Objective To investigate the effect of granulocyte colony-stimulating factor(G-CSF)and its effect on the cognation in the PDGF hAPPV717I transgenic mice of Alzheimer's disease model.Methods Totally 36 PDGF hAPPV717I transgenic mice were randomly divided into two groups:G-CSF group and control group.The G CSF group was subcutaneously injected with 50 μg · kg-1 · d-1 of G-CSF for 7 days.The control group was injected subcutaneously with an equal volume of PBS in parallel.The animals were tested in Morris water maze on the 7th,14th,and 28th days after the last day of the injection,and the escape latency was recorded.Once the test was completed,the peripheral blood was taken to evaluate the effect of G-CSF to induce hematopoietic stem cells (HSCs) via flow cytometry.Then the mice were killed,their brains were quickly removed and frozen on dry ice.With the immunohistochemical staining and double immunofluorescence staining,the neurogenesis could be observed in the model mice.Results We found that G-CSF significantly shortened the escape latencies in PDGF-hAPPV717I transgenic mice compared to controls on the 7th,14th,and 28th day after G-CSF treatment [7 d:(27.19±4.07) s and (46.07±7.21) s,P＜0.000; 14 d:(26.48±5.29) sand (42.99±11.70) s,P＜0.010; 28 d:(24.97±3.61) s and (45.54±9.55) s,P＜0.002)].At the same time,we found that the percentage of CD34+/CD45+ cells in the peripheral blood was 0.358±0.161,0.223±0.038,0.168±0.049 on the 7th,14th,and 28th day after G-CSF treatment,respectively.Compared with the control group (0.073±0.026,0.067±0.034,0.072± 0.037),the percentage of CD34′ /CD45+ cells in the peripheral blood were increased (P＜0.001).BrdU+ cells were found in dentate gyrus (DG) of hippocampus and the cortex of the G-CSF group,where the BrdU+ /Ncstin- and BrdU-/MAP-2+ cells were also detected positively.Conclusions Subcutaneous administration of G- CSF may improve the cognition in APP transgenic mouse model of AD.G-CSF may mediate the proliferation,differentiation of hcmatopoietic stem cells (HSCs).and may induce the neural stem cells into the brain.

OBJECTIVE: To study the effect of aquaporin 4(AQP4) in regulating the permeability of blood-brain barrier(BBB) induced by subacute 1,2-dichloroethane(1,2-DCE) inhalation. METHODS: Specific pathogen free healthy CD-1 male Aqp4 genetically engineered mice(Aqp4~(+/+)and Aqp4~(-/-)) were randomly divided into control and low-, medium-and high-dose groups. The mice were exposed to 1,2-DCE at the dosages of 0.00, 100.00, 350.00 and 700.00 mg/m~3 for 6 hours per day for consecutive 28 days by systemic dynamic inhalation. After the end of 1,2-DCE exposure, the BBB permeability was evaluated by Evans blue staining. Real-time fluorescence quantitative polymerase chain reaction method was used to detect the mRNA expression of genes related to BBB tight junction protein(Tjp)1, Tjp2, Tjp3, claudin(Cldn)3, Cldn5, Cldn11, occludin(Ocln), matrix metalloproteinase(Mmp)2, Mmp9 and Na-K-Cl cotransporter-1(Nkcc1). RESULTS: The BBB permeability in mice showed significant change with 1,2-DCE dose and Aqp4 genotype(P<0.01). The BBB permeability of Aqp4~(+/+) genotype mice was higher in low-, medium-and high-dose groups than that of control group(all P values were <0.05). The permeability of BBB was lower in Aqp4~(+/+) genotype mice in the control group than that of Aqp4~(-/-) genotype mice in the same group(P<0.05), but BBB permeability was higher in Aqp4~(+/+) genotype mice in the three dose groups than that of Aqp4~(-/-) genotype mice in the same group(all P values were <0.05). The Cldn3 and Olcn mRNA relative expression in the brain cortex had statistical difference in mice with different genotype(all P values were <0.01). The mRNA relative expressions of Cldn3 and Olcn in the brain cortex were higher in Aqp4~(-/-) genotype mice than that of Aqp4~(+/+) genotype mice(all P values were <0.01). The relative mRNA expression levels of Tjp1, Tjp2, Tjp3, Cldn5, Cldn11, Mmp2, Mmp9 and Nkcc1 in the cerebral cortex of mice were not statistically significant in aspect of 1,2-DCE exposure dose and genotype(all P values were >0.05). CONCLUSION: Exposure to 1,2-DCE can increase BBB permeability in mice, and the mechanism may be associated with 1,2-DCE-induced down-regulation of Aqp4 and up-regulation of mRNA expression of the cerebral cortex TJP-related molecules Cldn3 and Ocln.

