Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium(EF)and possess excellent therapeutic effects on various diseases.Encouragingly,in 2022,icaritin soft capsules were approved to reach the market for the treatment of hepatocellular carcinoma(HCC)by National Medical Products Administration(NMPA)of China.Moreover,recent studies demonstrate that icaritin can serve as immune-modulating agent to exert anti-tumor effects.Nonetheless,both production effi-ciency and clinical applications of epimedium flavonoids have been restrained because of their low content,poor bioavailability,and unfavorable in vivo delivery efficiency.Recently,various strategies,including enzyme engineering and nanotechnology,have been developed to increase productivity and activity,improve delivery efficiency,and enhance therapeutic effects of epimedium flavonoids.In this review,the structure-activity relationship of epimedium flavonoids is described.Then,enzymatic en-gineering strategies for increasing the productivity of highly active baohuoside I and icaritin are dis-cussed.The nanomedicines for overcoming in vivo delivery barriers and improving therapeutic effects of various diseases are summarized.Finally,the challenges and an outlook on clinical translation of epi-medium flavonoids are proposed.

Objective:To study the differences in the cumulative dose between deformable image registration (DIR) and simple dose-volume histogram (DVH) summation in the fractionated brachytherapy of cervical cancer, and to analyze the feasibility of the application of DIR in the dosimetry assessment of targets and organs-at-risk (OARs) in the brachytherapy.Methods:A retrospective analysis was conducted for 13 cases with primary cervical cancer treated with four fractions of interstitial brachytherapy guided by CT images. The four CT images of each cases were registered using an intensity-based DIR. Then, the cumulative doses (the D2 cm 3, D1 cm 3, and D0.1 cm 3 of the bladder, rectum, intestine, and colon and the D90for targets) after DIR were calculated and compared to those obtained using simple DVH summation. Afterward, the correlation between the dose difference and dice similarity coefficient (DSC) was analyzed. With the dose difference (the remaining dose of OARs caused by the DIR) as limits, a new plan was made for the latest CT to calculate the dose increase to targets. Results:Compared to simple DVH summation, DIR allowed the cumulative doses of the D2 cm 3 and D1 cm 3 of bladder to be decreased by (2.47±1.92) and (2.82±2.73) Gy, respectively on average ( t=-3.65, -2.93, P < 0.05), those of the D2 cm 3, D1 cm 3, and D0.1 cm 3 of rectum to be decreased by (2.05 ± 1.61) Gy, (1.51 ± 1.58), and (3.21 ± 2.50) Gy, respectively on average ( t=-4.02, -3.02, -4.06, P < 0.05), and those of the D2 cm 3, D1 cm 3, and D0.1 cm 3 to be decreased by (1.42 ± 0.99), (1.55 ± 1.28) Gy, and (2.43 ± 1.95) Gy, respectively on average ( t=-3.52, -2.96, -3.06, P < 0.05). There was no significant statistical difference in the D90 of targets, the D0.1 cm 3 of the bladder, and the D2 cm 3, D1 cm 3, D0.1 cm 3 of the colon ( P > 0.05) between both methods, and there was no distinct correlation between DSC and dose difference ( P > 0.05). The DIR increased the dose to targets, with a median value of 150 cGy. However, the accuracy of the DIR should be improved. Conclusions:In clinical practice of multiple fractions of brachytherapy for cervical cancer, it′s still recommended to adopt the simple dose summation method to assess the doses to targets and OARs.

Objective:To establish a dosimetric method based on the well-chamber to verify the accuracy of the source positioning and dwelling time for the afterloading machine, aiming to provide a new method for the quality control of afterloading machine.Methods:The principle of this method was explained according to the hardware structure of the well-chamber. Then, the precision of this method was analyzed by the simulation test and data fitting. The feasibility test was also performed. And the advantages and disadvantages of this method were compared with those of the traditional method.Results:The precision of this method for detecting the source positioning was 0.07 mm and the dwelling time was 0.09 s, respectively. In the feasibility test, the standard deviation of the measure value was below 3%.Conclusions:The well-chamber method has high precision and convenient operation. It can be applied in the rapid verification of the relative accuracy of the source positioning and dwelling time of well-chamber.

Objective: To study the feasibility of using the PTW729 2D array ion-chamber to verify the relative dose distribution calculated with the Acuros BV algorithm. Both advantages and disadvantages of the method were analyzed to provide reference for practical clinical practices. Methods: Based on self-built measurement phantoms, the dose distribution on the same slice of the phantom was measured with PTW729 and film, respectively, under the same measurement condition and plan. The dose distributions obtained by the two method were compared with the result calculated with Acuros BV, separately, by using γ analytical tool. And the stability of the PTW729 was tested. Results: The γ comparison value was 95.9% between the film and Acuros BV, 98.9% between the PTW729 and Acuros BV and 88.0% between the film and PTW729, with 95.0%, 100.0%, and 100.0%, in their stability test respectively. Conclusions PTW729 2D array ion-chamber can be applied to the rapid verification of Acuros BV algorithm-calculated relative dose distribution.

