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OBJECTIVE To re-eval uate the systematic review and meta-an alysis of umeclidinium bromide and vilanterol trifenatate（UMEC/VIL）in the treatment of chronic obstructive pulmonary disease （COPD），so as to provide evidence-based basis for the treatment of COPD. METHODS Retrieved from PubMed （Medline），the Cochrane library ，Embase，CNKI，CBM，VIP and Wanfang database ，etc.，the systematic review and meta-analysis of UMEC/VIL in the treatment of COPD were collected from the inception to Apr. 2021. Two reviewers independently screened the literatures and extracted the data. AMSTAR 2 scale，PRISMA statement，and GRADE evaluation system were used to evaluate the methodological quality of the included studies ，the quality of reports and the grade of outcome indexes. The efficacy and safety of UMEC/VIL in the treatment of COPD were reported. RESULTS Six systematic reviews were finally included. The results of AMSTAR 2 scale showed that 1 study was of high quality ， 2 were of medium quality and 3 were of low quality. The score of PRISMA statement was between 21.5 and 27，and the quality of the report was relatively perfect. The results of GRADE evaluation showed that more than 60％ of the 134 outcome indicators were of medium to high quality of evidence. Comparison of effectiveness and safety showed that UMEC/VIL was superior to placebo ， unilateral bronchodilator and salmeterol fluticasone in improving forced expiratory volume in one second （FEV1）trough，FEV1 peak and forced vital capacity （FVC）. In the improvement of transition dyspnea index （TDI），SGRQ and SOBDA scores ，UMEC/ VIL was better than placebo ，unilateral bronchodilator and fluticasone propionate/salme terol. The adverse reaction rate ，acute exacerbation rate ，mortality rate ，withdrawal rate ，pneumonia rate and other negative indicators of UMEC/VIL were not inferior to placebo，unilateral bronchodilator and fluticasone propionate/salme terol. CONCLUSIONS Compared with placebo and unilateral bronchodilator，UMEC/VIL can significantly improve lung function ，symptoms and quality of life ，and has non-inferior effect for negative indicators. Compared with β2 adrenoceptor agonists combined with glucocorticoid ，UMEC/VIL can improve lung function of COPD patients ，but they are similar in other aspects.
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Objective:To understand the correlation between urinary iodine, salt iodine and thyroid nodules in children aged 8 - 10 years and pregnant women in different regions of Fujian Province, and to explore the influencing factors of thyroid diseases.Methods:A cross-sectional study was conducted in Dongshan County and Pingtan County of Fujian Province from September to November 2019. According to the inclusion criteria, 140 pregnant women and 270 children aged 8 - 10 years were selected in Dongshan County, and 189 pregnant women and 368 children aged 8 - 10 years were selected in Pingtan County. Random urine and edible salt samples were collected to determine iodine content, and iodine nutrition was evaluated in each population. Thyroid was examined by B ultrasound and questionnaire survey of thyroid diseases was carried out. The correlation between urinary iodine, salt iodine and thyroid nodules in children aged 8 - 10 years and pregnant women in different regions was analyzed.Results:There were statistically significant differences in the median urinary iodine among children in different genders (male: 151.30 μg/L, female: 130.30 μg/L) and regions (Dongshan County: 160.30 μg/L, Pingtan County: 129.70 μg/L, P < 0.05); there was no significant difference in the median urinary iodine among children of different ages (8, 9, 10 years old: 141.60, 128.05, 150.30 μg/L, P > 0.05). The median urinary iodine among pregnant women was 119.30 μg/L, and there was no significant difference in median urinary iodine among pregnant women in different stages and regions ( P > 0.05). The medians of salt iodine from children and pregnant women were 20.30 and 23.65 mg/kg, respectively. Urinary iodine in children was positively correlated with salt iodine ( r = 0.13, P < 0.05). However, there was no correlation between urinary iodine and salt iodine in pregnant women ( P > 0.05). The detection rate of thyroid nodules in children was 21.79% (139/638). There was significant difference in the detection rate of thyroid nodules in children of different ages ( P < 0.05). The detection rate of thyroid nodules in pregnant women was 4.26% (14/329). There was no correlation between detection rate of thyroid nodules and urinary iodine or salt iodine in children and pregnant women ( P > 0.05). Thyroid volume of children in the two counties was within the normal range, and there was no correlation between thyroid volume and urinary iodine or salt iodine ( P > 0.05). Conclusions:The iodine nutrition of children in Dongshan County and Pingtan County is suitable (100 - 199 μg/L), while iodine deficiency (< 150 μg/L) exists in pregnant women. Urinary iodine in children is related to salt iodine, and urinary iodine increased with increase of salt iodine. The prevalence of thyroid nodules in children of different ages is different, which requires further study. The detection rate of thyroid nodules in children and pregnant women is not correlated with urinary iodine and salt iodine.
