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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: To observe the efficacy of ursodeoxycholic acid (UDCA) combined with Tongdan: Decoction () on immunological indices and histopathological changes in patients with primary biliary cirrhosis (PBC) of IIor III histological stage. METHODS: Sixty PBC patients were assigned randomly and equally: to the control group treated with UDCA alone and the treatment group treated with UDCA combined with Tongdan Decoction. The immunological indices and histopathological changes were detected before and after 24-week treatment, and the follow-up lasted for 1-3 years. RESULTS: After 24-week treatment, CD4(+)CD28(-) in the peripheral blood was lowered and CD4(+)CD25(+) was increased in both groups, and better effect was shown in the treatment group (P<0.01). The levels of IgM, IgG, and IgA decreased markedly after 96-week treatment in the treatment group (P< 0.05, P< 0.01), while in the control group, only the latter two showed significant decrease after 148 week (all P<0.05). At the end of the 3-year follow-up, the medians of histopathological

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.)

Objective: To examine how mental health interplays with menopausal status in relation to sleep patterns and rest-activity rhythms (RARs) among middle-aged women., Methods: This cross-sectional study recruited 87 women aged 45 to 60 years from community and a gynecology clinic in Taiwan. Participants wore actigraphy devices for 7 days and were also assessed with self-reported questionnaires. Hierarchical regression was used to examine the effects of menopausal status and mental health on sleep and RARs., Results: Perimenopausal and postmenopausal women had higher relative amplitude and interdaily stability of RARs than premenopausal women. There were no differences in actigraphy-based sleep parameters across menopausal statuses. There was no difference in depressive symptoms or loneliness across menopausal statuses. Higher levels of depressive symptoms were significantly associated with longer sleep latency ( β = 0.26, P = 0.022) and wake after sleep onset ( β = 0.28, P = 0.012), and lower sleep efficiency ( β = -0.30, P = 0.008) after adjusting for menopausal status and age. In addition, there was marginal significance of the positive association between loneliness and interdaily stability ( β = 0.18, P = 0.079). A moderating effect ( βmenopausal status*loneliness = -0.40, P = 0.025) showed that lonelier premenopausal women exhibited greater relative amplitude (RA) of rest-activity rhythms, but lonelier menopausal women had lower RA of RAR., Conclusion: Mental health plays an important role for middle-aged women with different menopausal statuses in relation to sleep patterns and RARs., Competing Interests: Financial disclosure/conflict of interest: None reported., (Copyright © 2023 by The Menopause Society.)

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.

Background: Midlife women experience menopausal transition at different ages with a variety of symptoms. This study aimed to identify the effects of age, menopausal status, and symptoms in women on their actigraphy-based sleep patterns and circadian rhythms., Methods: A total of 87 women aged 45-60 from the community and a gynecology clinic in Taiwan who had their sleep and circadian rhythms recorded with a 7-day actigraphy were analyzed. Multiple linear regression was used to estimate the association of age, menopausal status, and symptoms with sleep parameters and circadian rhythms., Results: A sleep efficiency below 85 % was observed in 46.0 % of women, and those with severe somatic-vegetative or psychological symptoms tended to have problems with sleep latency (β = 0.22 and β = 0.42, respectively) and efficiency (β = -0.26 and β = -0.36, respectively). Women with more severe urogenital symptoms only experienced significantly longer sleep latency (β = 0.33). There was a weak correlation between circadian rhythms and symptoms. Additionally, perimenopausal (β = 0.30 and β = 0.35, respectively) and late postmenopausal (β = 0.67 and β = 0.59, respectively) women had higher relative amplitude and stability in circadian rhythms than premenopausal women. Age had no significant effect on sleep parameters or circadian rhythms., Conclusions: Premenopausal women had the most unstable day-to-day rhythms compared to their peri- and postmenopausal counterparts. Women with higher somatic-vegetative, psychological, and urogenital symptoms showed greater sleep problems. Psychological symptoms (e.g., depression, irritability, anxiety, exhaustion) were the strongest predictors for all sleep parameters. The mechanisms underlying these associations warrant investigation., 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 Elsevier B.V. All rights reserved.)

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.

