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From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.
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ABSTRACT Background: Leprosy is a neglected dermato-neurologic, infectious disease caused by Mycobacterium leprae or M. lepromatosis. Leprosy is treatable and curable by multidrug therapy/MDT, consisting of 12 months rifampicin, dapsone and clofazimine for multibacillary/MB patients and for 6 months for paucibacillary/PB patients. The relapse rate is considered a crucial treatment outcome. A randomized Controlled Clinical Trial (U-MDT/CT-BR) conducted from 2007‒2012 compared clinical outcomes in MB patients after 12 months regular MDT/R-MDT and 6 months uniform MDT/U-MDT in two highly endemic Brazilian areas. Objectives: To estimate the 10 years relapse rate of MB patients treated with 6 months U-MDT. Methods: The statistical analyses treated the data as a case-control study, sampled from the cohort generated for the randomized trial. Analyses estimated univariate odds ratio and applied logistic regression for multivariate analysis, controlling the confounding variables. Results: The overall relapse rate was 4.08 %: 4.95 % (16 out of 323) in the U-MDT group and 3.10 % (9 out of 290) in the regular/R-MDT group. The difference in relapse proportion between U-MDT and R-MDT groups was 1.85 %, not statistically significant (Odds Ratio = 1.63, 95 % CI 0.71 to 3.74). However, misdiagnosis of relapses, may have introduced bias, underestimating the force of the association represented by the odds ratio. Conclusions: The relapse estimate of 10 years follow-up study of the first randomized, controlled study on U-MDT/CT-BR was similar to the R-MDT group, supporting strong evidence that 6 months U-MDT for MB patients is an acceptable option to be adopted by leprosy endemic countries worldwide. Trial registration: ClinicalTrials.gov: NCT00669643.
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Objective:To provide a basis for selecting the optimization method for intracavitary/interstitial brachytherapy (IC/ISBT) of cervical cancer by comparing graphical optimization (GO), inverse planning simulated annealing (IPSA), and hybrid inverse planning optimization (HIPO) using dosimetric and radiobiological models.Methods:This study selected 65 patients with cervical cancer who were treated with image-guided IC/ISBT. The afterloading therapy plans for these patients were optimized using GO, IPSA, and HIPO individually, with a prescription dose high-risk clinical target volume (HRCTV) D90 of 6 Gy. The non-parametric Friedman test and the non-parametric Wilcoxon rank test were employed to analyze the differences in duration, dose-volume parameters, and radiobiology between the three types of optimized plans. Results:Inverse planning optimization (IPSA: 46.53 s; HIPO: 98.36 s) took less time than GO (135.03 s). In terms of gross target volume (GTV) dose, the high-dose irradiation V150% (53.66%) was slightly higher in the HIPO-optimized plans, while the V200% (30.29%) was higher in the GO-optimized plans. The GO-optimized plans had a higher conformity index (CI; 0.91) than other plans, showing statistically significant differences. Compared with other plans, the HIPO-optimized plans showed the lowest doses of D1 cm 3 and D2 cm 3 at bladders and rectums and non-statistically significant doses at small intestines ( P > 0.05). In terms of the equivalent uniform biologically effective dose (EUBED) for HRCTV, the HIPO-optimized plans showed a higher value (12.35 Gy) than the GO-optimized plans (12.23 Gy) and the IPSA-optimized plans (12.13 Gy). Moreover, the EUBED at bladders was the lowest (2.38 Gy) in the GO-optimized plans, the EUBED at rectums was the lowest (3.74 Gy) in the HIPO-optimized plans, and the EUBED at small intestines was non-significantly different among the three types of optimized plans ( P = 0.055). There was no significant difference in the tumor control probability (TCP) predicted using the three types of optimized plans ( P > 0.05). The normal tissue complication probabilities (NTCPs) of bladders and rectums predicted using the HIPO-optimized plans were lower than those predicted using the GO- and IPSA-optimized plans( χ2 = 12.95-38.43, P < 0.01), and the NTCP of small intestines did not show significant differences ( P > 0.05). Conclusions:Among the three types of optimization algorithms, inverse optimization takes less time than GO. GO-optimized plans are more conformal than IPSA- and HIPO-optimized plans. HIPO-optimized plans can increase the biological coverage dose of the target volume and reduce the maximum physical/biological exposure and NTCP at bladders and rectums. Therefore, HIPO is recommended preferentially as an optimization algorithm for IC/ISBT for cervical cancer.
