Supplementing rehabilitation training with botulinum neurotoxin improves outcomes for Parkinson′s disease patients with striatal foot deformity / 中华物理医学与康复杂志

Objective:To observe any therapeutic effect of combining botulinum toxin type A (BTX-A) with rehabilitation training in treating Parkinson′s disease (PD) patients with striatal foot deformity (SFD).Methods:A total of 68 PD patients with SFD were randomly divided into a control group and a treatment group. Both groups were given routine medication with pramipexole and dopamine receptor agonists and received lower limb rehabilitation training, including passive activity training, strength training and walking training. The treatment group was additionally injected with BTX-A. Sciatic pain was quantified using a visual analogue scale. The Unified Parkinson′s Disease Rating Scale-lower limb motor lower limb motor function (UPDRS-LLM) scale, the Berg balance scale and the modified Barthel index were applied to test all of the participants before the experiment and on the 7th, 14th and 30th day of the treatment.Results:The average scores of the control group on all of measures at were significantly better than those of the control group at the same time points, and by the 14th and 30th day had improved significantly compared with those before treatment.Conclusion:Supplementing rehabilitation training with BTX-A can significantly improve foot deformity and relieve the muscle tension and spastic pain of PD patients with SFD, promoting the motor functioning of their lower limbs, their balance and their performance in the activities of daily living.

Research progress on the role of exosome in rejection after lung transplantation / 器官移植

Rejection after lung transplantation, including acute rejection (AR) and chronic rejection manifested with chronic lung allograft dysfunction (CLAD), is the main factor affecting the long-term survival of allografts. Exosome, a type of extracellular nanovesicle for intercellular communication among eukaryotic cells, could carry complex biological information and participate in various physiological and pathological processes. Exosome has become a critical immune medium in rejection, regulates the incidence and development of rejection through multiple pathways, and also plays a key role in the monitoring and management of rejection. In this article, the type of rejection after lung transplantation, the mechanism underlying the role of exosome in regulating rejection, exosome acting as biomarkers and the application in rejection treatment were reviewed, aiming to provide a novel direction for comprehensive diagnosis and treatment of rejection following lung transplantation.

Effects of milnacipran and paroxetine on anxiety state and headache severity of patients with generalized anxiety disorder / 中国医师进修杂志

Objective:To compare the effects of milnacipran and paroxetine on anxiety state and headache severity of patients with generalized anxiety disorder (GAD).Methods:Ninety-six patients with GAD treated in Zaozhuang Mental Health Center from January 2019 to September 2020 were selected and randomly divided into the paroxetine group (treatment with oral paroxetine) and the milnacipran group (treatment with oral milnacipran), each group with 48 cases. A course of treatment consists of 4 weeks. After 3 months of regular medication, the clinical efficacy, Hamilton Anxiety Scale (HAMA) scores, visual analogue scale (VAS) scores, migraine-specific quality of life questionnaire (MSQ V2.1) scores, and Headache Impact Test-6 (HIT-6) scores were compared between the two groups. Adverse reactions during the treatment were recorded in both groups.Results:The total effective rate in the milnacipran group at 4 weeks and 3 months after treatment were significantly higher than those in the paroxetine group: 47.92%(23/48) vs. 22.92%(11/48), χ2 = 6.56, P<0.05; 75.00%(36/48) vs. 51.47%(26/48), χ2 = 4.55, P<0.05. After treatment for 4 weeks and 3 months, the HAMA scores, VAS scores, MSQ V2.1 scores and HIT-6 scores in the milnacipran group were significantly lower than those in the paroxetine group ( P<0.05). The difference of incidence of adverse reactions in the two groups had no statistical significance ( P>0.05). Conclusions:For patients with GAD, the treatment effect of milnacipran is more significant than paroxetine, which can not only reduce patients′ anxiety state and headache degree, but also improve their specific quality of life, with high safety.

