The senescence accelerate mouse prone are a model of early learning and memory impairment,because they exhibit most of the characteristics of the pathogenesis of Alzheimer's disease,including abnormal expression of anti-aging factors,excessive increase of inflammatory factors,amyloid deposition,tau protein hyperphosphorylation,mitochondrial autophagy,the central mechanism of blood-brain barrier damage,and pathological damage of multiple systems and organs.Therefore,it has been widely used as an ideal model for Alzheimer's disease research.With the deepening of the experimental research on the mechanism of AD,it was found that SAMP8 mice showed obvious changes in behavior,histopathology and biochemical parameters compared with SAMR1,which were similar to human diseases.Therefore,this paper reviews the research progress of SAMP8 mice in recent years,in order to provide useful guidance and help for the application of SAMP8 mouse model in a variety of aging diseases.

Objective:To study the effects of the combined application of NaF and Nisin on Streptococcus mutans(S.mutans).Meth-ods:The minimum inhibitory concentration(MIC)of Nisin and NaF against S.mutans was determined by microdilution method respec-tively.The fractional inhibitory concentration(FIC)was calculated by checkerboard method.The inhibition effect of the combination of NaF and Nisin at(NF)the same MIC concentration on acid production and acid resistance of S.mutans was detected.Crystal violet staining was used to detect the effects of NF in the inhibition of the biofilm formation,and the damage and dispersion of the established biofilms.The changes of the biofilms were observed by CLSM.Results:The MIC of NaF and Nisin was 0.6 mg/mL and 20 mg/mL re-spectively.The FIC was 0.75.The 1/8×MIC NF showed significantly higher inhibition on acid production and biofilm formation than 1/4×MIC NaF or Nisin(P＜0.05),but it has no obvious dispersion effect on established biofilms.The 1/2×MIC NF showed stronger in-hibition effect on the acid resistance of S.mutans in the membrane than 1×MIC NaF or Nisin(P＜0.05).At the concentration of 2x MIC,any component didn't cause obvious damage on the established biofilm structure.Conclusion:Nisin and NaF have synergistic in-hibitory effects on the proliferation,acid production,acid resistance and biofilm formation of S.mutans.

The principles for surgical treatment of femoral neck fracture are anatomical reduction, rigid fixation and reduction of iatrogenic tissue damage to maintain sufficient blood supply and reduce the risk of complications such as avascular necrosis of the femoral head. In the evolution of internal fixation structures for femoral neck fracture, a variety of new products have been developed, such as the neck-shaft angle stabilization structure represented by dynamic hip screw, the multi-screw structure represented by three cannulated screws, and the plate-screw structure represented by multi-screw structure combined with a locked plate. These internal fixation structures have their own advantages and disadvantages in terms of stability and reduced risk of complications. However, none of them can perfectly meet the requirements of all the surgical principles. Femoral neck system (FNS) was firstly applied in clinic practice in 2017 to further improve the internal fixation of femoral neck fracture. In recent years, its mechanical properties and clinical effects have been widely reported in an attempt to further improve the implantation of this internal fixation device. This article reviews the researches on the mechanical properties and clinical efficacy of FNS and the suggestions put forward by orthopedic surgeons to improve the implantation methods of FNS.

Objective Constructing a risk prediction model of IgA nephropathy proteinuria treated by traditional Chinese medicine based on random survival forest model,Screening prognostic risk factors of IgA nephropathy proteinuria.Methods Collecting retrospectively clinical data of 129 cases diagnosed with IgA nephropathy,randomly divided them into training set(60%)and test set(40%).The risk prediction model of IgA nephropathy proteinuria was constructed in the training set with the random survival forest model,and the prognostic risk factors were screened by VIMP method.The accuracy of risk prediction model was validated in the test set with time-dependent ROC curve(tdROC).Results According to the result of VIMP,the prognostic risk factors for IgA nephropathy proteinuria are in the order of eGFR,hypertension,traditional Chinese medicine,24 hUPRO>1 g,genomo sclerosis ratio,Lee grading,fat,hyperlipidemia,hypertrophymia,hyparmane ledmia,Anemia,age and gender.The eGFR was negatively and non-linearly associated with the risk rate of developing persistent proteinuria.Glomerulosclerosis ratio greater than 0.3 is approximately linearly and positively associated with the risk rate of persistent proteinuria.Conclusion Random survival forest model has good predictive performance in the risk prediction model of IgA nephropathy proteinuria treated by traditional Chinese medicine.This risk model can determine the result of IgA nephropathy treated by traditional Chinese medicine,and which is helpful for clinical follow-up monitoring and formulation of individualized treatment plans.

