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Endothelial cells in the inner wall of blood vessels respond to physical and chemical signals of the body by regulating vascular homeostasis， vascular tension， cell adhesion， cell proliferation， coagulation resistance and inflammatory factors， to maintain the stability of blood vessels. Angiogenesis is the key condition for tumor evolution， and the pathological mode of tumor angiogenesis provides nutrients and oxygen for tumor growth and promotes its proliferation. In recent years， endothelial cells have participated in tumor vascular infiltration and driven angiogenesis， which is considered to be the point link in tumor metastasis. By regulating metabolic remodeling， vascular endothelial cells provide the materials and energy needed in the process of tumor angiogenesis， and their abnormal metabolic characteristics facilitate their adaption to the changes of tumor microenvironment， which is often regarded as an important basis for tumor angiogenesis. The ''Yin fire'' theory in traditional Chinese medicine， originating from Huangdi's Internal Classic （Huang Di Nei Jing）， originally meant Yin deficiency generates internal heat， and belonged to the category of fire of internal injury. After the deduction and changes by physicians over the ages， the pathogenesis of ''spleen and stomach Qi deficiency-Yin fire rising-Qi and fire disharmony'' was gradually formed. The pathogenesis of metabolic remodeling of endothelial cells manifests the pathological characterization of Yin fire in an objective way， which is consistent with the disease state of uncontrolled and hyperactive tumor neovascularization. Changes in spleen and stomach Qi deficiency as well as imbalance of Qi movement lead to the failure of water and food in distribution， and thus metabolic disorders occur. Long term retention turns in phlegm and blood stasis， which combat with blood vessels， and result in abnormal local environment （formation of tumor microenvironment）， adverse pulse channel （imbalance of endothelial cell metabolism）， and tumor neovascularization. Under the guidance of ''Yin fire'' syndrome elements and by focusing on the correlation between Qi and fire， prescriptions are made based on the treatment method of ''strengthening the body and regulating Qi'' to regulate the metabolic function of endothelial cells， thus achieving a relatively balanced state of the body and inhibiting tumor angiogenesis. As a result， this study， centering on the metabolic remodeling of endothelial cells and ''Yin fire'' theory， elucidated the academic ideas， with the purpose of providing some theoretical support for the intervention of tumor vascularization by Chinese medicine.
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Medical students need to have different levels of ability, so various examination forms are required to measure on levels of competency. The choice of different examination methods is very important to reflect the learning effect of the selected courses. The present work describes the examination design and its functions of the Medical University of Vienna, and the enlightenment to the evaluation of higher medical education of China. Learning from the advanced teaching evaluation concepts and methods in Austria may help to promote the reform of medical education evaluation methods and cultivate high-quality medical talents in our country.
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Objective:To evaluate the clinical application value of endoscopic ultrasonography (EUS) in the etiological diagnosis of patients initially diagnosed with idiopathic acute pancreatitis (IAP).Methods:Clinical data of 128 patients who underwent further EUS and magnetic resonance cholangiopancreatography (MRCP) after initial diagnosis of IAP at the Gastrointestinal Endoscopy Center of the First Affiliated Hospital of Naval Medical University between January 2015 and February 2022 were collected and divided into a single-episode group (single-episode group, 51 cases) and a multiple-episode group (recurrent group, 77 cases) based on the number of AP episodes. The data and the diagnosis of the etiology of IAP in the two groups by EUS were analyzed and compared with the etiological diagnosis results of MRCP.Results:The differences on basic information such as gender, age, history of smoking, history of alcohol consumption, family history of pancreatic disease, history of cholecystectomy, abnormality of liver function, and severity of pancreatitis between the single-episode group and recurrent group of IAP patients were not statistically significant. The etiology was clarified in 79 (62%) IAP patients after EUS examination, of which 55 (43%) cases had biliary disease (gallstones, microlithiasis, biliary sludge) and 24 (19%) cases had pancreatic disease (chronic pancreatitis, pancreatic divisum, pancreatic interstitial or pancreatic ductal changes). The percentage of patients with biliary disease as the cause of IAP was significantly higher in the single-episode group than in the recurrent group (59% vs 32%), while the percentage of patients with pancreatic disease as the cause of IAP was higher in the recurrent group than in the single-episode group (25% vs 10%), with statistically significant differences ( P values=0.004 and 0.035, respectively). The performance of EUS in diagnosing the etiology of IAP was significantly higher than that of MRCP (62% vs 19%, P=0.032), where EUS was more accurate in detecting biliary microlithiasis or biliary sludge (43% vs 9%, P<0.01). EUS was also superior to MRCP in identifying subtle changes in chronic pancreatitis lesions (small pancreatic nodules, patchy hyperechogenicity, etc.) and intraductal papillary mucinous neoplasms(17% vs 7%, P<0.05), but was inferior to MRCP in identifying pancreatic divisum (2 cases vs 4 cases). Conclusions:In view of high diagnostic accuracy and safety of EUS in diagnosing biliary diseases, and based on the fact that most IAPs in China are due to biliary diseases, EUS based management strategy can be considered to be a reasonable approach for evaluation of IAP patients. The MRCP can be used as a supplement to the EUS to identify a controversial etiology.