Effects of resveratrol on the activity of infantile hemangioma-derived endothelial cells / 中华皮肤科杂志

Objective:To investigate the effect of the glucose transporter 1 (Glut-1) inhibitor resveratrol on the activity of infantile hemangioma (IH) -derived endothelial cells (HemEC) .Methods:IH tissues were collected from 4 cases of proliferating IH and 4 cases of involuting IH, and immunohistochemical study was performed to determine the Glut-1 expression. Primary HemEC were extracted from 4 proliferating IH tissues, real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were performed to determine the mRNA and protein expression of Glut-1 in HemEC and human umbilical vein endothelial cells (HUVEC) , respectively. HemEC were cultured in vitro and treated with 0 (control group) , 50, 100, 200, 400 and 800 μmol/L resveratrol for 24 hours, respectively. Cell counting kit-8 (CCK8) assay was performed to evaluate the proliferative ability of HemEC in the above groups, and the 50% inhibitory concentration (IC50) was calculated. The migratory ability and apoptosis level of HemEC were assessed by Transwell assay and flow cytometry, respectively. Intergroup comparisons were performed using t test or analysis of variance, and multiple comparisons were performed using least significant difference- t test. Results:Immunohistochemical study showed that Glut-1 was expressed in vascular endothelial cells derived from both proliferating and involuting IH tissues, and the Glut-1 expression was abundant in the proliferating IH but markedly decreased in the involuting IH tissues. The mRNA and protein expression levels of Glut-1 were significantly higher in HemEC (1.793 ± 0.041, 1.959 ± 0.144, respectively) than in HUVEC (0.820 ± 0.073, 0.648 ± 0.046, t = 16.35, 12.28, respectively, both P < 0.001) . After the treatment with Glut-1 inhibitor resveratrol at different concentrations, the proliferative ability of HemEC significantly differed among the control group, 50-, 100-, 200-, 400- and 800-μmol/L resveratrol groups ( F = 1 043.00, P < 0.001) , and was significantly lower in all the resveratrol groups than in the control group (all P < 0.05) . The IC50 of resveratrol was calculated to be 150 μmol/L by using GraphPad Prism 8 software. Transwell assay and flow cytometry showed significantly decreased number of migratory HemEC but significantly increased apoptosis rate respectively in the 150 μmol/L resveratrol group (61 ± 5, 13.01% ± 0.45%, respectively) compared with the control group (150 ± 6, 3.93% ± 0.68%, t = 15.11, 19.34, respectively, both P < 0.001) . Conclusion:The key glycolytic enzyme Glut-1 was highly expressed in proliferating IH tissues and HemEC, and resveratrol could inhibit the proliferation and migration of HemEC, but promote their apoptosis.

Analysis of factors associated with infantile hemangioma: a multicenter case-control study / 中华皮肤科杂志

Objective:To analyze demographic and clinical characteristics of infantile hemangioma (IH) , and to explore related risk factors for IH.Methods:A multicenter case-control study was conducted. IH patients (case group) and healthy children (control group) were collected from West China Hospital of Sichuan University, West China Second University Hospital of Sichuan University and Yulin Community Central Hospital of Chengdu from October 2018 to December 2020. The data on patients′ demographic characteristics, and risk factors during their mothers′ pre-pregnancy, pregnancy and perinatal period were collected and retrospectively analyzed. Univariate and multivariate analyses were performed using binary logistic regression.Results:A total of 1 479 patients with IH and 1 086 healthy children were included in this study. There were 456 males and 1 023 females in the case group, with the age being 3.74 ± 2.82 months, and there were 359 males and 727 females in the control group, with the age being 3.95 ± 2.77 months. There was no significant difference in the gender ratio, age, ethnic composition, birth weight or birth height between the case group and control group (all P > 0.05) . IH lesions mostly affected the head and face (564 cases, 38.1%) , followed by the trunk (449 cases, 30.6%) and limbs (356 cases, 24.1%) . At the visit, 1 109 (75.0%) patients presented with proliferating IH, 1 059 (71.6%) with superficial IH, and 1 306 (88.3%) with focal IH. The IH lesion area ranged from 0.01 to 168.00 (6.24 ± 12.91) cm 2, and the segmental IH area ranged from 7.50 to 168.00 (32.17 ± 26.94) cm 2. Univariate logistic regression analysis showed some factors influencing the occurrence of IH (all P < 0.05) , including pre-pregnancy factors (delivery history and miscarriage history) , pregnancy factors (fetal distress, cord entanglement, history of threatened abortion, placenta previa, oligohydramnios, gestational hypothyroidism, gestational anemia, history of progesterone supplementation, history of thyroxine drug use, history of uterus myomas) , and perinatal factors (including fetal position, gestational weeks, premature rupture of membranes and preterm premature rupture of membranes) . Multivariate binary logistic regression adjusted analysis showed that fetal breech presentation, preterm birth, cord entanglement and history of thyroxine drug use during pregnancy did not influence the occurrence of IH (all P > 0.05) ; the delivery history was the strongest independent risk factor for IH (adjusted OR = 5.624, 95% CI: 4.275 to 7.398, P < 0.001) , and gestational hypothyroidism and history of uterus myomas were protective factors for IH. Conclusions:In this study, the average age of IH patients at visit was 4 months, skin lesions mostly occurred on the head and face, and most were superficial and focal in the proliferative stage. The occurrence and development of IH may be associated with placental diseases, hypoxia, maternal hormone levels during pregnancy, etc.

