Effects of plateau hypoxia on population pharmacokinetics and pharmacodynamics of metformin in patients with Type 2 diabetes / 中南大学学报(医学版)

OBJECTIVES@#Metformin is the basic drug for treating diabetes, and the plateau hypoxic environment is an important factor affecting the pharmacokinetics of metformin, but there have been no reports of metformin pharmacokinetic parameters in patients with diabetes mellitus type 2 (T2DM) in the high-altitude hypoxic environment. This study aims to investigate the effect of the hypoxic environment on the pharmacokinetics and assess the efficacy and safety of metformin administration in patients with Type 2 diabetes mellitus (T2DM).@*METHODS@#A total of 85 patients with T2DM taking metformin tablets in the plateau group (n=32, altitude: 1 500 m) and control group (n=53, altitude: 3 800 m) were enrolled according to the inclusion and exclusion criteria, and 172 blood samples were collected in the plateau group and the control Group. A ultra-performance liquid chromatography/tandem mass spectrometry (UFLC-MS/MS) method was established to determine the blood concentration of metformin, and Phoenix NLME software was used to establish a model of pharmacokinetics of metformin in the Chinese T2DM population. The efficacy and serious adverse effects of metformin were compared between the 2 groups.@*RESULTS@#The population pharmacokinetic modeling results showed that plateau hypoxia and age were the main covariates for model building, and the pharmacokinetic parameters were significantly different between the plateau and control groups (all P<0.05), including distribution volume (V), clearance (CL), elimination rate constant (Ke), half-life(T1/2), area under the curve (AUC), time to reach maximum concentration (Tmax). Compared with the control group, AUC was increased by 23.5%, Tmax and T1/2 were prolonged by 35.8% and 11.7%, respectively, and CL was decreased by 31.9% in the plateau group. The pharmacodynamic results showed that the hypoglycaemic effect of T2DM patients in the plateau group was similar to that in the control group, the concentration of lactic acid was higher in the plateau group than that in the control group, and the risk of lactic acidosis was increased after taking metformin in the plateau population.@*CONCLUSIONS@#Metformin metabolism is slowed down in T2DM patients in the hypoxic environment of the plateau; the glucose-lowering effect of the plateau is similar, and the attainment rate is low, the possibility of having serious adverse effects of lactic acidosis is higher in T2DM patients on the plateau than on the control one. It is probably suggested that patients with T2DM on the plateau can achieve glucose lowering effect by extending the interval between medication doses and enhancing medication education to improve patient compliance.

Correlation Analysis between Cerebrospinal Fluid Status and Prognosis in Childhood with Acute Lymphoblastic Leukemia by Flow Cytometry / 中国实验血液学杂志

OBJECTIVE@#To study the cerebrospinal fluid (CSF) status and prognosis value in patients with newly diagnosed acute lymphoblastic leukemia (ALL) by flow cytometry (FCM).@*METHODS@#The clinical features of the 75 newly diagnosed ALL patients from September 2020 to December 2021 in our centre were retrospective analyzed, as well as the bone marrow (BM) and CSF minimal residual disease (MRD) data, and the CSF conventional cytology data. Central nervous system infiltration(CNSI) positive was as CSF MRD positive by FCM or leukemia cells detected by conventional cytology. The status of CSF were compared and analyzed by FCM and conventional cytology, the clinical features and the prognosis value of different CNSI status in these patients were analyzed.@*RESULTS@#Among 75 newly diagnosed ALL, 16 cases (21%) with CNSI positive (CNSI+) were detected by FCM, while only 2 positive cases (3%) were detected by conventional cytology. The CNSI+ rate detected by FCM was significantly higher than conventional cytology(P<0.05). Compared with CNSI- ALL patients, the median age of CNSI+ ALL patients was significantly younger, and the median platelet count was significantly lower, the difference was statistically significant (P<0.05). Up to follow-up time (August 31, 2022), four ALL patients were died, including 3 patients were CNSI- and 1 patient was CNSI+. Furthermore, three cases were primary disease relapse, including 1 case was CNSI+. There was no significant difference in overall survival (OS) rate and relapse-free survival (RFS) rate of the patients with different CNSI status.@*CONCLUSION@#Compared with conventional cytology, FCM is a more sensitive assay to evaluate the central nervous system status in ALL patients. After active treatment, there was no significant difference in OS and RFS between patients with different CNSI status at diagnosis.

