Prognostic significance of prognostic nutritional index and systemic immune-inflammation index in patients after curative breast cancer resection: a retrospective cohort study.

BACKGROUND: Nutritional status and inflammation are closely associated with poor outcome in malignant tumors. However, the prognostic impact of postoperative in these variables on breast cancer (BC) remains inconclusive. We aimed to determine whether prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) affect two long-term outcomes among patients after curative resection of BC. METHODS: We retrospectively reviewed 508 patients with BC treated with curative surgery between February 5, 2013 and May 26, 2020. All patients were divided into 3 groups based on tertiles (T1-T3) of PNI, SII, NLR, and PLR. The effects of four indexes on disease-free survival (DFS) and overall survival (OS) have been evaluated using Cox proportional hazards models and Kaplan-Meier method. RESULTS: Compared with PNI-lowest cases, patients with highest PNI showed significantly longer DFS (multivariate adjusted hazard ratio [HR] = 0.37, 95% confident interval [CI] 0.19-0.70, P for trend = 0.002), whereas higher PLR seemed to be marginally associated with poorer DFS (P for trend = 0.086 and 0.074, respectively). Subgroup analyses indicate the potential modification effects of family history of BC and radiotherapy on the prognosis value of PNI to DFS in BC patients (P for interaction = 0.004 and 0.025, respectively). In addition, the levels of three inflammatory indices, namely SII, NLR, and PLR might be positively related with increased age at diagnosis (all P for trend < 0.001). CONCLUSIONS: A high PNI was associated with better DFS, supporting its roles as prognostic parameters for patients with BC. The nutritional status and systemic immune may exert great effects on patient prognosis. Further studies are warrant to explore the prognosis value of PLR.

Differential expression of microRNAs in postoperative radiotherapy sensitive and resistant patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and more resistant to radiotherapy. However, hetero-radiosensitivity occurs in different patients. MicroRNAs (miRNAs) play important roles in the initiation and progression of a multitude of tumors. The study aims to examine the different microRNAs expression profiles of postoperative radiotherapy sensitive and resistant patients with GBM, to make an inquiry about their potential role and discover a certain set of radio-sensitivity markers. Three paired samples from six GBM patients who had only been treated with postoperative radiotherapy were selected, and then, they were divided into radiotherapy sensitive group and resistant group according to their overall survivals, local recurrence rates, and Karnofsky Performance Scale scores. Expression profiles of miRNAs in these two groups were determined by the method of microarray assay. Comparing with resistant patients, 13 miRNAs were significantly upregulated and 10 miRNAs were greatly downregulated in sensitive group. Among them, four miRNAs were validated by quantitative RT-PCR. The differentially expressed miRNAs and their putative target genes were revealed by bioformatic analysis to play a role in cell signaling, proliferation, aging, and death. High-enrichment pathway analysis identified that some classical pathways participated in numerous metabolic processes, especially in cell cycle regulation, such as mTOR, MAPK, TGF-beta, and PI3K-Akt signaling pathways. Our research will contribute to identifying clinical diagnostic markers and therapeutic targets in the treatment of GBM by postoperative radiotherapy.

Long-Term Changes in Drug Craving and Nutritional Status of Opioid Addicts with Nucleus Accumbens Ablative Stereotactic Neurosurgery at Five Years Postoperatively.

BACKGROUND: The nucleus accumbens (NAcc) has been proven to be associated with drug and food craving. NAcc ablative neurosurgery has been suggested to modulate the balance of the brain reward system and thus alleviate drug dependence in patients. It has been hypothesized that it would also alleviate food craving in patients as well as altering their nutritional status. AIMS: This study aimed to estimate the effect of NAcc neurosurgery on drug craving and nutritional status in patients with drug dependence at 5 years postoperatively. METHODS: The study included 100 patients with NAcc surgery and 92 patients without surgery. Body mass index (BMI) and body fat percentage (BF%) were examined to assess nutritional status, and questionnaires were administered to assess drug craving. RESULTS: Compared with the nonsurgery group and the relapse patients from the surgery group, the nonrelapse patients from the surgery group had higher BMI and BF% but lower drug craving. There were no significant differences between the nonsurgery group and the relapse patients in BMI, but the relapse patients had higher drug craving than the nonsurgery group. CONCLUSIONS: Long-term follow-up suggested that NAcc ablative neurosurgery would alleviate drug craving and yield a better nutritional status if individuals sustained abstinence. It would increase drug craving but would not ruin the nutritional status of patients even when individuals relapsed postoperatively.