Mechanism of period gene regulating renin-angiotensin-aldosterone system in rhythm of blood pressure / 国际脑血管病杂志

Rhythm of blood pressure refers to the circadian variation of blood pressure, which is regulated by clock genes. However, the rhythm disorder of blood pressure increases the risk of stroke. Taking the process of blood pressure regulation as a clue and focusing on the clock gene pathway, this article explores the possible mechanism of period gene regulating renin-angiotensin-aldosterone system in rhythm of blood pressure, so as to provide reference for the in-depth study of the relevant mechanism of rhythm disorder of blood pressure and search for a new target for the primary prevention of cerebrovascular diseases.

NEDD8-conjugating enzyme E2 UBE2F confers radiation resistance by protecting lung cancer cells from apoptosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Lung cancer, which is exacerbated by environmental pollution and tobacco use, has become the most common cause of cancer-related deaths worldwide, with a five-year overall survival rate of only 19% (Siegel et al., 2020; Yang et al., 2020; Yu and Li, 2020). Nearly 85% of lung cancers are non-small cell lung cancers, of which lung adenocarcinoma is the most common subtype accounting for 50% of non-small cell lung cancer cases. At present, radiotherapy is the primary therapeutic modality for lung cancer at different stages, with significant prolongation of survival time (Hirsch et al., 2017; Bai et al., 2019; Shi et al., 2020). Irradiation can generate reactive oxygen species (ROS) through the radiolysis reaction of water and oxygen, cause DNA damage and oxidative stress, and subsequently result in cancer cell death (Kim et al., 2019). Nevertheless, radioresistance seriously hinders the success of treatment for lung cancer, owing to local recurrence and distant metastasis (Huang et al., 2021). Compared with small cell lung cancer, non-small cell lung cancer shows more tolerance to radiotherapy. Therefore, it is of great importance to decipher key mechanisms of radioresistance and identify effective molecular radiosensitizers to improve patient survival.

DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer

A significant proportion of non-small cell lung cancer (NSCLC) patients experience accumulating chemotherapy-related adverse events, motivating the design of chemosensitizating strategies. The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks (DSB). It is thus conceivable that DNA-dependent protein kinase (DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy. The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC. We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis. M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549, H460 and H1703 NSCLC cell lines. In the four combinations based on two NSCLC xenograft models and two chemotherapy, we also observed tumor regression at tolerated doses

Correlation between total cholesterol/high-density lipoprotein cholesterol ratio and asymptomatic carotid atherosclerotic plaque stability / 国际脑血管病杂志

