Search

Lysine-specific demethylase 1 (LSD1) is an important histone demethylase that mediates epithelial to mesenchymal transition (EMT). The E239K mutation of LSD1 was identified in a luminal breast cancer patient from the COSMIC Breast Cancer dataset. To investigate the functional effects of the E239K mutation of LSD1, a stable LSD1 knockdown MCF7 cell line was generated. Rescue with WT LSD1, but not E239K mutated LSD1, suppressed the invasion and migration of the LSD1 knockdown cells, indicating that the E239K mutation abolished the suppressive effects of LSD1 on the invasion and migration of MCF7 cells. Further analysis showed that the E239K mutation abolished LSD1-mediated invasion and migration of MCF7 cells through downregulation of estrogen receptor α (ERα). Most importantly, the E239K mutation disrupted the interaction between LSD1 and GATA3, which reduced the enrichment of LSD1 at the promoter region of the ERα gene; the reduced enrichment of LSD1 at the promoter region of the ERα gene caused enhanced histone H3K9 methylation, which subsequently suppressed the transcription of the ERα gene. In summary, the E239K mutation abolishes the suppressive function of LSD1 on migration and invasion of breast cancer cells by disrupting the interaction between LSD1 and GATA3.

Background Acupuncture is an important component of traditional Chinese medicine which is used to treat an array of health conditions. This study evaluates the effectiveness of acupuncture in the management of restless leg syndrome (RLS). Methods A comprehensive literature survey was conducted in electronic databases to identify studies evaluating the effectiveness of acupuncture in the treatment of RLS. Cure, marked effect, effective, ineffective, and total effective rates of individual studies were pooled to achieve their respective overall estimates and a meta-analysis of mean change from baseline in International Restless Legs Syndrome Rating Scale (IRLSRS) was performed. Results A total of 18 studies were included in this meta-analysis, among which 640 RLS patients were treated with acupuncture alone or combined with other therapies (acupuncture group) and 447 RLS patients were treated with non-acupuncture therapies (control group). Cure, marked effect, and effective rates were 47.8% [95% confidence interval (CI): 38.3% to 57.3%], 27.4% (95% CI: 20.3% to 34.8%), and 24.2% (95% CI: 16.9% to 31.5%) in patients treated with acupuncture either alone or combination with other treatments, and 21.7% (95% CI: 20.7% to 22.7%), 28.0% (95% CI: 20.0% to 32.9%), and 22.3% (95% CI: 17.0% to 27.6%) in patients treated with non-acupuncture therapies, respectively. The ineffective rate was 4.7% (95% CI: 4.3% to 5.0%) in the acupuncture group and 32.9% (95% CI: 22.2% to 43.7%) in non-acupuncture groups. IRLSRS scores improved significantly after acupuncture treatment [mean change from baseline -9.45 (95% CI: -18.42 to -0.49); P=0.04]. Discussion Although the overall quality of the included studies was low, the results of this meta-analysis suggested that acupuncture is an effective treatment option for RLS. Well-designed randomized controlled trials especially those involving a sham-acupuncture arm are needed to confirm these outcomes.

The c.194+2 TC variant of serine protease inhibitor Kazal type 1 (SPINK1) is a known genetic risk factor found in Chinese patients with idiopathic chronic pancreatitis (ICP), but the early-onset mechanisms of ICP are still unclear.Complementary experimental approaches were used to pursue other potential pathologies in the present study. The serum level of SPINK1 of ICP patients in the Han population in China was detected and verified by an enzyme-linked immunosorbent assay. Next, differentially expressed proteins and microRNAs from plasma samples of early-onset and late-onset ICP patients were screened by proteomic analysis and microarray, respectively.Combined with these advanced methods, the data strongly suggest that the regulatory effects of microRNAs were involved in the early-onset mechanism of the ICP by in vitro experiments. There was no significant difference in the plasma SPINK1 expression between the early-onset ICP and the late-onset patients. However, the expression of plasma glutathione peroxidase (GPx3) in early-onset ICP patients was markedly lower than that in late-onset ICP patients, although the level of hsa-miR-323b-5p was lower in late-onset patients compared to the early-onset ICP group. In vitro experiments confirmed that hsa-miR-323b-5p could increase apoptosis in caerulein-treated pancreatic acinar cells and inhibit the expression of GPx3.The up-regulated hsa-miR-323b-5p might play a crucial role in the early-onset mechanisms of ICP by diminishing the antioxidant activity through the down-regulation of GPx3.

