Pleotropic effects of hypoxia-inducible factor-prolyl hydroxylase domain inhibitors: are they clinically relevant?

Anemia is common in patients with chronic kidney disease (CKD) and is mainly caused by insufficient production of erythropoietin from fibrotic kidney. Because anemia impairs quality of life and overall prognosis, recombinant human erythropoietin-related products (erythropoiesis-stimulating agents, ESAs) have been developed to increase hemoglobin level for decades. However, many safety concerns have been announced regarding the use of ESAs, including an increased occurrence of cardiovascular events, vascular access thrombosis, cancer progression, and recurrence. Hypoxia-inducible factor (HIF) is crucial to erythropoietin production, as a result, prolyl hydroxylase domain (PHD) enzyme inhibitors have been new therapeutic agents for the treatment of anemia in CKD. They can be administered orally, which is a preferred route for patients not undergoing hemodialysis. In clinical trials, PHD inhibitor could induce noninferior effect on erythropoiesis and improve functional iron deficiency compared with ESAs. Although no serious adverse events were reported, safety is still a concern because HIF stabilization induced by PHD inhibitor has pleotropic effects, such as angiogenesis, metabolic change, and cell survival, which might lead to unwanted deleterious effects, including fibrosis, inflammation, cardiovascular risk, and tumor growth. More molecular mechanisms of PHD inhibition and long-term clinical trials are needed to observe these pleotropic effects for the confirmation of safety and efficacy of PHD inhibitors.

Characteristic of immune function decline in the process of “Declined of Vital Qi” caused by aging in mice / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：基于小鼠渐进衰老模型探讨衰老所致“正虚”的免疫功能衰退表征的特点。方法：使用不同月龄（2、6、15月龄）C57BL/6小鼠，通过流式细胞术检测并比较小鼠外周血和脾组织中T细胞、髓源性抑制细胞（MDSC）及其亚群的丰度变化。结果：外周血中T细胞亚群表型为CD3+CD4+CD44-CD62L+的幼稚CD4+ T细胞（2 vs 6月龄，P=0.137；2 vs 15月龄，P=0.004；6 vs 15月龄，P=0.105）和表型为CD3+CD8+CD44-CD62L+的幼稚CD8+ T细胞（2 vs 6月龄，P=0.179；2 vs 15月龄，P=0.001；6 vs 15月龄，P=0.015）出现与衰老有关的细胞比例降低，差异具有统计学意义。表型为CD3+CD4+CD44+CD62L+的中央记忆CD8+ T细胞出现与衰老有关的比例升高，差异具有统计学意义（2 vs 6月龄，P=0.01；2 vs 15月龄，P=0.007；6 vs 15月龄，P=0.164）。对脾组织的检测结果具有与外周血相同特点。同时，CD8+ T细胞比例随衰老逐渐升高（2 vs 6月龄，P=0.027；2 vs 15月龄，P<0.001；6 vs 15月龄，P<0.001）；表型为CD8+CD28+的活化CD8+ T细胞亚群比例也出现随月龄增长的上升（2 vs 6月龄，P=0.863； 2 vs 15月龄，P=0.016；6 vs 15月龄，P=0.024），差异均具有统计学意义。结论：衰老所致“正虚”过程中，不同免疫细胞亚群变化并不都反映免疫抑制特点，虽然总体免疫功能下降，但单一表型难以反应整体免疫功能变化。

Effect and Mechanism of Cinobufotalin Against Gastrointestinal Malignant Tumors： A Review / 中国实验方剂学杂志

