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Hao-Huan Tang,1,&ast; Lin-Feng Zhou,2,3,&ast; Chun-Xin Wang,4,&ast; Yang Zha,4 Chen Fan,1 Bin-Yan Zhong,2 Xiao-Li Zhu,2 Wei-Dong Wang1 1Department of Interventional Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 3Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430079, People’s Republic of China; 4Department of Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Li Zhu, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, 215006, People’s Republic of China, Tel/Fax +86 512 67780375, Email zhuxiaoli90@163.com Wei-Dong Wang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing, No. 299, Qingyang Road, Medical University, Wuxi, 214023, People’s Republic of China, Tel/Fax +86 510 85350121, Email wdoc@sina.comBackground and Aims: The objective of this study was to investigate the effect of neutrophil-to-lymphocyte ratio (NLR) on the survival of cirrhotic patients with esophagogastric variceal bleeding (EGVB) treated with transjugular intrahepatic portosystemic shunt (TIPS).Methods: A total of 293 patients treated with TIPS were included. The receiver operator characteristic curve (ROC) was used to calculate the optimal cut-off values of parameters such as NLR. The Kaplan-Meier curve and Cox proportional risk model were used to evaluate the effects of NLR and other variables on 2-year all-cause mortality.Results: The area under the ROC for NLR was 0.634, with an optimal cutoff value of 4.9. Two-year mortality rates for patients with high (≥ 4.9) and low (< 4.9) NLR were 22.1% and 9.3%, respectively (Log rank test: P = 0.002). After correcting for confounders, multivariate analysis demonstrated that NLR ≥ 4.9 (HR = 2.741, 95% CI 1.467– 5.121, P = 0.002), age ≥ 63 (HR = 3.403, 95% CI 1.835– 6.310, P < 0.001), and gender (male) (HR = 2.842, 95% CI 1.366– 5.912, P = 0.001) were independent risk factors for the mortality outcome. Considering the stratification of early and selective TIPS treatment, high NLR still significantly increased the risk of mortality for patients (Log rank test: P = 0.007, HR = 2.317, 95% CI 1.232– 4.356).Conclusion: NLR can help to predict survival in EGVB patients after TIPS, and the type of TIPS should also be considered in practical applications.Keywords: neutrophil-to-lymphocyte ratio, transjugular intrahepatic portosystemic shunt, esophagogastric variceal bleeding, prognostic factor

Hao-Huan Tang,1,&ast; Ming-Qing Zhang,2,&ast; Zi-Chen Zhang,3,&ast; Chen Fan,1 Yong Jin,2 Wei-Dong Wang1 1Department of Interventional Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China; 2Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 3Department of Interventional Vascular Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, Hefei, 230011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Jin, Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, No. 1055, Sanxiang Road, Suzhou, 215006, People’s Republic of China, Tel/Fax +86 512 67784269, Email jinyong@suda.edu.cn Wei-Dong Wang, Department of Interventional Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, No. 299, Qingyang Road, Wuxi, 214023, People’s Republic of China, Tel/Fax +86 510 85350121, Email Wdoc@sina.comObjective: To investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with PD-(L)1 inhibitors and molecular targeted therapies (MTT) for intermediate and advanced HCC that are unsuitable for transarterial chemoembolization (TACE).Methods: We conducted a retrospective analysis of data from patients with TACE-unsuitable HCC who were receiving triple therapy from January 2020 to December 2021 at two medical centers. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rates (ORR), disease control rates (DCR), and incidence of adverse events (AEs).Results: A total of 55 patients were enrolled in the study with median treatment periods of 4 and 6 for HAIC and PD-(L)1 inhibitors, respectively. The median OS and PFS were 15.0 and 10.0 months, respectively, with a median follow-up of 11.0 months (range: 4.0– 27.5 months). According to the mRECIST criteria, the optimal ORR was 43.6% (24/55) and the DCR was 61.8% (34/55). The incidence of AEs was 58.2%, with grade 3 and above accounting for 20.0%; elevated AST (18.2%), hyperbilirubinemia (16.4%), and thrombocytopenia (16.4%) were most common. There were no treatment-related fatalities and all AEs were effectively managed. Multifactorial analysis showed that NLR > 3.82 (HR 2.380, 95% CI 1.116-2-5.079, P = 0.025), ECOG 1 (HR 2.906, 95% CI 1.373– 6.154, P = 0.005), and extrahepatic metastases (HR 8.373, 95% CI 3.492– 20.078, P < 0.001) were associated with the median OS.Conclusion: Triple therapy with HAIC, PD-(L)1 inhibitors, and MTT was safe and effective for patients with intermediate and advanced HCC for TACE-unsuitability.Keywords: advanced hepatocellular carcinoma, hepatic arterial infusion chemotherapy, molecular targeted therapies, PD-(L)1 inhibitors

Objective: Hip subluxation is a common complication in children with spinal cord injury. This study aimed to investigate the incidence and influencing factors of hip subluxation and discuss prevention strategies. Methods: Medical records of children with spinal cord injury were reviewed. The inclusion criteria were as follows: (1) the patient was younger than 18 years old when injured; (2) absence of traumatic or congenital pathological changes of the hip at the time of injury. The migration percentage and acetabular index were selected to evaluate hip stability and acetabulum development. Influencing factors of sex, age, injury duration, severity, level, and spasticity were analyzed. Results: A total of 146 children were enrolled. Twenty-eight children presented with hip subluxation and were significantly younger at the time of injury than those with normal hips (P = 0.002). The incidence of hip subluxation increased with the prolonged injury duration. Injury before age 6, complete injury, and flaccid lower extremities were significant influencing factors (P = 0.003, 0.004, and 0.015, respectively). The risk of hip subluxation decreased by 18% for every year older in injury age (P = 0.031) and decreased by 85% in children with spasticity (P = 0.018) than those without. However, the risk of hip subluxation in children with injury duration longer than 1 year was 7.1 times higher than those with shorter injury duration (P < 0.001). Conclusions: The incidence of hip subluxation in children with spinal cord injury increased with the injury duration. Younger children had immature hip development. Due to complete injury and flaccid muscle, lack of protection around the hip may lead to subluxation. Follow-up and prevention of hip subluxation need the joint effort of medical staff and families.

