, which was acceptable, with grade 3 or 4 treatment-related adverse events occurring in three patients (10.7%). The phase 2 trial CU cohort (n = 12) showed an objective response rate of 16.7%, disease control rate of 83.4%, median PFS of 4.7 months and median OS of 14.2 months after pyrotinib treatment. The RWS cohort (n = 8) had no responses to physician's therapy of choice, while median PFS and OS were 3.0 and 12.2 months, respectively. Phase 2 umbrella trial, clinicaltrials.gov identifier: NCT03574402 . RWS, clinicaltrials.gov identifier: NCT03605602 ., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Despite advances in the development of photoelectrochemical (PEC) sensor, modulating the PEC response of assembled heterostructure interface is still a great challenge. Here, an ultrasensitive PEC aptasensor for tobramycin (TOB) assay was conducted based on one-dimensional/two-dimensional CdS nanorods@ZnIn 2 S 4 nanosheets (1D/2D CdS NRs@ZnIn 2 S 4 NSs) heterojunctions by tailoring enzymatic loading capacity. Firstly, alkaline phosphatase modified TOB aptamer (ALP-Apt) was linked via specific base complementary pairing, and insoluble precipitations were then produced through the ALP-triggered catalytic reaction with the aid of Ag + , which prevented the charge transfer and resulted in the decrement of photocurrent. In the presence of TOB, partial ALP-Apt detached from the electrode surface due to the strong affinity between TOB and its aptamer, leading to a reduction in the amount of ALP and insoluble precipitate, in turn the PEC response partially recovered. The photocurrents exhibited a wider linear range towards the TOB concentration of 1.0-5.0 × 10 4  pg mL -1 , with a low detection limit of 0.96 pg mL -1 . The constructed PEC aptasensor gained satisfactory results for TOB assay in milk samples as well, which also offered significant promise for other pollutants in environmental analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Physicians need an appropriate embryo transfer strategy to address the challenge of reducing multiple birth rates, while maintaining the couples' live birth rate during assisted reproductive technology., Methods: We included 10,060 frozen embryo transfer cycles from January 2015 to March 2020 in reproductive medical center of Ruijin hospital, Shanghai, China. Patients were grouped according to the number and grade of cleavage-stage embryo or blastocysts transferred. Live birth rate and multiple live birth rate were compared among groups of women of different ages. Multivariable logistic regression models were used to estimate the risk of multiple live birth using different combinations of transferred embryos., Results: The transfer of double good-quality embryos was an independent predictor for multiple birth in women aged <30 years and those aged 36-39 years [<30 years: aOR =1.54 (95% CI: 1.14-2.06, P < 0.01); 36-39 years: aOR =1.84 (95% CI: 1.0-3.4, P < 0.01)]. Further, for women aged <36 years, the transfer of good-quality + poor-quality blastocysts was an independent predictor for multiple birth rate [<30 years: aOR=2.46 (95% CI: 1.45-4.18, P < 0.01); 31-35 years: aOR =4.45 (95% CI: 1.97-10.06, P < 0.01)]., Conclusions: Single-good-quality blastocyst transfer is recommended for women of all ages. When good-quality cleavage embryos are available, the choice of single or double embryo transfer with good- or average-quality embryo should depend on the age of women. Double embryo transfer with the highest possible grade of embryos is recommended for women aged ≥40 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Zhou, Xu, Chen, Xia, Zhao, Xu, Zhang and Niu.)

