Objective: To evaluate the affect for quality by crushing technology, The dissolution of Yufengningxin Tablets being prepared by different crushing technology was determined by taking the dissolution of puerarin as test marker. Methods: The Tablets were prepared with the fine powder of Pueraria crude drug which was crushed by normal crusher or super fine crusher. The rotatory basket method was used, the cumulative dissolution percentage was determined by HPLC. Results: Statistics indicated there was a significant difference in dissolution parameter (T 50 ) between super fine crushing powder Tablets and normal fine crushing powder Tablets P

Objective To investigate the factors that influence the consistency of international normalized ra tio (INR) of prothrombin time. Methods Using the same automated blood coagulation analyzer and INR calibration plasma with two different types of prothrombin time (PT) reagent to assay the INR values of 19 controls (group 1), 12 patients who took long-term anticoagulant orally (group 2),12 patients who took it at the first time (group 3) and 8 patients who took long-tern anticoagulant togeth er with cephalosperin N (group 4). Results The two kinds of reagents gave quite different INR val ues in all four groups (P＜0.01). The INR difference in group 3 (0.23±0.07, n = 12) was larger than that in group 2 (0.51±0.20, n=12) (P＜0.01) .The difference in group 4 (0.61 ±0.21, n=8) was larger than that in group 2 ( P＜0.01). Conclusions The factors that may influence INR consistency are the source and sensitivity of the reagents , as well as the period of the anticoagulant been taken and the other drugs taken at the same time.

Panax notoginseng (PN) is one of the commonly used clinical medicines for cardiovascular diseases and possesses a variety of pharmacological effects. P. notoginseng saponins (PNS) are the most important bioactive components in PN. The purpose of this study was to explain the mechanism of PNS on molecular network level. 18 targets of the main medicinal ingredients of PNS were gained by virtual screening based on pharmacophores and data mining. A protein interaction network of PNS was constructed with 189 nodes and 721 interactions. By a graph theoretic clustering algorithm Molecular Complex Detection (MCODE), 14 modules were detected. Gene ontology (GO) enrichment analysis of the modules demonstrated that the roles of PNS played in cardiovascular disease related to multiple biological processes, which could represent the characteristics of traditional Chinese medicine (TCM) as a whole to regulate the disease. The results showed that the blood circulation and hemostasis efficacy of PN related with the biological processes such as positive regulation of cAMP metabolic and biosynthetic process, platelet activation and regulation of blood vessel size, regulation of T cell proliferation and differentiation and so on. Therefore, the module-based network analysis will be an effective method for better understanding TCM.
Drugs, Chinese Herbal ; chemistry ; Humans ; Panax notoginseng ; chemistry ; Protein Interaction Maps ; drug effects ; Proteins ; chemistry ; Saponins ; chemistry

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

OBJECTIVETo determine the mechanism underlying the therapeutic activities of glycogen synthase kinase 3b (GSK3b) against hepatic ischemia-reperfusion (H-IR) injury by investigating the inhibitive effects of GSK3b on inflammation mediated by Toll-like receptor 4 (TLR4).

METHODSC57BL/6 male mice were subjected to 90 min of warm liver cephalad lobe ischemia, followed by reperfusion for various lengths of time. The mice were divided into three groups: the H-IR untreated model (control group), and the H-IR inflammation-induced models that received an intraperitoneal injection of purified lipopolysaccharide (LPS) endotoxin alone (inflammation group) or with pretreatment of the SB216763 GSK3b-specific inhibitor (intervention group). To create a parallel isolated cell system for detailed investigations of macrophages, marrow-derived stem cells were isolated from femurs of the H-IR control group of mice and used to derive primary macrophages. The cells were then divided into the same three groups as the whole mouse system: control, LPS-induced inflammation model, and inflammation model with SB216763 intervention. Differential expressions of inflammation-related proteins and genes were detected by Western blotting and real-time quantitative PCR, respectively.

RESULTSThe phosphorylation levels of ERK, JNK and p38 MAPK were induced in liver at 1 h after reperfusion, but then steadily decreased and returned to baseline levels by 4 h after reperfusion. In addition, the phosphorylation levels of ERK and JNK were induced in macrophages at 15 min after LPS stimulation, while the phosphorylation level of p38 MAPK was induced at 1 h; SB216763 pretreatment suppressed the LPS-stimulated ERK, JNK and p38 phosphorylation in macrophages. In the mouse model, GSK3b activity was found to promote the gene expression of anti-inflammatory cytokine IL-10 (control: 0.21 ± 0.08, inflammation: 0.83 ± 0.21, intervention: 1.76 ± 0.67; F = 3.16, P = 0.027) but to significantly inhibit the gene expression of pro-inflammatory cytokines IL-12 (control: 0.11 ± 0.05, inflammation: 0.85 ± 0.11, intervention: 0.43 ± 0.10; F = 2.67, P = 0.038), TNF-a, (control: 0.052 ± 0.012, inflammation: 8.11 ± 0.98, intervention: 3.9 ± 0.82; F = 4.13, P = 0.016), IL-6 (control: 0.22 ± 0.08, inflammation: 6.37 ± 0.81, intervention: 2.11 ± 0.63; F = 3.21, P = 0.024), and IL-1b (control: 0.12 ± 0.07, inflammation: 2.51 ± 0.62, and intervention: 1.28 ± 0.33; F = 2.22, P = 0.030).