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In this study, nrDNA ITS sequences of Lycium cultivars were sequenced and used to test the existence of incomplete concerted evolution and pseudogenes. Together with 44 ITS sequences retrieved from GenBank, the pattern of base substitutions, GC content, 5.8S conserved motifs, the minimum free energy of secondary structures, nucleotide diversity and phylogenetic relationship of the samples were analyzed. While 83 of the 144 sequences were identified as pseudogenes, the results suggested a high degree of polymorphism and putative pseudogenes in Lycium, suggesting an incomplete concerted evolution of the ITS region. ITS polymorphism and pseudogene of Lycium were systematically tested for the first time. This research provides a references for ITS sequence to be used in the study of Lycium germplasm resources and DNA barcode identification.
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ObjectiveTo investigate the effect and mechanism of Mori Folium extract on the glucose and lipid metabolism disorders in the liver of rats with type 2 diabetes mellitus （T2DM） through the phosphatidylinositol 3-kinase/protein kinase B/peroxisome proliferation-activated receptor α/carnitine palmitoyl transferase-1 （PI3K/Akt/PPARα/CPT-1） signaling pathway. MethodThe T2DM model was induced by the high-fat diet combined with the intraperitoneal injection of streptozotocin （STZ）. The model rats were randomly divided into a model group， a metformin （0.2 g·kg-1） group， and a Mori Folium water extract （4.0 g·kg-1） group according to blood glucose and body weight. In the 8-week administration， fasting blood glucose was measured at the same time every week. The histomorphological and fat changes in the rat liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum were measured by biochemical methods. Western blot （WB） was used to quantitatively detect the protein expression of p-PI3K，PI3K，p-Akt，Akt，PPARα，and CPT-1 in the rat liver. ResultAfter 8-week administration， the blood glucose of rats was higher in the model group than that in the control group （P<0.01）， and lower in the Mori Folium water extract group than that in the model group （P<0.01）. The results of HE staining showed that the liver tissue structure of the control group was complete， and the hepatocytes were arranged radially around the central vein， while the hepatocyte injury in the model group was obvious. Compared with the model group， the Mori Folium water extract group showed improved vacuolar degeneration and no lesions such as small bile duct hyperplasia. Oil red O staining showed that there was no obvious steatosis and necrosis in the hepatocytes of rats in the control group， and no lipid droplets in the hepatocytes were observed， while the model group showed increased lipid droplets. Mori Folium significantly reduced the lipid droplets in the liver. Biochemical analysis showed that the levels of TC， TG， LDL-C， AST， and ALT in the model group were significantly higher than those in control group （P<0.01）. The levels of TC， TG， LDL-C， AST， and ALT in the Mori Folium water extract group were significantly lower than those in the model group （P<0.05，P<0.01）. WB showed that the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 in the model group were lower than those in the control group （P<0.01）. Mori Folium water extract could increase the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 （P<0.05 or P<0.01）. ConclusionThe hypoglycemic mechanism of Mori Folium water extract may be related to the regulation of the PI3K/Akt/PPARα/CPT-1 signaling pathway.
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ObjectiveTo study the possible molecular mechanism of baicalein （BAI）-mediated focal adhesion kinase （FAK） in the regulation of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to inhibit the proliferation and migration of gastric cancer HGC-27 cells. MethodThe gastric epithelial GES-1 cells and gastric cancer HGC-27 cells were respectively treated with BAI （0， 5， 15， 25， and 50 μmol·L-1） for 48 h， and then methyl thiazolyl tetrazolium （MTT） assay was adopted to detect effect of BAI on cell proliferation. Western blot （WB） was employed to detect the expression of FAK and the proteins related to epithelial-mesenchymal transition （EMT） and PI3K signaling pathway after intervention with different concentrations of BAI. The HGC-27 cells stably overexpressing FAK were constructed with lentivirus-mediated transfection technique， and the transfection of FAK was detected through WB and green fluorescent protein （GFP）. The cells were divided into empty vector （NC） group， BAI group， FAK overexpression group， and BAI-treated FAK overexpression group， and cell proliferation activity was detected by MTT assay. The colony formation and cell migration were observed via colony formation assay and Transwell migration assay， respectively. The expression of proteins involved in EMT and PI3K signaling pathways were detected by Western blot. ResultCompared with the NC group， BAI （15， 25 and 50 μmol·L-1） inhibited the proliferation of HGC-27 cells in a dose-dependent manner （P<0.05， P<0.01） while did not affect that of GES-1 cells. BAI （5， 15 and 25 μmol·L-1） down-regulated the expression level of p-FAK （P<0.05， P<0.01）. Compared with NC group， FAK overexpression group showed up-regulated expression level of FAK in HGC-27 cells. The HGC-27 cells in both NC group and FAK overexpression group had green fluorescence. Compared with NC group， BAI inhibited the growth， colony formation， and migration， while FAK overexpression promoted those of HGC-27 cells. The treatment of FAK overexpression group with BAI inhibited the enhancement of cell proliferation and migration （P<0.05）. WB showed that compared with NC group， BAI （15， 25 μmol·L-1） significantly up-regulated the expression of E-cadherin protein and down-regulated that of Vimentin， Snail， p-PI3K， and p-Akt protein in HGC-27 cells （P<0.05， P<0.01）. Compared with NC group， FAK overexpression group showed down-regulated expression of E-cadherin， up-regulated expression of p-FAK， Vimentin， and Snail， and increased ratios of p-FAK/FAK， p-PI3K/PI3K and p-Akt/Akt （P<0.05）. This phenomenon would be reversed after BAI treatment. ConclusionBAI can affect the proliferation and migration of gastric cancer HGC-27 cells by mediating FAK to regulate PI3K/Akt signaling pathway.
