BACKGROUND: It is discovered that trace elements in Chinese patent medicine play an important role in pharmaceutical efficacy and structural analysis. A new topic has been formed gradually in a further research on pharmaceutical efficacy and effective components of Chinese patent medicine in the view of inorganic trace elements. The fuzzy classified study on the interrelationship between trace and constant elements of Chinese herbs and therapeutic effects is to discuss the trace-element action of drugs in the holistic aspect of trace elenent and research rather scientifically the holistic coordination among trace elements in Chinese herbs.OBJECTIVE: To determine the contents of 21 kinds of trace and constant elements in Chinese patent medicines in the treatment of cardio-cerebral vascular disease. To study with fuzzy classified method the interdependence between trace, constant elements of drugs and therapeutic effects so as to provide a new approach for the quality evaluation of Chinese patent medicine.DESIGN: Testified observed study based on various Chinese patent medicines.SETTING: Chemistry teaching-research room in a university and department of cardiology in a general hospital of a chemical industrial group corporation.MATERIALS: Twenty-one kinds of common Chinese patent medicines for the treatment of cardio-cerebral vascular diseases in clinic, namely di' ao xinxuekang capsule(DXK), xueshuan xinmaining capsule(XMN), shan haidan capsule(SHD), buchang naoxintong capsule(NXT), linaoxin capsule(LNX), xinnaosu capsule(XNS), lixin wan(LXW), suxiao jiuxin wan (SJX), xinbao wan(XBW), yinxingye pian(YXY), fufang danshen pian (DSP), niuhuang jiangya wan(NHJY), naosaitong pian(NST), qiangli tianma duzhong wan ( TD W ) , tongsaimai pian ( TSM ) , tongmai ningxin infusion(TMNX), maitong capsule(MTC), fufang yinxing wan ( YXW ) , da huoluo dan(DHL), guanxin suhe capsule(GXSH) and xiaoshuan tongluo capsule (XSTL).METHODS: Wet digestion was used to manage samples, atomic absorption spectrophotometric method(AAS) method was used to determine the contents of 10 kinds of trace and constant elements in 21 Chinese patent medicines,namely Na, Ca, Mg, K, Fe, Cr, Ni, Cu, Zn and Mn. Data range method was applied for the standardized management of statistical indexes of various element contents in relevant drugs, dotprod(U, V) method was used to measure correlation coefficient(r) among the classified objects so as to determine fuzzy matrixes in universe. The interrelationship was analyzed between the contents of trace elements of various Chinese medicines and pharmaceutical efficacy. By the analysis of fuzzy matrixes in universe, it was to evaluate firmly on the efficacy similarity of various kinds of Chinese patent medicines with quantitative indexes.MAIN OUTCOME MEASURES: ① Results of element contents; ② Results of fuzzy cluster analysis on elements.RESULTS: The standardized management of statistical indexes was carried on the contents of Na, Ca, Mg, K, Fe, Cr, Ni, Cu, Zn and Mn in various drugs to determine correlation coefficient(r) among the classified objects so as to determine fuzzy matrixes in universe. When(r) = 0.55, there were 9 kinds of drugs similar in cluster, namely xueshuan xinmaining capsule, buchang naoxintong capsule, lixin wan, xin bao wan, qiangli tianmai duzhong wan,tongsaimai pian, maitong capsule, da h uoluo dan and xiaoshuan tongluo capsu le. When(r) =0. 65, there were 6 kinds of drugs similar in cluster,namely buchang naoxintong capsule, xin bao wan, qiangli tianmai duzhong wan, tongsaimai pian, maitong capsule and xiaoshuan tongluo capsule. When(r) =0. 87, there were 2 kinds of drugs similar in cluster, namely buchang naoxintong capsule and xin bao wan.CONCLUSION: It is indicated in the research that the drugs are in rich of trace and constant elements. The larger the correlation coefficient of drugs is,the more similar the pharmaceutical efficacy is. It is discovered the close interrelationship of the trace and constant elements in drugs with their pharmaceutical efficacy. In this research, fuzzy classified method is used to discuss, in the view of trace elements, the similarity of quantitative indexes in efficacy of Chinese patent medicine commonly administrated in the treatment of cardio-cerebral vascular disease, which has provided a new approach for the quality evaluation of Chinese patent medicine.