Digestive tract diseases， especially digestive tract tumors， including liver cancer， pancreatic cancer， and colorectal cancer， have high incidence in China. Digestive tract tumor is one of the top 10 cancers in terms of the number of new cases and deaths in the world， and the incidence and mortality of tumor diseases have been increasing year by year. Therefore， the prevention and treatment of tumors is particularly important. With the application and promotion of traditional Chinese medicine in the medical field and the rapid development of molecular biology and pharmacology， more and more potential active components of Chinese medicinal materials have been extracted and studied. These active components can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an effective component extracted from the skin of Bufo bufo gargarizans. It has been prepared into a variety of agents with anti-tumor， immunomodulatory， cardiac boosting， pain-easing， anti-inflammatory， and swelling-relieving activities. In clinical practice， cinobufotalin is mainly used to assist the treatment of liver cancer， lung cancer， colorectal cancer， gastric cancer and other malignant tumors， which can reduce the adverse reactions of patients in the middle and late stages and improve the quality of life and five-year survival rate of patients. The available studies of molecular mechanism have demonstrated that cinobufotalin can play a therapeutic role by inducing cell apoptosis， regulating cell cycle， inhibiting cell proliferation and angiogenesis， modulating immune response， reversing multidrug resistance， enhancing radiochemotherapy sensitivity， inhibiting tumor inflammation， invasion， and metastasis， etc. This review focuses on the clinical application and mechanism of cinobufotalin against digestive tract tumors in recent years， aiming to provide a theoretical basis for the anti-tumor research of cinobufotalin， promote the application of cinobufotalin in tumor treatment， and facilitate the further research and development of this compound.

Strike Velocity Prediction of Stick Blunt Instruments Based on Backpropagation Neural Network / 法医学杂志

OBJECTIVES@#To analyze and predict the striking velocity range of stick blunt instruments in different populations, and to provide basic data for the biomechanical analysis of blunt force injuries in forensic identification.@*METHODS@#Based on the Photron FASTCAM SA3 high-speed camera, Photron FASTCAM Viewer 4.0 and SPSS 26.0 software, the tester's maximum striking velocity of stick blunt instruments and related factors were calculated and analyzed, and inputed to the backpropagation (BP) neural network for training. The trained and verified BP neural network was used as the prediction model.@*RESULTS@#A total of 180 cases were tested and 470 pieces of data were measured. The maximum striking velocity range was 11.30-35.99 m/s. Among them, there were 122 female data, the maximum striking velocity range was 11.63-29.14 m/s; there were 348 male data, the maximum striking velocity range was 20.11-35.99 m/s. The maximum striking velocity of stick blunt instruments increased with the increase of weight and height, but there was no obvious increase trend in the male group; the maximum striking velocity decreased with age, but there was no obvious downward trend in the female group. The maximum striking velocity of stick blunt instruments has no significant correlation with the material and strike posture. The root mean square error (RMSE), the mean absolute error (MAE) and the coefficient of determination (R2) of the prediction results by using BP neural network were 2.16, 1.63 and 0.92, respectively.@*CONCLUSIONS@#The prediction model of BP neural network can meet the demand of predicting the maximum striking velocity of different populations.

Huangqin Decoction Attenuates DSS-Induced Mucosal Damage and Promotes Epithelial Repair via Inhibiting TNF-α-Induced NF-κB Activation / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effect of Chinese herbal formula Huangqin Decoction (HQD) on ulcerative colitis mouse model induced by dextran sulphate sodium (DSS) and human intestinal epithelial cell injury induced by tumour necrosis factor-α (TNF-α).@*METHODS@#In vivo, 30 male C57BL/6 mice were divided into 5 groups using a random number table (n=6 per group), including control, DSS, 5-aminosalicylic acid (5-ASA), HQD low- (HQD-L) and high-dose (HQD-H) groups. The colitis mouse model was established by 3% (w/v) DSS water for 5 days. Meanwhile, mice in the HQD-L, HQD-H and 5-ASA groups were administrated with 100, 200 mg/kg HQD or 100 mg/kg 5-ASA, respectively, once daily by gavage. After 9 days of administration, the body weight, disease activity index (DAI) score and colon length of mice were measured, the pathological changes of colons were analyzed by hematoxylin-eosin staining (HE) staining, and the levels of serum interleukin (IL)-6, IL-1β and TNF-α were measured by enzyme linked immunosorbent assay. In vitro, the human colon epithelial normal cells (FHC cells) were exposed to HQD (0.6 mg/mL) for 12 h and then treated with TNF-α (10 ng/mL) for 24 h. The tight junction (TJ) protein expression levels of Claudin-4 and Occludin, and the protein phosphorylation levels of p65 and inhibitor of nuclear factor kappaB (NF-κB)-α (IκBα) were measured by Western blot.@*RESULTS@#In vivo, compared with the DSS group, HQD-H treatment attenuated the weight loss and reduced DAI score of mice on the 8th day (P<0.05). Moreover, HQD-H treatment ameliorated the colon shortening in the DSS-induced colitis mice (P<0.05). HE staining showed HQD attenuated the pathological changes of colitis mice, and the histological scores of HQD-H and 5-ASA groups were significantly decreased compared with the DSS group (P<0.05). Meanwhile, HQD-H and 5-ASA significantly decreased the serum IL-1β, IL-6 and TNF-α levels of mice (P<0.05). In vitro experiments showed that HQD up-regulated Occludin and Claudin-4 protein expressions and inhibited p-p65 and p-IκBα levels in FHC cells compared with the TNF-α group (P<0.05).@*CONCLUSION@#HQD significantly relieved the symptoms in DSS-induced colitis mice by inhibiting pro-inflammatory cytokines expression and maintained the homeostasis of TJ protein in FHC cells by suppressing TNF-α-induced NF-κB activation.