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Objective:To investigate the effects of ligustrazine combined with emodin on angiogenesis of ascites carcinoma Walker-256 cells by observing their inhibition against nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）， hypoxia-inducible factor-1<italic>α</italic> （HIF-1<italic>α</italic>）， and vascular endothelial growth factor-C （VEGF-C） in HIF signaling pathway. Method:Fifty SD rats were randomly divided into sham operation group， model group， ligustrazine group， emodin group and ligustrazine combined with emodin group. Following the in situ injection of rat ascites carcinoma Walker-256 cells into the liver of normal rats， they were grouped and administered with ligustrazine （10 mg·kg<sup>-1</sup>）， emodin （10 mg·kg<sup>-1</sup>）， and ligustrazine （10 mg·kg<sup>-1</sup>） plus emodin （10 mg·kg<sup>-1</sup>） for seven days. Afterwards， the tumor-inoculated liver tissue was sampled from the experimental group and prepared into pathological sections for investigating tumor cell survival and VEGF expression. The <italic>in vitro</italic> hypoxia and hypoglycemia model （oxygen-glucose deprivation model）， hypoxia model， and hypoglycemia model of Walker-256 cells were constructed respectively. In the ligustrazine group， emodin group， and ligustrazine combined with emodin group， three consecutive concentrations that did not affect the proliferation of Walker-256 cells were selected for investigation. The drugs were administered before modeling， and the model treatment lasted for 4 h. The levels of HIF-1<italic>α</italic>， VEGF-C， and NF-<italic>κ</italic>B in the cell culture supernatant of each group were tested. Result:After the rat liver was inoculated with Walker-256 cells， the total liver mass was significantly increased（<italic>P</italic><0.05）， higher than that in the ligustrazine group， the emodin group， or the ligustrazine combined with emodin group（<italic>P</italic><0.05）. Histopathological examination showed that the response of VEGF expression in the liver tissue of each administration group was lower than that of the model group. At the cellular level， the levels of HIF-1<italic>α</italic>， VEGF-C， and NF-<italic>κ</italic>B in oxygen-glucose deprivation model of the ligustrazine group and the ligustrazine combined with emodin group were significantly reduced（<italic>P</italic><0.05）， exhibiting a certain dose-dependent response， followed by the reduction in the hypoxia model. The levels of HIF-1<italic>α</italic> and NF-<italic>κ</italic>B in the oxygen-glucose deprivation model and the hypoglycemia model of the emodin（1×10<sup>-2</sup>，1×10<sup>-3</sup> mol·L<sup>-1</sup>） group and the ligustrazine combined with emodin（1×10<sup>-2</sup>，1×10<sup>-3</sup> mol·L<sup>-1</sup>） group were significantly reduced， but there was no significant change in VEGF-C level of the hypoxia model of all the administration groups. Conclusion:Ligustrazine or emodin alone or their combination inhibits the abnormal increase in the weight of rat liver after inoculation with Walker-256 cells and the expression of VEGF in the liver tissue. Ligustrazine and emodin inhibit the protein expression of NF-<italic>κ</italic>B and HIF-1<italic>α</italic>， thereby reducing the gene and protein expression of metastasis-related target VEGF-A activated by HIF-1<italic>α</italic> transcription， restricting tumor cell neovascularization， and inhibiting the invasion and spread of ascites carcinoma cells. Among them， ligustrazine has the most significant effect against hypoxia. Glucose interferes with the effect of ligustrazine. The combination of ligustrazine with emodin is conducive to diminishing the intervention of glucose and stabilizing the inhibition against tumor cells.