[Evaluation of the effect of cattle calcined bone grafting material to repair alveolar bone defect after tooth extraction].

PURPOSE: To verify the efficacy and safety of calcined cattle bone grafting material in filling alveolar bone defect after tooth extraction. METHODS: A randomized, bind, parallel, positive-control multicenter clinical trial was conducted. A total of 280 subjects were randomly assigned to either the experimental group (calcined cattle bone group) or control group (Bio-Oss group) equally. The main efficacy indicator was the imaging changes 24 weeks after material implantation. Secondary efficacy indicators were wound healing, rejection, bone metabolism, post-filling symptoms and signs of bone infection. The safety of material was assessed by the incidence of adverse events and serious adverse events. SAS 8.2 software package was used for statistical analysis. RESULTS: A total of 280 cases were included, of them 267 cases completed the study while 13 cases fell off. The effective rate of FAS(PPS) was 90.58%(97.46%) in the experimental group and 87.05% (95.04%) in the control group. The difference of effective rate between the experimental group and control group (95%CI) was 3.53% (-3.88%, 10.94%) of FAS, 2.42% (-2.38%, 7.22%) of PPS, and there was no significant difference between the two groups. The incision healing of the two groups was good, and the incidence of rejection, bone infection signs, post-filling symptoms and bone metabolic changes was very low. The incidence of adverse events was similar in the two groups, and no serious adverse events related to the study materials occurred. CONCLUSIONS: The efficacy of calcined cattle bone grafting material in filling alveolar bone defect after tooth extraction is not inferior to that of Bio-Oss, and it is safe and effective for alveolar bone defect repair.

Oxidative parameters in the rat brain of chronic mild stress model for depression: relation to anhedonia-like responses.

The chronic mild stress (CMS) protocol is widely used to evoke depression-like behaviors in the laboratory. Some animals exposed to CMS are resistant to the development of anhedonia, whereas the remaining are responsive, CMS-resilient and CMS-sensitive, respectively. The aim of this study was to examine the effects of chronic stress on oxidative parameters in the rat brain. The consumption of sweet food, protein and lipid oxidation levels and superoxide dismutase and catalase activities in the rat hippocampus, cortex and cerebellum were assessed. We found a significant increase in protein peroxidation (hippocampus and cortex), a significant increase in catalase activity (cortex, hippocampus and cerebellum) and a decrease in superoxide dismutase activity (cortex, hippocampus and cerebellum) in the CMS-sensitive group compared to the CMS-resilient group and normal controls as well as an increase in lipid peroxidation (cerebellum) in the CMS-sensitive and CMS-resilient groups compared to normal controls. However, there was no significant difference in protein peroxidation (cerebellum) and lipid peroxidation (cortex and hippocampus) among the three groups. In conclusion, our results indicate that the segregation into CMS-sensitive and -resilient groups based on sucrose intake is paralleled by significant differences in oxidative parameters. CMS induces oxidative damage and alterations in the activity of antioxidants which may lead to increased oxidative damage, irrespective of the anhedonia-like status of the stressed animals.

Primary oral mucosal melanoma: advocate a wait-and-see policy in the clinically N0 patient.

