The effectiveness and safety of laparoscopic versus open hepatectomy for intrahepatic cholangiocarcinoma: a meta-analysis / 中华肝胆外科杂志

Objective:To compare the effectiveness and safety of laparoscopic hepatectomy (LH) versus open hepatectomy (OH) for intrahepatic cholangiocarcinoma(ICC).Methods:PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine Disc, China National Knowledge Infrastructure, Wanfang Database and VIP Database were searched from inception of these databases to May 2022 to compare LH versus OH for ICC. The duration of operation, intraoperative bleeding, proportion of patients with intraoperative blood transfusion, number of resected lymph nodes, proportion of patients with R 0 resection margin, duration of hepatic occlusion, hospital stay, incidence of postoperative complication and postoperative mortality were compared between the two groups. Meta-analysis was carried out using the Review Manager 5.1 software, and the mean difference ( MD) or odds ratio ( OR) was used as the effect index. Results:This meta-analysis included twelve articles, all of which were retrospective cohort studies, with 3 189 patients. There were 667 patients in the LH group and 2 512 in the OH group. Meta-analysis showed that when compared to the OH group, the LH group had significantly less intraoperative bleeding ( MD=-116.06, 95% CI: -173.07--59.06, P<0.001), less proportion of patients receiving intraoperative blood transfusion ( OR=0.25, 95% CI: 0.10-0.62, P=0.003), less number of lymph nodes removed ( MD=-101.91, 95% CI: -124.78--79.03, P<0.001), less patients underwent portal occlusion ( OR=0.37, 95% CI: 0.14 - 0.99, P=0.050), shorter hospital stay ( MD=-2.43, 95% CI: -4.59--0.28, P=0.030) and less postoperative complications ( OR=0.41, 95% CI: 0.28-0.61, P<0.001). However, the proportion of patients with R 0 margin ( OR=1.49, 95% CI: 1.14-1.95, P=0.003) in the LH group was significantly higher than the OH group. There were no significant differences in operative time and postoperative mortality between the 2 groups. Conclusion:LH was more effective and safe than OH in the treatment of ICC. However, its long-term effect still needs to be verified by large randomized controlled trials.

Management practice of Investigator-Initiated Trials in the new period / 中华医学科研管理杂志

Objective:In the context of China′s increasing standardized management requirements of clinical research, this article aims to explore the management methods of investigator-initiated trials in the new period, to provide possible reference for other medical institutions dedicated to clinical research.Methods:According to the requirements set forth by the＂Administrative Measures for Investigator-Initiated Trials in Medical and Health Institutions (Trial)", combined with the hospital management practice, experiences regarding the research management system construction and implementation, management system construction and its implementation effects are summarized and analyzed.Results:By exploring and summarizing the connotation of high-quality clinical research under the New Policy, tailored clinical research management system in our hospital was developed and implemented. And the hospital′s clinical research capability and level have been greatly improved, which enhancing the hospital academic influence, as well as its competence for serving the development of national and regional clinical research.Conclusions:Along with the rapid progress of clinical research, hospitals need to assure the compliance of national laws and regulations, and develop appropriate and applicable institutional management measures to empower the conduct of high quality clinical research.

Activation of Cannabinoid Receptor 1 in GABAergic Neurons in the Rostral Anterior Insular Cortex Contributes to the Analgesia Following Common Peroneal Nerve Ligation / 神经科学通报·英文版

The rostral agranular insular cortex (RAIC) has been associated with pain modulation. Although the endogenous cannabinoid system (eCB) has been shown to regulate chronic pain, the roles of eCBs in the RAIC remain elusive under the neuropathic pain state. Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve (CPN) ligation. The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice, glutamatergic, or GABAergic neuron cannabinoid receptor 1 (CB1R) knockdown mice with the whole-cell patch-clamp and pain behavioral methods. The E/I ratio (amplitude ratio between mEPSCs and mIPSCs) was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice. Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice. The analgesic effect of ACEA (a CB1R agonist) was alleviated along with bilateral dorsolateral funiculus lesions, with the administration of AM251 (a CB1R antagonist), and in CB1R knockdown mice in GABAergic neurons, but not glutamatergic neurons of the RAIC. Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.