Melanogenesis of quality markers in Vernonia anthelmintica Injection based on UPLC-Q-TOF-MS combined network pharmacology / 中国中药杂志

This study aimed to evaluate the biological effect and mechanism of Vernonia anthelmintica Injection(VAI) on melanin accumulation. The in vivo depigmentation model was induced by propylthiouracil(PTU) in zebrafish, and the effect of VAI on melanin accumulation was evaluated based on the in vitro B16F10 cell model. The chemical composition of VAI was identified according to the high-performance liquid chromatography quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Network pharmaco-logy was applied to predict potential targets and pathways of VAI. A "VAI component-target-pathway" network was established, and the pharmacodynamic molecules were screened out based on the topological characteristics of the network. The binding of active molecules to key targets was verified by molecular docking. The results showed that VAI promoted tyrosinase activity and melanin production in B16F10 cells in a dose-and time-dependent manner and could restore the melanin in the body of the zebrafish model. Fifty-six compounds were identified from VAI, including flavonoids(15/56), terpenoids(10/56), phenolic acids(9/56), fatty acids(9/56), steroids(6/56), and others(7/56). Network pharmacological analysis screened four potential quality markers, including apigenin, chrysoeriol, syringaresinol, and butein, involving 61 targets and 65 pathways, and molecular docking verified their binding to TYR, NFE2L2, CASP3, MAPK1, MAPK8, and MAPK14. It was found that the mRNA expression of MITF, TYR, TYRP1, and DCT in B16F10 cells was promoted. By UPLC-Q-TOF-MS and network pharmacology, this study determined the material basis of VAI against vitiligo, screened apigenin, chrysoeriol, syringaresinol, and butein as the quality markers of VAI, and verified the efficacy and internal mechanism of melanogenesis, providing a basis for quality control and further clinical research.

Influencing factors for dynamic changes in the severity of fatty liver in patients with acute pancreatitis and fatty liver / 临床肝胆病杂志

Objective To investigate the dynamic change of fatty liver (FL) in patients with fatty liver-related acute pancreatitis (FLAP) and related influencing factors. Methods A total of 136 FLAP patients who were admitted to The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, from December 2017 to December 2021 were enrolled as subjects. With the first CT examination after admission as the starting point and the last CT examination before discharge as the ending point, the subjects were divided into FL aggravation group (FLAG group), FL mild mitigation group (FLMMG group), and FL significant mitigation group (FLSMG group) according to the degree of change in FL. General information and clinical data were compared between groups. General information included age, sex, length of hospital stay, etiology of acute pancreatitis (AP), and changes in body weight and temperature, and clinical data included treatment modality and the changes in laboratory markers and AP severity. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test with Bonferroni correction was used for further comparison between two groups. Dynamic changes of data were expressed as the difference from the starting point to the ending point, and a covariance analysis was used for comparison of data with dynamic changes. The Spearman correlation analysis was used to investigate the correlation of indices with significant changes with the degree of change in FL. Results Among the 136 FLAP patients, 61 achieved mild mitigation of FL, 59 achieved significant mitigation of FL, and 16 experienced aggravation of FL at the ending point of the study. There were significant differences between the three groups in the length of hospital stay ( χ 2 =16.215, P < 0.001) and the change in body weight ( F =3.908, P < 0.05), and the FLSMG group had a greater reduction in body weight and a longer length of hospital stay. There were also significant differences between the three groups in the number of fasting days ( χ 2 =11.020, P =0.004) and the degree of changes in C-reactive protein (CRP) ( F =8.589, P < 0.001), white blood cell count (WBC) ( F =5.448, P =0.005), and CT severity index (CTSI) ( F =7.544, P =0.001), and the FLSMG group had greater reductions in CRP, WBC, and CTSI and a longer duration of fasting. Length of hospital stay, number of fasting days, and changes in CRP and CTSI were significantly correlated with the change in FL ( r =0.352, 0.372, -0.365, and -0.350, all P < 0.001). Conclusion Most FLAP patients tend to have mitigation of FL, and its dynamic changes are closely associated with the changes in CRP and CTSI.