PURPOSE: Oral mucosal melanoma (OMM) is a rare disease associated with a very poor prognosis. Because well-established treatment protocols for OMM are in short supply, prognostic information regarding recent treatment modalities for this disease were sought. PATIENTS AND METHODS: A retrospective chart review was performed of 61 patients who were treated for OMM from 1998 through 2005. The clinical features and treatment modalities were identified and correlated with the outcomes. RESULTS: There were 41 male and 20 female patients (ratio, 2.1:1) with a mean age of 54.1 years. The mean follow-up was 31.9 months, and the overall 2-year and 5-year survival rates were 51.1% and 30.3%, respectively. According to the seventh edition of the American Joint Committee on Cancer staging system, there were 31 patients (50.8%) with stage III tumors. A more advanced stage and a tumor of at least 2 cm were associated with worse survival (P < .001 and P = .036, respectively). Elective lymph node dissection and biochemotherapy were not associated with a higher total survival rate (P = .53 and P = .76, respectively). CONCLUSIONS: OMM has a male predilection. The seventh edition of the American Joint Committee on Cancer stage and tumor size are effective prognostic parameters for patients with OMM. The American Joint Committee on Cancer staging system provides useful information for predicting the ultimate outcome and should be used as the primary staging system. Elective node dissection and adjuvant biochemotherapy offer no additional advantage in increasing the patient survival rate. A wait-and-see policy is advocated for patients with clinical stage N0 cancer.

Clinical Study on a Modified Hematoma Puncture Drainage Treatment in Patients with Hypertensive Basal Ganglia Hemorrhage.

OBJECTIVE: We aim to investigate the clinical efficacy and safety of a modified hematoma puncture drainage treatment through the burr hole lateral to Kocher's point from the frontal lobe in patients with hypertensive basal ganglia hemorrhage. METHODS: Twenty-six patients were enrolled in the retrospective study. The volume of hematoma in those patients was between 25 and 35 mL, and the Glasgow Coma Scale scores were between 9 and 11; they were divided into a hematoma puncture drainage treatment group and a traditional conservative treatment group. The volume of remaining hematoma, neurological function defect scores, and life quality after treatment, duration of hospitalization, and cost of hospitalization were analyzed in these 2 groups. RESULTS: The volume of remaining hematoma was significantly less in the drainage group than that in the traditional group on the first day and the third day after treatment (P < 0.05). Posttreatment neurological function defect scores in the drainage group were statistically lower than those in the traditional group (P < 0.05). The duration of hospitalization was significantly shorter and the cost of hospitalization was also significantly less in the drainage group than that in the traditional group (P < 0.05). The Extended Glasgow Outcome Scale and Barthel Index scores were significantly higher in the drainage group than those in the traditional group (P < 0.05). There were no significant differences between the 2 groups in the complication rates (P > 0.05). CONCLUSIONS: The modified hematoma puncture drainage treatment represents an effective and safe way to treat hypertensive basal ganglia hemorrhage.

Preliminary clinical application of multimodal imaging combined with frameless robotic stereotactic biopsy in the diagnosis of primary central nervous system lymphoma.

Objective: To evaluate the clinical application of multimodal imaging combined with frameless robotic stereotactic biopsy in the diagnosis of primary central nervous system lymphoma (PCNSL). Methods: We retrospectively reviewed the clinical data of 8 patients who were considered suspected cases of PCNSL by multimodal imaging techniques. The final pathologic diagnosis were determined by the frameless robotic stereotactic biopsy. The postoperative related complications and pathological results were analyzed. Results: All patients underwent biopsies under general anesthesia with an average surgery time of 29.5 ± 4.5 min. The final pathological diagnostic accordant rate with the preoperative ones was 100%, and the pathologic examination of our patients showed features of diffuse large B-cell lymphoma. During the surgery, one patient suffered intratumoral hemorrhage without leading to serious cerebral edema, and conservative treatment was given. There was no death occurring during the study, and there were no significant differences in the Karnofsky Performance Scale Scores of all patients before and after surgery. Finally, they were transferred to the hematology department for standardized chemoradiotherapy according to the pathological results of PCNSL. Conclusion: This study shows that it may play a vital role in the early diagnosis of PCNSL with the technique of multimodal imaging. The technique of frameless robotic stereotactic biopsy for obtaining the pathology outcomes in suspected PCNSL patients has the advantages of safety, efficiency, and minimally invasiveness.