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Objective:To evaluate the practicability of dose volume histogram (DVH) prediction model for organ at risk (OAR) of radiotherapy plan by minimizing the cost function based on equivalent uniform dose (EUD).Methods:A total of 66 nasopharyngeal carcinoma (NPC) patients received volume rotational intensity modulated arc therapy (VMAT) at Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences from 2020 to 2021 were retrospectively selected for this study. Among them, 50 patients were used to train the recurrent neutral network (RNN) model and the remaining 16 cases were used to test the model. DVH prediction model was constructed based on RNN. A three-dimensional equal-weighted 9-field conformal plan was designed for each patient. For each OAR, the DVHs of individual fields were acquired as the model input, and the DVH of VMAT plan was regarded as the expected output. The prediction error obtained by minimizing EUD-based cost function was employed to train the model. The prediction accuracy was characterized by the mean and standard deviation between predicted and true values. The plan was re-optimized for the test cases based on the DVH prediction results, and the consistency and variability of the EUD and DVH parameters of interest (e.g., maximum dose for serial organs such as the spinal cord) were compared between the re-optimized plan and the original plan of OAR by the Wilcoxon paired test and box line plots.Results:The neural network obtained by training the cost function based on EUD was able to obtain better DVH prediction results. The new plan guided by the predicted DVH was in good agreement with the original plan: in most cases, the D 98% in the planning target volume (PTV) was greater than 95% of the prescribed dose for both plans, and there was no significant difference in the maximum dose and EUD in the brainstem, spinal cord and lens (all P>0.05). Compared with the original plan, the average reduction of optic chiasm, optic nerves and eyes in the new plans reached more than 1.56 Gy for the maximum doses and more than 1.22 Gy for EUD, and the average increment of temporal lobes reached 0.60 Gy for the maximum dose and 0.30 Gy for EUD. Conclusion:The EUD-based loss function improves the accuracy of DVH prediction, ensuring appropriate dose targets for treatment plan optimization and better consistency in the plan quality.
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@#Objective To prepare and verify a uniform antigen content detection kit for recombinant protein vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Methods Using goat anti-S protein polyclonal antibody prepared by National Institutes for Food and Drug Control(NIFDC) as coating antibody,one of four monoclonal antibodies(14C8,15F9,17A7 and 20D8)with high receptor-binding domain(RBD)binding activity and broad-spectrum resistance against major variants as HRP-labeled antibody,a uniform double-antibody sandwich ELISA kit for antigen content detection of recombinant SARS-CoV-2 vaccine was prepared,and the dilution of coating antibody(1∶125 ~ 1∶4 000)and enzymelabeled antibody(1∶250 ~ 1∶32 000)were optimized by chessboard titration. The specificity,linear range,accuracy,precision and durability of the kit were verified. The prepared uniform detection kits were distributed to 12 laboratories to detect15 batches of recombinant SARS-CoV-2 protein vaccine stock solutions(including 11 batches of stock solutions designed with WT strain and 4 batches of designed with Beta,Gamma and Delta variants as reference sequence)from different expression systems(CHO cells,Pichia pastoris,Sf9 cells or E. coli)and target proteins(RBD or S protein)prepared by each laboratory.Results Monoclonal antibody 20D8 was used as the enzyme-labeled antibody with the optimal dilution of 1 : 4 000,and the optimal dilution of coating antibody was 1 : 500. The uniform detection kit showed no cross reaction with recombinant S protein of severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS). The first generation national standard for recombinant SARS-CoV-2 protein vaccine antigen(national standard for short)showed a concentration of 0. 16 ~ 2. 50 U/mL with a good linear relationship with A450/630,and the linear equation was:y = 0. 791 x-0. 100 4,R2= 0. 993 7;The recoveries of 0. 16 ~ 2. 50 U/mL national standard in 6 repeated tests were 95% ~ 104% and the coefficients of variation(CVs)were less than 15%;The CVs in 3 repeated tests by 2 experimenters at different time were 4. 4% ~6. 6% and the recoveries were in the range of 80% ~ 120% under different temperature and time conditions. The antigen content of 15 batches of recombinant SARS-CoV-2 protein vaccine stock solutions showed good parallelism with the national standard. Conclusion The uniform detection kit for antigen content developed in this study had good specificity,accuracy,precision and durability,and might be used for the detection of antigen content of recombinant SARS-CoV-2 protein vaccines.
