As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients' physical and psychological health and quality of life. Medical practitioners take many strategies for the treatment of fracture healing, including Traditional Chinese Medicine (TCM). In the early stage of fracture healing, the local fracture is often in a state of hypoxia, accompanied by the expression of hypoxia inducible factor-1α (HIF-1α), which is beneficial to wound healing. Through literature mining, we thought that hypoxia, HIF-1α and downstream factors affected the mechanism of fracture healing, as well as dominated this process. Therefore, we reviewed the local characteristics and related signaling pathways involved in the fracture healing process and summarized the intervention of TCM on these mechanisms, in order to inspirit the new strategy for fracture healing, as well as elaborate on the possible principles of TCM in treating fractures based on the HIF molecular mechanism.

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.

Cathartic colon （CC） is a common and refractory digestive system disease， with the pathogenesis not fully clarified. The effective therapies other than laxatives and surgery remain to be developed for CC. Therefore， establishing the CC animal models that fit the disease characteristics of western medicine and syndrome characteristics of traditional Chinese medicine （TCM） is an important link to promote the research on this disease. The fitting degree of animal models with the latest Chinese and western medical diagnostic criteria is an indicator to assess the effectiveness of the animal models in simulating the disease characteristics of western medicine and syndrome characteristics of TCM. The literature review showed that the model animals， drugs and their dosage forms， doses， administration methods， and modeling period of CC varied in different studies， and the available CC animal models presented different fitting degrees with the disease characteristics of western medicine and syndrome characteristics of TCM. Rats were the preferred animals for the modeling of CC. Rhei Radix et Rhizoma preparations were commonly used for model inducing， which， however， may cause water electrolyte disorders， decreased immunity， and even death of animals at the late stage of modeling. The animals were modeled by gradually increasing the starting dose， while the starting dose and increasing dose varied. The maintenance dose was determined based on 50% of the animals having loose stools， and the end for a cycle was determined as the time when loose stools disappeared in 80% of animals. The modeling always lasted for 2-3 cycles， approximately 2-4 months. The CC models established with Rhei Radix et Rhizoma granules and rhein had high fitting degrees with the disease and syndrome characteristics. In addition， the CC animal models of TCM syndromes were still in the exploration stage. There were only the animal models of four TCM syndromes： liver depression and spleen deficiency， both Qi and Yin deficiency， Qi stagnation and blood stasis， and spleen and kidney deficiency. Efforts should be made to establish the animal models that meet the characteristics of disease of western medicine and syndromes of TCM， so as to facilitate the research on CC mechanism and drug development.

OBJECTIVES: Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer, with highmorbidity and mortality rate. Nove drug development for NSCLC is urgently needed.This study aims to investigate the activity of lathyrol derivatives and the mechanism for its inhibitory effect on the growth of NSCLC cells. METHODS: Three lathyrol derivatives were synthesized from lathyrol and their structures were verified by nuclear magnetic resonance. MTT assay was used to detect the effects of the lathyrol derivatives on the proliferation activity of NSCLC cells (A549 and H1299 cells), and the compound with the best activity was selected for subsequent experiments. Colony forming assay, wound-healing assay, and transwell assay were applied to detect in vitro cell proliferation, migration and invasion ability in A549 and H1299 cells, respectively. Quantitative real-time RT-PCR and Western blotting were performed to detect mRNA and protein levels of E-cadherin, N-cadherin, β-catenin, and MMP2 in A549 cells, respectively. RESULTS: Three lathyrol derivatives inhibited the growth of A549 and H1299 cells in a dose-dependent manner, and they showed a weak inhibitory effect on normal cells Beas-2B and 16HBE, indicating that they possessed certain selective toxic effects. Therefore, C-5 benzoylated lathyrol with the best activity was selected as the ideal drug for the subsequent experiments. Compared with the control group, the number and size of cell clusters in the treatment group of A549 and H1299 cells were significantly decreased, the relative mobility were significantly decreased, and the number of invaded cells were significantly decreased (all P<0.05), indicating that the in vitro cell proliferation, migration and invasion ability were decreased. The mRNA levels of integrin α2, integrin β1, MMP2, MMP9, β-catenin, and N-cadherin were decreased, while the expression of E-cadherin was increased (all P<0.05). The protein levels of N-cadherin, β-catenin, MMP2, and integrin αV were decreased, while the expression of E-cadherin was increased (all P<0.05). CONCLUSIONS The lathyrol derivatives synthesized in this study possess good inhibitory activity against NSCLC. Among them, C-5 benzoylated lathyrol significantly inhibits the proliferation, migration, and invasion ability of NSCLC cells in vitro through regulating the process of epithelial-mesenchymal transition.
Cadherins/genetics* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Humans ; Lung Neoplasms/drug therapy* ; Matrix Metalloproteinase 2/genetics* ; RNA, Messenger ; beta Catenin/genetics*