Rapid, accurate detection of TMPRSS6 gene causative mutations with a high-resolution melting assay.

Mutations of the TMPRSS6 gene are considered the major genetic factors for iron-refractory iron deficiency anemia (IRIDA). Artificial clone libraries containing 17 known mutations of the TMPRSS6 gene were used to develop a high-resolution melting (HRM) assay for the detection of 17 TMPRSS6 gene mutations. The melting temperatures and melting curves were able to distinguish the different genotypes of the 17 TMPRSS6 gene mutations. We used replicate experiments to evaluate the reproducibility of the assay, and the coefficients of variation were in the range 0.0091% to 0.0873%. A total of 145 Chinese patients with IDA were screened with this assay and no TMPRSS6 gene causative mutation was found in any patient. The HRM assay was proved to be rapid, accurate and cost-effective method to identify the TMPRSS6 gene mutations and can be used in the clinical diagnosis of IRIDA.

[Application of 3D printing technology under three-dimensional reconstruction in mandibular reconstruction].

PURPOSE: To explore the application value of 3D printing technology under three-dimensional reconstruction in mandibular reconstruction. METHODS: Eighty-four patients with mandibular defect reconstruction were divided into two groups by different operation methods: 3D group(n=42) and control group(n=42). Patients in the control group underwent routine operation, while patients in the experimental(3D) group underwent three-dimensional reconstruction with 3D printing technology. The operation conditions, incidence of complications, recovery of facial features and occlusal relationship were recorded. SPSS 23.0 software package was used for statistical analysis of the data. RESULTS: The operation time of 3D group was significantly shorter than that of the control group, and the amount of bleeding was significantly less than that of the control group(P<0.05). The recovery rate of facial appearance and occlusal relationship in 3D group was significantly higher than in the control group(95.24% vs 78.57%, P<0.05). Compared with the control group, the movement distance of mandibular points in 3D group was significantly smaller before and after operation(P<0.05). The satisfaction scores of chewing function and pronunciation recovery in the two groups were close(P>0.05), but compared with the control group, the satisfaction scores of appearance recovery in the 3D group were significantly higher(P<0.05). CONCLUSIONS: 3D reconstruction under 3D printing technology can reduce intraoperative bleeding, shorten the operation duration, and achieve good shape recovery with high degree of satisfaction.

[Effect of mi-138 targeting PLD2 gene on proliferation and migration of oral cancer cells].

PURPOSE: To investigate the effect of miR-138 targeting PLD2 gene on proliferation and migration of oral cancer cells. METHODS: After oral cancer cells were transfected with miR-138, the expression level of microRNA-138 was detected by RT-PCR assay, the proliferation ability was detected by MTT assay, and cell cycle distribution was detected by flow cytometry. Transwell migration assay was used to detect cell migration ability, Western blotting assay was used to detect the expression levels of MMP-9, PLD2 and cyclin D1 in gastric cancer cells. Luciferase assay was used to report the targeting relationship between microRNA-138 and PLD2 gene. SPSS 21.0 software package was used to analyze the data. RESULTS: After miR-138 was transfected into oral cancer cells, the relative expression level of miR-138 was 4.28±0.16, which was significantly higher than that of blank control and miR-NC group (P<0.05). Luciferase reporter gene assay showed that the relative activity of PLD2 wild plasmid luciferase was significantly lower in oral cancer cells transfected with microRNA-138 than in other groups (P<0.05); The expression level of PLD2 gene in miR-138 group was significantly lower than that in blank control group and miR-NC group (P<0.05). After oral cancer cells were transfected with miR-138, the proliferation ability of oral cancer cells in miR-373 group was significantly lower than that in control group and miR-NC group (P<0.05). Flow cytometry showed that the ratio of G0/G1 phase was (64.39±6.49)% in the group of miR-138, which was significantly higher than that in the blank control group and the group of miR-NC(P<0.05); The ratio of S phase in the group of miR-138 was(13.28±3.16)%, which was significantly lower than that in the blank control group and the group of miR-NC (P<0.05); There was no significant difference in the ratio of G2/M phase among the groups (P>0.05). Transwell experiment showed that the number of migrating cells transfected with miR-138 in oral cancer cells was 138.46±24.37, which was significantly lower than that in blank control group and miR-NC group(P<0.05). Western blotting experiments showed that the relative levels of MMP-9, vimentin and cyclin D1 in the miR-138 group were 0.14±0.04, 0.17±0.02 and 0.15±0.03, respectively, which were significantly lower than those in the blank control group and the miR-NC group(P<0.05). CONCLUSIONS: miR-138 can target PLD2 gene expression and inhibit the proliferation and migration of oral cancer cells.

