Synergistic effect of Hsp90 inhibitor ginkgolic acids C15 ꞉1 combined with paclitaxel on nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVES@#Nasopharyngeal cracinoma is a kind of head and neck malignant tumor with high incidence and high mortality. Due to the characteristics of local recurrence, distant metastasis, and drug resistance, the survival rate of patients after treatment is not high. Paclitaxel (PTX) is used as a chemotherapy drug in treating nasopharyngeal carcinoma, but nasopharyngeal carcinoma cells are easy to develop resistance to PTX. Inhibition of heat shock protein 90 (Hsp90) can overcome common signal redundancy and resistance in many cancers. This study aims to investigate the anti-tumor effect of ginkgolic acids C15꞉1 (C15:1) combined with PTX on nasopharyngeal carcinoma CNE-2Z cells and the mechanisms.@*METHODS@#This experiment was divided into a control group (without drug), a C15:1 group (10, 30, 50, 70 μmol/L), a PTX group (5, 10, 20, 40 nmol/L), and a combination group. CNE-2Z cells were treated with the corresponding drugs in each group. The proliferation of CNE-2Z cells was evaluated by methyl thiazolyl tetrazolium (MTT). Wound-healing assay and transwell chamber assay were used to determine the migration of CNE-2Z cells. Transwell chamber was applied to the impact of CNE-2Z cell invasion. Annexin V-FITC/PI staining was used to observe the effect on apoptosis of CNE-2Z cells. The changes of proteins involved in cell invasion, migration, and apoptosis after the combination of C15꞉1 and PTX treatment were analyzed by Western blotting.@*RESULTS@#Compared with the control group, the C15꞉1 group and the PTX group could inhibit the proliferation of CNE-2Z cells (all P<0.05). The cell survival rates of the C15꞉1 50 μmol/L combined with 5, 10, 20, or 40 nmol/L PTX group were lower than those of the single PTX group (all P<0.05), the combination index (CI) value was less than 1, suggesting that the combined treatment group had a synergistic effect. Compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the combination group significantly inhibited the invasion and migration of CNE-2Z cells (all P<0.05). The results of Western blotting demonstrated that the combination group could significantly down-regulate Hsp90 client protein matrix metalloproteinase (MMP)-2 and MMP-9. The results of double staining showed that compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the apoptosis ratio of CNE-2Z cells in the combination group was higher (both P<0.05). The results of Western blotting suggested that the combination group could decrease the Hsp90 client proteins [Akt and B-cell lymphoma-2 (Bcl-2)] and increase the Bcl-2-associated X protein (Bax).@*CONCLUSIONS@#The combination of C15꞉1 and PTX has a synergistic effect which can inhibit cell proliferation, invasion, and migration, and induce cell apoptosis. This effect may be related to the inhibition of Hsp90 activity by C15꞉1.

Exploration on training model of general practitioners in county medical community with the outreaching of medical consortium / 中华全科医师杂志

In recent years, a number of policies have been implemented to strengthen the cultivation of general practitioners in China. However, the development of community-level health professionals is still lagging behind, the development is uneven among regions, the overall number of general practitioners is insufficient, and the quality of medical services needs to be improved. Based on the Shanhai (Mountain and Sea) promotion project, with the close cooperation between the Second Affiliated Hospital and the medical consortium unit Suichang County People′s Hospital, a " Joint Cultivation by Dual-Teachers " model has been applied in training general practitioners for Suichang county community since March 2021. In this article we discuss the optimization and integration of medical and health resources through the outreaching assistance of high-quality personnel, management and system of medical service, to comprehensively upgrade the primary care and the quality of grass-roots general practitioners in remote mountainous areas.

Expression and significance of chemokine CXCL12 and receptor CXCR4 in adenomyosis / 中华妇产科杂志

Objective:To observe the expression, correlation and significance of chemokine (C-X-C motif) ligand 12 (CXCL12) and chemokine (C-X-C motif) receptor 4 (CXCR4) in endometrium and myometrium of adenomyosis.Methods:Totally 38 patients were selected in this study, who underwent hysterectomy for adenomyosis at Beijing Obstetrics and Gynecology Hospital from October 2017 to December 2018 as the adenomyosis group, and, in the same period, selected 31 patients with cervical intraepithelial neoplasia Ⅲ or cervical cancer undergoing hysterectomy served as control group. The expression levels of mRNA and protein for CXCL12, CXCR4 in the endometrium and myometrium of the two groups were detected by immunohistochemistry and real-time PCR.Results:(1) The protein levels of CXCL12 and CXCR4 in endometrium in uterus with adenomyosis (0.229±0.025 and 0.226±0.016) were significantly higher than those in endometrium in uterus without adenomyosis (0.153±0.018 and 0.178±0.026); compared with each other, the differences were statistically significant (all P<0.05). And the expressions of CXCL12 and CXCR4 proteins in uterine myometrium of adenomyosis were 0.222±0.045 and 0.126±0.058, respectively, which were higher than those in the control group (0.091±0.029 and 0.099±0.020); compared with each other, the differences were statistically significant (all P<0.05). (2) The expression levels of CXCL12 and CXCR4 mRNA in endometrium of patients with adenomyosis were 6.31±0.12 and 8.49±0.21, respectively, which were higher than those in the control group (1.23±0.10 and 1.36±0.13); compared with each other, the differences were statistically significant (all P<0.05). Moreover, the expression levels of CXCL12 and CXCR4 mRNA in myometrium of patients with adenomyosis were 9.11±0.12 and 8.45±0.16, respectively, which were higher than those in the control group (1.18±0.08 and 1.46±0.13); compared with each other, the differences were statistically significant (all P<0.05). (3) In endometrium and myometrium of uterus with adenomyosis, CXCL12 and CXCR4 mRNA expression levels were positively associated ( r=0.478, 0.542, all P<0.05). Conclusions:The levels of CXCL12 and CXCR4 in the endometrium and myometrium of adenomyosis are increased and positively correlated. The two chemokine may be involved in the development of adenomyosis.