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Objective To explore the value of generalized equivalent uniform dose (gEUD) optimization in radiotherapy for chest malignant tumors. Methods Sixty patients with chest malignant tumors who were treated in Center for Tumor Radiotherapy, Chizhou Municipal People’s Hospital, Anhui Province, China from October 2021 to June 2022 were enrolled; each patient underwent tumor localization with a conventional fixed computed tomography scan. The patients were divided into two groups using the same field direction and weight in the Varian Eclipse 15.6 planning system. The first group was planned using the conventional physical dose-volume objective function plus the Upper gEUD objective function, with organs at risks (OARs) optimized with the EUD values suggested by the Varian Eclipse 15.6 planning system. The second group only adopted the conventional physical dose-volume objective function for OARs optimization. The two groups were compared for the radiation doses delivered to the OARs. Results Compared with the conventional physical dose-volume objective function alone, the addition of Upper gEUD objective function resulted in no significant difference in lung V5Gy, but resulted in significant reductions in V20Gy and mean dose in the lungs; some reductions in V30Gy, V40Gy, and mean dose in the heart; and significant reductions in the maximum dose in the spinal cord. Conclusion The gEUD objective optimization can effectively protect the normal tissue in the radiotherapy for chest malignant tumors and thus is recommended in radiotherapy planning.
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Objective Screening of modified Foshou San to improve cerebral ischemia,determine the best prescription composition and the proper dose.Methods Using data mining method,the traditional Chinese medicine for hypertensive intracerebral hemorrhage(HICH)were screened,and cluster analysis was carried out to obtain Jiawei Foshou San combinations;According to the mixed uniform design U14(42×33×22),the auricular artery dilatation experiment and acute cerebral ischemia induced by saturated magnesium chloride in mice were used to observe the auricular artery dilatation index and survival time of mice,and the pharmacological effects of each prescription to improve cerebral ischemia were evaluated.On the basis of visual analysis of pharmacodynamics,stepwise multiple regression analysis was carried out,and the regression equation was used to calculate the best prescription composition and dose of Jiawei Foshou San.The optimized prescription was verified by acute cerebral ischemia experiment in mice.Results A total of 51 prescriptions that may be used for the treatment of HICH were selected by data mining,including 103 Chinese herbs,with a total frequency of 535 times.The results of mixed uniform design U14(42×33×22)test showed that the auricular artery index of mice in each prescription group of Jiawei Foshou San increased to varying degrees.The differences between prescription 4,8,12 and 13 were significant(P<0.05),and the differences between prescription 3,7,9,11 and 14 were extremely significant(P<0.01).The survival time of acute cerebral ischemia in mice was prolonged to varying degrees in each group of Jiawei Foshou San,and the difference between prescription 2-14 groups and the blank group was statistically significant(P<0.01).The prescription of the new Jiawei Foshou San was determined as 60 g of Astragalus membranaceus,60 g of Angelica sinensis,24 g of Ligusticum chuanxiong,15 g of Paeonia lactiflora and 9 g of Dilong from the intuitive analysis.The validation results showed that the high and middle dosage of the new Jiawei Foshou San could significantly prolong the breathing time,increase the number of breaths,and prolong the time of normal pressure hypoxia tolerance in mice with acute cerebral ischemia(P<0.01,P<0.05).Conclusion Using mixed uniform design combined with improving cerebral ischemia effect index can determine the best prescription composition and the best dose of Jiawei Foshou San,and the effect of improving cerebral ischemia is certain.