Construction of macrophage-specific MST1 knockout mouse model / 安徽医科大学学报

Objective @# To establish myeloid ( including macrophage and granulocyte) specific knockout mice of mammalian sterile line 20-like kinase 1 (MST1) gene for furtherinvestigating the role and the mechanism of MST1 in macrophages in related clinical diseases．@*Methods @#Mst1flox/flox LysM-Cre ( referred to as Mst1ΔM/ΔM hereafter) mice were generated by crossing Mst1flox/floxwith lysozyme (Lysm-Cre) mice．The loxP site and Cre gene were amplified by PCR for genotyping．The knockdown efficiency of MST1 in macrophages was verified by quantitative PCR and immunofluorescence．The main immune cell populations in the livers were detected by flow cytometry. @*Results@#Mst1flox/flox LysM-Cre (Mst1ΔM/ΔM ) was the genotype of macrophage specific knockout MST1 mice．The results of qPCR and immunofluorescence showed that the knock-out efficiency of MST1 was more than 70% in bone marrow- derived macrophages and peritoneal macrophages．Flow cytometry showed that macrophage knockout of MST1 had no significant effect on the main immune cell populations in the liver of mice．@*Conclusion @# Macrophage-specific knockout of MST1 mouse model is successfully established，which lays a foundation for further investigation on the role and mechanism of macrophage MST1 in clinical related disease.

Nomogram for predicting the response to chemoradiotherapy in advanced nasopharyngeal carcinoma based on arterial spin-labeled perfusion parameters and clinicopathological features / 中华放射学杂志

Objective:To explore the value of nomogram based on arterial spin labeling (ASL) MRI perfusion parameters and clinicopathological features in predicting the response to chemoradiotherapy (CRT) in advanced nasopharyngeal carcinoma (ANPC, stage Ⅲ and Ⅳ).Methods:From June 2018 to January 2021, 70 patients with ANPC confirmed by pathology were prospectively enrolled in Affiliated Hospital of Jiangnan University. Nasopharyngeal MRI plain scan, ASL and contrast-enhanced scan were performed before CRT, and routine MRI re-examination was performed within 1 week after the end of CRT. The pre-CRT perfusion parameter tumor blood flow (TBF) from ASL and clinicopathological features were recorded, and the maximum diameter (MD) of the tumor on T 1WI images was measured. The patients were divided into CRT effective group (48 cases) and ineffective group (22 cases) according to the response evaluation criteria in solid tumors. The independent sample t test was used to compare the differences of TBF, age and MD between effective group and ineffective group. The χ 2 test was used to compare the differences of gender, clinical stage and pathological type between the 2 groups. Using binary logistic regression analysis, clinicopathological model and TBF combined clinicopathological model were constructed, and the nomogram of combined model was constructed. The diagnostic efficacy of the models was obtained by receiver operating characteristic (ROC) curve analysis, and the area under the ROC curves (AUC) of the 3 models were compared by DeLong method. The calibration curve for the nomogram was generated, and the concordance index (C index) was acquired. Results:The TBF of the effective group and the ineffective group were (113±9) and (97±14) ml·100 g -1·min -1, with a statistical difference ( t=5.17, P<0.001). The MD value of the effective group was smaller than that of the ineffective group, with a statistical difference ( t=-2.24, P=0.028). There were statistical differences in clinical stage and pathological type between the 2 groups (χ 2 values were 12.21 and 12.95, respectively, both P<0.001). Three independent predictors, including TBF (OR=7.749), clinical stage (OR=0.129) and pathological type (OR=5.228), were included in logistic regression analysis. The AUC, sensitivity and specificity of TBF model in predicting the response to CRT were 0.843, 87.5% and 72.7%, of clinicopathological model were 0.822, 80.2% and 59.1%, of the nomogram model were 0.893, 81.2% and 90.9%. There was no statistical difference of AUC between the nomogram model and TBF model ( Z=1.23, P=0.215). However, the AUC of the nomogram model was greater than that of the clinicopathological model ( Z=2.47, P=0.031). The calibration curve showed that there was a good concordance index (C index=0.892) between the predicted value of nomogram and the actual clinical observation value. Conclusion:TBF, clinical stage and pathological type are independent predictors of the response to CRT in ANPC patients, and the nomogram based on these three factors has a good ability in predicting the response to CRT.

Efficacy of gastrodin injection combined with dexamethasone in the treatment of sudden deafness and its effect on hemorheology and hearing / 中国基层医药