Objective:To investigate the correlation between total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio and unstable carotid plaque.Methods:From February 2021 to May 2021, adult patients with asymptomatic carotid atherosclerotic plaque admitted to the Department of Neurology, the First People's Hospital of Lianyungang were retrospectively enrolled. The demographic and related clinical data were collected. Carotid artery plaques were detected by ultrasound, and the subjects were divided into a stable plaque group and an unstable plaque group. Multivariate logistic regression analysis was used to assess the independent risk factors for unstable carotid plaques. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of TC/HDL-C ratio for unstable carotid plaques. Results:A total of 362 patients with asymptomatic carotid atherosclerotic plaque were enrolled, including 226 (62.43%) in the stable plaque group and 136 (37.57%) in the unstable plaque group. Multivariate logistic regression analysis showed that after adjusting for confounding factors, only TC/HDL-C ratio was the independent risk factor for unstable carotid plaque (taking the 1 st quintile array of TC/HDL-C ratio as a reference, the 4 th quintile array: odds ratio 3.13, 95% confidence interval 1.50-6.55, P=0.002; the 5 th quintile array: odds ratio 6.75, 95% confidence interval 3.21-14.22, P<0.001). ROC curve analysis showed that the area under the curve of TC/HDL-C ratio for predicting unstable carotid plaque was 0.691 (95% confidence interval 0.634-0.748; P<0.001), the optimal cut-off value was 4.38, and the sensitivity and specificity were 50.0% and 82.7%, respectively. Conclusion:TC/HDL-C ratio is an independent risk factor for unstable carotid plaques and has a certain predictive value for unstable carotid plaques.

Circadian clock and ischemic stroke / 国际脑血管病杂志

Almost all life on Earth has a 24 h circadian rhythm. The circadian clock that controls the circadian rhythm is an important regulator of physiology and disease. Disturbance of circadian rhythm can negatively affect physiological homeostasis at the molecular, cellular, organ system, and whole organism levels. The circadian clock rhythm disorders are considered to be involved inmany cardiocerebrovascular diseases, such as ischemic stroke and myocardial infarction. Ischemic stroke is one of the main causes of long-term disability and death worldwide. The incidence is higher in the daytime and lower at night, but the exact mechanism of this time distribution is unclear. This article discusses the role of the circadian clock in stroke pathophysiological mechanism and the specific molecular mechanism of clock gene regulation. It is expected that molecular time can be used or changed to open up new targets for stroke treatment.

Sirolimus combined with prednisone in the treatment of Kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon: a preliminary study / 中华皮肤科杂志

Objective:To preliminarily assess the clinical value of sirolimus combined with prednisone in the treatment of Kaposiform hemangioendothelioma (KHE) complicated by Kasabach-Merritt phenomenon (KMP) .Methods:A retrospective study was conducted. General clinical data and relevant data on efficacy and adverse reactions were collected from 36 patients with KHE complicated by KMP, who received oral sirolimus combined with prednisone in Department of Pediatric Surgery, West China Hospital, Sichuan University from January 2011 to January 2018.Results:Among the 36 patients with KHE complicated by KMP, the male-to-female ratio was 1∶0.8; their average age was 15.0 months (range, 4.0 - 60.0 months) , and the average age of onset was 6.3 months (range, 0.8 - 48.0 months) ; 32 (88.9%) patients were diagnosed with mixed KHE, and 4 (11.1%) with deep KHE; the tumor size ranged from 2.5 cm × 4.0 cm to 20.0 cm × 24.0 cm. During the combined treatment, the average duration of prednisone administration was 6.4 weeks (range, 5.0 - 9.0 weeks) , and that of sirolimus administration was 19.3 months (range, 13.0 - 27.0 months) . After 1-5 weeks of combined treatment, platelet counts and fibrinogen levels of the 36 patients gradually returned to normal. After short-term prednisone combined with long-term sirolimus treatment, the average disease severity score decreased from 4.0 before treatment to 2.4 at 6 months and 1.6 at 12 months. After 12 months of the combined treatment, tumors mostly regressed in 32 (88.9%) patients, partially regressed in 3 (8.3%) , showed no obvious change in 1 (2.8%) . During the treatment, common adverse reactions included gastrointestinal discomfort and oral ulcers, no patient discontinued the treatment due to severe adverse reactions, and no drug toxicity-related death occurred.Conclusion:Sirolimus combined with prednisone is effective and safe for the treatment of KHE complicated by KMP.

