Many major neurodegenerative diseases are associated with proteins misfolding and aggregation, which are also called "neurodegenerative conformational disease". The interaction of gene mutation and environmental factors are probably primary events resulting in oligomer and aggregate formations of proteins. Moreover, the dysfunctions of protein control systems, i.e. the ubiquitin-proteasome system and autophagy-lysosomal system, also contribute to the neurodegenerative process. The present review mainly summarizes protein misfolding and aggregation in the development of neurodegenerative conformational disease and the underling mechanisms, as well as upregulation of heatshock proteins as a promising treatment method for this kind of disease.

Objective To study the antitumour, immunomodulating and enterobacteria regulating effects of exopolysaccharides (EPS). Method The suppressive rate of growth of sarcoma 180, the index of immunity, and the intestinal microflora were determined. Results (1) EPS inhibited the growth of sarcoma 180 by oral for BALB/c mice significantly. The suppressive rate at the dose of 120mg/kg bw?d was 42.7%. (2) At the dose of 120mg/kg bw?d the index of thymus and IL-2 in serum increased significantly. There was increasing trend in respect of TNF-? and killing activation of NK cell. (3) The amounts of Lactobacillus in groups treated with EPS increased significantly, and the amounts of Enterobacteriacea and Enterococcus droped significantly. Conclusion EPS had the antitumour effect in vivo, and could modulate the immune function, improve the microbial balance in the intestinal tract of tumour bearing mice to some extent. So the antitumour mechanism was probably correlated with the immunomodulating effect.

Objective To investigate the effect of high expression of functional IDO trom donor DCs on transplantation rejection in mice heterotopic cardiac transplantation.Method Adenovirus vector containing IDO gene was used to infect donor (C57BL/6) DCs to obtain IDO+ DCs.Mouse heterotopic cardiac transplantation models were established (C57BL/6-BALB/c) and the following groups were set up:control group,DCs injection group and IDO+ DCs injection group.Survival time of the donor heart in all groups was observed.Meanwhile,donor hearts were harvested at 7 th day post-transplantation for different examinations,including pathological examination,mRNA expression of IDO by real-time PCR,and IDO protein expression by Western blotting.Peripheral blood of recipients was also harvested for T lymphocyte apoptosis rate examination by FACS.Result Cardiac allograft median survival time in control group,DCs injection group and IDO+ DCs injection group was 7,7.5,and 17.5 days respectively.IDO+ DCs treatment significantly prolonged the survival time of donor hearts (P＜0.01).Pathological grading was significantly decreased (P＜0.01).The CD3+ T lymphocyte apoptosis rate in peripheral blood of recipients in IDO+ DCs injection group was (46.50 + 5.02)％,significantly higher than the other two groups (P＜0.01).Both IDO mRNA and protein expression showed significant increase (P＜0.01).Conclusion The preoperative medication with IDO+ DCs injection to the recipients could induce T lymphocyte apoptosis and significantly suppress the rejection in mice heterotopic cardiac homotransplantation.

Objective To observe the effects of nonylphenol(NP)on the intracellular calcium concentration changes and cell proliferation,and the involvement of GPR30 receptor in H9c2 cell. Methods The intracellular calcium concentration changes were recorded by using intracellular calcium determination method and cell proliferation was observed by MTT method in H9c2 cell. Results NP(1×10-10 mol/L)increased the intra?cellular calcium concentration changing amplitude and promoted the proliferation of H9c2 cells,while NP(1×10-6 mol/L)decreased intracellular calcium concentration changing amplitude and suppressed cell proliferation. G15 could block the promoting effect of 1×10-10 mol/L NP on the intracel?lular calcium concentration and cell proliferation,but could not block the inhibition of 1×10-6 mol/L NP on the intracellular calcium increase and cell proliferation. Conclusion The results indicate that NP affect rapid calcium signal changes and cell proliferation in non?monotonic dose dependent manner,and its mechanism may be due to the different involvement of GPR30 receptor in different concentrations.

