Breast Neoplasms ; diagnosis ; genetics ; metabolism ; Carcinoma, Intraductal, Noninfiltrating ; genetics ; metabolism ; Chromosomes, Human, Pair 17 ; genetics ; Female ; Genetic Heterogeneity ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Polyploidy ; Receptor, ErbB-2 ; genetics ; metabolism

We analyzed the anticancer effect and mechanism of the novel indoleamine 2,‍3-dioxygenase 1 (IDO1) inhibitor NLG-919 combined with temozolomide (TMZ) on human glioma cell lines. The anti-tumor activity of NLG-919 and temozolomide after single and combined treatments was detected by MTT assay. Colony formation assay, invasion assay and migration assays were used to detect the effects of NLG-919 and temozolomide alone or in combination on proliferation, invasion and migration of human glioma cells. A flow cytometry assay was used to detect cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) production and mitochondrial membrane potential damage (JC-1). An immunofluorescence assay was used to detect the expression level of IDO1 and HPLC was used to detect the expression level of L-kynurenine (Kyn) to explore the anti-tumor mechanism of NLG-919 and temozolomide. The results show that NLG-919 had a weak in vitro inhibitory effect compared to that of temozolomide. The IC₅₀ of NLG-919 on U251 cells and U87 after 72 h was 26.9 and 30.7 μmol·L^-1, respectively. However, when NLG-919 was used in combination with temozolomide, its anti-glioma activity was significantly increased. Compared with the single treatment, the combination treatment had a potent ability to inhibit proliferation, invasion and migration of glioma cells. Combination treatment improved the capacity of temozolomide to induce cell cycle arrest and inhibit the growth of glioma cells. NLG-919 significantly down-regulated the expression and activity of IDO1 in glioma cells, and the inhibitory effect was improved after combination with temozolomide, and effectively blocked the production of Kyn through the metabolism of L-tryptophan (Trp). In conclusion, the IDO1 inhibitor NLG-919 and temozolomide showed synergistic effects in the anticancer therapy of human glioma cell lines.

In the study, to explore the anti-tumor effects and mechanisms of chlorpromazine (CPZ) and perphenazine (PPZ) combined with temozolomide (TMZ) on human glioma cell lines, we performed MTT assays to determine the growth inhibitory rate of CPZ, PPZ and TMZ in mono and combined treatments. The anti-tumor effects of CPZ and PPZ alone or in combination with TMZ were determined by colony formation, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) detection (JC-1). The expression level of p53 was detected by immunofluorescence assay. Furthermore, autophagy under different administrations was detected by flow cytometry and confocal imaging to explore the anti-tumor mechanism of CPZ and TMZ. Protein phosphatase 2A (PP2A), cancerous inhibitor of protein phosphatase 2A (CIP2A) and proto-oncogene protein (c-Myc) were detected by immunofluorescence assay, tumor stem cell markers (CD44, CD133) and aldehyde dehydrogenase (ALDH) were detected by flow cytometry to explore the anti-tumor mechanism of PPZ and TMZ. The results showed that after 72 h treatments of combinations, the values of half maximal inhibitory concentration (IC₅₀) of TMZ on U87 and U251 cells were reduced, and the ability of TMZ to induce apoptosis and cycle arrest was improved. In addition, the combination of CPZ and TMZ could induce an increased effect of autophagy via activating the relevant pathway of p53 gene in glioma cells. The combination of PPZ and TMZ increased the sensitivity of glioma cells to TMZ, and the underlying mechanism might be related to the inhibition of CIP2A/PP2A/c-Myc signaling pathway. In conclusion, CPZ and PPZ combined with TMZ, showed the significant synergistic effects in cancer treatment, which are the novel and potential therapeutic regimens providing a new treatment strategy for human glioma.