Objective: To observe the clinical efficacy of combining two needling manipulations, Er Long Xi Zhu (two dragons playing with a pearl) and Guo Yan Re (heat produced to reach the eyes), in treating dry eye syndrome (DES) of lung-yin deficiency pattern. Methods: Fifty-six eligible DES patients of lung-yin deficiency were randomized into an observation group and a control group, with 28 cases in each group. Same acupoints were selected in the two groups: Cuanzhu (BL 2), Sizhukong (TE 23), Taiyang (EX-HN 5) and Fengchi (GB 20) were chosen as the major points and Feishu (BL 13) and Chize (LU 5) as the adjuvant. Er Long Xi Zhu and Guo Yan Re needling manipulations were applied in the observation group while twirling reinforcing manipulation was used in the control group. Treatment was conducted once per day in both groups, for two sets of 15 consecutive days at a 2-day interval. Changes in the symptom score, tear break-up time (BUT) and tear production were observed afterwards, and the clinical efficacy was also compared between the two groups. Results: The total effective rate was 92.8％ in the observation group, higher than 71.4％ in the control group, and the between-group difference was statistically significant (P<0.05). After treatment, the symptom score, tear BUT and tear production showed significant improvements in both groups (all P<0.05); the symptom score, BUT and tear production in the observation group were significantly different from those in the control group (all P<0.05). Conclusion: Given the same acupoint selection, combining Er Long Xi Zhu and Guo Yan Re needling manipulations can produce more significant clinical efficacy than twirling reinforcing manipulation in treating DES of lung-yin deficiency pattern.

The method of homogeneity evaluation for active pharmaceutical ingredient (API) spatial distribution in lyophilized product was investigated for the first time with confocal micro-Raman spectroscopy mapping, using pemetrexed disodium for injection as a model drug. Certain areas of the lyophilized product were scanned to obtain Raman spectra. The classical method ("peak clipping" method) was employed for mapping with characteristic Raman peaks of the API and the excipient. Due to the API being finely dispersed in the excipient in lyophilized products, the classical method cannot discriminate between the two ingredients making the distribution homogeneity difficult to evaluate. The "ratio of characteristic peak intensities" method was then utilized. Using this method, the relative intensity of the characteristic Raman peaks of the API to the excipient was applied for mapping and the relative content of API to excipient was calculated for a homogeneity evaluation of the drug distribution. The validation of this method showed a good linear relationship between the relative intensity and the relative content of API to excipient (r² > 0.99), and the precision and recovery were adequate for homogeneity evaluation of API by Raman spectroscopy mapping. Five products of pemetrexed disodium for injection from different manufacturers were tested through Raman maps applying this method and the histograms of relative Raman intensity were also plotted by frequency to help the homogeneity evaluation of drug distribution. The results showed that there were obvious differences in the drug distribution homogeneity from different products, where a more homogeneous API distribution was found in the brand product. This research provides a reliable method for the homogeneity evaluation of API distribution, which facilitates quality evaluation and process optimization of lyophilized products.

Objective:To explore the effect of enhanced recovery after surgery(ERAS)-based multidisciplinary collaboration model on shortening the time of forbidden eating before receiving surgery, provide the basis for the selection of the preoperative diet prohibition scheme.Methods:From January 2017 to February 2019, a total of 384 patients who received the operation in Qingdao Municipal Hospital were analyzed retrospectively. The patients who under the traditional preoperative diet prohibition scheme were taken as the control group(156 cases) while those who under the multidisciplinary cooperation mode nursing under the concept of eras were taken as the experimental group(228 cases). The experimental group formulated the perioperative diet prohibition process according to the guidelines of eras, and the experimental group carried out the perioperative diet management for the patients according to the procedure. The difference between the two groups in the time of fasting, hunger, thirst incidence, insulin resistance, temporary stop will be observed and compared.Results:The time of fasting was (4.01±1.55) h in the experimental group and (10.12±1.57) h in the control group,there was significant difference between the two groups( t value was -1.65, P < 0.01). The incidences of thirst,hunger were 13.2%(30/228), 11.8%(27/228) in the experimental group and 89.7%(140/156), 87.2%(136/156) in the control group, there were significant differences between the two groups(χ 2 values were 220.20, 215.20, P < 0.01). The levels of insulin resistance on the first and third day after operation were 1.85 ± 0.43,1.52±0.61 in the experimental group and 1.99±0.51, 1.67±0.49 in the control group, the differences were statistically significant ( t values were -2.90, -2.56, P < 0.05).The temporary stop rate was 1.75%(4/228) in the experimental group and 7.69%(12/156) in the control group, the difference was statistically significant( χ2 value was 8.19, P<0.01). Conclusions:The ERAS-based multidisciplinary collaboration model can effectively shorten the preoperative fasting time, reduce the level of insulin resistance, reduce the incidence of hunger and thirst, and improve the rate of temporary stop and adjustment.