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Skin wound healing tends to slow down with aging, which is detrimental to both minor wound recovery in daily life and the recovery after surgery. The aim of current study was to explore the effect of histone deacetylase 6 (HDAC6) on wound healing during aging. Cultured human dermal fibroblasts (HDFs) and mouse full-thickness skin wound model were used to explore the functional changes of replicative senescent dermal fibroblasts and the effect of aging on skin wound healing. Scratch wound healing assay revealed significantly decreased migration speed of senescent HDFs, and BrdU incorporation assay indicated their considerably retardant proliferation. The protein expression levels of collagen and HDAC6 were significantly decreased in both senescent HDFs and skin tissues from aged mice. HDAC6 activity inhibition with highly selective inhibitor tubastatin A (TsA) or HDAC6 knockdown with siRNA decreased the migration speed of HDFs and considerably suppressed fibroblast differentiation induced by transforming growth factor-β1 (TGF-β1), which suggests the involvement of HDAC6 in regulating fundamental physiological activities of dermal fibroblasts. In vivo full-thickness skin wound healing was significantly delayed in young HDAC6 knockout mice when compared with young wild type mice. In addition, the wound healing was significantly slower in aged wild type mice than that in young wild type mice, and became even worse in aged HDAC6 knockout aged mice. Compared to the aged wild type mice, aged HDAC6 knockout mice exhibited delayed angiogenesis, reduced collagen synthesis, and decreased collagen deposition in skin wounds. Together, these results suggest that delayed skin wound healing in aged mice is associated with impaired fibroblast function. Adequate expression and activity of HDAC6 are required for fibroblasts migration and differentiation.
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Humans , Animals , Mice , Aged , Histone Deacetylase 6 , Skin , Wound Healing , Cell Movement , Collagen/pharmacology , Fibroblasts , Mice, Knockout , Cells, CulturedABSTRACT
Objective:To evaluate the efficacy and safety of omeprazole and sodium bicarbonate suspension in the treatment of peptic ulcer.Methods:This present study was a multicenter, randomized, double-blind, double-dummy, positive drug parallel controlled phase Ⅱ clinical trial. According to different indications, the trial was divided into gastric ulcer (GU) and duodenal ulcer (DU) studies. Patients were stratified-block randomly divided with a 1∶1 ratio into experimental group and control group. The patients in the experimental group were administrated with omeprazole and sodium bicarbonate suspension omeprazole (20 mg for DU or 40 mg for GU, and 1 680 mg sodium bicarbonate) once a day. The patients in the control group received omeprazole magnesium enteric-coated tablet20 mg for DU or 40 mg for GU once a day. The treatment period was 4 weeks for DU and 8 weeks for GU. The main efficacy indicator was ulcer healing rate under endoscopy. The time of pain disappearance and the total effective rate of clinical symptom relief were used as the secondary efficacy indicators, and the incidence of adverse reactions was used as the safety indicator. The data set included full analysis set (FAS), per-protocol set (PPS) and safety set (SS). Independent sample t test, Wilcoxon rank sum test, chi square test, Fisher exact test method and non-inferiority test were used for statistical analysis. Results:Two hundred and seventy two DU patients and 237 GU patients were included in the FAS, 247 DU patients and 201 GU patients were included in the PPS, and 272 DU patients and 235 GU patients were included in the SS. The results of FAS analysis showed that after 4 weeks treatment, the healing rate of DU under endoscopy in the experimental group was 91.91% (125/136) and that in the control group was 94.85% (129/136), and the difference was not statistically significant ( P>0.05). After 8 weeks treatment the healing rate of GU under endoscopy in the experimental group was 86.44% (102/118) and that in the control group was 87.39% (104/119), and the difference was not statistically significant ( P>0.05). The results of non-inferiority analysis showed the lower limit of 95% confidence interval of difference in effective rate between the two groups was over -10% (-8.84% for DU and -9.54% for GU), which indicated that the effective rate of experimental group was not inferior to that of the control group. The results of PPS analysis were consistent with the results of FAS. The results of FAS analysis showed the median time of abdominal pain disappearance of DU patients in the experimental group and the control group was both 6 d, and the difference was not statistically significant ( P>0.05). The median time of abdominal pain disappearance of GU patients in the experimental group and the control group was both 8 d, and the difference was not statistically significant ( P>0.05). After 4 weeks of treatment, the total effective rates of clinical symptom relief of DU of the trial group and the control group were 95.59% (130/136) and 97.79% (133/136), respectively, and the difference was not statistically significant ( P>0.05). After 8 weeks of treatment, the total effective rates of clinical symptom relief of GU of the experimental group and the control group were 95.76% (113/118) and 93.28% (111/119), respectively, and the difference was not statistically significant ( P>0.05). The results of SS analysis showed that the incidence of adverse reactions of DU patients in the trial group and the control group was 5.15% (7/136) and 2.21% (3/136), respectively, and the difference was not statistically significant ( P>0.05). The incidence of adverse reactions of GU patients in the experimental group and the control group was 12.71% (15/118) and 6.84% (8/117), respectively, and the difference was not statistically significant ( P>0.05). Conclusions:Omeprazole and sodium bicarbonate suspension is not inferior to omeprazole magnesium enteric-coated tablet in healing efficacy under endoscopy in peptic ulcer, and has a good safety.
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In the era of artificial intelligence based on big data， data acquisition， storage and processing are more convenient， which provides a guarantee for accelerating the development of traditional Chinese medicine （TCM）， but it has not yet achieved organic integration with TCM theory. Based on preliminary research on the supramolecular "Qi chromatography" theory of TCM， combined with the current development trend of artificial intelligence， this paper analyzed the biological intelligence attribute of the function of TCM supramolecular "imprinting template"， in order to provide reference for the development of TCM drug innovation. Both the human body and Chinese materia medica are giant complex supramolecular bodies evolved from natural organisms. According to the "imprinting template"， the "social molecules" are controlled step by step to form the meridians and viscera. The interaction produces the original theory of TCM， in which the self-recognition， self-assembly， self-organization and self-replication of the "imprinting template" reflect the "intelligence" function attributes：the human body uses the "imprinting template" to self-identify and sense the ingredients of TCM， and store the memory information database in the meridian and collateral organs in the form of "imprinting template"， and then pass the "imprinting template". The comparison， analysis， and judgment of imprinting templates guide the self-assembly， self-organization and self-replication among "molecular society"， synthesize biological machines， produce biological functions， repair or strengthen biological supramolecular bodies， and present the most basic "intelligence" attribute. This suggests that the theory of theory-method-prescription-medicine of TCM is the weak embodiment of biological "intelligence"， while the human brain function is the strong embodiment of biological "intelligence". Since the intelligent function of supramolecular "imprinting template" runs through the natural world， artificial intelligence that can characterize the strong "intelligence" form of the human brain will also be integrated into all aspects of the natural world， suggesting the development direction of "intelligence" functionalization of drug innovation mode.