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Healthcare-associated infections (HAIs) have a major impact on public health worldwide. Till now, we are relying on hand washing and environmental disinfection, but the compliance rate of hand washing and adequate supply of materials is always a catch. Alongside patients, surfaces and supplies act as reservoirs of microorganisms in healthcare settings. The reduction in organisms may prove to be an effective strategy to decline HAIs. The use of gold and silver in commercial textiles is prohibited because of the high cost rather than having excellent antibacterial and antimicrobial properties, so copper has become the best choice for researchers as it possesses similar properties to gold and silver and has other characteristics such as its durability, corrosion resistance, prestigious appearance, and ability to form complex shapes. It has been found that copper brings down the microbial burden of high-touch surfaces in healthcare settings. The fundamental properties of copper offer a theoretical advantage to regular cleaning, as the effect is continuous rather than episodic. So the use of copper-impregnated textiles in hospital areas whether in form of bed linen or uniforms for health professionals, as well as patients, can be a viable alternative to decline the levels of infection in healthcare settings, and with the discovery of copper-encapsulated hospital beds and fabrics, dividends will likely be paid in improved patient outcomes, lives saved, and healthcare cost saved. The application of copper in fabrics for healthcare professionals will be a sound initiative to prevent HAIs. The fabric may help decline the infection rate and mortality among hospitalized patients.
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@#To investigate the effect of nucleoside diphosphate kinase (NDK) on the synthesis of hyaluronic acid, nucleoside diphosphate kinase gene (ndk) was overexpressed along with the hyaluronic acid-producing genes in recombinant B.subtilis. Two engineered strains named Hp8tg and Pn8tg were constructed.Uniform hyaluronic acid (HA) could be obtained from both engineered strains.HA produced by both recombinant strains was confirmed by monosaccharide composition analysis, Fourier transform infrared spectometry and nuclear magnetic resonance spectroscopy.Inducing conditions of HA fermentation were optimized by response surface methodology.Overexpression of ndk could increase the production and molecular weight of HA by 1.3-fold and 1.1-fold, respectively. This study revealed for the first time that overexpression of ndk could relieve the inhibition effect of uridine diphosphate (UDP) on Class II HA synthase and increase the production and molecular weight of HA, which proves to be an efficient strategy for the production of HA, and the preparation of other polysaccharides.
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In a granulometric analysis of coffee beans with different categories of defects, the data can be organized in contingency tables, and when considering the discrimination by harvest, they may have a structure that suggest a more complex model, by means of the counting of defective coffee beans compared to different crops interacting with the classification of defects and percentages of sieve grains, which characterizes a block design with multivariate responses. However, due to the techniques based on the analysis of variance, considering the uniform correlation structure for all plots, it becomes feasible to propose a model that allows contemplating different structures between the plots, associating the effects of the crops to the defects in the granulometric procedure applied to the coffee beans. Thus, the hypothesis of incorporating the effects of crops associated with defects arises using the biplot multivariate technique. This work aims to propose the use of corrected biplots by predictions obtained trhough the fit to the Generalized Linear Model in the coffee grain size classification, broken down by components of the effect of the harvests. In conclusion, the use of GEE models with the corrected biplot technique by the predictions is feasible for application to be applied to the granulometric analysis of defective coffee beans, presenting discrimination regarding the effects of harvests.
