Objective To explore the effect of baicalein on alveolar bone resorption in rats with periodontitis and its regulation of nucleotide-binding oligomerization domain-like receptor protein 3 / cysteine aspartate protease 1 (NLRP3 / Caspase-1) pathway. Methods A total of 40 rats with periodontitis were randomly divided into model group, baicalein group, activator group and baicalein + activator group, another 10 rats without any treatment were taken as the control group. The distance from the cemento-enamel junction to aleolar crest (CEJ-AC) of the rats were measured. The expressions of interleukin-6 ( IL-6) and transforming growth factor-β ( TGF-β) in the serum and the periodontal tissues were detected. The pathological changes in periodontal tissues were observed. The expression levels of NLRP3 and Caspase-1 proteins were detected. Results The CEJ-AC distance, the expression levels of IL-6 and TGF-β in the serum, the positive rates of IL-6 and TGF-β expression in the periodontal tissues, and the expression levels of NLRP3 and Caspase-1 proteins were all increased in the model group (P< 0. 05). After the intervention with baicalein, all those indexes above were decreased (P< 0. 05). The treatment of activator significantly attenuated the effect of baicalein on above indexes. Conclusion Baicalein reduces the inflammation response, and controls alveolar bone resorption by inhibition of NLRP3 / Caspase-1 pathway. 

Objective To explore the protective effect of running on hippocampal plasticity in stroke rats and its biological mechanism. Methods Adult male rats underwent middle cerebral artery occlusion (MCAO) for 90 minutes, and were randomly divided into exercise group and nonexercise group after 24 hours. Two weeks later, the neurological deficits of the rats were scored, the learning and memory functions of the rats were tested by the water maze. The cerebral infarction and brain histological damage of the rats were evaluated by the 2 3 5 triphenyltetrazolium chloride staining and HE staining, the neuronal damage of the rats was observed by NeuN staining. The expression levels of COX-2, IL-1β and TNF-α proteins were detected by Western blotting. Results The indexes for the neurological deficits and the learning and memory functions were improved in rats of the exercise group, and the volumes of the cerebral infarction in rats of the exercise group were smaller than those in rats of the non-exercise group after MCAO. Consistent with the above results, the number of damaged neurons in the brain tissues of rats in the exercise group was also significantly reduced, and the inflammatory response was suppressed in the brain tissues. Conclusion Our results show that exercise after MCAO improves neurological functions and reduces cerebral infarction volumes. The underlying mechanism is related to the protective effect of the inhibition of inflammation response on neurons.

Objective To explore the mechanism of miR-296-5p induced autophagy and inhibition of epithelial-mesenchymal transition ( EMT) in osteosarcoma (OS) cells. Methods The expression level of miR-296-5p in OS cells was detected by qRT-PCR. The target gene of miR-296- 5p was predicted by bioinformatic method. The direct binding relationship of miR-296-5p with its target gene PLK1 was verified. Cell lines overexpressed or silenced of miR-296-5p were constructed through cell transfection method. The effect of miR-296-5p on cell proliferation, invasion, apoptosis, autophagy, EMT, and the expression level of PTBP1 in U2OS cells were detected by CCK-8, colony formation assay, transwell chamber assay, flow cytometry, and Western blotting. Results The expression level of miR-296-5p was decreased in OS, while the expression level of PLK1 was increased when compared to the control group (P < 0. 05). The colony formation rate, the number of invasive cells, and the expression levels of PTBP1, p62, N-cadherin, Vimentin, p-PI3K/ PI3K and p-AKT / AKT were decreased in mimic group, while the apoptosis rate, the expression levels of Beclin-1, LC3-Ⅱ/ Ⅰ and E-cadherin were increased when compared to the miR-NC group (P< 0. 05). The colony formation rate, the number of invasive cells, the expression levels of PTBP1, p62, N-cadherin, Vimentin, p-PI3K/ PI3K and p-AKT / AKT were decreased in PLK1 + mimic group, while the apoptosis rate, the expression levels of Beclin-1, LC3-Ⅱ/ Ⅰ and E-cadherin were increased in PLK1 + mimic group when compared to the PLK1 group (P< 0. 05). Conclusion miR-296-5p may induce autophagy in OS cells and inhibit EMT through regulation of PI3K/ AKT pathways by targeting PLK1.