Hypertension is a common chronic disease affecting many people. White matter lesions (WMLs) are one of the imaging features of cerebrovascular disease. Predicting the possibility of developing syncretic WMLs in patients with hypertension may contribute to the early identification of serious clinical conditions. This study aims to build a model to identify patients who suffered from moderate-to-severe WMLs by using recognized WMLs risk factors including age and history of diabetes and a new factor named platelet-to-white blood cell ratio (PWR). A total of 237 patients were included in this study. The Affiliated ZhongDa Hospital of Southeast University Research Ethics Committee approved this study (Ethics No. 2019ZDSYLL189-P01). We developed a nomogram to predict the risk of syncretic WMLs in patients with hypertension using the above factors. Higher total scores on the nomogram indicated a higher risk of syncretic WMLs. This means older age, smaller PWR, and patients suffering from diabetes contributed to a greater chance for the patient to suffer from syncretic WMLs. We used a decision analysis curve(DCA) to determine the net benefit of the prediction model. The DCA we constructed showed that using our model to decide whether patients suffered from syncretic WMLs or not was better than assuming they all suffered from syncretic WMLs or all WMLs-free. As a result, the area under the curve of our model was 0.787. By integrating PWR, history of diabetes, and age, we could estimate integrated WMLs in hypertensive patients. This study provides a potential tool to identify cerebrovascular disease in patients with hypertension., 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 Elsevier B.V. All rights reserved.)

Serotonin (5-HT), a neurotransmitter, is essential for normal and pathological pigmentation processing, and its receptors may be therapeutical targets. The effect and behavior of the 5-HT7 receptor (5-HT7R) in melanogenesis in high vertebrates remain unknown. Herein, we examine the role and molecular mechanism of 5-HT7R in the pigmentation of human skin cells, human tissue, mice, and zebrafish models. Firstly, 5-HT7R protein expression decreased significantly in stress-induced depigmentation skin and vitiligo epidermis. Stressed mice received transdermal serotonin 5-HT7R selective agonists (LP-12, 0.01%) for 12 or 60 days. Mice might recover from persistent stress-induced depigmentation. The downregulation of tyrosinase (Tyr), microphthalmia-associated transcription factor (Mitf) expression, and 5-HT7R was consistently restored in stressed skin. High-throughput RNA sequencing showed that structural organization (dendrite growth and migration) and associated pathways were activated in the dorsal skin of LP-12-treated animals. 5-HT7R selective agonist, LP-12, had been demonstrated to enhance melanin production, dendrite growth, and chemotactic motility in B16F10 cells, normal human melanocytes (NHMCs), and zebrafish. Mechanistically, the melanogenic, dendritic, and migratory functions of 5-HT7R were dependent on the downstream signaling of cAMP-PKA-ERK1/2, JNK MAPK, RhoA/Rab27a, and PI3K/AKT pathway activation. Importantly, pharmacological inhibition and genetic siRNA of 5-HT7R by antagonist SB269970 partially/completely abolished these functional properties and the related activated pathways in both NHMCs and B16F10 cells. Consistently, htr7a/7b genetic knockdown in zebrafish could blockade melanogenic effects and abrogate 5-HT-induced melanin accumulation. Collectively, we have first identified that 5-HT7R regulates melanogenesis, which may be a targeted therapy for pigmentation disorders, especially those worsened by stress., (© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

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.)

Micro-electrochemical machining (micro-ECM) has been widely used for microscale and nanoscale processing of materials. The performance of the nanosecond pulse power supply is directly related to the precision of micro-ECM, which is one of the core technologies for micro-ECM. In this work, a nanosecond pulse power supply, with adjustable pulse frequency, duty cycle, and voltage, was designed with an STM32F103VET6 single-chip microcomputer as the control core and a metal-oxide-semiconductor field-effect transistor as the chopper switch component. The performance test has shown that the power supply can produce a continuous pulse with the highest frequency of 8 MHz, the shortest pulse width of 50 ns, the maximum peak current of 12 A, and the maximum voltage of 10 V. As compared with the power supply reported in the literature, the present power supply demonstrated the enhanced output current and improved waveform of the nanosecond pulse output, which could result in better machining accuracy and efficiency for micro-ECM.

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.)