Glypican-3 (GPC3) is an oncofetal protein anchored on the plasma membrane and highly expressed in hepatocellular carcinoma (HCC).GPC3 could he used as a biomarker for the diagnosis of HCC and the serum levels of GPC3 in liver cancer patients has a significant role for their prognosis.Moreover, GPC3 in HCC cells is immunoreactive, rendering it a suitable target for the treatment of HCC.Nowadays, several clinical trials targeting GPC3 for HCC therapy have already been conducted: new anti- GPC3 antibodies are generated; the clinical trials about its combination administration with other targeted medicines are being in progress; (tP(3-targeted TRAB, GPC3 vaccines and GPC3-based chimeric antigen receptor T-cells (CAR-T) therapy are under investigation.In this review, we briefly discuss the structure of GPC3, its role in HCC pathogenesis and summarize the recent development in the clinical application of GPC3.We firmly believe that GPC3 would be a promising target for HCC therapy.And further studies focusing on GPC3 should provide us more solid evidence.

Objective To discuss the important role of undergraduate students' social practice in medical education.Methods Questionnaires on social practice activity were answered by medical students,and the characteristics and shortages of social practice were analyzed.The development policy was proposed after expert inquiry and comparison with other universities. Results Undergraduate students' social practice in School of Medicine,Shanghai Jiaotong University presentd the four characteristics: positive participation,obvious characteristic,abundance items,and wide range of services.But there were insufficiencies in form of action,multiplication of selected topic,socialized operation method,and time arrangement. Conclusion The results suggest that further improvement is necessary in the service quality,advance in the activities' pertinence,development in innovation ability,and enhancement in base construction and support system.

OBJECTIVETo establish an efficient and stable method for protein extraction of Streptococcus mutans.

METHODSThe collected bacteria were treated by freeze-thaw and ultrasonic (method 1), ultrasonic (method 2), boiling (method 3), boiling and ultrasonic (method 4), respectively. The index such as state of bacteria broken, concentration of extracted protein and SDS-PAGE of protein were employed to evaluate the effects of above four methods.

RESULTSBeside the method 3, the other three methods could break the bacteria effectively, of which ultrasonic was the key factor. The pattern of SDS-PAGE which treated by method 1, method 2 and method 4 was almost same, but method 1 resulted in the best abundance. There was significantly difference among the four protein concentration extracted by four methods (P < 0.05). All methods exhibited good stability and reproducibility.

CONCLUSIONMethod of freeze-thaw and ultrasonic resulted in an efficient proteins extraction of Streptococcus mutans which demonstrated good stability and reproducibility and easy to handle.

Bacterial Proteins ; Reproducibility of Results ; Streptococcus mutans

OBJECTIVETo investigate the antibacterial activity of decoction of Radix glycyrrhizae against Streptococcus mutans (S. mutans) in vitro.

METHODSThe decoction of Radix glycyrrhizae was prepared by boiling particles of Radix glycyrrhizae, the diameter was 0.2-3.2 mm. In distilled water and filtered, the filtrate was collected for study. The minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of the decoction against S. mutans were detected using double dilution. The effect of decoction on growth and acidogenic profile of S. mutans were investigated by detecting the Abs of bacteria suspension and the pH value of medium at definite time intervals(0, 3, 7, 12, 23, 40 h) during cultured.

RESULTSThe MIC determined for decoction was 50 mg x mL(-1) and there was no bactericidal effect when concentration of decoction lower than 100 mg x mL(-1). The decoction inhibitted multiplication of bacteria significantly and the effects became stronger with concentration increasing. The decoction also inhibitted S. mutans producing acid and the effect became stronger with concentration increasing. The most efficient inhibition were observed when incubated 12 hours.

CONCLUSIONThe decoction of Radix glycyrrhizae can inhibite the growth and acid-production of S. mutans in vitro.

Anti-Bacterial Agents ; Bacteria ; In Vitro Techniques ; Microbial Sensitivity Tests ; Plant Extracts ; Streptococcus mutans

OBJECTIVETo study the advantages of Chinese medicine (CM) in treating insulin resistance and disorders of glucose and lipid metabolism in patients with polycystic ovarian syndrome (PCOS), and to explore its underlying mechanisms.