Objective To investigate the effect of isoflurane on malignant phenotype and chemotherapy sensitivity of bladder cancer cell line 5637. Methods The 5637 bladder cancer cells were divided into groups as follows: control group, isoflurane group, cisplatin group and isoflurane + cisplatin group. The number of BrdU positive cells was determined by BrdU staining. The cell apoptosis and cell cycle were measured by flow cytometry. The number of invasive cells were measured by transwell assay. The scratch healing rate was measured by wound healing experiment. The expression levels of Ki67, PCNA, Bax, Bcl-2, cleaved caspase-3 and caspase-3 proteins were detected by Western blotting. Results The number of BrdU positive cells, the expression levels of Ki67 and PCNA proteins, the G0 / G1 phase ratio, the number of S phase cells were decreased significantly in the isoflurane + cisplatin group compared to the cisplatin group, while the G2 / M phase ratio was increased significantly (P< 0. 05). The number of invasive cells and the scratch healing rate were decreased significantly in the isoflurane + cisplatin group when compared to the cisplatin group (P < 0. 05). The apoptosis rate, the Bax / Bcl-2 ratio, and the cleaved caspase-3 / caspase-3 ratio were increased significantly in the isoflurane + cisplatin group compared to the cisplatin group (P< 0. 05). Conclusion Isoflurane can induce apoptosis by inhibiting cell proliferation, invasion and migration, and enhance the sensitivity of 5637 cells to cisplatin. 

Objective To investigate the expression of programmed death ligand 1 (PD-L1) in serum exosomes of patients with hepatocellular carcinoma ( HCC ) and its clinical significance. Methods Exosomes from the serum samples of 75 HCC patients and 15 healthy controls were extracted by using ExoQuick kit, and were further identified through the methods of transmission electron microscopy, NanoSight and Western blotting. RT-qPCR assay was employed to detect the differential expression of PD-L1 mRNA in serum exosomes. Chi-square test was used to analyze the relationship between the expression level of serum exosomal PD-L1 mRNA and the clinicopathological features of HCC patients. Furthermore, Kaplan-Meier curve combined with the Cox regression analysis were used to investigate the prognostic value of the mRNA expression of serum exosomal PD-L1 in HCC. Results The transmission electron microscopy and NanoSight results showed that the particle sizes of most exosomes in the serum of HCC patients and healthy controls were about 100 nm. Western blotting analysis showed that the exosomes expressed the marker CD9 and TSG101 proteins, but did not express the cytoskeleton protein-Calnexin. RT-qPCR results showed that the expression level of PD-L1 mRNA in the serum exosomes of HCC patients was significantly higher than that of healthy controls (t = 11. 670, P< 0. 001). Further analyses exhibited that its high expression level was associated with the tumor diameter, tumor numbers, Child-Pugh grade, AFP levels, and portal vein tumor thrombin (all P< 0. 005). Kaplan-Meier survival analysis showed that the overall survival of HCC patients with higher mRNA expression level of serum exosomal PD-L1 was significantly shorter than that of those with lower expression level of serum exosomal PD-L1 (P = 0. 004). Moreover, univariate and multivariate Cox regression analysis demonstrated that the high expression of serum exosomal PD-L1 was an independent risk factor for the shortened overall survival in HCC patients (HR = 2. 013, 95 % CI: 1. 012-3. 669, P = 0. 015). Conclusion The expression level of PD-L1 in the serum exosomes of HCC patients is significantly up-regulated, which is closely related to tumor malignant progression and patient’s poor prognosis, indicating that the serum exosomal PD-L1 has a great potential to be a prognostic marker for HCC.

