The patent information of ultrasound countercurrent extraction used in traditional Chinese medicine was analyzed in this paper by the samples from Derwent World Patent Database (DWPI) and the Chinese Patent Abstracts Database (CNABS). The application of ultrasound countercurrent was discussed with the patent applicant,the amount of the annual distribution, and the pharmaceutical raw materials and other aspects. While the technical parameters published in the patent was deeply analyzed, such as material crushing, extraction solvent, extraction time and temperature, extraction equipment and ultrasonic frequency. Thought above research, various technical parameters of ultrasound countercurrent extraction used in traditional Chinese was summarize. The analysis conclusion of the paper can be used in discovering the technical advantages, optimizing extraction conditions, and providing a reference to extraction technological innovation of traditional Chinese medicine.
Medicine, Chinese Traditional ; Patents as Topic ; Solvents ; Technology, Pharmaceutical ; Temperature ; Ultrasonics

BACKGROUNDInoperable chronic thromboembolic pulmonary hypertension (CTEPH) is a severe clinical syndrome characterized by right cardiac failure and possibly subsequent liver dysfunction. However, whether serum markers of liver dysfunction can predict prognosis in inoperable CTEPH patients has not been determined. Our study aimed to evaluate the potential role of liver function markers (such as serum levels of transaminase, bilirubin, and gamma-glutamyl transpeptidase [GGT]) combined with 6-min walk test in the prediction of prognosis in patients with inoperable CTEPH.

METHODSFrom June 2005 to May 2013, 77 consecutive patients with inoperable CTEPH without confounding co-morbidities were recruited for this prospective cohort study. Baseline clinical characteristics and 6-min walk distance (6MWD) results were collected. Serum biomarkers of liver function, including levels of aspartate aminotransferase, alanine aminotransferase, GGT, uric acid, and serum bilirubin, were also determined at enrollment. All-cause mortality was recorded during the follow-up period.

RESULTSDuring the follow-up, 22 patients (29%) died. Cox regression analyses demonstrated that increased serum concentration of total bilirubin (hazard ratio [HR] = 7.755, P < 0.001), elevated N-terminal of the prohormone brain natriuretic peptide (HR = 1.001, P = 0.001), decreased 6MWD (HR = 0.990, P < 0.001), increased central venous pressure (HR = 1.074, P = 0.040), and higher pulmonary vascular resistance (HR = 1.001, P = 0.018) were associated with an increased risk of mortality. Serum concentrations of total bilirubin (HR = 4.755, P = 0.007) and 6MWD (HR = 0.994, P = 0.017) were independent prognostic predictors for CTEPH patients. Patients with hyperbilirubinemia (≥23.7 μmol/L) had markedly worse survival than those with normobilirubinemia.

CONCLUSIONElevated serum bilirubin and decreased 6MWD are potential predictors for poor prognosis in inoperable CTEPH.

Aged ; Antihypertensive Agents ; therapeutic use ; Bilirubin ; blood ; Exercise Test ; Female ; Humans ; Hypertension, Pulmonary ; blood ; drug therapy ; pathology ; Male ; Middle Aged ; Prognosis ; Prospective Studies