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Exosomes are lipid bilayer membranous vesicles actively secreted by various cells in the organism， which are like nanoparticles and have messenger targeting. Combining with the theory of supramolecular "Qi chromatography" of traditional Chinese medicine （TCM）， research ideas and strategies of modernization of TCM can be constructed. Exosomes are secreted by cells， and the membrane contains nucleic acids， proteins， lipids and small molecular metabolites and others， which can accurately coordinate the functions of each cell， concentrate and transmit the functional information of the parent cell， and is the concise form of reflecting cell functions. At the same time， it is loaded with the "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM. If the "imprinted templates" carrying rules among the gene-protein-lipid-small molecules wrapped in it is studied， the modern experimental research ideas and strategies of TCM theory can be established for revealing the functions of the body's meridians and viscera. Firstly， the present situation of exosomes， including discovery， secretion， characteristics， functions， attribution， uptake， research methods and application status， were reviewed in this paper. And the natural properties of its precise messenger targeted delivery vehicle were elaborated， reflecting the operation law of microscopic substances in meridians and viscera. Secondly， to explore it as an important carrier of the concentrated "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM， and integrating the research methods of exosomes and supramolecular chemistry of TCM， this paper proposes experimental research ideas and strategies on the microscopic material basis of meridians and viscera， compatibility of TCM compound， and targeting of TCM targeted preparations.
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Objective:To evaluate diagnostic value of contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) for pancreatic cystic lesions.Methods:Endoscopic and clinical follow-up data of patients with pancreatic cystic lesions diagnosed by EUS in Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University with CEH-EUS video from March 2013 to April 2020 was retrospectively analyzed.Results:A total of 36 patients were included. There were 16 cases of serous cystadenomas (SCA), 10 cases of mucinous cystic neoplasm (MCN), 5 cases of intraductal papillary mucinous neoplasms (IPMN, 3 with complex type, 2 with main pancreatic duct type) and 5 cases of pancreatic pseudocyst (PPC). 87.5%(14/16) of SCA and 86.7%(13/15) of MCN+ IPMN had hyperenhanced cystic wall with obvious peak and similar washout as surrounding tissue, whereas only 20%(1/5) PPC had hyperenhanced cystic wall. The hyperenhancing effect of PPC was significantly lower than that of SCA and MCN+ IPMN ( P=0.0035 and P=0.0048, respectively ). Mural nodules were detected in 17 cases of pancreatic cystic lesions by EUS, of which 3 cases had hyperenhanced mural modules and 14 cases had hypoenhanced mural nodules by CEH-EUS. Patients showing hyperenhanced mural modules were all finally diagnosed as pancreatic malignancy (1 IPMN, 2 MCN), and the accuracy was 100%. Conclusions:CEH-EUS can have a obvious advantage of differentiating pseudocyst and other pancreatic cystic lesions, while not very useful for differentiating SCA and MCN. Pancreatic cystic lesions showing hyperenhanced mural nodules under CEH-EUS may imply malignancy potential.
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Under the guidance of the theory of traditional Chinese medicine （TCM）， charcoal drugs are widely used in clinical treatment of various bleeding syndromes， in addition， they also have the effect in anti-diarrhea and anti-ulcer， but charcoal drugs are especially effective in stopping bleeding. According to the changes in the properties after processing， the hemostatic effect of charcoal drugs can be roughly divided into two categories. One is not used for hemostasis itself， but used for hemostasis after processing. The other is used for hemostasis itself， and the drug properties are changed or the hemostatic ability is enhanced after processing. By summarizing researches on historical evolution， processing mechanism and pharmacological effects of the commonly used hemostatic charcoal drugs， the author found that preservation or increase of active substances after processing was closely related to the hemostatic effect of charcoal drugs. The hemostatic mechanism mainly involves the influence of coagulation system and platelet function， etc. At the same time， combined with the theory of Qi chromatograph of TCM supramolecular， this paper puts forward the supramolecular research strategy on hemostatic mechanism of charcoal drugs， in order to provide reference for revealing the scientific connotation of charcoal drugs for hemostasis.