Background: In previous studies, alkaline phosphatase (ALP) level was a prognostic factor for patients with ischemic stroke, and globulin level was associated with hemorrhagic transformation (HT) after intravenous thrombolysis (IVT). However, the association between these serum biomarkers and prognosis in patients with acute ischemic stroke (AIS) who undergo IVT remains unclear. This study aimed to investigate the characteristics of serum ALP and globulin levels after IVT and to assess the relationship between these serum biomarkers and prognosis., Materials and Methods: This retrospective study used a prospectively collected database. We included patients with AIS who received recombinant tissue plasminogen activator (rt-PA) IVT. Demographic information, vascular risk factors, laboratory test results, and other stroke-related data were collected for analysis. Clinical outcomes included HT and 3-month poor outcome (modified Rankin Scale scores ≥ 2) after IVT. The association of ALP and globulin levels with HT and poor outcome was investigated using multivariate logistic regression analysis. An individualized prediction model based on ALP and globulin levels for functional outcomes was established., Results: We enrolled 750 patients in this study; 452 patients (60.3%) had poor outcome, and 117 patients (15.6%) had HT after IVT. After adjusting for all confounders, serum globulin level [OR = 1.055; 95% confidence intervals (CI): 1.006-1.107; P = 0.028] was independently associated with HT in patients with IVT. Serum ALP (OR = 1.009; 95% CI: 1.002-1.016; P = 0.010) and globulin levels (OR = 1.062; 95% CI: 1.020-1.107; P = 0.004) were associated with 3-month poor outcome in these patients. The constructed individualized prediction model for the 3-month poor outcome comprised the National Institutes of Health Stroke Scale (NIHSS) score, Trial of Org 10172 in Acute Stroke Treatment (TOAST), history of antihypertensive therapy, ALP and globulin levels. The area under the curve of the training and validation sets were 0.726 and 0.706, respectively, revealing that the model had good discriminating power. The P -values for the Hosmer-Lemeshow test in the training and validation sets were 0.978 and 0.148, respectively, indicating the model had good calibration., Conclusion: This study found that higher serum globulin levels were independently associated with HT. Additionally, higher serum ALP and globulin levels were independently associated with a poor outcome in patients after IVT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Sun, Guo, Qu, Sun, Jin, Wang, Xu and Yang.)

Background: Pleural effusion (PE) has been one of the promising sources of liquid biopsy in advanced lung cancer patients. However, its clinical utility is not widely accepted due to the lack of full estimation of its potential versus routine clinical samples., Method: A total of 164 advanced lung cancer patients were enrolled with 164 matched tumor tissue and PE-cfDNA, 153 accompanied plasma and 63 1 PE-sDNA., Result: PE-cfDNA displayed significantly higher median mutant allele frequency and an overall mutation concordance rate of 65% to tissue, which was higher than PE-sDNA (43%) and plasma-cfDNA (43%). The discrepancies between PE-cfDNA and tumor tissue were high in several genes, including SMARCA4, PIK3CA, ERBB2, KM T2A, ALK and NF1. For clinically actionable mutations, the concordance rate between PE-cfDNA and tumor tissue is 87%. Eleven patients were identified with actionable mutations in PE-cfDNA and four patients benefited from PE-cfDNA-guided targeted. Meanwhile, PE-cfDNA recapitulated mutations of diverse tissue origins and provided more mutational information under the circumstance that tumor tissue or tumor tissue of different origins were unavailable. The combination of tumor tissue and PE-cfDNA profiling increased positive detection rates of patients compared to tumor tissue alone. Our finding highlighted the importance of PE-cfDNA in the optimal selection of patients for targeted therapy., Conclusion: The PE-cfDNA-based liquid biopsy displays better performance in the characterization of gene alterations than PE-sDNA and plasma-cfDNA. PE-cfDNA together with tumor tissue profiling optimizes comprehensively genomic profiling of lung cancer patients, which might be important for selecting patients for better treatment management., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Atherosclerosis is a chronic inflammatory disease with high prevalence and mortality. The rupture of atherosclerotic plaque is the main reason for the clinical events caused by atherosclerosis. Making clear the transcriptomic and proteomic profiles between the stabe and unstable atherosclerotic plaques is crucial to prevent the clinical manifestations. In the present study, 5 stable and 5 unstable human carotid atherosclerotic plaques were obtained by carotid endarterectomy. The samples were used for the whole transcriptome sequencing (RNA-Seq) by the Next-Generation Sequencing using the Illumina HiSeq, and for proteome analysis by HPLC-MS/MS. The lncRNA-targeted genes and circRNA-originated genes were identified by analyzing their location and sequence. Gene Ontology and KEGG enrichment was carried out to analyze the functions of differentially expressed RNAs and proteins. The protein-protein interactions (PPI) network was constructed by the online tool STRING. The consistency of transcriptome and proteome were analyzed, and the lncRNA/circRNA-miRNA-mRNA interactions were predicted. As a result, 202 mRNAs, 488 lncRNAs, 91 circRNAs, and 293 proteins were identified to be differentially expressed between stable and unstable atherosclerotic plaques. The 488 lncRNAs might target 381 protein-coding genes by cis -acting mechanisms. Sequence analysis indicated the 91 differentially expressed circRNAs were originated from 97 protein-coding genes. These differentially expressed RNAs and proteins were mainly enriched in the terms of the cellular response to stress or stimulus, the regulation of gene transcription, the immune response, the nervous system functions, the hematologic activities, and the endocrine system. These results were consistent with the previous reported data in the dataset GSE41571. Further analysis identified CD5L, S100A12, CKB (target gene of lncRNA MSTRG.11455.17), CEMIP (target gene of lncRNA MSTRG.12845), and SH3GLB1 (originated gene of hsacirc&#95;000411) to be critical genes in regulating the stability of atherosclerotic plaques. Our results provided a comprehensive transcriptomic and proteomic knowledge on the stability of atherosclerotic plaques., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bao, Zhang, Huang, Zhou, Guo, Xu and Liu.)

