Suppression of NLRP3 inflammasome attenuates stress-induced depression-like behavior in NLGN3-deficient mice.

Depression, regulated by central nervous system (CNS), is a significant inflammatory disorder. Neuroligin3 (NLGN3) has been implicated in brain functions. In the study, a chronic unpredictable mild stress (CUMS) model in wild type (WT) or NLGN3-knockout (KO) mice was established to explore the role of NLGN3 in regulating depression and to reveal the underlying molecular mechanism. The results indicated that NLGN3-knockout markedly reversed the loss of body weight, the reduction of sucrose consumption, the decrease of immobile time in the forced swimming tests (FST) and tail suspension tests (TST) induced by CUMS paradigm. CUMS up-regulated corticosterone (CORT) in serum, and down-regulated serotonin (5-HT), norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) in hippocampus of mice, which were significantly reversed by NLGN3 deficiency. The results further demonstrated that NLGN3-knockout improved the degenerative neurons in cortex and hippocampus of CUMS-treated mice, accompanied with a significant decrease of ionized calciumbinding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) expressions. Additionally, NLGN3-KO mice challenged with CUMS showed a significant reduction of pro-inflammatory cytokines and chemokine, including tumor necrosis factor-alpha (TNF-α), interleukin-18 (IL-18), interleukin-1 beta (IL-1ß), interleukin-4 (IL-4), CC-chemokine ligand-1 (CCL-1) and CXC-chemokine ligand-1 (CXCL-1), in cortex, hippocampus and amygdala tissue samples. Western blot analysis suggested that NLGN3-knockout inhibited the activation of nod-like receptor protein 3 (NLRP3) inflammasome and its adaptor of apoptosis-associated speck like protein (ASC), and reduced the expression of Caspase-1, along with the inactivation of nuclear factor-κB (NF-κB) in CUMS-challenged mice. The role of NLGN3 in regulating depression in mice was confirmed in vitro using astrocytes stimulated by LPS that NLGN3 knockdown reduced LPS-induced inflammation. Importantly, the suppressive effects of NLGN3-knockdown on inflammatory response were reversed by NLRP3 or ASC over-expression in AST exposed to LPS. In sum, our findings indicated that suppressing NLGN3 played a potential antidepressant role in CUMS animal model by inactivating NLRP3 inflammasome, providing a new therapeutic avenue for depression.

Effects of Transcutaneous Electrical Acupoint Stimulation (TEAS) on Postoperative Recovery in Patients with Gastric Cancer: A Randomized Controlled Trial.

PURPOSE: Transcutaneous electrical acupoint stimulation (TEAS) is an innovative choice for postoperative pain management. However, the safety and effectiveness of this traditional Chinese medicine (TCM) therapy for patients who underwent gastrectomy is largely unknown. So, the purpose of this study is to evaluate the safety and effectiveness of TEAS for patients who underwent gastrectomy. PATIENTS AND METHODS: We recruited 96 patients with gastric cancer from May 2019 to November 2019; 82 patients were enrolled, and 81 patients completed. Patients were randomly assigned to TEAS group (TG) received TEAS on postoperative day (POD) 1-3 or control group (CG) at a 1:1 ratio. The primary outcomes were pain score and consumption of analgesics. The secondary were the time of first postoperative flatus and defecation, frequency of postoperative nausea, vomiting, distention, diarrhea, comfort of semi-fluid diet, Clavien-Dindo grade (C-D grade) and length of postoperative day. We performed hematological analysis to explore the possible mechanisms. RESULTS: Overall, 81 patients were enrolled included in the analysis. Compared with CG, pain scores in TG were lower on POD 1-5 (average: 2.55±0.21 vs 3.10±0.42, P<0.001), and the use rate of opioids was lower (43.9 vs 75.0, P=0.004); time of first postoperative flatus (55.63±16.74 vs 72.60±20.92, P<0.001) and defecation (72.20±16.24 vs 95.78±17.75, P<0.001) were shorter; the frequency of nausea were fewer (1.88±1.09 vs 2.58±0.77, P=0.029) and patients were more comfortable with semi-fluid diet (7.63±0.63 vs 6.93±0.69, P<0.001); among the hematologic results, ß-endorphin (ß-End), interleukin-2 (IL-2), motilin (MTL) on POD 3, POD 5 were lower, 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were higher. And no adverse event was reported. CONCLUSION: TEAS can relieve postoperative pain and promote the recovery of gastrointestinal function. Consequently, it can be an adjunctive therapy to enhance postoperative recovery for patients after gastrectomy.

