TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

Membrane lipid remodeling and autophagy to cope with phosphorus deficiency in the dinoflagellate Prorocentrum shikokuense.

Dinoflagellates, which are responsible for more than 80% of harmful algal blooms in coastal waters, are competitive in low-phosphate environments. However, the specific acclimated phosphorus strategies to adapt to phosphorus deficiency in dinoflagellates, particularly through intracellular phosphorus metabolism, remain largely unknown. Comprehensive physiological, biochemical, and transcriptomic analyses were conducted to investigate intracellular phosphorus modulation in a model dinoflagellate, Prorocentrum shikokuense, with a specific focus on membrane lipid remodeling and autophagy in response to phosphorus deficiency. Under phosphorus deficiency, P. shikokuense exhibited a preference to spare phospholipids with nonphospholipids. The major phospholipid classes of phosphatidylcholine and phosphatidylethanolamine decreased in content, whereas the betaine lipid class of diacylglyceryl carboxyhydroxymethylcholine increased in content. Furthermore, under phosphorus deficiency, P. shikokuense induced autophagy as a mechanism to conserve and recycle cellular phosphorus resources. The present study highlights the effective modulation of intracellular phosphorus in P. shikokuense through membrane phospholipid remodeling and autophagy and contributes to a comprehensive understanding of the acclimation strategies to low-phosphorus conditions in dinoflagellates.

Research on Material Basis of Homologous and Heterogeneous Effect of Aurantii Fructus Immaturus and Aurantii Fructus Based on Total Statistical Moment Analysis and Molecular Connectivity Index / 中国实验方剂学杂志

ObjectiveTo investigate the material basis of homologous and heterogeneous effect of Aurantii Fructus Immaturus（AFI） and Aurantii Fructus（AF） based on the total statistical moment analysis and molecular connectivity index（MCI）. MethodRelevant literature at home and abroad and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） were consulted to establish the chemical composition database of AFI and AF， and set up their fingerprints by ultra-high performance liquid chromatography（UPLC）， and the total statistical moments and similarity parameters of the fingerprint were calculated. According to MCI， all components of AFI and AF were divided into different component groups， the average values of 0-8th order（0χ-8χ） MCI of the common component groups of AFI and AF were calculated. ResultThe values of total zero-order moment（AUCT） of AFI and AF were （10.57±2.45）×106， （5.09±0.89）×106 μV·s， the values of total first-order moment（MCRTT） were （11.57±1.58）， （12.10±1.29） min， the values of total second-order moments（VCRTT） were（24.49±2.30）， （26.49±2.54） min2， respectively. It showed that qualitative and quantitative parameters of AFI and AF were significantly different. The components with high similarity such as neohesperidin， hesperidin and narirutin were screened as the common potential pharmacodynamic components of AFI and AF. The non-common components of AFI， such as alysifolinone and imperatorin， and the non-common components of AF， such as neoeriocitrin and isosakuranin， with high similarity were screened out as potential heterogeneous components of AFI and AF. The composition groups of AFI and AF were classified into six categories， and the similarities between the composition groups of AFI and AF and the total constituents were 0.872-0.979 and 0.918-0.997， the average values of 0χ-8χ MCI of alkaloids in AFI and AF were 3.65 and 3.14， the average values of 0χ-8χ MCI of flavonoids were 8.47 and 8.47， the average values of 0χ-8χ MCI of volatile oils were 2.71 and 3.48， respectively. It showed that there were some differences in MCI of chemical constituents（groups） between AFI and AF. ConclusionThe chemical constituents（groups） of AFI and AF not only differ in content and species， but also in structural characteristics and structure-activity relationship， which can provide a basis for further explaining the scientific connotation of homologous and heterogeneous effect of AFI and AF.

Variation in intracellular polyphosphate and associated gene expression in response to different phosphorus conditions in the dinoflagellate Karenia mikimotoi.