Sensory processing is strongly modulated by different brain and behavioral states, and this is based on the top-down modulation. In the olfactory system, local neural circuits in the olfactory bulb (OB) are innervated by centrifugal afferents in order to regulate the processing of olfactory information in the OB under different behavioral states. The purpose of the present study was to explore the organization of neural networks in olfactory-related cortices and modulatory nuclei that give rise to direct and indirect innervations to the glomerular layer (GL) of the OB at the whole-brain scale. Injection of different recombinant attenuated neurotropic viruses into the GL showed that it received direct inputs from each layer in the OB, centrifugal inputs from the ipsilateralanterior olfactory nucleus (AON), anterior piriform cortex (Pir), and horizontal limb of diagonal band of Broca (HDB), and various indirect inputs from bilateral cortical neurons in the AON, Pir, amygdala, entorhinal cortex, hippocampus, HDB, dorsal raphe, median raphe and locus coeruleus. These results provide a circuitry basis that will help further understand the mechanism by which olfactory information-processing in the OB is regulated.

The material base of TCM of preventing and curing diseases is an organic whole composed of many ingredients,and which has the characteristics of multi component,multi link and multi target.After many years of exploration and accumulation,the component structure theory of TCM based on the whole concept has been improved and developed.This paper systematically discussed cognition of material base of TCM and scientific connotation of innovative structural components of TCM focused on component structure theory,so as to provide strategies and methods for the research and development of modern innovative Chinese medicine preparations.

OBJECTIVE To investigate the bone development activity and differences in safety of ethanol extract (EE) and water decoction (WD) of Psoralea corylifolia L.efficiently.METHODS Zebrafish larvae were co-exposed to prednisolone 25 μmol· L-1 and different concentrations of EE and WD (0.1,1.0,10 and 100 mg crude drug· L-1),and etidronate disodium (ED) 30 mg·L-1.All these groups were incubated at 28.5℃ until 9 dpf.The medium solution was changed every other day.Zebrafish skeleton at 9 dpf was stained with alizarin red and inspected under an optical microscope,in addition,the death toll and organ toxicity of zebrafish were also observed.The mRNA expression of osteoprotegrin (OPG) and receptor activator of NF-κB ligand (RANKL) in 9 dpf zebrafish were determined with fluorescence quantitative PCR.Zebrafish embryos (1 dpf) were exposed to various concentrations of EE (10,20,30,35,40,50 and 60 mg crude drug· L-1),WD (10,50,100,125,150,175,200 and 500 mg crude drug· L-1),psoralen (12.5,25.0,50.0,100.0,200.0 and 400.0 μmol·L-1) and bakuchiol (1,5,10,25 and 50 μmol· L-1).Embryonic morphology of zebrafish (3 dpf) was inspected with an optical microscope and the death toll of embryos or larvale was counted from 2 dpf to 9 dpf and LC50was calculated.Components of EE and WD ware analyzed by HPLC method.RESULTS Both EE (0.1 mg crude drug· L-1) and WD (1.0 mg crude drug· L-1) groups could increase the staining area and optical density values of zebrafish skeleton compared with prednisolone group (P＜0.01),indicating the increase in bone mineralization;the OPG mRNA expression in both EE and WD (1.0 mg crude drug· L-1) groups increased,while the RANKL mRNA expression decreased (P＜0.01) and the ratio of OPG/RANKL improved obviously (P＜0.01).Embryos exposed to EE,WD,psoralen and bakuchiol showed swelling of the heart and yalk sac,and decrease in GOT.The LC50 of WD and psoralen was 5～8 and 5～21 times that EE and bakuchiol,respectively.The composition and relative content of EE and WD also varied considerably.CONCLUSION Bone development activity and toxicity of EE are both stronger than those of WD.The lipid soluble characteristic components of Psoralea corylifolia L.,may be critical components of toxicity.