Polystyrene nanoplastics (PS NPs) contamination is a serious problem for human and animal health. Excessive exposure to PS NPs can affect the structure and function of the heart. And lipopolysaccharide (LPS) induces myocardial damage, leading to myocardial fibrosis (MF). To investigate whether PS NPs exacerbate LPS-induced myocardial autophagy and fibrosis, we established in vivo and in vitro models of PS NPs/LPS exposure alone and in combination. We found that PS NPs/LPS exposure disrupts myocardial structure, significantly increases reactive oxygen species (ROS), triggers oxidative stress, promotes TGF-β1/Smad pathway activation, and leads to elevated levels of fibrotic proteins and collagen. Meanwhile, activation of AMPK/mTOR/ULK1 signaling pathway induced autophagy onset, and combined exposure of PS NPs/LPS exacerbated MF and autophagy. H9C2 cells were used for in vitro experiments, and the experimental results showed that the addition of TGF-β receptor inhibitor LY2109761 to the exposed group not only inhibited the upregulation of fibrotic genes but also effectively reduced the expression of autophagic signals, indicating that combined exposure of PS NPs and LPS mediates and regulates cardiac autophagy through TGF-β1. The above results suggest that PS NPs exacerbate LPS-induced MF and autophagy in mice via ROS/TGF-β1/Smad. Our study provides some new evidence to clarify the potential mechanisms of PS NPs-induced cardiotoxicity.

ObjectiveHospital workplace violence is one of the most frequently reported types of workplace violence in the world, and it harms the mental and physical health of medical staff. Existing research on workplace violence focused more on cross-sectional studies, than longitudinal studies. Therefore, this study examined the dynamic impact of hospital workplace violence on the mental health of medical staff, with the aim of providing appropriate countermeasures and suggestions for hospitals to develop targeted psychological intervention measures in time for medical staff who experience workplace violence.DesignA prospective cohort study.ParticipantsA total of 112 medical staff who had experienced workplace violence in the hospital for the first time were chosen.SettingAn unconditional latent variable growth curve model was established based on the average value of the general health scale scores of medical staff, and gender and violence types (intimidation threats, physical violence) as control variables. Each medical staff was assessed for depression and anxiety at 4 different time points and the changes in the trajectories was observed.ResultsThere were significant differences in the incidence of mental health and anxiety among medical staff at different observation times. There were significant individual differences in the initial mental health status, growth rate of anxiety and depression of medical staff.ConclusionsHospitals should undertake various psychological intervention strategies based on the staff's mental health to safeguard those who have experienced workplace violence.

Despite recent in advances in the management of nasopharyngeal carcinoma (NPC), development of targeted therapy remains challenging particularly in patients with recurrent or metastatic disease. To search for clinically relevant targets for the treatment of NPC, we carried out parallel genome-wide functional screens to identified essential genes that are required for NPC cells proliferation and cisplatin resistance. We identified lymphocyte-specific protein tyrosine kinase (LCK) as a key vulnerability of both proliferation and cisplatin resistance. Depletion of endogenous LCK or treatment of cells with LCK inhibitor induced tumor-specific cell death and synergized cisplatin sensitivity in EBV-positive C666-1 and EBV-negative SUNE1 cells. Further analyses demonstrated that LCK is regulating the proliferation and cisplatin resistance through activation of signal transducer and activator of transcription 5 (STAT5). Taken together, our study provides a molecular basis for targeting LCK and STAT5 signaling as potential druggable targets for the management of NPC.

Based on the standards for wireless sensor system identification, the sensor node identity OID identification and the management object OID identification in the SNMP MIB are merged, and a management object OID identification coding mechanism for the SNMP-based wireless sensor system is proposed to make the node management system only. The identity, attributes, and multiple entities of the target sensor node in the wireless sensor network can be identified and managed by the node management object OID. The source of abnormal medical big data generally uses two models of multidimensional data and sliding window for detection and verification. First, the sliding window can be used to detect abnormalities. The result is that under this condition, the detection rate of medical big data is more than 95%; the effect is very good, but in different dimensions, the detection rate of four-dimensional data is 2.9% higher than that of a single-dimensional one. On the basis of the ZigBee wireless network, the terminal signal transmission of fracture treatment can be realized. On this basis, combined with the actual needs of fracture treatment, it can be built with its wireless module. The wireless network has a certain basic function. The reform of the nursing system was carried out on the basis of the safety and reliability of the nursing system, the efficiency of the nursing system was improved, and timely and safe nursing services were achieved.

Prostate cancer (PCa) is a frequent malignant tumor worldwide with high morbidity along with mortality. MicroRNAs (miRNAs) have been identified as key posttranscriptional modulators in diverse cancers. Herein, we purposed to explore the impacts of miR-363-3p on PCa growth, migration, infiltration along with apoptosis.The expressions of miR-363-3p along with Dickkopf 3 (DKK3) were assessed in clinical PCa specimens. We adopted the PCa cell line PC3 and transfected it using miR-363-3p repressors or mimic. The relationship of miR-363-3p with DKK3 was verified by a luciferase enzyme reporter assay. Cell viability along with apoptosis were determined by MTT assay coupled with flow cytometry analysis. Cell migration along infiltration were detected via wound healing, as well as Transwell assays. The contents of DKK3, E-cadherin, vimentin along with N-cadherin were analyzed via Western blotting accompanied with qRT-PCR.MiR-363-3p was found to be inversely associated with the content of DKK3 in clinical PCa specimens. Further investigations revealed that DKK3 was miR-363-3p's direct target. Besides, overexpression of miR-363-3p decreased the contents of DKK3, promoted cell viability, migration coupled with infiltration, and reduced cell apoptosis, while silencing of miR-363-3p resulted in opposite influence. Upregulation of miR-363-3p diminished E-cadherin contents but increased vimentin along with N-cadherin protein contents in PC3 cells; in contrast, miR-363-3p downregulation produced the opposite result.Our study indicates that miR-363-3p promotes PCa growth, migration coupled with invasion while dampening apoptosis by targeting DKK3.