METHODSOne hundred PCOS patients were assigned to three groups: 40 patients in the CM group treated by CM, 30 in the WM1 group treated by metformin, and 30 in the WM2 group treated by cyproterone. Before treatment and at 3 cycles and 6 cycles after treatment, changes of body mass index (BMI), fasting serum insulin (FINS) and fasting blood sugar (FBG) levels as well as lipid spectrum were measured and the homeostasis model of insulin resistance (HOMA-IR) was calculated. Meanwhile, the recovery of ovulation was observed.

RESULTSThere were 30, 22 and 23 patients in the CM, WM1 and WM2 group respectively completed their 6-month treatments. Levels of FINS, FBG, HOMA-IR, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were lowered and high-density lipoprotein cholesterol (HDL-C) level increased in the CM group after 6-month treatment, showing significant difference as compared with the baseline (P < 0.05), and the difference in comparing with the WM2 group was statistically significant in terms of MBI, FINS, FBG, HOMA-IR, TC and LDL-C (P < 0.05). The ovulation rate was 53.3% (16/30) in the CM group, 27.3% (6/22) in the WM1 group and 21.7% (5/23) in the WM2 group, comparison between them showed a significant difference between the CM group and the WM2 group (P < 0.01).

CONCLUSIONCM is effective for the treatment of PCOS in improving insulin resistance, adjusting blood sugar and lipids levels and recovering ovulation.

Adolescent ; Adult ; Blood Glucose ; metabolism ; Cholesterol, HDL ; blood ; Cyproterone ; therapeutic use ; Drugs, Chinese Herbal ; Female ; Humans ; Insulin ; blood ; Insulin Resistance ; Lipids ; blood ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Metabolic Diseases ; blood ; Metformin ; therapeutic use ; Polycystic Ovary Syndrome ; blood ; drug therapy ; Young Adult

OBJECTSTo investigate the distribution of vitamin D receptor (VDR) genotypes among the Hans of a lead contaminated mine in Shanxi and explore the relationship between blood lead levels and the genetic polymorphism of VDR gene.

METHODSVDR genotypes were determined by polymerase-chain-reaction and restrictive fragment length polymorphism (PCR-RFLP) and the blood lead level was measured by using the graphite furnace atomic absorption spectrometry in a population of 120 pre-school children aged 5 - 6 years who were from the mine kindergarten and were unrelated Hans. An environmental questionnaire in relation to blood lead level was filled for each subject.

RESULTS(1) The gene distribution of the VDR phenotypes in these children was VDRBB, 1.7%; VDRBb, 9.2%; VDRbb, 89.2%. (2) The mean blood lead level of the children who had VDR B allele [(0.910 8 +/- 0.265 0) micromol/L] was significantly higher than that whose VDR genotype was bb [(0.740 1 +/- 0.270 1) micromol/L (mean +/- standard deviation)] (t = 2.155, P < 0.05). (3) Many factors were found to affect the blood lead levels, such as the VDR genotype, the type of fuel, educational level of mothers and so on. After controlling the possible confounding variables by multiple regression, the contribution of the VDR phenotype to the blood lead levels was still statistically significant.

CONCLUSIONThese results indicated that the frequency distribution of the VDR genotype in these children was apparently different from that in Caucasians who had high frequencies of VDR B. The results also indicated that the individuals carrying the VDR B allele were more susceptible to lead poisoning.

Child ; Child, Preschool ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lead ; blood ; Lead Poisoning ; genetics ; Multivariate Analysis ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Receptors, Calcitriol ; genetics ; Regression Analysis ; Surveys and Questionnaires

The expressions of vimentin and NF-?B were detected in thyroid tissue by immuno- histoehemistry in 26 cases with Hashimoto′s thyroiditis and 9 normal subjects.The results showed that there was a significantly increased expression of vimentin in Hashimoto′s thyroiditis as compared with the normal controls.It indicated that epithelial-mesenchymal transformation existed in follicular epithelial ceils of Hashimoto′s thyroiditis. Furthermore,the expression of vimentin was closely related with NF-?B.