Objective: Leptomeningeal metastases (LM) occur in up to 5% of non-small cell lung cancer (NSCLC) patients and often develop after previous systemic treatments. In this article, we explored whether immune checkpoint inhibitors (ICIs) enhanced the dismal survival of patients with LM., Materials and Methods: Data on NSCLC patients with LM prescribed ICIs were collected at the Guangdong Lung Cancer Institute. Furthermore, relevant literature was reviewed., Results: A total of 255 NSCLC patients diagnosed with LM were screened from January 2015 to March 2020 at our institute. Cases reported by literature were also included. Finally, 32 NSCLC patients received ICIs after LM diagnosis; their median age was 55 years. Druggable genes were detected in 37.5% of all patients. The ICI regimens included nivolumab (n = 21), pembrolizumab (n = 9), and atezolizumab (n = 2). Ultimately, 62.5% of patients evidenced neurological symptom controlled. Two patients exhibited both intracranial and extracranial complete tumour response; one patient showed both intracranial and extracranial partial response (PR), one patient indicated intracranial PR and a systemic PR, and one patient showed central nervous system PR without extracranial response reported. The median progression-free survival (PFS) in the single-agent subgroup was 2.1 months (95% confidence interval [CI]: 1.4-2.9 months), and the median overall survival (OS) was 4.0 months (95% CI: 0.1-13.3 months). In the combined subgroup, the median PFS and OS were 3.0 months (95% CI: 1.1-4.9 months) and 5.4 months (95% CI: 0.5-10.3 months), respectively. Three patients exhibited remarkable PFS of over 20 months: all patients had ICI single agent, received cranial radiotherapy before ICI prescription, and took ICIs as second-line therapy, and two patients were EGFR/ALK wild type. Multivariate analysis showed that a better Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score was associated with prolonged PFS (P = 0.04). No difference in survival was seen between monotherapy and combination therapy groups., Conclusion: NSCLC patients with LM may benefit from ICIs of both monotherapy and combination with other therapies, especially those with good ECOG-PS scores. Further work in this regard is required., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Atherosclerosis is a chronic inflammatory disease which is responsible for many clinical manifestations. The present study was to investigate the anti-inflammatory functions and mechanisms of TNK1 in atherosclerosis., Methods: The ApoE(-/-) mice and human carotid endarterectomy (CEA) atherosclerotic plaques were used to investigate the differential expression of TNK1. The ApoE(-/-) mice were fed with high-fat diet (HFD) or normal-fat diet (NFD) for 8 weeks; the aorta was separated and stained with oil red O to evaluate the formation of atherosclerosis. TNK1 in mice aorta was measured by qPCR. The human CEA were obtained and identified as ruptured and stable plaques. The level of TNK1 was measured by qPCR and Western-blot staining. Further studies were conducted in THP-1 cells to explore the anti-inflammatory effects of TNK1. We induced the formation of macrophages by incubating THP-1 cells with PMA (phorbol 12-myristate 13-acetate). Afterwards, oxidized low-density lipoprotein (oxLDL) was used to stimulate the inflammation, and the secretion of inflammatory factors was measured by ELISA and qPCR. The levels of TNK1, total STAT1 and Tyk2, and the phosphorylation of STAT1 and Tyk2 were measured by western blot to uncover the mechanisms of TNK1., Results: The oil red O staining indicated obvious deposition of lipid on the aorta of ApoE(-/-) mice after 8-week HFD treatment. The TNK1 level was much higher in both the HFD-fed ApoE(-/-) mice aorta arch and the ruptured human CEA plaques. We found that TNK1 was highly expressed in THP-1 cells, compared to other atherosclerotic related cells (HUVEC, HBMEC, and HA-VSMC), indicating TNK1 might be involved in the inflammation. Suppressing the expression of TNK1 by shTNK1 inhibited the oxLDL-induced secretion of inflammatory factors, such as IL-12, IL-6, and TNF- α . ShTNK1 also inhibited the uptake of lipid and decreased the cellular cholesterol content in THP-1 cells. Furthermore, the shTNK1 suppressed the oxLDL-induced phosphorylation of Tyk2 and STAT1., Conclusion: TNK1 participated in the inflammation in atherosclerosis. shTNK1 suppressed the oxLDL-induced inflammation and lipid deposition in THP-1 cells. The mechanism might be related to the Tyk2/STAT signal pathway., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Mei-Hua Bao et al.)