The aim of the study was to identify the effects of combined motor imagery and action observation therapy on vascular cognitive impairment.Thirty vascular cognitive impairment patients were randomly assigned into three groups. Cognitive training group was given conventional cognitive training, motor imagery + action observation group was treated with motor imagery and action observation therapy, and mixed therapy group was given conventional cognitive training and motor imagery + action observation therapy, for 8 wks continuously. The Montreal Cognitive Assessment Scale, Rivermead Behavioral Memory Test, and event-related potential were used to evaluate the cognitive function at baseline, 4- and 8-wk posttreatment, and 1-mo follow-up.There were significant time × group interactions in Montreal Cognitive Assessment Scale (F6,4.20 = 8.38, P0.001), event-related potential latent period (F6,294.24 = 5.10, P0.001), event-related potential amplitude (F6,1.68 = 23.08, P0.001), and Rivermead Behavioral Memory Test (F6,312.61 = 5.42, P0.001). Intragroup comparisons showed that Montreal Cognitive Assessment Scale and Rivermead Behavioral Memory Test scores and event-related potential amplitude increased significantly (P0.05), and event-related potential latency decreased significantly (P0.05) in all groups. Intergroup comparisons showed that the changes of all outcomes in mixed therapy group were greater than those in cognitive training and motor imagery + action observation group (P0.05) after treatment.These results suggest that the combination of cognitive training with motor imagery and action observation therapy is an effective treatment on cognitive function in people with vascular cognitive impairment.

Objective: Hospital violence remains a global public health problem. This study aims to analyze serious hospital violence causes in China and the characteristics of perpetrators. It likewise seeks to understand frontline personnel's needs and put forward targeted suggestions.Methods: Serious hospital violence cases from 2011 to 2020 in the China Judgment Online System (CJOS) were selected for descriptive statistical analysis. A total of 72 doctors, nurses, hospital managers, and security personnel from 20 secondary and tertiary hospitals in China were selected for semi-structured interviews.Results: Of the incidents, 62.17% were caused by patients' deaths and dissatisfaction with their treatment results. Moreover, it was found that out-of-hospital disputes (11.14%) were also one of the main reasons for serious hospital violence. The perpetrators were mainly males (80.3%), and had attained junior high school education or lower (86.5%). Furthermore, most of them were family members of the patients (76.1%). Healthcare workers urgently hope that relevant parties will take new measures in terms of legislation, security, and dispute handling capacity.Conclusion: In the past 10 years, serious hospital violence's frequency in China has remained high. Furthermore, their harmful consequences are more serious. The causes of hospital violence are diverse, and the characteristics of perpetrators are obvious. Frontline healthcare workers urgently need relevant parties to take effective measures in terms of legislation, security, and dispute handling capacity, to prevent the occurrence of violence and protect medical personnel's safety.

Background Chronic kidney disease (CKD) is a major global health problem. Short-term self-management has been considered to effect some renal and psychological endpoints. However, there are currently very few studies about self-management for CKD that a) have been scientifically designed by a theory-based framework and b) that evaluate the long-term effects and working mechanism. This study presents the rationale and design of a theory-based cohort study to explore how this self-management intervention works and its effectiveness on the Chinese CKD population. Methods In this ambispective intervention cohort study,1,200 patients with CKD stages 1–5 will be recruited from July 2015 to July 2024 in 3 branches of Guangdong Provincial Hospital of Chinese Medicine (GPHCM) in Guangdong province, China. The patients in the self-management cohort will choose to receive an intervention that consists of education, nutrition/diet modification, lifestyle change recommendation, medication review, and psychology support based on Social Cognition Theory (SCT). The patients in the control cohort will do regular follow-ups based on the clinic rules. All the patients will be followed up for 5 years, or until the occurrence of a primary outcome. Detailed clinical, laboratory markers, nutritional status, psychological exposures and outcome questionaries will be collected semiannually in CKD stage 1–2 and trimonthly in stage 3–5 patients. The primary outcome is the occurrence of composite clinical endpoints (doubling of serum creatinine level, ESKD, loss of renal function (≥ 40% decline in GFR from baseline), death, major cardiovascular or cerebrovascular events). The main secondary outcomes include the absolute change and slope of eGFR, absolute changes of urinary protein creatinine ratio, 24-h urine proteinuria, intact parathyroid hormone level, and self-management adherence rate and quality of life from baseline to end of the study. The effectiveness of self-management will be analyzed and the association between longitudinal trajectories of self-management and renal outcomes will be evaluated. Discussion This study aims to provide further evidence for the effectiveness of theory-based self-management in CKD patients and to improve the lives of patients with CKD by slowing progression, improving psychological well-being and overall quality of life. Trial registration Chinese Clinical Trial Register (ChiCTR1900024633). 19 July, 2019. http://www.chictr.org.cn/showproj.aspx?proj=38378

