ObjectiveTo analyze and determine the differential components of freeze-dried and sun-dried Panacis Quinquefolii Radix（PQR）， and to compare the differences in their pro-angiogenic activities. MethodFingerprints of freeze-dried and sun-dried PQR were established based on ultra performance liquid chromatography（UPLC）， and chemometrics methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were combined to determine the differential saponin composition of the two decoction pieces， and six representative saponins were selected and their contents in freeze-dried and sun-dried PQR were determined by UPLC. Transgenic zebrafish line Tg（fli1a∶EGFP） embryos fertilized for 24 h were selected， and different doses of 70% methanol extracts of freeze-dried and sun-dried PQR（10， 30 mg·L^-1） were used to intervene in normal zebrafish and in a zebrafish model of intersegmental vascular（ISV） injury induced by vascular endothelial growth factor（VEGF） receptor tyrosine kinase inhibitor Ⅱ（PTK787）， then the development of subintestinal vein（SIV） and ISV of zebrafish was observed， SIV diameter， mean number of crossings and mean number of germinations were determined， and the ISV vascular index was calculated， in order to compare the pro-angiogenic activities of the two decoction pieces. ResultThe similarity of the fingerprints of freeze-dried and sun-dried PQR decoction pieces was>0.950， and 17 common peaks were identified， of which 6 common peaks were designated as peak 6（ginsenoside Rg₁）， peak 7（ginsenoside Re）， peak 8（ginsenoside Rb₁）， peak 11（ginsenoside Rc）， peak 13（ginsenoside Rb₂）， and peak 16（ginsenoside Rd）， respectively. A total of 11 differential saponin components were screened by PCA and OPLS-DA， indicating that there were some differences in the contents of the components in the two decoction pieces. The results of determination showed that the contents of ginsenosides Rg₁， Re， Rb₁ and Rb₂ in freeze-dried PQR were higher than those in sun-dried PQR， while the contents of ginsenosides Rc and Rd were lower than those in sun-dried PQR（P<0.05， P<0.01）. In the study of the pro-angiogenic effect on normal zebrafish embryos， compared with the blank group， and the SIV vessel diameter， mean germination rate and mean crossover rate were significantly higher in the high-dose groups of freeze-dried and sun-dried PQR（P<0.01）， and the vessel diameter， mean numbers of crossings and germinations in the freeze-dried PQR group were higher than those of the sun-dried PQR group（P<0.05）. In the study of the pro-angiogenic effect on zebrafish embryos with ISV injury， the development of ISV in the model group was significantly inhibited when compared with the blank group， compared with the model group， different dose groups of freeze-dried and sun-dried PQR could promote the growth and sprouting of ISV， and the number of normal blood vessels in the freeze-dried PQR group was significantly higher than that in the sun-dried PQR group at the same dosage（P<0.05）. ConclusionFreeze-drying can effectively avoid the loss and secondary transformation of ginsenosides in PQR， and its angiogenic activity is better than that of sun-dried PQR， which can provide a reference for the production and development of high-quality PQR decoction pieces.