Objective The frequency of BRCA1 / 2 gene mutations varies greatly in different regions and ethnic groups. This study aimed to analyze the BRCA1 / 2 gene mutations in breast cancer patients in western Hainan and their impacts on the prognosis. Methods A total of 256 patients who were diagnosed with primary breast cancer and hospitalized in Hainan Western Central Hospital from October 2015 to December 2020 were regarded as the research objects. Denaturing high-performance liquid chromatography ( DHPLC) was applied to screen the BRCA1 / 2 gene mutations in breast cancer patients. The BRCA1 / 2 gene mutation status and clinical characteristics of the 256 patients were analyzed, the 5-year survival rate of the patients with BRCA1 / 2 gene mutations was analyzed, and the factors that affect the prognosis of the patients were analyzed by COX regression. Results Among the 256 breast cancer patients in this study, 53 patients had BRCA1 / 2 gene mutations, in which the BRCA1 mutation rate was 12. 11 % (31 / 256), the BRCA2 mutation rate was 8. 59 % (22 / 256), and the rate of harmful variants was 7. 03 % (18 / 256). There were significant differences in family medical history, gynecological disease history, breast disease history, positive ratios of estrogen receptor (ER) and CerbB-2 proteins, clinicopathological grade and clinical stage between patients with BRCA1 / 2 mutations and those without BRCA1 / 2 mutations (P < 0. 05). The overall survival rate of the 256 patients was 83. 59 % , and the survival rate of patients with BRCA1 / 2 gene mutations was lower than that of patients without mutations (P< 0. 05). COX regression analysis showed that BRCA1 / 2 mutations, breast disease history, clinical stage, CerbB-2 positive, CEA and CA199 were all risk factors affecting the survival of breast cancer patients ( P < 0. 05). Conclusion DHPLC can effectively screen out the harmful variants of BRCA1 / 2 gene in breast cancer patients, and the BRCA1 / 2 gene mutations are closely related to the clinicopathological features and prognosis of breast cancer patients. 

Objective To investigate the expression of transmembrane protease serine 4 (TMPRSS4) and LAD1 in cervical cancer tissues and their relationship with the prognosis of cervical cancer patients. Methods A total of 79 patients with cervical cancer who underwent surgical treatment in Danyang People’s Hospital from June 2015 to June 2018 were selected as the research objects. The 79 cancerous tissue specimens and 60 para-cancerous tissue specimens were collected from cervical cancer patients during the operation. The immunohistochemical staining method and realtime fluorescent quantitative PCR (qRT-PCR) method were used to detect the protein and mRNA expression levels of TMPRSS4 and LAD1 in tissues. The clinical pathological parameters of the patients were collected and the patients were followed up for 3 years. The relationship between the expression levels of TMPRSS4 and LAD1 and the clinical pathological parameters of patients, as well as the factors that affect the prognosis of patients with cervical cancer were analyzed. The correlation between TMPRSS4 and LAD1 expression was analyzed with Pearson method. The predictive value of TMPRSS4 and LAD1 levels on the prognosis of patients was analyzed with the receiver operating characteristic curve (ROC). Results The expression levels of TMPRSS4 and LAD1 in cervical cancer tissues were higher than those in adjacent tissues (P < 0. 05). The expression levels of TMPRSS4 and LAD1 in cervical cancer tissues were significantly positively correlated (r = 0. 249, P< 0. 05). The expression levels of TMPRSS4 and LAD1 proteins in cervical cancer tissue were related to the FIGO stage and tumor differentiation degree (P < 0. 05). FIGO staging, tumor differentiation, TMPRSS4 and LAD1 protein expression levels were the factors affecting the prognosis of patients (P< 0. 05). The expression levels of TMPRSS4 and LAD1 in the cancer tissues of patients in survival group were significantly lower than those in death group ( P < 0. 05 ). The ROC results showed that the areas under the curve (AUCs) for TMPRSS4 and LAD1 to assess the prognosis of patients were 0. 756 and 0. 909, respectively, the corresponding sensitivities of the assessment were 91. 11 % and 52. 94 % respectively, and the specificities were 85. 29 % and 85. 29 % respectively. The AUC for the combination of using TMPRSS4 and LAD1 to assess the prognosis of patients was 0. 952, the sensitivity of the assessment was 88. 89 % , and the specificity was 88. 24 % . Conclusion TMPRSS4 and LAD1 are both highly expressed in cervical cancer tissues. The expression levels of TMPRSS4 and LAD1 are significantly positively correlated, and they can be used for the prognosis of cervical cancer patients.