Glutamate transporter-1 (GLT-1) removes most glutamate in the synaptic cleft. Sulbactam confers neuronal protection against ischemic insults in the hippocampal CA1 region accompanied by the upregulation of GLT-1 expression in rats. The present study further investigates the effect of sulbactam on the binding property and uptake capacity of GLT-1 for glutamate, and the change in extracellular glutamate concentration in the hippocampal CA1 region of rats with global brain ischemia. The binding property and uptake capacity of GLT-1 were measured using a radioligand binding and uptake assay, respectively, with L-3H-glutamate. The extracellular glutamate concentration was detected using microdialysis and high-performance liquid chromatography-mass spectrometry. Neuropathological evaluation was performed based on thionin staining. It was shown that sulbactam pre-treatment changed GLT-1 binding property, including increased Bmax and decreased Kd values, increased GLT-1 uptake capacity for glutamate, and inhibited the elevation of extracellular glutamate concentration in rats with global cerebral ischemia. These effects of sulbactam were accompanied by its neuronal protection on the hippocampal CA1 neurons against delayed neuronal death resulted from ischemic insult. Furthermore, administration of GLT-1 antisense oligodeoxynucleotides, which inhibited the expression of GLT-1, blocked the aforementioned sulbactam-related effects, which suggested that GLT-1 upregulation mediated the above effect although other mechanisms independent of the upregulation of GLT-1 expression could not be excluded. It could be concluded that sulbactam improves the binding property and uptake capacity of GLT-1 for glutamate and then reduces the glutamate concentration and excitotoxicity during global cerebral ischemia, which contributes to the neuroprotection of sulbactam against brain ischemia.

Ischemia-reperfusion injury (IRI) is the key reason of injury after testicular torsion and may eventually lead to male infertility. Oleuropein, a natural antioxidant isolated from Olea europaea, has shown beneficial effects in different models of ischemia. We evaluated the effects of oleuropein on testicular IRI and explored the underlying protective mechanisms.A mouse testicular torsion/detorsion (T/D) model and an oxygen-glucose deprivation/reperfusion (OGD/R) germ cell model were established and treated with oleuropein. HE staining was used to evaluate testicular pathological changes. Apoptosis and apoptosis-associated protein levels in testis tissues were assessed by TUNEL staining, immunohistochemical staining and western blot. Apoptosis levels and apoptosis-associated protein levels in GC-1 were evaluated by flow cytometry, immunofluorescence and western blot. Oxidative stress levels were assessed by malondialdehyde (MDA) and superoxide dismutase (SOD) kits. Cell viability and inflammatory protein levels were evaluated by CCK-8 assay coupled with qRT-PCR.Relative to the control group, SOD activity was markedly suppressed, while MDA, Bax, Caspase-3, TNF-α as well as IL-1β levels were significantly increased in the T/D model and OGD/R model. However, all of the aforementioned alterations were relieved by oleuropein treatment.Our findings indicate that oleuropein may be a promising treatment option to attenuate testicular IRI via its anti-oxidant, anti-inflammatory as well as anti-apoptotic properties.

Background: Despite the continued development of modern medicine, chronic wounds are still a critical issue in clinical treatment, placing a great physiological, psychological, and financial burden on patients. Researchers have investigated many methods to solve this problem, with bioactive peptides gaining increasing attention due to their considerable advantages and diverse functions, as well as low cost, simple storage, and easy transportation. Methods: In this research, a novel peptide (named OA-FF10) was identified from the skin secretions of the odorous frog species Odorrana andersonii. The sequence of mature OA-FF10 was “FFTTSCRSGC”, which was produced by the post-translational processing of a 61-residue prepropeptide. Results: Similar to most frog peptides, OA-FF10 showed an intramolecular disulfide bridge at the C-terminus. OA-FF10 demonstrated no antibacterial, antioxidant, hemolytic, or acute toxic activity, but promoted wound healing and proliferation of human keratinocytes (HaCaT) both time- and dose-dependently. Furthermore, while OA-FF10 had no effect on wound healing of Human Skin Fibroblasts (HSF), it did accelerate healing in a full-thickness skin-wound mouse model. Conclusion: Our research revealed the strong wound-healing activity of OA-FF10 in vivo and in vitro, thus providing a new candidate for the development of novel wound-healing drugs.

