Short-lasting unilateral neuralgiform headache attacks （SUNHA） are a rare type of disabling primary headache within the category of trigeminal autonomic cephalalgias （TACs）， and it has two subtypes of SUNCT （with conjunctival injection and tearing） and SUNA （with other autonomic features）. SUNHA is characterized by severe unilateral （often V1） stabbing/shock-like pain （lasting for 1-600 s）， high frequency （2‒600 attacks a day）， and prominent ipsilateral cranial autonomic symptoms （such as conjunctival injection，tearing， and nasal obstruction）. Trigger factors are observed in 86% of patients. The diagnosis of SUNHA should meet the ICHD-3 criteria （≥20 attacks）， and brain MRI （especially for the pituitary gland/posterior cranial fossa） should be performed to exclude secondary causes （such as neurovascular conflict and pituitary tumor）. Lamotrigine is used as first-line prophylaxis， while lidocaine aids acute relief in the transitional phase； occipital nerve stimulation， deep brain stimulation， or microvascular decompression can be used for refractory cases. It is of great importance to enhance awareness， achieve precise differentiation（from trigeminal neuralgia or other types of TACs）， and provide individualized treatment.

Objective:To discuss the damage effect of vesicular stomatitis virus(VSV)on the vascular endothelial(VE)barrier,and to clarify its mechanism.Methods:The canine kidney cells were used to amplify VSV.The half tissue culture infective dose(TCID50)of VSV was determined using mouse brain endothelial tumor bEnd.3 cells,and subsequent experiment was conducted using 300 times the TCID50.The bEnd.3 cells were divided into infection 0 h group,infection 4 h group,infection 8 h group,and infection 12 h group for VE barrier damage experiments due to VSV infection.The bEnd.3 cells were also divided into control group,infection group,and correction group for experiments to inhibit the VSV replication and restore the VE barrier.The bEnd.3 cells were inoculated into Transwell chambers to construct an in vitro VE barrier model.Cell voltage resistance meter was used to detect the transepithelial resistance(TER)in various groups after the bEnd.3 cells were infected with VSV at different time points;fluorescein isothiocyanate-dextran leakage assay was used to detect the permeability coefficients of the cells in various groups;immunofluorescence staining was used to observe the localization changes of VE-cadherin,β-catenin,and phosphorylated β-catenin(p-β-catenin)in cytoskeleton and adherens junctions(AJs)of the bEnd.3 cells after VSV infection;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Wnt and β-catenin mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Wnt,β-catenin,and p-β-catenin proteins in the cells in various groups.Results:The TCID50 of VSV was 10-4.5·100 μL-1.TheTranswell chamber experiment results showed that compared with infection 0 h group,the TERs in the cells in the other groups were significantly decreased(P＜0.05),and the permeability coefficients were significantly increased(P＜0.05).The immunofluorescence staining results showed that compared with control group,the cytoskeleton of the bEnd.3 cells in infection group was disordered,the cell gaps was increased,the linear index of AJs was significantly decreased(P＜0.05),and β-catenin and p-β-catenin translocated from the cell membrane to the perinuclear area.The RT-qPCR results showed that compared with infection 0 h group,the expression levels of Wnt mRNA in the cells in the other groups were significantly decreased(P＜0.05),while the expression levels of β-catenin mRNA showed no statistically significant difference(P＞0.05).The Western blotting results showed that compared with infection 0 h group,the expression levels of Wnt protein in the cells in the other groups were significantly decreased(P＜0.05),the expression levels of β-catenin showed no statistically significant differences(P＞0.05),and the expression levels of p-β-catenin were significantly increased(P＜0.05).After inhibiting the VSV replication and correcting the low density lipoprotein receptor(LDLR)abnormalities,the Transwell chamber experiment results showed that compared with infection group,the TER in the cells in correction group was significantly increased(P＜0.05),and the permeability coefficient was significantly decreased(P＜0.05).The immunofluorescence staining results showed that compared with infection group,the gaps in the cells in correction group were reduced,and the perinuclear aggregation of β-catenin and p-β-catenin in the cells was restrained.The RT-qPCR results showed that compared with infection group,the expression level of Wnt mRNA in the cells in correction group was significantly increased(P＜0.05).The Western blotting results showed that compared with infection group,the expression level of Wnt protein in the cells in correction group was significantly increased(P＜0.05),the expression level of β-catenin showed no statistically significant difference(P＞0.05),and the expression level of p-P-catenin was significantly decreased(P＜0.05).Conclusion:VSV infection can cause the LDLR inactivation,reduce the expression level of Wnt protein,increase the phosphorylation level of β-catenin and cause its internalization,disrupt the stability of AJs,and ultimately lead to VE barrier damage.

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

In the face of DNA damage caused by various factors, cells have a set of response and repair mechanisms. Cell cycle arrest plays an important role in the DNA damage repair, which provides enough time for repairing damaged DNA. Research on cell cycle regulation focuses on cyclin-dependent protein kinases (CDKs) and cell cycle checkpoints. In the process of DNA damage repair, phosphatidylinositol-3-kinase like kinases (PIKKs) which are recruited to the DNA damage sites can activate cell cycle checkpoint-related proteins to halt cell cycle. In the common DNA damage repair pathways, such as base excision repair (BER), nucleotide excision repair (NER) , mismatch repair (MMR) , and DNA double-strand break repair, the recruitment of repair-related proteins also plays a role in the cell cycle regulation. In this paper, the relationship between the main forms of DNA damage repair and cell cycle arrest and relevant research progress were reviewed.