Background: To identify the association between daytime activity with objectively monitor and subjective variables at a different time-zone of day as well as the sex differences., Methods: Participants aged 50 years and older living in the community in Taiwan were recruited. The activity was measured by wearable actigraphy devices, diaries, and self-reported questionnaires. The study used nonparametric analysis to examine the association between mean activity level and demographic and subjective measurement variables., Results: Among the 55 participants enrolled in the study, data of 34 (62 %) participants who meet the criteria that wore a wearable actigraphy device for at least 7 completed days were analyzed. There is no significant relationship between each demographics and subjective measurement variables. However, actigraphy counts are significantly related to female's nutrition (Z = -2.367, p = 0.017*), and male's retirement status (Z = -2.132, p = 0.033*)., Conclusions: The activity in morning is highest of the day with significant correlation to evening activities. Moreover, actigraphy counts that indicating objective measure of physical activity in female is significantly related to physiological variables (nutritional status), while male are predicted by social variables (retired status)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jia-Chian Hu reports financial support was provided by Ministry of Science and Technology. Jia-Chian Hu reports financial support was provided by National Cheng Kung University College of Medicine. Jia-Chian Hu reports a relationship with Ministry of Science and Technology that includes: funding grants. Jia-Chian Hu reports a relationship with National Cheng Kung University College of Medicine that includes: funding grants. If there are other authors, they 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Vascular invasion (VI) profoundly impacts the prognosis of hepatocellular carcinoma (HCC), yet the underlying biomarkers and mechanisms remain elusive. This study aimed to identify prognostic biomarkers for HCC patients with VI., Methods: Transcriptome data from primary HCC tissues and HCC tissues with VI were obtained through the Genome Expression Omnibus database. Differentially expressed genes (DEGs) in the two types of tissues were analyzed using functional enrichment analysis to evaluate their biological functions. We examined the correlation between DEGs and prognosis by combining HCC transcriptome data and clinical information from The Cancer Genome Atlas database. Univariate and multivariate Cox regression analyses, along with the least absolute shrinkage and selection operator (LASSO) method were utilized to develop a prognostic model. The effectiveness of the model was assessed through time-dependent receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis., Results: In the GSE20017 and GSE5093 datasets, a total of 83 DEGs were identified. Gene Ontology analysis indicated that these DEGs were predominantly associated with xenobiotic stimulus, collagen-containing extracellular matrix, and oxygen binding. Additionally, Kyoto Encyclopedia of Genes and Genomes analysis revealed that the DEGs were primarily involved in immune defense and cellular signal transduction. Cox and LASSO regression further identified 7 genes (HSPA8, ABCF2, EAF1, MARCO, EPS8L3, PLA3G1B, C6), which were used to construct a predictive model in the training cohort. We used X-tile software to calculate the optimal cut-off value to stratify HCC patients into low-risk and high-risk groups. Notably, the high-risk group exhibited poorer prognosis than the low-risk group ( P < 0.001). The model demonstrated area under the ROC curve (AUC) values of 0.815, 0.730, and 0.710 at 1-year, 3-year, and 5-year intervals in the training cohort, respectively. In the validation cohort, the corresponding AUC values were 0.701, 0.571, and 0.575, respectively. The C-index of the calibration curve for the training and validation cohorts were 0.716 and 0.665. Decision curve analysis revealed the model's efficacy in guiding clinical decision-making., Conclusions: The study indicates that 7 genes may be potential prognostic biomarkers and treatment targets for HCC patients with VI., Competing Interests: None., (AJTR Copyright © 2024.)

Background and Objectives: Older adults keep transforming with Baby Boomers and Gen Xers being the leading older population. Their lifestyle, however, is not well understood. The middle-aged and older Chinese adults' health using actigraphy in Taiwan (MOCHA-T) collected both objective and subjective data to depict the health and lifestyle of this population. The objectives, design, and measures of the MOCHA-T study are introduced, and the caveats and future directions related to the use of the data are presented., Methods: People aged 50 and over were recruited from the community, with a subset of women aged 45-49 invited to supplement data on menopause and aging. Four instruments (i.e., self-reported questionnaires, diary, wrist actigraphy recorder, and GPS) were used to collect measures of sociodemographic, health, psychosocial, behavioral, temporal, and spatial data., Results: A total of 242 participants who returned the informed consent and questionnaires were recruited in the MOCHA-T study. Among them, 94.6%, 95.0%, and 25.2% also completed the diary, actigraphy, and GPS data, respectively. There was almost no difference in sociodemographic characteristics between those with and without a completed diary, actigraphy, and GPS data, except for age group and educational level for those who returned completed actigraphy data., Conclusion: The MOCHA-T study is a multidimensional dataset that allows researchers to describe the health, behaviors, and lifestyle patterns, and their interactions with the environment of the newer generation of middle-aged and older adults in Taiwan. It can be compared with other countries with actigraphy and GPS-based lifestyle data of middle-aged and older adults in the future., (© 2023. The Author(s).)

Objective: To investigate the clinical characteristics of children with traumatic spinal cord injury (SCI) admitted to a research rehabilitation center between 2011 and 2020, with a view to generate crucial data for understanding and prevention of pediatric traumatic SCI., Design: Retrospective cohort study., Setting: The National Rehabilitation Research Center of China, Beijing, China., Participants: Medical records and imaging data of children with traumatic SCI admitted to the rehabilitation research center from 2011 to 2020., Interventions: Not applicable., Outcome Measures: Data on age, sex, cause of injury, neurological level of injury, impairment scale of SCI and details of spine fracture or dislocation were all collected and analyzed., Results: A total of 351 patients were included in the study, including 133 males (37.9%) and 218 females (62.1%). There were 231 cases (65.8%) without spine fracture or dislocation. SCI without fracture or dislocation (SCIWORA) was the most common in children between the age of 5 and 14 years (77.9%), and injuries caused by sports were the most common in girls (90.8%). Among sports injuries, those due to a special dance movement called "Xia-Yao" in Chinese, which involves hyperextension of the trunk, constituted the majority, with the neurological level of injuries located predominantly in the middle (34.6%) and lower (44.2%) thoracic levels., Conclusion: Girls between the ages of 5 and 14 years constituted the majority of SCIWORA injuries at the thoracic levels, which were caused mainly by "Xia-Yao". Overall, careful attention should be paid to prevent this kind of injury in children.

Differentiated cardiomyocytes (CMs) must undergo diverse morphological and functional changes during postnatal development. However, the mechanisms underlying initiation and coordination of these changes remain unclear. Here, we delineate an integrated, time-ordered transcriptional network that begins with expression of genes for cell-cell connections and leads to a sequence of structural, cell-cycle, functional, and metabolic transitions in mouse postnatal hearts. Depletion of histone H2B ubiquitin ligase RNF20 disrupts this gene network and impairs CM polarization. Subsequently, assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis confirmed that RNF20 contributes to chromatin accessibility in this context. As such, RNF20 is likely to facilitate binding of transcription factors at the promoters of genes involved in cell-cell connections and actin organization, which are crucial for CM polarization and functional integration. These results suggest that CM polarization is one of the earliest events during postnatal heart development and provide insights into how RNF20 regulates CM polarity and the postnatal gene program., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Secoisolariciresinol (SECO) is one of the major lignans occurring in various grains, seeds, fruits, and vegetables. The gut microbiota plays an important role in the biotransformation of dietary lignans into enterolignans, which might exhibit more potent bioactivities than the precursor lignans. This study aimed to identify, synthesize, and evaluate the microbial metabolites of SECO and to develop efficient lead compounds from the metabolites for the treatment of osteoporosis. SECO was fermented with human gut microbiota in anaerobic or micro-aerobic environments at different time points. Samples derived from microbial transformation were analyzed using an untargeted metabolomics approach for metabolite identification. Nine metabolites were identified and synthesized. Their effects on cell viability, osteoblastic differentiation, and gene expression were examined. The results showed that five of the microbial metabolites exerted potential osteogenic effects similar to those of SECO or better. The results suggested that the enterolignans might account for the osteoporotic effects of SECO in vivo. Thus, the presence of the gut microbiota could offer a good way to form diverse enterolignans with bone-protective effects. The current study improves our understanding of the microbial transformation products of SECO and provides new approaches for new candidate identification in the treatment of osteoporosis.

MicroRNAs have been suggested to be signatures for predicting recurrence in breast cancer. This study aimed to identify miR-640 and miR-525-5p as relapse-associated microRNAs in systematically untreated and lymph node negative patients with primary breast cancer. GEO datasets GSE126125 and GSE103161 were analyzed to find the differential microRNAs in primary breast cancer with and without relapse. Systematically untreated patients (n = 180) with low-risk primary breast cancer were selected in this independent validation set, and 48 patients developed relapse within 5 years. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect miR-640 and miR-525-5p expressions in tumor tissues. Based on the retrieved data from GSE126125, miR-640 and miR-525-5p expressions were significantly lower in tumors from patients with relapse compared to tumors from patients without relapse, accompanying by highly predictive potential to discriminate cases with and without relapse. The decreased miR-640 and miR-525-5p expressions were revealed in dead patients as compared to alive patients. In the independent validation set, patients with low expression of miR-640 and miR-525-5p showed poor outcome as compared to those with high expression. The receiver operating characteristic (ROC) curves of miR-640 and miR-525-5p for evaluation as diagnostic markers were depicted with the area under curves (AUCs) of 0.940 and 0.886, respectively. Tumors with larger size and higher grade had lower expression of miR-640 and miR-525-5p. MiR-640, miR-525-5p and histologic grade were significant predictors of relapse-free survival (RFS). Our study validated the values of miR-640 and miR-525-5p in predicting relapse of systematically untreated and lymph node negative patients with primary breast cancer.