Alzheimer's disease (AD) is a neurodegenerative disease that leads to progressive loss of neurons which often results in deterioration of memory and cognitive function. The development of AD is highly associated with the formation of senile plaques and neurofibrillary tangles. Amyloid β (Aβ) induces neurotoxicity and contributes to the development of AD. Recent evidences also highlighted the importance of neuroglobin (Ngb) in ameliorating AD. This study assessed the ability of fucosterol, a phytosterol found in brown alga, in protecting SH-SY5Y cells against Aβ-induced neurotoxicity. Its effects on the mRNA levels of APP and Ngb as well as the intracellular Aβ levels were also determined in Aβ-induced SH-SY5Y cells. SH-SY5Y cells were exposed to fucosterol prior to Aβ treatment. The effect on apoptosis was determined using Annexin V FITC staining and mRNA expression was studied using RT-PCR. Flow cytometry confirmed the protective effects of fucosterol on SH-SY5Y cells against Aβ-induced apoptosis. Pretreatment with fucosterol increased the Ngb mRNA levels but reduced the levels of APP mRNA and intracellular Aβ in Aβ-induced SH-SY5Y cells. These observations demonstrated the protective properties of fucosterol against Aβ-induced neurotoxicity in neuronal cells.

ObjectivesTo develop and validate a nomogram model to predict chronic kidney disease (CKD) stages 3–5 prognosis.DesignA retrospective cohort study. We used univariate and multivariate Cox regression analysis to select the relevant predictors. To select the best model, we evaluated the prediction models’ accuracy by concordance index (C-index), calibration curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). We evaluated the clinical utility by decision curve analysis.SettingChronic Disease Management (CDM) Clinic in the Nephrology Department at the Guangdong Provincial Hospital of Chinese Medicine.ParticipantsPatients with CKD stages 3–5 in the derivation and validation cohorts were 459 and 326, respectively.Primary outcome measureRenal replacement therapy (haemodialysis, peritoneal dialysis, renal transplantation) or death.ResultsWe built four models. Age, estimated glomerular filtration rate and urine protein constituted the most basic model A. Haemoglobin, serum uric acid, cardiovascular disease, primary disease, CDM adherence and predictors in model A constituted model B. Oral medications and predictors in model A constituted model C. All the predictors constituted model D. Model B performed well in both discrimination and calibration (C-index: derivation cohort: 0.881, validation cohort: 0.886). Compared with model A, model B showed significant improvement in the net reclassification and integrated discrimination (model A vs model B: NRI: 1 year: 0.339 (−0.011 to 0.672) and 2 years: 0.314 (0.079 to 0.574); IDI: 1 year: 0.066 (0.010 to 0.127), pConclusionsWe constructed a prediction model to predict the prognosis of patients with CKD stages 3–5 in the first and second year. Applying this model to clinical practice may guide clinical decision-making. Also, this model needs to be externally validated in the future.Trial registration numberChiCTR1900024633 (http://www.chictr.org.cn).

Few studies have assessed knee range of motion (ROM) and moments of patients with mobile-bearing unicompartmental knee arthroplasty (MB UKA) during active deep flexion activities. We analyze knee kinematic and kinetic parameters during postoperative squatting-standing activity, aiming to evaluate the efficacy of MB UKA and postoperative rehabilitation progress. This was a clinical cohort study. We followed up with 37 patients diagnosed with medial knee osteoarthritis (OA) with primary UKA. After screening 31 patients were recruited to take gait tests. Squatting-standing activities were performed under the test of 10-camera motion analysis system and force plates preoperatively at different stages after UKA (12, 18, and 24 months). The average duration of follow-up was 24.4 months (from 22.8 to 26.7 months). Hip-knee-ankle angle improved significantly compared with pre-UKA as well as scores of American Knee Society Score, numeric rating scale, ORS, and Western Ontario and McMasters. University Osteoarthritis Index. About 83.6% (31/37) of follow-up patients completed squatting-standing activity independently. At 1-year follow-up, peak varus angle (20.6 ± 2.8 degrees), internal rotation angle (13.6 ± 1.8 degrees), extensor moment (1.44 ± 0.04N*m/kg), and internal rotator moment (0.02 ± 0.005N*m/kg) of UKA knees were inferior to contralateral knees. Peak adductor moment (0.76 ± 0.05N*m/kg) was superior to contralateral knees. At 2-year follow-up, peak flexion angle (125.0 ± 2.8 degrees) showed a growing trend meanwhile extensor (1.70 ± 0.03N*m/kg) and adductor (0.68 ± 0.06 N*m/kg) moment closely resembled those of the contralateral knee. MB UKA could alleviate the affected knee mainly in flexion-extension ROM and moment meanwhile did not affect the biomechanical indicators of healthy limbs. OA knees in the early postoperative period showed decreased extensor moment and increased adductor moment during active deep flexion activity. Better ROM and relatively more natural extensor and adductor moment of UKA knee with rehabilitation time increasing may predict ideal rehabilitation outcome in the medium or longer term.