Objective:To investigate the efficacy of gastrodin injection combined with dexamethasone in the treatment of sudden deafness and its effect on hemorheology and hearing.Methods:Eighty patients with sudden deafness who received treatment in the Department of Otolaryngology, General Hospital of Taiyuan Iron and Steel (Group) Co., Ltd., from August 2018 to March 2020 were included in this study. These patients were randomly assigned to receive either intratympanic injection of dexamethasone (control group, n = 40) or intratympanic injection of dexamethasone combined with gastrodin injection (treatment group, n = 40). Total effective rate was compared between the two groups. The auditory threshold at 0.5, 1.0, 2 and 4 kHz was measured in each group. Before and after treatment, plasma viscosity, low shear whole blood viscosity, fibrinogen and erythrocyte deformability index were compared between the two groups. Drug-related adverse reactions were recorded in each group. Results:Total effective rate in the treatment group was significantly higher than that in the control group [92.50% (37/40) vs. 75.00% (30/40), χ2 = 4.401, P < 0.05]. After treatment, the auditory threshold at 0.5, 1.0, 2 and 4 kHz was significantly decreased compared with before treatment in each group (all P < 0.001). After treatment, the auditory threshold at 0.5, 1.0, 2 and 4 kHz was (42.71 ± 7.06) dB, (44.01 ± 9.35) dB, (48.06 ± 11.37) dB and (52.40 ± 14.26) dB, respectively, in the treatment group and (50.14 ± 8.09) dB, (53.70 ± 10.46) dB, (55.10 ± 13.47) dB and (59.26 ± 15.77) dB respectively in the control group. There were significant differences between the two groups ( t = 4.376, 4.368, 2.526 and 2.267, all P < 0.05). After treatment, plasma viscosity, low shear whole blood viscosity and fibrinogen in each group were significantly decreased (all P < 0.001). After treatment, erythrocyte deformability index in each group was significantly increased ( P < 0.001). After treatment, plasma viscosity, low shear whole blood viscosity and fibrinogen were significantly decreased, and erythrocyte deformability index was significantly increased, compared with before treatment in each group. After treatment, plasma viscosity, low shear whole blood viscosity and fibrinogen, and erythrocyte deformability index were (1.68 ± 0.39) mPa · s, (19.07 ± 3.65) mPa · s, (3.11 ± 0.58) g/L, (0.68 ± 0.08), respectively in the treatment group, and (2.01 ± 0.41) mPa · s, (22.10 ± 4.49) mPa · s, (3.89 ± 0.75) g/L, (0.60 ± 0.07) respectively in the control group. There were significant differences in plasma viscosity, low shear whole blood viscosity and fibrinogen, and erythrocyte deformability index between the two groups ( t = 3.688, 3.312, 5.203, 4.760, all P < 0.05). There was no significant difference in the incidence of adverse reactions between the treatment and control groups (10.00% vs. 15.00%, χ2 = 0.457, P > 0.05). Conclusion:Gastrodin injection combined with dexamethasone can enhance the curative effect on sudden deafness, effectively improve patient's hemorheology and hearing, and is highly safe.

Expression of serum Cav-1 and YKL-40 in acute cerebral infarction and the value of combined detection in prognosis evaluation / 中国医师杂志

Objective:To explore the expression of caveolin-1 (Cav-1) and Chitinase-40 (YKL-40) in acute cerebral infarction and the value of combined detection in prognosis evaluation.Methods:118 patients with acute cerebral infarction admitted to the First Affiliated Hospital of Hebei Northern University from January 2016 to June 2019 were selected as the research objects. According to the cerebral infarction volume, the patients were divided into small infarction group (<5 cm 3), middle infarction group (5-10 cm 3) and large infarction group (>10 cm 3). 108 healthy people were selected as the healthy control group. The serum levels of Cav-1 and YKL-40 were compared in the 3 groups, and the correlation between the degree of cerebral infarction and serum levels of Cav-1 and YKL-40 was analyzed. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of the expression levels of Cav-1 and YKL-40 in patients with acute cerebral infarction; the patients were followed up for one year and the prognosis was evaluated by modified Rankin Scale (mRS); the correlation between serum Cav-1 and YKL-40 and prognosis was analyzed. Results:The expression levels of serum Cav-1 and YKL-40 in patients with acute cerebral infarction were significantly higher than those in healthy group ( P<0.001). The serum levels of Cav-1 and YKL-40 were positively correlated with the infarct volume of acute cerebral infarction ( r=0.854, P=0.004; r=0.867, P=0.002). ROC curve analysis showed that the sensitivity, Youden index and area under ROC curve of Cav-1 (21.78 μg/L) combined with YKL-40 (158.69 ng/ml) in the diagnosis of acute cerebral infarction were 85.59%, 0.532 and 0.896 (95% CI: 0.741-0.932), respectively, which were significantly higher than those of single index ( P<0.05). At 8 and 12 months of follow-up, the proportion of death and mRS score in the positive group were significantly higher than those in the negative group ( P<0.05). Conclusions:The serum Cav-1 and YKL-40 levels are significantly higher in patients with acute cerebral infarction. The combined examination of Cav-1 and YKL-40 can improve the diagnostic efficiency and has potential application value for early diagnosis and prognosis prediction of patients.