Ginsenoside Rg_1 protects PC12 cells against Aβ-induced injury through promotion of mitophagy by PINK1/parkin activation / 中国中药杂志

Amyloid β-protein(Aβ) deposition in the brain is directly responsible for neuronal mitochondrial damage of Alzheimer's disease(AD) patients. Mitophagy, which removes damaged mitochondria, is a vital mode of neuron protection. Ginsenoside Rg_1(Rg_1), with neuroprotective effect, has displayed promising potential for AD treatment. However, the mechanism underlying the neuroprotective effect of Rg_1 has not been fully elucidated. The present study investigated the effects of ginsenoside Rg_(1 )on the autophagy of PC12 cells injured by Aβ_(25-35) to gain insight into the neuroprotective mechanism of Rg_1. The autophagy inducer rapamycin and the autophagy inhi-bitor chloroquine were used to verify the correlation between the neuroprotective effect of Rg_1 and autophagy. The results showed that Rg_1 enhanced the viability and increased the mitochondrial membrane potential of Aβ-injured PC12 cells, while these changes were blocked by chloroquine. Furthermore, Rg_(1 )treatment increased the LC3Ⅱ/Ⅰ protein ratio, promoted the depletion of p62 protein, up-regulated the protein levels of PINK1 and parkin, and reduced the amount of autophagy adaptor OPTN, which indicated the enhancement of autophagy. After the silencing of PINK1, a key regulatory site of mitophagy, Rg_1 could not increase the expression of PINK1 and parkin or the amount of NDP52, whereas it can still increase the LC3Ⅱ/Ⅰ protein ratio and promote the depletion of OPTN protein which indicated the enhancement of autophagy. Collectively, the results of this study imply that Rg_1 can promote autophagy of PC12 cells injured by Aβ, and may reduce Aβ-induced mitochondrial damage by promoting PINK1-dependent mitophagy, which may be one of the key mechanisms of its neuroprotective effect.

Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors / 中华肿瘤杂志

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

Metabolic reprogramming and tumor microenvironment in pancreatic cancer / 中华内分泌外科杂志

Pancreatic cancer is a lethal disease and highly resistant to all forms of therapy. Cancer cells reprogram their metabolism extensively to promote their survival and growth, reflecting the vital role of altered metabolism. In this review, we summarize the vital role of metabolic reprogramming and microenvironmental crosstalk.

Factors Related to Curative Effect of Brain-computer Interface Training on Upper Limb Paralysis after Stroke / 中国康复理论与实践

Objective:To explore the factors affecting curative effect of motor imagery brain-computer interface (MI-BCI) training on upper limb paralysis for subacute stroke patients. Methods:From January, 2018 to July, 2019, 23 inpatients with post-stroke upper limb paralysis accepting MI-BCI training were reviewed. The gender, age, course of disease, aphasia, location and nature of lesion, history of Botulinum toxin, hemisphere injured and modified Ashworth Scale (MAS) score of affected fingers were recorded, and they were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE) before and four weeks after MI-BCI training. According to improvement of FMA-UE wrist and hand scores (≥ 2), the patients were divided into effective group (n = 11) and inefficacy group (n = 12). Results:The MAS scores before MI-BCI training (t = 2.677, P < 0.05) and history of botulinum toxin (Z = 0.000, P < 0.05) were more in the inefficacy group than in the efficacy group. FMA-UE scores (total and dimensions) after training were correlated to their baseline levels (r > 0.831, P < 0.01), FMA-UE total scores (Eta = 0.453, P < 0.05) and upper arms scores (Eta = 0.506, P < 0.05) were correlated to aphasia, FMA-UE scores of hands were correlated with MAS (r = -0.521, P < 0.05). Conclusion:Poor baseline motor function, spasticity and complication with aphasia were the factors unfavorable to MI-BCI training for subacute stroke patients with upper limb paralysis.