Purpose: The aim of this study was to validate and compare the prognostic performance of the albumin-bilirubin (ALBI) grade, platelet-albumin-bilirubin (PALBI) grade, Child-Pugh (CP) grade, and Model for End-Stage Liver Disease (MELD) score in predicting the 1-year variceal rebleeding probability using artificial intelligence for patients with cirrhosis and variceal bleeding undergoing early transjugular intrahepatic portosystemic shunt (TIPS) procedures., Materials and Methods: This dual-center retrospective study included two cohorts, with patients enrolled between January 2016 and September 2018 in the training cohort and January 2017 and September 2018 in the validation cohort. In the training cohort, independent risk factors associated with the 1-year variceal rebleeding probability were identified using univariate and multivariate logistic analyses. ALBI-, PALBI-, Child-Pugh-, and MELD-based nomograms and an artificial neural network (ANN) model were established and validated internally in the training cohort and externally in the validation cohort, which included patients with variceal bleeding who were treated with preventive TIPS., Results: A total of 259 patients were included. The median follow-up periods were 24.1 and 18.9 months, and the 1-year variceal rebleeding rates were 12.3% (14/114) and 10.3% (15/145) in the training and validation cohorts, respectively. In the training cohort, all four variables were identified as independent risk factors. Four nomograms were then established and showed comparable prognostic performances after internal (C-index: 0.879, 0.829, 0.874, and 0.798) and external (C-index: 0.720, 0.719, 0.718, and 0.703) validation. The ANN demonstrated that these four variables had comparable importance in predicting the 1-year variceal rebleeding probability., Conclusion: None of the four variables are optimal in predicting the 1-year variceal rebleeding probability for patients with cirrhosis and variceal bleeding undergoing early TIPS., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Objective: To assess the efficacy of a bioabsorbable steroid-eluting sinus stent in improving surgical outcomes when placed in the frontal sinus ostium (FSO) following full endoscopic sinus surgery (ESS) in patients with whole group chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients with whole group CRSwNP who had similar lesions on bilateral sinus between September 2019 and March 2020 in Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Changhai Hospital were chosen. Patients with CRSwNP who underwent extended ESS were randomly assigned to receive a steroid-eluting sinus stent in one FSO whereas the contralateral side received surgery alone. Endoscopic evaluations recorded at 30, 90 days postoperative were graded by an independent assessment panel to assess the need for interventions in the FSO. Semi-quantitative data with CT and endoscopic score were performed by rank sum test. The need for postoperative intervention and the patency rate of FSO were analyzed using the McNemar test. Results: Thirty-one patients with whole group CRSwNP met all eligible criteria, including 17 males and 14 females, with the age of (44.5±11.8) years(x¯±s). Stents were successfully placed in one FSO of all patients. At 30 days post-ESS, the assessment panel reported that steroid-eluting stents reduced the need for postoperative interventions by 41.0% (χ 2 =5.314, P =0.021), the need for oral steroid interventions by 40.0% (χ 2 =4.133, P =0.042) and the need for surgical interventions by 74.8% (χ 2 =4.292, P =0.038) compared to control sinuses with no stents. Clinical surgeons also reported greater diameter of FSO compared to control sinuses at 30 days post-ESS (74.2% vs 48.4%, χ 2 =4.351, P =0.037). These results at 90 days post-ESS were consistent with those at 30 days post-ESS. Conclusion: Bioabsorbable steroid-eluting sinus stents in the FSO can reduce polyp formation, adhesion, and the need for postoperative interventions in FSO of CRSwNP patients and improve the early postoperative outcomes.

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.