Analysis on patent intelligence of COVID-19 prevention technology based on Regional Patent Information Dervice (Nanjing) Center / 中华医学科研管理杂志

Objective:This study analyzes COVID-19 prevention and treatment technology patents from 103 countries and regions worldwide, in order to have a good grasp of the most-current trends in COVID-19 prevention and treatment technology research worldwide, discuss the research directions of such technologies, provide theoretical foundations for interdisciplinary and multi-team cooperation.Methods:The retrieval strategies were constructed utilizing the retrieval and analysis system by the Regional Patent Information Service (Nanjing) Center of The State Intellectual Property Office and IncoPat's scientific and technological innovation platform, using third-level branches as the unit and separating the retrieval and proof processes, the queries built using IPC classification numbers and key words; the search was limited to invention patents, with utility models and designs excluded.Results:On February 14, 2020, there had been a total number of 136 087 invention patent applications for COVID-19 prevention and treatment technologies globally. In terms of the country of origin, the U. S. ranked first with 56 095 patents, followed by China (18 096). In terms of technical field, the top three were chemical therapeutic agents (47 634), vaccines (47 248) and diagnostic tests (12 991), with the U. S. possessing absolutely advantageous patent portfolios in all three fields. The applicants were mainly comprised of large enterprises abroad and universities and research institutes in China.Conclusions:China′s COVID-19 related patent applications are relatively scattered. In the field of chemotherapy, there is room for improvement compared with the advanced countries, and cooperation between scientific institutions and enterprises is insufficient. Therefore, China should further increase investment in chemical drug research and development and seize the opportunity to actively promote the research and development of vaccine technology. On the other hand, we need to consolidate the technical advantages and product advantages of epidemic prevention and control which are already accumulated, and strengthen the protection and layout of intellectual property rights. Furthermore, the technological innovation system combining production, education and research is the breakthrough point to encourage enterprises to become the subject of technological innovation.Last but not least, we should build a service platform for the transfer and transformation of scientific and technological achievements to enhance intellectual property rights and promote the transformation of scientific and technological achievements.

Therapeutic effect and mechanism of hydrogel-encapsulated human umbilical cord mesenchymal stem cells on traumatic brain injury in rats / 解剖学报

Objective To investigate the therapeutic effect of hydrogel-encapsulated human umbilical cord mesenchymal stem cells (hUC-MSCs) on traumatic brain injury in rats and its related mechanism. Methods SD rat models of traumatic brain injury were constructed, which were divided into control group, chitosan group, stem cell group and combined treatment group. Results During the treatment, there was no significant difference in mNSS score between the control group and the chitosan group (P>0.05). On the 15th, 22nd, 29th and 36th day, the mNSS score of the combined treatment group decreased most significantly than that of the control group, followed by the stem cell group (P0.05), and the expression of related proteins in the stem cell group and the combined treatment group increased significantly. The expression level of the related protein in the combined treatment group was the highest, followed by stem cell group, the lowest in the control group and chitosan group (P<0.05). Conclusion Compared with stem cell transplantation alone, hydrogel-encapsulated hUC-MSCs transplantation can improve the motor and learning and memory abilities of rats with traumatic brain injury more effectively.

Risk Factors for Intraprocedural Rerupture during Embolization of Ruptured Intracranial Aneurysms

Background@#Intraprocedural rupture (IPR) is a devastating complication in endovascular treatment of ruptured intracranial aneurysms, but its risk factors have not been fully assessed. This study was performed to explore the risk factors for IPR during embolization of ruptured cerebral aneurysms. @*Methods@#A total of 1,494 patients with ruptured intracranial aneurysms who underwent endovascular interventional embolization were enrolled. Clinical characteristics were collected for each patient. Univariate and multivariate logistic regression analysis was employed to identify the factors independently associated with IPR. A receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff values of continuous variables predicting IPR. @*Results@#Forty-one patients suffered from IPR (2.7%). Multivariate logistic regression analysis indicated that aneurysm size (odds ratio [OR], 0.819; 95% confidence interval [CI], 0.732–0.916), aneurysms with irregular morphology (OR, 2.162; 95% CI, 1.143–4.091), time from symptom onset to intervention (OR, 1.615; 95% CI, 1.207–2.161), and vasospasm during embolization (OR, 2.021; 95% CI, 1.038–3.934) were the independent risk factors of IPR. ROC curve analysis showed that the area under the curve for aneurysm size and time from onset to intervention were 0.697 (cutoff value, 3.4 mm; sensitivity, 78.8%; and specificity, 53.7%) and 0.659 (cutoff value, 2 days; sensitivity, 78.0%; and specificity, 45.2%), respectively. @*Conclusion@#Aneurysms with irregular morphology, aneurysms ≤ 3.4 mm in diameter, time from onset to intervention > 2 days and cerebral vasospasm during embolization are independent risk factors for IPR during coil embolization of ruptured aneurysms. More attention should be paid to the factors increasing the risk of IPR in patients with ruptured aneurysms so as to minimize this complication.