Objective To calculate the pre-stretching of the microscopic components of the aortic wall under physiological homeostasis by considering a three-dimensional(3D)residual stress field.Methods The aortic wall was simplified into a double-layer ideal circular tube,and the 3D residual stress field of the vascular wall was calculated based on a 3D expansion angle experiment.Then,the in vivo stress distribution characteristics under mean blood pressure and the pre-stretching of each microscopic constituent of the vascular wall under a physiologically steady state were obtained.The inverse problem was constructed according to the internal pressure-radius relationship measured in vivo.Physiological homeostasis of the aorta was considered the reference state,and inversion identification of the material parameters of the aorta in vivo was realized while integrating the three residual stress fields.Results When residual stress was not considered,the mean stress of the middle membrane was greater than that of the outer membrane.When residual stress was considered,the outer membrane bore more stress than the middle membrane,and the outer membrane protected the middle membrane.The pre-stretching of the middle film with residual stress was lower than that without residual stress,whereas the pre-stretching of the outer film was higher than that without residual stress.Moreover,the pre-stretching of the outer membrane collagen fibers was greater than that of the middle membrane collagen fibers.The in vivo calculations of the material parameters of the aorta were performed using physiological homeostasis as the reference configuration,and the proportion of each component was consistent with the experimental results.However,the proportion of elastin in the outer membrane was significantly overestimated when the non-stress configuration was used as the initial configuration,which was inconsistent with the experimental results.Conclusions Residual stress significantly influences the pre-stretching and physiologically steady mechanical states of the microscopic components of the aortic wall.Therefore,it is necessary to fully consider the influence of residual stress to establish the physiologically steady state of the aortic wall accurately.Furthermore,it is also necessary to fully consider the 3D characteristics and layer specificity of residual stress in the in vivo identification of material parameters.

Objective:To explore the efficacy and safety of urethroplasty combining the reconstruction of urethral plate with the enlargement of urethral cavity in the treatment of short penile urethral atresia or severe stricture.Methods:From January 2017 to September 2020, 10 patients, 22 to 78 years old and the average age 48, with short penile urethral atresia or severe stricture were treated in the Department of Urology, Henan University People’s Hospital, Henan Provincial People’s Hospital. The lengths of the stenotic or atresic segment were 0.2-0.5 cm, with an average length of 0.3 cm. They were all treated with one-stage urethroplasty to reconstructe urethral plate and enlarge urethral cavity with free prepuce skin grafts or pedicled flaps adjacent to the stenosis. By the guidance of urethral dilator, the strictured urethra was incised longitudinally on the ventral side of penis to the distance of 0.5 cm into the normal urethral mucosa at both ends. The stricture or atresic scar tissue of the urethra was removed. The distal and proximal corpus spongiosum were appropriately dissociated, and the urethral mucosa at the both ends of the dorsal side was anastomosed intermittently to reconstruct the urethral plate. Free prepuce skin grafts were used in 4 cases, and pedicled flaps adjacent to the stenosis were used in 6 cases to enlarge the urethral cavity.Results:In this study, the operation time ranged from 75 minutes to 100 minutes, with an average of 85.6 minutes. Intraoperative blood loss ranged from 20 ml to 65 ml, with an average of 45.5 ml. Followed up from 3 months to 3 years postopreatively, all of them did not have painful erection and penile curvature during erection, and felt the same as before in sexual life. Urinary flow rates were significantly improved in 9 cases, and the maximum flow rate was more than 15 ml/s. One recurred patient was cured after urethral dilatation.Conclusions:The one-stage urethroplasty combined the reconstruction of urethral plate with the enlargement of urethral cavity. The urethral plate was reconstructed through urethral resection of narrow segment and the urethral cavity was enlarged with free skin or pedicled flap. This technique has the advantages of a simple and safe operation with a high success rate and a less complication rate. It is an effective procedure to repair short penile urethral atresia or severe stricture.

Objective:To explore the efficacy and safety of urethroplasty combining the reconstruction of urethral plate with the enlargement of urethral cavity in the treatment of short penile urethral atresia or severe stricture.Methods:From January 2017 to September 2020, 10 patients, 22 to 78 years old and the average age 48, with short penile urethral atresia or severe stricture were treated in the Department of Urology, Henan University People’s Hospital, Henan Provincial People’s Hospital. The lengths of the stenotic or atresic segment were 0.2-0.5 cm, with an average length of 0.3 cm. They were all treated with one-stage urethroplasty to reconstructe urethral plate and enlarge urethral cavity with free prepuce skin grafts or pedicled flaps adjacent to the stenosis. By the guidance of urethral dilator, the strictured urethra was incised longitudinally on the ventral side of penis to the distance of 0.5 cm into the normal urethral mucosa at both ends. The stricture or atresic scar tissue of the urethra was removed. The distal and proximal corpus spongiosum were appropriately dissociated, and the urethral mucosa at the both ends of the dorsal side was anastomosed intermittently to reconstruct the urethral plate. Free prepuce skin grafts were used in 4 cases, and pedicled flaps adjacent to the stenosis were used in 6 cases to enlarge the urethral cavity.Results:In this study, the operation time ranged from 75 minutes to 100 minutes, with an average of 85.6 minutes. Intraoperative blood loss ranged from 20 ml to 65 ml, with an average of 45.5 ml. Followed up from 3 months to 3 years postopreatively, all of them did not have painful erection and penile curvature during erection, and felt the same as before in sexual life. Urinary flow rates were significantly improved in 9 cases, and the maximum flow rate was more than 15 ml/s. One recurred patient was cured after urethral dilatation.Conclusions:The one-stage urethroplasty combined the reconstruction of urethral plate with the enlargement of urethral cavity. The urethral plate was reconstructed through urethral resection of narrow segment and the urethral cavity was enlarged with free skin or pedicled flap. This technique has the advantages of a simple and safe operation with a high success rate and a less complication rate. It is an effective procedure to repair short penile urethral atresia or severe stricture.