Background: Constraint-induced movement therapy (CIMT) is a prominent neurorehabilitation approach for improving affected upper extremity motor function in children with unilateral cerebral palsy (UCP). However, the restraint of the less-affected upper extremity and intensive training protocol during CIMT may decrease children's motivation and increase the therapist's workload and family's burden. A kinect-based CIMT program, aiming to mitigate the concerns of CIMT, has been developed. The preliminary results demonstrated that this program was child-friendly and feasible for improving upper extremity motor function. However, whether the kinect-based CIMT can achieve better or at least comparable effects to that of traditional CIMT (i.e., therapist-based CIMT) should be further investigated. Therefore, this study aimed to compare the effects of kinect-based CIMT with that of therapist-based CIMT on upper extremity and trunk motor control and on daily motor function in children with UCP., Methods: Twenty-nine children with UCP were recruited and randomly allocated to kinect-based CIMT (n = 14) or therapist-based CIMT (n = 15). The intervention dosage was 2.25 h a day, 2 days a week for 8 weeks. Outcome measures, namely upper extremity and trunk motor control and daily motor function, were evaluated before and after 36-h interventions. Upper extremity and trunk motor control were assessed with unimanual reach-to-grasp kinematics, and daily motor function was evaluated with the Revised Pediatric Motor Activity Log. Between-group comparisons of effectiveness on all outcome measures were analyzed by analysis of covariance (α = 0.05)., Results: The two groups demonstrated similar improvements in upper extremity motor control and daily motor function. In addition, the kinect-based CIMT group demonstrated greater improvements in trunk motor control than the therapist-based CIMT group did (F(1,28) > 4.862, p < 0.036)., Conclusion: Kinect-based CIMT has effects comparable to that of therapist-based CIMT on UE motor control and daily motor function. Moreover, kinect-based CIMT helps decrease trunk compensation during reaching in children with UCP. Therefore, kinect-based CIMT can be used as an alternative approach to therapist-based CIMT., Trial Registration: ClinicalTrials.gov Identifier: NCT02808195. Registered on 2016/06/21, https://clinicaltrials.gov/ct2/show/NCT02808195 ., (© 2023. The Author(s).)

Purpose: The long-term situation of children with spinal cord injury (SCI) was investigated, and suggestions for helping them better return to the society were provided., Methods: SCI patients less than 18 years old hospitalized in Beijing Boai Hospital from January 2011 to December 2020 were retrospectively analyzed. Information including motor function, complications, characteristic changes, self-care abilities, school attendance and social participation were collected by telephone interview and electronic questionnaire. All the answers were statistically analyzed., Results: A total of 86 cases were enrolled, 77 girls and 9 boys, with a median injury age of 6 years and 2 months. The follow-up time was 3-130 months. The main cause of trauma in these children was sport injury (66.3%), the thoracic spinal cord was involved the most (91.9%), and complete SCIs accounted for the majority (76.7%). In terms of complications, children with complete SCIs were more likely to have urinary incontinence, constipation and characteristic changes (p < 0.05); whereas the incomplete SCIs often have spasticity (p < 0.05). As to the daily living abilities, children with incomplete lumbar SCIs were more capable to accomplish personal hygiene, transfer, and bathing independently than those with complete injuries, or cervical/thoracic SCIs, respectively (p < 0.05). Moreover, children older than 9 years care more able to dress and transfer independently than the youngers (p < 0.05). Wheelchair users accounted for 84.9% and more than half of them were able to propel wheelchair independently, and those who move passively in wheelchairs were mostly introverted kids (p < 0.05). Almost all (93.8%) children with incomplete injuries were able to walk independently. Most (79.1%) children continued to attending school, and 41.9% participated in interest classes. Unfortunately, 67.4% of the children spent less time playing with their peers than before the injury., Conclusion: SCIs impair physical structures and function of children, affect their independence in daily living, and restrict school attendance and social interaction. Comprehensive rehabilitation after injury is a systematic work. Medical staff and caregivers should not only pay attention to neurological function, but also help them improve self-care abilities. It is also important to balance rehabilitation training and school work and social participation., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Background: This study aimed to evaluate whether a large paraumbilical vein (L-PUV) was independently associated with the occurrence of overt hepatic encephalopathy (OHE) after the implantation of a transjugular intrahepatic portosystemic shunt (TIPS). Methods: This bi-center retrospective study included patients with cirrhotic variceal bleeding treated with a TIPS between December 2015 and June 2021. An L-PUV was defined in line with the following criteria: cross-sectional areas > 83 square millimeters, diameter ≥ 8 mm, or greater than half of the diameter of the main portal vein. The primary outcome was the 2-year OHE rate, and secondary outcomes included the 2-year mortality, all-cause rebleeding rate, and shunt dysfunction rate. Results: After 1:2 propensity score matching, a total of 27 patients with an L-PUV and 54 patients without any SPSS (control group) were included. Patients with an L-PUV had significantly higher 2-year OHE rates compared with the control group (51.9% vs. 25.9%, HR = 2.301, 95%CI 1.094−4.839, p = 0.028) and similar rates of 2-year mortality (14.8% vs. 11.1%, HR = 1.497, 95%CI 0.422−5.314, p = 0.532), as well as variceal rebleeding (11.1% vs. 13.0%, HR = 0.860, 95%CI 0.222−3.327, p = 0.827). Liver function parameters were similar in both groups during the follow-up, with a tendency toward higher shunt patency in the L-PUV group (p = 0.067). Multivariate analysis indicated that having an L-PUV (HR = 2.127, 95%CI 1.050−4.682, p = 0.037) was the only independent risk factor for the incidence of 2-year OHE. Conclusions: Having an L-PUV was associated with an increased risk of OHE after a TIPS. Prophylaxis management should be considered during clinical management.

Objectives: We determined if the time interval between two ovulation induction intrauterine artificial insemination (IUI) treatment cycles should be extended by one or more natural menstrual cycles in patients undergoing successive cycles of ovulation stimulation, and whether this affects clinical pregnancy rate (CPR)., Design: This study was conducted on infertility patients treated under the ovulation induction programme IUI in a large reproductive centre in China. Study participants were assigned into continuous and discontinuous groups. Differences in baseline clinical pregnancy and abortion rates were compared between the groups. A multivariate logistic model was used to evaluate the effects of time interval on clinical pregnancy outcomes., Setting: Reproductive Centre of Maternal and Child Health Hospital of Lianyungang city., Interventions: None., Primary and Secondary Outcome Measures: The primary outcome measure was CPR, the secondary outcome measure was the abortion rate., Results: A total of 550 IUI treatment cycles involving 275 couples were included in this study. Differences in CPR and abortion rate between the groups were not significant (20.5% vs 21.9% and 27.8% vs 22.0%, p≥0.05). Stratified analyses based on infertility factors did not reveal any significant differences in pregnancy and abortion rates between the groups (p≥0.05). Multivariate analysis showed that increased endometrial thickness correlates with CPR (OR 1.205, 95% CI 1.05 to 1.384, p = 0.008). Compared with primary infertility, secondary infertility significantly correlated with improved CPR (OR 2.637, 95% CI 1.313 to 5.298, p = 0.006). The effects of time interval between the first two ovulation induction IUI treatment cycles on clinical pregnancy were not significant (OR 1.007, 95% CI 0.513 to 1.974, p=0.985)., Conclusions: Longer time intervals between the first two ovulation induction IUI treatment cycles did not significantly improve CPR. Therefore, in the absence of clear clinical indications, it may not be necessary to deliberately prolong the interval between two ovulation induction IUI treatment cycles., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Targeting ferritin via autophagy (ferritinophagy) to induce ferroptosis, an iron- and reactive oxygen species (ROS)-dependent cell death, provides novel strategies for cancer therapy. Using a ferroptosis-specific inhibitor and iron chelator, the vulnerability of triple-negative breast cancer (TNBC) MDA-MB-231 cells to ferroptosis was identified and compared to that of luminal A MCF-7 cells. Saponin formosanin C (FC) was revealed as a potent ferroptosis inducer characterized by superior induction in cytosolic and lipid ROS formation as well as GPX4 depletion in MDA-MB-231 cells. The FC-induced ferroptosis was paralleled by downregulation of ferroportin and xCT expressions. Immunoprecipitation and electron microscopy demonstrated the involvement of ferritinophagy in FC-treated MDA-MB-231 cells. The association of FC with ferroptosis was strengthened by the results that observed an enriched pathway with differentially expressed genes from FC-treated cells. FC sensitized cisplatin-induced ferroptosis in MDA-MB-231 cells. Through integrated analysis of differentially expressed genes and pathways using the METABRIC patients' database, we confirmed that autophagy and ferroptosis were discrepant between TNBC and luminal A and that TNBC was hypersensitive to ferroptosis. Our data suggest a therapeutic strategy by ferroptosis against TNBC, an aggressive subtype with a poor prognosis.