Risk Factors for Intraprocedural Rerupture during Embolization of Ruptured Intracranial Aneurysms

Background@#Intraprocedural rupture (IPR) is a devastating complication in endovascular treatment of ruptured intracranial aneurysms, but its risk factors have not been fully assessed. This study was performed to explore the risk factors for IPR during embolization of ruptured cerebral aneurysms. @*Methods@#A total of 1,494 patients with ruptured intracranial aneurysms who underwent endovascular interventional embolization were enrolled. Clinical characteristics were collected for each patient. Univariate and multivariate logistic regression analysis was employed to identify the factors independently associated with IPR. A receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff values of continuous variables predicting IPR. @*Results@#Forty-one patients suffered from IPR (2.7%). Multivariate logistic regression analysis indicated that aneurysm size (odds ratio [OR], 0.819; 95% confidence interval [CI], 0.732–0.916), aneurysms with irregular morphology (OR, 2.162; 95% CI, 1.143–4.091), time from symptom onset to intervention (OR, 1.615; 95% CI, 1.207–2.161), and vasospasm during embolization (OR, 2.021; 95% CI, 1.038–3.934) were the independent risk factors of IPR. ROC curve analysis showed that the area under the curve for aneurysm size and time from onset to intervention were 0.697 (cutoff value, 3.4 mm; sensitivity, 78.8%; and specificity, 53.7%) and 0.659 (cutoff value, 2 days; sensitivity, 78.0%; and specificity, 45.2%), respectively. @*Conclusion@#Aneurysms with irregular morphology, aneurysms ≤ 3.4 mm in diameter, time from onset to intervention > 2 days and cerebral vasospasm during embolization are independent risk factors for IPR during coil embolization of ruptured aneurysms. More attention should be paid to the factors increasing the risk of IPR in patients with ruptured aneurysms so as to minimize this complication.

Screening of Potential Biomarkers for Chronic Atrophic Gastritis Based on Urine Dynamic Metabolomics / 中国药学杂志

OBJECTIVE: To explore the mechanism of chronic atrophic gastritis (CAG) and screen the potential biomarkers. METHODS: CAG model was established in rats by using sodium deoxycholate solution and aqueous ammonia solution in combination with hunger and satiety method. After 10 weeks, the plasma and gastric tissues of model rats and control rats were collected to detect plasma biochemical parameters and pathological conditions of gastric tissues. The urine of model rats at 0, 4, 6, 8, and 10 weeks was collected during modeling, and 1H-NMR technique was used to monitor the metabolic profile of urine in different modeling periods of CAG rats. Multivariate statistical analysis method and relative distance formula were used to describe the dynamic changes of its metabolic profile. RESULTS: Significant differences in urine metabolism were found between the control group and the model group at the 8th week. Eighteen potential biomarkers of CAG were screened out, which participated in the biosynthesis of valine, leucine and isoleucine, TCA cycle, gut flora metabolism, glycine, serine and threonine metabolism, fatty acid metabolism, purine metabolism, and urea cycle. MetPA analysis demonstrated that glycine, serine and threonine metabolism, TCA cycle, valine, leucine and isoleucine biosynthesis are the most important metabolic pathway for CAG development. CONCLUSION: The pathogenesis of chronic atrophic gastritis may be related to the changes of glycine, serine and threonine metabolism, TCA cycle and the biosynthesis of valine, leucine and isoleucine. This finding laid the foundation for the study of the pathogenesis of CAG.

Endoscopic surgery for thalamic hemorrhage breaking into ventricles: Comparison of endoscopic surgery, minimally invasive hematoma puncture, and external ventricular drainage / 中华创伤杂志(英文版)

