Effects of electroacupuncture on the PI3K/Akt/CREB signaling pathway and hippocampal neuronal apoptosis in diabetic cognitive impairment rats. / ç”µé’ˆå¯¹ç³–å°¿ç— è®¤çŸ¥åŠŸèƒ½éšœç¢å¤§é¼ PI3K/Akt/CREBä¿¡å·é€šè·¯å’Œæµ·é©¬ç¥žç»å ƒå‡‹äº¡çš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture (EA) on the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/cAMP response element binding protein (CREB) signaling pathway-related proteins and hippocampal neuron apoptosis in diabetic cognitive impairment (DCI) rats, and to explore the mechanisms of EA in treating DCI. METHODS: Adult male SD rats were randomly divided into normal, model, and EA groups, with 12 rats in each group. The animal model of DCI was replicated using a high-fat, high-sugar diet combined with low-dose streptozotocin. The EA group received EA stimulation at "Yishu" (EX-B6), "Zusanli" (ST36), "Baihui" (GV20), and "Dazhui" (GV14). Blood glucose contents of the rats in each group were measured. The Morris water maze test was used to assess the learning and memory abilities of rats. Transmission electron microscopy was used to observe the ultrastructure of hippocampal CA1 neurons. Nissl staining was used to observe the pathological changes in hippocampal CA1 neurons. TUNEL staining was used to detect the apoptosis in hippocampal CA1 neurons. Western blot was used to detect the protein expression levels of p-PI3K/PI3K and p-Akt/Akt, as well as CREB, p-CREB, cysteine aspartate pro-tease (Caspase)-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2 related X protein (Bax) in the hippocampal tissue of rats. RESULTS: Compared with the normal group, the rats' random blood glucose contents were significantly increased (P<0.01), the escape latency prolonged (P<0.01), and the original platform crossing counts reduced (P<0.01) in the model group. Significant damage to hippocampal CA1 neurons, a significantly increased neuronal apoptosis index (P<0.01), decreased ratio of p-PI3K/PI3K and p-Akt/Akt and expression of CREB, p-CREB and Bcl-2 proteins, increased expression of Caspase-3 and Bax proteins (P<0.01) were observed in the hippocampal tissue of rats in the model group. Compared with the model group, the rats in the EA group showed decreased random blood glucose content (P<0.01), shortened escape latency (P<0.01), increased original platform crossing counts (P<0.01), improved quantity and pathological morphology and ultrastructure of hippocampal CA1 neurons, reduced neuronal apoptosis index (P<0.01), increased ratio of p-PI3K/PI3K and p-Akt/Akt, and expression of CREB, p-CREB and Bcl-2 proteins (P<0.05, P<0.01) in the hippocampal tissue, and decreased expression of Caspase-3 and Bax proteins (P<0.01). CONCLUSIONS: EA can improve the learning and memory abilities of rats with DCI, and the mechanism may be related to the regulation of the expression of PI3K/Akt/CREB signaling pathway-related proteins, which attenuates the neuronal apoptosis in the hippocampus of rats, and improves the neural function.

Targeting of MALT1 May Improve Functional Recovery and Attenuate Microglia M1 Polarization-Mediated Neuroinflammation During Spinal Cord Injury.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is involved in neural injury, neuroinflammation, microglia activation, and polarization, while its function in spinal cord injury (SCI) remains unclear. Thus, this study aimed to evaluate the role of MALT1 modification on SCI recovery and its underlying mechanism. SCI surgery or sham surgery was performed in Sprague-Dawley rats. Then, MALT1 knockdown or negative control lentivirus was injected into SCI rats. Subsequently, MALT1 expression, locomotor capability, neural injury, markers for microglia activation and polarization, inflammatory cytokine expressions, and nuclear factor (NF)-κB pathway were detected. SCI rats exhibited higher MALT1 expression, microglia activation and M1 polarization, neuroinflammation, and NF-κB pathway activation, while worse locomotor capacity compared to sham rats (all P < 0.05). In SCI rats, MALT1 knockdown alleviated Basso, Beattie, and Bresnahan score from 10 to 28 days and attenuated HE staining reflected neural injury (all P < 0.05). Besides, MALT1 knockdown declined the number of IBA1+ cells, IBA1+ iNOS+ cells, and IBA1+ CD86+ cells, while enhanced the number of IBA1+ Arg1+ cells and IBA1+ CD206+ cells in SCI rats (all P < 0.05). Meanwhile, MALT1 knockdown declined the expressions of IL-1ß, IL-6, and TNF-α in SCI (all P < 0.05), but did not affect IL-10 expression (P > 0.05). Furthermore, MALT1 knockdown suppressed NF-κB pathway activation validated by immunofluorescence staining and western blot assays (all P < 0.05). MALT1 knockdown improves functional recovery, attenuates microglia activation, M1 polarization, and neuroinflammation via inhibiting NF-κB pathway in SCI.