This study aimed to investigate whether β-elemene could improve the dysfunction of vascular endothelial cells induced by low shear force (LSS), and the proliferation and migration of vascular smooth muscle cells induced by oxidized low-density lipoprotein (ox-LDL). Parallel plate flow chambers and ox-LDL were used to establish vascular endothelial cells (ECs) dysfunction model and vascular smooth muscle cell (VSMCs) proliferation and migration model, respectively, and the effects of β-elemene on ECs dysfunction and VSMCs proliferation and migration were examined. The activity of ROS in ECs was measured by DHE and the activity of NO in ECs was tested by DAF-FM DA. The protein phosphorylation of Akt and ERK in ECs were detected by Western blot. The proliferation of VSMCs was measured by MTT. The migration of VSMCs was examined by cell scratch test and Transwell assay. The gene expression of MMP-2 and MMP-9 in VSMCs was measured by RT-qPCR. In ECs, β-elemene could significantly reduce the LSS-induced increase in ROS, significantly increase the LSS-induced decrease in NO, decrease the phosphorylation of ERK, and increase the phosphorylation of Akt. In VSMCs, β-elemene could significantly reduce the proliferation and migration of VSMCs induced by ox-LDL, and reduce the gene expression of MMP-2 and MMP-9. To conclude, β-elemene can improve the LSS-induced ECs dysfunction and ox-LDL-induced VSMCs proliferation and migration.

A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.
Biological Transport ; Blood-Brain Barrier ; Bornanes ; chemistry ; Cell Line, Tumor ; Dendrimers ; Doxorubicin ; pharmacology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Folic Acid ; chemistry ; Glioma ; Humans

Polymerase chain reaction was employed to amplify the whole HBV CP region from the serum of patients with chronic hepatitis B virus(HBV) infection, and then the PCR products were subcloned into pGEM Teasy vectors. Clones were randomly selected to be sequenced and the selected clones were compared to look for the difference.The sequencing results suggested that each sequence of selected clones was different and there were HBV quasispecies groups in patients. There were hot deletion region and point mutation near the TATA like box of CP gene. To address whether the mutations were responsible for the transcriptional activity, the wild type(wt) and the mutants of HBV CP genes were subcloned into pcDNA3 1( ) vectors, respectively. The reverse oriented clones were digested with KpnI and XhoI, and cloned into the KpnI and XhoI sites of the chloramphenicol acetyltransferase (CAT) expressing vector (pCAT3 basic).The recombinant CAT plasmids were transfected into HepG2 cells using lipofectamine PLUS reagent, and the CAT expression which indirectly represented the transcriptional activity of HBV CP lying upstream of CAT gene was detected with a CAT ELISA kit. The restriction enzyme digesting results indicated that the recombinant CAT plasmids were successfully constructed, and the transfection tests indicated that the transcriptional activity of the mutants with deletion or substitute point mutation of TATA like box were reduced in comparison with that of CPwt. The HBV CP gene heterogeneity downregulated the transcriptional activity to some extent.

Objective To observe changes of erythropoietin (EPO) and rheology in moderate and severe obstructive sleep apnea hypopnea syndrome (OSAHS) patients after the noninvasive positive pressure ventilation (NPPV) treatment. Methods Healthy adults were selected as control group (n=40) while moderate to severe OSAHS patients were selected as OSAHS group. OSAHS group was underwent NPPV treatment then, Levels of sleep apnea hypopnea index (AHI), sleep mean minimum oxygen saturation (LSaO2) and serum erythropoietin (EPO) were assessed, routine blood test and hemodynam-ic indexes were also checked before treatment and 1 and 3 months after treatment in both groups. Results In both groups serum EPO, blood, blood rheology indexes, AHI, LSaO2 were analysised at each time point by ANOVA repeated measures, all of which show significant different between groups and between each time points within the same group. Indexes in OSAHS group improved with prolonged treatment , but they are in the normal range in the control. Conclusion OSAHS pa-tients with NPPV therapy can significantly relieve hypoxia, reduce serum EPO level and blood viscosity. So NPPV has impor-tant clinical significance in prevention and treatment of OSAHS.