Purpose:@#Thalamic hemorrhage breaking into ventricles (THBIV) is a devastating disease with high morbidity and mortality rates. Endoscopic surgery (ES) may improve outcomes, although there is no consensus on its superiority. We investigated the efficacy and safety of ES and compared the outcomes of different management strategies by ES, hematoma puncture and drainage (HPD), and external ventricular drainage (EVD) in patients with THBIV.@*Methods:@#We retrospectively analyzed patients with THBIV treated by ES, HPD, or EVD at our hospital from June 2015 to June 2018. Patients were categorized into anteromedial and posterolateral groups based on THBIV location, and then the two groups were further divided into ES, HPD, and EVD subgroups. Individualized surgical approach was adopted according to the location of the hematoma in the ES subgroups. Patient characteristics and surgical outcomes were investigated.@*Results:@#We analyzed 211 consecutive patients. There were no significant differences in clinical characteristics or incidence of perioperative procedure-related complications (postoperative rebleeding and intracranial infection) in either anteromedial or posterolateral groups. Compared with other therapeutic methods, the ES subgroups had the highest hematoma evacuation rate, shortest drainage time, and lowest incidence of chronic ventricular dilatation (all p < 0.05). Among the three anteromedial subgroups, ES subgroup had the best clinical outcomes which was assessed by the modified Rankin Scale, followed by HPD and EVD subgroups (p < 0.01); while in the posterolateral subgroups, clinical outcomes in the ES and HPD subgroups were similar and better than that in the EVD subgroup (p = 0.037).@*Conclusion:@#Individualized surgical ES approach for removal of thalamic and ventricular hematomas is a minimally invasive, safe, and effective strategy for the treatment of THBIV with a thalamic hematoma volume of 10-30 mL.

Integrated 3D bioprinting-based geometry-control strategy for fabricating corneal substitutes / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

BACKGROUND@#The shortage of donor corneas is a severe global issue, and hence the development of corneal alternatives is imperative and urgent. Although attempts to produce artificial cornea substitutes by tissue engineering have made some positive progress, many problems remain that hamper their clinical application worldwide. For example, the curvature of tissue-engineered cornea substitutes cannot be designed to fit the bulbus oculi of patients.@*OBJECTIVE@#To overcome these limitations, in this paper, we present a novel integrated three-dimensional (3D) bioprinting-based cornea substitute fabrication strategy to realize design, customized fabrication, and evaluation of multi-layer hollow structures with complicated surfaces.@*METHODS@#The key rationale for this method is to combine digital light processing (DLP) and extrusion bioprinting into an integrated 3D cornea bioprinting system. A designable and personalized corneal substitute was designed based on mathematical modelling and a computer tomography scan of a natural cornea. The printed corneal substitute was evaluated based on biomechanical analysis, weight, structural integrity, and fit.@*RESULTS@#The results revealed that the fabrication of high water content and highly transparent curved films with geometric features designed according to the natural human cornea can be achieved using a rapid, simple, and low-cost manufacturing process with a high repetition rate and quality.@*CONCLUSIONS@#This study demonstrated the feasibility of customized design, analysis, and fabrication of a corneal substitute. The programmability of this method opens up the possibility of producing substitutes for other cornea-like shell structures with different scale and geometry features, such as the glomerulus, atrium, and oophoron.

Analysis of death causes for patients aged 60 years and over at a level A tertiary hospital in Beijing / 中华老年医学杂志

Objective To investigate the death causes in recent years,the ranking of causes and changes in ranking in elderly patients at a level A tertiary hospital in Beijing,in order to provide suggestions and a basis for effective prevention and management of diseases,achieve better utilization of medical resources and improve quality of life in the elderly.Methods Death records of 3991 patients aged over 60 years in the People's Hospital of Peking University from January 2010 to October 2016 were collected and retrospectively analyzed with SPSS 20.0 by using descriptive statistics,the linear-by-linear association test and the Pearson correlation coefficient.Results In the past 7 years,the top four causes of death were diseases of the circulatory system(1074 cases,30.1 ％),the respiratory system(1074 cases,26.9 ％),tumors (927 cases,23.2 ％) and the digestive system (284 cases,7.1 ％).There was no significant difference in the ranking of death causes between males and females.Of the death causes,the mortality rate of respiratory diseases increased and the mortality rates of the circulatory system and tumors decreased year by year.Diseases of the circulatory system ranked first in the death causes from 2010-2013,and diseases of the respiratory system ranked first from 2014-2016.The primary death cause was different in different age groups,with cancer for the 60-74 years old group,diseases of the circulatory system for the 75-84 years old group,diseases of the circulatory system for the over 85 years old group.The leading causes for death were coronary heart disease for diseases of the circulatory system,pulmonary infections for diseases of the respiratory system and digestive system tumors for tumors.Conclusions In recent years,the primary death cause in elderly patients at our hospital is circulation system diseases.The mortality rate of respiratory diseases has increased year by year.Death causes vary in different age groups,suggesting it is necessary to provide different screening and prevention measures for the elderly at different ages.