ObjectiveTo explore the mechanism of Yishen Huoxue prescription in renal interstitial fibrosis （RIF） from the perspective of endothelial cell and cell energy metabolism. MethodThe model was successfully established by unilateral ureteral obstruction （UUO）. Seventy-five SPF C57BL/6 mice were randomly divided into a model group， a resveratrol group （50 mg·kg^-1·d^-1）， three Yishen Huoxue prescription low， medium， and high-dose groups （7.1， 14.2， 28.4 g·kg^-1·d^-1）， with 15 mice in each group. In addition， another 15 mice were used to prepare sham operation model. Mice in the sham operation group and the model group were gavaged with equal volume of normal saline. All mice were sacrificed on 7， 14， and 21 d after modeling. The protein expression of platelet endothelial cell adhesion molecule 31 （CD31） was detected by immunohistochemical S-P method. The expression of α-smooth muscle actin （α-SMA）， collagen Ⅳ （Col-Ⅳ）， angiopoietin 1（Ang-1） and tyrosine kinase receptors 2 （Tie-2）， vascular endothelial growth factor （VEGF）， vascular endothelial cadherin （VE-cadherin）， and occludin in renal tissues was detected by Western blotting. The mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin in renal tissues were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the levels of reactive oxygen species （ROS） in mice were detected by enzyme linked immunosorbent assay （ELISA）. ResultAs compared with the sham operation group， the expression of CD31 in renal tissues of the model group was significantly decreased and worsened with the extension of modeling time （P<0.05）， α-SAM and Col-Ⅳ protein expression levels were significantly increased （P<0.01）， but the expression of CD31 was stable in 14-21 d. ROS levels were significantly increased （P<0.01）， and the protein and mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin were significantly down-regulated （P<0.01）. As compared with the model group， the expression of CD31 was increased （P<0.05）， and α-SAM and Col-Ⅳ in the resveratrol group and the medium and high-dose Yishen Huoxue prescription groups were significantly decreased （P<0.01）. The ROS content was significantly decreased （P<0.01）， and the protein and mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin were up-regulated （P<0.01）， As compared with the resveratrol group， the protein expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin in the medium and low-dose Yishen Huoxue prescription groups were significantly different （P<0.01）. There was no significant difference in the mRNA expressions of CD31 and Ang-1/Tie-2 in the high-dose Yishen Huoxue prescription group， and no significant difference in the ROS level in the medium-dose Yishen Huoxue prescription group. ConclusionThe anti-RIF effect of Yishen Huoxue prescription may be related to promoting vascular endothelial repair， regulating mitochondrial ROS to reduce oxidative stress， protecting the integrity of renal endothelial structure， delaying cell apoptosis， and maintaining cell energy metabolism.

Objective:To study the effect of Sanjie Xiaoliu Recipe on transplanted tumors in breast cancer mice through in vivo experiments, in order to explore the efficacy and mechanism of Sanjie Xiaoliu Recipe on breast cancer patients. Methods:45 BaL B/c female mice were selected to establish the transplanted tumor model of breast cancer. All the transplanted tumor models of breast cancer mice were randomly divided into five groups: the control group (intragastric administration of normal saline), the low, medium and high dose group of Sanjie Xiaoliu Recipe (intragastric administration of different doses of Sanjie Xiaoliu Decoction), and the paclitaxel group (intraperitoneal injection of paclitaxel). After 24 days of continuous administration, the diet and activities of mice were observed; the body weight, weight and volume changes of transplanted tumor mice were recorded, and the tumor inhibition rate was calculated. Western blot was used to detect the expression of epithelial mesenchymal transformation related proteins (E-cadherin, N-cadherin, Vimentin) in the transplanted tumor tissues of mice in each group.Results:(1) The food intake and activity status of mice treated with Sanjie Xiaoliu Recipe were less affected by the transplanted tumor of breast cancer. (2) The volume and weight of transplanted tumor in the treat groups were smaller than those in the control group (all P<0.01), and the volume of transplanted tumor in the middle dose group of Sanjie Xiaoliu Recipe was smaller than that in the low dose group ( P<0.05). The tumor inhibition rates among the treatment groups were: Sanjie Xiaoliu Recipe medium dose group 52.4%, paclitaxel group 40.3%, Sanjie Xiaoliu Recipe low dose group 39.5%, Sanjie Xiaoliu Recipe high dose group 34.1%. (3) The results of Western blot showed that the expression level of E-cadherin in the transplanted tumor tissue of the treat groups was higher than that in the control group, and the expression levels of N-cadherin and Vimentin were lower than that in the control group, with statistically significant difference (all P<0.05). Conclusions:The Sanjie Xiaoliu Recipe can improve the weakness and reduced consumption of breast cancer mice, which can inhibit the tumor mass growth in mice to a certain extent. Its mechanism may be that Sanjie Xiaoliu Recipe can inhibit the epithelial mesenchymal transformation of breast cancer and the invasion and metastasis of breast cancer.