Objective To explore the effect of circUBE2D2 on the proliferation, migration and invasion of SW620 colorectal cancer cells and its underlying mechanism. Methods The cancer tissues and the corresponding para-cancerous tissues from 45 patients with colorectal cancer admitted to our hospital from January 2020 to May 2020 were collected. The expression levels of circUBE2D2 and miR-376a-3p were detected by qRT-PCR. Human colorectal cancer cell line SW620 was used in this research and were divided into groups as follows: si-NC group, si-circUBE2D2 group, miR-NC group, miR-376a-3p group, si-circUBE2D2 + anti-miR-NC group, and si-circUBE2D2 + anti-miR-376a-3p group. The CCK-8 and plate colony formation assay were used to measure the proliferation and colony formation of cells. The migration and invasion of cells were determined by the wound healing assay and the transwell assay. The dual luciferase reporter experiment was used to assay the effect of miR-376a-3p overexpression on the luciferase activity of the wild-type vector WT-circUBE2D2. The expression levels of E-cadherin and N-cadherin proteins were detected by Western blotting. Results The expression level of circUBE2D2 was increased in colorectal cancer tissues, while that of miR-376a-3p was decreased when compared with adjacent tissues (P< 0. 05). The cell viability and scratch healing rate were reduced, the number of colonies formed, the number of invasive cells and the expression level of N-cadherin were decreased in the si-circUBE2D2 group and the miR-376a-3p group when compared with the si-NC group and the miR-NC group, while the expression level of E-cadherin was increased respectively ( P < 0. 05 ). Overexpression of miR-376a-3p could inhibit the luciferase activity of wild-type vector WT-circUBE2D2 (P< 0. 05). The cell viability, the scratch healing rate, the number of cell colony formed, the number of invasive cells, and the expression level of N-cadherin were increased in the si-circUBE2D2 + anti-miR-376a-3p group, while the expression level of E-cadherin was decreased when compared with the si-circUBE2D2 + anti-miR-NC group (P< 0. 05). Conclusion Interference of circUBE2D2 expression could reduce the proliferation, colony formation, migration and invasion of colorectal cancer cells by targeting miR-376a-3p.

Objective To investigate the effect of dexmedetomidine (DEX) on the growth and motility of oral squamous cell carcinoma (OSCC) cells. Methods Human OSCC cell line CAL27 were treated with DEX and were divided into groups of DEX 0, 5, 10 and 20 nmol / L. The proliferation of CAL27 cells was evaluated by colony formation assay and BrdU assay. Cell invasion was detected by transwell assay. Flow cytometry was employed to measure the apoptosis rate. The levels of superoxide dismutase ( SOD ) and malondialdehyde ( MDA ) in cells were determined by ELISA. The ability of cell microtubule formation was evaluated by the microtubule formation assay. Western blotting was performed to detect the expression levels of vascular endothelial growth factor (VEGF), fibronectin ( FN), B cell lymphoma 2 ( Bcl-2) and Bcl-2 associated X protein (Bax). Results DEX treatment significantly decreased the colony formation rate and BrdU positive cell rate, reduced the number of invasive cells and microtubule nodules, and down-regulated the expression levels of VEGF and FN in CAL27 cells when compared with the control group. Meanwhile, the treatment of DEX promoted the oxidative stress and increased the Bax / Bcl-2 ratio in cells. Conclusion DEX treatment can inhibit the proliferation, invasion and microtubule formation, and promote the oxidative stress and apoptosis in CAL27 cells.