Objective: To identify a diagnostic indicator of lumbar spondylolysis visible in plain X-ray films., Methods: One hundred and seventy-two patients with low back pain who received X-ray and computerized tomography (CT) examinations were identified and studied. They were divided into three groups: the spondylosis without spondylolisthesis (SWS) group, comprising 67 patients with bilateral pars interarticularis defects at L5 and without spondylolisthesis, the isthmic spondylolisthesis (IS) group, comprising 74 patients with L5/S1 spondylolisthesis and bilateral L5 pars interarticularis defects, and the control group, comprising 31 patients with low back pain but without spondylolysis. The sagittal diameters of the vertebral arch (SDVAs) of L4 and L5 were measured in lateral X-ray image, and the differences in SDVA between L4 and L5 (DSL4-5) in each case were calculated and analyzed., Results: There were no significant differences in demographic characteristics among the three groups. In the SWS and IS groups, the SDVA of L5 was significantly longer than the SDVA of L4 (p < 0.001), whereas no significant difference found in the control group (p > 0.05). DSL4-5, in which the SDVA of L4 was subtracted from the SDVA of L5, significantly differed among the three groups (p < 0.001), and the normal threshold was provisionally determined to be 1.55 mm., Conclusions: In bilateral L5 spondylolysis, the SDVA of L5 is wider than the SDVA of L4, and this difference is greater in isthmic spondylolisthesis. This sign in lateral X-rays may provide a simple and convenient aid for the diagnosis of spondylolysis.

As Traditional Chinese Medicine (TCM) becomes widely used in many countries around the world, global demand for intelligent and modernized medical devices of TCM is increasing. Medical devices of TCM have played an important role in diagnosis and treatment of disease. Standardization on medical devices of TCM cannot only be beneficial to ensuring the life safety of patients, but also to enhancing the effectiveness of diagnosis and treatment. This paper includes (1) classification and trends in medical devices of TCM; (2) status review on international standardization of medical devices of TCM; (3) key technical factors in developing international standards for medical devices of TCM and (4) prospects for international standardization development of medical devices of TCM., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

Beef is a common staple food in many countries, and there is a growing concern over misinformation of beef products, such as false claims of origin, species and production methods. In this study, we used a mass spectrometry-based metabolomics approach to study the metabolite profiles of beef samples purchased from local retailers in Hong Kong. Using multivariate analysis, beef samples from different a) geographical origins, namely the United States (US), Japan and Australia, and b) feeding regimes could be differentiated. We identified twenty-four metabolites to distinguish beef samples from different countries, ten metabolites to identify Angus beef samples from others and seven metabolites to discriminate Australian beef produced by the organic farming from that produced using other farming modes. Based on results of this study, it is concluded that metabolomics provides an efficient strategy for tracing and authenticating beef products to ensure their quality and to protect consumer rights., 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 © 2020. Published by Elsevier Ltd.)

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 .

Objective: To study the role of neutrophil density and molecular mechanism in neutrophils-mediated inflammatory response induced by monosodium urate (MSU) crystals. Methods: Polymorphonuclear neutrophils (PMNs) isolated from healthy human peripheral blood were treated with MSU crystals at different density (5×10(6)/ml, 20×10(6)/ml, 100×10(6)/ml) in vitro. The mean fluorescence intensity (MFI) of PMNs and production of reactive oxygen species (ROS) were detected by flow cytometry. The distribution of MSU crystals was observed by polarized light microscopy. The neutrophil extracellular traps (NETs) formation was detected by immune fluorescence. The cytokines in cell supernatant were measured by beads assay including interleukin 1β (IL-1β) , tumor necrosis factor α (TNFα) , interleukin 8 (IL-8) , interferon inducible protein 10 (IP-10) , macrophage inflammatory protein 1 (MIP-1) , monokine induced by interferon-γ (MIG) , macrophage inflammatory protein 1α (MIP-1α) , macrophage inflammatory protein 1β (MIP-1β) . Results: (1) After MSU crystal intervention, the side scatters (SSC) of neutrophils with medium-cell density (20×10(6)/ml) and high-cell density (100×10(6)/ml) were 128±13 and 93±9 respectively, both significantly lower than 170±19 in low-cell density (5×10(6)/ml) group.(2) Similarly, compared with low-cell density group, the MFI (lucifer yellow) of PMNs with high-cell density was 1.8±0.2, also significantly decreased ( P< 0.05). When co-treated with oxygenated adenosine triphosphate (oxATP), MFI of PMNs were all enhanced consistently. (3) In MSU crystals stimulated PMNs, after adding 2',7'-dichlorodihydrofluorescein diacetate, the MFI values were 0.85±0.32, 2.49±0.78, 4.54±1.02 in low cell density groups, medium cell density groups, and high cell density groups respectively, indicating that the generation of ROS was positively correlated with the increase of PMN density ( P< 0.05). After the intervention of oxATP, the ROS production was significantly reduced. (4) MSU crystal induced NETs formation, especially at high cell density. NETs formation promotes MSU crystal aggregation, which could be partially overcome by oxATP pretreatment. (5) The expression of cytokines were all significantly decreased in the supernatant of PMNs at high cell density exposed to MSU crystals compared with PMNs at medium cell density ( P< 0.05) . Conclusion: The PMN-mediated inflammation induced by MSU crystals is cell density dependent, and ATP may play a role in partially overcoming the process.