Objective To investigate the effectiveness and safety of volumetric modulated arc therapy (VMAT) hypofractionated radiotherapy and intensity modulated conformal radiotherapy technique (IMRT) conventional fractionated radiotherapy after breast cancer radical operation.Methods Eighty-five patients with breast cancer modified radical operation admitted and treated in this hospital from March 1,2021 to De-cember 30,2021 were selected as the research subjects and divided into the VMAT group (n=41) and the IM-RT group (n=42) according to the random number table method.The VMAT group adopted the hypofrac-tionated radiotherapy,with the single fractionated dose of 2.9 Gy/frequency and radiotherapeutic total dose of 43.5 Gy/15 frequencies;the IMRT group adopted the IMRT conventional fractionated radiotherapy,with the single fractionated dose of 2.0 Gy/frequency and radiotherapeutic total dose of 50.0 Gy/25 frequencies.The planning target region V95,V110,conformity index,homogeneity index,treatment time,V5,V20,V30,average dose (Dmean) in the affected side lung,humeral head Dmean and heart V30,Dmean were compared between the two groups.Meanwhile,local recurrence,distant metastasis,disease-free survival and acute and chronic radiation injury were compared between the two groups.Results Compared with the IMRT group,V95 in the VMAT was higher,V110 and homogeneity index were lower,the treatment time was shorter,V5 in the affected lung,Dmean and Dmean in the affected humeral head were lower,V30 in the affected lung was higher,heart V30 in the left side breast cancer was lower,heart Dmean in the right side breast cancer was lower,and the differences were statistically significant (P<0.05).All patients survived without local relapse.The distant metastasis rate and disease free survival rate had no statistical difference between the two groups (P>0.05).Follow up lasted for 12 months,the incidence rates of grade Ⅰ-Ⅱ acute radiodermatitis,radiation esophagitis,chronic radioder-matitis and radiation pneumonia had no statistical differences between the two groups (P>0.05).The inci-dence rate of grade Ⅰ-Ⅱ shoulder dysfunction in the VMAT group was lower than that in the IMRT group with statistical difference (P<0.05).No grade Ⅱ and above acute and chronic radiation injury in the two groups occurred.Conclusion VMAT hypofractionated radiotherapy after breast cancer radical operation is safe and effective.

Objective To propose a one-way fluid-structure interaction (FSI) method based on an idealized aortic dissection model, so as to analyze the hemodynamics and wall stress in the false lumen (FL) under the influence of multiple overlapping uncovered stents (MOUS). Methods Upon establishment of the numerical model, the models were divided into two categories according to whether the model involved FL perfused branch artery. The characteristics of hemodynamics and wall stress state in the post-operative scenarios were simulated under different surgical strategies. The wall stress state of the FL before and after thrombosis formation was also compared and analyzed. ResultsThe release process of the stents had little influence on wall stress of the FL. The high velocity and high wall shear stress (WSS) area in the FL could not be reduced by using the MOUS alone. If only the proximal entry tear was blocked with a covered stent-graft, the distal end would maintain a region of high flow rate and high WSS. The combination of covered stent-graft and MOUS would result in a region of low flow rate and low WSS, as well as reduced wall pressure and wall stress in the FL. Compared with the model with FL perfused branch arteries, the model without it was more likely to form a region of low flow rate and low WSS after surgery. However, blood pressure in the FL was relatively higher. The formation of thrombus in the FL could greatly reduce wall stress in the area covered by the thrombus. Conclusions The method proposed in this study can simultaneously investigate hemodynamics and wall stress characteristics of the FL, and provide support for studying mechanical mechanism of FL thrombolysis induced by MOUS and the post-operative aortic expansion.

Multidrug resistance (MDR) is the main factor of tumor recurrence and chemotherapy failure in clinical practice. Its mechanism is relatively complex, and one of the most thoroughly studied mechanism is the overexpression of P-glycoprotein (P-gp) on tumor cell membrane. Most of the chemotherapy drugs are p-gp substrates, and tumor cells will transport the chemotherapy drugs to the extracellular through p-gp mediated active transport, so that the concentration of effective drugs in the cell is reduced, resulting in drug resistance, leading to the decline of clinical efficacy. The reversal agent of P-gp can reduce the intracellular pumping of chemotherapeutic drugs by regulating the expression and transport activity of P-gp, and enhance the sensitivity of tumor cells to chemotherapeutic drugs, thus improving the therapeutic effect. In this paper, we will summarize the natural plant active ingredients that can reverse P-gp mediated MDR to provide reference for clinical and related studies.