Expression profiling of long noncoding RNAs and mRNAs in infantile hemangioma / 中华皮肤科杂志

Objective:To investigate differentially expressed long noncoding RNAs (lncRNAs) and mRNAs between proliferating and involuting infantile hemangioma (IH) .Methods:Eight IH specimens were surgically resected from 4 children with proliferating IH and 4 with involuting IH in Department of Pediatric Surgery, West China Hospital, Sichuan University from January to March in 2019. Differentially expressed lncRNAs and mRNAs between proliferating and involuting IH (a P value < 0.05 and a fold change ≥ 2.0) were screened by microarray analysis, and verified by real-time fluorescence-based quantitative PCR (qRT-PCR) . Bioinformatics analysis was further performed, including GO and KEGG pathway analyses of differentially expressed mRNAs, construction of a lncRNA-mRNA co-expression network, and prediction of cis-acting target genes of differentially expressed lncRNAs. Results:A total of 405 differentially expressed lncRNAs and 772 differentially expressed mRNAs were identified between the proliferating and involuting IH specimens by using microarray technology. Of them, 108 lncRNAs and 107 mRNAs were downregulated, 297 lncRNAs and 665 mRNAs were upregulated in the proliferating IH specimens. Four lncRNAs (n335248, ENST00000450864, n333319, and n335185) and 4 mRNAs (EDNRA, IFI6, HK2, and ITGA1) were verified by qRT-PCR, and the results were consistent with those of microarray analysis. GO and KEGG enrichment analyses showed that differentially expressed mRNAs were mainly involved in the biological processes blood coagulation, axon guidance, angiogenesis and cell adhesion. Besides, differentially expressed mRNAs were mostly enriched in the metabolic pathways focal cell adhesion, regulation of actin cytoskeleton, leukocyte transendothelial migration and phosphatidylinositol 3-kinase/serine-threonine protein kinase and other signaling pathways. In addition, a lncRNA-mRNA co-expression network was constructed with 23 mRNAs and 58 lncRNAs with the degree ≥ 15.Conclusion:Lots of differentially expressed lncRNAs and mRNAs were identified between proliferating and involuting IH tissues, and these lncRNAs may play important roles in the development of IH by regulating corresponding target mRNAs.

Effects of Donepezil treatment on the expression of high-mobility group box 1 in serum and cerebrospinal fluid in Alzheimer's disease patients / 中华老年医学杂志

Objective:To investigate the effect of Donepezil treatment on the expression of high mobility group box 1 protein(HMGB1)in serum and cerebrospinal fluid in Alzheimer's disease patients.Methods:This is a single-center observational stady.A total of 120 Alzheimer's disease patients admitted in our hospital from March 2017 to may 2019 were randomly divided into the control group receiving the routine drug therapy(n=60)and the Donepezil group receiving Donepezil hydrochloride(5 mg/d)as an add-on to medicine of control group(n=60). The expression levels of HMGB1 in serum and cerebrospinal fluid, Alzheimer's disease assessment scale(ADAS-Cog), mini-mental state examination(MMSE)scores, activities of daily living(ADL)and neuropsychiatric inventory(NPI)were compared before versus after 1 month of treatment.Results:After the Donepezil treatment, the ADAS-Cog score was lower, MMSE score was higher, ADL score was higher and NPI score was lower in the Donepezil group than in the control group(25.2± 2.7 vs.33.4± 3.6, 23.3± 2.1 vs.19.4±1.9, 56.3±2.1 vs.46.9±1.6, 16.2±2.3 vs.22.3± 2.6, P<0.05). After the Donepezil treatment, the levels of HMGB1 in serum[(45.3±5.3)μg/L vs.(56.3±4.4)μg/L]and in cerebrospinal fluid[(39.2±3.3)μg/L vs.(47.1±3.9)μg/L]were lower in the Donepezil group than in the control group(all P<0.05). Conclusions:Donepezil treatment can downregulate the HMGB1 expression levels in serum and cerebrospinal fluid in Alzheimer's disease patients, which may related to the improvement of cognitive function in Alzheimer's disease patients.