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.

Six pigs underwent implantation of a portal vein infusion port by transjugular access. The technical success rate was 100% (n = 6), with no surgical complications or deaths. At 1 month after implantation, the catheter tip had moved from the splenic vein to the main portal vein, while the catheter protruded into the right ventricle through the right atrium in all cases. Hence, the infusion port system has not been used in clinical practice due to its obvious displacement after implantation. However, this study provides a new idea for future exploration of portal vein infusion pathways., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

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.)

Curcumin, a major yellow pigment and spice in turmeric and curry, has been demonstrated to have an anticancer effect in human clinical trials. Mutation of KRAS has been shown in 35%-45% of colorectal cancer, and regorafenib has been approved by the US FDA to treat patients with colorectal cancer. Synthetic lethality is a type of genetic interaction between two genes such that simultaneous perturbations of the two genes result in cell death or a dramatic decrease of cell viability, while a perturbation of either gene alone is not lethal. Here, we reveal that curcumin significantly enhanced the growth inhibition of regorafenib in human colorectal cancer HCT 116 cells (KRAS mutant) to a greater extent than in human colorectal cancer HT-29 cells (KRAS wild-type), producing an additive or synergistic effect in HCT 116 cells and causing an antagonistic effect in HT-29 cells. Flow cytometric analysis showed that the addition of curcumin elevated apoptosis and greatly increased autophagy in HCT 116 cells but not in HT-29 cells. Mechanistically, curcumin behaved like MEK-specific inhibitor (U0126) to enhance regorafenib-induced growth inhibition, apoptosis and autophagy in HCT 116 cells. Our data suggest that curcumin may target one more gene other than mutant KRAS to enhance regorafenib-induced growth inhibition (synthetic lethality) in colorectal cancer HCT 116 cells, indicating a possible role of curcumin in regorafenib-treated KRAS mutant colorectal cancer., (Copyright © 2019 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.

Lung adenocarcinoma (LAD) is the leading cause of cancer death worldwide. Long noncoding RNAs (lncRNAs) have been shown to play an important regulatory role in cancer biology, including that of LAD. The aim of this experiment was to explore the interaction of LINC00483, microRNA-144 (miR-144), and homeobox A10 (HOXA10), and their effects on radio sensitivity and epithelial-mesenchymal transition (EMT) of LAD. Initially, microarray analysis was used to screen out miRNAs and lncRNAs, as well as the differentially expressed genes related to LAD. Following the screening process, the targeting relationship of LINC00483, miR-144, and that of miR-144 and HOXA10 was determined. Following that, the expression of LINC00483, miR-144, messenger RNA (mRNA), as well as protein expression of HOXA10, MMP-2, MMP-9, E-cadherin, vimentin, and N-cadherin that followed in cells was determined. Also, the effect of LINC00483 on cell migration and invasion ability, and cell tumorigenic ability was detected. LINC00483 and HOXA10 were found to be upregulated whereas miR-144 was downregulated in LAD. Silencing of LINC00483 could competitively bind to miR-144, thereby upregulating HOXA10. LINC00483 or HOXA10 silencing led to decreased HOXA10, MMP-2, MMP-9, vimentin, and N-cadherin but elevated miR-144 and E-cadherin. Moreover, after being transfected with silenced LINC00483, the cell proliferation, migration, and invasion were inhibited with enhanced radiosensitivity. Consequently, the data of the study indicates that interference of LINC00483 weakens its competitive binding ability to miR-144, thus reducing HOXA10 expression, and enhancing radiosensitivity in LAD., (© 2019 Wiley Periodicals, Inc.)