Polyphosphate (polyP) has long been recognized as a crucial intracellular reservoir for phosphorus in microorganisms. However, the dynamics of polyP and its regulatory mechanism in eukaryotic phytoplankton in response to variations in external phosphorus conditions remain poorly understood. A comprehensive investigation was conducted to examine the intracellular polyP-associated metabolic response of the dinoflagellate Karenia mikimotoi, a harmful algal bloom species, through integrated physiological, biochemical, and transcriptional analyses under varying external phosphorus conditions. Comparable growth curves and Fv/Fm between phosphorus-replete conditions and phosphorus-depleted conditions suggested that K. mikimotoi has a strong capability to mobilize the intracellular phosphorus pool for growth under phosphorus deficiency. Intracellular phosphate (IPi) and polyP contributed approximately 6-23 % and 1-3 %, respectively, to the overall particulate phosphorus (PP) content under different phosphorus conditions. The significant decrease in PP and increase in polyP:PP suggested that cellular phosphorus components other than polyP are preferred for utilization under phosphorus deficiency. Genes involved in polyP synthesis and hydrolysis were upregulated to maintain phosphorus homeostasis in K. mikimotoi. These findings provide novel insights into the specific cellular strategies for phosphorus storage and the transcriptional response in intracellular polyP metabolism in K. mikimotoi. Additionally, these results also indicate that polyP may not play a crucial role in cellular phosphorus storage in phytoplankton, at least in dinoflagellates.

Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS: Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

Isoflavones from Sojae Semen Praeparatum Regulate Lipid Metabolism in Atherosclerotic Mice Through PPARγ/LXRα/ABCA1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the effect of isoflavones from Sojae Semen Praeparatum （ISSP） on lipid metabolism in atherosclerotic mice， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor gamma/liver X receptor alpha/ATP-binding cassette transporter A1 （PPARγ/LXRα/ABCA1） signaling pathway. MethodFifty ApoE-/- mice were randomly assigned into the model group， western medicine （atorvastatin calcium， 3.03 mg·kg-1） group， and low-， medium-， and high-dose ISSP （2.5， 5， 10 mg·kg-1， respectively） groups， with 10 rats in each group. Atherosclerosis model mice were established by bilateral ovariectomy and feeding high-fat diet. Another 10 ApoE-/- mice receiving ovariectomy and high-fat diet were taken as the sham group. Some mice died of postoperative infection， and finally 6 mice were included in each group. One week after operation， each group was administrated with corresponding drugs or equivalent amount of normal saline. After 12 weeks， the levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and non-esterified fatty acids （NEFAs） in serum and liver tissue were measured. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining and oil red O staining were used for observation of aortic plaque formation and liver lipid deposition. The mRNA and protein levels of PPARγ， LXRα， ABCA1， and ATP-binding cassette transporter G1 （ABCG1） in liver were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the sham group， the modeling of atherosclerosis increased the aortic plaque area （P<0.01）， elevated the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the level of HDL-C （P<0.01）， increased the liver index （P<0.05） and the levels of TC， TG， and NEFAs in liver （P<0.01）， and caused obvious hepatic fat vacuoles and lipid deposition. In addition， the modeling down-regulated the mRNA levels of PPARγ， LXRα， ABCA1 in liver （P<0.05， P<0.01），and regulated the mRNA and protein levels of ABCG1（P<0.05， P<0.01）. Compared with the model group， atorvastatin calcium and middle-， high-dose ISSP reduced the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the liver index （P<0.01）， alleviated the liver fat vacuoles and lipid deposition， and increased the levels of TC， TG， and NEFAs in the liver （P<0.05， P<0.01）. Furthermore， they up-regulated the mRNA and protein levels of PPARγ， LXRα， ABCA1， and ABCG1 in the liver （P<0.05， P<0.01）. ConclusionISSP may regulate lipid metabolism through PPARγ/LXRα/ABCA1 signaling pathway to down-regulate the expression of inflammatory cytokines in serum and alleviate liver lipid deposition， thereby suppressing the formation of atherosclerotic plaque.

Discussion on Material Basis of Different Parts of Mulberry with Different Effects Based on Molecular Connectivity Index / 中国实验方剂学杂志