To compare the therapeutic effect of electroacupuncture (EA) of single-acupoint Zusanli (ST36) and multi-acupoints Zusanli (ST36), Shangjuxu (ST37) and Neiguan (PC6) in promoting the recovery of gastrointestinal movement in laparoscopic cholecystectomy (LC) patients undergoing general anesthesia.A total of 70 LC patients (American Society of Anesthesiologists [ASA] grade I and II) were recruited and randomly divided into control (Compared to the control group, the time of borborygmus recovery, first anal exhaust and defecation were markedly earlier in both single ST36 and ST36＋ST37＋PC6 groups (EA of both single ST36 and ST36＋ST37＋PC6 can promote gastrointestinal function recovery in LC patients, without remarkable difference between them.

To evaluate the effectiveness and safety of cervical spondylosis formula granules in reducing the symptoms of patients with the nerve root type and the vertebral artery type of cervical spondylosis.This was a multicenter, single-blind, randomized, controlled trial. From April 2002 to November 2003, 499 patients were randomly assigned to either the treatment or the control group. The treatment group was orally administered granules prepared with a formula for cervical spondylosis, while the control group was given Jingfukang granules. The treatment course was 1 month for both groups.In patients with the nerve root type of cervical spondylosis, the total effect rate in the treatment group (87.21% ) was significantly higher than that in the control group (80.70%, P0.01). After the treatment period in both groups, the treatment group had a significantly greater rate of resolution of pain, numbness of the upper limbs, muscle strength of the upper limbs, and fatigue than the control group (all P0.05). In patients with the vertebral artery type of cervical spondylosis, the total effect rate in the treatment group (82.07%) was similar to that in the control group (71.21% , P0.05). After the treatment period in both groups, the treatment group had a significantly greater rate of resolution of weakness of the waist and knees than the control group (P0.05).The cervical spondylosis formula granules significantly improve numbness, muscle strength, and fatigue, and reduce pain in patients with the nerve root type of cervical spondylosis, and improve the weakness of the waist and knees in patients with the vertebral artery type of cervical spondylosis.

We investigated the adoption of World Health Organization (WHO) naming of COVID-19 into the respective languages among the Group of Twenty (G20) countries, and the variation of COVID-19 naming in the Chinese language across different health authorities. On May 7, 2020, we identified the websites of the national health authorities of the G20 countries to identify naming of COVID-19 in their respective languages, and the websites of the health authorities in mainland China, Hong Kong, Macau, Taiwan and Singapore and identify their Chinese name for COVID-19. Among the G20 nations, Argentina, China, Italy, Japan, Mexico, Saudi Arabia and Turkey do not use the literal translation of COVID-19 in their official language(s) to refer to COVID-19, as they retain “novel” in the naming of this disease. China is the only G20 nation that names COVID-19 a pneumonia. Among Chinese-speaking jurisdictions, Hong Kong and Singapore governments follow the WHO’s recommendation and adopt the literal translation of COVID-19 in Chinese. In contrast, mainland China, Macau, and Taiwan refer to COVID-19 as a type of pneumonia in Chinese. We urge health authorities worldwide to adopt naming in their native languages that are consistent with WHO’s naming of COVID-19.

BACKGROUND: In perioperative settings, formal frailty assessment has been shown to reduce mortality. This study examined the cost-effectiveness associated with a frailty assessment initiative among patients aged 65 with coronary artery disease who are under consideration for CABG. METHODS: A combined decision tree and Markov model was developed to estimate costs and quality-adjusted life years (QALYs) over a 21-year time horizon. Clinical parameters were obtained from published literature. Utilities were derived from the published literature and Canadian Community Health Survey. Costs were obtained from the Ontario fee schedule and published literature. Sensitivity analysis and scenario analysis were conducted to assess the robustness of results. Expected value of perfect information (EVPI) analysis was conducted to estimate the expected value of further research. RESULTS: The frailty assessment initiative had a lower average cost per patient than no frailty assessment ($19,567 compared to $20,062). QALYs with frailty assessment were 6.82, which was 0.47 years more than with no frailty assessment. Frailty assessment was dominant compared to no frailty assessment. Results were robust to changes in the input parameters. Probabilistic sensitivity analysis showed frailty assessment was cost-effective. At a willingness to pay (WTP) threshold of $50,000/QALY, there was 100% probability of frailty assessment being cost-effective and the EVPI per patient was $0. Scenario and sensitivity analysis showed frailty screening remained cost-effective when changing the cohort average age, removing health benefits for non-frail patients and using subjective judgement to modify effectiveness parameters. CONCLUSIONS: Frailty assessment may be good value for money. However, when considering the the Ontario health care system, and limited availability of geriatric consultation services, inadequate health system capacity may hinder full implementation of frailty assessment. Thus, the estimated benefits of frailty screening may not be achievable in practice.