Purpose: Previous studies found that silicosis was majorly associated with occupation-related risks. However, little evidence was available to clarify the relation between Asian dust storm (ADS) and silicosis hospital admissions. This present paper aims to investigate the association between ADS events and hospital admissions for silicosis., Methods: We applied a Poisson time-series regression on the 2000-2012 National Health Insurance Research Database in Taiwan, linking air quality data and ambient temperature data to estimate the impact of ADS on silicosis hospital admissions in the age-specific groups., Results: A total of 2154 hospital admissions were recorded for silicosis in Taiwan, for a daily average number of 0.45. The number rises from 0.43 on a day without ADS to 0.70 on the outbreak day and continues increasing to 0.83 one day after outbreak. Among patients under 45, the effect of ADS appears on the event day as well as several post-event days (lag2-6) at the significant level of p < 0.1. There is also a significant lag effect on post-event day 2 (p < 0.05) for those aged above 74., Conclusion: Asian dust storms do result in a rise of silicosis hospital admissions, particularly for those above 74, those under 45, and for females., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Springer Nature Switzerland AG 2022.)

Introduction: Cerebral palsy (CP) is the leading cause of childhood-onset physical disability. Children with CP often have impaired upper limb (UL) function. Constraint-induced therapy (CIT) is one of the most effective UL interventions for children with unilateral CP. However, concerns about CIT for children have been repeatedly raised due to frustration caused by restraint of the child's less-affected UL and lack of motivation for the intensive protocol. Virtual reality (VR), which can mitigate the disadvantages of CIT, potentially can be used as an alternative mediator for implementing CIT. Therefore, we developed a VR-based CIT program for children with CP using the Kinect system. Aims: The feasibility of the Kinect-based CIT program was evaluated for children with unilateral CP using a two-phase study design. Materials and Methods: In phase 1, ten children with unilateral CP were recruited. To confirm the achievement of the motor training goals, maximal UL joint angles were evaluated during gameplay. To evaluate children's perceptions of the game, a questionnaire was used. In phase 2, eight children with unilateral CP were recruited and received an 8 weeks Kinect-based CIT intervention. Performance scores of the game and outcomes of the box and block test (BBT) were recorded weekly. Results: In phase 1, results supported that the design of the program was CIT-specific and was motivational for children with unilateral CP. In phase 2, game performance and the BBT scores began showing stable improvements in the fifth week of intervention. Conclusion: It suggested the Kinect-based CIT program was beneficial to the motor function of the affected UL for children with unilateral CP. According to the results of this feasibility study, larger and controlled effectiveness studies of the Kinect-based CIT program can be conducted to further improve its clinical utility. Clinical Trial Registration: ClinicalTrials.gov, NCT02808195; Comparative effectiveness of a Kinect-based unilateral arm training system vs. CIT for children with CP., 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 Chen, Lin, Yeh, Chen, Tang, Ruan and Wang.)

Nitrogen and sulfur codoped carbon dots (NSCDs) were synthesized via a one-pot hydrothermal method, and citric acid, ethylenediamine, and methyl blue were used as precursors. The obtained NSCDs were spherical with an average size of 1.86 nm. The fluorescence emission spectra of the NSCDs were excitation independent and emitted blue fluorescence at 440 nm with an excitation wavelength at 350 nm. The quantum yield of the NSCDs was calculated to be 68.0%. The NSCDs could be constructed as fluorescent probes for highly selective and sensitive sensing mercuric (Hg 2+ ) and hypochlorite (ClO - ) ions. As the addition of Hg 2+ or ClO - ions to the NSCDs, the fluorescence intensity was effectively quenched due to dynamic quenching. Under the optimal conditions, the linear response of the fluorescence intensity ranged from 0.7 μM to 15 μM with a detection limit of 0.54 μM and from 0.3 μM to 5.0 μM with a limit of detection of 0.29 μM for Hg 2+ and ClO - ions, respectively. Finally, the proposed method was successfully used for quantifying Hg 2+ and ClO - ions in spiked tap water samples.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide with high rates of transmission and substantial mortality. To date, however, no effective treatments or enough vaccines for COVID-19 are available. The roles of angiotensin converting enzyme 2 (ACE2) and spike protein in the treatment of COVID-19 are major areas of research. In this study, we explored the potential of ACE2 and spike protein as targets for the development of antiviral agents against SARS-CoV-2. We analyzed clinical data, genetic data, and receptor binding capability. Clinical data revealed that COVID-19 patients with comorbidities related to an abnormal renin-angiotensin system exhibited more early symptoms and poorer prognoses. However, the relationship between ACE2 expression and COVID-19 progression is still not clear. Furthermore, if ACE2 is not a good targetable protein, it would not be applicable across a wide range of populations. The spike-S1 receptor-binding domain that interacts with ACE2 showed various amino acid mutations based on sequence analysis. We identified two spike-S1 point mutations (V354F and V470A) by receptor-ligand docking and binding enzyme-linked immunosorbent assays. These variants enhanced the binding of the spike protein to ACE2 receptors and were potentially associated with increased infectivity. Importantly, the number of patients infected with the V354F and V470A mutants has increased with the development of the SARS-CoV-2 pandemic. These results suggest that ACE2 and spike-S1 are likely not ideal targets for the design of peptide drugs to treat COVID-19 in different populations.

Study Design: Retrospective analysis., Setting: China Rehabilitation Research Center, Beijing, China., Objective: To explore possible mechanisms underlying spinal cord injury (SCI) in children caused by hyperextension of the spine while dancing., Methods: The clinical records of 88 children with SCI (mean age, 5.97 years; age range, 4-10 years) admitted to our hospital from January 1989 to October 2019 were retrospectively reviewed. Computed tomography and magnetic resonance imaging were performed on the day of injury. The time from injury to development of paralysis, as well as post-injury activities were surveyed, while abnormal patterns on images, the range of the involved vertebrae, and the extents of edema and atrophy were assessed., Results: Among the 88 patients, 6 (6.8%) were unable to move immediately after SCI, while paralysis occurred in 42, 23, and 17 patients at <30, 30-60, and >60 min after SCI, respectively. The neurological level of injury of 84 patients was between T4 and T12. On sagittal T2-weighted images (T2WIs), the longitudinal range of spinal cord edema was more than one vertebral body in 65 patients, while spinal cord atrophy below T8 was found in 40 patients. On axial T2WIs, although three patients had none, long T2 signals were found in the central gray matter of seven patients. Meanwhile, necrosis of the central area combined with the peripheral white matter was observed in 57 patients, while three patients had total involvement on a cross section., Conclusion: Ischemia-related damage, rather than direct trauma to the spinal cord, may play an important role in SCI due to spinal hyperextension during dancing.