Objective To explore the effect of ATR inhibitor combined with carboplatin treatment on the growth of breast cancer xenografts in nude mice and its influences on Brahma related gene 1 (BRG1), recombinase 51 (RAD51) and breast cancer susceptibility gene 2 localization collaboration protein ( PALB2) expression in tumor tissues. Methods A total of 40 nude mice bearing breast cancer xenografts were randomly divided into control group, carboplatin group, ATR inhibitor M6620 group and carboplatin + M6620 group (n = 10). The volume and mass of the tumors were measured, the mRNA and protein expression levels of Ki67, MMP2, N-cadherin and E-cadherin were detected by RT-qPCR and Western blotting. The expression levels of BRG1, RAD51, PALB2 proteins were determined by immunohistochemistry. Results The mass and volume of the tumors, the expression levels of Ki67, MMP2, N-cadherin, and the expression levels of BRG1, RAD51, PALB2 proteins in the carboplatin group and the M6620 group were significantly lower than those in the control group, while the expression level of E-cadherin was significantly higher than that in control group (P< 0. 05). The mass and volume of the tumors, the expression levels of Ki67, MMP2, N-cadherin, and expression levels of BRG1, RAD51, PALB2 proteins in the carboplatin + M6620 group were significantly lower than those in the carboplatin group and those in the M6620 group, while the expression level of E-cadherin was significantly higher than that in the carboplatin group and that in the M6620 group (P< 0. 05). Conclusion The treatment of ATR inhibitor combined with carboplatin could significantly inhibit the growth of breast cancer xenografts inude mice, and inhibit the expression of BRG1, RAD51 and PALB2 in tumor tissues.

Objective To investigate the effect of electroacupuncture combined with running wheel training on nerve cell autophagy, apoptosis and neurogenesis in the middle cerebral artery embolism (MCAO) rat model. Methods A total of 30 SD rats were randomly divided into MCAO model group (n = 10), combined intervention group ( n = 10) and sham operation group ( n = 10). The neurological score was recorded and the infarct volume was measured. The expression levels of the autophagy effector Beclin1, the membranous microtubule-associated protein 1A/ 1B-light chain 3 (LC3) (LC3B-Ⅱ) / cytoplasmic LC3 (LC3B-Ⅰ), the apoptosis related proteins [B-cell lymphoma-2 (Bcl-2), the BCL2-associated X protein (BAX), and caspase-3], p-AMPK, and p-mTOR were detected. The apoptosis of nerve cells was detected. The superoxide dismutase (SOD) and catalase ( CAT) activities, and the malondialdehyde ( MDA) content were assayed. Results In the MCAO model group, the number of Tunel positive cells, the nervous system score, the cerebral infarction volume, the expression levels of BAX, caspase-3, Beclin-1, LC3B- Ⅱ/ LC3B-Ⅰ, p-AMPK, and the MDA content were increased, while the SOD activity, the CAT activity, and the expression levels of p-mTOR and Bcl-2 were decreased (P < 0. 05). In the combined intervention group, the number of Tunel positive cells, the nervous system score, the cerebral infarction volume, the expression levels of BAX, caspase-3, Beclin-1, LC3B-Ⅱ/ LC3B-Ⅰ, p-AMPK, and the MDA content were decreased, while the SOD activity, the CAT activity, and the expression levels of Bcl-2 and p-mTOR expression were increase (P< 0. 05). Conclusion The intervention treatment of electroacupuncture combined with running wheel training inhibits the oxidative stress, suppresses the expression of Beclin-1, LC3B-Ⅱ/ LC3B-I, BAX, caspase-3, and enhances the expression of Bcl-2 in nerve cells.

Polycystic ovary syndrome (PCOS) is a common disease in women of childbearing age. Its main clinical manifestations are menstrual disorders, infertility, acne, hirsutism, etc. , and may be accompanied by abnormal glucose and lipid metabolism. Adropin is a newly discovered secretory protein, which has been proved to be effective in regulating glucose and lipid metabolism and improving insulin resistance. However, its underlying mechanism in PCOS and its clinical significance are not fully understood. In this paper, we briefly reviewed the mechanism of adropin on regulating PCOS, and the research progress and clinical significance of adropin in PCOS.