Accurate detection of copy number variations (CNVs) from short-read sequencing data is challenging due to the uneven distribution of reads and the unbalanced amplitudes of gains and losses. The direct use of read depths to measure CNVs tends to limit performance. Thus, robust computational approaches equipped with appropriate statistics are required to detect CNV regions and boundaries. This study proposes a new method called CNV_IFTV to address this need. CNV_IFTV assigns an anomaly score to each genome bin through a collection of isolation trees. The trees are trained based on isolation forest algorithm through conducting subsampling from measured read depths. With the anomaly scores, CNV_IFTV uses a total variation model to smooth adjacent bins, leading to a denoised score profile. Finally, a statistical model is established to test the denoised scores for calling CNVs. CNV_IFTV is tested on both simulated and real data in comparison to several peer methods. The results indicate that the proposed method outperforms the peer methods. CNV_IFTV is a reliable tool for detecting CNVs from short-read sequencing data even for low-level coverage and tumor purity. The detection results on tumor samples can aid to evaluate known cancer genes and to predict target drugs for disease diagnosis.

To evaluate and analyze the accuracy of three-dimensional camera system acquisition based on stereophotography for the photographic acquisition of images of facial deformities.3D digital models of 45 waxen facial models of patients with facial deformities were obtained via a 3D camera system based on stereophotography. A total of 19 feature lines were measured on each 3D model by using the software. The measurements taken by the coordinate-measuring machine were accepted as standard values. Statistical analysis was performed to evaluate the accuracy of the system and the corresponding factors.Statistical analysis results showed that the measured values of the characteristic distance obtained by 3D camera system were statistically different from the standard values (P0.001). Convex deformities had significant influence on the measuring error of 3D camera system (P0.05), while cleft deformities had no significant influence on the measuring error (P0.05). The facial regions significantly influenced measuring error (P0.05). The deformities had no significant influence on the percentage of measurement values (P0.05). The middle facial regions had significant difference with bilateral facial regions on the percentage of measurement values (P0.05), while the left and right facial regions had no significant difference (P0.05).The accuracy of 3D camera system based on stereophotography for the photographic acquisition of facial deformities are influenced by the morphology of the facial deformities and facial regions. Moreover, the measuring error is acceptable in clinical settings.目的 探究基于立体摄影技术的三维照相系统获取畸形面部影像的精确性及其影响因素。方法 采用基于立体摄影技术的三维照相系统采集45个面部畸形的蜡制脸模的表面数据，测量19个面部软组织特征线距，以三坐标仪采集测量结果作为标准值，分析三维照相系统获取畸形面部影像的精确性，以及不同畸形形态与面部区域对测量结果精确性的影响。结果 三维照相系统获取的特征线距的测量值与标准值具有统计学差异（P0.001）。凸起畸形对三维照相系统的测量误差有显著性影响（P0.05），裂隙畸形对三维照相系统的测量误差无显著性影响（P0.05）。不同面部区域的三维照相系统测量误差有统计学差异（P0.05）。畸形形态对三维照相系统测量偏大百分比无显著性影响（P0.05）。中间区域与面部两侧区域的测量偏大百分比具有统计学差异（P0.05），左侧区域与右侧区域的测量偏大百分比无统计学差异（P0.05）。结论 对畸形面部影像的分析，基于立体摄影技术的三维照相系统测量正畸临床常规线性项目的精确性受畸形形态与面部区域的影响，但误差在临床可接受范围内。.

Background: A systematic review and meta-analysis was made to see whether extracorporeal membrane oxygenation (ECMO) in liver transplantation could improve non-heart-beating donors (NHBDs) recipients’ outcomes compared with donors after brain death (DBDs) recipients. Methods: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for eligible studies. The study eligible criteria are cohort or case–control studies using ECMO in all NHBDs; studies involved a comparison group of DBDs; and studies evaluated 1-year graft and patient survival rate in NHBDs and DBDs groups. Results: Four studies with 704 patients fulfilled the inclusion criteria. The pooled odds ratio (OR) of 1-year patient survival rate in NHBDs recipients compared with DBDs recipients was 0.8 (95% confidence interval [CI], 0.41–1.55). The pooled OR of 1-year graft survival rate in NHBDs recipients compared with DBDs recipients was 0.46 (95% CI, 0.26–0.81). NHBDs recipients were at greater risks to the occurrence of primary nonfunction (PNF) (OR = 7.12, 95% CI, 1.84–27.52) and ischemic cholangiopathy (IC) (OR = 9.46, 95% CI, 2.76–32.4) than DBDs recipients. Conclusions: ECMO makes 1-year patient survival acceptable in NHBDs recipients. One-year graft survival rate was lower in NHBDs recipients than in DBDs recipients. Compared with DBDs recipients, the risks to develop PNF and IC were increased among NHBDs recipients.

Association of early menopause with increased risk of cardiovascular events has been confirmed in previous studies. SYNTAX score (SX-score) can comprehensively quantify severity of coronary artery disease (CAD) and predict the outcomes of patients with CAD. However, the association of early menopause with SX-score has never been reported. We prospectively included 1875 consecutive postmenopausal patients who underwent coronary angiography (CAG) and were angiographically diagnosed with CAD from January 2011 to December 2013. SX-score was calculated using the SX-score algorithm based on diagnostic angiogram. Ordinal logistic regression analysis was used to investigate the association between early menopause and SX-score. Patients with early menopause were more likely to have a history of hypertension, diabetes, hyperlipidemia, and less likely to smoking. Besides, they have higher fasting glucose, hemoglobin A1C (HbA1c), total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), and body mass index (BMI) compared with the patients without early menopause. Moreover, patients with early menopause have higher SX-score and multi-vessel diseases. Ordinal logistic regression analysis showed that age, hypertension, diabetes, and early menopause exerted independent influences on SX-score. The patients undergone oophorectomy, early menopause was highly associated with SX-score. Early menopause was an independent predictor of SX-score in postmenopausal patients with CAD.