Background::The preferred therapeutic regimen for Toxoplasma encephalitis (TE) is a combination of pyrimethamine and sulfadiazine, and trimethoprim-sulfamethoxazole (TMP-SMX) plus azithromycin is the widespread alternative therapeutic regimen. The synergistic sulfonamides tablet contains TMP, sulfadiazine, and SMX and hypothetically could be used for TE treatment. This study aimed to compare the efficacy and safety of synergistic sulfonamides plus clindamycin (regimen B) with TMP-SMX plus azithromycin (regimen A) for the treatment of human immunodeficiency virus (HIV) associated TE.Methods::This was an open-labeled, multi-center randomized controlled trial recruited from 11 centers. Each recruited patient was randomly assigned to receive regimen A or regimen B for at least 6 weeks. The overall response was evaluated by assessment of the clinical response of TE-associated clinical features and the radiological response of TE-associated radiological findings. The overall response rate, clinical response rate, radiological response rate, and adverse events were assessed at 2, 6, and 12 weeks. Death events were compared between the two regimens at 6, 12, and 24 weeks.Results::A total of 91 acquired immunodeficiency syndrome (AIDS)/TE patients were included in the final analysis (44 in regimen A vs. 47 in regimen B). The overall response rate, which refers to the combined clinical and radiological response, was 18.2% (8/44) for regimen A and 21.3 % (10/47) for regimen B at week 6. The results of clinical response showed that, in comparison with regimen A, regimen B may perform better with regards to its effect on the relief of clinical manifestations (50.0% [22/44] vs. 70.2% [33/47], P = 0.049). However, no significant differences in radiological response, mortality events, and adverse events were found between the two regimens at week 6. Conclusions::Synergistic sulfonamides plus clindamycin, as a novel treatment regimen, showed no significantly different efficacy and comparable safety in comparison with the TMP-SMX plus azithromycin regimen. In addition, the regimen containing synergistic sulfonamides may exhibit advantages in terms of clinical symptom alleviation.Trial Registration::ChiCTR.org.cn, ChiCTR1900021195.

Objective:To identify the molecular mechanisms of the effects of the Buyin Qianzheng formula (BYQZF)on the mitochondrial dynamics in a Parkin overexpression Parkinson's disease (PD) cell model.Methods:First,a stable Parkin overexpression cell model was constructed using plasmid transfection.Then,we examined the protective effect of BYQZF on the mitochondrial dysfunction of the Parkin overexpression PD cell model induced by neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+).The mRNA expression level of Parkin was evaluated using real-time quantitative PCR.The cell survival rate was detected using the Cell Counting Kit-8 assay.We evaluated the cellular adenosine triphosphate (ATP)levels using luciferase assays.A laser scanning confocal microscope was used to observe the mito-chondrial morphology,activity,and mitochondrial membrane potential (ΔΨm).Western blot was con-ducted to evaluate the levels of the fusion proteins mitofusin1,mitofusin2,optic atrophy 1,dynamin-related protein 1,and mitochondrial fission protein 1.Results:Parkin overexpression attenuated MPP+-induced mitochondrial damage,increased mitochon-drial activity and AΨm.BYQZF increased the survival of MPP+-induced cells that overexpressed Parkin and upregulated the mitochondrial form factor and activity.It also inhibited a decrease in the ΔΨm and ATP levels.These findings suggested that BYQZF protected against MPP+-induced mitochondrial dysfunction and enhanced the protective effect of Parkin overexpression.Furthermore,the formula upregulated the expression of the fusion proteins mitofusin1,mitofusin2,and optic atrophy 1 (closely related to mitochondrial quality remodeling),and reduced the expression of the fission protein dynamic-related protein 1,as well as mitochondrial fission protein 1.Conclusion:The mechanism by which BYQZF increased the mitochondrial protective effect of Parkin gene overexpression in MPP+-induced cells may be related to improving mitochondrial function and regulating the balance of mitochondrial division and fusion proteins.