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Objective:To understand the epidemic situation of drinking-water-borne endemic fluorosis in Fujian Province, and to provide more information for control and evaluation of the disease.Methods:In 2019, all villages in the 36 drinking-water-borne endemic fluorosis areas in Fujian Province were selected, in which the situation of water improvement was investigated, fluorine content of drinking water was tested and dental fluorosis of all the children aged 8 to 12 was examined. The urinary fluoride content and skeletal fluorosis of people over 25-year old was investigated in some of those villages.Results:A total of 153 disease affected villages were investigated, in which the water improvement projects were all completed. The fluoride content in each tap water sample of the water improvement project ranged from 0.00 to 1.05 mg/L, and the qualified rate was 100.00% (153/153). The normal operation rate of the water improvement projects was 95.42% (146/153). The detection rate of dental fluorosis in children aged 8 to 12 was 2.72% (76/2 789) with a dental fluorosis index 0.07. The detection rate of children's dental fluorosis was statistically different in different age groups, so was it in areas with different coverage rate of water improvement projects ( P < 0.05). The geometric mean of urinary fluorine level in adults was 0.80 mg/L ( n = 3 765), and the detection rate of skeletal fluorosis was 2.00% (6/300). Conclusion:Although some achievements have been made in the prevention and control of drinking-water-borne endemic fluorosis in Fujian Province, it is still necessary to further consolidate and enhance the water improvement projects.
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Autophagy represents one of the essential cellular mechanism to maintain homeostasis within cells, performing multiple biological functions during tumorigenesis. Base on the unique physicochemical properties of inorganic nanomaterials, supplemented by easy modification and targeting and so on, they could be used to regulate autophagy, controlling the occurrence and development of tumor and finally achieve treatment. This article primarily reviews the application of several representative inorganic nanomaterials, such as Gold nanoparticles, Silver nanoparticles, Iron oxide nanoparticles, Fullerene C60 nanomaterials, Graphene oxide nanomaterials in regulating autophagy of tumor cells and achieving treatment in recent years.
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Objective:To investigate the role of miRNA-181 targeting phosphatase and tensin homologue deleted on chromosome ten (PTEN) in regulating phosphatidylinositol-3-kinase/Akt signaling pathway (PI3K/Akt) signaling pathway in renal injury of hyperuricemia rats.Methods:Forty male Wistar rats were randomly divided into control group, model group, negative control group and miRNA-181 inhibition group. Their serum uric acid, creatinine and urea nitrogen were tested. HE staining was used to observe the renal histopathological changes in each group. The expression of miRNA-181, PTEN, PI3K and Akt mRNA in renal tissue of rats in each group was detected by quantitative real time-polymerase chain reaction (qRT-PCR). Western blotting analysis of PTEN, PI3K, Akt and p-Akt protein expression in renal tissue of rats in each group. The targeting relationship between miRNA-181 and PTEN was confirmed by double luciferase reporter gene experiment. One-way analysis of variance (ANOVA) was used for the comparison between multiple groups, with the same variance. LSD- t test was used for further comparison between the two groups. If the variance was not the same, Tamhane's T2 test was used for further comparison between the two groups. Independent sample t-test was used to compare between the two groups. Results:Compared with the control group (135±21) mmol/L; (27.8±2.1) μmol/L; (6.8±0.5) μmol/L, the contents of uric acid [(213±28) mmol/L, (214±23) mmol/L, creatinine (49.2±2.3) μmol/L, (48.6±2.2) μmol/L and urea nitrogen (11.5±2.7) μmol/L; (11.7±2.5) μmol/L] in the model group and the negative control group were significantly increased ( Furic acid=26.739, Fcreatinine=259.055, Furea nitrogen=12.921, all P<0.05); compared with the nega-tive control group, the contents of uric acid (169±21) mmol/L, creatinine (33.7±1.8) μmol/L and urea nitrogen (9.1±1.7) μmol/L in the miRNA-181 inhibition group were decreased (LSD- turic acid=4.356, LSD- tcreatinine=15.773, LSD- turea nitrogen=2.858, all P<0.05). The expression level of miRNA-181 in renal tissue of the model group and the negative control group (1.88±0.16, 1.84±0.18) was significantly higher than that of the control group (0.53±0.08) ( F=193.554, P<0.05), while the expression level of PTEN protein (0.18±0.02, 0.16±0.02) and mRNA (0.48±0.08, 0.44±0.07) were lower than that of the control group (1.27±0.06, 1.27±0.16) ( Fprotein=515.116, FmRNA=141.470, all P<0.05) ); after inhibiting miRNA-181, the expression level of miRNA-181 (1.35±0.58) in renal tissue increased significantly (LSD- t=10.341, P<0.05), and the expression level of PTEN protein (0.84±0.05) and mRNA (0.90±0.08) increased on average (LSD- tprotein=20.471, Tamhane's T2 mRNA=13.881, all P<0.05). The results of double luciferase reporter gene analysis showed that PTEN was the target gene of miRNA-181. Compared with the control group (0.18±0.02, 0.09±0.01, 0.05±0.02, 1.06±0.07, 0.96±0.06), the expression level of PI3K (1.01±0.06, 1.00±0.06), Akt (0.90±0.05, 0.95±0.04), p-Akt protein (0.99±0.07, 0.97±0.05) and the expression level of PI3K (3.63±0.18, 3.68±0.22), Akt mRNA (2.38±0.05, 2.34±0.12) in the renal tissue of the model group and the negative control group were significantly increased ( FPI3K protein=169.979, FAkt protein=393.411, Fp-Akt protein=164.201, FPI3K mRNA=563.944, FAkt mRNA=141.470, all P<0.05); after inhibiting the expression of miRNA-181, the expression level of PI3K (0.69±0.06), Akt (0.42±0.03), p-Akt protein (0.50±0.05) and the expression level of PI3K (2.40±0.09), Akt mRNA (1.40±0.12) in the renal tissue of the rats were decreased (LSD- tPI3K protein=7.432, LSD- tAkt protein=18.291, LSD- tp-Akt protein=9.595, Tamhane's T2 PI3K mRNA=17.070, Tamhane's T2 Akt mRNA=17.357, all P<0.05). Conclusion:Inhibition of miRNA-181 expression can target PTEN to inhibit PI3K / Akt signaling pathway to protect renal injury in hyperuricemia rats.
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Objective:To analyze the epidemiological and clinical characteristics of hand-feet-mouth disease (HFMD).Methods:The clinical and pathogenic data of 1 976 cases with HFMD hospitalized in Public Health Clinical Center of Chengdu from August 2018 to September 2019 were retrospective analyzed.Results:Among the 1 976 cases of HFMD, 1 094 cases (55.36%) were one to two years old, and 803 cases (40.64%) lived in the main urban area. The majority were scattered patients (1 344 cases, 68.02%). There were 1 348(72.7%) of 1 854 cases mainly infected by Coxsackie virus 6 (CV-A6). The main distribution of rashes in children infected by CV-A6 were palm/soles, trunks, limbs, oral ulcer and perioral areal, lips and hip. The types of rash were maculopapule, vesicle, and bulla. Fever (1 543 cases, 78.09%) was the main concomitant symptom. Acute tonsillitis (811 cases, 41.04%), myocardial injury (767 cases, 38.82%), and herpetic angina (658 cases, 33.30%) were the most common complications. The incidence of onychomadesis were nine (7.03%) among the 128 patients during follow-up.Conclusions:CV-A6 is the main pathogen of the HFMD prevalence. Children less than two years old are susceptible and the main symptoms of HFMD are rash and fever.
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Objective:To analyze the disease burden of iodine deficiency disorders (IDD) and its changes in China in 1990 and 2016.Methods:Based on the data of Global Burden of Disease Study 2016 (GBD 2016), a descriptive statistical method was used to compare and analyze the changes of deaths number, mortality, disability adjusted life year [DALY, including years of life lost (YLL) and years lived with disability (YLD)], DALY rate and other disease burden indicators caused by IDD in China in 1990 and 2016.Results:The GBD 2016 data showed that the deaths number from IDD in China decreased from 259.31 in 1990 to 116.41 in 2016, the mortality decreased from 0.022 827/100 000 in 1990 to 0.008 515/100 000 in 2016; and the mortality in different age groups had decreased, the children mortality in the < 5 years old group had decreased from 0.088 639/100 000 to 0.009 875/100 000. The DALY and YLD due to IDD in China increased from 406.13 thousand person-years and 391.68 thousand person-years in 1990 to 455.05 thousand person-years and 451.95 thousand person-years in 2016, while YLL decreased from 14.45 thousand person-years to 3.10 thousand person-years; the DALY rate, YLL rate, and YLD rate decreased from 35.75 person-years per 100 000, 1.27 person-years per 100 000 and 34.48 person-years per 100 000 in 1990 to 33.29 person-years per 100 000, 0.23 person-years per 100 000 and 33.06 person-years per 100 000 in 2016. The main component of DALY for IDD was YLD, and the proportion increased from 96.44% in 1990 to 99.32% in 2016.Conclusions:The mortality of IDD in China has decreased, and IDD in the younger age group has been effectively controlled; however, the disease burden, especially the burden caused by disability has increased, and the disability of the population due to IDD should be given special attention.