ObjectiveTo explore the material basis for the difference in the efficacy of different parts of mulberry based on molecular connectivity index （MCI）. MethodBy referring to the relevant literature at home and abroad and traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） database， the chemical composition database of mulberry-source medicinal materials was established. Venn analysis was carried out on the components among mulberry-source medicinal materials. The components in the database were divided into 10 categories， and the composition information was analyzed. According to MCI value， all components of mulberry-source medicinal materials were divided into different groups. The angle cosine method was used to calculate the MCI similarity. The average MCI values of the common component group from 0-8 orders and CI of mulberry-source medicinal materials were calculated. ResultThe components with high similarity such as （+）-cycloolivil， 1′-methoxy-2′-hydroxydihydromollugin， kuwanon， morusin and 1-deoxynojirimycin were selected as potential pharmacodynamic components. Mulberry-source medicinal materials could be divided into five component groups. The similarity between component groups and total components was 0.760-0.999， and the similarity between component groups was 0.248-0.999. In Mori Ramulus， Mori Folium， Mori Cortex and Mori Fructus， the average MCI values of their flavonoids from 0-8 orders were 4.57， 4.59， 6.41， 4.24， respectively. The average MCI values of alkaloids from 0-8 orders were 2.65， 4.55， 2.58， 2.78， respectively. The average CI values from 0-8 orders were 5.51， 5.49， 5.44 and 2.88， respectively. ConclusionIt is preliminarily concluded that there are differences in the flavonoids and pathways of hypoglycemic effects between Mori Cortex and the other three mulberry-source medicinal materials. The MCI values of alkaloids from 0-8 orders in Mori Folium and Mori Fructus were higher， but their inhibitory activity of α-glucosidase were lower than those of Mori Ramulus and Mori Cortex. The structural characteristics of the total components of Mori Fructus represented by CI were quite different from the other three mulberry-source medicinal materials.

Clinical efficacy of Infliximab in pediatric Crohn′s disease / 中华实用儿科临床杂志

Objective:To evaluate the clinical efficacy and safety of Infliximab (IFX) in pediatric Crohn′s disease (CD).Methods:The efficacy of IFX therapy in 30 patients suffering from active CD who were not completely improved with traditional medicine and enteral nutrition or had intolerance to the medicine in Beijing Children′s Hospital Affiliated to Capital Medical University from December 2014 to December 2019 were retrospectively analyzed.Pediatric Crohn′s Disease Activity Index (PCDAI), blood biochemistry indices, mucosal healing, nutritional status, and adverse reactions were compared and evaluated.Results:Thirty active CD cases, with 18 males and 12 females, were enrolled, and the average age was (8.63±4.76) years old.Three cases who didn′t complete 3 times of IFX injection and 1 case who lost to be followed up were excluded.A total of 26 cases of CD in active period were enrolled in this study on efficacy.The clinical remission and response rate of 26 cases were 61.5% and 84.6%, respectively, at 14-week of IFX therapy.The clinical remission and response rate of 21 cases were 71.4% and 85.7%, respectively, at 30-week.The clinical remission and response rate of 15 cases were 86.7% and 93.3%, respectively, at 54-week.At week 14 th, PCDAI score [(9.56±8.05) scores vs.(29.02±10.86) scores] decreased compared with before treatment ( t=7.339, P<0.05). The levels of erythrocyte sedimentation rate [(15.54±10.26) mm/1 h vs.(33.77±21.30) mm/1 h] and C-reactive protein [(4.79±12.94 ) mg/L vs.(16.33±23.43) mg/L] were obviously decreased, and the hemoglobin [(126.27±16.51) g/L vs.(110.58±16.45) g/L], hematocrit [(37.03±3.95)% vs.(33.52±4.32)%], and albumin levels [(42.30±3.03) g/L vs.(37.13±5.68) g/L] were remarkably increased compared with those before treatment ( t=3.932, 1.993, -3.398, -3.060, -4.009, all P<0.05). Height for age Z score and body mass index Z score were increased after IFX treatment, without statistically significant differences (all P>0.05). Conclusions:IFX therapy had good clinical efficacy in controlling inflammatorys and inducing clinical remission in pediatric CD.

Anticancer Effect of Tanshinones on Female Breast Cancer and Gynecological Cancer.

Female breast cancer, ovarian cancer, cervical cancer, and endometrial cancer are the most common tumors and the most common causes of cancer-related mortality worldwide in women. Drugs derived from natural plants play important roles in malignant tumor therapy. Salvia miltiorrhiza is a commonly used Chinese herb which has been used in the treatment of liver diseases and cardiovascular diseases because of its positive effect of promoting blood circulation, increasing oxidative stress, and removing blood stasis. Recently, studies have found that fat-soluble components of Salvia miltiorrhiza such as tanshinone II, tanshinone I, cryptotanshinone, and dihydrotanshinone I displayed good antitumor activity in vivo and in vitro for gynecological cancer by different molecular mechanisms. In this study, the latest research progress on the antitumor effect and mechanism of tanshinone compounds in breast cancer and gynecological cancer was reviewed to provide references for the research and clinical application of these compounds (tanshinone II, tanshinone I, cryptotanshinone, and dihydrotanshinone I).