ObjectiveTo explore the possible mechanism of Danggui Sini Granules （当归四逆颗粒） in treatment of coronary heart disease with cold congealing and blood stasis syndrome. MethodsFifty SD rats were randomly divided into a blank group， a model group， a Danshen Pill （丹参滴丸） group， and a low- and high-dosage Danggui Sini Granules group， with 10 rats in each group. Except for the blank group， the rat model of coronary heart disease with cold congealing and blood stasis syndrome was established by repeated cold stimulation at low temperature combined with intraperitoneal injection of posterior pituitary hormone in all other groups. In the 6th week of modelling， 0.073 g·kg^-1·d^-1 of compound Danshen Pill was given to the Danshen Pill group， 20.2 and 40.4 g·kg^-1·d^-1 of Danggui Sini Granules were given to the low- and high-dose Danggui Sini Granules groups， respectively， and 0.2 ml/10 g of sterile water was given to the blank group and the model group， all for 2 consecutive weeks. The general conditions of the rats were recorded， and the body mass was compared weekly. At the end of the intervention， electrocardiogram， blood rheological indexes， including whole blood low-cut viscosity， whole blood high-cut viscosity， erythrocyte aggregation index， and cardiac index were detected to evaluate the effect of the medication， and HE staining was used to observe the myocardial histopathological changes， TUNEL staining to detect the apoptotic situation of cardiomyocytes， and ELISA to detect the serum thyroid-stimulating hormone （TSH）， free triiodothyronine （FT₃）， free tetraiodothyronine （FT₄） levels and thromboxane B₂ （TXB₂）， 6-keto-prostaglandin F1α （6-Keto-PGF_1α）， endothelin 1 （ET-1）， and nitric oxide （NO） levels. ResultsCompared with the blank group at the same time point， the body mass of rats in the remaining groups decreased at all time points （P＜0.05 or P＜0.01）； compared with the model group at the same time point， the body mass of rats in high-dose Danggui Sini Granules group and Danshen Pill group increased at the 6th and 7th weeks （P＜0.05 or P＜0.01）. In the blank group， the S-T segment of the electrocardiogram was close to the isoelectric line， the myocardial structure was regular， the fibres were closely arranged， and the nuclei of the cells were intact and neatly aligned； in the model group， the S-T segment of the electrocardiogram significantly elevated， and the arrangement of the myocardial fibres was obviously disordered， with myocardial cells appearing to be swollen， necrotic， and infiltrated by inflammatory cells， and the apoptosis-positive cells of the cardiac muscle cells obviously increased； in each of the medication groups， the electrocardiogram had a lowered S-T segment， and myocardial fibres were aligned， myocyte structure and morphology were improved， inflammatory cells reduced， and the number of apoptosis-positive cells significantly reduced. Compared with the blank group， the cardiac index， whole blood high cut viscosity， whole blood low cut viscosity， erythrocyte aggregation index increased in the model group， and the serum levels of TSH， FT₃， FT₄， NO， 6-Keto-PGF_1α significantly reduced， and the levels of ET-1 and TXB₂ significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， the levels of cardiac index， whole blood high cut viscosity， whole blood low cut viscosity， erythrocyte aggregation index， ET-1 and TXB₂ significantly decreased and the levels of NO and 6-Keto-PGF_1α significantly increased in each medication group， and the serum levels of TSH， FT₃， and FT₄ elevated in the high-dose Danggui Sini Granules group and Danshen Pill group （P＜0.05 or P＜0.01）. The serum TSH level of rats in the low-dose Danggui Sini Granules group was lower than that in Danshen Pill group and the high-dose Danggui Sini Granules group （P＜0.01）. ConclusionDanggui Sini Granules have the effect of alleviating myocardial injury in coronary heart disease with cold congealing and blood stasis syndrome， and its mechanism may be related to reducing myocardial cell apoptosis， improving energy metabolism， and regulating the level of vasoactive factors.

It is found that acupuncture can significantly improve the clinical symptoms of rheumatoid arthritis (RA) such as pain and joint stiffness, and improve rheumatoid factor, high-sensitivity CRP, ESR and other clinical indicators. It can inhibit the proliferation of synovial cells, the apoptosis of chondrocytes, and regulate polarization balabce of mononuclear macrophages, T cells, as well as inhibit the inflammatory function of multiple immune cells, in order to improve inflammation state of RA joints. In clinical treatment of RA, bladder meridian, stomach meridian, spleen meridian , and Governor Vessel are mostly selected. Acupoints with the efficacy of warming meridian, dispelling coldness and dredging collaterals were commonly selected such as Zusanli (ST36), Yanglinquan (GB34), Dazhui (GV14), Quchi (LI11). Several researches have proved that combined therapy of acupuncture and medicine is worthy promotion in clinic.

