A migraine is a common essential headache in clinical practice. Studies in recent years have found that cortical spreading depression (CSD) may be one of the important mechanisms for the cause of migraine. This article reviews the relationship between SCD and neurobiological mechanism of migraine,particular expounding the significance in the gene mutations of familial hemiplegic migraine, CSD in migraine pathophysiological mechanisms and their prophylactic treatment.

Objective To explore the effect of glucose regulated protein (GRP)78 on the neuronal apoptosis after cerebral ischemia reperfusion injury in rats. Methods Middle cerebral artery ischemia reperfusion rat's models were used with the modified filament method. The expression of GRP78 in the ischemic penumbra tissue was detected by RT-PCR, Western blot and immunohistochemistry at different time points. Primary cultured rat's neurons were exposed to hypoxia and subsequently reoxygenation. Western blot was used to investigate the expression of GRP78. The changes of the neuronal apoptosis after overexpression of GRP78 induced by 2-deoxyglucose were detected. Results The expression of GRP78 in the ischemic penumbra tissue in model group was significantly increased (mRNA : 0.7367±0.0651, F= 477.160, P < 0.01 ; Protein : 0. 8129±0. 0748, F=39.857, P < 0.01). The neuronal survival status was increased after overpression of GRP78 (increased by 39.22% ± 0. 44%, t=46.374, P < 0.01) while the neuronal apoptosis was decreased (decreased by 16.60±1.02, t=7.530, P <0.01). Conclusion Focal cerebral ischemia reperfusion can induce endoplasmic reticulum stress which plays a role in the neuronal apoptosis. The increased expression of GRP78 may protect the ischemic tissue from neuronal apoptosis.

Objective To explore the feasibility of radical cholecystectomy for early gallbladder car cinoma found during or after laparoscopic cholecystectomy.Methods A retrospective study was conducted on patients who received laparoscopic cholecystectomy between January 2007 to August 2013 and were diagnosed to have gallbladder cancer during or after the operation.There were 34 patients.In 29 patients intraoperative frozen section diagnosed gallbladder carcinoma.In 5 patients postoperative histopathological study diagnosed stage Ⅰ or Ⅱ gallbladder carcinoma.Results Surgery was conducted successfully on these 34 patients.In 20 patients with stage Ⅰ,Ⅱ and Ⅲ,the tumor had invaded the serosa,or into the liver with a depth of less than 2 cm,laparoscopic cholecystectomy alone or radical/extended radical cholecystectomy were carried out.In 9 patients,the laparoscopic surgery was converted to open surgery and these patients underwent cholecystectomy with resection of the adjacent liver segments/sections.In 5 patients who were diagnosed to have gallbladder carcinoma after laparoscopic cholecystectomy,they were re-operated with laparoscopic radical cholecystectomy.Conclusions Stage Ⅰ,Ⅱ and Ⅲ gallbladder carcinoma with tumor invasion into serosa,or patients with tumor invasion into the liver with a depth of less than 2 cm should undergo radical or extended radical cholecystectomy.Laparoscopic assisted radical or extended radical cholecystectomy could achieve the same operation as with open surgery but with better short-term results.There were less pain,smaller incisions,better scars and shorter hospitalization stay.

Objective To observe the morphological changes of rats' pancreas and nitric oxide (NO) and endothelin(ET) in the blood serum in rats after exposure to different pulses of high power pulse microwave (HPPMW).Methods SD-rats were irradiated with 104,105 and 4 × 105 pulses of HPPMW,respectively.After gloss observation,the histopathological changes of pancreas were observed through biological microscope and electroscope.The changes of amylase,nitric oxide and endothelin in blood serum were detected by biochemical and radio-immunological methods. Results Compared with the blank control,no apparent abnormality could be observed in the pancreas of all groups.The dilatation of capillary could be observed in each experimental group by microscope.The ultrastructure changes of pancreas were most serious in 4 × 105 pulse group,especially at 24 and 48 h after irradiation.Compared with the control group,the levels of serum amylase were decreased (F =12.58,11.73,P ＜ 0.05),while ET were increased (F =4.50,4.49,P ＜0.05) at 24 and 48 h after irradiation.The levels of NO in serum were increased ( F =17.51,41.72,19.98,32.64,P ＜ 0.05 ) at each time-point.The level of NO went up with the increase of pulses.Conclusions HPPMW has damage effects on the pancreas in rats.The pulses with the pancreas can lead to severity of the damage. The mechanism of HPPMW may be involved in the enhancement of ET and NO in serum.