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Objective::To explore the efficacy of modified Jingui Shenqitang in the treatment of renal hypertension with spleen-kidney yang deficiency syndrome and its effect on blood lipids, renal function and vascular endothelial function. Method::Totally 110 patients were randomly divided into control group and observation group by random number table method, with 55 cases in each group. Control group was given levamlodipine (2.5-5 mg every time, once/day) and enalapril maleate (10 mg every time, once/day), and observation group was given modified Jingui Shenqitang in addition to the therapy of control group (1 dose/day). They were treated for 12 weeks. Blood pressure monitoring was performed, the systolic blood pressure (SBD) and diastolic blood pressure (DBP) were compared before and after treatment, and the blood pressure compliance was calculated. The 24 h urinary protein quantification (24 hUpr), serum creatinine (SCr), albumin (ALB) and urea nitrogen (BUN) were detected before and after treatment, the glomerular filtration rate (eGFR) was calculated, and the triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HLD-C) and low-density lipoprotein( LDL-C) were detected before and after treatment. The spleen-kidney Yang deficiency syndromes were scored before and after treatment. The levels of nitric oxide (NO), plasma endothelin (ET) and angiotensin Ⅱ (Ang Ⅱ) were detected before and after treatment. Result::The blood pressure efficacy in observation group was better than that in control group (Z=1.905, P<0.05). The efficacy of traditional Chinese medicine(TCM) syndromes in observation group was better than that in control group (Z=2.416, P<0.01). The compliance rate of causal blood pressure in observation group was higher than that in control group (88.89% vs 71.25%) (χ2=7.861, P<0.01). SBP and DBP in observation group were lower than those in control group (P<0.05). TC and LDL-C in observation group were lower than those in control group (P<0.01). The 24 hUpr, BUN and SCr in observation group were lower than those in control group (P<0.05), while the eGFR was higher than that in control group (P<0.05). The levels of ET-1 and Ang Ⅱ in observation group were lower than those in control group (P<0.05), whereas the NO level was higher than that in control group (P<0.01). Conclusion::In addition to the routine intervention with western medicine, modified Jingui Shenqitang for patients with spleen-kidney Yang deficiency syndrome can further control blood pressure level, improve blood pressure compliance rate, regulate lipid metabolism, protect kidney function, and regulate vascular endothelial function, with a better clinical efficacy than pure western medicine.
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Chuanxiong Qingfengteng mixture (CQM) is an analgesic developed based on clinical evidence and traditional Chinese medicine theory, which majorly consists of Ligusticum chuanxiong and Sinomenium acutum extracts. The current study aims to establish an UHPLC-UV method for the quantification of sinomenine and ligustrazine after CQM administration to rats, mice and cells, and to study the brain permeability of sinomenine and ligustrazine. The selectivity, linearity, accuracy, precision and stability of the established method demonstrated that it was suitable for the determination of sinomenine and ligustrazine in biological samples such as plasma, brain tissue and cellular fluid. After CQM was intravenously administered to rats and mice, both sinomenine and ligustrazine were detected in the brain from 5 min-2 h. The CSF/plasma partition coefficients (Kp, C/P) of each component were higher than those of brain tissue/plasma partition coefficient (Kp, B/P), the Kp, C/P and Kp, B/P of ligustrazine were higher than those of sinomenine. The concentrations between CSF and brain tissue were strongly correlated (Pearson's R>0.86, P<0.001). The unbound fraction in plasma of sinomenine and ligustrazine was 78.92% and 34.07%, respectively. The plasma protein binding rates displayed concentration-independent behavior within their respective in vivo concentration ranges. After CQM co-cultured with Caco-2 cell monolayers, the apparent permeability coefficient (Papp) of sinomenine and ligustrazine were 1.30×10-6 and 3.64×10-6 cm·s-1, respectively, following into the range of the intermediate and high permeability compounds. The efflux ratio (Papp(basolateral→apical)/Papp(apical→basolateral)) of sinomenine and ligustrazine were 0.67 and 0.85, respectively. When combined with P-glycoprotein inhibitor, the Papp of each component did not increase. In conclusion, the UHPLC-UV assay was successfully applied for the brain permeability study of CQM, the components of CQM can be quickly distributed to cerebrospinal fluid and pass through the blood-brain barrier. The brain permeability of ligustrazine is higher than that of sinomenine. The transmembrane transport of sinomenine and ligustrazine may not be affected by efflux transporters. All animal care and use complied with the Regulations for the Administration of Affairs Concerning Experimental Animals approved by the State Council of the People's Republic of China. All animal studies were implemented according to protocols, which were reviewed and approved by the Institutional Animal Care and Use Committee at Experimental Research Center, China Academy of Chinese Medical Sciences.