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Objective:To construct the targeting evaluation method of traditional Chinese medicine （TCM） preparations based on supramolecular Qi chromatography theory， and to study the liver targeting effect of Bupleuri Radix on Pien Tze Huang. Method:The molecular connectivity index （MCI） was used to analyze the characteristics of imprinted template and liver targeting tendency of TCM mainly attributed to liver meridian and components of Pien Tze Huang， and combined with target dynamics and total statistical moment principle， aimed at the independent action characteristics of multi-component imprinted template of TCM， a method for evaluating the targeting of TCM preparations was established. Hepatoma rats in Pien Tze Huang group， Bupleuri Radix<italic> </italic>group， Pien Tze Huang+Bupleuri Radix group and blank group were tested and verified. Result:After the average value of MCI of TCM mainly attributed to liver meridian was deducted， the MCI similarity between Pien Tze Huang group and Bupleuri Radix group was 0.376 8， Pien Tze Huang+Bupleuri Radix group and Bupleuri Radix group was 0.988 2， so it was predicted that Bupleuri Radix could enhance the liver targeting of Pien Tze Huang. A system for evaluating the targeting of TCM compounds was established， including relative total uptake efficiency （RUE<sub>T</sub>）， relative total concentration （RC<sub>T</sub>）， relative imprinted tendency （RIT<sub>T</sub>） and relative imprinted variance （RIV<sub>T</sub>）. The RUE<sub>T</sub> and RC<sub>T</sub> of liver were the highest in all tissues （RUE<sub>T</sub>=1.88>1，RC<sub>T</sub><italic>=</italic>2.30>1）， and the corresponding values of other tissues were all <1， indicating that Pien Tze Huang combined with Bupleuri Radix could increase its distribution in liver and enhance liver targeting. Except for plasma， the RIT<sub>T</sub> and RIV<sub>T</sub> of other tissues fluctuated around 1.0， indicating that targeted modification did not change imprinted tendency of Pien Tze Huang and had no significant effect on the types of components. Conclusion:Under the guidance of supramolecular Qi chromatography theory， a targeting evaluation parameter system can be established to characterize the multi-component imprinted effect of TCM preparations by MCI and total statistical moment parameters， so as to realize the evaluation of targeting of TCM preparations. The addition of Bupleuri Radix can increase the liver targeting of Pien Tze Huang.
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Objective:To establish high performance liquid chromatography （HPLC） fingerprint and multi-component determination for the substance benchmark of Yiweitang， and to evaluate its quality in combination with chemical pattern recognition method. Method:Fifteen batches of substance benchmark of Yiweitang were prepared， the "Chinese medicine chromatographic fingerprint similarity evaluation system" （2012 edition） was used to calculate similarity. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were employed to handle the common peaks for evaluating the quality difference among 15 batches of the substance benchmark. The contents of catalpol， verbascoside and methylophiopogonanone A were determined with mobile phase system of acetonitrile-phosphoric acid solution at detection wavelengths of 210 nm and 334 nm. Result:There were 22 common peaks in HPLC fingerprint of the substance benchmark， among them， peaks 1， 9， 12， 14-17， 19 and 20 belonged to Rehmanniae Radix， peaks 3， 4， 6， 7 and 21 belonged to Glehniae Radix， peaks 5 and 22 belonged to Ophiopogonis Radix， peaks 2 and 18 belonged to Polygonati Odorati Rhiaoma， peak 8 was the common peak of Ophiopogonis Radix and Rehmanniae Radix， peak 10 was shared by Ophiopogonis Radix， Polygonati Odorati Rhiaoma<italic> </italic>and<italic> </italic>Rehmanniae Radix， peak 11 was the common peak of these four herbs， and peak 13 was shared by Polygonati Odorati Rhiaoma and Rehmanniae Radix. The similarities between HPLC fingerprints of 15 batches of the substance benchmark and the control fingerprint were all >0.90， the samples could be divided into four categories by three chemical pattern recognition methods. Quantitative analysis showed that the contents of catalpol， verbascoside and methylophiopogonanone A among 15 batches of samples ranged from 0.37% to 1.14%， 0.002% to 0.054% and 0.016% to 0.079%， respectively. Conclusion:The established fingerprint and determination for the substance benchmark of Yiweitang have good separation and high accuracy， which reflect the overall chemical composition characteristics of Yiweitang， and can provide experimental basis for the further development and quality control of the compound preparations of this famous classical formula.
