To study the compatible mechanisms and compatible proportion of Shaoyao Gancao decoction, the intestinal absorption of main ingredients in Shaoyao Gancao decoction SG11 (Baishao-Zhigancao 1: 1) , SG31 (Baishao-Zhigancao 3: 1), Baishao water decoction S and Zhigancao (G) were investigated and compared using in vitro everted intestinal sac model and in situ single pass intestinal perfusion (SPIP) model. The concentration of paeoniflorin (PF), liquiritin (LQ) and mono-ammonium glycyrrhizinate (GL) in test samples and samples of intestinal sac and intestinal perfusion was determined by HPLC. The intestinal absorptive amount and absorption parameters were calculated. Results showed that in the everted intestinal sac model, three ingredients could be absorbed by duodenum, jejunum and ileum, and the absorption in the jejunum was best for all 3 ingredients. The absorption rate of three ingredients in SG11 was significantly higher than that in single decoction (P < 0.05), but had no significant difference compared with SG31. In SPIP model, the absorption rate constant K(a), the apparent absorption coefficient P(app) and the absorption rate of three ingredients in SG11 were significantly higher than those in single decoction. Parameters of PF and GL in SG11 were significantly higher than those in SG31, but had no differences of LQ. It proved that the compatibility of Baishao and Zhigancao could improve the intestinal absorption of PF, LQ and GL. The absorption of each ingredient in SG11 was better than that in SG31.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; Intestinal Absorption ; drug effects ; Intestines ; blood supply ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

Objective To analyze the genetic etiology of lateral ventriculomegaly fetal on the genome-wide level with chromosomal microarray analysis (CMA),and investigate the relationship between copy number variations (CNVs) and lateral ventriculomegaly and the application value of CMA in prenatal diagnosis of fetuses with lateral ventriculomegaly.Methods Seventy fetuses with lateral ventriculomegaly but normal or uncertain karyotype were selected and invasive prenatal diagnosis was performed in Xi Jing Hospital of the Fourth Military Medical University from Jan.2015 to Nov.2016.Microarray testing was performed using Affymetrix CytoScanTM 750k arrays and the results were analyzed according to biological information science database.The fetal development was regularly inspected,and follow up was conducted to find out the pregnancy outcome and fetal postnatal conditions.Results In 70 cases of lateral ventriculomegaly fetuses,there were 9 fetuses with pathogenic copy number variations (CNVs),3 fetuses with likely pathogenic CNVs and 1 fetus with likely pathogenic 1 oss of heterozygosity (LOH).During the 70 fetuses with lateral ventriculomegaly,2 pathogenic CNVs were detected in 6 fetuses with severe and non isolated lateral ventriculomegaly (33.3％).Pathogenic CNVs was not detected but 1 likely pathogenic CNV was detected in 3 fetuses with severe and isolated lateral ventriculomegaly (33.3％).Six pathogenic CNVs were detected in 31 mild and non isolated lateral ventriculomegaly (19.4％),and 2 likely pathogenic CNVs were also detected in these group (6.5％).One pathogenic CNV and 1 likely pathogenic CNV were detected in 30 fetuses with mild and isolated fetal lateral ventriculomegaly.Conclusions CMA can identify chromosome abnormality microdeletion/microduplication which was unrecognizable by conventional karyotyping analysis.The application of CMA may increase the detection rate of pathogenic CNVs in fetuses with lateral ventriculomegaly,and benefit evaluation of fetal prognosis in prenatal genetic counselling.

This study was aimed to investigate the effects of different stimulatory factors on proliferation and function of cytokine induced killer (CIK) cells. Peripheral blood mononuclear cells (PBMNC) were separated by Ficoll-Hypacue gradient. According to supplement of different stimulatory factors (CD28 mAb, IL-15 and IL-21), the experiment was divided into five groups:control group (CIK), CB28+IL-15+IL-21 group, IL-15+IL-21 group, CD28+IL-15 group and CD28+IL-21 group. Effects of different stimulatory factors on the proliferation of CIK cells were assayed by an automated hematology analyzer. Changes of granzyme B,perforin and CD107a were detected by flow cytometry. IL-10, IL-12, INF-γ and TNF-α were quantified by ELISA. Cytotoxicities on lung cancer cell line A549, breast adenocarcinoma cell line MFC-7 and human melanoma cell line HME1 were examined by lactate dehydrogenase release method. The results showed that there were significant differences among different groups. The highest proliferation index on days 10 was observed in group CD28mAb, IL-15 and IL-21(255.3 ± 6.3), which was higher than control group, IL-21+IL-15 group and CD28 mAb+IL-21 group (166.6 ± 13.5, 199.4 ± 15.0 and 228.8 ± 16.6) (P < 0.05). The expression of perforin in CD28 mAb+IL-15 group was higher than the other groups. The expression of perforin,GranB and CD107a of costimulatory groups was higher than control group. The cytotoxicities of CD28 mAb+IL-15 group on A549, MFC-7 and HME1 cells (82.2%, 59.3% and 70.6%) were much higher than that of control group (60.9%, 49.6% and 48.4%) (P < 0.05). The highest IFN-γsecretion was found in CD28 mAb, IL-15 and IL-21 groups. It is concluded that there are significant difference of proliferative capacity, cytokine secretion and cytotoxicity after being activated by different stimulatory factors. Adding corresponding stimulatory factors into the culture system displays a great value for target cells culture.
Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cytokine-Induced Killer Cells ; cytology ; drug effects ; Humans ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-15 ; pharmacology ; Interleukins ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVECellular senescence as one of the important steps against tumor is observed in many cancer patients receiving chemotherapy and is related to chemotherapeutic response. To investigate the effect of cisplatin on hepatocellular carcinoma, we treated HepG2 cells exhibiting wild-type TP53 with gradient concentrations of cisplatin.