Objective:To explore the role of nuclear transcription factor erythrocyte line-2p45 (NF-E2) related factor-2 (NRF2) on autophagy during malignant transformation of immortalized human keratinocytes (HaCaT) induced by sodium arsenite (NaAsO 2). Methods:Using cell culture methods, long-term cultured HaCaT cells in DMEM high-glucose medium containing 0.0 (control group) and 1.0 μmol/L NaAsO 2 (arsenic-exposed group) to the 35th generation were used to construct a cell malignant transformation model, and 0, 1, 7, 14, 21, 28 and 35th generation cells of control group and arsenic-exposed group were collected during establishment of cell malignant transformation model. The NRF2 siRNA, phosphatidylinositol-3-hydroxykinase (PI3K) inhibitor LY294002 and mammalian target of rapamycin (mTOR) inhibitor Rapamycin were used to treat the 35th generation of malignant transformed HaCaT cells in arsenic-exposed group (T-HaCaT). The protein expressions of NRF2, PI3K-protein kinase B (Akt)-mTOR signaling pathway related indicators PI3K, Akt, mTOR, phosphorylated (p)-PI3K, p-Akt, p-mTOR, autophagy-related proteins p62, Beclin1, microtubule-associated protein-1 light chain (LC)3Ⅰ, and LC3Ⅱof different generations HaCaT cells in control group and arsenic-exposed group, and T-HaCaT cells of each treatment group were determined by Western blotting. Results:There were significant differences in the NRF2 protein and the ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR between different generations HaCaT cells in arsenic-exposed group ( F = 9.371, 16.035, 15.932, 27.739, P < 0.05), and they were higher than NRF2 protein and ratio of p-mTOR/ mTOR of the same generation in control group ( P < 0.05). Compared with HaCaT cells of the same generation, the expressions of NRF2, p-PI3K, p-Akt, p-mTOR and p62 proteins in T-HaCaT cells were significantly higher, Beclin1 protein expression and the ratio of LC3Ⅱ/LC3Ⅰ were significantly lower ( P < 0.05). The NRF2 silenced T-HaCaT cells had higher expression of Beclin1 and the ratio of LC3Ⅱ/LC3Ⅰ, and lower expressions of NRF2, p-mTOR and p62 than the corresponding control siRNA (Con siRNA) group ( P < 0.05). The T-HaCaT cells in LY294002 treatment group had higher expression of Beclin1 and the ratio of LC3Ⅱ/LC3Ⅰ, and lower expressions of NRF2, p-PI3K, p-Akt and p-mTOR proteins than the corresponding non-treatment group ( P < 0.05). The T-HaCaT cells in Rapamycin treatment group had higher expression of Beclin1 and the ratio of LC3Ⅱ/LC3Ⅰ, and lower expression of p-mTOR protein than the corresponding non-treatment group ( P < 0.05). Conclusions:During the arsenic-induced malignant transformation of HaCaT cells, NRF2 can act as a downstream factor of PI3K-Akt and an upstream factor of mTOR in PI3K-Akt-mTOR signaling pathway, an important regulatory mechanism of autophagy. This abnormal expression of autophagy may eventually lead to malignant transformation of cells.

Objective: To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas. Methods: Hot spot mutations of TERT and IDH1/2 genes were detected by DNA sequencing in 236 cases of gliomas at West China Hospital from 2012 to 2016, including pilocytic astrocytoma (WHO grade Ⅰ, 16 cases), diffuse astrocytoma and oligodendroglioma (WHO grade Ⅱ, 89 cases), anaplastic astrocytoma and oligodendroglioma (WHO grade Ⅲ, 72 cases) and glioblastoma (WHO grade Ⅳ, 59 cases). The prognostic significance of TERT and IDH1/2 hot spot mutations was evaluated. Results: No IDH or TERT mutations were detected in pilocytic gliomas. TERT promoter mutation frequency was higher in patients aged ≥40 years(60.8%, 93/153) than in patients aged <40 years (32.8%, 22/67; P<0.01). TERT promoter mutation rate was also significantly higher in oligodendroglioma (87.5% , 56/64) than that in astrocytoma(37.8%, 59/156; P<0.01). Young age (<40 years), oligodendroglioma and IDH1 mutation were favorable prognostic factors for diffusely infiltrating astrocytic and oligodendroglial tumors. TERT mutation alone was not of prognostic significance. Diffusely infiltrating astrocytic and oligodendroglial tumors were divided into four molecular subtypes according to TERT and IDH1 mutation status: IDH(+ )/TERT(+ ), IDH(+ )/TERT(-), IDH(-)/TERT(-) and IDH(-)/TERT(+ ). There was significant prognostic difference among the 4 subtypes. Conclusions Combined IDH and TERT gene mutation analysis may be useful for prognostic subgrouping. Notably, IDH1 wild-type cases can be further subdivided into TERT(+ ) or (-) subgroups with significant prognostic difference.