The rupture of atherosclerotic plaques is essential for cardiovascular and cerebrovascular events. Identification of the key genes related to plaque rupture is an important approach to predict the status of plaque and to prevent the clinical events. In the present study, we downloaded two expression profiles related to the rupture of atherosclerotic plaques (GSE41571 and GSE120521) from GEO database. 11 samples in GSE41571 were used to identify the differentially expressed genes (DEGs) and to construct the weighted gene correlation network analysis (WGCNA) by R software. The gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment tool in DAVID website, and the Protein-protein interactions in STRING website were used to predict the functions and mechanisms of genes. Furthermore, we mapped the hub genes extracted from WGCNA to DEGs, and constructed a sub-network using Cytoscape 3.7.2. The key genes were identified by the molecular complex detection (MCODE) in Cytoscape. Further validation was conducted using dataset GSE120521 and human carotid endarterectomy (CEA) plaques. Results: In our study, 868 DEGs were identified in GSE41571. Six modules with 236 hub genes were identified through WGCNA analysis. Among these six modules, blue and brown modules were of the highest correlations with ruptured plaques (with a correlation of 0.82 and -0.9 respectively). 72 hub genes were identified from blue and brown modules. These 72 genes were the most likely ones being related to cell adhesion, extracellular matrix organization, cell growth, cell migration, leukocyte migration, PI 3 K-Akt signaling, focal adhesion, and ECM-receptor interaction. Among the 72 hub genes, 45 were mapped to the DEGs (logFC > 1.0, p-value < 0.05). The sub-network of these 45 hub genes and MCODE analysis indicated 3 clusters (13 genes) as key genes. They were LOXL1, FBLN5, FMOD, ELN, EFEMP1 in cluster 1, RILP, HLA-DRA, HLA-DMB, HLA-DMA in cluster 2, and SFRP4, FZD6, DKK3 in cluster 3. Further expression detection indicated EFEMP1, BGN, ELN, FMOD, DKK3, FBLN5, FZD6, HLA-DRA, HLA-DMB, HLA-DMA, and RILP might have potential diagnostic value.