Circ_0048856 competes with ABCC1 for miR-193a-5p/miR-98-5p binding sites to promote the cisplatin resistance and tumorigenesis in lung cancer.

Although cisplatin (DDP)-based therapy is the most predominant chemotherapeutic strategy used for lung cancer, drug resistance usually occurs after several cycle use of it. Circular RNAs (circRNAs) are found to be involved in the chemoresistance in lung cancer. Hence, this study aimed to clarify the role and mechanism of circ_0048856 in lung cancer tumorigenesis and DDP resistance. The levels of circ_0048856, miR-193a-5p, miR-98-5p and ABCC1 (ATP Binding Cassette Subfamily C Member 1) were determined by qRT-PCR and western blotting. In vitro assays were conducted by cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine (EDU) assay, flow cytometry and transwell assay, respectively. The binding interaction was verified using dual-luciferase reporter assay and RIP assay. In vivo experiment was performed by the establishment of murine xenograft model. Circ_0048856 was highly expressed in DDP-resistant lung cancer tissues and cells. Functionally, circ_0048856 silencing re-sensitized DDP-resistant lung cancer cells to DDP, as well as suppressed cell growth and invasion in lung cancer in vitro and in vivo. Mechanistically, circ_0048856 acted as the sponge for miR-193a-5p or miR-98-5p, which targeted ABCC1. Furthermore, rescue experiments showed that inhibition of miR-193a-5p or miR-98-5p reversed the effects of circ_0048856 knockdown on lung cancer cells. Besides that, overexpression of miR-193a-5p or miR-98-5p suppressed cell tumorigenesis and reduced DDP resistance in lung cancer, which were attenuated by ABCC1 up-regulation. Circ_0048856 knockdown suppressed tumor growth and reduced DDP resistance in lung cancer by miR-193a-5p/ABCC1 or miR-98-5p/ABCC1 axis, indicating a novel strategy for efficient application of DDP in lung cancer.

A 44-Year-Old Man With Right Limb Convulsion and Cavitary Lung Lesion With Diffuse Interstitial Abnormalities.

CASE PRESENTATION: A 44-year-old man with a history of asthma presented with intermittent convulsion of the right limb, fever in the late afternoon, and decreased exercise tolerance over 2 months. Occasional productive cough, no hemoptysis, and weight loss of nearly 6 kg were observed during this period. Neither chemotherapy nor oral immunosuppressive drugs had been administered, and no exposure to toxic substances was known. He was a cook and had smoked approximately one pack of cigarettes per day for the past 20 years. The living environment was relatively humid. The patient presented to a local hospital, where the workup was notable for low-density shadows in the left parieto-occipital lobe and a cavity in the right upper lobe of the lung with bilateral diffuse interlobular septal thickening and multiple patchy ground-glass opacities. The brain and lung lesions were 18F-fluorodeoxyglucose avid on PET/CT scan. Bronchoscopy with BAL and transbronchial biopsy were nondiagnostic. While preparing for another diagnostic procedure, the patient gradually developed increasing dyspnea and more frequent convulsions with the progression of lesions on the follow-up chest CT scan. The patient was transferred to our hospital.

Both subthalamic and pallidal deep brain stimulation are effective for GNAO1-associated dystonia: three case reports and a literature review.

Background: Mutations in the G-protein subunit alpha o1 (GNAO1) gene have recently been shown to be involved in the pathogenesis of early infantile epileptic encephalopathy and movement disorders. The clinical manifestations of GNAO1-associated movement disorders are highly heterogeneous. However, the genotype-phenotype correlations in this disease remain unclear, and the treatments for GNAO1-associated movement disorders are still limited. Objective: The objective of this study was to explore diagnostic and therapeutic strategies for GNAO1-associated movement disorders. Methods: This study describes the cases of three Chinese patients who had shown severe and progressive dystonia in the absence of epilepsy since early childhood. We performed genetic analyses in these patients. Patients 1 and 2 underwent globus pallidus internus (GPi) deep brain stimulation (DBS) implantation, and Patient 3 underwent subthalamic nucleus (STN) DBS implantation. In addition, on the basis of a literature review, we summarized and discussed the clinical characteristics and outcomes after DBS surgery for all reported patients with GNAO1-associated movement disorders. Results: Whole-exome sequencing (WES) analysis revealed de novo variants in the GNAO1 gene for all three patients, including a splice-site variant (c.724-8G > A) in Patients 1 and 3 and a novel heterozygous missense variant (c.124G > A; p. Gly42Arg) in Patient 2. Both GPi and STN DBS were effective in improving the dystonia symptoms of all three patients. Conclusion: DBS is effective in ameliorating motor symptoms in patients with GNAO1-associated movement disorders, and both STN DBS and GPi DBS should be considered promptly for patients with sustained refractory GNAO1-associated dystonia.

A 66-Year-Old Woman With Progressive Dyspnea and Obstructive Pneumonia.

CASE PRESENTATION: A 66-year-old woman with a history of diabetes presented with an intermittent low-grade fever, cough, shortness of breath, and decreased activity tolerance over a 3-month period. She is a farmer, and denied a history of chronic pulmonary disease. Her only medical history was type 2 diabetes managed without medication. She denied smoking or tobacco use. She did not report any recent travel and denied having birds at home. Imaging at a local hospital showed left lower lobe atelectasis with a small pleural effusion. An infection with mucormycosis was diagnosed through transbronchial biopsy. The patient was given nebulized amphotericin B along with concurrent IV liposomal amphotericin B for a total of 15 days. She experienced no significant improvement in symptoms during therapy and, in fact, developed worsening, progressive dyspnea.

Contents and yields of copper, iron, manganese and zinc would be affected by lucerne age and cut.

BACKGROUND: Lucerne is a perennial legume forage, which can produce multiple cuts in 1 year. Microelements play fundamental roles in the function, maintenance and adaptation to the environment for lucerne growth. However, the role of the accumulation of copper (Cu), iron (Fe), manganese (Mn) and Zinc (Zn), which vary with lucerne ages or cuts, has not been previously determined. Therefore, a hypothesis on the Cu, Fe, Mn and Zn in lucerne varying with age and cut was tested. METHODS: A total of 11, 8, 5, 4 and 1 year old lucerne (Medicago sativa Longdong) were selected as the material (until 2012 year), and samples were taken as three cuts at the cutting periods (early flowering stage) in 2012. Then, the contents and yields of Cu, Fe, Mn and Zn in lucerne were measured and calculated. RESULTS: The highest contents of Cu, Fe, Mn and Zn in lucerne were found in the 1 year old among the five ages, at the 3rd cut compared to the other two cuts, and in the leaf among the three organs. The highest yields of Cu, Fe, Mn and Zn were found in the older ages (11 and 8 years old), at the 3rd cut, and in the root among the three organs. The most positive correlations were found between contents, yields and biomass. CONCLUSIONS: The hypothesis was supported by the results. And the contents and yields of lucerne Cu, Fe, Mn and Zn were affected by the age, cut and organ. Furthermore, the yields of lucerne Cu, Fe, Mn and Zn were determined by their contents and lucerne biomass.

Tenascin C Promotes Glioma Cell Malignant Behavior and Inhibits Chemosensitivity to Paclitaxel via Activation of the PI3K/AKT Signaling Pathway.

The present study aimed to detect the effect of tenascin C (TNC) on cell function and chemosensitivity to paclitaxel and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling in glioma cells.Human glioma cells U87, LN-229, T98G and U251 and normal human astrocytes were obtained, in which TNC expression was detected. The U87 cells and U251 cells were chosen and infected with lentivirus of control overexpression, TNC overexpression, control knockdown, and TNC knockdown for functional experiments. Rescue experiments were then performed to evaluate the effect of PI3K/AKT activator 740 Y-P on cell function and chemosensitivity to paclitaxel in TNC knockdown U251 cells. TNC mRNA and protein expression was elevated in glioma cells, including U87, LN-229, U251 and T98G cells, compared to normal human astrocytes. In U87 and U251 cells, TNC promoted proliferation while inhibiting apoptosis. In addition, TNC upregulated PI3K and p-AKT protein expression in U87 and U251 cells. As for chemosensitivity, TNC increased relative viability in U251 cells treated with 400 ng/mL and 800 ng/mL paclitaxel. In terms of stemness, TNC increased the sphere number per 1000 cells, CD44+CD133+ cell percentage and 1/stem cell frequency (assessed by extreme limiting dilution analysis) in U251 cells. In rescue experiments, 740 Y-P reduced the effect of TNC on proliferation, apoptosis, chemosensitivity to paclitaxel, and stemness in U251 cells. TNC acts as an oncogenic factor by promoting cancer cell proliferation and stemness while inhibiting apoptosis and chemosensitivity to paclitaxel in glioma via modulation of PI3K/AKT signaling.

Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma presenting as a solitary colonic mass: two rare cases and a literature review.

AIMS: Follicular dendritic cell (FDC) sarcoma is a rare neoplasm originating from follicular dendritic cells in germinal centres. It is classified as conventional and Epstein-Barr virus (EBV)-positive inflammatory FDC sarcoma according to the 2019 World Health Organization classification of digestive system tumours; the latter is rarer. So in view of the rarity and difficulty in diagnosis, the aim of the manuscript is to share our experience of diagnosing EBV-positive inflammatory FDC sarcoma. METHODS AND RESULTS: Here, we describe the clinicopathological features, gross description, histomorphology, immunophenotype, EBV-encoded mRNA (EBER) in-situ hybridisation, gene rearrangement and clinical follow-up of two patients with EBV-positive inflammatory FDC sarcoma in the colon, and review the relevant literature. The tumours were found in two males, aged 53 and 48 years, respectively, with a tumour diameter between 10 and 45 mm. Both cases occurred in the colon and presented as pedunculated colonic masses. Microscopically, scanty atypical ovoid to spindle neoplastic cells were mixed in a background of florid lymphoplasmacytic infiltration. The nuclei of these atypical cells showed vesicular chromatin and small, distinct nucleoli. Immunohistochemistry demonstrated that the atypical stromal cells were positive for CD21, CD23, CD35, and D2-40. EBER in-situ hybridisation also gave positive results in two cases. There was a mean follow-up of 9 months (range, 7-11 months). CONCLUSION: EBV-positive inflammatory FDC sarcoma is an extremely rare tumour with a distinct morphology and phenotype. Therefore, it is very important to recognise it particularly for correct diagnosis and prevention of misdiagnosis and mistreatment.

Expression of Twist associated to microcirculation patterns of human glioma correlated with progression and survival of the patient.

Twist is a transcription factor involved in the process of epithelial to mesenchymal transition (EMT) of carcinoma cells, and the promotion of invasion of gliomas through the mesenchymal adjusting process. However, its clinical significance in human glioma has not yet to be understood. To delineate the clinical-pathological significance and prognostic value of Twist, the expression of Twist was evaluated by Immunohistochemistry for 187 glioma samples. We found that Twist demonstrated frequent nuclear expression in the glioma samples and its expression levels were associated with tumor grade (P<0.001). Furthermore, high Twist expression was correlated with a poor outcome in patients with glioma (P=0.001), particularly with high grade glioma (P=0.026). Interestingly, Twist expression showed positive correlation with microvascular density (MVD) (r=0.145, P=0.048) as well as vasculogenic mimicry (VM) (r=0.273, P<0.001) in the tumors. These results suggest that Twist could be a predictor for poor prognosis in glioma patients. Additionally, Twist expression was associated with two major microcirculation patterns: endothelial-dependent vessels and VM in glioma, indicating that Twist could be a potential molecular target for anti-glioma therapy.

Association between glioblastoma cell-derived vessels and poor prognosis of the patients.

BACKGROUND: Vessels with different microcirculation patterns are required for glioblastoma (GBM) growth. However, details of the microcirculation patterns in GBM remain unclear. Here, we examined the microcirculation patterns of GBM and analyzed their roles in patient prognosis together with two well-known GMB prognosis factors (O6 -methylguanine DNA methyltransferase [MGMT] promoter methylation status and isocitrate dehydrogenase [IDH] mutations). METHODS: Eighty GBM clinical specimens were collected from patients diagnosed between January 2000 and December 2012. The microcirculation patterns, including endothelium-dependent vessels (EDVs), extracellular matrix-dependent vessels (ECMDVs), GBM cell-derived vessels (GDVs), and mosaic vessels (MVs), were evaluated by immunohistochemistry (IHC) and immunofluorescence (IF) staining in both GBM clinical specimens and xenograft tissues. Vascular density assessments and three-dimensional reconstruction were performed. MGMT promoter methylation status was determined by methylation-specific PCR, and IDH1/2 mutations were detected by Sanger sequencing. The relationship between the microcirculation patterns and patient prognosis was analyzed by Kaplan-Meier method. RESULTS: All 4 microcirculation patterns were observed in both GBM clinical specimens and xenograft tissues. EDVs were detected in all tissue samples, while the other three patterns were observed in a small number of tissue samples (ECMDVs in 27.5%, GDVs in 43.8%, and MVs in 52.5% tissue samples). GDV-positive patients had a median survival of 9.56 months versus 13.60 months for GDV-negative patients (P = 0.015). In MGMT promoter-methylated cohort, GDV-positive patients had a median survival of 6.76 months versus 14.23 months for GDV-negative patients (P = 0.022). CONCLUSION: GDVs might be a negative predictor for the survival of GBM patients, even in those with MGMT promoter methylation.

Clinical significance of CD133 and Nestin in astrocytic tumor: The correlation with pathological grade and survival.

BACKGROUND: We aimed to investigate the interaction between CD133 and Nestin and further assessed the correlation of CD133 and Nestin with clinicopathological characteristics and survival in patients with astrocytic tumor. METHODS: Totally 127 patients with astrocytic tumor underwent surgical resection were enrolled. Patients' age, gender, and World Health Organization (WHO) grade were recorded, and the survival data were extracted from the follow-up records. The expressions of CD133 and Nestin in astrocytic tumor tissues were analyzed by immunohistochemistry assay. The WHO grade I and II astrocytic tumors were defined as low-grade astrocytic tumors (LGA), the WHO grade III and IV astrocytic tumors were defined as high-grade astrocytic tumors (HGA). RESULTS: There were 79 (62.2%), 34 (26.8%), 14 (11.0%), and 0 (0.0%) patients with CD133 negative, low, moderate, and high expression, respectively; 7 (5.5%), 47 (37.0%), 20 (15.7%), 53 (41.7%) patients with Nestin negative, low, moderate, high expression, respectively. CD133 and Nestin were both correlated with advanced WHO grade but not with age or gender, and positive correlation was observed between CD133 and Nestin. For survival, both CD133 and Nestin were correlated with unfavorable overall survival (OS), and further analysis illustrated that Nestin but not CD133 independently predicted poor OS. Subgroup analysis also revealed that Nestin but not CD133 negatively associated with shorter OS in LGA patients, while both CD133 and Nestin were correlated with poor OS in HGA patients. CONCLUSION: CD133 and Nestin present as potential biomarkers for advanced pathological grade and poor survival in patients with astrocytic tumor.

Selenium nanoparticles reduce glucose metabolism and promote apoptosis of glioma cells through reactive oxygen species-dependent manner.

Gliomas are the most common, malignant, and lethal tumors in adults. Furthermore, gliomas are highly resistant to current chemotherapeutic drugs. Thus, new effective anticancer drugs for glioma are urgently needed. Selenium nanoparticles have been reported to have potent anti-tumor activity, although the specific mechanism is not fully understood. This study aimed to test the anti-tumor effect of selenium nanoparticles and its mechanism. We used selenium nanoparticles to treat commercial glioma cell lines, and patient-derived glioma cells, and then used the MTT assay to determine selenium nanoparticles effect against these. Apoptotic cell death was determined by annexin V-Fluos staining kit. Glucose uptake, lactate, and adenosine triphosphate production, together with hexokinase 2 and pyruvate kinase activities were measured to determine the glucose metabolism level. Reactive oxygen species production was tested using 2',7'-dichlorodihydrofluorescein diacetate. Our results showed that selenium nanoparticles had a potent cytotoxic effect in glioma cells, regardless of whether they were drug-resistant or not, whereas it showed less toxic effect in normal healthy cells. Further tests showed that selenium nanoparticles treatment leads to apoptotic cell death enhancement and glucose metabolism reduction, and this process was in a reactive oxygen species pathway-dependent manner. These results may provide a novel direction for glioma therapy in the future.

Different effects of allergic rhinitis on nasal mucosa remodeling in chronic rhinosinusitis with and without nasal polyps.

BACKGROUND: Allergic rhinitis (AR) has been reported to be associated with chronic rhinosinusitis (CRS). The objective of this study was to investigate the effect of AR on nasal mucosa remodeling in CRS. METHODS: Patients were enrolled and divided into the following groups: CRS with nasal polyps (NP) with allergic rhinitis (AR)(CRSwNPwAR; n = 20), CRS with NP without AR (CRSwNPsAR; n = 20), CRS without NP with AR (CRSsNPwAR; n = 20), CRS without NP without AR (CRSsNPsAR; n = 20), AR without CRS (AR; n = 20) and controls (n = 14). Eosinophil infiltration, mucus production, and collagen deposition were examined by hematoxylin and eosin, periodic acid schiff and masson's trichrome staining, respectively. VEGF-A and microvessel density were detected by immunohistochemistry. The expression of remodeling markers, including TGF-ß1, MMP-7, MMP-9 and TIMP-1 were measured by Western blot. RESULTS: The expression of remodeling factors, including VEGF-A, CD31, CD34 and TIMP-1 were significantly increased in CRSwAR compared to CRSsAR. Goblet cell hyperplasia, as well as VEGF-A, CD31, CD34, and MMP-9 expression were significantly higher in CRSwNPwAR compared to CRSwNPsAR. However, the expression of collagen fibers, MMP-7 and TGF-ß1 were significantly higher in CRSsNPwAR compared to CRSsNPsAR. CONCLUSIONS: AR could enhance the remodeling process in CRS. Moreover, AR had different effects on CRSwNP and CRSsNP.

Sca1(+) mesenchymal stromal cells inhibit graft-versus-host disease in mice after bone marrow transplantation.