Short- and long-term outcomes associated with enhanced recovery after surgery protocol vs conventional management in patients undergoing laparoscopic gastrectomy.

BACKGROUND: At present, the enhanced recovery after surgery (ERAS) protocol is widely implemented in the field of gastric surgery. However, the effect of the ERAS protocol on the long-term prognosis of gastric cancer has not been reported. AIM: To compare the effects of ERAS and conventional protocols on short-term outcomes and long-term prognosis after laparoscopic gastrectomy. METHODS: We retrospectively analyzed the data of 1026 consecutive patients who underwent laparoscopic gastrectomy between 2012 and 2015. The patients were divided into either an ERAS group or a conventional group. The groups were matched in a 1:1 ratio using propensity scores based on covariates that affect cancer survival. The primary outcomes were the 5-year overall and cancer-specific survival rates. The secondary outcomes were the postoperative short-term outcomes and inflammatory indexes. RESULTS: The patient demographics and baseline characteristics were similar between the two groups after matching. Compared to the conventional group, the ERAS group had a significantly shorter postoperative hospital day (7.09 d vs 8.67 d, P < 0.001), shorter time to first flatus, liquid intake, and ambulation (2.50 d vs 3.40 d, P < 0.001; 1.02 d vs 3.64 d, P < 0.001; 1.47 d vs 2.99 d, P < 0.001, respectively), and lower medical costs ($7621.75 vs $7814.16, P = 0.009). There was a significantly higher rate of postoperative complications among patients in the conventional group than among those in the ERAS group (18.1 vs 12.3, P = 0.030). Regarding inflammatory indexes, the C-reactive protein and procalcitonin levels on postoperative day 3/4 were significantly different between the two groups (P < 0.001 and P = 0.025, respectively). The ERAS protocol was associated with significantly improved 5-year overall survival and cancer-specific survival rates compared with conventional protocol (P = 0.013 and 0.032, respectively). When stratified by tumour stage, only the survival of patients with stage III disease was significantly different between the two groups (P = 0.044). CONCLUSION: Adherence to the ERAS protocol improves both the short-term outcomes and the 5-year overall survival and cancer-specific survival of patients after laparoscopic gastrectomy.

[Microsurgical anatomy and quantitative assessment of suboccipital median transcerebellomedullary fissure keyhole approach].

OBJECTIVE: To assess the suboccipital median transcerebellomedullary fissure keyhole approach in a cadaver model by using a neuronavigation system and explore its feasibility and operative indications. METHODS: Six 10% formaldehyde-fixed adult cadaveric head and neck specimens injected with colored latex were chosen for the study. First the suboccipital median transcerebellomedullary fissure keyhole approach was performed and the anatomical structures were observed under operative microscope. The exposed floor area of the fourth ventricle and the vertical and transverse angles at the point where the line between the lateral apertures crossing the median sulcus, vertical angle at the apertures of midbrain aqueduct and the obex were measured with the aid of a frameless stereotactic navigation device. Parameters were compared with those when C1 posterior arch was removed, and also with those under conventional approach with or without C1 arch. RESULTS: By means of adjusting specimen positions and the angle of operative microscope, as tela choroidea and inferior medullary velum were dissected gradually, the structures of floor, lateral recesses and lateral apertures of the fourth ventrical, vermian and aperture of midbrain aqueduct were exposed. There were no significant difference in the exposed floor area of the fourth ventricle between the keyhole approach and conventional approach (P = 0.06), and the C1 arch removal can't increase the exposed area (P = 0.84). The conventional approach have wider angles than the keyhole approach (P < 0.01), and the C1 arch removal increased the vertical angle (P < 0.05), but not the horizontal angle (P > 0.05). CONCLUSION: The suboccipital median transcerebellomedullary fissure keyhole approach can expose similar anatomic architectures as that of the conventional approach. Thus it can be used to remove the tumors located in the fourth ventricle, dorsum of pons and medullary oblongata and cerebellar vermis.