The accumulation of glutamate (Glu) in the synaptic cleft during cerebral ischemia triggers the death of neurons, causing mental or physical handicap. However, the mechanisms of the alteration in Glu homeostasis and the imbalance between the release and clearance of Glu in ischemia are not yet completely understood. Additionally, the role of Glu transporters in regulating Glu concentration in the synaptic cleft is controversial. This review aims to provide readers with an in-depth understanding of Glu transporters in the early or later stages of ischemic events, or in mild or severe cerebral ischemia via alteration of Glu transporter expression, reversal of Glu transporters function, and trafficking between membrane and cytoplasm, to further clarify whether the Glu transporters are neuroprotective or neurodegenerative during cerebral ischemia. We provide the insights for deeper understanding of the mechanism of Glu transporters regulation after different periods and severities of cerebral ischemia.

PURPOSE To investigate the effect(s) of screw-access hole (SAH) in different diameters on the cement-retained implant prosthodontic systems and surrounding cortical bones. MATERIALS AND METHODS Twenty finite element models were divided into 4 groups: 2 types of full-contour (FC) crowns (Y-TZP, gold alloy) and 2 types of porcelain-fused-to-metal crowns (based on Co-Cr, Au-Pd alloy). For each group, 5 crowns were simulated by varying the diameter of SAH (0, 1, 2, 3, and 4 mm). A vertical load of 200 N and an oblique load of 100 N (45°s) were applied. All models were analyzed with finite element analysis software. RESULTS The stress on the occlusal surface of crowns was almost unchanged when the SAH was within 0 to 3 mm, whereas it showed an obvious increase when it reached 4 mm. The stress concentration was also suddenly changed from the loading area to the hole margin under vertical loading. As for the screw, a lower stress level was observed in vertical loading when an FC crown with an SAH within 0 to 1 mm was applied. The stress concentration was constantly located at the beginning of the first thread. Stresses of other components remained almost unchanged. CONCLUSIONS From the aspect of biomechanics, an FC crown with a 1-mm access hole is recommended when a combined cement- and screw-retained crown was used in the posterior region.

MicroRNAs (miRNAs) are a type of small non-coding RNAs that are often play important roles in carcinogenesis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the function and the mechanism of miR-638 in carcinoma (GC). The expression of miR-638 in GC and the DNA copy number of miR-638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by counting kit-8 assay. Different assays, including bioinformatics algorithms (TargetScan and miRanda), luciferase report assay and Western blotting, were used to identify the target gene of miR-638 in GC. The expression of miR-638 target gene in clinical CRC tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in GC tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in GC than NCTs, which may induce the corresponding downregulation of miR-638 in GC. Ectopic expression of miR-638 inhibited GC cell growth in vitro. Subsequently, we identified that PLD1 is the target gene of miR-638 in GC, and silencing PLD1 expression phenocopied the inhibitory effect of miR-638 on GC cell proliferation. Furthermore, we observed that PLD1 was overexpressed in GC tissues, and high expression of PLD1 in GC predicted poor overall survival. In summary, we revealed that miR-638 functions as a tumor suppressor in GC through inhibiting PLD1. Electronic supplementary material The online version of this article (doi:10.1007/s13238-015-0187-8) contains supplementary material, which is available to authorized users.

Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization.

This study was to determine the efficacy of vincristine and irinotecan in children with relapsed hepatoblastoma (HB).A total of 10 patients with relapsed HB were enrolled. Three patients were excluded. Patients received irinotecan 50 mg/m(2)/day, day 1-5 and vincristine 1.5 mg/m(2)/day, day 1, repeated every 3 weeks. The maximum cycles were eight. Reevaluation of tumor was performed every two cycles. The primary outcome was the rate of complete resection. Secondary outcomes were event-free survival (EFS) and overall survival (OS).Of the seven patients assessable for response, one patient with normal AFP level showed a progressive disease and withdrew. He finally died 6 months later. Four had PR, all of them underwent a second surgery and achieved complete resection. Two patients had SD, one patient relapsed 6 months after orthotopic liver transplantation and died, the other one undergoing surgery had micro margin positive, he relapsed again but alive. The rate of complete resection was 71.4% (including orthotopic liver transplantation). The 2-year EFS and OS for the whole group were 57.1% (95% CI, 12.7% to 34.2%) and 71.4% (95% CI, 16.39% to 37.4%), respectively.The combination of irinotecan and vincristine has a significant antitumor activity and acceptable toxicity in children with relapsed HB.