Three-dimensional morphological changes in the temporomandibular joints of patients with anterior disc displacement with reduction / 华西口腔医学杂志

OBJECTIVES@#To investigate the differences in the temporomandibular joints (TMJs) between patients with anterior disc displacement with reduction (ADDwR) and asymptomatic subjects by using 3D morphometric measurements.@*METHODS@#A total of 15 patients with ADDwR and 10 asymptomatic subjects were enrolled. Then, 3D models of the maxilla and mandible were reconstructed using MIMICS 20.0. Nine morphologic parameters of TMJs on both sides were measured on the 3D solid model. The differences in the parameters were analyzed between the patients and the asymptomatic subjects and between the left and right sides of each group.@*RESULTS@#The horizontal and coronal condylar angles on the ipsilateral side of the patients were significantly greater than those of the asymptomatic subjects (@*CONCLUSIONS@#ADDwR will increase the condylar angles to be significantly greater than the normal level and decrease SRA and articular spaces to be significantly smaller than the normal level. The condyles will be displaced upward, closer to the fossa.

Absence of BAX differentially affects astrocyte density in the mouse cortex and hippocampus / 生理学报

Astrocytes are a heterogenous group of macroglia present in all regions of the brain and play critical roles in many aspects of brain development, function and disease. Previous studies suggest that the B-cell lymphoma-2 associated X protein (BAX)-dependent apoptosis plays essential roles in regulating neuronal number and achieving optimal excitation/inhibition ratio. The aim of the present paper was to study whether BAX regulates astrocyte distribution in a region-specific manner. Immunofluorescence staining of SOX9 was used to analyze and compare astrocyte density in primary somatosensory cortex, motor cortex, retrosplenial cortex and hippocampus in heterozygous and homozygous BAX knockout mice at age of six weeks when cortical development has finished and glia development has reached a relatively steady state. The results showed that astrocyte density varied significantly among different cortical subdivisions and between cortex and hippocampus. In contrast to the significant increase in GABAergic interneurons, the overall and region-specific astrocyte density remained unchanged in the cortex when BAX was absent. Interestingly, a significant reduction of astrocyte density was observed in the hippocampus of BAX knockout mice. These data suggest that BAX differentially regulates neurons and astrocytes in cortex as well as astrocytes in different brain regions during development. This study provided important information about the regional heterogeneity of astrocyte distribution and the potential contribution of BAX gene during development.

Functional network connectivity in default mode for preschoolers with autism: an fMRI study / 中华行为医学与脑科学杂志

Objective:To estimate the predictive ability of group differences on autistic traits of social communication impairment by comparing the intrinsic functional network connectivity between default mode network and other brain networks between preschoolers with autism and typically developing control.Methods:Sixty preschoolers diagnosed autism according to DSM-5 and 60 typical developing individuals matched by age and sex were analyzed using resting-state functional magnetic resonance imaging (MRI). Establish functional network connections between the default mode network and other brain networks based on the results of the data-driven approach (independent component analysis). Subsequently, the correlation between the connectivity strength with statistical differences and the autistic traits of social communications impairments was analyzed.Results:Relative to typically developing control participants, preschoolers with autism showed increased functional connectivity between the medial prefrontal cortex and subcortical networks (basal ganglia and thalamus, Bg/Th) ( t=3.758, P<0.01, FDR-corrected). The strength of such connections was significantly associated with the severity of autistic core social communication disorders ( r=0.34, P=0.007). Furthermore, the average connection strength of DMN showed a hyper-FNC with the basal ganglion network ( t=3.455, P<0.01, FDR-corrected). Conclusion:There is an excessive functional connection between medial prefrontal cortex and subcortical nucleus in preschool autism children. The abnormal functional connection of DMN may be the key factor of core social disorder in preschool autism children.