Poor-Grade Aneurysmal Subarachnoid Hemorrhage: Risk Factors Affecting Clinical Outcomes in Intracranial Aneurysm Patients in a Multi-Center Study.

Objective: Patients with poor-grade aneurysm subarachnoid hemorrhage (SAH) have commonly been considered to have a poor prognosis. The objective of this study was to investigate the independent risk factors affecting clinical outcomes in intracranial aneurysm patients with poor-grade aneurysm subarachnoid hemorrhage (aSAH) underwent different intervention therapies. Methods: A multicenter observational registry of 324 poor-grade aSAH patients treated at tertiary referral centers from October 2010 to March 2012 were enrolled in this study. The clinical data including patient characteristics on admission and during treatment course, treatment modality, aneurysm size and location, radiologic features, signs of cerebral herniation (dilated pupils), and functional neurologic outcome were collected. Clinical outcomes were assessed via a modified Rankin Scale at 12 months. Multivariate logistic regression models were used to develop prognostic models. The area under the receiver operator characteristic curves (AUC) and Hosmer-Lemeshow tests were used to assess discrimination and calibration. WAP score was developed to predict risk of poor outcome. Results: Older age, female gender, ventilated breathing status, non-reactive pupil response, pupil dilation, lower GCS score, a WFNS grade of V, intraventricular hemorrhage, a higher Fisher grade, a higher modified Fisher grade, and conservative treatment were calculated to be associated with a relatively poor outcome. Multivariate analyses revealed that older age, lower Glasgow coma scale score (GCS), the absence of pupillary reactivity, higher modified Fisher grade, and conservative treatment were independent predictors of poor outcome, showed good discrimination and calibration. Patients with WFNS grade V, older age and non-reactive pupillary reactivity were predicted to have a poor outcome by WAP risk score. Conclusions: A simple WAP risk score had good discrimination and calibration in the prediction of outcome. The risk score can be easily measured and may complement treatment decision-making.

Comparison of Aggressive Surgical Treatment and Palliative Treatment in Elderly Patients with Poor-Grade Intracranial Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To compare the current treatment approach in elderly patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) and identify the independent predictors of the outcome after aggressive surgical treatment. METHOD: This prospective, multicenter cohort study included 104 poor-grade aneurysmal SAH elderly patients, 60 years or older, treated in our institution from October 2010 to March 2013. Patients were grouped according to three treatment arms. Neurological outcome was assessed using the Glasgow Outcome Scale (GOS) at baseline and at a 12-month follow-up. Univariate and multivariate analysis were performed using the following factors: sex, age, smoking history, breathing ability, alcohol consumption, cerebral hernia, aneurysm location, aneurysm diameter, WFNS grade, CT Fisher grade, treatment approach, and the timing of the aneurysm surgery. RESULTS: At the 12-month follow-up, patients in the coiling group and clipping group had better prognosis than patients in the palliative treatment group. Univariate analysis confirmed that the treatment approach, WFNS grade, CT Fisher grade, and age are critical factors for neurological outcomes in poor-grade SAH. Multivariate analysis indicated that WFNS grade V, CT Fisher grades 3-5, and palliative treatment were independent predictors of poor prognoses. CONCLUSION: Aggressive surgical treatment improves the prognoses in poor-grade aneurysm elderly patients with SAH. Elderly Patients of WFNS grade IV and CT Fisher grades 1-2 are more likely to have a better outcome.

Five-year experience of 101 adult patients with moyamoya disease at a single institution in Eastern China.

This retrospective study included 101 adult moyamoya disease (MMD) patients of whom 58 were females and 43 were males in Wenzhou, China. Clinical and diagnostic features, surgical treatment, follow-up information and outcomes constitute this review. The modified Rankin Scale (mRS) was used to determine the neurological functional outcome. The Kaplan-Meier method was used to estimate recurrent stroke and mortality risk based on drug treatment alone or in combination with revascularization. The mean age at symptom onset was 43.3 (range, 18-64)years. The initial symptom was either hemorrhage, ischemia or transient ischemic attack (TIA) in 90, 6 and 5 patients, respectively. The median follow-up time in 84 patients was 26.5 (range, 6-62)months. Ten patients were treated with revascularization. In the remaining drug-treated group, the 5-year risk of recurrent stroke and death was 8% following onset of initial symptoms, while it was 25% in the revascularization group. However, the difference between these two groups was not significant (p>0.05). There was also no difference in mRS between these two groups upon patient discharge, but in the revascularization group was lower than that in the drug-treated group at their last follow-up (p<0.05). Adult MMD patients were most ikely to present with hemorrhage and had a better neurological functional outcome after revascularization than from medical therapy. However, revascularization did not decrease the recurrent stroke incidence or mortality risk. These results are different from those reported by other Chinese and foreign institutions.