Research progress on deep eutectic solvents in extraction of Chinese materia medica ingredients / 中草药

Traditional solvents have the shortcomings of toxic, easy to cause environmental pollution, volatile and low extraction rate. In recent years, there have been a lot of researches focusing on deep eutectic solvents (DESs) studies in the field of Chinese materia medica (CMM), especially in the extraction of active ingredients and improvement of stability of unstable compounds. This paper mainly reviews and sorts out the researches on DESs in the field of CMM reported at home and abroad in recent years, so as to provide references for the application of DESs in the field of CMM in the future.

Sequential Therapy Based on Evolvement of Patterns: A New Model for Treatment of Alzheimer's Disease.

In order to solve the problem of long-term (>9 months) efficacy in the treatment of Alzheimer's disease (AD) by conventional therapy (CT), a staged and multiply-targeted sequential therapy based on the evolvement of patterns (STEP) was developed. Its main innovations include: (1) the time order of evolution of patterns defined by Chinese medicine (CM) in AD was found, that is, "the orderly pattern evolution starting from Shen (Kidney) deficiency, progressing to phlegm, stasis and fire, and worsening to severe toxin as well as functional collapse"; (2) the cascade hypothesis of Shen deficiency in AD and its sequential therapy based on Shen-reinforcing was proposed, that is, "reinforcing Shen in the early stage and throughout the whole process, resolving phlegm, activating blood and purging fire in the middle stage, detoxifying and replenishing vitality to stop the collapse in the advanced stage", and through meta-analysis, clinical drug use was optimized, thus the leap from "inferential selection" to "evidence-based selection" was realized; (3) the STEP regimen combined with CT maintained cognitive and behavioral stability in AD patients for at least 12 months, with cognitive enhancement and behavioral synergy after 9 months, and cognitive benefit was superior to CT at 9, 12, 15, 18, 21, and 24 months, respectively. The 2-year cognitive improvement rate was increased by 25.64% (P=0.020) and the cognitive deterioration rate was decreased by 48.71% (P=0.000). Among them, the cognitive and functional benefits of Shen-reinforcing therapy for very early AD (350 cases) for 1 year were better than the placebo (P<0.001), and the dementia conversion rate was reduced by 8.85% (P=0.002). The behavioral symptomatic relief of patients with vascular dementia received fire-purging therapy (540 cases) was superior to those received CT (P=0.016). These data suggested that the STEP regimen has synergistic effects on CTs at least in terms of cognitive benefit, and the earlier the use, the greater the benefit will have. Therefore, the STEP regimen should be considered as one of the clinical options, particularly for the dearth of effective pharmaceutical or immunological interventions that are currently available for AD.

Consistency Analysis of “Imprinting Templates” of Chinese Medicine Preparations Based on Dynamic Volatile Components in Houttuyniae Herba / 中国实验方剂学杂志

Objective:The homogeneity regularity of "imprinting templates" of compound preparation of traditional Chinese medicine(TCM) was revealed, which provided the basis for effectively controlling the quality of compound preparation of TCM, by clarifying the dynamic changeability in number and content of volatile ingredients in different batches of Houttuyniae Herba. Method:The volatile oil of Houttuyniae Herba was extracted by steam distillation.The volatile components in 11 batches of Houttuyniae Herba were determined by GC-MS(electron ionization, ion source temperature of 230℃, detection range of m/z 40-500) combined with literature and ChemicalBook database.The relative content of each component was calculated by peak area normalization method and analyzed by the total quantum statistical moments of fingerprint. Result:There were only 15 common ingredients in the volatile oil from 11 batches of Houttuyniae Herba, accounting for 3.35%of total number and 73.94%of total content, while the number of non-common ingredients was 433, accounting for 96.65%of total number.However, the RSD of total quantum first moment of GC-MS fingerprint was 6.8%, the RSD of total quantum second moment was 14.8%(RSD of standard deviation was 7.4%), and the RSD of similarity of total quantum statistical moment was 3.8%.The type and content of volatile ingredients in Houttuyniae Herba were heterogeneous, but their chromatographic behavior of GC-MS fingerprint was uniform, the whole "imprinting templates" was similar. Conclusion:The total quantum statistical moment(similarity) of TCM fingerprint is applicable to quality control of dynamic Chinese medicines, which will play a breakthrough role in the study of homogeneity and stability of material reference and compound preparation for ancient classical formulas.