Clinical characteristics of Kaposiform lymphangiomatosis: a report of 8 cases / 中华外科杂志

Objective@#To investigate the clinical symptoms, treatment intervention and prognosis of Kaposiform lymphangiomatosis(KLA).@*Methods@#Medical information and clinical characteristics data of 8 KLA patients who were admitted to Department of Pediatric Surgery of West China Hospital of Sichuan University from January 2016 to February 2019 were retrospectively reviewed and analyzed. There were 5 males and 3 females with age of 5.8 years old (from 8 months to 29 years old).@*Results@#The lesions in all patients were diffusely distributed. In all 8 patients, the lung and mediastinum were involved with different degrees. Three cases had lesions involving pelvic and abdominal organs. Three cases had lesions involving bones. One case simultaneously involved pelvic and abdominal organs, and 1 case was involved laryngeal and neck. The clinical characteristics were mainly respiratory symptoms. In the laboratory tests, 6 patients had different degrees of thrombocytopenia (minimum 3 × 109/L), and 4 patients had severe fibrinogen reduction (minimum 0.42 g/L). Three patients had prolonged activated partial thromboplastin time (up to 64.2 seconds) and 3 patients had prolonged prothrombin time (up to 18.6 seconds). After surgery (including thoracotomy, chest tube, pericardiocentesis, splenectomy) and empiric medicine therapy (vincristine, sirolimus and corticosteroid), the symptoms improved in 1 case, 2 cases died of complications, 2 cases were stable and 3 cases progressed up to February 2019.@*Conclusions@#KLA is a rare disease that should be differentiated from other types of vascular diseases. Currently, there is no consensus treatment guidelines exist. Accurate diagnosis in KLA can be a challenge. The situation in patients with KLA is prone to rapid deterioration and progress. Future research efforts should seek to develop target-specific drugs for KLA.

Hemodynamic analysis of a new retrievable vena cava filter / 生物医学工程学杂志

Vena cava filter is a filter device designed to prevent pulmonary embolism caused by thrombus detached from lower limbs and pelvis. A new retrievable vena cava filter was designed in this study. To evaluate hemodynamic performance and thrombus capture efficiency after transplanting vena cava filter, numerical simulation of computational fluid dynamics was used to simulate hemodynamics and compare it with the commercialized Denali and Aegisy filters, and in vitro experimental test was performed to compare the thrombus capture effect. In this paper, the two-phase flow model of computational fluid dynamics software was used to analyze the outlet blood flow velocity, inlet-outlet pressure difference, wall shear stress on the wall of the filter, the area ratio of the high and low wall shear stress area and thrombus capture efficiency when the thrombus diameter was 5 mm, 10 mm, 15 mm and thrombus content was 10%, 20%, 30%, respectively. Meanwhile, the thrombus capture effects of the above three filters were also compared and evaluated by in vitro experimental data. The results showed that the Denali filter has minimal interference to blood flow after implantation, but has the worst capture effect on 5 mm small diameter thrombus; the Aegisy filter has the best effect on the trapping of thrombus with different diameters and concentrations, but the low wall shear stress area ratio is the largest; the new filter designed in this study has a good filtering and capture efficiency on small-diameter thrombus, and the area ratio of low wall shear stress which is prone to thrombosis is small. The low wall shear stress area of the Denali and Aegisy filters is relatively large, and the risk of thrombosis is high. Based on the above results, it is expected that the new vena cava filter designed in this paper can provide a reference for the design and clinical selection of new filters.