Alterations of caveolin-1 expression in a mouse model of delayed cerebral vasospasm following subarachnoid hemorrhage.

The aim of the present study was to evaluate the expression levels of caveolin-1 in the basilar artery following delayed cerebral vasospasm (DCVS) in a rat model of subarachnoid hemorrhage (SAH), in order to investigate the association between caveolin-1 and DCVS, and its potential as a treatment for DCVS of SAH. A total of 150 Sprague Dawley rats were randomly allocated into blank, saline and SAH groups. The SAH and saline groups were subdivided into days 3, 5, 7 and 14 following the establishment of the model. The murine model of SAH was established by double injection of autologous arterial blood into the cisterna magana and DCVS was detected using Bederson neurological severity scores. Hematoxylin and eosin (HE) staining was used to observe the inner perimeter of the basilar artery pipe and variations in the thickness of the basilar artery wall. Alterations in the levels of caveolin-1 protein in the basilar artery were measured using immunofluorescence and western blot analysis; whereas alterations in the mRNA expression levels of caveolin-1 were detected by reverse transcription-quantitative polymerase chain reaction. In the present study, 15 mice succumbed to SAH-induced DCVS in the day 3 (n=3), 5 (n=5) and 7 (n=2) groups. No mortality was observed in the blank control and saline groups during the process of observation in the SAH group, All mice in the SAH groups exhibited Bederson neurological severity scores ≥1; whereas no neurological impairment was detected in the blank and normal saline groups, demonstrating the success of the model. HE staining was used to assess vasospasm and the results demonstrated that the inner perimeter of the basal artery pipe decreased at day 3 in the SAH group; whereas values peaked in the day 7 group. The thickness of the basal artery wall significantly increased (P<0.05), as compared with the blank and saline groups, in which no significant alterations in the wall thickness and the inner perimeter of the basal artery pipe were detected. As detected by immunofluorescence and western blot analysis, the expression levels of caveolin-1 protein significantly decreased in the day 7 of SAH group, as compared with the blank and saline groups (P<0.01), in which no significant alterations were detected. Caveolin-1 mRNA expression levels significantly increased at the day 7 in the SAH group, as compared with the blank and the saline groups (P<0.01), as detected by RT-qPCR. Furthermore, significant differences were detected at day 14 in the SAH group, as compared with the blank and the saline groups (P>0.05), in which no significant alterations were detected. Therefore, the results of the present study demonstrated that caveolin-1 protein was downregulated in the basilar artery of a rat modeling SAH, which may be associated with DCVS. This suggested that caveolin-1 may be a potential target for the treatment of DCVS.

Surgical Treatment of Cervical Spondylotic Myelopathy Associated Hypertension--A Retrospective Study of 309 Patients.

Hypertension is the most prevalent cardiovascular disease, and various risk factors are known to be involved in it. Cervical spondylotic myelopathy (CSM) is the most common non-traumatic cause of myelopathy, which displays neurological symptoms and may induce systemic symptoms. To date, it is still unknown whether CSM is associated with hypertension, and if so, whether the decompression operations can attenuate CSM associated hypertension. Here, a total of 309 patients with CSM who received anterior or posterior decompression surgery were enrolled as subjects. Blood pressure measurements were performed before and within one week after the surgery. Among the 309 subjects, 144 (46.6%) of them exhibited hypertension before surgery, a significantly higher ratio than that of the whole population. One week after surgery, blood pressure of 106 (73.6%) patients turned back to normal. Blood pressure of another 37(25.7%) patients decreased with different degrees, although still higher than normal. Moreover, it appears that both approaches were effective in improving blood pressure, while the posterior approach was more effective in decreasing systolic blood pressure. We speculate this type of hypertension might result from hyperactivity of sympathetic nervous system as the heart rate of these patients decreased after surgery as well. Collectively, compression of spinal cord in CSM patients might be associated with hypertension, and decompression surgery largely attenuated this type of hypertension. These findings prove CSM to be a potential associated factor of high blood pressure and may shed light on therapies of hypertension in clinics.