Objective:To estimate the deaths and life expectancy losses attributed to diet with high salt in Shandong province.Methods:Based on 24 h urinary sodium and blood pressure levels from the final evaluation survey of Shandong-Ministry of Health Action on Salt and Hypertension Project (SMASH) in 2016 and death cause data from Shandong Mortality Surveillance System, the population attributable fractions (PAF) and the deaths due to high-salt diet were calculated based on the framework of comparative risk assessment and the life expectancy loss was calculated by life table method.Results:A total of 32 987 deaths caused by high-salt diets were reported in 2016, accounting for 11.74% of related disease deaths and 4.95% of all deaths. The proportion of deaths due to high-salt diet in men (13.51%) was higher than that in women (9.17%). Cardiovascular diseases were the major causes of deaths due to high salt diet, accounting for 90.82% of all disease deaths caused by high-salt diets. The other causes were gastric cancer (8.10%) and chronic kidney disease (1.08%). The PAF in urban residents (13.87%) was higher than that in rural residents (10.87%). A loss of 0.58 years of the life expectancy were attributed to the high-salt diet. The different diseases caused by high-salt diet had different effects on life expectancy loss, ischemic heart disease ranked first, followed by cerebral hemorrhage and cerebral infarction.Conclusions:The proportion of deaths attributed to high-salt diets was high in Shandong. Cardiovascular diseases were the most important causes of deaths caused by high-salt diets. High-salt diet is still seriously affecting the health of residents in Shandong, indicating that salt reduction interventions need to be strengthened.

Objective:To investigate the distribution characteristics and trends of mortality and spatial aggregation of gastric cancer in Shandong Province from 1970 to 2013.Methods:The mortality data of gastric cancer from 1970 to 1974, 1990 to 1992 and 2004 to 2005 were collected from the first, second and third retrospective sampling survey of causes of death in Shandong Province, respectively. The mortality data of gastric cancer from 2011 to 2013 were collected from the all-cause surveillance data of Shandong Province. The crude mortality rate and age-standardized mortality rate were used to describe the death level of gastric cancer. The age-standardized mortality rate of Shandong Province was calculated based on Segi′s world standard population, and the age-standardized mortality rate of counties (cities and districts) was calculated based on the Chinese population in 1964.The factors influencing the difference of gastric cancer mortality in different periods were decomposed by using the method of differential decomposition of mortality, and the contributions of population and non-population factors in different periods were estimated.Using ArcGIS 10.2 software, the death level of gastric cancer in different counties (cities and districts) in Shandong province from 1970 to 1974 and 2011 to 2013 were visualized. DeoDa 1.12 software was used for global and local spatial autocorrelation analysis.Results:The crude death rate and age-standardized death rate of gastric cancer in Shandong province increased firstly and then decreased during 1970-2013, and the crude death rate of gastric cancer increased from 18.33/100 000 in 1970-1974 to 28.51/100 000 in 2011-2013. Segi′s age-standardized mortality rate for gastric cancer decreased from 20.94 per 100 000 in 1970-1974 to 18.17 per 100 000 in 2011-2013.From 1990 to 1992, from 2004 to 2005 and from 2011 to 2013, the contribution value of non-population factors to the increase of crude gc mortality was 95.59%, 48.45% and -20.57%, respectively, showing a continuous downward trend. The Moran′s I index of crude mortality of gastric cancer in Shandong province from 1970 to 1974 and from 2011 to 2013 were 0.77 and 0.57, respectively, and the Moran′s I index of age-normalized mortality was 0.75 and 0.44, respectively. Local autocorrelation analysis showed that there were 31 and 19 high aged-mortality areas of gastric cancer in 1970-1974 and 2011-2013 respectively, and 7 overlapping counties (cities and districts), 6 of which were located in Jiaodong area. Conclusion:The crude mortality and age-standardized mortality of gastric cancer in Shandong province increased first and then decreased from 1970 to 2013, and the distribution of gastric cancer mortality had obvious spatial aggregation and changed with time.