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Objective To validate a developing method for determination of iodine in serum by inductively coupled plasma mass spectrometry (ICP-MS).Methods Ammonium chloride,ethanolamine,ascorbic acid and water were mixed at a certain ratio,adding ethanol as sensitization,to dilute samples in the ratio of 1 ∶ 20,and then the diluted samples were analyzed by ICP-MS.Re was used as the internal standard.Serum samples were from 8 different individuals.After combining,they were divided into 4 groups,control group and low,medium and high iodine groups.Iodine groups were added with potassium iodide (100 mg/L),iodine standard solution 1.5,9.0,15.0 μl.The methodological evaluation of this method was done through standard curve linearity,sample detection limit,precision,recovery and accuracy in determining biological sample.And the results were compared with the current serum iodine arsenic cerium catalytic spectrophotometry standard method (WS/T 572-2017).Results The linear range of the calibration curve was 0-300 μg/L and the linear correlative coefficients of the standard curve were 0.999 8-1.000 0.The detection limit was 0.38 μg/L (the sample amount was 0.2 ml).The coefficients of variation (CV) were all below 2％ for 4 serum samples in precision.The recovery rate was in a range of 95.8％-108.5％.No significant difference was found between the results of the 15 serum samples determined by the standard method andthis new method (t =1.139,P ＞ 0.05).Conclusions The newly developed method in determination of iodine in serum by ICP-MS,has wide linear range,high sensitivity,good precision,and wide applicability.It is suitable for application in determining serum iodine.
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The therapeutic application of artemisinin (ART) is restricted in application due to its poor water solubility and stability. In this study, the long-circulating liposomes (L-Lip) were constructed to improve the solubility and stability of ART. The preparation method, physicochemical properties, serum stability, in vitro release profile and cytotoxicity of the ART loaded long-circulating liposomes were investigated. Using the particle size and entrapment efficiency (EE) as the evaluation index, the preparation procedure was optimized by the Box-Behnken response surface design based on the single factor screening method. The ART loaded long-circulating liposomes were prepared by filming rehydration method, and evaluated with particle size and entrapment efficiency. The optimal formulation was as follows:lipid-cholesterol=5.22:1 (mass ratio), drug-lipid=1:23.15 (mass ratio), lipid concentration=14.35 mg·mL-1, and molar percentage of mPEG=2%. The morphology of L-Lip was uniformly spherical shape according to optimal formulation. The mean size and polydispersity index (PDI) were about (113.3 ±4.7) nm and 0.227 ±0.022 respectively, the zeta potential was (-12.9 ±2.6) mV, and the entrapment efficiency (EE) of ART was (95.88 ±4.8)%. The L-Lip had good stability at 4℃ for 15 days and the particle sizes did not exhibit significant variations in 50% rat plasma over 24 h at 37℃. The in vitro release study of formulation showed a sustained release. Moreover, the cytotoxicity exhibited that blank liposomes were of great safety. Compared with the free ART, the liposome formulation achieved lower cytotoxicity at the high concentration. The L-Lip successfully prepared by a simple filming-rehydration method exhibited ideal physicochemical properties and were enhanced safety, which may sever as a promising nanoplatform for clinical application.
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The therapeutic application of deoxypodophyllotoxin (DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers (mPEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg mPEG-PDLLA, the weight ratio of 1 : 4 (mPEG-PDLLA : DPT), 30 mL hydration volume and the hydration temperature at 40 °C. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles (DPT-PM) were about (20 ± 2.84)% and (98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10 mol·L, which showed significant difference from free DPT (P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.
Subject(s)
Humans , Antineoplastic Agents , Chemistry , Toxicity , Cell Survival , Drug Carriers , Chemistry , Drug Delivery Systems , Methods , Drug Design , HeLa Cells , Micelles , Particle Size , Podophyllotoxin , Chemistry , Toxicity , Polyesters , Chemistry , Polyethylene Glycols , Chemistry , Solubility , Surface PropertiesABSTRACT
The therapeutic application of deoxypodophyllotoxin (DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers (mPEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg mPEG-PDLLA, the weight ratio of 1 : 4 (mPEG-PDLLA : DPT), 30 mL hydration volume and the hydration temperature at 40 °C. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles (DPT-PM) were about (20 ± 2.84)% and (98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10 mol·L, which showed significant difference from free DPT (P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.