Anatomical study and clinical application of medial sural artery perforator flap for oral cavity reconstruction.

The present study aims to provide anatomical evidence for clinical application of the medial sural artery perforator (MSAP) flap. The current study investigated the vascular anatomy of the flap, evaluated the postoperative appearance and function of the donor and recipient sites, and investigate the clinical value in reconstruction of oral cavity. Six lower limbs of Chinese adult cadavers were microsurgically dissected. The locations and courses of the medial sural artery perforators were identified and recorded, which provided an anatomical basis for clinical application. Then, 16 clinical cases employing this flap were evaluated, ranging from 3×4cm to 6×8cm, and were employed for defects in the oral cavity region. Sixteen clinical cases with intraoral soft tissue defects, which included four clinical cases with inner cheek defects, were successfully followed up for 10-47 months (24 months on average). The donor site function, contour of recipient site and oral function recovery were evaluated as acceptable or better in cases with intraoral soft tissue defect, which were further verifying the value of clinical application of MSAP in repairing oral cavity defects. Moreover, two typical clinical cases were described in detail. To conclude, the MSAP flap is a favorable choice for small- to medium-size defects based on minor donor site morbidity, satisfactory oral function recovery, perforator stability and adaptation of the pedicle for anastomosis in the oral cavity region.

[Pharmacognostic identification of Centipeda minima].

OBJECTIVE: To conduct pharmacognostic identification of Centipeda minima. METHODS: To conduct characteristic identification, micro-identification and TLC identification of Centipeda minima. RESULTS: We established a systematic pharmacognostic identification method including characteristic identification, micro-identification and TLC identification. CONCLUSION: Brevilin is used as chemical reference firstly in TLC identification of Centipeda minima, and combined with characteristic identification and micro-identification, it will raise the rapidity and accuracy of the identification of Centipeda minima.

FOXM1 is a novel predictor of recurrence in patients with oral squamous cell carcinoma associated with an increase in epithelial­mesenchymal transition.

Although forkhead box protein M1 (FOXM1) is markedly upregulated in human premalignant and oral squamous cell carcinoma (OSCC) tissues and cultured cells, the association of FOXM1 expression with OSCC prognosis is not well understood. The present study investigated the possible association of FOXM1 expression in patients with OSCC with their clinicopathological characteristics and clinical outcomes. The expression of FOXM1 protein in OSCC tissues from 119 patients was evaluated by immunohistochemistry, and the results demonstrated that FOXM1 overexpression in patients with OSCC was associated with tumour recurrence and poor prognosis. To study the in vitro effects of FOXM1, its expression was decreased by small interfering RNA (siRNA) in OSCC cell lines, and FOXM1 knockdown decreased the proliferative, migratory and invasive capacities of cells. FOXM1 inhibition by siRNA gave rise to reduced expression of vimentin and increased expression of E­cadherin. The present study reported FOXM1 as a novel predictor of tumour recurrence in patients with OSCC and its potential involvement in epithelial­mesenchymal transition in OSCC cells.