Objective:To determine the derivative chromosome 9 by the method of detecting the ASS gene,and to explore the relationship between the deletion of derivative chromosome 9 and the efficacy and prognosis of the chronic myeloid leukemia (CML)patients. Methods:The materials of 34 CML patients with positive BCR-ABL fusion gene whose ASS genes were detected were retrospectively analyzed. All patients were treated with Extra-signal (ES)probe to detect the derivative chromosome 9.All patients were divided into two groups according to whether they carried the derivative chromosome 9.The blastic phase or the accelerated phase rates in two groups were compared by using Fisher exact probability. Results:All patients were detected by FISH (BCR-ABL ES probe),and all the BCR-ABL fusion signals were positive.6 of 34 patients were found the deletion of ASS gene, among them 1 case blonged to chronic phase,and 5 cases developed into blastic phase or accelerated phase. In the patients without ASS gene deletion,there were 22 cases in chronic phase,and 6 cases in plastic phase or accelerate phase,there was significant difference of blastic phase rate/accelated phase rate between them (P<0.05).A total of 26 patients were treated with tyrosine kinase inhibitors (TKI).5 of 26 patients belonged to the ASS gene deletion group,1 of 5 patients treated with TKI got molecular remission,4 of 5 patients developed into blastic phase or accelerated phase.21 of 26 patients belonged to the group without ASS gene deletion,and among them,19 cases got molecular remission,2 cases developed into plastic phase or accelerated phase after treatment of TKI,there was significant difference between them (P < 0.05 ). 6 patients were treated with traditional chemotherapy (hydroxyurea,interferon);1 of 6 patients belonged to the ASS gene deletion group,finally developed into the blastic phase or accelerated phase;5 of 6 patients belonged to the group without ASS gene deletion,2 cases got the hematological remission,and 3 patients developed into blastic phase or accelerated phase after treatment,and there was no significant difference of blastic phase rate/ accelerated phase rate between them (P > 0.05 ). Conclusion:The CML patients with derivative chromosome 9 (ASS gene deletion)prone to get disease progression, and have a higher proportion in the blastic phase or accelerated phase patients.Derivative chromosome 9 is related to the bad treatment efficacy of TKI and the poor prognosis of CML.

Objective To clarify the inhibitory effect of low molecular weight chitosan(LMCTS)on hepatic fibrosis induced by carbon tetrachloride (CCl4 )in the rats, and to investigate its effect on the expression of Toll-like receptor-4(TLR4 )and to lay the foundation for the development of the clinical candidate drug of liver fibrosis. Methods 72 male Wistar rats were randomly divided into blank control group, CCl4 group (model group), glycyrrhizinate (DG)group,50,100 and 150 mg·kg-1 LMCTS groups (low,middle and high doses of LMCTS groups).In addition to blank control group,the rats in the remaining groups were given 40% CCl4-vegetable oil (1.75 mL·kg-1 ),2 times per week for 8 weeks,by intraperitoneal injection to establish the model of rat hepatic fibrosis.And the rats in blank control group were injected with the same amount of 100% vegetable oil agent. From the ninth week, the rats in DG and LMCTS groups were given DG and LMCTS by intragastric administration, 1 time/week for 4 weeks. Then all rats were sacrificed, the activities of serum glutamic acid aminotransferase (ALT),aspartate aminotransferase (AST)and alkaline phosphatase (ALP)were detected with ELISA kit;the pathological changes in liver tissue were observed under light microscope, and the TLR4 expressions were detected by RT-PCR and Western blotting method. Results The serum ALT, AST and ALP activities in middle and high doses of LMCTS groups were lower than those in model group (P<0.05).The serum ALT activity in middle dose of LMCTS group was lower than that in low dose of LMCTS group (P<0.05),but the activities of AST and ALP had no statistically significant change(P>0.05).There were statistically significant differences in the serum ALT, AST and ALP activities between high dose of LMCTS group and middle dose of LMCTS group (P<0.05).There were obvious hepatocyte steatosis,inflammatory cell infiltration,collagen fiber hyperplasia and hepatic lobule damage in the rats in model group.However,all the changes in liver tissue of the rats in LMCTS group were significantly reduced, especially in high dose group. The results of RT-PCR and Western blotting method showed that the expression of TLR4 was declined in LMCTS groups compared with model group (P<0.05,P<0.01),especially in high dose of LMCTS group,and there were statistically significant differences between different doses of LMCTS groups (P<0.05).Conclusion High dose of LMCTS can decrease the serum transaminase activity of liver fibrosis rats and improve liver function,and this process may be related to declining the expression of TLR4 .