Taxus chinensis ameliorates diabetic nephropathy through down-regulating TGF-ß1/Smad pathway.

Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg-1 body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L-1 were selected for experiments. The DN rats were treated with Taxus chinensis orally (0.32, 0.64, and 1.28 g·kg-1) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-ß1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-ß1/Smad signaling pathway.

Druggability and preparation modification of Chinese materia medica based on supramolecular “imprinted template” / 中草药

Chinese materia medica (CMM) is a multi-component system. In addition to the study on single-component druggability, the focus should be also on how to integrate the rules of single-component druggability to construct a research system of suitable multi-component druggability of CMM. According to the basic theory of CMM guidance, the druggability of CMM has been accumulated by long-term clinical practice experience, and the curative effect is affirmed. The most critical issue is how to determine the attribution and intermolecular interaction of the well-defined CMM component group and develop a component CMM. However, how to integrate the physicochemical and biological apparent properties of the multi-component based on the apparent physical and chemical properties of the single-component is the key to the study on druggability and preparation modification of CMM. Therefore, the druggability study of the single-component medicine and the study of the change rules of multi-component CMM druggability by using compatibility principle of CMM and modern supramolecular chemistry theory are needed to performed to study on the druggability of CMM. The combination of CMM druggability, preparations and chemical modifications can maximize the success rate of the development of new CMMs. The characteristic of the autonomous “Qi-xi” for CMM “imprinting template” of supramolecules has an important guiding role in druggability research of CMM both in theory and practice.

Determination of paeoniflorin in Chinese traditional herbal preparation Fuzheng-pingxiao capsule using HPLC method / 药学实践杂志

Objective To determine the content of paeoniflorin in Fuzhengpingxiao capsule by HPLC method .Methods The content of paeoniflorin were determined by HPLC ,and the column was an Agilent Zorbax SB-C18 column (150 mm × 4 .6 mm ,5 μm);The mobile phase was acetonitrile and 5 mmol/L sodium dihydrogen phosphate (10:90) ,and the flow rate was set at 1 ml/min .Column temperature was 25°C ,detection wavelength was 230 nm ,injection volume was 10 μl ,and running time was 25 min .Results Paeoniflorin was linear (r=0 .9999) in the concentration of 25 .0-500 .0 μg/ml ,the linear equation was Y=12 .65 X +43 .54 ,and the average recovery was 92 .69％ with RSD value was 1 .77％ .Conclusion The method was easy to operate ,reliable and reproducible ,which could be used in the determination of paeoniflorin in FuzhengPingxiao capsule .

Study on Extraction Kinetic Comparison of Chlorogenic Acid in Lonicerae Japonicae Flos and Lonicerae Flos / 中国中医药信息杂志