CONCLUSIONInhibition of GSK3b selectively regulates the expression of anti-inflammatory and pro-inflammatory cytokines in liver Kupffer cells (liver macrophages). This process may be one of the mechanisms underlying the ability of GSK3b to ameliorate hepatic ischemia-reperfusion injury, possibly because inhibition of pro-inflammatory cytokines may indirectly mediate liver cell apoptosis.

Animals ; Cells, Cultured ; Cytokines ; metabolism ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Inflammation ; metabolism ; pathology ; Lipopolysaccharides ; adverse effects ; Liver ; pathology ; Macrophages ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury ; Toll-Like Receptor 4 ; metabolism

OBJECTIVETo investigate the role of the key intracellular signaling molecule glycogen synthase kinase-3 beta in the mechanism of liver ischemia reperfusion (IR).

METHODSC57BL/6 mice were subjected to 90 min warm liver cephalad lobe ischemia, followed by various length of reperfusion. Experiment groups included sham control group, liver IRI model group and glycogen synthase kinase-3 beta inhibitor-treated group (SB216763 in DMSO, 25 g/kg, i.p, 2 hour prior to the onset of liver ischemia). The expression of glycogen synthase kinase-3 beta protein was analysed by Western blotting. The serum ALT levels were determined to reflect the function of liver. The affected liver lobes were harvested for histology analysis. The inflammatory gene expression was detected by Quantitative PCR.

RESULTSBy western blot analysis, we found that ischemia itself activated glycogen synthase kinase-3 beta by a significant decrease of its phosphorylation. Glycogen synthase kinase-3 beta inhibitor SB216763-pretreatment ameliorated the liver damages significantly as compared to the controls (sALT: 2046+/-513 U/L vs 5809+/-1689 U/L, P = 0.0153), and suppressed the gene expressions of IL-12, TNFa, IL-1b and IL-6.

CONCLUSIONSThis study demonstrated that the ischemia process modulated liver innate immune activation via a GSK-3-dependent mechanism which favored the development of a pro-inflammation response and lead to liver tissue damages. GSK-3b may be a new therapeutic target to ameliorate liver IRI in transplant patients.

Animals ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Inflammation ; metabolism ; Liver ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury ; metabolism ; pathology

OBJECTIVETo observe the effect of RNA interference on CHK1 and CHK2 expression and change of G2/M phase arrest in esophageal carcinoma cells after irradiation.

METHODSFour sequences short hairhip RNA (shRNA) of each CHK1 and CHK2 genes were constructed and connected with vector of pENTR/U6 plasmid, respectively, and then transfected into Eca109 cells with lipofectamine 2000 reagent. Protein and mRNA expression of CHK1 and CHK2 genes were detected with Western blotting and RT-PCR, respectively. Cell cycling was measured by flow cytometry after 5 Gy irradiation. Cell survival rate after 5 Gy irradiation was evaluated by clonegenetic assay.

RESULTSFour shRNA vector each of CHK1 and CHK2 genes were successfully constructed and transfected into Ecal09 cells, respectively. Protein expression of CHK1 and CHK2 were obviously decreased. Their mRNA expressions were also decreased after transfected with shRNA of CHK1 and CHK2. Arrest of G2/M stage in Eca109 cells were obviously decreased only in cells transfected with CHK1 shRNA but not with CHK2 shRNA at 12 h after 5 Gy irradiation. In first progeny Eca109 cells transfected with CHK1 and CHK2 shRNA, expression of CHK1 and CHK2 protein was also decreased. The level of phosphorylated CHK2-T68 expression was decreased at 1 h after 5 Gy irradiation, and at 72 h only transfected with CHK2 shRNA but not with CHK1 shRNA. Phosphorylation level of CHK1-S345 was not increased after transfected with CHK1 or CHK2 shRNA, but arrest of G2/M stage still remained at 12 h after 5 Gy irradiation and at 72 h accordingly. The cell survival rate was decreased in Eca109 cells transfected with CHK1 or CHK2 shRNA after 5 Gy irradiation.

CONCLUSIONAfter transfected with shRNA of CHK1 or CHK2, their expressions of mRNA and protein in Ecal09 cells are markedly inhibited and this inhibition effect can be observed in their first progeny cells and at least hold for 3 days. Arrest of G2/M phase can be reduced after irradiation when teansfected with shRNA of CHK1 and the radiosensitivity of Ec109 cells can be increased.