Affinity characterization of GE11 peptide to brain metastases from epidermal growth factor receptor-overexpressing human breast cancer / 中华核医学与分子影像杂志

Objective@#To investigate the feasibility of GE11 peptide targeting to brain metastases from epidermal growth factor receptor (EGFR)-positive breast cancer and thereby explore the potential for the construction of specific targeting molecular probe.@*Methods@#The EGFR expression level of triple negative breast cancer cell line (MDA-MB-231-BR) was detected using Western blot and flow cytometry. GE11 peptide targeting property was tested using immunofluorescence staining and flow cytometry in MDA-MB-231-BR cells and in the subcutaneous tumor model. GK-13 peptide was selected as the control peptide. Two-sample t test was used for data analysis.@*Results@#Western blot and flow cytometry showed that EGFR expression in MDA-MB-231-BR cells was 88.60%, significantly higher than those in other cells. Flow cytometry results indicated that the cell binding rate of MDA-MB-231-BR with GE11 peptide (10 μmol/L) was significantly higher than that with control peptide (38.4% vs 0.6%; t=16.941, P<0.01). Cell immunofluorescence staining results showed GE11 peptides were detected with stronger signal after being incubated with cells, and the combination was concentration- and temperature-dependent. In vivo experiment results showed that the signal of GE11 peptide was stronger in tumor site than that in other organs or tissues.@*Conclusion@#GE11 peptide may specifically target the brain metastases of EGFR-positive breast cancer.

Regulatory effect of faciogenital dysplasia 6 gene on hepatic stem cell differentiation / 中华肝脏病杂志

Objective@#To investigate the regulatory effect of faciogenital dysplasia 6 (FGD6) gene on hepatic stem cell differentiation.@*Methods@#FGD6 gene was selected for the co-intervention of target sequence, the AdEasy system was used for the construction of adenovirus vector and the packaging and multiplication of the recombinant adenovirus vector pSES-FGD6-siRNA, and the HP14.5 cells were infected. Immunofluorescence assay was used to measure the expression of FGD6 protein in HP14.5 cells, quantitative real-time PCR was used to measure the mRNA expression of FGD6, alpha-fetoprotein (AFP), and albumin (Alb), and Western blot was used to measure the protein expression of FGD6, AFP, and Alb. The empty pSES-Ad-RFP adenovirus vector was constructed as control in each group. All data were expressed as x±s, and a one-way analysis of variance was performed.@*Results@#FGD6 protein was mainly expressed in the nucleus of HP14.5 cells. The pSES-FGD6-siRNA adenovirus vector was successfully constructed and it downregulated the expression of FGD6 gene and the mRNA and protein expression of AFP in HP14.5 cells and upregulated the mRNA and protein expression of Alb (P < 0.01).@*Conclusion@#The inhibition of the expression of FGD6 gene in HP14.5 cells may differentiate HP14.5 cells into hepatocytes. Therefore, FGD6 gene plays an important role in the differentiation regulation of hepatic stem cells.

Role of Mitogen-activated Protein Kinase Pathways in Expression of Aquaporin-4 in Astrocytes after Oxygen-glucose Deprivation in Rats / 中国康复理论与实践

@#Objective To investigate whether mitogen-activated protein kinases(MAPKs),which were involved in changes in osmolali-ty,might mediate aquaporin-4(AQP4)expression in astrocytes after oxygen-glucose deprivation(OGD)in rats.Methods Astrocytes were obtained from new born Sprague-Dawley rats.The P2cells were divided into control group,OGD group and inhibitors of U0126,SB203580 and SP600125 groups. The latter groups underwent OGD for five hours and reoxygenated, the inhibitors of U0126, SB203580 and SP600125(1 μmol/L and 10 μmol/L,respectively)groups,named U1,U10,SB1,SB10,SP1 and SP10 groups,respectively,were cultured with the inhibitors for twelve hours.The volume of cells in OGD group was measured half,one,one and half,two,three,four,eight and twelve hours after reoxygenation,and the expression of AQP4 was detected half,one,one and half,eight and twelve hours after reoxygen-ation with Western blotting.The expression of AQP4,and phosphorylation of extracellular regulated protein kinases(p-ERK),c-Jun N-termi-nal kinase(p-JNK)and p38 MAPK(p-p38 MAPK)was detected 24 hours after reoxygenation in all the groups,while the activity of lactate dehydrogenase(LDH)was measured.Results The volume of cells increased in OGD group one and half,two,three and four hours after re-oxygenation compared with those in the control group(P<0.001),and the expression of AQP4 also increased in OGD group after reoxygen-ation(P<0.001),especially 1.5 hours of reoxygenation.The expression of AQP4,p-ERK,p-JNK and p-p38 MAPK increased in OGD group after five hours of OGD compared with those in the control group(P<0.001),and the expression of p-ERK,p-JNK and p-p38 MAPK de-creased in the inhibitors groups compared with those in OGD group(P<0.001),and the expression of AQP4 decreased in SB10 group(P<0.001).The activity of LDH was less in all the inhibitors groups except SP1 and SB1 groups than in OGD group(P<0.01),and was the least in SB10 group (P<0.001). Conclusion MAPKs signal pathway, especially p38 MAPK, may promote AQP4 expression in astrocytes after OGD in rat,and play a role in cells death.