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The application of modern scientific theories and technologies to explore the mechanism of Chinese medicine and its compounds is one of the key issues in realizing the modernization of traditional Chinese medicine （TCM） research. Chinese medicine and its compounds produce comprehensive pharmacodynamics through multiple components acting on multiple targets， the core of clarifying the mechanism is to solve the key scientific problems of static correlation and dynamic integration verification between the components and the target network topology. At present， the effective method to clarify the mechanism of Chinese medicine and its compounds is to statically correlate the topological network of in vitro components and targets through network pharmacology. Although there are also component-target verification studies， they often learn from research idea of single component-single target， it is urgent to establish a quantitative integration and overall verification method that conforms to the characteristics of TCM. According to supramolecular Qi chromatography theory of TCM， the microscopic mechanism of interaction between Chinese medicine and human body is actually the two supramolecular host and object groups （the active ingredient group of Chinese medicine and the target group of human body） based on imprinted template， which shows the macroscopic properties and pharmacodynamics. Based on this， the author proposes to use supramolecular Qi chromatography theory as the guidance， combined with supramolecular chemistry， network dynamics， quantitative pharmacology and other methods to quantitatively integrate and verify the compositions and the target groups with imprinted template as the core predicted by network pharmacology， looking for the optimal quality markers， greatly reducing the difficulty of multi-component-multi-target experimental verification of Chinese medicine and its compounds.
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Ophthalmology is one of the important professional courses for clinical medical students. At present, these students are not interested and enthusiastic in learning this course, they have a poor concentration in class, which leads to higher requirements for clinical teachers of ophthalmology. In order to improve the quality of clinical ophthalmology course, the teachers can make use of "empathy", "profit-seeking thinking" and "case stories" in the preparation of teaching, and combine with multimedia tools to simplify, visualize and interest the key and difficulties in the course, thus improving the teaching effect and quality of clinical ophthalmology course.
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The abnormality of pupil function in diabetic patients is the clinical manifestation of autonomic nervous system damage in diabetic patients, which seriously affects the examination and treatment of diabetic retinopathy. At present, it is still difficult to handle this disorder. This paper reviewed the pathogenesis, clinical manifestations and treatment measures of pupil dysfunction in diabetic patients.
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In this paper, based on the supramolecular "Qi chromatography" of traditional Chinese medicine (TCM), combined with the characteristics of corona virus disease 2019 (COVID-19), the historical origin and characteristics of theoretical research on the treatment of epidemic diseases by TCM were analyzed retrospectively, and the key scientific problems for achieving its modernization were proposed, and the countermeasures were illustrated. In fact, the emergence and development history of TCM epidemic theory is a comprehensive and scientific understanding of biomolecular chemistry for epidemic caused by pathogen. From the exploration of the cause of abnormal Qi to the epidemic pathogenic factor, from the treatment based on syndrome differentiation by six meridians to by the defensive Qi and nutrient blood and the triple energizer, which is gradually close to the modern theoretical system of infectious diseases and immunology, all of which are stamped with brand of TCM supramolecular "Qi chromatography" theory. In the long history of biological evolution in nature, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as epidemic pathogenic factor in TCM, human body and Chinese materia medica are biological supramolecules at a specific stage of evolution in nature, which are controlled by the "imprinting templates" of molecular society in gradual biomolecules, with the unchanged laws of mutual advancement, mutation, suitability and mutual restriction. Based on the analysis of the law of supramolecular action hiding in the prevention and treatment of epidemic diseases dealt with TCM on procession of principle-method-recipe-medicines, this paper discusses the key scientific problems of its modernization and puts forward the solutions. It can not only clarify the scientific principle of the prevention and treatment with TCM, develop the multi-component Chinese medicine, accelerate the control of the epidemic situation, but also promote the solution of original frontier key scientific problems such as the material basis of meridians, viscera and syndromes, and the compatibility law of the TCM prescription, in order to protect the existing medical resources and open up a new situation in the modernization of TCM research.