The Effect of Doctor-patient Relationship Perception on Work Performance among Medical Staff in Public Hospitals:A Moderated Mediation Model / 中国医学伦理学

To explore the effect of doctor-patient relationship perception on work performance among medical staff in public hospitals and its mechanism. The convenient sampling method was used to select 380 medical staff working in four public tertiary hospitals in Sichuan Province, Zhejiang Province, and Fujian Province from August 2022 to October 2022 as the research objects, and the General Information Questionnaire, Doctor-Patient Relationship Scale, General Self-Efficacy Scale, Perceived Organizational Support Scale, Work Performance Questionnaire were used. This paper showed that the doctor-patient relationship perception of medical staff was negatively correlated with self-efficacy (r=-0.392, P<0.01) and work performance (r=-0.286, P<0.01), self-efficacy was positively correlated with perceived organizational support (r=0.538, P<0.01) and work performance (r=0.507, P<0.01), perceived organizational support was positively correlated with work performance (r=0.510, P<0.01). Self-efficacy played a partial mediating role between doctor-patient relationship perception and work performance, and its effect value was -0.241, accounting for 64.78% of the total effect. Perceived organizational support weakened the negative predictive effect of doctor-patient relationship perception on self-efficacy, which moderates the first half path of the mediating model that doctor-patient relationship perception affects work performance through self-efficacy. It indicated that the doctor-patient relationship perceived by medical staff in public hospitals is poor. Measures should be taken from the aspects of policy support, hospital and society levels to alleviate the doctor-patient relationship, play the mediating role of self-efficacy and the moderating role of organizational support, minimize the negative impact of doctor-patient relationship on the work performance among medical staff, and improve the work performance of medical staff, so as to improve the overall quality of medical services.

Application value of inferior vena cava compression combined with modified Valsalva maneuver in patent foramen ovale / 中华超声影像学杂志

Objective:To comparatively analyze the diagnostic value of patent foramen ovale and the degree of right-to-left shunt among the traditional Valsalva maneuver (VM), the modified Valsalva maneuver (mVM) and the compression of the inferior vena cava combined with modified Valsalva maneuver (CM).Methods:A total of 132 patients with migraine, dizziness, chest pain and other symptoms in Longgang District People′s Hospital of Shenzhen from January 2021 to December 2021 were prospectively enrolled. The detection rate of patent foramen ovale and the degree of right-to-left shunt were assessed among the rest state and after performing the auxiliary maneuvers including VM, mVM and CM respectively.Results:After performing the auxiliary maneuvers, the detection rate of patent foramen ovale was significantly increased (88.6% vs 59.8%) with statistical significance (χ 2=36.026, P<0.001). There was a significant difference in the degree of right-to-left shunt among the three auxiliary maneuvers (χ 2=25.581, P<0.001). CM was the most effective for the detection of the large right-to-left shunt, and the difference was statistically significant compared with VM and mVM ( P<0.001, P=0.002). Conclusions:Auxiliary maneuvers is crucial for the diagnosis of patent foramen ovale. Compared with VM and mVM, performing CM can further improve the detection rate of patent foramen ovale and increase the degree of right-to-left shunt.

Clinical Analysis of Pediatric Acute Myeloid Leukemia with CCLG-AML 2015 Regimen / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical effects of CCLG-AML-2015 protocol on newly diagnosed children with acute myeloid leukemia (AML).@*METHODS@#The clinical data of 60 newly diagnosed AML children in the Department of Hematology and Oncology, Wuhan Children's Hospital from August 2015 to September 2019 were summarized, the effect of chemotherapy using the CCLG-AML-2015 regimen (hereinafter referred to as the 2015 regimen) were retrospectively analyzed. 42 children with AML treated by the AML-2006 regimen (hereinafter referred to as the 2006 regimen) from February 2010 to July 2015 were used as control group.@*RESULTS@#There were no statistical differences between the 2015 regimen group and the 2006 regimen group in sex, age at first diagnosis, and risk stratification (P>0.05). The complete remission rate of bone marrow cytology after induction of 1 course of chemotherapy (84.7% vs 73.1%, P=0.155), and minimal residual disease detection (MRD) negative (42.3% vs 41.4%, P=0.928) in the 2015 regimen group were not statistically different than those in the 2006 regimen group. The bone marrow cytology CR (98.1% vs 80.6%, P=0.004) and MRD negative (83.3% vs 52.8%, P=0.002) in the 2015 regimen group after 2 courses of induction were higher than those in the 2006 regimen group. The 5-year overall survival (OS) rate in the 2015 regimen group (62.3%±6.4% vs 20.6%±6.4%, P=0.001), the 5-year disease-free survival (EFS) rate (61.0%±6.4% vs 21.0% ±6.4% , P=0.001) were better than those in the 2006 regimen group. The 5-year OS and EFS of high-risk transplant patients in the 2015 regimen group were significantly better than those of high-risk non-transplant patients (OS: 86.6%±9.0% vs 26.7%±11.4%, P=0.000; EFS: 86.6%±9% vs 26.7%±11.4%, P=0.000).@*CONCLUSION@#The 2015 regimen can increase the CR rate after 2 courses of induction compared with the 2006 regimen. High-risk children receiving hematopoietic stem cell transplantation can significantly improve the prognosis.