We aimed to study the association between sperm DNA fragmentation and recurrent pregnancy loss (RPL) in the Chinese population via a retrospective observational study of Chinese couples who had experienced RPL between May 2013 and August 2018. The study population included 461 men from couples with RPL and 411 men from a control group (couples with clinical pregnancy via in vitro fertilization owing to female causes). Routine semen analysis, sperm chromatin analysis, and microscopic (high-power) morphological analysis were performed using semen samples. Semen samples were assessed for volume, sperm count, and motility. The sperm DNA fragmentation index (DFI) was calculated, and the median DFI was obtained. Men were categorized as having normal (37.8%; DFI ≤ 15.0%), moderate (33.6%; 15.0% < DFI < 30.0%), or severe (28.6%; DFI ≥ 30.0%) DNA fragmentation levels. The percentage of men with severe DNA fragmentation was significantly higher in the RPL (42.3%) group than that in the control group (13.1%), whereas the percentage of men with normal levels of DNA fragmentation was significantly lower in the RPL group (22.8%) than that in the control group (54.7%). Subsequent analysis also demonstrated that the sperm DNA fragmentation rate had a moderate reverse correlation with the sperm progressive motility rate (r = -0.47, P < 0.001) and the total motile sperm count (r = -0.31, P < 0.001). We found a positive correlation between RPL and sperm DNA fragmentation. The results suggest that increased sperm DNA damage is associated with RPL., Competing Interests: None

Recent studies have shown that exosomes play a role in pathogenesis and in the treatment of inflammatory diseases and tumours. We explored the effects of Treponema pallidum-induced macrophage-derived exosomes on vascular endothelial cells to determine whether they are involved in the pathogenesis of syphilis. A syphilis infection model was established using rabbits to harvest T. pallidum at the peak of proliferation. Exosomes derived from macrophages were extracted using commercial kits and characterized by transmission electron microscopy, western blot assays, and nanoparticle tracking analysis. Secreted cytokine levels and the adhesion and permeability of human umbilical vein endothelial cells were evaluated in a co-culture model using the extracted exosomes. The results of this study revealed that exosomes derived from T. pallidum-infected macrophages enhanced cell adhesion and permeability. The levels of the secreted cytokines, including ICAM-1, VCAM-1, VEGF, and IL-8 were higher in the experimental group than in the control group. Our findings suggest that exosomes derived from T. pallidum-infected macrophages affect the cell adhesion and permeability of vascular endothelial cells. These changes may play important roles in syphilis pathogenesis. This study is the first to reveal the effects of exosomes derived from T. pallidum-infected macrophages on the adhesion, permeability, and secreted cytokines of human umbilical vein endothelial cells.

Syphilis is a sexually transmitted disease caused by the infection of Treponema pallidum subspecies pallidum. T-helper type 17-related genes, vitamin D receptor (VDR) gene, and chemokine/chemokine receptor genes are crucial in microbial infection. A total of 16 single-nucleotide polymorphisms (SNPs) in eight genes (interleukin [IL]-17A, IL-17F, IL-23R, VDR, C-C motif chemokine ligand [CCL] 2, CCL5, C-C chemokine receptor [CCR] 2, and CCR5) were analyzed in 188 patients with syphilis and 216 healthy controls. The results showed a strong correlation of IL-17A rs2275913 (AA vs AG + GG: odds ratio [OR], 1.78; 95% confidence interval [CI], 1.09 to 2.92; P = 0.020; A vs G: OR, 1.33; 95% CI, 1.01 to 1.76; P = 0.043) and rs3819024 (GG vs AA + GA: OR, 1.76; 95% CI, 1.06 to 2.91; P = 0.028; G vs A: OR, 1.36; 95% CI, 1.03 to 1.80; P = 0.030) with syphilis. In haplotype analysis, IL-17A rs2275913A/rs3819024G showed a risk effect (OR, 1.38; 95% CI, 1.04 to 1.82; P = 0.026), whereas IL-17A rs2275913G/rs3819024A showed a protective effect (OR, 0.76; 95% CI, 0.57 to 0.998; P = 0.048). The expression levels of IL-17A messenger RNA (mRNA) in peripheral blood mononuclear cells and IL-17A secretion in plasma were further examined. No significant differences were found between patients with syphilis and healthy controls. The study also explored whether IL-17A rs2275913 and rs3819024 were associated with the expression of IL-17A mRNA and IL-17A secretion in patients with syphilis. Similar negative results were found. In conclusion, the polymorphisms of IL-17A rs2275913 and rs3819024 and the haplotype containing these two SNPs influenced the susceptibility to syphilis in a Han Chinese population., (© 2018 Wiley Periodicals, Inc.)