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Objective: To observe the effect of hydroxysafflower yellow A (HSYA) on the apoptosis of human umbilical vein endothelial cells EA.hy926 induced by hypoxia-reoxygenation. Methods: MTT colorimetry method was used to detect the effects of different hypoxia time (8, 12 h) and different reoxygenation time (4, 8, 12 h) on the cell viability. And after the cell had been in the status of hypoxia for 12 h and reoxygenation for 8 h, this method was adapted once again to evaluate the effects of different concentrations of HSYA (0.1, 1, 10, and 100 μmol/L) on cell viability in different time stages. After the cell had been in the status of hypoxia for 12 h, reoxygenation for 8 h, Western blotting was used to test its effects on the expressions of the following proteins in different time stages, which contained Bcl-2, Bax, cleaved Caspase-3, and activated cleaved Caspase-9. This method was also used to detect whether it had an improvement effect on the above proteins after the pr-treat the cells with HSYA. Real-time PCR was used to evaluate the mRNA expressions of Bax, Bcl-2 after the cell had been in the status of hypoxia for 12 h, reoxygenation for 8 h, and this method was also used to test the effect of HSYA on the expressions of Bax, Bcl-2 after the same time stages. Hoechest staining and flow cytometry were used to detect the apoptosis situation of the cell after it was in the status of hypoxia for 12 h and reoxygenation for 8 h. And this method was also adapted to detect the effect of HSYA on apoptosis of the cell after the same time stage. Results: Compared with the control group, the EA.hy926 cell viability decreased significantly after hypoxia for 8, 12 h, reoxygenation for 4, 8, and 12 h (P < 0.01). The cell viability decreased the most significantly after hypoxia for 12 h and reoxygenation for 8 h (P < 0.01), and during this period, the expression of Bax, cleaved Caspase-9, cleaved Caspase-3 protein increased significantly, and Bcl-2 protein was decreased significantly. Compared with the H/R group, HSYA (10 μmol/L) significantly increased the cell viability (P < 0.01) after hypoxia-reoxygenation, and significantly up-regulated the protein expression of Bcl-2, and down-regulated the protein expressions of Bax, cleaved Caspase-9, and cleaved Caspase-3. Conclusion: Hydroxysafflor yellow A can effectively inhibit the apoptosis of EA.hy926 induced by hypoxia and reoxygenation. The mechanism may be related to the down-regulation of Bax, cleaved Caspase-9, cleaved Caspase-3 protein as well as the up-regulation of Bcl-2 protein.
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The safety and effectiveness of Chinese materia medica (CMM) depend on its quality, and the modernization of CMM quality control system is an important prerequisite for the internationalization of traditional Chinese medicine (TCM). Up to now, the quality research approach of CMM is the key technology for TCM industry. In recent years, with the development of modern life science, chemistry science, analytical science and technology, the quality research level of CMM has been greatly improved, but it still stays on the two evaluation models based on chemical composition and biological effect. For single compound, because the effect is proportional to the content of components, the chemical composition can be used for quality control. However, for multi-component system of CMM, how to establish the dose-effect relationship between effects and components and find the markers reflecting their quality has become the focus of the quality control of CMM for TCM industry. Based on the theory of supramolecular “imprinting template” and “Qi-xi” put forward earlier, this paper first analyzed the characteristics of supramolecular “imprinting template” for the quality of CMM, clarified the essence of quality control of CMM, and proposed the attributes of supramolecular “imprinting template” to reflect the main effect of CMM. The control strategy of quality markers of CMM represented by core index will provide a new and more accurate characterization and calculation model for quality control of CMM.
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Objective:To establish a mathematical model of total statistical moment, information amount and one-time steady-state feeding quantity of HPLC fingerprint of traditional Chinese medicines (TCMs) and their classical prescriptions, and to carry out experimental verification. Method:The total statistical moment principle, Hardy-Weinberg equilibrium principle and one-time steady-state feeding quantity calculation method were used to study the total statistical moment parameters and one-time steady-state feeding quantity of 15 batches of original medicinal materials, decoction pieces and compound preparations of Taohong Siwutang, these original medicinal materials were from three producing areas. Result:In addition to the total first-order moment, RSD of total zero-order moment, total second-order moment, information entropy and information amount of each medicinal material, decoction piece and compound were all greater than 10%. In the case of single original medicinal material, except for Angelicae Sinensis Radix (142.34 kg), the one-time steady-state feeding quantity calculated according to the RSD change of the accumulated information amount of the whole prescription was the largest (59.10 kg), and according to ratio of the whole prescription, one-time steady-state feeding quantity was the largest (958.57 kg). In the case of processed products, the one-time steady-state feeding quantity of the whole prescription was the largest (73.18 kg) except for Carthami Flos processed with wine (83.28 kg), while according to the whole prescription, one-time steady-state feeding quantity of each processed products was the same as that of the original medicinal material. The one-time steady-state feeding quantity of the compound consisted of the original medicinal materials or processed products was often higher than that of the single medicinal material. Conclusion:The components of TCM are controlled by genetic polymorphism, the chromatographic characteristics (types of components) of Chinese medicine is similar and the intensity of action (content of components) is different. The stability of total first-order moment and information entropy indicates that the overall chemical structure of TCM multi-component system has a stable imprinting trend. The one-time steady-state feeding quantities of each medicinal material in Taohong Siwutang and this compound are far greater than the prescription amount, which can provide reference for the industrial production.