Objective:To evaluate the efficacy of the domestic D-Shant device for the treatment of patients with chronic heart failure (CHF) using echocardiography.Methods:Twenty-four CHF patients who were treated with domestic D-Shant device in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from September 2020 to December 2021 were enrolled in the study. Pulmonary capillary wedge pressure (PCWP)/ left atrial pressure (LAP), right atrial pressure (RAP), pulmonary artery pressure, interatrial septal gradient pressure, cardiac index and pulmonary/systemic blood flow ratio (Qp/Qs) were measured before and after implantation using right heart catheterization.Left atrial end-diastolic area index (LAEDAI), left atrial end-diastolic volume index (LAEDVI), left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular ejection fraction (LVEF), right atrial end-diastolic diameter, right ventricular end-diastolic diameter, tricuspid annular plane systolic excursion (TAPSE), right ventricular tractional area change (RVFAC), device shunt aperture, velocity and pressure, together with mitral and tricuspid regurgitation severity were measured using echocardiography before, and 1 month as well as 3 months after D-Shant device implantation. Clinical data were collected and analyzed including 6-minute walking test (6MWT), New York Heart Association (NYHA) classification and the Kansas City Cardiomyopathy Questionnaire (KCCQ). Spearman correlation analysis was used to determine the relation between the changes in PCWP/LAP as well as echocardiographic parameters before and 3 months after implantation and NYHA classification. Binary Logistic regression analysis was performed to determine the predictive factors of NYHA classification improvement at 3-month follow-up after D-Shant device implantation.Results:①D-Shant devices were successfully implanted in all patients. ②Compared with preoperative values, invasive PCWP/LAP systolic, diastolic and mean pressures, transatrial septal gradient, and pulmonary systolic, diastolic and mean pressures decreased significantly after implantation(all P<0.001); Qp/Qs increased significantly after implantation( P<0.001). ③Compared with preoperative values, TAPSE, RVFAC and pulmonary artery flow velocity increased at 1 month after implantation(all P<0.05), whereas a significant reduction in mitral regurgitation grade, and an increase in LVEF and pulmonary artery flow velocity at 3 months after implantation(all P<0.05). Right atrial end-diastolic diameter, right ventricular end-diastolic diameter, LAEDAI, LAEDVI, LVEDVI, LVESVI, ratio of early to late diastolic peak velocities of mitral inflow(E/A), systolic peak velocity of mitral annulus at septal site(S′), ratio of early diastolic peak velocity of mitral inflow to diastolic peak velocity of mitral annulus(E/e′), pulmonary artery diameter, inferior vena cava diameter and degree of tricuspid regurgitation did not change among before, and 1 month as well as 3 months after implantation. There were no significant changes in the device shunt aperture, velocity and pressure between 1 month and 3 months after implantation(all P>0.05). ④The significant improvements in NYHA classification, KCCQ scores and 6MWT were observed at 1 and 3 months after implantation compared with preoperative values (all P<0.01). ⑤NYHA classification at 3 months after implantation was correlated with LVEF pre-post, PCWP/LAP pre-post, TAPSE pre-post and RVFAC pre-post ( rs=0.738, -0.730, 0.738, 0.723; all P<0.001). Logistic regression analysis showed that LVEF pre-post was an independent predictor for NYHA classification improvement at 3 months after implantation ( OR=0.687, 95% CI=0.475-0.992, P=0.045) . Conclusions:Domestic D-Shant device can effectively improve the cardiac function and clinical symptoms in patients with CHF. Echocardiography is a feasible and effective method to evaluate the benefits of domestic D-Shant device for the treatment of CHF.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.