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Café , Productos Agrícolas , Análisis MultivarianteRESUMEN
Objective:In order to make up for the gap in the digital model of twins in the study of fetal radiation dosimetry, this study intends to construct a computational twins phantom based on low-dose CT images.Methods:The low-dose CT images of a pregnant patient were segmented by the combination of threshold automatic segmentation and manual segmentation, which were derived into stereolithography files. The maternal contour, fetal contour and bone structure were constructed using 3D modeling software, and the organ mass was adjusted according to the reference values of ICRP Publication 89 and WHO report after the organs were scaled on a specific scale.Results:The first set of Non-Uniform Rational B-Splines (NURBS) surface phantom of twins in China was established. The external contours, bones, size, position and posture of the phantom were completely consistent with those of the real human body. Each fetus had 25 organs or tissues. After optimization and adjustment, the relative deviation between the twin phantom and the reference value of organ mass was less than 10%.Conclusions:In this study, a personalized computational phantom of twins based on low-dose CT images is constructed, which fills the gap in the twin model. It is helpful in estimating the dose by the fetus from ionizing radiation received in the process of radiation diagnosis of pregnant women with twins.
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Objective To compare the dosimetric difference between the biological function based on equivalent uniform dose (EUD) and the physical function based on dose volume (DV) in the intensity modulated radiotherapy for stage Ⅲ non-small cell lung cancer. Methods Four different radiotherapy plans were designed for 15 stage Ⅲ non-small cell lung cancer patients: Group A, physical function optimization (DV + DV) was used for target area and organs at risk; GroupB, in the target region, biological function optimization conditions were added on the basis of physical function optimization, and physical function optimization of organs at risk (DV-EUD + DV) was added. Group C, biological function optimization (EUD + EUD) was used for target area and organs at risk. Group D, in the target area, physical function optimization conditions were added on the basis of biological function optimization, and biological function optimization of organs at risk (EUD-DV + DV) was added. The differences in dosimetric parameters of the four plans were compared. Results Target area: PTV: D2%, D98%, D50%, D105% and Dmax values of group C (P < 0.05) is the highest while group B and group D were relatively small (P > 0.05); The homogeneity index: the results of the group B and the group D were better than those of the other two groups (P < 0.05). conformity index: The results of the four groups were similar (P>0.05). Organ at risk: lung tissue mean dose (MLD), V5, V10, V20, V30 and heart V30, V40, Dmean dose parameters were similar (P > 0.05). Spinalcord: Group C and group D D1% were better than the other two groups (P < 0.05). There was no statistical difference in the number ofmonitor unit (MU) among the four groups (P > 0.05). Conclusion The optimization method combining physical and biological function optimization in the target area can improve the conformity of the target area on the premise of ensuring the treatment. The Spinalcord load would be significantly reduced when using biological function optimization or the combination of biological function and physical function optimization.
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Objective:Arrange long-term toxicity experiments by a uniform design method, so as to explore the effect of different extracts of Psoraleae Fructus on liver toxicity in rats and mice, and find the drug factors that cause psoralen liver toxicity. Method:Based on the factors of processing, extraction technology, dosage and treatment course, each experimental group was arranged by uniform design method. A total of 220 SD rats and 220 Kunming mice with half male and half female were divided into normal groups and drug groups 1 to 8. The corresponding drugs (50% alcohol extract of salt Psoraleae Fructus in rats 2.57 g·kg-1, mice 5.14 g·kg-1, 95% alcohol extract of Psoraleae Fructus in rats 0.51 g·kg-1, mice 1.02 g·kg-1, 70% alcohol extract of salt Psoraleae Fructus in rats 1.71 g·kg-1, mice 3.42 g·kg-1, water extract of Psoraleae Fructus in rats 1.03 g·kg-1, mice 2.06 g·kg-1, water extract of salt Psoraleae Fructus in rats 1.03 g·kg-1, mice 2.06 g·kg-1, 70% alcohol extract of Psoraleae Fructus in rats 1.71 g·kg-1, mice 3.42 g·kg-1, 95% alcohol extract of salt Psoraleae Fructus in rats 0.51 g·kg-1, mice 1.02 g·kg-1, 50% alcohol extract of Psoraleae Fructus in rats 2.57 g·kg-1, mice 5.14 g·kg-1) were administered by gavage daily. The body weight and food intake of the rats and mice were measured once a week. After the treatment course, the rats were anesthetized with sodium pentobarbital, and blood was taken from the abdominal aorta, and the mice were sacrificed by removing the eyeballs, and the liver and brain were taken to calculate the organ coefficients. Serum was taken to determine liver function-related indicators, and the liver