METHODSThe inhibitory effects of cisplatin on human hepatoma HepG2 cells were detected by MTT assay and colony formation test. The changes in cell cycle were analyzed by flow cytometry, and cellular senescence was detected with senescence associated β-galactosidase (SA β-gal) staining. The relative mRNA expression levels of TP53, P21 and P19 was estimated using semi-quantitative real-time RT-PCR, and the protein expressions of P53 and P21 were detected using Western blotting.

RESULTSCisplatin induced irreversible proliferation inhibition and G1 phase arrest of HepG2 cells. Elevated levels of senescence-associated β-galactosidase was observed in HepG2 cells exposed to low doses of cisplatin. P19 expression immediately increased following cisplatin exposure and reached the maximum level at 48 h, followed then by a rapid decrease to the baseline level, whereas the expressions levels of TP53 and P21 mRNA increased continuously. Western blotting confirmed P53 and P21 expression changes similar to their mRNA expressions during cisplatin-induced cellular senescence in HepG2 cells.

CONCLUSIONOur results revealed a functional link between cisplatin and hepatocellular senescence. Cellular senescence induced by cisplatin as a stabile senescent cellular model can be used for further research.

Cell Cycle ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cellular Senescence ; Cisplatin ; pharmacology ; Cyclin-Dependent Kinase Inhibitor p19 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Hep G2 Cells ; Humans ; Tumor Suppressor Protein p53 ; metabolism ; Up-Regulation

Objective: To understand the harm degree of underground noise and provide basis for noise control. Methods: In November 2019, 13 typical coal mines in Sichuan Province were selected as the research objects, and a total of 1203 sites and 609 jobs of noise exposure were investigated. Results: The noise intensity P75 >80 dB (A) was measured. The noise intensity of the inspection place of the air compressor is >86 dB (A) , the noise intensity of the inspection place of the gas drainage and the operation place of the main fan is between 80-85 dB (A) . Conclusion: Besides the harm of dust, noise exposure should also be paid attention to, and the measures of sound absorption and sound insulation should be taken or personal protection should be strengthened.
Coal ; Coal Mining ; Dust/analysis* ; Noise ; Occupational Exposure

In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.
Animals ; Male ; Rats ; Caspase 3/metabolism* ; Collagen ; Disease Models, Animal ; Hypertension, Pulmonary/drug therapy* ; Monocrotaline/adverse effects* ; Panax notoginseng/chemistry* ; Proliferating Cell Nuclear Antigen/pharmacology* ; Pulmonary Arterial Hypertension ; Pulmonary Artery/metabolism* ; Rats, Sprague-Dawley ; Receptor, Notch3/genetics* ; RNA, Messenger ; Saline Solution ; Signal Transduction ; Saponins/pharmacology*