Objective: To explore whether cephalic artery peak velocity variation during passive leg raising (ΔVpeak(CA)-PLR) could effectively predict fluid responsiveness in mechanically ventilated severe sepsis patients with spontaneous breathing. Methods: Total of 38 patients on mechanical ventilation with spontaneous breathing admitted to the Fourth Departments of Intensive Care Unit (ICU) of Fujian Provincial Hospital from January to December in 2017 were enrolled.The patients were diagnosed with severe sepsis or sepsis shock.The peak velocity in cephalic artery (Vpeak(CA)) during PLR was measured by bedside portable ultrasonic, and then ΔVpeak(CA)-PLR was calculated.All patients received volume expansion (VE) test and the changes of stroke volume during VE test (ΔSV-VE) were measured.Patients were classified as responsive group or non-responsive group according to the ΔSV-VE increased ≥15% or not after VE test.Furthermore, the sensitivity and specificity of ΔVpeak(CA)-PLR for predicting fluid responsiveness were evaluated by receiver operating characteristic (ROC) curve.The comparisons between groups were performed with Student's unpaired two-tailed t test, and Pearson's test was used for the correlation analysis. Results: Among the patients, 22 cases responded to VE test and the rest 16 cases did not.There were no significantly differences in age, gender, body mass index, infection site, sepsis-related organ failure assessment score, acute physiology and chronic health evaluation Ⅱ score, ventilator parameters and dose of vasoactive agent between the two groups.The ΔVpeak(CA)-PLR in responsive group was markedly higher than that in non-responsive group (15.7%±4.2% vs 6.9%±4.3%, t =6.240, P <0.05), and the ΔVpeak(CA)-PLR in the responsive group was positively related to the ΔSV-VE ( r =0.723, P <0.05). Furthermore, the area of ΔVpeak(CA)-PLR under ROC curve was 0.912.The sensitivity and specificity of ΔVpeak(CA)-PLR≥12.2% to predict fluid responsiveness in the patients with sepsis were 81.8% and 87.5%, respectively. Conclusion: ΔVpeak(CA)-PLR measured by bedside portable ultrasonic can predict the fluid responsiveness in mechanically ventilated severe sepsis patients with spontaneous breathing, and it can be used to guide further fluid resuscitation.

Activation of swelling-induced Cl - current (I Cl,swell ) during neonatal hypoxia-ischemia (HI) may induce brain damage. Hypoxic-ischemic brain injury causes chronic neurological morbidity in neonates as well as acute mortality. In this study, we investigated the role of I Cl,swell in hypoxic-ischemic brain injury using a selective blocker, 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl) oxybutyric acid (DCPIB). In primary cultured cortical neurons perfusion of a 30% hypotonic solution activated I Cl,swell , which was completely blocked by the application of DCPIB (10 μmol/L). The role of I Cl,swell in neonatal hypoxic-ischemic brain injury in vivo was evaluated in a modified neonatal hypoxic-ischemic brain injury model. Before receiving the ischemic insult, the mouse pups were injected with DCPIB (10 mg/kg, ip). We found that pretreatment with DCPIB significantly reduced the brain damage assessed using TTC staining, Nissl staining and whole brain imaging, and improved the sensorimotor and vestibular recovery outcomes evaluated in neurobehavioural tests (i.e. geotaxis reflex, and cliff avoidance reflex). These results show that DCPIB has neuroprotective effects on neonatal hypoxic-ischemic brain injury, and that the I Cl,swell may serve as a therapeutic target for treatment of hypoxic-ischemic encephalopathy.