Objective:To investigate the distribution characteristics and trends of mortality and spatial aggregation of gastric cancer in Shandong Province from 1970 to 2013.Methods:The mortality data of gastric cancer from 1970 to 1974, 1990 to 1992 and 2004 to 2005 were collected from the first, second and third retrospective sampling survey of causes of death in Shandong Province, respectively. The mortality data of gastric cancer from 2011 to 2013 were collected from the all-cause surveillance data of Shandong Province. The crude mortality rate and age-standardized mortality rate were used to describe the death level of gastric cancer. The age-standardized mortality rate of Shandong Province was calculated based on Segi′s world standard population, and the age-standardized mortality rate of counties (cities and districts) was calculated based on the Chinese population in 1964.The factors influencing the difference of gastric cancer mortality in different periods were decomposed by using the method of differential decomposition of mortality, and the contributions of population and non-population factors in different periods were estimated.Using ArcGIS 10.2 software, the death level of gastric cancer in different counties (cities and districts) in Shandong province from 1970 to 1974 and 2011 to 2013 were visualized. DeoDa 1.12 software was used for global and local spatial autocorrelation analysis.Results:The crude death rate and age-standardized death rate of gastric cancer in Shandong province increased firstly and then decreased during 1970-2013, and the crude death rate of gastric cancer increased from 18.33/100 000 in 1970-1974 to 28.51/100 000 in 2011-2013. Segi′s age-standardized mortality rate for gastric cancer decreased from 20.94 per 100 000 in 1970-1974 to 18.17 per 100 000 in 2011-2013.From 1990 to 1992, from 2004 to 2005 and from 2011 to 2013, the contribution value of non-population factors to the increase of crude gc mortality was 95.59%, 48.45% and -20.57%, respectively, showing a continuous downward trend. The Moran′s I index of crude mortality of gastric cancer in Shandong province from 1970 to 1974 and from 2011 to 2013 were 0.77 and 0.57, respectively, and the Moran′s I index of age-normalized mortality was 0.75 and 0.44, respectively. Local autocorrelation analysis showed that there were 31 and 19 high aged-mortality areas of gastric cancer in 1970-1974 and 2011-2013 respectively, and 7 overlapping counties (cities and districts), 6 of which were located in Jiaodong area. Conclusion:The crude mortality and age-standardized mortality of gastric cancer in Shandong province increased first and then decreased from 1970 to 2013, and the distribution of gastric cancer mortality had obvious spatial aggregation and changed with time.

Objective:To explore the spatial clustering and trend of liver cancer mortality in different counties of Shandong province from 1970 to 2013, and provide scientific basis for the development of liver cancer prevention and control plan.Methods:Cancer mortality data were obtained from Shandong Death Registration System and three national death cause surveys in China. Mortality rate and age adjusted mortality rate were used to describe the trend of liver cancer in different years. Difference decomposing method was applied to estimate the contribution of demographic and non-demographic factors to the change of mortality. Software ArcGIS 10.2 was used for spatial analysis, and software SaTScan 9.4 was used for spatial clustering analysis on liver cancer mortality.Results:From 2011 to 2013, the crude mortality rate of liver cancer (29.89/100 000) in Shandong increased by 208.00 % and 35.37 % respectively compared with that during 1970-1974 (9.72/100 000) and 1990-1992 (22.08/100 000) and was similar to that during 2004-2005 (30.44/100 000). While age standardized mortality rate (ASMR) increased first and then decreased. The ASMR during 2011-2013 (12.62/100 000) increased by 60.97 % compared with that during 1970-1974 and decreased by 22.38 % and 21.81 % compared with that during 1990-1992 and 2004-2005, respectively. According to the difference decomposition analysis on liver cancer mortality in different years, the contribution of population factors to the liver cancer mortality rate increased from 3.38 % during 1990-1992 to 29.36 % during 2004-2005 and 46.16 % during 2011-2013. However, the contribution of non-population factors to the increase of liver cancer mortality decreased. According to the spatial distribution of liver cancer mortality, the crude mortality rate of liver cancer in different counties were quite different, ranging from 9.33/100 000 to 65.33/100 000. Using the spatial scanning statistical software to analyze the spatial clustering of liver cancer mortality, multi areas with high mortality rate of liver cancer were found, and they were mainly distributed in Jiaodong peninsula from 2011 to 2013, covering 20 counties (cities, districts) in Qingdao, Yantai and Weihai. The risk of liver cancer mortality in this area was 1.54 times higher than that in other areas. The spatial clustering distribution of liver cancer mortality during 1970-1974 was significantly different from that during 2011-2013, the areas with high mortality rate during 1970-1974 were mainly distributed in central and western Shandong. Conclusions:There were significant temporal and spatial distribution changes in the mortality rate of liver cancer in Shandong from 1970 to 2013. According to these trends and their geographical and spatial distribution, we should further explore the risk factors of liver cancer, and formulate feasible and area specific prevention and control measures for liver cancer.