was taken for histopathological examination by hematoxylin-eosin (HE) staining. Result:The liver visceral-brain ratio of female rats in group 3 were significantly increased (P<0.05). The liver quality, visceral-body ratio and visceral-brain ratio of male mice in groups 1 to 3 were significantly increased (P<0.05, P<0.01). Histopathological manifestations in mice were more obvious than those in rats. Histopathology showed hepatocyte hypertrophy in the central area of liver lobules in mice, in particular in group 3. According to the multiple regression equation, there were interactions between extraction technology, processing, dosage and treatment course, and the extraction technology was positively correlated with the pathological score of liver injury. Based on the results of visual analysis and other indicators, it is concluded that the extraction technology factor is most relevant to psoralen liver toxicity of Psoraleae Fructus. Conclusion:Psoraleae Fructus has the hepatotoxicity, which is related to ethanol extraction technology; alcohol extraction is more toxic than water extraction, and 70% ethanol extraction is the most toxic. Besides, there are species differences, with a more significant hepatotoxicity in mice than that in rats.
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Recently, the hepatotoxicity issue regarding to Psoraleae Fructus (PF) has attracted remarkable concerns, which highlights the urgent need to explore the toxicity attenuation method for PF. In this study, we proposed an alcohol soaking and water rinsing method for pre-processing PF based on the record in the classics - "Lei Gong Pao Zhi Lun", aiming to attenuate the potential hepatotoxicity of PF. The optimal pre-processing methods and parameters were investigated by U*12(108) uniform design coupled with 3D-cultured human-derived liver organoids model and high-content imaging. The results showed that there were significant variations among the hepatotoxicity intensities of different pre-processed PF products. Four factors, including the concentration of alcohol, the ratio of material and alcohol in alcohol soaking, the time of alcohol soaking and the times of water rinsing, were found as independent significant factors (all P<0.01). The optimal pre-process parameters were further predicted and verified as follows: the alcohol concentration is 80%, the times of alcohol soaking is 3, the ratio of alcohol and material of alcohol soaking is 3, the time for alcohol soaking is 30 h, the ratio of water and material of water rinsing is 2, the times of water rinsing is 3, the time water rinsing is 12 h and the time of steaming is 5 h. This research demonstrated that the alcohol soaking and water rinsing method can effectively reduce the potential hepatotoxicity of PF. This method provides a reference for reducing the risk of PF liver injury from the perspective of Chinese medicinal materials pre-processing.
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OBJECTIVE:To optimi ze the optimal composition proportion of 4 ingredients (Panax ginseng ,Astragalus membranaceus,Polygonatum sibiricum ,Lycium chinensis )in Compound ginseng immune-enhancing formula (CGIF),and to study immune activity and acute toxicity of the extracts with the optimal ratio. METHODS :The cell activity test was used to screen the crude drug concentration range of 4 ingredients. After treated with different crude drug concentrations of each medicinal material,using the contents of NO ,IL-6 and TNF-α as indexes,uniform design was used to determine the optimal ratio of each ingredient in CGIF. Totally 240 mice were taken and randomly divided into 4 batches,with 60 mice in each batch. Each batch of mice was randomly divided into blank group (normal saline ),model group (normal saline ),positive drug group [levamisole ,4 mg/(kg·d)],and optimal proportion extract of CGIF low-dose ,medium-dose and high-dose groups [ 0.952 8,1.905 6,3.811 2 g/(kg·d)],with 10 mice in each group ;they were given medicine intragastrically ,qd,for consecutive 30 d. Except for blank group,mice in the other groups were intraperitoneally injected with cyclophosphamide [ 40 mg/(kg·d)] on the 24th day after first administration,qd,for consecutive 3 d to induce immunocompromised model. The immune activity of the optimal proportion extract was evaluated by determining visceral coefficients ,spleen lymphocyte transformation capacity ,serum contents of hemolysin,IL-2,IgM,IgG and IgA ,phagocytosis function of peritoneal macrophages. Another 20 mice were collected and given the optimal proportion extract 20 mL/kg intragastrically ,twice;acute toxicity of the formula was investigated with oral maximum tolerated dose (MTD). RESULTS :The optimal ratio of CGIF was that crude drug mass ratio of P. ginseng , membranaceus,P. sibiricum ,L. chinensis was 1 ∶ 2 ∶ 2 ∶ 4. The immunological activity experiment showed that theoptimal proportion extract can significantly improve visceral indexes of mice , spleen lymphocyte proliferation ability serum contents of hemolysin ,IL-2,IgM,IgG and IgA as well as macrophage phagocy tosis ability (P<0.05 or P< 0.01). The acute toxicity test indicated that oral MTD was over 15 g/kg,which was non-toxic. CONCLUSIONS :The optimal proportion extract of CGIF can significantly enhance the immune function of mice and are non-toxic.