A free-vortex wake (FVW) model is developed in this paper to analyse the unsteady aerodynamic performance of offshore floating wind turbines. A time-marching algorithm of third-order accuracy is applied in the FVW model. Owing to the complex floating platform motions, the blade inflow conditions and the positions of initial points of vortex filaments, which are different from the fixed wind turbine, are modified in the implemented model. A three-dimensional rotational effect model and a dynamic stall model are coupled into the FVW model to improve the aerodynamic performance prediction in the unsteady conditions. The effects of floating platform motions in the simulation model are validated by comparison between calculation and experiment for a small-scale rigid test wind turbine coupled with a floating tension leg platform (TLP). The dynamic inflow effect carried by the FVW method itself is confirmed and the results agree well with the experimental data of a pitching transient on another test turbine. Also, the flapping moment at the blade root in yaw on the same test turbine is calculated and compares well with the experimental data. Then, the aerodynamic performance is simulated in a yawed condition of steady wind and in an unyawed condition of turbulent wind, respectively, for a large-scale wind turbine coupled with the floating TLP motions, demonstrating obvious differences in rotor performance and blade loading from the fixed wind turbine. The non-dimensional magnitudes of loading changes due to the floating platform motions decrease from the blade root to the blade tip., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)

The crude polysaccharides of Dendrobium huoshanense were fractionated by anion-exchange chromatography and gel permeation chromatography, giving one homogeneous fraction DHP-4A with molecular weight of 2.32 × 10(5)Da. UV spectrum indicated that there was no existence of proteins and nucleic acids in DHP-4A. Monosaccharide analysis revealed that DHP-4A was made up of glucose, arabinose, mannose and rhamnose with a molar ratio of 13.8:3.0:6.1:2.1. The backbone of DHP-4A consisted of (1 → 6)-linked glucose, (1 → 6)-linked mannose and (1 → 3,6)-linked mannose. The βL-Rhap-(1 → 2)-β-L-Rhap-(1 → 4)-β-D-Manp-(1 → and α-L-Araf-(1 → 3)- α-L-Araf -(1 → 3)-α-L-Araf-(1 → were regarded as the branches attached to the C-3 position of (1 → 6)-linked mannose in the backbone. The sugar residue sequence was further determined by NMR spectra including (1)H NMR, (13)C NMR, HSQC and HMBC. Pharmacological tests showed that DHP-4A can significantly stimulate RAW 264.7 macrophage cells to secrete NO, TNF-α, IL-6 and IL-10 via activation of p38, ERK, JNK and translocation of nuclear NF-κB, indicating this polysaccharide possesses good immunoregulatory activity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Lymphoplasmacyte-rich meningioma (LPM) is one of the rarest variants of meningioma and those LPMs that arise in the intraventricular space are even rarer. LPMs are classified as grade I (benign) tumors with a low proliferative rate and diagnosis is made through the histological identification of high numbers of inflammatory cells (lymphocytes and plasma cells) in the resected tumor tissue. In the current case, magnetic resonance imaging of a 37-year-old woman who presented at our neurosurgery department following a generalized tonic-clonic seizure revealed a partially mortified intraventricular mass, which had caused pronounced peritumoral edema and had a relatively rough surface. Surgical resection was performed. Histological analysis revealed large numbers of inflammatory cells, confirming the diagnosis of LPM, but also indicated that the lesion was positive for the proliferation marker Ki-67. Follow-up magnetic resonance imaging 3 months after surgery revealed no residual tumor or recurrence.