Effects of all-trans retinioc acid on expressions of COL1α2,MMP-2,TIMP-1, and signaling pathway in TGF-β1-simulated rat hepatic stellate cells / 西安交通大学学报(医学版)

Objective To investigate the effects of all-trans retinioc acid (ATRA)on proliferation of rat hepatic stellate cells (HSC-T6)and expressions of collagen Ⅰ,matrix metalloproteinase-2 (MMP-2),tissue inhibitor of metalloproteinases-1 (TIMP-1 )and signal protein Smad2/3 in TGF-β1-simulated HSC-T6 so as to explore the impact and molecular mechanisms of ATRA on liver fibrosis in vitro .Methods Cultured HSC-T6s were treated with different concentrations of ATRA (0.1,1,10 μmol/L)for fixed time (12,24,48 hours).After intervention time,cell proliferation was evaluated by MTT.Meanwhile,HSC-T6s stimulated by TGF-β1 (5 ng/mL)were treated with different concentrations of ATRA for 24 h.The mRNA expressions of COL1α2,MMP-2 and TIMP-1 were quantified by RT-PCR;the expression of Smad 2/3 protein was determined by cell immunochemistry.Results The proliferation of hepatic stellate cells was inhibited by ATRA in a dose-dependent manner (P < 0.05 ).After induced by TGF-β1,the mRNA expressions of COL1α2,MMP-2 and TIMP-1 and the expression of Smad 2/3 protein were increased significantly compared with control group (P <0.05).However,ATRA could obviously reduce themRNA expressions of COL1α2,MMP-2 and TIMP-1 and the expression of Smad 2/3 protein in HSC-T6 induced by TGF-β1 (P < 0.05 ).Conclusion ATRA can inhibit the proliferation of HSC-T6s and reduce the mRNA expressions of COL1α2,MMP-2 and TIMP-1 in HSC-T6 which were induced by TGF-β1.The anti-hepatic fibrosis function of ATRA may be related to its inhibition on the expression of Smad 2/3 protein in HSC-T6 to influence TGF-β1/Smad signaling pathway.

The study of the effect of the different heat preservation methods preventing craniocerebral surgery patients with hypothermia / 中国实用护理杂志

Objective To explore the effect of prevention intraoperative hypothermia of different heat preservation measures during craniotomy cerebroma resection surgery in the department of neurosurgery. Methods According to the inclusion criteria, a total of 90 patients with craniocerebral surgery were recruited and randomly divided into A, B, C groups with random number table method, and 30 patients in each group. And the three groups were respectively given different heat preservation measures of regular cover, regular cover with infusion heating, regular cover with force-air warming. Meanwhile the rectal temperatures of just entered into the operating room, immediately after anesthesia induction and every 30 minutes after induction of anesthesia, as well as the HR, BP, the amount of infusion and flushing liquor, operation time, incidence of chills during operation, the condition of surgical site infection and hospitalization days were recorded and analyzed statistically by means of the software of SPSS 13.0. Results Rectal temperatures of the three groups were no statistically significant difference (P>0.05) ,when the patients just were moved into the operating room, immediately after anesthesia induction and 0.5 h、1 h after anesthesia induction. The rectal temperatures of the three groups had statistically significant difference (P<0.05) from the 1.5h after anesthesia induction to the end of the surgery.The incidence rates of introperative hypothermia and chill of group C were 26.7%(8/30)and10.0% (3/30),lower than group A and group B:60.0%(18/30), 33.3%(10/30)and 53.3%(16/30), 13.3%(4/30), meanwhile the statistically significant difference was found in these three groups (χ2=7.500, P=0.024;χ2=6.237, P=0.044).The volume of intraoperative blood loss and transfusion were 200(100, 300), 45(0, 60) ml, which lower than group A and group B:300(200, 525), 215(0, 400) ml and 250(150, 500), 120(0, 200) ml, and statistically significant difference was also found in these three groups(H=7.612, P=0.022;H=6.194, P=0.045). Conclusions Regular cover with force-air warming can effectively reduce the incidence of intraoperative hypothermia and chills of craniotomy cerebroma resection patients in the department of neurosurgery and reduce intraoperative bleeding and transfusion volume, as well as ensure the effect of surgical treatment. So it′s worth popularizing in clinic.