Advances in the application of claudins to tumor therapy / 生物工程学报

Claudin proteins are the most crucial components of tight junctions, and play an essential role in maintaining cell polarity, regulating cell permeability and the intercellular ion. In recent years, many studies have shown that abnormality of claudins expression is implicated in the tumor progression. The expression correlates with tumor prognosis and can serve as a biomarker of prognosis and potential therapeutic targets. This review summarizes the current knowledge regarding claudin dysregulation in cancer and highlights the progress in claudin-based treatments.

Fabrication of multifunctional bismuth-doped iron nanoparticle and its radiotherapy sensitization in glioblastoma / 中国组织工程研究

BACKGROUND:Bismth-doped iron nanoparticles modified by hyaluronic acid (HA-BiIOPs) not only act as an effective MRI contrast agent, but also as a radiotherapy sensitizer.OBJECTIVE:To fabricate the HA-BiIOPs and to observe its effect to enhance the radiosensitivity of glioblastoma cells U87MG under X-ray radiation.METHODS:HA-BiIOPs were synthesized using hydrothermal polyol method. (1) Cytotoxicity: A cytotoxicity test was carried out on U87MG cells and rat vascular smooth muscle cells (VSMCs). Cell proliferation rate of two kinds of cells cultured with different concentrations of HA-BiIOPs (0, 12.5, 25, 50, 100, 200, 400 mg/L) at 24 hours after culture were determined by cell counting kit-8 assay. (2) Histological analysis: ICR mice were sacrificed after intravenous injection of HA-BiIOPs, and pathological changes of mouse visceral organs were observed under an optical microscope. (3) Cellular uptake: The HA-BiIOPs after entered into the cytoplasm were observed by Prussian blue staining. (4) Radiosensitization test: U87MG cells at Logarithmic growth stage were cultured in culture medium as control group, subjected to X-ray irradiation (0, 3, 6, 9 Gy) as radiotherapy group, cultured in HA-BiIOPs (0, 12.5, 25, 50, 100, 200 and 400 mg/L) as HA-BiIOPs group or subjected to HA-BiIOPs culture plus X-ray irradiation as combined therapy group. Then, the cell proliferation rate and cloning efficiency were measured at 24 hours after treatment.RESULTS AND CONCLUSION:(1) The HA-BiIOPs at different concentrations were non-cytotoxic for VSMC and U87MG cells. (2) After intravenous injection of HA-BiIOPs, there was no obvious toxicity to the mouse susceptible organs. (3) After 6 hours of culture, the HA-BiIOPs could be internalized by U87MG cells. (4) The proliferation rate of U87 cells was negatively correlated with the concentration of HA-BiIOPs (0-200 mg/L) and X-ray dose (0-9 Gy). Especialy, the combination of 6 Gy X-ray irradiation with 200 mg/L HA-BiIOPs dramatically decreased the cell viability that was decreased to (41±7)%. In the combined therapy group with 6 Gy X-ray and 100 mg/L HA-BiIOPs, the cells proliferation rate was significantly lower than that in the control and radiotherapy groups (P < 0.05). These results indicate that HA-BiIOPs have a radiosensitizative effect on glioblastoma cells U87MG.

Tissue-engineered bone with vascular bundles or sensory nerve tracts for repairing large bone defects / 中国组织工程研究

