Leucine-rich repeats containing 4 protein (LRRC4) in memory, psychoneurosis, and glioblastoma / 中华医学杂志(英文版)

Leucine-rich repeats containing 4 ( LRRC4 , also named netrin-G ligand 2 [NGL-2]) is a member of the NetrinGs ligands (NGLs) family. As a gene with relatively high and specific expression in brain, it is a member of the leucine-rich repeat superfamily and has been proven to be a suppressor gene for gliomas, thus being involved in gliomagenesis. LRRC4 is the core of microRNA-dependent multi-phase regulatory loops that inhibit the proliferation and invasion of glioblastoma (GB) cells, including LRRC4/NGL2-activator protein 2 (AP2)-microRNA (miR) 182-LRRC4 and LRRC4-miR185-DNA methyltransferase 1 (DNMT1)-LRRC4/specific protein 1 (SP1)-DNMT1-LRRC4. In this review, we demonstrated LRRC4 as a new member of the partitioning-defective protein (PAR) polarity complex that promotes axon differentiation, mediates the formation and plasticity of synapses, and assists information input to the hippocampus and storage of memory. As an important synapse regulator, aberrant expression of LRRC4 has been detected in autism, spinal injury and GBs. LRRC4 is a candidate susceptibility gene for autism and a neuro-protective factor in spinal nerve damage. In GBs, LRRC4 is a novel inhibitor of autophagy, and an inhibitor of protein-protein interactions involving in temozolomide resistance, tumor immune microenvironment, and formation of circular RNA.

Changes and distribution of antibodies in plasma before and after infection of SARS-CoV-2 Omicron strain / 中国输血杂志

【Objective】 To determine the best collection time period of plasma which can be used for human COVID-19 immunoglobulin for intravenous injection through SARS-CoV-2-IgG change and neutralizing antibody distribution against different virus strain in representative mixed plasma before and after Omicron strain infection by ELISA and pseudovirus neutralization test. 【Methods】 An ELISA method for quantitative detection of SARS-CoV-2-IgG was established and its linear range,accuracy and precision was verified. SARS-CoV-2-IgG potency was detected in 25 convalescent plasma which were collected 20-40 days after confirmed Omicron infection, two groups of mixed plasma samples WP1 and WP2 were prepared according to the SARS-CoV-2-IgG results, and pseudovirus neutralization experiments with different virus strain (prototype strain, BA. 1,BA.2, BA.4/5, BF.7, BQ.1.1) were carried out to determine the distribution of neutralizing antibodies against different virus strain. SARS-CoV-2-IgG potency of representative mixed plasma collected from 14 plasma stations subordinate to the company before and after Omicron strain infection was detected, including Omicron convalescent plasma (OP) collected from different plasma stations from December 2022 to May 2023 and normal pool plasma (VN) feed in March 2023 which collected from March 2022 to December 2022. According to the results, the difference and the change rule with time of SARS-CoV-2-IgG before and after Omicron strain infection were analyzed. 【Results】 The linearity of SARS-CoV-2-IgG ranged from 6.25 to 200 EIU/mL, the accuracy in-batch ranged from 81.793% to 106.985%, the precision in-batch ranged from 1. 100% to 13.000%, and the total error in-batch ranged from 2.988% to 22.679%. The accuracy between batches ranged from 90.788%to 96.893%, the precision between batches ranged from 4.870% to 6.272%, and the total error between batches ranged from 9.192% to 15.399%. The results of pseudovirus neutralizing antibody showed that the potency of different virus strain neutralizing antibodies were in the order of prototype strain>BA.2>BA.4/5>BF.7≈ BQ.1.1>BA.1 and the correlation between WP1 and WP2 was high (Pearson r=0. 931 1, P=0.002 3) which indicated that the potency distribution of neutralizing antibodies of different virus strain in Omicron convalescent plasma was basically stable. Compared with the mixed convalescent plasma sample G128 collected in June 2022, the potency of Omicron neutralizing antibodies of WP series were significantly higher, the ratio of BA.2 antibody to prototype antibody increased from 26.9% (before infection) to 82.6%-87.5% (after infection). The results of VN series before Omicron infection were < 100 EIU/mL, and the results of OP series after Omicron infection showed that the plasma collected from the beginning of December 2022 was the peak of antibody in the same month,and then dropped sharply, entering a short plateau in February-March 2023 (potency was about 40% of the peak value),and then dropped sharply again in April (potency was about 20% of the peak value). 【Conclusion】 The potency and proportion of neutralizing antibody against Omicron subtype in convalescent plasma after COVID-19 Omicron strain infection increased significantly. IgG antibody of plasma donors in different regions reached its peak in the month of infection, then continued to dropped sharply. The best collection period of plasma that can be used for human COVID-19 immunoglobulin for intravenous injection was 1 to 2 months after infection.