Cross-sectional investigation of nosocomial infection in a tertiary general hospital and construction of a prediction model / 公共卫生与预防医学

Objective To understand the prevalence of nosocomial infection and its potential risk factors through a cross-sectional study, to construct a predictive model of the probability of nosocomial infection, and to provide a basis for nosocomial infection management. Methods The prevalence rate of nosocomial infection and potential risk factors of all inpatients in a tertiary general hospital were investigated on a certain day. The possible risk factors of nosocomial infection were analyzed, and a nomogram prediction model on the probability of nosocomial infection was established. The calibration curve and ROC curve were used to evaluate the predictive efficiency of the model. Results A total of 419 hospitalized patients were investigated, and the prevalence rate of nosocomial infection was 3.58%. The top three nosocomial infections were in ICU, neurosurgery, and cardiac surgery. The top three infection sites were surgical site infections, lower respiratory tract infections, and urinary tract infections. The results of univariate analysis showed that the length of hospital stay, surgery, antimicrobial use and underlying diseases were statistically related to the occurrence of nosocomial infections (all P<0.05). Logistic regression analysis showed that compared with the length of stay (LOS)＜14, the risk of nosocomial infection in patients with long LOS (≥14) was 5.48 (95% CI: 1.68-19.16). The risk of nosocomial infection in patients with two basic diseases was 7.61 times that (95%CI: 1.50-44.79) of patients without underlying diseases. The risk of nosocomial infection in patients with surgery was 4.88 times that of patients without surgery (95%CI: 1.47-19.6). According to the coefficients of the related risk factors calculated by logistic regression, a nomogram model of the occurrence probability of nosocomial infection was established. The C-index of the model was 0.839, and the area under the ROC curve for predictive efficiency was 0.809 (95%CI: 0.740-0.942). Conclusion Nosocomial infection control and management should be strengthened. Individual risk assessment of patients' nosocomial infection should consider about the age, underlying diseases, surgical status, glucocorticoid or immunosuppressive agents, and antimicrobial drug use. It is essential to identify the high-risk groups as soon as possible and take prevention and control measures to reduce the prevalence rate of nosocomial infection.

Ankle stretching can improve stroke survivors′ ankle biomechanics, balance, walking and ability in the activities of daily living / 中华物理医学与康复杂志

Objective:To observe the effect of ankle stretching on ankle biomechanics, balance, walking ability and ability in the activities of daily living among stroke survivors.Methods:Eighteen hemiplegic stroke survivors were randomly divided into an experimental group ( n=9) and a control group ( n=9). In addition to routine medication and rehabilitation training, the experimental group received 20 minutes of ankle joint stretching daily while the control group underwent an additional twenty minutes of routine rehabilitation training. Before and after the treatment, both groups′ ankle joint stiffness (K), muscle strength, active range of motion (AROM) and passive range of motion (PROM) were evaluated. They were also assessed using the modified Ashworth scale (MAS), the Fugl-Meyer lower extremity assessment (FMA-LE), the Berg balance scale (BBS), the 6-minute walking test (6MWT) and the modified Barthel Index (MBI). Results:After two weeks of treatment significant improvement was observed in the AROM and muscle strength of both groups in dorsiflexion and plantarflexion. The average BBS and FMA-LE scores of both groups had also improved significantly. Significant improvement in the average PROM of plantarflexion and the K of dorsiflexion, as well as in average MBI score was observed only in the treatment group. After two weeks the treatment group′s average muscle strength in plantarflexion and dorsiflexion was significantly better than the control group′s.Conclusions:Stretching can reduce ankle stiffness, improve the range of motion, muscle strength, and ability of in the activities of daily living after a stroke.