BACKGROUND: Neuropeptides, a kind of endogenous active substance in nerve tissues, can modulate physiological functions of multiple body systems.OBJECTIVE: To observe the effects of vascular bundles or sensory nerve tracts implanted into tissue-engineered bone for rabbit large bone defects on the expression levels of calcitonin gene-related peptide (CGRP) and neuropeptide-Y.METHODS: Fifty-four New Zealand rabbits were enrolled to make model of large bone defects, and then, the animal models were randomly divided into three groups, including sensory nerve tract, vascular bundle, and control groups (n=18 per group), followed by implanted with sensory nerve tracts, vascular bundle, and tissue-engineered bone without sensory tracts or vascular bundle, respectively. The defected bone received gross and Masson staining at 4, 8 and 12 weeks after modeling, to compare the expression levels of CGRP and neuropeptide-Y in each group.RESULTS AND CONCLUSION: mRNA expression levels of CGRP and neuropeptide-Y in the sensory nerve tract and vascular bundle groups were significantly higher than those in the control group at different time points after modeling (P < 0.05). mRNA expression levels of CGRP and neuropeptide-Y in the tissue-engineered bone began to be increased and peaked at the 8th week, and then decreased (P < 0.05), which were the lowest at the 4th week (P < 0.05).Immunohistochemical staining results showed that CGRP was mainly found in the bridge, periosteum of newly born bones and around blood vessels; while neuropeptide-Y mainly localized in the medullary cavity and around blood vessels. These results indicate that the implantation of vascular bundle and sensory nerve tracts for bone defects can upregulate the expression levels of CGRP and neuropeptide-Y, and promote bone repair. However, sensory tract implantation may cause sensory impairment; thereafter, vascular bundle implantation is more suitable for ideal tissue-engineered construction to meet physical requirements.

Implantation of tissue-engineered bone with vascular bundles or sensory nerve tracts for large femoral defects:the middle-and long-term expression of calcitonin gene related peptide type Ⅰ receptor / 中国组织工程研究

BACKGROUND:Previous study has proved that implantation of the tissue-engineering bone with vascular bundles or sensory nerve tracts can promote bone formation, which may be related to the expression of sensory neuropeptide receptors. OBJECTIVE:To investigate the effect of implantation of tissue-engineered bone containing vascular bundles and sensory nerve tracts on the middle-and long-term expression of calcitonin gene-related peptide type Ⅰ receptor (CGRP1R) in the repair of rabbit large femoral defects. METHODS:Thirty-six New Zealand white rabbits were enrol ed and modeled into 1.5 cm femoral defects, and then randomized into three groups. Bone marrow mesenchymal stem cells (BMSCs) were subjected to osteoblastic induction for 7 days, and then seeded onto the β-calcium phosphate scaffold to construct the tissue-engineered scaffold.In sensory nerve group, the tissue-engineered scaffold was implanted into the defect region, and autologous sensory nerve bundles were implanted into the lateral groove of the tissue-engineered bone;in vascular bundle group, the tissue-engineered scaffold was implanted, and autologous femoral blood bundles were implanted into the lateral groove of the tissue-engineered bone;in blank control group, only the tissue-engineered scaffold was implanted. X-ray examination, immunohistochemistry and real-time PCR were performed at 24 and 48 weeks postoperatively. RESULTS AND CONCLUSION:The X-ray scores in the sensory nerve and vascular bundle groups were significantly higher than that in the control group (P<0.05), but no significant difference was found between sensory nerve and vascular bundle groups. Real-time PCR found that the expression level of CGRP1R mRNA in the vascular bundle group was significantly higher than that in the other two groups (P<0.05), but showed no significant difference between sensory nerve and blank control groups.Immunohistochemistry findings showed that CGRP1R positive expression rate in the sensory nerve and vascular bundle groups was higher than that in the blank control group. These results reveal that implantation of the tissue-engineered bone containing vascular bundles can promote the CGRP1R expression.

Effect of Selective beta-1 Adrenoreceptor Blocker on Exercise Tolerance in Patients with Hypertention / 中国康复理论与实践

Objective To explore the effect of selective beta-1 adrenoreceptor blocker on exercise tolerance in patients with hyperten-sion. Methods From May, 2015 to May, 2016, 72 patients with hypertension were divided into two groups, according to whether taking the selective beta-1 receptor blocker. Group A (n=35) took the selective beta-1 receptor blocker two weeks before cardiopulmonary exercise, while group B (n=37) did not take anything at the same time. The exercise tolerance was compared between two groups. Results The maxi-mal systolic blood pressure, peak heart rate, one-minute heart rate after exercise (HR1) and rate-pressure product were lower in group A than in group B (t>2.012, P0.05). Conclusion The selective beta-1 adrenore-ceptor blocker could reduce myocardial oxygen consumption, and improve vagus nerve activity, but did not reduce exercise tolerance in pa-tients with hypertension.