Objective: To study the mechanism of hypoxia inducing factor-1α (HIF-1α) pathway in establishment of hypoxia inducing low endometrial receptivity., Methods: RL95-2 cell lines, the ideal model of study ER, were cultured in hypoxia condition induced by CoCl2, and the expression of mRNA and protein of HIF-1α and tumor necrosis factor like weak inducer of apoptosis (TWEAK) were measured by reverse transcription-PCR and western blot. The apoptosis rate was analyzed by flow cytometry. Then the mechanism confirmed by comparing the two factors in endometrium and the ultra-appearance of inflammatory reaction and apoptosis between recurrent spontaneous abortion women and control women., Results: (1) On different time point (0, 12, 24, 48 hour), mRNA expression of HIF-1α were 0.272 ± 0.010, 0.354 ± 0.020, 0.591 ± 0.020, 0.890 ± 0.020, while the expression of TWEAK were 0.104 ± 0.010, 0.510 ± 0.020, 1.021 ± 0.020, 1.237 ± 0.040, respectively, the expression level between 12, 24, 48 and 0 hour all showed significant differences (P < 0.05). (2) Protein expression of HIF-1α were 0.853 ± 0.010, 0.931 ± 0.030, 1.124 ± 0.010, 1.317 ± 0.020 respectively, while was 0.042 ± 0.010, 0.091 ± 0.010, 0.131 ± 0.020, 0.205 ± 0.030 in TWEAK expression, the different level were statistically significant (P < 0.05). (3) With longer culture under hypoxia, the cell apoptosis rate increased obviously. The apoptosis rate of each time point were (3.2 ± 1.4)%, (16.2 ± 3.2)%, (26.3 ± 3.5)%, (31.8 ± 3.5)%, the differences between 12, 24, 48 and 0 hour had significance (P < 0.05). (4) The positive rate of HIF-1α stained in epithelium cells and stroma cells of test group were 32.3%, 8.4% and 16.7%, 7.3% in control group. The positive rate of TWEAK were 28.3%, 3.9% in recurrent spontaneous abortion group and 11.6%, 2.7% in control group (P < 0.05). The ultra-appearance of inflammatory cell infiltrated and apoptosis were obvious in test group., Conclusions: Cell inflammation reaction and apoptosis induced by HIF-1α pathway may participate the mechanism of hypoxia inducing low endometrial receptivity. HIF-1α might become a novel target for improving poor endometrial receptivity.

Objectives: To compare the expression of pinopodes, LIF, integrin beta(3) and MUC1 in the peri-implantation endometrium of women with and without hydrosalpinx., Study Design: A prospective observational study in an assisted reproductive unit in a university teaching hospital, including 20 women with hydrosalpinx and 21 women without hydrosalpinx. Endometrial biopsies were performed on day LH+7 or +8. The proportion and density of pinopodes were assessed by scanning electron microscopy. LIF, integrin beta3 and MUC1 were evaluated with immunohistochemical staining., Results: The proportion and the density of pinopodes were not significantly different between the hydrosalpinx and control groups. The LIF, integrin beta(3), and MUC1 expression were significantly reduced in both glandular epithelial cells and endometrial lumen of the hydrosalpinx group when compared with those of the control group. The expression of integrin beta(3) in stromal cells was also significantly lower in the hydrosalpinx group., Conclusions: The proportion and the density of pinopodes in the peri-implantation endometrium were not affected by the presence of hydrosalpinx while LIF, integrin beta(3) and MUC1 were significantly reduced in patients with hydrosalpinx., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

With hydroponic culture, this paper studied the effects of different nitrogen (N) supply levels (0, 0.15, 0.3, 0.45, 0.6, 0.75 g N x L(-1)) on the seedling morphology and N allocation of Parthenocissus tricuspidata. The results showed that lower N supply retarded the development of P. tricuspidata seedling's branch; while higher N supply had significant effects in promoting the seedling's early branching and lowering the branching position on the main stem. Supplying higher amount of N increased the plant biomass and the N concentration in root, leaf and stem significantly. Compared with stem and root, leaf had the highest biomass, accounting for 50% of the total biomass, and the highest N accumulation, accounting for 60%-70% of the total accumulated N.

Objective: To develop a computer-aided mandibular repositioning system (CAMRS) and investigate its preliminary application in efficacy prediction of oral appliance in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS)., Methods: CAMRS was mainly consisting of a step motor and a screw that was remote-controlled by a computer. This system could work with polysomnography (PSG). Fourteen OSAHS patients diagnosed by PSG were recruited. With CAMRS, six mandibular positions were titrated with PSG for every hour., Results: Stable mandible positioning and little sleeping disturbance were observed. Apnea hypopnea index (AHI) was improved progressively with mandibular advancement. The extent of mandibular advancement was correlated with the severity of OSAHS (r = 0.72747)., Conclusions: CAMRS could reproductively and effectively reposition mandible with little sleeping disturbance. Through CAMRS, an individualized optimal mandibular position could be obtained for each OSAHS patient treated with oral appliance.