Effects of high-flow nasal cannulae on the rate of tracheal intubation after extubation / 中国实用护理杂志

Objective To observe whether the high-flow nasal cannulae (HFNC) can reduce the rate of re intubation after extubation in patients with tracheal intubation in the intensive care unit (ICU). Methods 134 patients with mechanical ventilation in ICU were divided into 2 groups according to the order of ICU. The control group and the observation group were divided into 67 groups. Patients in control group were used routine oxygen inhalation (nasal duct and mask) after weaning, while the observation group was HFNC. All the other patients with the same treatment and care. The rate of re intubation was compared between the 2 groups. Results In the observation group, the rate of reintubation was 4.48%(3/67) of all. The control group was 14.92%(10/67), two groups of patients with reintubation rate difference was statistically significant (χ2= 4.17, P < 0.05). Conclusions HFNC can decrease the rate of re intubation after extubation in patients with tracheal intubation.

Microstructural changes of the corpus cavernosum in hypoxia-induced erectile dysfunction / 中华男科学杂志

Hypoxia is an independent risk factor of erectile dysfunction (ED), and the mechanisms of hypoxia causing ED are varied and complicated. Traditional studies related are concentrated on the changes of the corpus cavernosal endothelium and hormone levels in the body but have failed to achieve notable breakthroughs. Recent researches have demonstrated that such alterations in the corpus cavernosal microstructure as decreased corpus cavernosum smooth muscle cells of the contractile phenotype and fibrillation of the corpus cavernosum may be two important factors of hypoxia-induced ED. This review gives a brief introduction of the management of hypoxia-induced ED with the strategies of intervening in the corpus cavernosal microstructural changes, such as gene therapy, stem cell therapy, and induction of cell autophagy.

Autophagy and phenotypic modulation of corpus cavernosum smooth muscle cells in hypoxia-induced erectile dysfunction / 中华男科学杂志

The correlation between hypoxia and erectile dysfunction (ED) has been universally acknowledged for decades in the academic world. The phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) is regarded as one of the factors of hypoxia-induced ED, but the underlying mechanisms remain unclear. Recent researches show some correlation between autophagy and phenotypic modulation of CCSMCs, which may be associated with the overexpressions of PDGF, TGF-β, and vasoactive factors in the organism following hypoxia.