Objective To evaluate the left ventricular(LV)myocardial mechanical changes with contrast agent and different power irradiation in open-chest beagle canines.Methods The anesthetized open-chest beagle canines were assigned into two groups randomly:group A(n=6)for baseline,diagnostic ultrasound power irradiation(300 mW)5 min,combined with contrast agent irradiation 5 min and contrast agent 20 min conditions;group B(n=6)for baseline and intensity ultrasound irradiation(1 W,2 W and 3 W,5 min respectively)conditions.The peak circumferential strain(CS),longitudinal strain(LS)and radial strain(RS)of LV myocardial wall were measured and analyzed using a dedicated Syngo velocity vector imaging(VVI)method.Results In group A,the peak CS and LS were increased significantly on diagnostic power irradiation,contrast agent irradiation 5 min and contrast agent 20 min(all P <0.05,respectively) compared with baseline condition;there was no significant difference of the peak RS on diagnostic power irradiation,contrast agent irradiation 5 min and contrast 20 min compared with baseline condition(P >0.05).In group B,the peak CS and LS were higher on power 1 W than on baseline condition(P <0.05), the peak RS was increased gradually on power 1 W than on baseline condition(P >0.05);the peak CS,LS, RS were lower on power 2 W than on baseline condition(P >0.05);the peak of CS,LS were lower on power 3 W than on baseline condition(P <0.05);the peak of RS was decreased gradually without significant changes between power 3 W on baseline condition(P >0.05).Conclusions These findings indicate potential positive inotropic effects with diagnostic ultrasound power irradiation 5 min,combined with contrast agent irradiation 5 min,contrast agent 20 min conditions,power 1 W and negative inotropic effects with power 3 W on LV myocardial CS,LS deformation.LV myofiber deformation reactions appear no significant differences on LV myocardial RS deformation in same disturbed setting.

Objective To investigate the incidence of left ventricular hypertrophy (LVH) in peritoneal dialysis (PD) patients with different hydration statuses,and analyze the risk factors of LVH in PD patients.Methods PD patients in Renji Hospital,Shanghai Jiao Tong University School of Medicine from September 2016 to January 2017 were enrolled.Demographic data of patients were collected and biochemical parameters were measured.Hydration status index overhydration (OH) was measured by bioimpedance spectroscopy,and LVH was diagnosed by echocardiography.Logistic regression was used to analyze the risk factors of LVH.Results A total of 113 PD patients aged 58.98(48.89,65.33) years with median PD duration 46.20(18.08,72.75) months were enrolled in present study,among whom 60 patients (53.1％) had LVH.OH ＞ 1.1 L was detected in 80 patients (70.8％),among whom 34 patients (42.5％) had subclinical overhydration (SCOH).LVH was however diagnosed in 33(71.7％) clinical overhydrated (COH) patients and 17(50.0％) SCOH patients (n=34).In the normal hydrated (OH≤1.1 L) patients (n=33),LVH was detected in 10 patients (30.3％).Multivariate logistic regression showed that high OH (OR=1.730,95％CI 1.274-2.348,P ＜ 0.001) and low hemoglobin (OR=0.965,95％CI 0.940-0.991,P=0.008) were the independent risk factors of LVH.Conclusions LVH is common in PD patients,especially in overhydrated patients.High OH and low hemoglobin were the independent risk factors of LVH.

Objective To investigate the prevalence and risk factors of sarcopenia in peritoneal dialysis (PD) patients.Methods The patients who underwent regular peritoneal dialysis at Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine between November 2016 and March 2018 were enrolled.Handgrip strength (HGS) was measured to assess muscle strength.Bioelectrical impedance spectroscopy (BIS) was applied to measure the lean tissue index (LTI).Reduced LTI plus decreased HGS was defined as sarcopenia.The prevalence of sarcopenia in PD patients was evaluated.According to the presence or absence of sarcopenia,they were divided into the sarcopenia group and the non-sarcopenia group,and the differences in clinical indicators between the two groups were compared.Multivariate logistic regression was used to explore the risk factors of sarcopenia in PD patients.Results A total of 207 patients were enrolled in the study with age of (55.3±13.7) years and a median PD duration of 22.9(7.3,60.9) months.Of them,122 patients (58.9％) were male,45 patients (21.7％) had diabetics and 32 patients (15.5％) suffered from cardiovascular diseases.There were 27 patients (13.0％) diagnosed with sarcopenia.These patients presented with longer PD duration,more prevalent diabetics,lower residual renal function (RRF) and serum pre-albumin,greater ratio of extracellular water to intracellular water (ECW/ICW) and high sensitive C-reactive protein in contrast with those in the non-sarcopenia group (all P ＜ 0.05).Multivariate logistic analysis showed that male (OR=3.94,95％ CI 1.35-11.50,P=0.O12),longer PD duration (OR=1.01,95％CI 1.00-1.02,P=0.029) and higher ECW/ICW (OR=1.09,95％CI 1.05-1.14,P ＜ 0.001) were independent risk factors of sarcopenia in PD patients.Conclusions Sarcopenia is common in PD patients.Male,longer PD duration and higher ECW/ICW were independent risk factors of sarcopenia in PD patients.