Research on the clinical application of drainage tube after the operation of percutaneous endoscopic lumbar discectomy / 中国骨伤

OBJECTIVE@#To investigate the clinical significance and related factors of drainage tube after percutaneous endoscopic lumbar discectomy(PELD).@*METHODS@#The clinical data of 151 patients with lumbar disc herniation who underwent PELD from January 2019 to September 2019 was retrospectively analyzed. According to whether the drainage tube was used after operation, the patients were divided into drainage tube group and non drainage tube group. The placement time and total drainage volume were recorded. The characteristics of patients, such as age, gender, body mass index, lumbar disc herniation segment, smoking history, basic diseases and whether taking anticoagulants, were analyzed by single factor and multiple factor.@*RESULTS@#Drainage tubes were used in 32 patients after PELD. There were statistical differences in visual analogue scale(VAS) and Japanese Orthopaedic Assiciation(JOA) scores between postoperative and preoperative of that in two groups(P<0.05). There were statistical differences in VAS and JOA scores at discharge between two groups(P<0.05), while there were no statistical differences at other time points(P>0.05). Univariate analysis showed that age, basic diseases and whether taking anticoagulants were related to the use of drainage tube, but gender, body mass index, lumbar disc herniation segment and smoking history were not significantly related to the use of drainage tube. Multivariate analysis showed that elderly patients, complicated with hypertension and diabetes, taking anticoagulants were related to the use of drainage tube.@*CONCLUSION@#The use of drainage tube after percutaneous endoscopic lumbar discectomy can improve the symptoms of lumbar and leg pain in early stage. For elderly patients with hypertension, diabetes and taking anticoagulants drugs, drainage tube can be considered after transforaminal endoscopy.

Ershiwuwei Shanhu Pills regulate Akt/mTOR/GSK-3β signaling pathway to alleviate Alzheimer's disease mice / 中国中药杂志

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.

Predictive value of peripheral blood CD34-positive cell count for the stem cell mobilization effect of plerixafor in patients with multiple myeloma / 白血病·淋巴瘤

Objective:To explore the predictive value of peripheral blood CD34-positive cell count for the stem cell mobilization effect of plerixafor in patients with multiple myeloma (MM).Methods:The clinical data of 12 MM patients who used plerixafor for stem cell mobilization in the First Affiliated Hospital of Guangxi Medical University from December 2019 to February 2021 were retrospectively analyzed. The changes of peripheral blood CD34-positive cell count and the collection status of stem cell in all patients before and after the mobilization of plerixafor were analyzed.Results:Twelve patients were included in this study. These patients were in international staging system (ISS) stage Ⅱ-Ⅲ, and the induction therapy was mainly VRD regimen. The CD34-positive cell count was increased after the use of plerixafor in all patients no matter which mobilization strategies were used before plerixafor. The CD34-positive cell count was 3.63/μl (0.72-13.53/μl) and 32.11/μl (8.52-53.68/μl) before and after the use of plerixafor, and the difference was statistically significant ( Z = -0.40, P<0.001); the median increasing time was 11.50 times (1.61-23.71 times). The mobilization failure occurred in 1 patient. The CD34-positive cell count in his blood was less than 1/μl before the use of plerixafor; though increased 11.83 times after the use of plerixafor, the CD34-positive cell count was still less than 10/μl. Pearson analysis showed that among the patients with CD34-positive cell count less than 4/μl before the use of plerixafor, there was a positive correlation in peripheral blood CD34-positive cell count before and after the use of plerixafor ( r = 0.80, P = 0.032). Conclusions:The peripheral blood CD34-positive cell count has a certain predictive value for the stem cell mobilization effect of plerixafor in MM patients.