Clinical values and optimal cut-off points of basic vital signs in early identification of critical hand, foot, and mouth disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical values of basic vital signs in early identification of critical hand-foot-mouth disease (HFMD).</p><p><b>METHODS</b>The clinical data of 358 children with severe HFMD [212 cases in stage 2 (central nervous system involvement) and 146 cases in stage 3 (earlier stage of cardiopulmonary failure, critical type)] were reviewed. The diagnostic values of peak temperature and duration of fever, as well as the heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) in different age groups, for critical HFMD (stage 3) were analyzed using the receiver operating characteristic (ROC) curve.</p><p><b>RESULTS</b>HFMD might progress to critical type in case of HR≥148.5 beats/minutes, RR≥36.5 times/minutes, SBP≥95 mm Hg, and DBP≥59 mm Hg among children aged 0-1 year. HR≥142.5 times/minutes, RR≥31.5 times/mintes, SBP≥103 mm Hg, and DBP≥60.5 mm Hg in children aged 1-2 years had a certain diagnostic value for critical HFMD. HFMD might progress to critical type in case of HR≥139.5 times/minutes, RR≥29.5 times/minutes, and SBP≥103 mm Hg among children≥3 years of age. The sensitivity and specificity of every indicator were higher than 0.517 and 0.769, respectively. The area under the ROC curve (AUC) for peak temperature was 0.507 (P=0.816, compared with AUC=0.5). When the duration of fever was ≥5.5 days, the sensitivity and specificity were 0.589 and 0.571, respectively.</p><p><b>CONCLUSIONS</b>HR, RR, and BP are good indicators to identify critical HFMD (stage 3) early. The optimal cut-off points conform to the age characteristics of children. DBP in children≥3 years of age, peak temperature, and duration of fever have a low value in early identification of critical HFMD.</p>

Regulation of human G-coupled protein kinase 4 A142V on AT1 receptor in rat vascular smooth muscle cells / 重庆医学

Objective To study the effect of human G-coupled protein kinase 4(GRK4) A142V overexpression on angiotensin Ⅱ1 type(AT1 ) receptor and its-mediated proliferation of rat vascular smooth muscle cells .Methods We constructed a lentiviral vec-tor carrying human GRK4-EGFP gene and observed its expression in A10 cells .Expression of AT1 receptor were determined by im-munoblotting ,GRK4 activity were checked by spectrophotometry ;the linkage between GRK4 and AT1 receptor were determined by co-immunoprecipitation .[3 H] thymidine incorporation was used to detect changes of cell proliferation .Results As compared with the control cells ,A142V-transfected cells had higher GRK4 activity and higher AT1 receptor expression ;there was linkage between GRK4 and AT1 receptor ,the co-immunoprecipitation levels were lower in A142V cells .The basal levels of VSMC proliferation was higher in A142V cells ,Ang Ⅱ increased VSMC proliferation to a greater extent in A 142V cells .Conclusion GRK4 A142V ,via in-creasing GRK4 activity ,increases AT1 receptor expression and function in vascular smooth muscle cell proliferation .

Protective effects of Ginkgo biloba extract on the lung injury of dogs undergoing hypothermic cardiopulmonary bypass / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the protective effects of Ginkgo biloba extract (EGb) on the lung injury of dogs undergoing hypothermic cardiopulmonary bypass (CPB).</p><p><b>METHODS</b>Fourteen healthy hybrid dogs were randomly divided into the control group and the EGb group, 7 in each group. EGb (8 mg/kg) was intravenously dripped to dogs in the EGb group before thoracotomy after anesthesia, while equal volume of normal saline was intravenously dripped to those in the control group. The lung tissue was collected after 60-min CPB and 120-min recovery of heart beat. The lung tissues were collected to detect the wet weight-dry weight ratio and the permeability. The contents of malondialdehyde (MDA), the activities of myeloperoxidase (MPO) and total superoxide dismutase (T-SOD) in the lung tissues were detected by biochemical assay. The levels of IL-1beta, IL-8, tumor necrosis factor alpha (TNF-alpha), platelet activating factor (PAF) in the lung tissue were detected by enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Compared with the control group, the wet weight-dry weight ratio was reduced and the permeability of the lung tissue decreased (P < 0.05), the MDA content was reduced, the activity of MPO decreased, and the activity of T-SOD increased (P < 0.05), and the levels of IL-1beta, IL-8, and PAF obviously decreased (P < 0.05).</p><p><b>CONCLUSIONS</b>EGb showed better protective effects on the lung injury of dogs undergoing hypothermic CPB. Its possible mechanisms might be associated with alleviating ischemia-reperfusion injury of in vitro circulation and systemic inflammatory response.</p>