Application of lateral arm free flap in oral and maxillofacial reconstruction following tumor surgery.

OBJECTIVE: To describe the application of lateral arm free flap (LAFF) in reconstruction of defects in the oral and maxillofacial regions following ablative oncological surgery. SUBJECTS AND METHODS: The study included 16 patients (13 male, 3 female, mean age 56, range 35-69 years). Sixteen LAFF were harvested to reconstruct defects caused by the dissection of malignant tumors of the oral and maxillofacial regions. The tumor was squamous cell carcinoma of the tongue (6 cases), floor of the mouth (4), retromolar area (3), inner cheek (2), and lower gingival (1). Flap sizes ranging from 5 x 7 to 6 x 9 cm were harvested using a sterile tourniquet for bloodless technique. The anastomoses were carried out using a magnifier or microscope. All donor defects were closed primarily. RESULTS: Fourteen flaps healed without venous insufficiency. One flap, in a female patient, survived with mild local microcirculatory obstruction but that of another female patient developed necrosis. There was no significant complication at the donor sites. The advantages of this flap include anatomically reliable vascular supply, accessible donor site, and the aesthetic quality of donor tissue is good. Compared with the radial artery, the posterior radial collateral artery is a nonessential vessel of the arm. The disadvantages are the relatively smaller vessel size for anastomosis and thicker subcutaneous tissue. CONCLUSIONS: For the repair of moderate-sized defects of the maxillofacial area, especially in male patients, the LAFF can be recommended.

GSH depletion and consequent AKT inhibition contribute to the Nrf2 knockdown-induced decrease in proliferation in glioblastoma U251 cells.

Nuclear factor erythroid 2-related factor 2 (Nrf2), a pivotal transcription regulator that controls the expression of numerous antioxidant and cytoprotective genes, was recently defined as a proto-oncogene. However, the role and mechanism of Nrf2 in glioma pathoetiology remain unclear. In the present study, we first evaluated the expression patterns of Nrf2 in normal human astrocytes and 3 glioblastoma (GBM) cell lines (U251, U87 and A172) and found that all 3 GBM cell lines overexpressed Nrf2, with the highest level observed in the U251 cells. We further assessed the biological effects of Nrf2 in U251 cells by specific knockdown of Nrf2 using lentivirus­mediated RNA interference. We discovered that Nrf2 deficiency led to a decrease in U251 cell proliferation and caused intracellular redox imbalance [diminished glutathione (GSH) levels and increased reactive oxygen species (ROS) levels]. Both N-acetylcysteine and glutathione monoethyl ester (GMEE) supplementation completely eliminated the increased levels of ROS that were present in the Nrf2­deficient U251 cells. However, only GMEE supplementation both reversed Nrf2 deficiency-induced cell growth arrest and restored intracellular GSH levels. Moreover, AKT and ERK1/2 signaling were both impaired in the Nrf2-knockdown U251 cells, but GMEE supplementation restored AKT signaling but not ERK1/2 signaling, and blocking AKT signaling with an AKT-specific inhibitor greatly diminished the GMEE-induced Nrf2-deficient cell proliferation. In conclusion, our findings revealed novel functions for Nrf2 in the regulation of redox status and cell proliferation, and that intracellular GSH levels and AKT signaling are required for this process, a new viewpoint by which to comprehend the role and underlying mechanism of Nrf2 in tumorigenesis.

[Expression and correlation of HPV16E6 and tumor suppressor gene p53 in oral squamous cell carcinoma].