A metabolite of Danshen formulae (IDHP) induces angiogenesis and protects rat brains against focal ischemia via CaMKKβ/AMPK(Thr172)/eNOS(Ser1177) signaling / 中国药理学与毒理学杂志

OBJECTIVE Only limited number of drugs are currently available for treating ischemic stroke. Therapeu?tic angiogenesis has recently emerged as one of the most promising therapies for cerebral ischemic injury. Isopropyl-β-(3,4-dihydroxyphenyl)-α-hydroxypropanoate (IDHP) is a metabolite derived from the botanical formulation for Dantonic?. Here, we investigated the angiogenic efficacy of IDHP in cerebral ischemia. METHODS The in vivo effects of IDHP were evaluated in the C57BL/6 mouse Matrigel plug and rat transient middle cerebral artery occlusion (tMCAO) models. Primary human umbilical vein endothelial cells (HUVEC) and human brain microvascular endothelial cells (HBMEC) were used to explore the effects of IDHP on stimulating proliferation, migration and tube formation in vitro. ELISA and Western blotting were used to quantitate the release and expression of relevant target molecules and signaling path?ways. RESULTS IDHP reduced infarct volume and improved sensorimotor function in rats subjected to tMCAO by pro?moting angiogenesis, and promoted Matrigel neovascularization in mice. Moreover, IDHP produced a biphasic modula?tion on proliferation and migration both in HUVEC and HBMEC. It also induced tube formation in a 12-day HUVEC-HDF co-culture model and in Matrigel assays. IDHP-induced angiogenesis was accompanied by increased levels of p-AMPKα (Thr172) and p-eNOS (Ser1177) both in vitro and in vivo, and the decreased level of VEGF in rat brains on day 1 whereas enhanced level of VEGF on day 3 and 7 after tMCAO. Mechanistically, AMPK knockdown or pharmacologi?cally inhibiting AMPK and its upstream kinases (CaMKKβ) inhibited the eNOS phosphorylation induced by IDHP in HUVEC. Furthermore, selective eNOS inhibitor (L-NIO), selective CaMKKβ inhibitor (STO) and AMPKa inhibitor (Com?pound C) blocked the capillary-like tube formation in the co-culture model induced by IDHP (10 nmol · L-1). CONCLU?SION Collectively, these findings showed that IDHP protected rats from cerebral ischemia-reperfusion injury by promot?ing angiogenesis via activating CaMKKβ/AMPK(Thr172)/eNOS(Ser1177) signaling, and suggest it to be a promising new drug candidate for the prevention and/or treatment of cerebral ischemia and other vascular occlusive diseases.

Severe hypothyroidism after orthognathic surgery: a case report / 华西口腔医学杂志

Hypothyroidism is a common endocrine disease with reduced systemic metabolism, but the initial diagnosis is rare in oral and maxillofacial surgery. Due to the nonspecific symptoms, it is easy to be misdiagnosed and missed diagnosis which results in serious consequences. This paper presents a case of severe hypothyroidism which was characterized by airway obstruction, facial swelling, unexplained anaemia and bipedal edema after orthognathic surgery. With review of relevant literatures, this article discusses the risk factors, symptoms, diagnosis and therapy of hypothyroidism.

Data-mining of Adverse Drug Events Signals for Tocilizumab Based on US FAERS Database / 中国药房