Objective To explore the extraction kinetic deviation of the chlorogenic acid (ChA) in Lonicerae Japonicae Flos and Lonicerae Flos through established extract kinetic model of closed system of Chinese materia medica. Methods The content of ChA (W0) and ρ2in Lonicerae Japonicae Flos and Lonicerae Flos were determined by HPLC; The V1and V2were measured by water absorbing further to calculate V0; The value of M, N, L, α, β, and π were estimated by curve fitting using SPSS19.0 edition; The extraction kinetic parameters k, k1′, k2′, ρ1, tmax, cmax, AUC, P%, and D% were calculated by Excel; their similarity was calculate by the total quantum statistical moment similarity (TQSMS). Results The V0, V1,and V2for Lonicerae Japonicae Flos were 18.69, 9.50, and 30.20 mL, respectively. The W0for the ChA in Lonicerae Japonicae Flos were 3.75%, and ρ2was 0.884; The V0, V1, and V2for Lonicerae Flos were 12.79, 7.80, and 37.00 mL, respectively. The W0for the ChA in Lonicerae Flos were 5.67%, and ρ2was 1.020; The extraction kinetic profiles for ChA in Lonicerae Japonicae Flos and Lonicerae Flos were fitted three compartment model. The main kinetic parameters as k were 0.1101, 0.3755 h-1; k1′ were 3.632, 3.288 h-1; k2′ were 53.12, 55.28 h-1; ρ1were 2.731, 2.751; tmaxwere 0.299 5, 0.216 3 h; cmaxwere 0.134 0, 0.252 7 mg/mL; AUC were 3.405, 1.560 h; P% were 35.73% and 44.57%; D% were 0.916 2% and 2.680 7%, respectively. Their TQSMS was 0.963 8, which indicated that the extraction kinetics of ChA in Lonicerae Japonicae Flos and Lonicerae Flos had good similarity. Conclusion The extraction kinetic model described the dissolution behavior and deviation of extraction kinetic profiles for ChA in Lonicerae Japonicae Flos and Lonicerae Flos objectively and effectively. This research can provide some references for further study on extraction processes and preparation of Lonicerae Japonicae Flos and Lonicerae Flos.

Developing an integrated model of toxicity and efficacy of Chinese medicine based on supramolecular “imprinting template” analysis / 药学学报

Chinese material medica (CMM) is the foundation for treating disease using traditional Chinese medicine (TCM), which is not only guided by the basic theory of TCM but also follows the general rules of drug action. There are both toxicity and efficacy in TCM. For TCM the integrated regularities of its toxicity and efficacy were demonstrated in their prescription, which were qualitatively characterized by compatible experiences such as "seven emotions", "Yin" and "Yang" compatibility, etc. When the toxicity is still produced by oral administration according to the prescription of TCM theory or administration is not abided by original requirement, the integral regularities of toxicity and efficacy that depends on experience appears to be at a loss what to do. Especially in recent years, with the modernization of TCM and the continuous advantages in new medicinal innovation, the CMM safety incidents occurred frequently. It is very urgent for us how to establish a set of integrated methods that are adequately situated to multiple components for TCM. With the combination of the biological supramolecular chemistry and the basic theory of TCM, an integrated model of toxicity and efficacy based on TCM supramolecular "imprinting template" has begun to take shape. The CMM and the human body are both biological supramolecular bodies that follow the autonomic action rules of their "imprinting template". The integrated trends of toxicity and efficacy are able to build on systematical results of single components in CMM based on the theory of TCM to treat diseases by prescription on syndromes. It is also the systematic actions resulting from single effective components in CMM by the supramolecular "imprinting template" self-acted regularities. Through the qualitative and quantitative analysis of supramolecular "imprinting templates" characteristics and actions and their network chromatotoxicometrology (chromatopharmacometrology), a toxic and effective integrated analysis methods will be established on an integrated "therapeutic window" for components in the CMM. This effort will finally permit the description of the components of the pharmacokinetic overlaid law of "therapeutic window", plotted to lower-overflow, entering and higher-overflow profiles.

Effect of GAPT extract on expression of tau protein and its phosphorylation related enzymes in hippocampal neurons of APPV717I transgenic mice.

OBJECTIVE: To investigate the effect of GAPT, an extract mixture from Radix Ginseng, Rhizoma Acor tatarinowii, Radix Polygalae and Radix Curcuma (containing ingredient of turmeric), etc. on expression of tau protein and its phosphorylation related enzyme in hippocampal neurons of APPV717I transgenic mice. METHODS: Sixty three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil group [0.92 mg/(kg•d)], the low, medium and high dosage of GAPT groups [0.075, 0.15, 0.30 g/(kg•d), 12 in each group], and 12 three-month-old C57BL/6J mice were set as a normal control group, treatments were administered orally once a day respectively, and both the normal group and model group were given 0.5% sodium carboxymethyl cellulose solution. Immunohistochemistry (IHC) and Western blot analysis were used to detect the expression of total tau protein (Tau-5), cyclin-dependent kinase 5 (CDK5) and protein phosphatase 2A (PP2A) in hippocampal neurons of experimental mice after 8-month drug administration (11 months old). RESULTS: In the model group, the expression of Tau-5 and CDK5 were increased, whereas the expression of PP2A was decreased in hippocampal neurons, which were signifificantly different compared with that in the normal group (all P<0.01). IHC test indicated the number and area of either Tau-5 or CDK5 positive cells were decreased with a dose-depended way in GAPT groups, and an increase of PP2A. Compared with the model group, the changes were signifificant in GAPT groups (P<0.05 or P<0.01). Similar results were shown by Western blot. CONCLUSION: GAPT could attenuate abnormal hyperphosphorylation of tau protein in hippocampal neurons of APPV717I transgenic mice via inhibiting the expression of CDK5 and activating the expression of PP2A.