Objective:To investigate the therapeutic effect of rat bone marrow mesenchymal stem cells (BMSCs) transfected with recombinant rat platelet-derived growth factor BB (rrPDGF-BB) gene on the distraction osteogenesis.Methods:From October, 2019 to June, 2020, 48 batches of BMSCs were cultured from 48 young SD rats, 24 of which were transfected with rrPDGF-BB gene by lentivirus. Meanwhile, other 72 male adult SD rats were randomly selected to establish the right femoral distraction osteogenesis model. The rats were equally divided into 3 groups. PBS, BMSCs without intervention and BMSCs transfected with rrPDGF-BB gene were injected into the distraction space of each group of rats assigned as Blank group, Negative group and Experimental group, respectively. Results of the experiment were evaluated by means of imaging and immunohistochemistry. P<0.05 indicated a statistically significant difference. Results:The cultured BMSCs grew well. The expression of CD34(0.1%) and CD45(2.8%) in the third generation of BMSCs was low, and that of CD29 (95.1%) was high, which was consistent with the phenotype of BMSCs described in literatures. After transfection, the expression of green fluorescence gradually increased with the extension of transfection time, confirming the success of transfection. After 14 days, all rats reached the expected distance of distraction. The rats were observed at assigned time points in 2, 4 and 8 weeks. The photos of femur specimen showed that continuous callus could be seen in the experimental group, the hardness and colour were close to the normal bone tissue, and the activity of the distraction space was poor, which was lower than that of the blank group. X-ray examination showed that there were more new callus in the experimental group, and the bone marrow cavity was re-canalized earlier than that of the blank group; Micro-CT examination, in sagittal plane, showed that the distraction space of the experimental group healed well, the broken end was connected, and the recanalization of bone marrow cavity was earlier than that of the blank group; Micro-CT parameters of each group showed that trabecular thickness[(0.297±0.005) mm], trabecular number [(1.663±0.032) mm], bone volume fraction[(59.832±2.187)%] and bone mineral density[(0.586±0.014) g/cm 3] of the experimental group were the greatest, while trabecular separation[(0.399±0.051) mm] of the experimental group was the smallest. There was statistical difference between each group( P < 0.05); HE staining and VEGF immunohistochemistry showed that the vessels and chondrocytes formed earlier and were more in the experimental group than that in the blank group. In 8 weeks, the new callus joined into one piece under the microscope in the experimental group, and the bone marrow cavity was re-canalized with a large number of red blood cells. Conclusion:Studies have shown that BMSCs transfected with rrPDGF-BB gene can promote the formation of callus in the distraction area of rats, shorten the mineralisation time of new callus, and promote the maturation of new bone in the area of distraction osteogenesis.

Objective To investigate the effectiveness and cost of 50% and 80% wettable powder of niclosamide ethanolamine salt (NESWP) and 26% metaldehyde and niclosamide suspension concentrate (MNSC) in hilly schistosomiasis-endemic regions, so as to provide insights into the selection of chemical molluscicides in hilly regions. Methods In September 2020, a wasteland in Guanshanqiao Village, Yanrui Township, Yushan County of Jiangxi Province was selected as the experimental region, which was sectioned into five blocks and defined as four experimental groups (A₁, A₂, B, C) and a blank control group (D). 80% NESWP were given at doses of 1 g/m² and 1.5 g/m² in groups A₁ and A₂ using the spraying method, 50% NESWP was given at a dose of 2 g/m² in Group B using the spraying method, and 26% MNSC was at a dose of 4 g/m² in Group C using the spraying method, while no chemical treatment was given in Group D. Snail survey was performed using a systematic sampling method before chemical treatment and 1, 3, 7 d and 15 d post-treatment to examine the molluscicidal effect, and all molluscicidal costs were estimated to calculate the cost of chemical treatment per 1 m² and the cost of the reduction in the mean density of living snails per 1%. Results The highest mortality of snails was 78.95% and the lowest density of living snails was 0.2388 snails/0.1 m² in the experimental groups within 7 d of chemical treatment, and the highest mortality of snails was 94.74% and the lowest density of living snails was 0.058 0 snails/0.1 m² 7 d post-treatment. There were no significant differences in the snail mortality among the A₁, A₂, B and C groups 1 (χ² = 2.250, P > 0.05), 3 (χ² = 1.779, P > 0.05) or 15 d post-treatment (χ² = 2.286, P > 0.05), while a significant difference was detected in the snail mortality among the four groups 7 d post-treatment (χ² = 7.990, P = 0.046). In addition, there were no significant differences in the snail mortality between A₁ and A₂ groups 1 (χ² = 0.724, P > 0.05), 3 (χ² = 0.584, P > 0.05), 7 (χ² = 0.400, P > 0.05) or 15 d post-treatment (χ² = 0.251, P > 0.05). The costs of chemical treatment per 1 m² were 0.58, 0.60, 0.64 Yuan and 0.73 Yuan in groups A₁, A₂, B and C, and the costs of the mean density of living snail per 1% reduction were 19.29, 20.44, 21.68 Yuan and 23.53 Yuan in groups A₁, A₂, B and C, respectively. Conclusion 80% NESWP shows a high molluscicidal efficacy and low cost in hilly schistosomiasis-endemic regions.