OBJECTIVE：To provide reference for clinical safe and rational drug use by mining adverse drug events （ADE） signals for tocilizumab. METHODS ：Data of ADE reports related to tocilizumab in the first quarter of 2015 to second quarter of 2020 were collected from US FDA adverse event reporting system. After data standardization ，the proportional imbalance method was used for ADE signal mining. RESULTS ：A total of 163 718 ADE reports were extracted ，in which tocilizumab was primary suspected drug ，involving 26 674 patients. In 26 674 patients，the proportion of female （73.69％）was higher than that of male （19.04％），and the age was mainly 60-74 years old （21.19％）. Among the 163 718 ADE reports ，the main reporting countries were the United States （70.15％），Canada（15.95％），Japan（3.33％），Australia（3.05％）and Brazil （1.43％）；consumers （31.35％）and doctors （24.94％）were the main reporting staff. A total of 747 ADE signals for tocilizumab were obtained ， commonly rheumatoid arthritis ，joint pain and pain ；and the signals as the increase of disability assessment scale score ，the decrease of disability assessment scale score ，abnormal diastolic blood pressure and abnormal systolic blood pressure were strong. A total of 33 kinds of ADE signals were found ，which were not recorded in the instructions of tocilizumab ，and mainly abnormal laboratory indicators such as decreased oxygen saturation ，decreased blood pressure and abnormal heart rate. ADE mainly involved 27 system organs ，including musculoskeletal and connective tissue ，various reactions of systemic diseases and drug delivery site ， various examinations. CONCLUSIONS ：In addition to the ADE mentioned in the drug instructions ，when using tocilizumab in clinic，attention should also be paid close to blood oxygen saturation ，blood pressure ，blood routine indexes and other laboratory indicators，and intervention measures should be taken early when ADE occurs ，so as to ensure the safety and effectiveness of drug use.

Risk factors of perivalvular leakage after transcatheter aortic valve replacement with Venus-A valve / 中华心血管病杂志

Objective: To investigate the risk factors of moderate or severe perivalvular leakage (PVL) after transcatheter aortic valve replacement (TAVR) with Veneus-A valve. Methods: This study was a single-center case-control study. The clinical data of patients with severe aortic stenosis, who underwent TAVR in the Department of Cardiology of Second Affiliated Hospital of Army Medical University from October 2017 to January 2021, were analyzed. According to the circumferential extent of prosthetic valve paravalvular regurgitation measured by transthoracic echocardiography before discharge (patients who died in hospital were referred to transesophageal echocardiography results after valve implanted), the patients were divided into moderate or severe PVL group and mild or non-PVL group. The clinical features, CT scan and analysis results of aortic root were compared between the two groups. Multivariate logistic regression analysis was used to identify the independent risk factors of postoperative moderate or severe PVL, and receiver operating characteristic (ROC) curve was used to explore the predictive value of related factors. Results: Eighty-two patients (mean age: (70.9±6.5) years, 46 males) were included in the analysis, there were 16 patients in the moderate or severe PVL group and 66 patients in the mild or non-PVL group. The proportion of male gender, depth of valve implantation, size of valve annulus and left ventricular outflow tract (LVOT), and coverage index of LVOT were significantly higher in moderate or severe PVL group than those in mild or non-PVL group (Pall<0.05). As there was a strong collinearity among the valve annular short diameter, LVOT short diameter and LVOT coverage index (partial correlation coefficient R 0.251-0.779, P<0.05), these parameters were not entered in regression model. Multivariate logistic regression analysis showed that valve implantation depth(OR=1.239,95%CI 1.036-1.442,P=0.023), aortic angulation(OR=1.128, 95%CI 1.044-1.312,P=0.038)and LVOT tract coverage index (OR=1.123, 95%CI1.003-1.315, P=0.032) were independent risk factors for moderate or severe PVL after TAVR. The ROC curve showed that the valve implantation depth could predict the occurrence of moderate or severe PVL after TAVR (area under ROC curve (AUC)=0.697, 95%CI 0.554-0.851, P=0.039). Conclusion: Among patients with severe aortic stenosis who undergo TAVR with Venus-A valve, the implantation depth, aortic angulation and LVOT coverage index are independent risk factors of moderate/severe PVL after TAVR, among which valve implantation depth could be used to predict the occurrence of moderate/severe PVL after TAVR.

Expression and significance of EGFL7 in malignant meningioma cells and tissues / 中国医师杂志

Objective:To investigate the expression and significance of epidermal growth factor-like domain 7 (EGFL7) in malignant meningioma.Methods:Human malignant meningeal cell lines (IOMM-LEE, CH157-MN) and normal meningeal cells (HMC-1400) were cultured in vitro. The expressions of EGFL7 mRNA and protein in cells were detected by real time fluorescent quantitative polymerase chain reaction (qRT-PCR), reverse polymerase chain reaction (RT-PCR), and Western blot. The expression levels of EGFL7 mRNA and protein in 25 cases of malignant meningioma, the corresponding normal arachnoid tissue around the tumor and the invasive skull tissue were detected. Results:The results of qRT-PCR, RT-PCR and Western blot showed that the expression levels of EGFL7 mRNA and protein in human malignant meningeal cell lines (IOMM-LEE, CH157-MN) were higher than those in normal meningeal cells (HMC-1400) ( P<0.05). The expression levels of EGFL7 mRNA and protein in malignant meningiomas were higher than those in normal arachnoid tissues around the tumors ( P<0.05); the expression levels of EGFL7 mRNA and protein in invasive cranial tissues, primary malignant meningiomas and normal arachnoid tissues around the tumors decreased in turn ( P<0.05). Conclusions:EGFL7 is highly expressed in malignant meningioma tissues and cell lines, and its high expression may be associated with malignant meningioma invasion.