Analysis of various public databases revealed that HRAS gene mutation frequency and mRNA expression are higher in bladder urothelial carcinoma. Further analysis revealed the roles of oncogenic HRAS, autophagy, and cell senescence signaling in bladder cancer cells sensitized to the anticancer drug cisplatin using the phytochemical pterostilbene. A T24 cell line with the oncogenic HRAS was chosen for further experiments. Indeed, coadministration of pterostilbene increased stronger cytotoxicity on T24 cells compared to HRAS wild-type E7 cells, which was paralleled by neither elevated apoptosis nor induced cell cycle arrest, but rather a marked elevation of autophagy and cell senescence in T24 cells. Pterostilbene-induced autophagy in T24 cells was paralleled by inhibition of class I PI3K/mTOR/p70S6K as well as activation of MEK/ERK (a RAS target) and class III PI3K pathways. Pterostilbene-induced cell senescence on T24 cells was paralleled by increased pan-RAS and decreased phospho-RB expression. Coadministration of PI3K class III inhibitor 3-methyladenine or MEK inhibitor U0126 suppressed pterostilbene-induced autophagy and reversed pterostilbene-enhanced cytotoxicity, but did not affect pterostilbene-elevated cell senescence in T24 cells. Animal study data confirmed that pterostilbene enhanced cytotoxicity of cisplatin plus gemcitabine. These results suggest a therapeutic application of pterostilbene in cisplatin-resistant bladder cancer with oncogenic HRAS .

Ferroptosis, a recently discovered form of iron-dependent cell death, requires an increased level of lipid-reactive oxygen species (ROS). Ferritinophagy, a ferritin degradation pathway, depends on a selective autophagic cargo receptor (NCOA4). By screening various types of natural compounds, formosanin C (FC) was identified as a novel ferroptosis inducer, characterized by attenuations of FC-induced viability inhibition and lipid ROS formation in the presence of ferroptosis inhibitor. FC also induced autophagic flux, evidenced by preventing autophagic marker LC3-II degradation and increasing yellow LC3 puncta in tandem fluorescent-tagged LC3 (mRFP-GFP) reporter plasmid (ptfLC3) transfected cells when combined with autophagic flux inhibitor. It is noteworthy that FC-induced ferroptosis and autophagic flux were stronger in HepG2 cells expressing higher NCOA4 and lower ferritin heavy chain 1 (FTH1) levels, agreeing with the results of gene expression analysis using CTRP and PRISM, indicating that FTH1 expression level exhibited a significant negative correlation with the sensitivity of the cells to a ferroptosis inducer. Confocal and electron microscopy confirmed the pronounced involvement of ferritinophagy in FC-induced ferroptosis in the cells with elevated NCOA4. Since ferroptosis is a non-apoptotic form of cell death, our data suggest FC has chemotherapeutic potential against apoptosis-resistant HCC with a higher NCOA4 expression via ferritinophagy.

Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain unknown. Here, we aimed to identify and characterize genetic variants with pleiotropic effects on cytokines. Using three population-based cohorts (n = 9,263), we performed multivariate genome-wide association studies (GWAS) for a correlation network of 11 circulating cytokines, then combined our results in meta-analysis. We identified a total of eight loci significantly associated with the cytokine network, of which two (PDGFRB and ABO) had not been detected previously. In addition, conditional analyses revealed a further four secondary signals at three known cytokine loci. Integration, through the use of Bayesian colocalization analysis, of publicly available GWAS summary statistics with the cytokine network associations revealed shared causal variants between the eight cytokine loci and other traits; in particular, cytokine network variants at the ABO, SERPINE2, and ZFPM2 loci showed pleiotropic effects on the production of immune-related proteins, on metabolic traits such as lipoprotein and lipid levels, on blood-cell-related traits such as platelet count, and on disease traits such as coronary artery disease and type 2 diabetes., (Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Study Design: Retrospective analysis., Setting: China Rehabilitation Research Center, Beijing, China., Objective: A retrospective study that documents the modalities and clarifies the heterogeneity among spinal cord injuries (SCIs) caused by trauma to the thoracolumbar vertebral junction., Methods: X-ray and MRI imaging, neurological records, and the urodynamics results of 190 patients were reviewed and used to categorize different SCI modalities. First, injuries were divided into complete and incomplete injuries using the International Standard for Neurological Classification of Spinal Cord Injury. Next, the complete injuries were further grouped using the neurological level of injury and Long T2 signal from mid-sagittal MRI images, whereas the bulboconvernosus reflexes were also used as a reference to detect injury to the sacral cord., Results: The SCI modalities were classified into five categories: pure complete epiconus lesion with caudal cord intact (G1), complete epiconus injury with conus medullaris (CM) totally involved in the lesion (G2), CM syndrome, cauda equine syndrome without sacral sparing (G3 and G4), and incomplete injury (G5)., Conclusions: The heterogeneity of SCIs at the thoracolumbar junction was documented, a criterion we propose to be of great significance when selecting patients for clinical trials. In particular, the G2 group, which comprises nearly one third of the patients with epiconus lesions, is sometimes mistaken as G1, an observation that has thus far received insufficient attention.

Background: The present study evaluated the clinical outcomes and safety of expansive open-door laminoplasty, when securing with C4 - C6 lateral mass screw and fusion., Methods: A total of 110 patients with cervical spondylotic myelopathy (CSM) were enrolled. There were 88 male and 22 female, with mean age at 60.55 ± 10.95 years. All of the patients underwent expansive open-door laminoplasty with unilateral or bilateral C4-6 lateral mass screws fixation and fusion. Clinical data, including age, gender, operation-related information, pre- and post-operation Japanese Orthopedic Association (JOA) scores, and cervical curvatures were collected., Results: The mean follow-up time of the cohort was 13.61 ± 9.53 months. Among the 110 patients, 33 of them were allocated to Unilateral group, and 77 of them were in Bilateral group. The mean JOA score of the 110 patients before surgery was 10.07 ± 2.39, and the score was improved significantly to 12.85 ± 2.45 after surgery. There were no reported cases of neurological deterioration or symptom worsening. Patients in both the Unilateral group and Bilateral groups had significant improvement of JOA scores. Among all patients, the most frequently observed complications were axial symptoms (n = 7). The average preoperative cervical curvature among all patients was 15.17 ± 5.26, and the post-surgery curvature was 14.41 ± 4.29. Similar observations were found between Unilateral and Bilateral groups., Conclusion: The modified surgical approach provided satisfactory clinical outcome in patients with CSM. The unilateral and bilateral fixation appeared to provide similar outcomes, in terms of cervical curvature maintenance and improvement of clinical symptoms. However, the examination of the exact differences between the two fixation methods await further biomechanical studies.

The Mawangdui tomb No.1 cadaver, a female corpse from the Western Han Dynasty, was unearthed in 1972. Forensic examination at the time of discovery indicated fairly remarkable presence of bodily constituents at the anatomical, histological, and molecular levels. The cadaver was preserved in a formalin-based fixative afterward, and maintained in the Hunan Museum. To better protect this rare human corpse, a reappraisal of the status of preservation was carried out using noninvasive approaches, including X-ray radiography, gross anatomical examination, and histological, microbiological, and molecular analyses of sampled tissues. The cadaver remained essentially intact from a gross anatomical perspective, with radiography of the skeletal system and arterial contrast filling appeared comparable with the original documentation. The light microscopic features of the skin, cartilage, and skeletal muscle remained detectable, as were the stratified ultrastructure of the collagen and muscle fibers. The levels of nitrogen and amino acidic elements appeared elevated in the cadaver and liver preservation fixatives, with a higher calcium and phosphate concentration in the former. These findings suggest that there existed a certain degree of macromolecule degradation and bone decalcification in the cadaver, likely irrelevant to biological decomposition. The reappraisal also led to the implementation of stronger scientific measures to better protect the cadaver through a renovated Museum-University coadministrative management agreement.