Objective To evaluate left ventricular ( LV ) myocardial mechanical transmural longitudinal displacement ( LD ) and radial displacement ( RD ) with contrast agent and different power irradiation in open‐chest Beagle canines by ultrasound velocity vector images ( VVI) workstation . Methods T he anesthetized open‐chest Beagle canines were assigned into two groups randomly :Group A ( n ＝6) for baseline ,diagnostic ultrasound power irradiation ( 300 mW) 5 min ,combined with contrast agent irradiation 5 min and contrast agent 20 min conditions ; Group B ( n ＝ 6 ) for baseline and intensity ultrasound irradiation ( 1 W ,2 W and 3 W ,5 min respectively) conditions . T he standard short‐axis and long‐axis gray‐scale view s during three complete cardiac cycles in open‐chest Beagle canine models were acquired . T he peak LD subendomyocardium ( LD‐subendo) ,LD subepimyocardium ( LD‐subepi) ,RD subendomyocardium ( RD‐subendo) and RD subepimyocardium ( RD‐subepi ) of LV were analyzed using a dedicated Syngo VVI method . Results In group A ,the LV LD‐subendo ,LD‐subepi ,RD‐subendo and RD‐subepi in the most of segments showed increasing trend in diagnostic power irradiation ,contrast agent irradiation 5 min and contrast agent 20 min compared with baseline condition ,however the differences were not significant ( P ＞0 .05 ,respectively) . T he peak LD‐subendo and LD‐subepi ,RD‐subendo and RD‐subepi of LV in group A with the same condition were significant different ( all P ＜0 .05) . In group B ,LV LD‐subendo in ultrasonic power 3 W was lower than baseline condition ( P ＜ 0 .05 ) ,LV RD‐subendo was higher compared with baseline condition ( P ＜0 .05) . T he peak LD‐subendo and LD‐subepi ,RD‐subendo and RD‐subepi of LV in group B with the same condition were significant different ( all P ＜ 0 .05) . Conclusions On ultrasonic power 3 W ,LV LD‐subendo is decreased resulting to negative inotropic effect and RD‐subendo is increased to maintain the normal heart work .LV LD and RD on diagnostic ultrasound power irradiation 5 min , combined with contrast agent irradiation 5 min ,contrast agent 20 min conditions ,ultrasonic power 1 W and 2 W are not prominent changes .

Objective: To study the correlation between the fingerprint of different polar parts of Huanbei Zhike recipe and its antitussive effect,identify the chromatographic peaks greatly contributing to its pharmacological effect,and ascribe the chromatographic peaks. Method: Gradient elution method was used to establish the chromatographic peaks of different polar parts of Huanbei Zhike recipe. The common peaks and corresponding peak areas of each part were obtained by referring to the water extract chromatogram and after being processed by chromatographic workstation. The cough frequency,the latent period of cough and the contents of interleukin (IL)-4,interferon-γ(IFN-γ),immunoglobulin (Ig)E and IL-5 in lung lavage fluid of mice were used as the detection indexes to investigate the antitussive effect of different polar parts of Huanbei Zhike recipe. The correlation analysis among cough frequency,cough latent period and common peak area was carried out,and the peaks greatly contributing to the effect of medicine were pointed out,which were assigned according to the fingerprint of single drug. Result:Bivariate correlation analysis showed that seven chromatographic peaks, i.e. No.12,13,29,32,33,35 and 39,contributed significantly to the antitussive effect. The higher the content of the compounds represented by these peaks,the stronger the antitussive effect. There was a significant correlation between No. 32 peak and the latent period of cough,while No. 13 and No. 32 peaks were significantly correlated with cough frequency. These chromatographic peaks were assigned and found to be present in Scutellaria baicalensis,Crepis Herba, Aurantii Fructus,Glycyrrhiza uralensis,etc. Conclusion:The chromatographic peaks of No.13 and No.32 peaks contribute greatly to the antitussive effect of Huanbei Zhike recipe,while Crepis turczaniowii,S. baicalensis and Aurantii Fructus are of significant significance for the whole recipe.

Radix Semiaquilegiae(Tiankuizi in Chinese),the root of Semiaquilegia adoxoides,has been widely used in China,according to the traditional Chinese medicine(TCM)principle,it has effect of heat clearing and detoxicating,detumes-cence,lump dissipation.The main components of Radix Semiaquilegiae are alkaloids,cyano compounds and nitro com-pounds,phenolic acids.This review summarizes the achievements of the investigations in phytochemistry on Radix Semiaqui-legiae in order to provide reference for further study.