Experience of treating severe cases of 2019 novel coronavirus pneumonia in Changde area / 中华危重病急救医学

Since the cluster of the 2019 novel coronavirus (2019-nCoV) pneumonia, a large number of patients gathered, the mortality of critical patients has remained high and the treatment was unclear. In this outbreak, Hunan Changde region immediately set up a hospital and intensive care unit. The patients relieved through respiratory support, hemodynamics management, nutritional support, the application of antiviral drugs, analgesic and sedation. The treatment experience in severe cases of 2019-nCov pneumonia patients were summarized as follows: in terms of respiratory support, we needed to pay attention to the advantages of high-flow nasal cannula oxygen therapy (HFNC) and the intervention of mechanical ventilation, pay attention to the ventilator parameters, and adopt prone position timely. In the aspects of fluid resuscitation and volume management, we should pay attention to the characteristics of severe patients' volume status, perform early evaluation, and clinicians should focused on hemodynamic management beside the bed. In the aspect of nutritional support and evaluation and maintenance of intestinal function, early enteral nutrition should be adopted in time. However, the trade-off between the risk of intestinal function and nutritional support in patients with mechanical ventilation and the antiviral benefits of Kaletra needed to be reevaluated, the optimized way of analgesia and sedation was adopted, at the same time, the usage and side effects of antiviral drugs should be paid attention to. We should grasp the opportunity of transportation for severe patients. It is suggested that some warning scores should be used to facilitate early recognition of patients with severe infection and then they should be earlier transferred to the designated hospital for intensive care.

Experience of treating severe cases of 2019 novel coronavirus pneumonia in Changde area / 中华危重病急救医学

Since the cluster of the 2019 novel coronavirus (2019-nCoV) pneumonia, a large number of patients gathered, the mortality of critical patients has remained high and the treatment was unclear. In this outbreak, Hunan Changde region immediately set up a hospital and intensive care unit. The patients relieved through respiratory support, hemodynamics management, nutritional support, the application of antiviral drugs, analgesic and sedation. The treatment experience in severe cases of 2019-nCov pneumonia patients were summarized as follows: in terms of respiratory support, we needed to pay attention to the advantages of high-flow nasal cannula oxygen therapy (HFNC) and the intervention of mechanical ventilation, pay attention to the ventilator parameters, and adopt prone position timely. In the aspects of fluid resuscitation and volume management, we should pay attention to the characteristics of severe patients' volume status, perform early evaluation, and clinicians should focused on hemodynamic management beside the bed. In the aspect of nutritional support and evaluation and maintenance of intestinal function, early enteral nutrition should be adopted in time. However, the trade-off between the risk of intestinal function and nutritional support in patients with mechanical ventilation and the antiviral benefits of Kaletra needed to be reevaluated, the optimized way of analgesia and sedation was adopted, at the same time, the usage and side effects of antiviral drugs should be paid attention to. We should grasp the opportunity of transportation for severe patients. It is suggested that some warning scores should be used to facilitate early recognition of patients with severe infection and then they should be earlier transferred to the designated hospital for intensive care.

Effects of different culture systems on the culture of prepuberal buffalo (Bubalus bubalis) spermatogonial stem cell-like cells in vitro