ObjectiveTo explore the effect of health locus of control on the early rehabilitation after anterior cruciate ligament（ACL） reconstruction. MethodsFrom July 2019 to October 2019， a prospective cohort study of 155 ACL patients receiving reconstruction （male=124 and female=31） in our hospital was conducted. The general data questionnaire， MHLC-C， Tegner activity score， IKDC Score， Lysholm Score and Y-Balance Test were used for further analysis. The correlation between HLC and early rehabilitation after ACL reconstruction was explored by Wilcoxon signed-rank tests， correlation analysis and Logistics regression analysis. ResultsPositive correlations were found between the internality health locus of control （IHLC） and the IKDC score （r_3m=0.77， r_6m=0.70， P<0.001）， as well as the Lysholm scores （r_3m=0.68， r_6m=0.64， P<0.001） and the Tegner activity score （r_3m=0.24， r_6m=0.46， P<0.05） in 3 and 6 months after surgery， and higher IHLC score indicated a better y-balance test outcome［OR 95%CI=0.86（0.76， 0.97）， P=0.016］. Chance health locus of control （CHLC） was negatively correlated with the IKDC score （r_3m=-0.71， r_6m=-0.67， P<0.001）， the Lysholm score （r_3m=-0.49， r_6m=-0.43， P<0.001） and the Tegner activity score （r_3m=-0.22， r_6m=-0.35， P<0.05） in 3 and 6 months after surgery， and higher CHLC score indicated worse outcome of y-balance test ［OR 95%CI=1.26（1.12， 1.41）， P<0.001］. There was a negative correlation between the Powerful others health locus of control （PHLC） and the IKDC score （r_3m=-0.51， r_6m=-0.50， P<0.001）， the Lysholm scores （r_3m=-0.36， r_6m=-0.40， P<0.001）， but there was no correlation with the Tegner activity score in 3 and 6 months after surgery（P>0.05）. The risk of poor y-balance test increased by higher score of PHLC ［OR 95%CI=1.74（1.29， 2.34）， P<0.001］. ConclusionA significant correlation was found between the health locus of control and the early rehabilitation effect after ACL reconstruction. Higher internality health locus of control scores indicated a better rehabilitation outcome， while higher scores of external loci of control indicated higher risk of worse rehabilitation outcome.

Professor is a well-known national veteran doctor with over 70 years of clinical experience. He has unique academic thoughts and clinical experience for common diseases and some difficult and complicated diseases. This paper mainly introduces professor 's syndrome-differentiation thought and experience of acupoint selection for hot flashes. It is emphasized that common hot flashes, such as hot flashes and night sweats, are different between and . While regulating and , more attention should be paid to - harmony, which is not only suitable for women's perimenopausal syndrome, but also for a series of clinical diseases caused by refractory drugs such as endocrine therapy after breast cancer surgery. At the same time of acupoint selection based on syndrome differentiation, a more rational prescriptions should be made according to the duration of the disease and the experience acupoints to improve the clinical efficacy.
Acupuncture Points ; Acupuncture Therapy ; Breast Neoplasms ; surgery ; Female ; Hot Flashes ; therapy ; Humans ; Syndrome

Objective: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT) . Methods: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2) . Group 2 (n=96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2) . Results: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1-62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG) . The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%, the median time of neutrophil engraftment for group 1 and 2 was 16 (10-41) days vs 17 (11-33) days (P=0.705) . The ratio of platelet engraftment was 88.5% for group 1 and 87.5% for group 2, the median time of platelet engraftment was 35 (11-113) days vs 38.5 (13-96) days (P=0.317) . The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7% (95%CI 31.4%-45.9%) for group 1 and 50.0% (95%CI 39.6%-59.6%) for group 2 (P=0.075) , but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P=0.036) . Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2) : 17.7% (95%CI 11.7%-24.9%) vs 22.7% (95%CI 4.4%-32.2%) after 3 years (P=0.288) . The median follow-up time was 742 (335-2 512) days. The 3-year OS was 72.1% for group 1 and 60.5% for group 2 (P=0.079) . There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9% (95%CI 56.2%-72.3%) vs 55.4% (95%CI 44.4%-65.0%) (χ(2)=3.027, P=0.082) ]. Non-relapse mortality for group 1 was 12.1% (95%CI 7.7%-17.4%) and for group 2 was 16.7% (95%CI 10.0%-24.8%) (P=0.328) . Conclusion: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.
Adolescent ; Adult ; Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; Female ; Graft vs Host Disease ; HLA Antigens ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Receptors, KIR ; Retrospective Studies ; Young Adult

The samples of Huangqi injection (HI) were analyzed by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-TOF-MS), and both positive and negative ion modes were employed to obtain the LC-TOF-MS analysis information of chemical compounds in HI. Then the mass defect filtering (MDF) approach, which was developed based on the previously published articles, was utilized to rapidly screen the astragalosides from the obtained LC-TOF-MS data. Each screened astragaloside was confirmed by the presence of no less than 2 quasi-molecular ions. All the screened astragalosides were then tentatively assigned according to the parent ion and daughter ion information. Finally, a total of 62 astragalosides were screened and characterized from the HI samples, including 15 new detected ones. The identification results indicated that acetylation, hydrogenation, dehydrogenation, methoxylation and hydration might be the major conversion reactions involved in the formation of the astragalosides. The LC-TOF-MS-based MDF approach was proved to be a feasible and efficient tool to screen the chemical constituents in complex matrices such as herbal medicines.