Brain-computer Interface and Comprehensive Training for Stroke: A Resting State Functional Magnetic Resonance Imaging Study / 中国康复理论与实践

Objective:To investigate the topological alterations in brain functional networks following comprehensive treatment including brain-computer interface (BCI) training in subacute stroke subjects. Methods:From January, 2018 to June, 2019, 14 subacute stroke patients with moderate to severe upper limbs paralysis accepted routine physical therapy, occupational therapy and BCI training based on motor imagery, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT) and Wolf Motor Function Test (WMFT) before and after treatment, while the functional connectivity (FC) was investigated with resting state functional magnetic resonance imaging. Results:The scores of FMA-UE, ARAT and WMFT increased after treatment (|t| > 5.298, Z = -3.297, P < 0.01). The FC also increased across the whole brain, including temporal, parietal, occipital lobes and subcortical regions. The FC between left piriform cortex of parietal lobule (BA5L) and right medial surface of temporal lobe (BA48R), as well as those between left precentral gyrus (BA4L) and right anterior transverse temporal gyrus (BA41R) (r > 0.416, P < 0.05). Conclusion:Comprehensive rehabilitation including BCI training may promote recovery of motor function and activities of FC in brain in subacute stroke patients.

Effects of Functional Electrical Stimulation-assisted Cycling on Motor Function and Cardiopulmonary Fitness in Subacute Stroke Patients / 中国康复理论与实践

Objective:To explore the effects of functional electrical stimulation (FES)-assisted rehabilitation cycling on motor function, cardiopulmonary fitness and activities of daily living in patients with subacute stroke. Methods:From January, 2016 to April, 2019, 60 patients with first-onset stroke at subacute stage were divided into control group (n = 30) and experimental group (n = 30). The experimental group and the control group received cycling training with or without FES based on the routine treatment for four weeks. They were assessed with Fugl-Meyer Assessment (FMA) and modified Barthel Index (MBI), and measured peak oxygen uptake (VO2peak) before and after treatment. Results:The scores of FMA and MBI, and VO2peak increased in both groups after treatment (|t| > 7.889, P < 0.001), and the scores of FMA and VO2peak increased more in the experimental group than in the control group (|t| > 3.332, P < 0.01). Conclusion:FES-assisted rehabilitation cycling could promote the recovery of motor function, cardiopulmonary fitness and activities of daily living in subacute stroke patients.

Effect of Curricular Reforms of Physical Medicine and Rehabilitation in Medical Engineering Interdisciplinary Crossing on Eight-year Medical Students / 中国康复理论与实践

Objective:To observe the effect of curricular reforms of physical medicine and rehabilitation in medical engineering interdisciplinary on learning of eight-year medical students. Methods:The eight-year medical students studying Physical Medicine and Rehabilitation in Tsinghua University in 2018 and 2019 were enrolled into control group (n = 20) and observation group (n = 18), respectively. The control group used routine courses and studied with teachers of rehabilitation medicine; while the observation group added neuroscience theory and new advances, the development of functional magnetic resonance and application in rehabilitation medicine, new technology and progress in medical engineering in the course, and studied with teachers of electronic engineering, mechanical engineering and medicine. Their performances were compared. The observation group was surveyed with self-designed questionaire. Results:The performance of paper test, general test and total test were higher in the observation group than in the control group (t > 2.694, P < 0.01). The questionnaire showed that the observation group could better understand the course of Physical Medicine and Rehabilitation and the development of medical engineering interdisciplinary crossing and translational research within physical medicine and rehabilitation, and they thought it was more necessary to study the new course after the curriculum finished (|Z| > 2.304, P < 0.05). The proportion of students who were interested and very interested in medical engineering interdisciplinary crossing and translational research within physical medicine and rehabilitation increased from 77.78% to 94.44% (P = 0.222), and the the proportion of students who were probably and very probably engaged in physical medicine and rehabilitation increased from 61.11% to 83.33% (P =0.043). Conclusion:The curricular reforms in medical engineering interdisciplinary crossing could raise the interest and improve the test performance of eight-year students with physical medicine and rehabilitation.