This study prospectively collected the clinical data of patients who received sacral neuromodulation(SNM)variable-frequency stimulation (VFS) mode from June 2020 to December 2020, in order to explore the efficacy and safety of VFS mode in the treatment of refractory lower urinary tract dysfunction. The inclusion criteria were as follows: ①SNM was implanted; ②age ≥18 years old; ③The traditional constant-frequency stimulation (CFS) mode has poor therapeutic effect, and can not be improved after repeated adjustment of stimulation parameters; ④Patients with overactive bladder (OAB) symptoms, who fail to respond to conservative treatment or are intolerant to conservative treatment; ⑤The drugs that affect the lower urinary tract symptoms and pelvic function should not be increased or decreased during the trial; ⑥provision of informed consent. A total of six patients meeting the criteria were included in the study, with three males and three females. The age ranged from 47 to 74 years, with an average age of 55 years. Among those patients, three cases were diagnosed of OAB, two cases were diagnosed of interstitial cystitis, and one case was diagnosed of neurogenic bladder. All patients had received CFS-SNM for an average of 20.6 months before upgrading to VFS mode, and suffered from severe frequency of urination at the same time. Compared with the severity of symptoms during the baseline period and the CFS period, a trend of improvement was found among four patients during the VFS period. The severity of symptoms was mainly based on the average daily urination frequency and OAB-Q score. For the two patients with interstitial cystitis, OAB symptoms worsened during the VFS period, while the VAS score did not change significantly. In general, VFS-SNM is not inferior to CFS-SNM in improving the symptoms of frequent micturition. For patients with interstitial cystitis, multiple sets of VFS parameters can be tried under the premise of satisfactory pain management.

An implantable axial blood pump was designed according to the circulation assist requirement of severe heart failure patients of China. The design point was chosen at 3 L/min flow rate with 100 mm Hg pressure rise when the blood pump can provide flow rates of 2-7 L/min. The blood pump with good hemolytic and anti-thrombogenic property at widely operating range was designed by developing a structure that including the spindly rotor impeller structure and the diffuser with splitter blades and cantilevered main blades. Numerical simulation and particle image velocimetry (PIV) experiment were conducted to analyze the hydraulic, flow fields and hemolytic performance of the blood pump. The results showed that the blood pump could provide flow rates of 2-7 L/min with pressure rise of 60.0-151.3 mm Hg when the blood pump rotating from 7 000 to 11 000 r/min. After adding the splitter blades, the separation flow at the suction surface of the diffuser has been reduced efficiently. The cantilever structure changed the blade gap from shroud to hub that reduced the tangential velocity from 6.2 m/s to 4.3-1.1 m/s in blade gap. Moreover, the maximum scalar shear stress of the blood pump was 897.3 Pa, and the averaged scalar shear stress was 37.7 Pa. The hemolysis index of the blood pump was 0.168% calculated with Heuser's hemolysis model. The PIV and simulated results showed the overall agreement of flow field distribution in diffuser region. The blood damage caused by higher shear stress would be reduced by adopting the spindle rotor impeller and diffuser with splitter blades and cantilevered main blades. The blood could flow smoothly through the axial blood pump with satisfactory hydraulics performance and without separation flow.
China ; Computer Simulation ; Equipment Design ; Heart Failure ; therapy ; Heart-Assist Devices ; Hemolysis ; Humans ; Models, Cardiovascular

Regarding to the sharply increased applications and relatively lower rate of successful funding for major projects in the fields of Critical Care/Wounds and Injuries/Burns/Plastic Surgery from the National Natural Science Foundation of China in recent years, the author summarized the funded projects in this specific field from 2014 to 2018, discussed the characteristics and trends of these applications and grants, and summarized the hotspot issues and frontier researches so as to help the applicants in the future.

To summarize the projects granted by National Natural Science Foundation of China related to tumor biomarkers in laboratory medicine from 2010 to 2018. The projects are categorized and analyzed according to tumor classification, biochemical properties of biomarkers. What′s more, characters of granted projects of tumor biomarkers in recent 9 years are summarized and development trends are pointed out.

Objective:To determine the equilibrium solubility and the apparent oil/water partition coefficients of nicotinate-curcu-min ester,so as to provide basis for the new formula design. Methods:Nicotinate-curcumin ester was dissolved in buffer solution with pH of 1.2-7.8. HPLC was used to detect the equilibrium solubility of nicotinate-curcumin ester in various solutions. The apparent oil/water partition coefficients in octanol-water and octanol-buffer solution system were measured by a shaking-flask method. Results:The solubility of nicotinate-curcumin ester in pH 6.8 was the highest. The apparent oil-water partition coefficients of nicotinate-curcumin ester in pH 1.2,5.8,6.5 and 7.8 were lgPapvalues within the range(lgPap=1.69-1.98) beneficial to the absorption in vivo. But in pH 2,5 and 6.8,the lgPapvalues were greater than 2 with strong lipophilicity. Conclusion:The equilibrium solubility as well as ap-parent oil/water partition coefficients of nicotinate-curcumin ester is greatly influenced by the pH value of media. In the pH value with relatively high solubility,lipophilicity is stronger,suggesting it is difficult to be absorbed by the body and needs to be further studied on dosage forms.

Objective:To determine the equilibrium solubility and n-octanol/water partition coefficients (Papp)of cinnamon acid and cinnamaldehyde. Methods:The equilibrium solubility of cinnamon acid and cinnamaldehyde in different solutions was determined by HPLC,and their n-octanol/water partition coefficients were determined by a shaking flask method combined with HPLC-DAD. Results:When the pH of solution was 7.8,the equilibrium solubility of cinnamon acid was the largest,while that of cinnamaldehyde was the largest in pH 6.8 solution. The scopes of lgPappof cinnamon acid and cinnamaldehyde in different buffer solutions(pH 1.2-7.8) were -1.04-2.27 and 0.29-1.67, respectively, while those in n-octanol/water solvent were 0.85 and 1.26, respectively. Conclusion:The method is simple,accurate and fast to predicate the absorption of chemical components. In gastrointestinal physiological environment,cinnamaldehyde has good absorption, while cinnamon acid is with poor absorption in stomach and with better absorption in intestinal.