Erythrocyte protective effects of ginaton in patients undergoing hypothermic cardiopulmonary bypass / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the erythrocyte protective effects of Ginaton, a ginkgo biloba extract, in patients undergoing hypothermic cardiopulmonary bypass (CPB).</p><p><b>METHODS</b>Sixty patients, who suffered from rheumatic heart disease of ASA grade II-III and scheduled for mitral valve replacement with intravenous anesthesia, were randomly assigned to two groups equally, the Ginaton group and the control group. They were administered with Ginaton 1 mg/kg and saline respectively via intravenous dripping before open heart surgery before beginning CPB. Blood samples were taken from radial artery at different time points, i.e., before CPB (T1), nasopharyngeal temperature (30-31 degrees C) stabilized stage (T2), nasopharyngeal temperature restoration (36 degrees C) stage (T3), 30 min after CPB (T4) and 3 h after CPB (T5), for determination of malondialdehyde (MDA) and superoxide dismutase (SOD) levels in plasma and erythrocyte (P-MDA, E-MDA, P-SOD and E-SOD), as well as the Na+ -K+ -ATPase and Ca+ -Mg2+ -ATPase activities in erythrocytes.</p><p><b>RESULTS</b>As compared with those at T1, in the control group, P-MDA, E-MDA, and E-SOD at T2-T5 and E-SOD at T2 were higher, but E-SOD at T3-T5 were lower (P < 0.01); while in the Ginaton group P-MDA, E-MDA, and E-SOD at T3-T4 were higher (P < 0.05 or P < 0.01). As compared with those in the control group, the levels of P-MDA and E-MDA at T2-T5 were significantly lower, and E-SOD at T3-T5 were higher (P < 0.05 or P < 0.01). Activities of Na+ -K+ -ATPase and Ca+ -Mg2+ -ATPase significantly increased at T2 and gradually decreased after then in both groups (P < 0.05 or P < 0.01), but those at T2-T5 were significantly higher in Ginaton group than in control group (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Ginaton displays an erythrocyte protecting effect by way of alleviating the lipid peroxidation in erythrocytes' membrane.</p>

Effect of ginkgo biloba extract on plasma vascular endothelial growth factor during peri-operative period of cardiac surgery / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect and clinical value of ginkgo biloba extract (Ginaton) on the plasma vascular endothelial growth factor (VEGF) in patients during peri-operative period of cardiac surgery.</p><p><b>METHODS</b>Twenty patients scheduled to receive cardiac operation were randomly assigned to 2 groups by a digital table. For the 10 patients in the control group, the cardiopulmonary bypass (CPB) was established in routine and received cold (4 degrees C) St. Thomas' cardioplegia perfusion (15 mL/kg) via aortic root after ascending aorta blocking, as for the 10 patients in the Ginaton group, the same was done but with 0.5 mg/kg of Ginaton added to the cardioplegia perfusion. Plasma VEGF contents were detected by ELISA at different time points, i.e., before and after anesthesia induction (T1, T2), after aorta intubation (T3), 0.5 h after aorta clamping (T4), 0.5 h after aorta declamping (T5), immediate after terminating the operation (T6), 6 h after operation (T7), and 24 h after operation (T8).</p><p><b>RESULTS</b>In the control group, VEGF level began to rise at T, and reached the peak at T7(P < 0.01), while in the Ginaton group, it reached the peak early at T, (P < 0.01), and began to drop at T (P < 0.01).</p><p><b>CONCLUSION</b>Ginaton could induce the production of VEGF, which may be one of the mechanisms for its myocardial protection.</p>

Effects of Ginkgo biloba extract (ginaton) on mRNA expression of bcl-2 and bcl-xL in myocardium of patients underwent hypothermic cardiopulmonary bypass / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effects of Ginkgo biloba extract (Ginaton) on bcl-2 and bcl-xL mRNA expression in the myocardium of patients underwent hypothermic cardiopulmonary bypass (CPB).</p><p><b>METHODS</b>Thirty congenital heart disease patients were randomly assigned to 2 groups, the control group and the treated group. Patients in both groups received St. Thomas' cardioplegic solution via radix aortae, while Ginaton (0.5 mg/kg) was added in the treated group. Cardiac surgery was started after complete heart arrest. Myocardium was taken before the aorta ascendens was unblocked and mRNA expression of bcl-2 and bcl-xL in the ventricular tissue was detected by RT-PCR.</p><p><b>RESULTS</b>The gene expressions of bcl-2 and bcl-xL were significantly higher in the treated group than those in the control group (P < 0.05).</p><p><b>CONCLUSION</b>Ginaton could promote the mRNA expressions of the antiapoptotic gene bcl-2 and bcl-xL in myocardium of patients underwent CI'PB.</p>