Effect of methanol-ethyl acetate partitioned fractions from on proliferation and apoptosis of human non-small cell lung cancer H1975 cells / 南方医科大学学报

OBJECTIVE@#To investigate the effects of methanol-ethyl acetate partitioned fractions from (MEDS) on the proliferation and apoptosis of human non-small cell lung cancer H1975 cells.@*METHODS@#The systemic solvent extraction method was used to preliminary separation of the effective fractions in the methanol extract of . The cytotoxicity of each extract (5, 10, 20, 40, and 80 μg/mL) was tested using MTT assay. Colony cloning method was used to assess the effect of different concentrations of methanol-ethyl acetate partitioned fractions from MEDS (5, 10, 20, 40, and 80 μg/ mL) on the proliferation of H1975 cells. Flow cytometric analysis with Annexin V-FITC/PI staining was performed to detect the apoptosis of the cells after treatment with different concentrations of MEDS fractions (10, 20, and 40 μg/mL). Western blotting was used to evaluate the effects of MEDS fractions on the expressions of apoptosis-related proteins Akt, Bax, and Bcl-2. The anti-tumor activity of 100 mg/kg MEDS fractions was tested in a nude mouse model bearing H1975 cell xenografts.@*RESULTS@#MTT assay and colony forming experiment showed that MEDS fractions significantly inhibited the proliferation of H1975 cells in a dose-and time-dependent manner ( < 0.05). The results of flow cytometry showed that MEDS fractions induced obvious apoptosis of H1975 cells in a concentration-dependent manner ( < 0.05). MEDS fractions also significantly decreased the expressions of Bcl-2 and Akt protein and increased the protein expression of Bax ( < 0.05). In the tumor-bearing nude mouse model, MEDS fractions showed potent anti-tumor effects with a low toxicity to affect the body weight and organs of the mice.@*CONCLUSIONS@#The methanol-ethyl acetate partitioned fractions from MEDS show potent anti-tumor activity both and , suggesting their value as promising therapeutic agents against lung cancer.

A cone beam computed tomography study on the anatomical position of accessory mandibular foramina in Jiangxi adults / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study used cone beam computed tomography (CBCT) to access the distribution and position of accessory mandibular foramina in the mandibular body of Jiangxi adults, and some safety rules of operation for clinics were provided.</p><p><b>METHODS</b>Two hundred CBCT image subjects of Jiangxi adults were selected, which were divided into 4 groups by age with the same sex ratio. The number and position of accessory mandibular foramina in mandibular anterior teeth, premolars and molars region were described and the relationship between accessory mandibular foramina incidence and factors of age, gender and lateral were analyzed.</p><p><b>RESULTS</b>A total of 1 123 accessory mandibular foramina were found, with a mean of 5.62±2.10 per person. The accessory mandibular foramina incidence decreased from the mesial region to the distal, and the lingual was higher than the buccal. There was no significant difference in the number of accessory mandibular foramina in male and female (P=0.195). However, the number of accessory mandibular foramina was negatively correlated with age (r(s)=-0.301). Three highest frequency regions of accessory mandibular foramina were mandibular symphysis area (98.0%), lingual alveolar area of lower medial (88.0%) and lateral incisors and inferior area of lingual premolar (55.0%).</p><p><b>CONCLUSIONS</b>Accessory mandibular foramina are widely presented in the body of everyone's mandible, addition attention should be paid to avoid the complications causing by the damage of canal contents in the clinics.</p>

Sinus floor grafting using calcium phosphate nano-crystal coated xenogenic bone and autologous bone

or=2mm and < or=6mm. Lateral window approach was used, with grafting using Bio-ceraTM only(n=1) or mixed with autogenous bone from ramus and/or maxillary tuberosity(n=13). After 6 months of healing, implant sites were created with 3mm diameter trephine and biopsies taken for histomorphometric analysis. The parameters assessed were area fraction of new bone, graft material and connective tissue. Immediate and 6 months after grafting surgery, and 6 months after implantation, computed tomography (CT) was taken and the sinus graft was evaluated morphometric analysis. After implant installation at the grafted area, the clinical outcome was checked.RESULTS:Histomorphometry was done in ten patients. Bio-ceraTM particles were surrounded by newly formed bone. The graft particles and newly formed bone were surrounded by connective tissue including small capillaries in some fields. Imaging processing revealed 24.86+/-7.59% of new bone, 38.20+/-13.19% connective tissue, and 36.92+/-14.51% of remaining Bio-ceraTM particles. All grafted sites received an implant, and in all cases sufficient bone height was achieved to install implants. The increase in ridge height was about 15.9+/-1.8mm immediately after operation (from 13mm to 19mm). After 6 months operation, ridge height was reduced about 11.5+/-13.5%. After implant installation, average marginal bone loss after 6 months was 0.3+/-0.15mm.CONCLUSION: Bio-ceraTM showed new bone formation similar with Bio-Oss(R) histomorphometrically and appeared to be an effective bone substitute in maxillary sinus augmentation procedure with the residual bone height from 2 to 6mm.