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Uniform design-comprehensive scoring method was used to investigate the effects of ethanol dosage, ethanol concentration and extraction time, based on the evaluation index from transfer rates of epimedin A, epimedin B, epimedin C, icariin and baohuoside Ⅰ, which are the main active components in Epimedii Folium. Furthermore, the optimum conditions for the ethanol extraction process were determined by multiple linear stepwise regression and empirical test. Then, the ethanol extract of Epimedii Folium prepared according to the optimized technological conditions was used to intervene the injury model of chondrocyte induced by interleukin-1 beta(IL-1β). Annexin V-FITC/PI staining flow cytometry was used to detect the apoptotic rate of chondrocyte and analyze the effect of ethanol extract of Epimedii Folium on chondrocyte injury model. The optimum conditions of ethanol extraction were as follows. Crude powder of Epimedii Folium was added with 18 times of 70% ethanol solution, and extracted for twice in the refluxing process, for 60 minutes each time. Under the conditions, the extraction rates of the above five active components were 94.21%, 94.76%, 93.85%, 96.17% and 96.85%, respectively. The optimized ethanol extraction process of Epimedii Folium was reasonable, feasible and reproducible. This ethanol extract could significantly reduce the early apoptotic rate, late apoptotic and necrotic rate, total apoptotic rate(P<0.05 or P<0.01) of chondrocyte injury model induced by IL-1β, suggesting that the ethanol extract of Epimedii Folium can inhibit the apoptosis of chondrocytes induced by IL-1β to a certain extent, which lays a foundation for further study on its prevention and treatment of osteoarthritis.
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Humanos , Condrocitos/efectos de los fármacos , Epimedium/química , Etanol , Interleucina-1beta , Extractos Vegetales/farmacología , Hojas de la Planta/químicaRESUMEN
Uniform mixing of liquid substances is difficult to attain. Recently, mixtures of fat and platelet-rich plasma (PRP) have been used extensively in autologous fat transfer. Although various methods have been utilized to mix the fat and PRP involved in this procedure, these methods still carry disadvantages in the time taken and the potential for cell damage, and it is questionable whether effective mixing can occur using these techniques. To facilitate mixing that is as uniform as possible, the authors of this study invented a special cannula. Use of the conventional luer-lock-to-luer-lock connector method has been found to cause cell damage and makes it difficult to achieve uniform mixing, while random injection-type mixing has been shown to have limited accuracy and effectiveness. We expect that the newly designed cannula will solve the problem detailed above.