Subject(s)
Humans , Antineoplastic Agents , Chemistry , Toxicity , Cell Survival , Drug Carriers , Chemistry , Drug Delivery Systems , Methods , Drug Design , HeLa Cells , Micelles , Particle Size , Podophyllotoxin , Chemistry , Toxicity , Polyesters , Chemistry , Polyethylene Glycols , Chemistry , Solubility , Surface PropertiesABSTRACT
<p><b>OBJECTIVE</b>To compare the effects of electroacupuncture (EA) at "Dachangshu" (BL 25) or "Tianshu" (ST 25) for visceral sensitivity, gene expression product c-kit of colonic Cajal interstitial cells (ICC) and capsaicin receptor 1 (TRPV1) of irritable bowel syndrome (IBS) rats, so as to investigate the effect and mechanism differences of EA at the back point and the front point of large intestine for IBS rats.</p><p><b>METHODS</b>Forty-two Wistar neonatal rats were randomly divided into a blank group (9 rats) and a model group (33 rats). IBS model was established with mother and child separation, acetic acid enema in young rats and colorectal dilatation method. Twenty-seven IBS rats in life were randomly divided into a model control group, a Dachangshu group and a Tianshu group, 9 rats in each group. EA (disperse-dense wave, 2 Hz/100 Hz, 0.1-0.3 mA) for 20 min was used at "Dachangshu" (BL 25) and "Tianshu" (ST 25) respectively in the Dachangshu and Tianshu groups, once every other day, totally 5 times. The rats in the model control group were fixed with soft cloth sleeve for 20 min, without acupuncture. No intervention was used in the blank group. The stool property Bristol grading score was recorded before and after intervention in each group. The visceral sensitivity was evaluated by abdominal withdrawal reflex. The latency until the first systolic wave occurred and the number of systolic wave within 90 s were observed. Immunohistochemical was used to detect the positive expressions of c-kit and TRPV1, the ICC colon specific marker.</p><p><b>RESULTS</b>Compared with the blank group, the Bristol score increased，latency period shortened, systolic wave number increased, c-kit and TRPV1 positive expressions increased in the model control group (all <0.01). Compared with the model control group, the Bristol score decreased, latency period increased, systolic wave number decreased, c-kit and TRPV1 positive expressions decreased after intervention in the Dachangshu and Tianshu groups (<0.05, <0.01). Compared with the Dachangshu group, the TRPV1 positive expression decreased after intervention in the Tianshu group (<0.05).</p><p><b>CONCLUSION</b>EA at "Dachangshu" (BL 25) or "Tianshu"(ST 25) can improve the diarrhea in IBS model rats, reduce the visceral sensitivity, and its mechanism may be related to regulating the expressions of colon c-kit and TRPV1. EA at "Tianshu" (ST 25) is more apparent for TRPV1 than at "Dachangshu" (BL 25).</p>
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The researches on the acupoint effect specificity were summarized to explore whether the integrality of the acupoint effect specificity existed and analyze the connection between the relativity and integrality of the acupoint effect specificity. The literature on the clinical and experimental researches relevant with the acupoint effect specificity was retrieved through CNKI from January 2007 to October 2017. A total of 39 papers met the retrieving criteria. Separately, in terms of the holism of TCM theory, the holism of meridian theory and modern research, the integrality of acupoint effect specificity was analyzed. The relativity and the integrality are indicated in the acupoint effect specificity. The integrality of acupoint effect specificity is closely related to the holism of TCM theory as well as the meridians. Just because of its integrality, the acupoint effect specificity is relative, rather than absolute.
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<p><b>OBJECTIVE</b>To study the value of Pediatric Early Warning Score (PEWS) in identifying the condition of critically ill children.</p><p><b>METHODS</b>A total of 120 children who were transferred to the pediatric intensive care unit (PICU) from the general ward during hospitalization or admitted to the PICU after emergency treatment in the Xiangya Hospital of Central South University from January to December, 2016 were enrolled as the PICU group. The other 120 children who were admitted to the general ward in the hospital were used as the control group. According to the disease type, the PICU group was further divided into two subgroups: respiratory/circulatory system diseases (n=55) and nervous/other system diseases (n=65). The PEWS score on admission was recorded, and the receiver operating characteristic (ROC) curve was used to analyze the value of PEWS in evaluating patients' condition.</p><p><b>RESULTS</b>The PICU group had a significantly higher PEWS score than the control group (P<0.05). The respiratory/circulatory system disease subgroup had a significantly higher PEWS score than the nervous/other system disease subgroup (P<0.05). In predicting whether the child was admitted to the PICU, PEWS had a sensitivity of 85%, a specificity of 95%, and an area under the ROC curve (AUC) of 0.951 (95% confidence interval: 0.923-0.980) at the optimal cut-off value of 3.5 (PEWS score). The AUC of PEWS was 0.768 in the nervous/other system disease subgroup and 0.968 in the respiratory/circulatory system disease subgroup. The mortality rate of children with a PEWS score of >6, 4-6 and ≤3 was 40%, 21% and 0 respectively (P<0.001).</p><p><b>CONCLUSIONS</b>PEWS can well identify disease severity in critically ill children, and it has different sensitivities in children with different varieties of diseases. PEWS has a good value in predicting children's prognosis.</p>