Objective Preliminarily discussing the effects of VEGF and SOX2 on metastasis and progno-sis of squamous cell lung carcinoma(SCLC).Methods Using immunohistochemical method to detect 47 cases of pulmonary squamous cell carcinoma and 30 cases of para-carcinoma tissue in the expression of VEGF and SOX2, using statistical methods to analyze the expression of VEGF and SOX2 and the relationship between clinical parame-ters and its relationship with prognosis. Results The positive expression rates of VEGF,SOX2 in SCLC tissues were higher than adjacent normal tissues.There was a significant correlation between VEGF and SOX2 expression. VEGF expression was associated with lymph node metastases and TNM stage.SOX2 expression was associated with tumor differentiation and lymph node status.Survival analysis indicated that VEGF(+)/SOX2(+)patients had the worst prognosis.Furthermore,multivariate analysis suggested that tumor diameter and lymph node metastases were independent prognostic factors for SCLC. Conclusion The expression of VEGF was positively correlated with lymph node metastasis and clinical stage,the expression of SOX2 was positively correlated with tumor differentia-tion degree and lymph node metastasis,and high expression of VEGF and SOX2 may indicate lung squamous can-cer patients with poor prognosis.

Objective:To study the risk factors for ipsilateral severe hearing impairment in patients with hemifacial spasm (HFS) after microvascular decompression (MVD).Methods:MVD was performed in 3700 patients with HFS, admitted to our hospital from October 2007 to August 2020; according to the existence of ipsilateral severe hearing impairment, these patients were divided into severe hearing impairment group and non-severe hearing impairment group. The clinical data of these patients were compared. Multivariate linear regression analysis was used to determine the independent influencing factors for ipsilateral severe hearing impairment.Results:Forty-five patients (1.2%) had ipsilateral severe hearing impairment after MVD; no one got recovery of hearing impairment during the follow-up period (0.6-11.8 years, 6.3 years in average). As compared with those in the non-severe hearing impairment group, patients in the severe hearing impairment group had significantly older age, significantly higher percentages of male patients, and patients with left HFS, hypertension, and diabetes mellitus, statistically higher percentage of patients having small posterior fossa volume, arachnoid thickening and adhesion, and vertebral artery compression, significantly lower percentage of patients with anterior inferior cerebellar artery compression, significantly higher percentage of patients with arteriosclerosis of offending arteries and difficult decompression ( P<0.05). Multivariate linear regression analysis revealed that hypertension, vertebral artery compression, arteriosclerosis of offending artery and difficult decompression were independent risk factors for severe hearing impairment in patients with HFS after MVD. Conclusion:It's difficult to get recovery for severe hearing impairment in patients with HFS after MVD; this complication is much common in patients with hypertension, vertebral artery compression, arteriosclerosis of offending artery or difficult decompression.

Background/Aims: Lipopolysaccharide (LPS) is the key factor inducing mucosal and systemic inflammation in various intestinal and parenteral diseases, which could initially disrupt the epithelial barrier function. EphrinA1/ephA2 is speculated to increase the epithelial permeability for its “repulsive interaction” between adjacent cells. This study aim to investigate the role of ephrinA1/ephA2 in LPS-induced epithelial hyperpermeability. Methods: In vivo model challenged with oral LPS in C57BL/6 mice and in vitro model exposed to LPS in Caco2 monolayer were established. The barrier function was assessed including expression of tight junction proteins (occludin and claudin-1), transepithelial electrical resistance, and permeability to macromolecules (fluorescein isothiocyanate-labeled fluorescent dextran 4 kDa [FD4]). Moreover, the expression and phosphorylation of ephrinA1/ephA2 were quantified, and its roles in the process of epithelial barrier disruption were confirmed via stimulating ephA2 with ephrinA1-Fc chimera (ephrinA1-Fc) and inactivating ephA2 with ephA2-Fc chimera (ephA2-Fc), or ephA2 monoclonal antibody (ephA2-mab), as well as inhibiting extracellular signal-regulated kinase 1/2 (ERK1/2) with PD98059. Results: LPS induced significant barrier dysfunction with dismissed occludin and claudin-1 expression, reduced transepithelial electrical resistance and increased FD4 permeability, accompanied by upregulated ephrinA1/ephA2 pathway and phosphorylation of ephA2 receptor. Furthermore, ephA2-Fc, and ephA2-mab ameliorated LPS-induced epithelial hyperpermeability, which was also inhibited by PD98059. Additionally, ephrinA1-Fc led to apparent epithelial leakage in Caco2 monolayer by promoting the phosphorylation of ERK1/2, which could be obviously blocked by ephA2-mab and PD98059. Conclusion EphrinA1/ephA2 promotes epithelial hyperpermeability with an ERK1/2-dependent pathway, which involves in LPS-induced intestinal barrier dysfunction.