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Catéteres , Vestuario , Métodos , Plasma Rico en Plaquetas , Estrés MecánicoRESUMEN
Objective: To screen the best compatibility proportion of total alkaloids of Coptidis Rhizoma and Notoginseng Radix et Rhizoma total saponins (HS composition)by uniform design and pharmacological model and to observe the effect on diabetic complications. Method: The total alkaloids of Coptidis Rhizoma and Notoginseng Radix et Rhizoma total saponins were used as the research objects, U6(62) table was choosed for grouping design.The content of triglyceride fasting blood-glucose (FBG), prothrombin time (PT) and active partial thromboplastin time (APTT) was chosen as index. The best dose ratio was obtained by multipleregression analysis. Rats with type 2 diabetes mellitus induced by high-fat diet combined streptozotocin were divided into blank group, model group, metformin group (150 mg·kg-1), HS composition group (total alkaloids of Coptidis Rhizoma 360 mg·kg-1+ Notoginseng Radix et Rhizoma total saponins 40 mg·kg-1). Rats were administered orally for 10 weeks.By observing the blood glucose, glucose tolerance,area under the curve (AUC), triglyceride (TG), high-density lipoprotein (HDL-C)and low-density lipoprotein (LDL-C), hemorheological indexes and pathological changes of pancreas, heart, kidney and retina in rats of each group, the effect of this composition on diabetic complications was verified. Result: Combination of 625 mg·kg-1 total alkaloids of Coptidis Rhizoma and 60 mg·kg-1 Notoginseng Radix et Rhizoma total saponins was the optimal dosage ratio of HS composition.The validation test showed that compared with blank group, the fasting blood glucose and lipid levels in the model group were significantly increased (PPPPPPPPPPPConclusion: The optimum compatibility dose of HS composition have a good therapeutic effect on diabetic complication rats induced by high-fat diet and streptozotocin.
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Objective:To optimize proportion of couplet medicine of Bupleuri Radix and Scutellariae Radix in the treatment of anti-depression, and to explore the possible antidepressant mechanism of this couplet medicine. Method:The dosages of Bupleuri Radix and Scutellariae Radix in the 2015 edition of Chinese Pharmacopoeia were taken.According to U7(72) uniform design table, Bupleuri Radix and Scutellariae Radix were carried out into 7 groups.The chronic unpredictable mild depression model mice were induced by intragastric administration of decoction of this couplet medicine and the antidepressant effect was observed by the behavior tests, which included sucrose preference test, tail suspension test, forced swimming test and open field test(crossing scores).The regression equations were established by selecting the effective indexes.The experiments of retest were taken to check the results and the possible antidepressant mechanism was primarily investigated by measuring the phosphorylation level of cyclic adenosine monophosphate(cAMP)-response element binding protein(CREB) and expression of brain-derived neurotrophic factor(BDNF). Result:Compared with the blank group, sucrose preference rate of the model group was significantly decreased(PPPPPPPPPPPPPPConclusion:Compatibility of Bupleuri Radix and Scutellariae Radix can ameliorate depressive-like behavior of model mice, and the best antidepressant compatibility proportion of Bupleuri Radix and Scutellariae Radix is 1:1, the optimal amounts of them are about 5 g.The antidepressant effect may relate to promoting phosphorylation level of CREB and the expression of BDNF in the hippocampus.
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Objective To propose a treatment planning optimization algorithm which can make full use of OAR dose distribution prediction meanwhile improving the output planning quality as much as possible.Methods We had reformulated an FMO function under the guidance of dose distribution prediction and also integrated equivalent uniform dose (gEUD) based on the consideration of prediction uncertainty,for providing optimal solution.Performance of the method was evaluated by comparing the optimized IMRT plan quality of 8 cervical cancers in the term of DVH curves,dose distribution and dosimetric endpoints with the original ones.Results The proposed method had a feasible,fast solution.Compared with original plan,its output plan had better plan quality in better dose homogeneity,less hot spot and further dose sparing for OARs.V30,V45 of rectum was decreased by (6.60±3.53)% and (17.03±7.44)%,respectively,with the statistically significant difference (t=-4.954,-6.055,P<0.05).V30,V45 of bladder was decreased by (14.74 ± 5.61) % and (14.99 ± 4.53) %,respectively,with the statistically significant difference (t=-6.945,-8.759,P<0.05).Conclusions We have successfully developed a predicted dose distribution and equivalent uniform dose-based planning optimization method,which is able to make good use of 3D dose prediction and ensure the output plan quality for intensity modulated radiation therapy.