Objective: To investigate the association between aflatoxin exposure and primary hepatocellular carcinoma (PHC) development. Methods: From December 2013 to May 2016, we selected 214 patients newly diagnosed with PHC as cases, and 214 patients as controls from three hospitals in Chongqing. Cases were confirmed with PHC diagnosis standard. And cases caused by clear reasons such as drug-induced liver injury, alcoholic liver damage, fatty liver and gallstones etiology, were excluded. Controls were included with no cancer and no digestive system disease, and recruited simultaneously with cases. Cases and controls were frequency-matched (1∶1) by same gender and age (±3 years). Peripheral blood and random urine samples were collected and analyzed for serum HBsAg status by biochemistry analyzer, and serum AFB₁-ALB adduct and urinary AFB₁-N⁷-GUA adduct by ELISA. Basic information, living habits and history of disease for patients were obtained by questionnaires. We used wilcoxon rank sum test to compare the median of serum AFB₁-ALB adduct and urinary AFB₁-N⁷-GUA adduct in cases and controls. Logistic regression analyses were performed to assess risk factors for PHC, and synergism index (S) of aflatoxin with other factors was estimated by the method of Andersson. Results: There was no significant difference in age between PHC cases (50.74±9.67) years and controls (51.15±9.90) years. Logistic regression showed that the odds ratio of HBV infection for PHC development was 46.3 (95% CI: 23.3-88.0). There was a significant difference in median concentrations of serum AFB₁-ALB adduct (cases vs controls: 146.23 vs 74.42 ng/g albumin, P<0.001), but no difference in median concentrations of urinary AFB₁-N⁷-GUA adduct was observed (cases vs controls: 0.17 vs 0.14 ng/mg creatinine, P<0.210). The odd ratios for PHC risk after adjustment were 1.9 (95%CI: 1.1-3.4) for AFB₁-ALB adduct, and 2.1 (95%CI: 1.0-4.2) for AFB₁-N⁷-GUA adduct. Moreover, we observed a positive interaction of aflatoxin exposure with HBV, alcohol drinking, and diabetes. The S was 4.7 (95%CI: 2.8-7.9), 3.5 (95%CI: 1.0-12.0), and 12.4 (95%CI: 1.8-84.2), respectively for serum AFB₁-ALB adduct with each of the three factors mentioned, and was 1.9 (95%CI:1.1-3.1), 2.0 (95%CI: 1.1-3.6), and 2.0 (95%CI: 1.1-3.6), respectively for urinary AFB₁-N⁷-GUA adduct with each of the three factors mentioned. Conclusion HBV was still the main risk factor, and AFB₁ exposure was also an independent risk factor for PHC in Chongqing. There was a positive interaction of aflatoxin with HBV, alcohol drinking, and diabetes.

OBJECTIVE:To study the cardiac and skeletal toxicity of retinoic acid (RA) in Danio rerio at early life stage. METHODS:Danio rerio embryos of 24 hours post fertilization(hpf)were used as toxicity model and were exposed under medium with various concentrations of RA(0.1,1,10,25,100 μmol/L). The morphology of embryos and larvae hearts were observed 24,48 h after exposed. LC50 was calculated. Danio rerio larvae of 4 days post fertilization (dpf) were used as skeletal deformity model and were exposed with a series of RA at various concentration(0.1,1,10,25,50μmol/L). They were sacrificed 5 d later, and then Danio rerio skeleton were fixed for staining with alizarin red. The microscopic was used to observe the difference of stained skeleton area. RESULTS:RA caused significant adverse effects on hatching capabilities of Danio rerio embryos,and the ob-vious malformation features were produced during the culture process. 1-100 μmol/L RA could cause heart malformation in Danio rerio embryos and larvae,and the main heart malformation characteristics included heart linearization,pericardial edema,yolksa-cedema,hemocytes accumulation incardiac region. 100 μmol/L RA could inhibit the hatching capabilities of Danio rerio embryos, and caused lethal effects on embryos and larvae. The LC50 were 36.44,23.69 μmol/L after exposed for 24,48 h. 0.1-50 μmol/L RA induced vertebral column sclerotization of Danio rerio embryos and larvae in advance,which was positively associated with the con-centration of RA. CONCLUSIONS:RA can cause cardiac and skeletal toxicity in Danio rerio embryo and larvae,which is positive-ly associated with the concentration of RA.

Objective To construct training course for specialized wound nurses based on Delphi method. Methods Firstly, the consultation list on context of training course for specialized wound nurses was designed by self between January 2015 to May 2015. The expert consultation involving eleven clinical nurse specialists, ten nursing managers, four nursing teachers from fifteen cities of provinces was performed via three rounds to determine the content of training course for specialized wound nurses. Results The content determined of training course for specialized wound nurses included three indicators in level one ( course components) involving professional attitude, knowledge and skills, 14 indicators in level two ( course name) involving medical ethics value of wound nursing, history of wound nursing, importance of specialized wound nurses and so on, 58 indicators in level three ( course context) involving personal and family burden caused by chronic wounds, development situation of wound nursing in China, working pattern of specialized wound nurses, professional development requirements and so on. Conclusions The context of training course for specialized wound nurses is determined from three dimensions including professional attitude, knowledge and skills. Besides, this study provides suggestions and theoretical support for the training of specialized wound nurses.