Objective:To evaluate the effect of sleep deprivation on cognitive function in septic rats and its relationship with neuronal glycolysis isoenzyme phosphofructokinase-2/fructose-2,?6-diphosphatase 3 (PFKFB3).Methods:Fifty-six healthy male Sprague-Dawley (SD) rats were randomly divided into 4 groups ( n = 14): control group (Con group), sepsis group (LPS group), sepsis+sleep deprivation group (LPS+SD group), sepsis+sleep deprivation+glycolysis inhibitor 3-PO treatment group (LPS+SD+3-PO group). The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg. Rats in LPS+SD group were treated with sleep deprivation using a sleep deprivation instrument 24 hours after LPS injection. The LPS+SD+3-PO group was intraperitoneally injected with LPS for 24 hours, and then injected with 3-PO 50 mg/kg, followed by sleep deprivation. Novel object recognition experiments were performed 72 hours after LPS injection. Subsequently, blood and brain tissue samples were collected. The contents of lactate (Lac), reactive oxygen species (ROS) and serum tumor necrosis factor-α(TNF-α), neuron-specific enolase (NSE), pyruvate in brain tissue were detected by enzyme-linked immunosorbent assay (ELISA). Then, the lactate/pyruvate ratio was calculated. Na +-K +-ATPase activity in brain tissue was detected by colorimetry. Morphological changes in hippocampus were detected by hematoxylin-eosin (HE) staining. And the protein expression levels of PFKFB3, ZO-1 and cleaved caspase-3 were measured by Western blotting. Results:Compared with Con group, the novel object recognition index of LPS group was decreased, the levels of NSE, TNF-α, lactate/pyruvate ratio in serum and the levels of Lac, ROS and dry-wet weight ratio in brain tissue were significantly increased, Na +-K +-ATPase activity in brain tissue was decreased, the protein expressions of PFKFB3, caspase-3 were up-regulated, ZO-1 expression was down-regulated, and the neurons in hippocampus were slightly degenerated. Compared with LPS group, the novel object recognition index of LPS+SD group was further decreased [(39.4±5.3)% vs. (54.5±7.6)%)], serum NSE, TNF-α, lactate/pyruvate ratio and brain tissue Lac, ROS, dry-wet weight ratio were further increased [NSE (μg/L): 3.21±0.42 vs. 2.55±0.36, TNF-α (ng/L): 139.4±19.7 vs. 92.2±13.5, lactate/pyruvate ratio: 29.7±5.5 vs. 19.2±4.2, Lac (μmol/g): 19.51±2.33 vs. 11.34±1.52, ROS (kU/g): 117.4±18.7 vs. 78.2±11.8, dry-wet weight ratio: (81.3±9.2)% vs. (64.3±6.6)%], and Na +-K +-ATPase activity was further decreased (mmol·L -1·h -1: 1.88±0.34 vs. 2.91±0.39), the protein expressions of PFKFB3, caspase-3 were further up-regulated and ZO-1 expression was further down-regulated (PFKFB3/β-actin: 0.80±0.11 vs. 0.45±0.07, caspase-3/β-actin: 0.71±0.09 vs. 0.37±0.05, ZO-1/β-actin: 0.31±0.05 vs. 0.61±0.08). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly aggravated. Compared with LPS+SD group, the novel object recognition index of LPS+SD+3-PO group was increased [(50.8±5.9)% vs. (39.4±5.3)%], NSE, TNF-α, lactate/pyruvate ratio of serum and Lac, ROS, dry-wet weight ratio of brain tissue were significantly decreased [NSE (μg/L): 2.60±0.33 vs. 3.21±0.42, TNF-α (ng/L): 103.7±18.3 vs. 139.4±19.7, lactate/pyruvate ratio: 17.4±5.1 vs. 29.7±5.5, Lac (μmol/g): 13.68±2.02 vs. 19.51±2.33, ROS (kU/g): 86.9±14.5 vs. 117.4±18.7, dry-wet weight ratio: (67.7±6.9)% vs. (81.3±9.2)%], and Na +-K +-ATPase activity was increased (mmol·L -1·h -1: 2.82±0.44 vs. 1.88±0.34). The protein expressions of PFKFB3, caspase-3 were down-regulated and ZO-1 expression was up-regulated (PFKFB3/β-actin: 0.50±0.06 vs. 0.80±0.11, caspase-3/β-actin: 0.43±0.06 vs. 0.71±0.09, ZO-1/β-actin: 0.52±0.06 vs. 0.31±0.05). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly improved. Conclusions:Sleep deprivation could aggravate neuroinflammation, neuronal degeneration and apoptosis in septic rats, resulting in destruction of blood-brain barrier and cognitive impairment. 3-PO treatment significantly alleviate the injury and degeneration of hippocampal neurons in septic rats, inhibit neuroinflammation and apoptosis, and improve cognitive dysfunction, which may be related to the inhibition of glycolytic isoenzyme PFKFB3.