Elderly patients with acute myeloid leukemia comparative study on the clinical curative effect of Cimicifuga Biejia decoction, decitabine combined with Ara-c+ ACR+ G-CSF chemotherapy / 中国生化药物杂志

Objective To compare the clinical efficacy of shenmabiejia and decitabine combined with CAG chemotherapy regimens in elderly patients with acute myeloid leukemia, so as to provide suggestions for the treatment of elderly patients with acute myeloid leukemia.Methods120 elderly patients with acute myeloid leukemia were randomly divided into Chinese medicine group (40 cases) and Western medicine group (40 cases) and control group (40 cases).The traditional Chinese medicine group were treated with shenmabiejia combined with CAG chemotherapy regimens;the western medicine group with decitabine combined with CAG chemotherapy regimens;the control group received CAG therapy only.Clinical data, effect, ECOG score and adverse reactions were collected.ResultsCompared with control group, CR (χ2=10.131,8.020, P=0.001,0.005) and ORR (χ2=14.245,8.791, P=0.000,0.003) of Chinese medicine group and Western medicine group were higher, NR were lower than those in the control group(χ2=14.245,8.791, P=0.000,0.397).Compared with the control group, ECOG physical scores of Chinese medicine group and Western medicine group were lower (t=5.125,3.427, P=0.000,0.000).The incidence of group, pulmonary infection, fever, thrombocytopenia, nausea and vomiting, diarrhea, liver injury of traditional Chinese medicine was lower than in the control group (t=10.286,5.556,15.126,4.800,7.207,21.344, P=0.001,0.018,0.000,0.028,0.007,0.000).The incidence of pulmonary infection, fever and nausea and vomiting the probability in Western medicine group is higher than that of control group (t=11.782,8.456,4.036, P=0.000,0.004,0.045).The probability of adverse reaction of traditional Chinese medicine is lower than that of western medicine group.ConclusionShenmabiejia combined with CAG chemotherapy is superior to docetaxel combined with CAG chemotherapy for elderly patients with AML.

The effects of delayed cord clamping in preterm infants: a meta-analysis / 中国新生儿科杂志

Objective To study the short-term effects of delayed cord clamping (DCC) in preterm infants.Method A thorough search was conducted on medical databases including Cochrane Library,PubMed,Ovid,Medline,VIP citation databases,Wanfang database and CNKI.Randomized control trials (RCTs) of DCC in preterm infants were retrieved from medical literature published during January 1,2000 to January 1,2016.DCC group had cord clamping 30 ～60 s after birth,and immediate cord clamping (ICC) group had cord clamping within 30 s after birth.Methodological quality was evaluated using Cochrane Handbook for systematic reviews and RevMan 5.1 software.Meta-analysis was performed using RevMan 5.1 software.Result Seventeen RCTs were included.Meta-analysis showed that:the blood pressure within 4 hours after birth (WMD =2.49,95％ CI 0.74 ～ 4.24),the hemoglobin concentration (WMD =15.92,95 ％ CI 6.37 ～ 25.47) and the hematocrit (WMD =4.84,95 ％ CI 3.47 ～ 6.22) within 24 hours after birth in the DCC group were higher than the ICC group,P ＜0.05;the risk of anemia (RR =0.62,95％ CI 0.47 ～ 0.81),intraventricular hemorrhage (RR =0.64,95 ％ CI 0.45 ～ 0.91) and mortality (RR =0.42,95％ CI 0.20 ～0.86) in the DCC group were lower than the ICC group,P ＜0.05;there were no statistically significant differences between the two groups in peak of serum bilirubin,phototherapy duration,rate of phototherapy treatment and blood transfusion,the incidence of hyperbilirubinemia and polycythemia (P ＞ 0.05).Conclusion DCC is safe and feasible for premature infants,and can improve the outcome of premature infants.