[Expression of cyclin D1 in brain gliomas and its significance].

BACKGROUND & OBJECTIVE: Overexpression of cyclin D1 was shown in many tumors. The excessive expression of cyclin D1 is an important cause of many tumors. But there are still some controversies of whether the overexpression of cyclin D1 exists in brain gliomas. This study was to determine the expression level of cyclin D1 in glioma tissues of human brain, and to analyze the relationship of cyclin D1 with the malignancy and prognosis of gliomas. METHODS: The expression levels of cyclin D1 in 84 specimens were determined by SP immunohistochemical assay. The correlation of expression intensity of cyclin D1, positive cell ratio of glioma tissues with the tumors malignancy, and the prognosis of the patients was analyzed. RESULTS: (1) The average percentages of cyclin D1 positive cells were (9.82+/-9.75)% and (27.45+/-21.03)% in the low grade gliomas and the high grade gliomas, respectively. There was significant difference between two groups (P< 0.01). (2) The cyclin D1 positive ratios were 31.25% (10/32) and 61.53% (32/52) in the low grade gliomas and the high grade gliomas, respectively. There was significant difference between two groups (P< 0.01). (3) The cyclin D1 positive ratios were 76.19% (16/21) and 24.00% (6/25) in recurrence group and non-recurrence group,respectively. There was significant difference between two groups (P< 0.01). (4) The cyclin D1 positive ratios were 66.67% (14/21) and 32.00%(8/25) in dead group and survival group, respectively. There was significant difference between two groups (P< 0.05). In dead group, the cyclin D1 positive ratios were 86.66%(13/15) and 16.66%(1/6) in the high grade gliomas and the low grade gliomas, respectively. There was significant difference between two groups (P< 0.05). CONCLUSIONS: (1) The expression of cyclin D1 increased with the increased grade of glioma. (2) The higher cyclin D1 expressed, the worse prognosis the patients had. (3) The expression of cyclin D1 can act as a biological marker in evaluating malignancy of gliomas and prognosis of patients.

[Expression of nm23 and proliferating cell nuclear antigen (PCNA) in human brain gliomas and their significance].

BACKGROUND & OBJECTIVE: Brain gliomas seldom undergo extracranial metastasis. Local recurrence is the main reason of tumor patient's death. Therefore, it is important to detect tumor biological features through determination of gene expression. This study was designed to investigate the expression of nm23 (non-metastasis gene, nm23)and PCNA (proliferating cell nuclear antigen) and evaluate the malignancy, recurrence, and prognosis of the tumor. METHODS: In 50 specimens of different malignant gliomas,the expression of nm23 and PCNA were examined using SP immunohistochemical staining. RESULTS: (1)The label indexes of nm23 and PCNA in low-grade gliomas were 3.40+/-0.27 and 3.60+/-0.05, respectively; while the label indexes of nm23 and PCNA in high-grade gliomas were 1.72+/-0.18 and 6.20+/-0.23, respectively.There was significant difference between the two groups(P< 0.05). (2)The positive rates of nm23 and PCNA were 56% (14 cases) and 64% (16 cases) in 25 cases of low-grade gliomas, while the positive rates of nm23 and PCNA were 12% (3 cases) and 88% (22 cases) in 25 cases of high-grade gliomas. There was significant difference between the two groups (P< 0.05). (3)The positive rates of nm23 and PCNA were 0% (0 cases) and 100% (9 cases) in 9 cases of recurrent gliomas, while the positive rates of nm23 and PCNA were 50%(34 cases) and 50%(4 cases) in 8 cases of non-recurrent gliomas. There was significant difference between the two groups (P< 0.05). (4)The label indexes of nm23 and PCNA in gliomas were inversely correlated (r=-0.5335,P< 0.001). CONCLUSION: (1)The expression of nm23 is inversely correlated with the malignancy of gliomas,i.e.the lower expression indicates the higher malignancy. (2)The expression of PCNA is associated with the increased malignancy. (3)Both nm23 and PCNA may be useful biological markers to evaluate the malignancy and prognosis of patients with gliomas.