Objective:To compare the clinical efficacy of laparoscopic inguinal lymph node dissection(L-ILND)and open inguinal lymph node dissection(O-lLND)in the treatment of penile cancer after radical penile cancer surgery. Methods:The clinical outcomes of 63 patients who were diagnosed with penile cancer(TNM staging:T1_3,N0-3,M0)and received L-ILND(41 cases)or O-ILND(22 cases)after radical penile cancer surgery in Department of Urology,Hubei Cancer Hospital,Tongji Medical College,Huazhong University of Science and Technology from 2008 to 2020 were retrospectively studied.The primary endpoint of this study was overall survival,and the secondary endpoints were 5-year overall survival and 5-year cancer-specific survival.The different clinical characteristics were compared between the L-ILND group and O-ILND group.Univariate and multivariate logistic regression analysis was used to study the risk facotrs for postoperative wound complications.Kaplan-Meier method was used for prognosis analysis.COX regression analysis was used to investigate the factors for overall survival prediction. Results:Among the 63 penile cancer patients studied,41 patients received L-ILND and the remaining 22 received O-ILND.There were no statistically significant differences in the baseline characteristics between the two groups of patients.The median overall survival(78 months vs 72 months,P=0.844),5-year overall survival rate(74.5％vs 78.3％,P=0.144),5-year cancer-specific survival rate(77.2％vs 71.4％,P=0.228)showed no obvious difference between L-ILND and O-ILND group.The rate of postoperative wound complications in the O-ILND group was significantly higher than that in the L-ILND group(74％vs 15％,P=0.01 2).The result of multivariate COX regression analysis showed that tumor grade[hazard ratio(H-R)=2.774,P=0.021]and lymph node pathological stage(HR=1.482,P=0.024)were significantly correlated with patients'prognosis. Conclusion:The clinical efficacy of L-ILND and O-ILND is similar,but L-ILND has a higher safety profile and lower incidence of postoperative wound complications.Therefore,L-ILND is a more ideal surgical approach for inguinal lymph node dissection after radical penile cancer surgery.

Objective:To explore the relationship between the expressions of P21,P27 and proliferating cell nuclear antigen(PCNA)in glomerular mesangial tissue and poor renal prognosis in patients with immunoglobulin A(IgA)nephropathy.Methods:A total of 145 patients with IgA nephropathy treated in Xiaogan Central Hospital from April 2017 to August 2019 were selected as the research object.The expressions of P21,P27 and PCNA in glomerular mesangial tissue were detected by immunohistochemistry.All patients were followed up for 24 months,and the prognosis were counted.The expressions of P21,P27 and PCNA in glomerular mesangial tissue of patients with different prognosis were compared and the influencing factors of poor prognosis in patients with IgA nephropathy were analyzed by Logistic regression analysis.Results:The expression rates of P21,P27 and PCNA positive cells in glomerular mesangial tissue of patients with IgA nephropathy were(38.69±6.83)%,(55.94±8.08)%,(33.47±5.72)%,respectively.The incidence rete of poor prognosis in patients with IgA nephropathy was 17.24%,and the expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of patients with poor prognosis were higher than those in good prognosis group(P<0.05),while the expression rate of P27 positive cells was lower than that in good prognosis group(P<0.05).Logistic multiple regression analysis showed that elevated diastolic blood pressure,increased 24 h proteinuria,mesangial cell proliferation,segmental glomerulosclerosis,renal tubular atrophy/interstitial fibrosis,crescentic body,increased expression rates of P21 and PCNA positive cells and decreased expression rate of P27 positive cells were all risk factors affecting the poor prognosis of patients with IgA nephropathy(P<0.05).Conclusion:There are positive expressions of P21,P27 and PCNA in glomerular mesangial tissue of IgA nephropathy.The expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of of patients with poor prognosis of IgA nephropathy are higher than those with good prognosis,while the expression rate of P27 protein positive cells is lower than those with good prognosis,which are risk factors for poor prognosis of patients with IgA nephropathy.