Background: To analyze the cardio-protective effects of ticagrelor in patients with acute coronary syndrome with S-T segment elevation., Methods: The sample was 200 patients who had been diagnosed with acute coronary syndrome accompanied by diabetes Mellitus type II. Only patients having ST segment elevation before the treatment were included. Then, the subjects were further randomly divided into an observation group and a control group. The control group of 100 patients received clopidogrel; the observation group of 100 patients of ticagrelor. The serous creatine kinase CK-MB, functional cardiac indexes of left ventricular end diastolic diameter (LVDD), cardiac troponin I, ventricular ejection fraction, and relevant major adverse cardiovascular events (MACE) were compared between the two groups., Results: One month after a percutaneous coronary intervention (PCI) the observation group showed better results against angina, stent thrombosis, and all-cause mortality compared with those of the control subjects. Six months after treatment, both groups suffered adverse reactions. The number of patients who suffered adverse reactions in respiratory tract in the observation group was higher than in the control group. The inhibition of platelet aggregation IPA of ticagrelor was found to be significantly higher than clopidogrel, having a significant p value., Conclusion: Ticagrelor can effectively protect myocardial function for patients with ST-segment elevation acute coronary syndrome accompanied by diabetes and can reduce the incidence of adverse reactions.., Competing Interests: Conflict of interest Conflict of interest statement: Authors state no conflict of interest.

Background: Clinical evidence gathered in Chinese communities suggested that acupoint sticking therapy could be an alternative treatment for asthma-related diseases. However, its underlying mechanism is still poorly understood., Aim/hypothesis: In this study, we aimed to investigate the mechanism of the anti-inflammatory effect of acupoint sticking application with 'Treatment of Winter Disease in Summer' (TWDS) prescription by using metabolomics., Methods: Allergic asthma in guinea pig was sensitized and challenged by ovalbumin (OVA). Histopathological evaluation of the lung tissue was performed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. The levels of Th2 cytokine and IgE level in serum were measured using enzyme-linked immunoassay (ELISA). The mRNA expression levels of IL-4, IL-5, IL-13 and orosomucoid-like 3 (ORMDL3) were measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Proteins of NF-κB signaling pathway were measured using western blot. The serum metabolomics profiles were obtained by using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS)., Results: The overall results confirmed that AST with TWDS prescription had a significant protective effect against OVA-induced allergic asthma in guinea pig. This treatment not only attenuated airway inflammation and collagen deposition in the airway, but also decreased the levels of IL-4, IL-5, IL-13 and IgE in serum. In addition, metabolomics results indicated that metabolisms of phospholipid, sphingolipid, purine, amino acid and level of epinephrine were restored back to the normal control level. Moreover, results of the gene expression of ORMDL3 in lung tissues indicated that AST using TWDS could alter the sphingolipid metabolism. Further western blotting analysis also showed that its anti-inflammatory mechanism was by decreasing the phosphorylation of p65 and IκB., Conclusion: The study demonstrated that metabolomics provides a better understanding of the actions of TWDS acupoint sticking therapy on OVA-induced allergic asthma., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: Apelin plays a key beneficial role in energy metabolism by increasing glucose uptake and insulin sensitivity; however, apelin has a short half-life because it is rapidly cleared from the circulation limiting its therapeutic benefit. The aim of this study is to create a new approach to treat type 2 diabetes by inducing prolonged expression of apelin in Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs)., Methods: A type 2 diabetic rat model was given a high-fat diet combined with low-dose streptozotocin (STZ) injection. The human WJ-MSCs were isolated and subsequently transduced with apelin-expressing lentiviral particles (WJMSCs-apelin), and expression was verified by flow cytometry, Western blot, ELISA, and RT-PCR analysis. Type 2 diabetic rats were infused with either WJMSCs-apelin (2 × 10 6 cells) or an equivalent dose of saline through the tail vein injection 7 days after STZ injection. The therapeutic effects of each infusion group were evaluated by monitoring plasma glucose levels and performing glucose tolerance tests (OGTTs), insulin tolerance tests (IPITTs), confocal microscopy, and immunocytochemical analysis for quantitating islet beta cells. Plasma inflammatory cytokines IL-6 and TNF-α and anti-inflammatory factors adiponectin were measured as well., Results: Type 2 diabetic rats infused with WJ-MSCs-apelin significantly decreased levels of blood glucose (from 26.03 ± 2.83 to 15.85 ± 2.13 mmol/L on 7 days P < 0.001, and to 9.41 ± 2.05 on 14 days, P < 0.001). Infusion of WJMSCs-apelin not only improved significantly insulin sensitivity and glucose disposal, but also promoted endogenous pancreatic ß cell proliferation (9.6-fold increase compared to the control group). Furthermore, infusion of the WJMSCs-apelin consistently increased insulin and C-peptide levels in the plasma, and the above effects persisted up to 42 days. The inflammatory cytokines IL-6 and TNF-α were significantly decreased, whereas anti-inflammatory factor adiponectin was significantly increased after WJ-MSC-apelin infusion., Conclusion: In this study, we report a novel approach to treat type 2 diabetic rats that combines apelin gene therapy with WJ-MSC cell therapy, which could provide a promising therapeutic option for management of type 2 diabetes clinically.

Events in early life contribute to subsequent risk of asthma; however, the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma. Similarly, not all atopic individuals develop wheeze, and vice versa. The reasons for these differences are unclear. Using unsupervised model-based cluster analysis, we identified latent clusters within a prospective birth cohort with deep immunological and respiratory phenotyping. We characterised each cluster in terms of immunological profile and disease risk, and replicated our results in external cohorts from the UK and USA. We discovered three distinct trajectories, one of which is a high-risk 'atopic' cluster with increased propensity for allergic diseases throughout childhood. Atopy contributes varyingly to later wheeze depending on cluster membership. Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis and provide a foundation for improving management and prevention of childhood asthma., Competing Interests: HT, ST, DB, ME, DJ, MB, MK, SJ, JG, RL, AS, AC, PS, PH, KH, MI No competing interests declared, (© 2018, Tang et al.)

Objective: To investigate the diagnostic performance of whole-tumor volume analysis of mono-exponential and intravoxel incoherent motion (IVIM)parameters in the preoperative grading of hepatocellular carcinoma (HCC). Methods: A total of 106 patients who undewent parital hepatectomy were prospectively enrolled and underwent with routine MR and IVIM examination.112 HCCs were confirmed by the surgical pathology.The original images of IVIM were imported into the GE AW 4.6 workstation.Two independent radiologist who were blinded to the histopathological results analyzed the data.Freehand ROI was used to cover the whole tumor volume, ADC, ADC(slow), ADC(fast) and f was calculated.Intra-class correlation coefficient (ICC) was used to evaluate the inter-observer agreement, One - way ANOVA and Kruskal - Wallis sign rank test were used to evaluate the difference of these parameters in grading HCC, Spearman correlation analysis was used to determine the correlation between these parameters and histologic grade, receiver operating characteristics (ROC) curves were performed to evaluate the diagnostic performance. Results: ICC value of ADC, ADC(slow), ADC(fast) and f were 0.948, 0.966, 0.901 and 0.940, respectively.Statistical significances were obtained from the ADC(slow)(R1: χ(2)=74.403, P <0.001; R2: F =44.973, P <0.001) and ADC (R1: χ(2)=52.987, P <0.001; R2: F =30.851, P <0.001) in grading HCC.Between the multiple-comparison in grading HCC, the ADC(slow) and ADC (except for E-S 3 and 4, R1: P =0.134; R2: P =0.069) also demonstrated a statistical significant difference (all P <0.05). Area under curve (AUC) value of two radiologists for ADC(slow) were 0.905 and 0.917, for ADC were 0.831 and 0.829, a negative correlation was obtained from the ADC and ADC(slow) (all P <0.05). Conclusion: Mono-exponential and intravoxel incoherent motion (IVIM) model can be used to evaluate the pathological differentiated grade of HCC, ADC and ADC(slow) value entailed the highest diagnostic performance.