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The ancient famous classical formulas were developed based on the characteristics of excellent curative effect, small toxic and side effects, and wide clinical application. Its development will promote the development of traditional Chinese medicine (TCM) with huge social and economic benefits. TCM and TCM compounds are multi-component systems, which are multi-component, multi-target and multi-pathway effect on human body, their curative effect is the result of synergistic effect of multi-component. Because of its characteristics, its mechanism of action is still unclear and quality is difficult to control. Therefore, on the basis of biological properties of the multi-components of TCM, it is the key issue to study the preparation process of the medicinal materials-decoction pieces-preparations and the transferability, stability and homogeneity of the quality attributes. Moreover, the supramolecular theory can explain the basic theory of TCM from the macroscopic and microscopic aspects, the study of ancient famous classical formulas can use the supramolecular theory. Both TCM and human body are giant complex supramolecules, and their components are clustered objects reflecting the characteristics of the original imprinting template with genetic polymorphism. The quality attributes, processing, formulation preparation and quality attribute evaluation of TCM are all affected by supramolecular chemistry, which is finally reflected in the preparation of imprinting template and the transfer law of quality properties. Therefore, the application of supramolecular imprinting template theory to study the biogenetic polymorphism of TCM, processing, formulation preparation and quality attribute evaluation of medicinal materials can improve the availability rate of successful research and development of ancient famous classical formulas.
ABSTRACT
<p><b>Background:</b>Previous studies have found that schoolchildren with attention-deficit/hyperactivity disorder (ADHD) showed difficulties in neuropsychological function. This study aimed to assess neuropsychological function in Chinese preschoolers with ADHD using broad neuropsychological measures and rating scales and to test whether the pattern and severity of neuropsychological weakness differed among ADHD presentations in preschool children.</p><p><b>Methods:</b>The 226 preschoolers (163 with ADHD and 63 controls) with the age of 4-5 years were included and assessed using the Behavior Rating Scale of Executive Function-Preschool Version (BRIEF-P) and a series of tests to investigate neuropsychological function.</p><p><b>Results</b>Preschoolers with ADHD showed higher scores in all domains of the BRIEF-P (inhibition: 30.64 ± 5.78 vs.20.69 ± 3.86, P < 0.001; shift: 13.40 ± 3.03 vs.12.41 ± 2.79, P = 0.039; emotional control:15.10 ± 3.53 vs.12.20 ± 2.46, P < 0.001; working memory: 28.41 ± 4.99 vs.20.95 ± 4.60, P < 0.001; plan/organize: 17.04 ± 3.30 vs.13.29 ± 2.40, P < 0.001) and lower scores of Statue (23.18 ± 7.84 vs.28.27 ± 3.18, P = 0.001), Word Generation (15.22 ± 6.52 vs.19.53 ± 7.69, P = 0.025), Comprehension of Instructions (14.00 ± 4.44 vs.17.02 ± 3.39, P = 0.016), Visuomotor Precision (P < 0.050), Toy delay (P = 0.048), and Matrices tasks (P = 0.011), compared with normal control. In terms of the differences among ADHD subtypes, all ADHD presentations had higher scores in several domains of the BRIEF-P (P < 0.001), and the ADHD-combined symptoms (ADHD-C) group had the poorest ratings on inhibition and the ability to Plan/Organize. For neuropsychological measures, the results suggested that the ADHD-C group had poorer performances than the ADHD-predominantly inattentive symptoms (ADHD-I) group on Statue tasks (F = 7.34, η = 0.12, P < 0.001). Furthermore, the ADHD-hyperactive/impulsive symptoms group had significantly poorer performances compared to the ADHD-C group in the Block Construction task (F = 4.89, η = 0.067, P = 0.003). However, no significant group differences were found between the ADHD-I group and normal control.</p><p><b>Conclusion:</b>Based on the combined evaluation of performance-based neuropsychological tests and the BRIEF-P, preschoolers with ADHD show difficulties of neuropsychological function in many aspects.</p>