Effects of IGF-1 mediated enrichment environment on visual cortex plasticity in adult amblyopic mice / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the effect and possible mechanism of enriched environment on regulating the plasticity of visual cortex in adult monocular deprivation amblyopia mice.<p>METHODS: In this experimental study, a total of 72 Kunming mice were randomly divided into control group(Nor), monocular deprivation+ standard environment group(MD+SE), monocular deprivation + enriched environment group(MD+EE)and monocular deprivation+ fluoxetine group(MD+FLX). MD model of mice were established at postpartum 21d, and then fed the mice under SE or EE for 4wk. For the mice in MD+FLX group, they were fed by water with fluoxetine. The visual acuity and flash visual evoked potential of mice in each group were detected. Ultrastructral modifications of synaptic junctions in each group were detected using the electronic microscope. We also applied the molecular biology to study the role of enriched environment in visual cortex of adult amblyopic mice whether through regulating the expression of IGF-1, IGF-1R and IGFBP5.<p>RESULTS: 1)Visual acuity examination: the successful rate of forepaw-reaching reflex in MD+SE group mice is lower than that in Nor group(<i>P</i><0.001). Compared to MD+SE group, the successful rate of forepaw-reaching reflex improved in MD+EE group(<i>P</i><0.001)and MD+FLX group(<i>P</i><0.001). The difference is not significant between the MD+EE group and MD+FLX group(<i>P</i>=0.816); 2)Flash-visual evoked potential examination: compare to the Nor group, the P2 latency was prolonged(<i>P</i><0.01), and the P2 amplitude was decreased(<i>P</i><0.01)of flash-visual evoked potential(F-VEP)in the deprived eye in MD+SE group mice; After raring in enriched environment, the P2 latency was shortened(<i>P</i>=0.003)and P2 amplitude was increased(<i>P</i>=0.000)in the deprivated eye detected with F-VEP, which is not significant in P2 latency and amplitude when compare to MD+FLX group(<i>P</i>>0.05); 3)The structural modifications of synaptic junctions examined by electromicrographs: Compare to the Nor group, the synaptic clefts increased(<i>P</i><0.01), the synaptic active zone shortened(<i>P</i><0.01), and the thickness of PSD decreased(<i>P</i><0.01)in MD+SE group mice. After raring in enriched environment, the synaptic clefts decreased(<i>P</i>=0.0035), the synaptic active zone prolonged(<i>P</i>=0.000)and the thickness of PSD increased(<i>P</i>=0.000)in the visual cortex contralateral to the deprived eye, which is not significant in all of the structural parameters of the synaptic junction in visual cortex when compare to MD+FLX group(<i>P</i>>0.05); 4)IGF-1, IGF-1R and IGFBP5 expression detected by Western-blot: Compare to the Nor group, the IGF-1 and IGF-1R expression in visual cortex contralateral to deprivated eye are both down-regulated in MD+SE group(<i>P</i><0.01; <i>P</i><0.01). After raring in enriched environment, the expression of IGF-1 and IGF-1R in MD+EE group was significantly higher than that in MD+SE group(<i>P</i>=0.016; <i>P</i>=0.041), but still lower than that in Nor group(<i>P</i>=0.001; <i>P</i>=0.001). The different expression of IGFBP5 in each group is not significant(<i>P</i>>0.05). <p>CONCLUSION: Environmental enrichment can improve the visual function through reactivating the plasticity of monocular deprivation amblyopia mice. The mechanism is presumed to be related to the expression of IGF-1 and IGF-1R.

Effects of different culture systems on the culture of prepuberal buffalo (Bubalus bubalis) spermatogonial stem cell-like cells in vitro

Currently, the systems for culturing buffalo spermatogonial stem cells (SSCs) in vitro are varied, and their effects are still inconclusive. In this study, we compared the effects of culture systems with undefined (foetal bovine serum) and defined (KnockOut Serum Replacement) materials on the in vitro culture of buffalo SSC-like cells. Significantly more DDX4- and UCHL1-positive cells (cultured for 2 days at passage 2) were observed in the defined materials culture system than in the undefined materials system (p < 0.01), and these cells were maintained for a longer period than those in the culture system with undefined materials (10 days vs. 6 days). Furthermore, NANOS2 (p < 0.05), DDX4 (p < 0.01) and UCHL1 (p < 0.05) were expressed at significantly higher levels in the culture system with defined materials than in that with undefined materials. Induction with retinoic acid was used to verify that the cultured cells maintained SSC characteristics, revealing an SCP3⁺ subset in the cells cultured in the defined materials system. The expression levels of Stra8 (p < 0.05) and Rec8 (p < 0.01) were significantly increased, and the expression levels of ZBTB16 (p < 0.01) and DDX4 (p < 0.05) were significantly decreased. These findings provided a clearer research platform for exploring the mechanism of buffalo SSCs in vitro.