The aim of the present study was to investigate whether the proliferation and metastasis of hilar cholangiocarcinoma cells can be suppressed and whether apoptosis can be induced by small interfering RNA (siRNA) repression of vascular endothelial growth factor (VEGF). siRNA sequences targeting the VEGF gene were designed and the human hilar cholangiocarcinoma QBC939, HCCC-9810 and RBE cell lines were transfected with VEGF-siRNA plasmids for 48 h. Reverse transcription-quantitative polymerase chain reaction and western blotting measured the levels of VEGF-A, VEGF-C and matrix metalloproteinase 2 (MMP2) mRNA expression and protein content. The cell invasion potential was evaluated using the Transwell invasion and migration assay and the MTT assay was employed to detect the proliferation of hilar cholangiocarcinoma cells. Flow cytometry was used to quantify cell apoptosis and necrosis. Following the transfection of VEGF-siRNA, a significant reduction of mRNA and protein levels of VEGF-A, VEGF-C and MMP2 was observed in the hilar cholangiocarcinoma cells. The invasion, migration and proliferation of tumor cells were also notably decreased. The rate of tumor cell apoptosis was increased in the VEGF-siRNA group (15.42%) compared with the non-siRNA control (2.22%) and the negative control (2.71%) groups. It was concluded that blocking the expression of VEGF via VEGF-siRNA effectively inhibited the invasion, migration and proliferation, and induced apoptosis in hilar cholangiocarcinoma cells. These observations suggested that targeting VEGF with RNAi may be an effective therapeutic strategy for treating hilar cholangiocarcinoma.

Two mononuclear and one binuclear ytterbium complexes with dual near-infrared (NIR) photoluminescence and reversible trans-to-cis photoisomerization functions were synthesized and characterized. The central ytterbium(III) ion coordinates with two β-diketonate (4,4,4-trifluoro-1-phenylbutane-1,3-dionate (tfd)) ligands and one deprotonated azobenzene-containing tetradentate ligand [( E )-4-(phenyldiazenyl)- N , N -bis(pyridin-2-ylmethyl) benzohydrazide (HL), ( E )-4-((4-(dimethylamino)phenyl)diazenyl)- N , N -bis(pyridin-2-ylmethyl)benzohydrazide (HNL), or ( E )-4,4'- N ', N '-bis(pyridin-2-ylmethyl)benzohydrazide azobenzene (H 2 DL)] to form a neutral ternary complex ([Yb(tfd) 2 L], [Yb(tfd) 2 (NL)], or [Yb 2 (tfd) 4 (DL)], respectively), where the ytterbium(III) ion is eight-coordinated to N 3 O 5 donor sets. X-ray crystallographic analysis shows that all three complexes form a trigonal dodecahedron geometry with similar -N=N- distances that are slightly longer than those of the pure azobenzene-containing ligands. The NIR luminescence properties of the Yb(III) complexes were determined at a wavelength of about 980 nm with quantum yields in the range of 0.4-0.6% in ethanol and acetonitrile solutions at room temperature, and trans-to-cis photoisomerization was determined with the quantum yields (Φ t→c = 10 -2 ) at the same level as their pure ligands. The trans-to-cis photoisomerization rates of the complexes (10 -4 s -1 ) are slightly higher than those of the pure ligands and similar to azobenzene (10 -5 to 10 -4 s -1 ). From time-dependent density functional theory calculations of the energy levels of the first excited triplet states of the ligands, the energies of the lowest excited triplet states of all of the ligands are higher than the resonance level of Yb 3+ (2F 5/2 , 1.2722 eV). We suggest that these azo-containing ligands may participate in energy transfer to the ytterbium ion, in addition to the main "antenna effect" ligand tfd. This is the first report of azobenzene group-functionalized ytterbium complexes with dual NIR luminescence and photoisomerization properties, indicating that azobenzene-containing lanthanide(III) complexes have potential applications as dual function materials in biological systems., Competing Interests: The authors declare no competing financial interest.

The resolution of conventional terahertz (THz) imaging techniques is limited to about half wavelength, which is not fine enough for applications of biomedical sensing and nondestructive testing. To improve the resolution, a new superlens, constructed by a monolayer graphene sheet combining with a grating voltage gate, are proposed in this paper to achieve deep super-resolution imaging in the THz frequency range. The main idea is based on the Fabry-Perot resonance of graphene edge plasmon waves. By shaping the voltage gate into a radial pattern, magnified images of subwavelength targets can be obtained. With this approach, the finest resolution can achieve up to λ/150. Besides, the superlens can be conveniently tuned to work in a large frequency band ranging from 4.3 THz to 9 THz. The proposal could find potential applications in THz near-field imaging systems.

A compact metallic meta-structure is proposed to realize directional conversion between spoof surface plasmon polaritons (SSPPs) and propagating waves at millimeter wave and THz frequencies. The structure is constructed by embedding two slits or multi-slits array into a subwavelength metallic reflection grating. When the back-side of the structure is illuminated by an oblique beam with a fixed incident angle, the propagating wave will be unidirectionally converted into SSPPs with a considerable efficiency. Both the simulations and experiments demonstrate that the excitation ratio of the SSPPs between the two possible propagating directions (left and right) reaches up to about 340. Furthermore, assisted by the structure, near-field SSPPs can be also converted into far-field narrow beams with particular directions. Through frequency sweeping, wide-angle beam scanning is verified by theory and experiments. The work paves a new way for SSPPs launching and also provides fresh ideas for super-resolution imaging in the longer wavelength range.

A new gradient-index (GRIN) lens that can realize enhanced spatial Fourier transform (FT) over optically long distances is demonstrated. By using an anisotropic GRIN metamaterial with hyperbolic dispersion, evanescent wave in free space can be transformed into propagating wave in the metamaterial and then focused outside due to negative-refraction. Both the results based on the ray tracing and the finite element simulation show that the spatial frequency bandwidth of the spatial FT can be extended to 2.7k(0) (k(0) is the wave vector in free space). Furthermore, assisted by the enhanced spatial FT, a new long-distance (in the optical far-field region) super-resolution imaging scheme is also proposed and the super resolved capability of λ/5 (λ is the wavelength in free space) is verified. The work may provide technical support for designing new-type high-speed microscopes with long working distances.

Neuropeptide FF (NPFF) is known to be an endogenous opioid-modulating peptide. Nevertheless, very few researches focused on the interaction between NPFF and endogenous opioid peptides. In the present study, we have investigated the effects of NPFF system on the supraspinal antinociceptive effects induced by the endogenous µ-opioid receptor agonists, endomorphin-1 (EM-1) and endomorphin-2 (EM-2). In the mouse tail-flick assay, intracerebroventricular injection of EM-1 induced antinociception via µ-opioid receptor while the antinociception of intracerebroventricular injected EM-2 was mediated by both µ- and κ-opioid receptors. In addition, central administration of NPFF significantly reduced EM-1-induced central antinociception, but enhanced EM-2-induced central antinociception. The results using the selective NPFF1 and NPFF2 receptor agonists indicated that the EM-1-modulating action of NPFF was mainly mediated by NPFF2 receptor, while NPFF potentiated EM-2-induecd antinociception via both NPFF1 and NPFF2 receptors. To further investigate the roles of µ- and κ-opioid systems in the opposite effects of NPFF on central antinociception of endomprphins, the µ- and κ-opioid receptors selective agonists DAMGO and U69593, respectively, were used. Our results showed that NPFF could reduce the central antinociception of DAMGO via NPFF2 receptor and enhance the central antinociception of U69593 via both NPFF1 and NPFF2 receptors. Taken together, our data demonstrate that NPFF exerts opposite effects on central antinociception of endomorphins and provide the first evidence that NPFF potentiate antinociception of EM-2, which might result from the interaction between NPFF and κ-opioid systems.