PURPOSE: To exploring the expression of PV16E6 gene and p53 gene in patients with oral carcinoma and the correlation between pathological grade and clinical stage of oral cancer and expression of HPV16E6 gene and p53 gene. METHODS: One hundred and seventy-three cases of oral cancer, 98 cases of oral precancerous lesions and 79 cases of peri-cancerous normal tissue were selected. The expression of HPV16E6 and p53 was detected by immunohistochemistry. The data were analyzed using SPSS 21.0 software package. RESULTS: In oral carcinoma, the expression rate of HPV16E6 was 81.5% (141/173), the expression rate of p53 was 23.7% (41/173); in oral precancerous lesions, the expression rate of HPV16E6 was 39.8% (39/98), the expression rate of p53 was 57.1% (56/98); in peri-cancerous normal tissues, the expression rate of HPV16E6 was 2.5%(2/79), the positive expression rate of p53 was 89.9%(71/79). There was significant difference in the positive expression rate of p53 and HPV16E6 among 3 groups. The expression of HPV16E6 in oral cancer was significantly higher than in the other two groups(P<0.05); the expression rate of p53 in oral cancer was significantly lower than the other two groups. In addition, with the advance of clinical stage and pathological grade, the positive expression rate of HPV16E6 increased gradually, while the positive expression rate of p53 was significantly decreased (P<0.05). CONCLUSIONS: HPV16E6 protein and p53 protein may play an important role in the occurrence and progress of oral cancer.

Monocarboxylate transporter 4 facilitates cell proliferation and migration and is associated with poor prognosis in oral squamous cell carcinoma patients.

Monocarboxylate transporter 4 (MCT4) is a cell membrane transporter of lactate. Recent studies have shown that MCT4 is over-expressed in various cancers; however, its role in cancer maintenance and aggressiveness has not been fully demonstrated. This study investigated the role of MCT4 in oral squamous cell carcinoma (OSCC), and found that it is highly expressed in OSCC patients by using immunohistochemistry. Moreover, this over-expression of MCT4 was closely associated with tumor size, TNM classification, lymphatic metastasis, distant metastasis and tumor recurrence, and also poor prognosis. To further study mechanisms of MCT4 in vitro, we used small-interfering RNA to silence its expression in OSCC cell lines. The results showed that knock-down of MCT4 decreased cell proliferation, migration, and invasion. The inhibition of proliferation was associated with down-regulation of p-AKT and p-ERK1/2, while decreased cell migration and invasion may be caused by down-regulation of integrin ß4-SRC-FAK and MEK-ERK signaling. Together, these findings provide new insight into the critical role of MCT4 in cell proliferation and metastasis in OSCC.

Ghrelin alleviates early brain injury after subarachnoid hemorrhage via the PI3K/Akt signaling pathway.

Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). Although the neuroprotective effects of ghrelin have been demonstrated in several studies, whether ghrelin reduces EBI after SAH remains unknown. In this study, we hypothesized that treatment with ghrelin would attenuate EBI after SAH, and that this protection would be mediated, at least in part, by activation of the PI3K/Akt signaling pathway. Adult male Sprague-Dawley rats (n=100) were randomly divided into the following groups: control group (n=20), SAH group (n=20), SAH+vehicle group (n=20), SAH+ghrelin group (n=20) and SAH+ghrelin+LY294002 group (n=20). The rats were injected with autologous blood (0.3mL) into the prechiasmatic cistern to induce SAH. Ghrelin (80µg/kg, IP), or an equal volume of vehicle, was administered immediately after surgery. The PI3K inhibitor, LY294002, was applied to manipulate the proposed pathway. Mortality, neurological scores, brain edema, cell apoptosis, and the expression of p-Akt, and cleaved caspase-3 proteins were assayed after 24h SAH. Ghrelin significantly improved neurological function and reduced neuronal apoptosis and brain edema at 24h after SAH. The level of p-Akt, expressed mainly in neurons, was markedly up-regulated. Additionally, the level of cleaved caspase-3 was decreased by ghrelin treatment. The beneficial effects of ghrelin in SAH rats were partially suppressed by LY294002. These results demonstrate that ghrelin may reduce EBI after SAH, via a mechanism involving the PI3K/Akt signaling pathway.