In 2016, the median of 24-hour urinary sodium, sodium-to-potassium ratio, and sodium intake per capita of residents in Jiaodong area of Shandong Province were 161.7 ( IQR:120.5, 218.9) mmol/d, 3.4 ( IQR: 2.4, 5.0) and 9.5 ( IQR:7.1, 12.8) g/d, all were lower than that of 2011[193.3( IQR:149.2,243.3)mmol/d, 4.5( IQR:3.3,5.9), 11.3( IQR:8.7, 14.2)g/d] ( P<0.05); the median of 24-hour urinary potassium was 47.2 ( IQR:34.4, 66.5) mmol/d, higher than that of 2011[42.9( IQR:33.6,56.0)] ( P<0.05); the proportion of salt intake per capita per day exceeding 5 g (89.9%) was lower than that in 2011 (90.0%). The results of the generalized linear regression model showed that the 24-hour urinary sodium was positively correlated with systolic and diastolic blood pressure [β values were 0.04 (95% CI: 0.00, 0.07), 0.03 (95% CI 0.01, 0.05), respectively], and the sodium-to-potassium ratio was positively correlated with diastolic blood pressure [β(95% CI): 0.78 (0.09, 1.47)].

In 2016, the median of 24-hour urinary sodium, sodium-to-potassium ratio, and sodium intake per capita of residents in Jiaodong area of Shandong Province were 161.7 ( IQR:120.5, 218.9) mmol/d, 3.4 ( IQR: 2.4, 5.0) and 9.5 ( IQR:7.1, 12.8) g/d, all were lower than that of 2011[193.3( IQR:149.2,243.3)mmol/d, 4.5( IQR:3.3,5.9), 11.3( IQR:8.7, 14.2)g/d] ( P<0.05); the median of 24-hour urinary potassium was 47.2 ( IQR:34.4, 66.5) mmol/d, higher than that of 2011[42.9( IQR:33.6,56.0)] ( P<0.05); the proportion of salt intake per capita per day exceeding 5 g (89.9%) was lower than that in 2011 (90.0%). The results of the generalized linear regression model showed that the 24-hour urinary sodium was positively correlated with systolic and diastolic blood pressure [β values were 0.04 (95% CI: 0.00, 0.07), 0.03 (95% CI 0.01, 0.05), respectively], and the sodium-to-potassium ratio was positively correlated with diastolic blood pressure [β(95% CI): 0.78 (0.09, 1.47)].

Obeticholic acid (OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl-injured mice, d-galactosamine/LPS (GalN/LPS)-treated mice and cycloheximide/TNF (CHX/TNF)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell (HSC) activation/proliferation and prevented fibrosis. Elevated bile acid (BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis.