Long noncoding RNA MALAT1 contributes to inflammatory response of microglia following spinal cord injury via the modulation of a miR-199b/IKKß/NF-κB signaling pathway.

Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was widely recognized to be implicated in human cancer, vascular diseases, and neurological disorders. This study was to explore the role and underlying mechanism of MALAT1 in acute spinal cord injury (ASCI). ASCI models in adult rats were established and demonstrated by a numerical decrease in BBB scores. Expression profile of MALAT1 and miR-199b following ASCI in rats and in vitro was determined using quantitative real-time PCR. RNA pull-down assays combined with RIP assays were performed to explore the interaction between MALAT1 and miR-199b. In the present study, MALAT1 expression was significantly increased (2.4-fold that of control) in the spinal cord of the rat contusion epicenter accompanied by activation of IKKß/NF-κB signaling pathway and an increase in the level of proinflammatory cytokines TNF-α and IL-1ß. Upon treatment with LPS, MALAT1 expression dramatically increased in the microglia in vitro, but knockdown of MALAT1 attenuated LPS-induced activation of MGs and TNF-α and IL-1ß production. Next, we confirmed that LPS-induced MALAT1 activated IKKß/NF-κB signaling pathway and promoted the production of proinflammatory cytokines TNF-α and IL-1ß through downregulating miR-199b. More importantly, MALAT1 knockdown gradually improved the hindlimb locomotor activity of ASCI rats as well as inhibited TNF-α, IL-1ß levels, and Iba-1 protein, the marker of activated microglia in injured spinal cords. Our study demonstrated that MALAT1 was dysregulated in ASCI rats and in LPS-activated MGs, and MALAT1 knockdown was expected to attenuate ASCI through repressing inflammatory response of MGs.

Downregulation of miR-199b promotes the acute spinal cord injury through IKKß-NF-κB signaling pathway activating microglial cells.

Inflammatory response played an important role in the progression of spinal cord injury (SCI). Several miRNAs were associated with the pathology of SCI. However, the molecular mechanism of miRNA involving in inflammatory response in acute SCI (ASCI) was poorly understood. Sprague-Dawley (SD) rats were divided into 2 groups: control group (n=6) and acute SCI (ASCI) group (n=6). The expression of miR-199b and IκB kinase ß-nuclear factor-kappa B (IKKß-NF-κB) signaling pathway were evaluated by quantitative reverse transcription-PCR (qRT-PCR) in rats with ASCI and in primary microglia activated by lipopolysaccharide (LPS). We found that downregulation of miR-199b and activation of IKKß/NF-κB were observed in rats after ASCI and in activated microglia. miR-199b negatively regulated IKKß by targeting its 3'- untranslated regions (UTR) through using luciferase reporter assay. Overexpression of miR-199b reversed the up-regulation of IKKß, p-p65, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in LPS-treated BV2 cells assessed by western blotting analysis. In addition, BMS-345541 reversed the up-regulation effects of miR-199b inhibitor on the expression of TNF-α and IL-1ß. In the SCI rats, overexpression of miR-199b attenuated ASCI and decreased the expression of IKKß-NF-κB signaling pathway and TNF-α and IL-1ß. These results indicated that miR-199b attenuated ASCI at least partly through IKKß-NF-κB signaling pathway and affecting the function of microglia. Our findings suggest that miR-199b may be employed as therapeutic for spinal cord injury.

Treatment of hypertensive intracerebral hemorrhage through keyhole transsylvian approach.

The present study investigated the therapeutic effects and indications of keyhole transsylvian approach (KTA) in the treatment of hypertensive intracerebral hemorrhage (HICH). Clinical data of 65 cases of HICH were retrospectively analyzed. All the patients were treated by open surgical evacuation either through KTA (KTA group) or through conventional craniotomy approach (CCA group). The operative time, intraoperative bleeding quantity, the length of hospitalization, mortality, and favorable outcome were compared between the 2 groups. Compared with the CCA group, the KTA group had smaller bleeding quantity and shorter length of hospitalization. Favorable outcome at 3 months after admission was higher in the KTA group than that in the CCA group. The present study suggests that treatment of HICH through KTA is a practical and effective surgical procedure.

Posttransplantation lymphoproliferative disorder involving the central nervous system in liver transplant recipients.

BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) involving the central nervous system (CNS) is a rare and serious complication associated with solid organ transplantation. We treated a case of PTLD with CNS involvement in a liver transplant recipient and reviewed the literature. METHOD: The clinicopathological features of a 53-year-old man were retrospectively analyzed. RESULTS: Metastasis of the hepatoma was preoperatively considered on the basis of clinical findings. Craniotomy was performed and PTLD was diagnosed pathologically. The patient was treated with antiviral agents, radiation therapy, and chemotherapy; the immunosuppressive medication was reduced. The patient is still alive after follow-up for 14 months. CONCLUSIONS: Definitive diagnosis of PTLD is only established on the basis of histopathologic evaluation of the tissue. Although there are several ways to manage PTLD with CNS involvement, the prognosis is still poor.

Congenital bronchoesophageal fistula in an adult: a case report.

Bronchoesophageal fistulas are usually diagnosed in the neonatal period. As such, the condition is rare in adults. We present a case of a congenital bronchoesophageal fistula in a 62-year-old man with the complaint of severe bouts of cough and choking after swallowing liquid. His workup included a barium esophagogram that revealed a fistula between the esophagus and a right lower lobe bronchus. The diagnosis should be considered in certain individuals with suggestive symptomatology and unexplained respiratory pathology. The fistula was divided and resected, The patient had an uneventful recovery.

[Surgical treatment of primary thymoma].

OBJECTIVE: To summarize the clinical and pathologic features of thymoma and assess surgical treatment thereof. METHODS: The clinical data of 66 thymoma patients, 35 males and 31 females, aged 40.8 (30 approximately 59), who underwent surgical treatment in the past 20 years, were analyzed. By Masaoka staging system, underwent extensive or radical or palliative operation, most commonly performed through a median sternotomy and frequently requires en-bloc resection of one or more adjacent structures. RESULTS: Fourteen of the 66 patients had associated myasthenia gravis (MG). The most common symptoms included chest pain, MG, cough, and dyspnea; only 11 of the 66 (16.7%) patients had no symptom. Masaoka staging revealed stage I in 29 patients (43.9%), stage II in 16 (24.2%), stage III in 19 (28.8%), and stage IV in 2 (3.0%). Fourteen of the 66 patients underwent radical resection, resection of the whole thymus and thymoma, 40 underwent simple resection of thymus, 5 underwent palliative resection of thymoma, and 6 underwent thymectomy exploration. Recurrence of tumor was observed in 4 patients. Postoperative radiotherapy and chemotherapy were performed 24 h after the operation, mainly in the cases of invasive or metastatic thymoma. One patient died within 30 days after the operation. CONCLUSIONS: Resection and postoperative radiotherapy or chemotherapy are necessary in treatment of thymoma, particularly complete thymectomy.

[Clinical value of computed tomography and fluorine-18 fluorodeoxyglucose positron remission tomography in diagnosis of mediastinal metastasis of non small cell lung cancer].

OBJECTIVE: To compare the clinical values of computed tomography (CT) and fluorine-18 fluorodeoxyglucose positron remission tomography (FDG-PET) in diagnosis of mediastinal metastasis of non-small cell lung cancer (NSCLC). METHODS: Sixty patients with respectable NSCLC underwent CT and FDG-PET with an interval of 2 weeks and then underwent thoracotomy for clearance of the lymph nodes or biopsy of the mediastinal lymph nodes via mediastinoscopy. The specimens of mediastinal lymph node underwent HE staining and PCNA/Ki67 immunohistochemical staining. The sensitivity, specificity, accuracy, positive prediction value, and negative prediction value in diagnosis of metastasis of mediastinal lymph nodes of these 2 procedures were compared. RESULTS: The sensitivity, specificity, accuracy, positive prediction value, and negative prediction value in diagnosis of metastasis of mediastinal lymph nodes were 92.3%, 87.5%, 91.2%, 96.0%, and 77.7% respectively for FDG-PET, and were 76.9%, 50.0%, 70.6%, 83.3%, and 40.0% respectively for CT. The sensitivity rate was 98% for CT plus FDG-PET. CONCLUSION: PET is superior to CT in diagnosis of metastasis of NSCLC to mediastinal lymph nodes. PET + CT significantly increases the sensitivity in diagnosis.

[The value of postoperative arterial infusion chemotherapy in patients with T3 esophageal squamous carcinoma after radical surgery].

OBJECTIVE: To studying the porgnostic factors after curative esophagetomy for the thoracic segment T3 esophageal after radical surgery. METHODS: 190 patients suffering from T3 squamous carcinoma of lower thoracic esophagus who underwent radical surgery from January 1990 to January 1999, 158 males and 32 females, aged 62.98 (40 approximately 81), were divided into 2 groups: 108 patients (experimental group, T3N0M0 56 cases and T3N1M0 52 cases) underwent surgery and arterial infusion (cisplatin 80 mg/m(2) and fluorouracil (800 mg/m(2)) with or without epirubicin since 3 approximately 4 weeks postoperatively, the interval of each periods is 4 - 6 weeks. and the other 82 patients (T3N0M0 48 cases and T3N1M0 34 cases) underwent surgery only. Fifty-six out of the 108 cases in the experimental group (T3N0M0 26 cases and T3N1M0 30 cases) underwent 3 periods of chemotherapy for less than 3 periods of chemotherapy with an interval between 2 periods of 4 approximately 6 weeks, and the other 52 patients (T3N0M0 30 cases and T3N1M0 22 cases) underwent chemotherapy for 3 periods or over. All cases were followed up for more than 5 years. Kaplan-Meier survival curve was used to analyze the survival rate. Cox regression model was used to analyze the influencing factors of prognosis. RESULTS: There was no significant difference in the overall long-term survival rate between the experimental group and control group, however, the survival rate of those receiving 3 periods of chemotherapy and over was significantly higher than those receiving less than 3 periods of chemotherapy Lymph node metastatic status was an important factor in prognosis of esophageal squamous carcinoma. CONCLUSION: Without severe side effects, postoperative chemotherapy by transcatheter arterial infusion prolongs the survival rate of the patients with esophageal squamous carcinoma who have been previously treated by radical surgery.

[Interleukin-2 induced endothelium-dependent relaxation of rat thoracic aorta].

Interleukin-2 (IL-2) therapy often results in potentially life-threatening side effects including hypotension. However, the mechanism has not been completely elucidated. In order to determine whether IL-2 modifies vascular tone, we investigated the effect of IL-2 on rat thoracic aorta rings and the underlying mechanisms. Effects of IL-2 on the contraction of high KCl and phenylephrine (PE) preconstricted rat thoracic aorta with or without endothelium were determined by organ bath technique. To explore the mechanism, nitric oxide synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), guanylyl cyclase inhibitor methylene blue, and cyclooxygenase inhibitor indomethacin were used. IL-2 (10-1000 U/ml) caused concentration-dependent relaxation of aorta rings preconstricted with PE (10 micromol/L) in endothelium-intact rings, but had no effect on KCl (120 mmol/L) preconstricted rings. Removal of the endothelium, or pretreatment with L-NAME (0.1 mmol/L) or methylene blue (10 micromol/L) or indomethacin (10 micromol/L), inhibited the relaxation of IL-2. The results indicate that the relaxation by IL-2 in rat aorta ring is endothelium-dependent and is possibly mediated by the NO-guanylyl cyclase pathway and cyclooxygenase-dependent pathway.