Pharmaceutics, outcomes and predictors of dilated cardiomyopathy in children / 国际儿科学杂志

Pediatric dilated cardiomyopathy(DCM)is a myocardial disorder characterized by a dilated left ventricular chamber and systolic dysfunction that often manifested as heart failure, arrhythmia, thrombosis, thromboembolism and sudden death.Survival free from transplantation was 54%-72% 5 years after diagnosis, and 46%-62% at 10 years.Several factors indicating better prognosis are higher left ventricular ejection fraction, and the presence of myocarditis.Other predictors such as older age at diagnosis, a family history of cardiomyopathy, arrhythmias, severe mitral regurgitation, lager left ventricular end-diastolic dimension and end-systolic dimension, and cardiothoracic ratio greater than 65% suggest that the prognosis may be poor.The cornerstone of pediatric DCM therapy is drug therapy including angiotensin-converting enzyme inhibitors, β-blockers and aldosterone antagonists.Ivabradine, myocardial metabolic drugs and intravenous immunoglobulins may be associated with better improvement of systolic left ventricular function.

MicroRNA-98-5p Inhibits Tumorigenesis of Hepatitis B Virus-Related Hepatocellular Carcinoma by Targeting NF-κB-Inducing Kinase

Purpose@#MicroRNAs play key regulatory roles in the tumorigenesis of hepatitis B virus-related hepatocellular carcinoma (HBVHCC). This study aimed to explore the regulatory effects of microRNA-98-5p (miR-98-5p) on the proliferation, migration, invasion, and apoptosis of HBV-HCC cells, as well as the underlying mechanisms involving nuclear factor-κB-inducing kinase (NIK). @*Materials and Methods@#The expressions of miR-98-5p and NIK in HBV-HCC tissues and cells, and the level of HBV DNA in HBVHCC cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, invasion, and apoptosis of HBV-HCC cells were analyzed by cell counting kit-8, wound healing, transwell, and flow cytometry assay, respectively. The targeting relationship between miR-98-5p and NIK was predicted by StarBase3.0 and verified by dual-luciferase reporter assay. HBV-HCC xenograft tumor model was constructed in mice to observe the tumor growth in vivo. @*Results@#The expression of miR-98-5p was declined in HBV-HCC tissues and cells. Overexpression of miR-98-5p markedly reduced the level of HBV DNA; inhibited the proliferation, migration, and invasion; and promoted the apoptosis of HBV-HCC cells. NIK was a target of miR-98-5p. Overexpression of miR-98-5p markedly decreased the protein expression of NIK in MHCC97H-HBV cells. NIK reversed the tumor-suppressing effect of miR-98-5p on HBV-HCC cells. Furthermore, overexpression of miR-98-5p significantly inhibited the xenograft tumor growth and decreased the expression of NIK in mice. @*Conclusion@#MiR-98-5p inhibits the secretion of HBV, proliferation, migration, and invasion of HBV-HCC cells by targeting NIK.

Abnormal eye movements in patients with idiopathic rapid eye movement sleep behavior disorder / 浙江大学学报·医学版

OBJECTIVE@#To analyze the characteristics of eye movements in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD).@*METHODS@#Twenty two patients with iRBD and 20 controls were enrolled between January 2017 and May 2019 from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Clinical data including polysomnogram (PSG) results were collected. Videonystagmography (VNG) including spontaneous nystagmus, gaze, saccade, tracking and optokinetic test were performed. The difference of VNG results between iRBD patients and controls were analyzed. The factors related to the abnormal VNG results were analyzed by using logistic regression analysis.@*RESULTS@#No significant differences were found between the iRBD and control groups in the spontaneous nystagmus, gaze nystagmus, square wave jerk, involuntary eye movement, saccade and optokinetic nystagmus (all >0.05). In smooth pursuit of 0.4-0.5 Hz and 0.6-0.7 Hz, iRBD patients had more type Ⅲ-Ⅳ curve than controls (=5.177 and 5.301, both <0.05). Logistic regression analysis indicated that less sleep time of N3 stage was related to the abnormal results in smooth pursuit of 0.4-0.5 Hz (=0.963, <0.05). iRBD patients with Ⅲ-Ⅳ type curve in smooth pursuit of 0.4-0.5 Hz had less N3 sleep time than iRBD patients with Ⅰ-Ⅱ type curve (52±28 min vs. 76±23 min, =2.197, <0.05).@*CONCLUSIONS@#Abnormal smooth pursuit was found in iRBD patients, which might be related to the pathological mechanism of iRBD.