Blotting, Western ; Cell Division ; genetics ; physiology ; radiation effects ; Cell Line, Tumor ; Cell Survival ; genetics ; physiology ; radiation effects ; Checkpoint Kinase 1 ; Checkpoint Kinase 2 ; Esophageal Neoplasms ; genetics ; pathology ; physiopathology ; G2 Phase ; genetics ; physiology ; radiation effects ; Gamma Rays ; Genetic Vectors ; Humans ; Protein Kinases ; genetics ; metabolism ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; RNA Interference ; RNA, Small Interfering ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection

Objective: To investigate the expression of TSLP in human lung cancer tissue and the correla-tion between TSLP expression and number of regulatory T cells (Tregs). Methods: The expression of TSLP mRNA and protein was detected in different pathological lesions of the lung by Q-RT-PCR and immunohisto-chemistry. Immunohistochemistry was used to detect Foxp3+ Tregs. The correlation of TSLP with the number of Tregs was analyzed. Results: TSLP gene was expressed in tumor tissues (n=37), latero-tumor tissues (n=29) and non-tumor lung tissues (n=24), without statistical difference (P=0.148). TSLP protein was expressed in the cytoplasm and was observeed in 69.57% of tumor tissues, 13.33% of benign lesions and 30.00% of non-tumor lung tissues, with a significant difference (P<0.05). The expression of TSLP protein was correlated with tumor size (P=0.000) and lymph node metastasis (P=0.018). The number of Tregs in TSLP positive group was more than that in TSLP negative group (P<0.05). Conclusion: The expression of TSLP in lung tu-mor tissues is increased and is correlated with the number of Tregs, indicating that TSLP could induce Treg to play an important role in tumor immunotolerance.

Objective To evaluate the prevalence of depressive symptoms and influencing factors among adolescents. Methods A total of 635 students aged 13 to 18 years were selected in March 2017 and were investigated with general information questionnaire, CES-D and CTQ-SF. Results 630 questionnaires are effective and the positive rate of depression was 29.84％(188/630) . The average score of CTQ was 32.15±2.98; 38.73％ of the students were disregarded and only 2.22％ of that were abused during their childhood. 40.00％ of the students had no CTQ, 1 kinds of CTQ accounted for 31.43％ , 2 kinds of CTQ accounted for 18.25％, and more than 3 CTQ accounted for 10.32％. Multivariate logistic regression analysis show that gender (OR=1.034, 95％ CI: 1.012-1.056) , parents' marital status (OR=1.124, 95％ CI: 1.087-1.162) , family atmosphere (OR=1.025, 95％ CI: 1.024-1.158) , CTQ cumulative number (ORCTQ=1=1.528, 95％ CI: 1.214-1.923; ORCTQ=2=3.067, 95％ CI: 1.325-7.102; ORCTQ≥3=10.361, 95％ CI: 3.059-35.093) were the risk factors for depression. Conclusion Gender, parents' marital status, family atmosphere and CTQ cumulative number were risk factors for depression in adolescents.

OBJECTIVETo study the clinical characteristics, diagnosis and surgical effects of thyroid-stimulating hormone pituitary adenomas (TSH-omas).

METHODSThe clinical data of 19 patients (14 female and 5 male) with TSH-omas were analyzed retrospectively in this study from January 2001 to December 2008. The patients ranged from 20 to 70 years old (average 40.5 years old) and had disease histories from 1 to 228 months (average 55 months). Among these patients, 15 of them complained of thyrotoxicosis symptoms, while the other 4 patients' symptoms were associated with headache and/or visual disturbance caused by the tumor mass effect. Initially, 12 of the 15 patients with thyrotoxicosis symptoms were misdiagnosed with Grave's disease. As a result 2 of them received (131) Iodine, and one received subtotal thyroidectomy. All of these patients underwent transsphenoidal microsurgery.

RESULTSAverage follow-up period was 3.6 years (6 months-7 years). Pathological analysis of the surgical specimen showed pituitary adenoma in all patients, immunohistochemistry were positive for TSH in 17 cases, negative for TSH in 2, positive for growth hormone in 2, positive for prolactin in 1, and positive for adrenocorticotrophic hormone in 1. Postoperative MRI revealed that the tumors in 15 patients were removed totally, though 4 patients still had residual tumors. The thyroid hormone level tests suggested that 13 patients could be considered normal 3 months after their tumors were removed, though 2 of patients with normal postoperative MRI and thyroid hormones showed increased levels of TSH. For these 2 patients, tumors did not recur and their thyroid hormone levels returned to normal after pituitary radiotherapy. The cure rate was 11/19 after surgery and 13/19 after surgery plus pituitary radiotherapy.

CONCLUSIONSThe screening test for hyperthyroidism patients with high TSH levels is a key point to improve the accuracy rate in early diagnoses of TSH-omas. The transsphenoidal microsurgery is first choice to treat TSH-omas, while pituitary radiotherapy and somatostatin analogs are beneficially adjunctive therapies.

Adult ; Aged ; Female ; Humans ; Hyperthyroidism ; metabolism ; Male ; Middle Aged ; Pituitary Neoplasms ; diagnosis ; metabolism ; surgery ; Retrospective Studies ; Thyrotropin ; metabolism ; Young Adult