Effects of Ginaton on the markers of myocardial injury during cardiopulmonary bypass / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the effects of Ginaton (Ginkgo biloba leaf extract) on the myocardial injury markers (MIMs) during cardiopulmonary bypass (CPB).</p><p><b>METHODS</b>Forty patients with congenital heart diseases, scheduled to take atrial septum or ventricular septum repairing operation, were randomly divided into the Ginaton group and the control group, 20 cases in each group. Patients in both groups received St. Thomas' cardioplegic perfusion via radix aortae, while Ginaton (0.5 mg/kg) was added into the perfusion for the Ginton group. Cardiac surgery were started after complete heart arrest. Central venous blood was obtained before and at 0, 6th, 12th, 24th and 48th hour after operation for detection of serum C reaction protein (CRP) by immunoturbidimetry, as well as creation kinase-MB isoenzyme (CK-MB), cardiac troponin T (cTnT) and cardiac troponin I (cTnI) with enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>There was no difference in serum concentration of CRP, CK-MB, cTnT and cTnI between the two groups before operation (P > 0.05). These indexes increased immediately after operation in both groups ( P < 0.05). They reached the peak value 12 hrs after CPB and reduced to normal level 48 hrs post-operation in the control group, with the value significantly higher than that in the Ginaton group at all the corresponding time points (P < 0.05, or P < 0.01).</p><p><b>CONCLUSION</b>Perfusion with Ginaton during CPB could significantly decrease the release of MIMs and improve post-CPB cardiac function recovery, exerting favorable myocardium-protective effects.</p>

Brain protective effects of ginkgo biloba leaf extract (ginaton) in patients undergoing hypothermic cardiopulmonary bypass / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the brain protective effects of Ginkgo biloba leaf extract (Ginaton) in patients who underwent hypothermic cardiopulmonary bypass (CPB).</p><p><b>METHODS</b>Sixty patients with rheumatic heart disease of ASA grade II-III, who were scheduled for mitral valve replacement with intravenous anaesthesia, were randomly assigned to two groups, the Ginaton group (30 patients) treated with Ginaton 1 mg/kg by intravenous dripping before open heart for CPB, and the control group (30 patients) with normal saline instead. Blood was synchronously collected from arteriae radialis and vena jugularis interna at 5 time points, namely, before CPB (T1), nasopharyngeal temperature (lowered to 30-31 degrees C) stabilized stage (T2), nasopharyngeal temperature restoration (36 degrees C) stage (T3), 30 min after CPB (T4) and 3 after CPB (Ts) for determining blood gas, lactate acid concentration, activity of superoxide dismutase (SOD) and malonaldehyde (MDA) content. And the oxygen content in artery (CaO2) and jugular vein (CjvO2), the difference of oxygen contents in arterial and jugular vein (Ca-jvO2), the cerebral oxygen extraction ratio (ERO2) as well as the arteriojugular lactate difference (ADVL) were calculated.</p><p><b>RESULTS</b>After the beginning of CPB, as compared with those in the control group, in the Ginaton group, the reduction of Ca-jvO2 and ERO2 was significantly higher (P < 0.05 or P < 0.01) and the increase of lactate acid, ADVL and MDA were significantly lower, and with a remarkably higher SOD activity (P < 0.01).</p><p><b>CONCLUSION</b>Ginaton could improve cerebral oxygen supply, promote SOD activity to inhibit production of free radicals in patients undergoing CPB, and thus shows an evident protective effect in the brain.</p>