Background/aims: To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing., Methods: An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay., Results: The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation., Conclusions: CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.

Objective: Perineural invasion of cholangiocarcinoma happens in the early stage of the disease but is often not recognized until its later stages. Research about the behaviour and mechanism of perineural invasion by cholangiocarcinoma is urgently needed for a useful new model. The aim of this work is to establish a novel model to address the problem., Design: Neural cells and cholangiocarcinoma cells were co-cultured to mimic the neurotropic invasion of cholangiocarcinoma., Setting: Human embryonic stem cells were induced to form neural cells by glial cell-derived neurotropic factor and retinoic acid; neural cells and cholangiocarcinoma cells were co-cultured in Transwell chamber., Participants: Human embryonic stem cells and cholangiocarcinoma cells were applied., Main Outcome Measures: Paired t-test was used to compare the counts of penetrating cholangiocarcinoma cells in co-culture and control group., Results: Formation of neurospheres and neural-like cells were observed following induction at 24 and 48 h, respectively; synapses were viewed to protrude from neural-like cell bodies after incubation for 96 h. Forty-eight hours after incubation, immunocytochemical staining of the cells showed that synaptophysin and glial fibrillary acidic protein were expressed in the neuron-like cells and gliocytes-like cells, respectively. The cholangiocarcinoma cells that had penetrated through the Matrigel/polyethylene terephthalate membrane from the upper chamber to the lower chamber of the Transwell in the co-culture group were significantly more numerous than those in the control group (68 ± 8.3/field versus 46 ± 5.7/field, P < 0.05)., Conclusion: The novel model is a valuable tool to study the perineural invasion of cholangiocarcinoma.

Background/aims: We aimed to investigate the correlation between a disintegrin and metalloprotease with thrombospondin motif 2 (ADAMTS-2) and transforming growth factor-β1 (TGF-β1) in clinical human cirrhotic tissues., Methods: The liver tissues of 24 patients (16 cases with cirrhotic portal hypertension as the cirrhosis group and eight cases with healthy livers as the normal group) were collected. Immunohistochemistry and Western blots were performed to evaluate the protein expression levels of ADAMTS-2 and TGF-β1. Western blots for other key mediators of cirrhotic progression, including SMAD2, SMAD3, TGF-β receptor II (TGFβRII), matrix metalloproteinases 2 (MMP2), and tissue inhibitor of matrix metalloproteinases 2 (TIMP2), were also performed., Results: Cirrhotic tissues showed higher percentages of collagen. The protein expression levels of ADAMTS-2 and TGF-β1 were significantly higher in the cirrhotic group as compared to the matched normal group (p<0.05), and there was a positive correlation between these two proteins (r=0.862, p<0.01). The protein expressions of MMP2, TIMP2, and TGFβRII, as well as the phosphorylated forms of SMAD2 and SMAD3, were significant higher in the cirrhotic group (p<0.01 or p<0.05)., Conclusions: These findings suggested that ADAMTS-2 and TGF-β1 may play important roles in the pathogenesis of human cirrhosis; specifically, TGF-β1 may induce the expression of ADAMTS-2 through the TGFβ/SMAD pathway.

Objective: In this study, we investigated the developmental potential of single blastomeres that were obtained from 4-cell mice embryos that were split during the blastocyst stage., Materials and Methods: Imprinting Control Region (ICR) mice (age: 6-8 weeks), were superovulated and mated with a single fertile male of the same strain. We obtained 2-cell embryos that were then cultured in 4 groups (×4) with Human tubal fluid (HTF) supplemented with 12% fetal bovine serum. When these embryos reached the 4-cell stage, their zonae pellucidae were removed and every single blastomere was isolated by repeated pipetting with Ca/Mg(2+)-free medium. The isolated blastomeres (study group) and the intact embryos (control group) were then cultured to determine the blastocyst formation rate and quality., Results: We collected a total of 936 embryos from 524 morphologically intact, top-grade embryos in the 4-cell stage from 80 stimulated mice. We used 356 of these embryos to isolate the blastomeres. The remaining 168 embryos were cultured as controls. A total of 1312 single blastomeres were obtained and cultured in vitro. Among these, 620 blastocysts were harvested from the original embryos compared with 136 blastocysts that were harvested from the control group. The overall blastocyst formation rate was 174.2% (620 blastocysts from 356 embryos) for the study group compared with 81.5% (136 blastocysts from 168 embryos) for the control group. The study group was 43.3% (268 of 620) top-grade blastocysts compared with 91% (152 of 168) of the control group. Taken together, the percentage of top-grade blastocysts obtained per original embryo in the split group was 75.4% (174.2%×43.3%) compared with 74.2% (81.5%×91%) for the control group., Conclusions: Embryo splitting can increase the number of blastocysts. However, the percentage of available top-grade blastocysts is the same compared with nonsplit embryos. Embryo splitting may not be a cost-effective technique for the generation of high-quality mouse blastocysts., (Copyright © 2012. Published by Elsevier B.V.)

Objective: To study the success rate, predictors for success, and pregnancy outcomes after external cephalic version., Design: Historical cohort study., Setting: Regional hospital, Hong Kong., Patients: All women who had singleton term breech pregnancies at term and opted for external cephalic version during 2001 and 2009. Their demographic data, clinical and ultrasound findings, procedure details, complications, and delivery outcomes were analysed., Main Outcome Measures: Predictive factors for successful external cephalic version., Results: A total of 209 external cephalic versions were performed during the 9-year period. The success rate was 63% (75% for multiparous and 53% for nulliparous women). There was no significant complication. On univariate analysis, predictors of successful external cephalic version were: multiparity, unengaged presenting part, higher amniotic fluid index (≥ 10 cm), thin abdominal wall, low uterine tone, and easily palpable fetal head (subjective assessment by practitioners before external cephalic version). On multivariate analysis, only multiparity, non-engagement of the fetal buttock and thin maternal abdomen were associated with successful external cephalic version. In all, 69% of those who had successful external cephalic version succeeded in the first roll (P<0.001), and 82% of the women with successful external cephalic versions had vaginal deliveries (93% in multiparous and 69% in nulliparous women). Uptake rate of external cephalic version was studied in the latter part of the study period (2006-2009). Whilst 735 women were eligible for external cephalic version, 131 women chose to have the procedure resulting in an uptake rate of 18%., Conclusion: External cephalic version was effective in reducing breech presentations at term and corresponding caesarean section rates, but the uptake rate was low. Further work should address the barriers to the low acceptance of external cephalic version. The results of this study could encourage women to opt for external cephalic version.

Objective: To examine the urinary level of tissue factor (uTF) and its procoagulant activity (PCA) in patients with diabetes mellitus, and explore the relationship between uTF and renal damage in diabetes mellitus., Methods: Eighty-six patients with type 2 diabetes mellitus were divided into 3 groups according to urine albumin excretion (UACR), namely normal albuminuria group, microalbuminuria group and macroalbuminuria group. The levels of uTF, PCA, blood urea nitrogen (BUN), serum creatinine (CRE), serum cystatin C (CYSC), glycohemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were measured in all the patients and 21 healthy controls., Results: Compared with normal control, the diabetic patients showed significantly increased levels of uTF and PCA. The urinary TF-PCA was positively correlated to BUN, CYSC, CRE, UACR, fasting glucose and hs-CRP, but not to uTF; only hs-CRP, UACR were positively correlated to uTF., Conclusion: uTF is probably implicated in the development and progression of diabetic nephropathy.