Mesenchymal stromal cells (MSCs) have therapeutic potential for the prevention and treatment of graft-versus-host disease (GVHD). However, MSCs comprise several subpopulations, which have not been individually assessed for their role in GVHD suppression. In this study, we assessed the immunosuppressive effect of bone-related Sca1(+) MSCs on acute GVHD in a MHC-mismatched mouse model of allogeneic hematopoietic stem cell transplantation (HCT). Our results showed that Sca1(+) MSCs decreased the severity of acute GVHD (aGVHD) and prolonged the survival period of allogeneic HCT recipients. This effect was exerted through lowered T lymphocyte infiltration in target organs and by inhibition of CD80/86 expression on host dendritic cells. Furthermore, the expression of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of T cells, was elevated in the recipient splenocytes. In conclusion, bone-related Sca1(+) MSCs subpopulation suppressed GVHD and could be a novel treatment for acute GVHD.

Kinetics of apoptosis and expression of apoptosis-related proteins in rat CA3 hippocampus cells after experimental diffuse brain injury.

The present study examined kinetics of apoptosis and expression of apoptosis-related proteins Bcl-2, Bax, and caspase-3 in the CA3 hippocampus cells after diffuse brain injury (DBI) induced experimentally in rats. Percentage of apoptotic cells and expressions of above proteins were examined by flow cytometry and immunohistochemistry. Substantial neuronal apoptosis was documented in the CA3 hippocampus cells after DBI (22.26 ± 2.97% at 72 h after DBI vs. 2.92 ± 0.88% in sham-operated animals). Expression of Bc1-2 decreased, while expression of Bax and caspase-3 increased after DBI, with caspase-3 expression peaking after that of Bax (72 vs. 48 h, respectively). Further, the Bc1-2/Bax expression ratio decreased prior to increase of caspase-3 expression. In conclusion, cell apoptosis and altered expressions of Bcl-2, Bax, and caspase-3 are present in the CA3 region of hippocampus after experimental DBI. Changes in the Bc1-2/Bax expression ratio may facilitate activation of caspase-3 and aggravate neuronal apoptosis after brain injury.

Traumatic tympanic membrane perforations: a study of etiology and factors affecting outcome.

OBJECTIVE: The purposes of this study were to determine the factors involved in the spontaneous healing and to profile the various etiologies of traumatic tympanic membrane (TM) perforation. METHODS: A retrospective review was performed on 729 cases of traumatic TM perforation diagnosed in the emergency department and outpatient clinic from January 2007 to March 2011. RESULTS: A total 641 patients with traumatic TM perforations were enrolled in the study. The group consisted of 320 male and 321 female patients with a mean age of 33.6 years (3-79 years). The types of trauma included compression injury (554 patients), blast injury (55 patients), and instrumental injury (32 patients). The causes of conflict by a slap or a fist were spouse or lover (52%), parents and sibling (3%), school teachers (4%), schoolmate (12%), state police and prisoner (7%), and blow against the ear during street fight (22%). Of the 641, 137 were lost during follow-up; of the remaining 504, perforations closed spontaneously in 451 (89%), within a mean of 27.4 days. Wet perforations with bloody or watery discharge significantly improved the healing rate (P < .01) and shortened the average perforation closure time (P < .01), as compared with dry perforations. Although the perforation that involved malleus or umbo damage did not significantly affect the healing rate (P > .05), a significantly prolonged closure time (41.6 vs 23.8 days) was observed as compared with no damage. However, the curled edges did not also affect the outcome of spontaneous healing; the healing rate was 91% and 88% (P > .05), and the average closure time was 28.1 and 26.7 days (P > .05), respectively, for with and without curler edges. By perforation size, the overall healing rate was 92% and 54% (P < .01), and the average closure time was 22.8 and 47.3 days (P < .01), respectively, for small and larger perforations. Moreover, 7 patients had neomembrane formation on follow-up, 2 developed cholesteatoma, 1 developed tympanosclerosis, and 1 developed facial paralysis. CONCLUSION: In our experience, domestic violence and street fight were the most common causes of the traumatic TM perforation. Traumatic TM perforations have excellent prognosis. However, preexisting tympanosclerosis and the perforation that involved malleus or umbo damage could lengthen the healing time of perforation, Wet perforations with bloody or watery discharge accelerate the healing, but the curled edges did not affect the outcome of spontaneous healing.