Objective To study the stability of anticoagulant peptide Hirulog-S and its lyophilized product, and to provide data on the storage conditions and clinical applications.Methods RP-HPLC was used to determine the content and the related substances of Hirulog-S and its lyophilized powder with influence factor test, accelerated test and long-term storage test.Results Light, temperature and humidity had no significant effect on the stability of Hirulog-S and its lyophilized powder in the influence factor test.The content and related substances of Hirulog-S and its lyophilized powder did not significantly change in the accelerated test ( 40℃, RH75%) and 24-month long-term storage test at room temperature and 4℃.Conclusion Hirulog-S and its lyophilized product are very stable, even after being stored at room temperature for two years.

Objective To investigate the diagnosis and treatment of pancreatic carcinoma with acute and chronic pancreatitis as the initial symptoms.Methods The clinical data of 13 patients with pancreatic carcinoma who were admitted to the First Affiliated Hospital of Dalian Medical University and the Affiliated Central Hospital of Dalian Medical University from January 2003 to June 2014 were retrospectively analyzed.The first symptoms were acute and chronic pancreatitis.Laboratory and imaging examinations were carried out on all the patients,and the treatment plan was designed according to the location and stage of the tumor as well as the patient's wishes.Surgery,radiotherapy,chemotherapy and other symptomatic treatment were selected.All the patients were followed up by telephone interview till July 2014.Results The major symptoms included abdominal pain and lumbodorsal pain (7 patients).Of the 13 patients,1 patient refused to received laboratory examination,and the levels of CA19-9 of the other 12 patients were elevated (the levels of CA19-9 of 11 patients were above 1 × 105 U/L).The levels of carcinoembryonic antigen (CEA) of 5 patients were elevated.Thirteen patients received plain or enhanced abdominal computed tomography (CT),3 received magnetic resonance imaging (MRI) and 3 received sonography.The tumors located at the head of the pancreas wcrc observed in 9 patients,tumors located at the neck of the pancreas was observed in 2 patients,and tumors located at the tail of the pancreas were observed in 2 patients.The sizes of the tumors ranged between 1.7 cm × 1.7 cm and 4.9 cm × 4.8 cm.The common bile duct,intrahepatic bile duct and pancreatic duct of 7 patients were dilated.The superior mesenteric vein of 3 patients were invaded by the tumor.The lymph nodes of 4 patients were swollen,and 3 patients had peritoneal effusion.The results of CT confirmed that 2 patients were with cholecystolithiasis,and the results of magnetic retrograde cholangiopancreatography (MRCP) confirmed that 1 patient had choledocholithiasis.The size of he pancreas of all the patients were increased using ultrasonography,and the main pancreatic ducts of 2 patients were dilated.Ten patients were diagnosed as with advanced pancreatic carcinoma.All the patients were staged by the imaging findings,5 patients belonged to stage Ⅱ and 8 belonged to stage Ⅳ.Two patients underwent pancreaticoduodenectomy,and 1 of them underwent postoperative radiotherapy and chemotherapy,and the other patient underwent palliative biliary enteric anastomosis and gastrojejunostomy.Two patients were treated by chemotherapy and 1 by radiotherapy in the 10 patients who did not received surgery.The rest 7 patients were treated with symptomatic therapy.The pathological results of the 2 patients who underwent pancreaticoduodenectomy were both moderately and poor-differentiated adenocarcinoma,and the size of the tumors were 4.0 cm × 3.0 cm × 2.5 cm and 2.5 cm × 2.0 cm × 1.0 cm.Three patients lost to follow-up among the 13 patients.The survival time of the patients with acute pancreatitis as the initial symptom ranged from 2.0 months to 6.0 months,and the median survival time was 4.5 months.The survival time of the patients with chronic pancreatitis as the initial symptom ranged from 0.5 months to 10.0 months,and the median survival time was 3.0 months.The median survival time of the 4 patients with elevated level of CEA was 3.5 months,and the median time of the 5 patients with normal level of CEA was 5.4 months.All the 10 patients who were followed up died of tumor recurrence and metastasis.Conclusion The clinical presentation of patients with acute and chronic pancreatitis as the initial symptoms is atypical,and it is difficult to achieve early diagnosis.Dynamic monitoring and combined diagnosis with laboratory and imaging examinations will improve the accuracy of diagnosis.Surgery based treatment is the preferred option.

Objective To design and synthesize a series of new type four hydrogen quinoline-benzyl/benzimidazole amine derivatives as a potential new inhibitor targeting auxiliary receptor CXCR 4, and determine their inhibitory activities to HIV-1.Methods Based on HIV-1 receptor CXCR4 inhibitors containing three nitrogen structure-activity motif and CCR5 partial hydrophobic pharmacophore , a series of new compounds were designed , synthesized and characterized by 1 HNMR and MS.The inhibitory activities of these compounds were determined using HIV-1 IIIB virus.Results and Conclusion Ten target compounds are synthesized .Four hydrogen quinoline-benzimidazole amine derivatives exhibit good anti-HIV activity(IC50 <1 μmol/L), but four hydrogen quinoline-benzyl amine compounds are less active ((IC50 >8 μmol/L).

Objective To assess the effect of low-dose cytarabine and aclarubicin in combination with gran-ulocyte colony-stimulating factor (G-CSF) protocol (CAG) in patients with acute myeloid leukemia (AML),and to understand the potential factors affecting the outcome of CAG induction therapy, therefore to find the optimum pa-tients for CAG therapy. Methods Twenty-one AML patients were enrolled in the current study. All patients were treated with CAG regimen including cytarabine (10 mg/m~2, subcutaneously, every 12 h, days 1 - 14), lacinomycin (5～7 mg/m~2,intravenously,every day, days 1 -8) ,and G-CSF (200 μg/m~2,subcutaneously, every day,12 h be-fore Ara-C was given) priming. Results The overall complete remission (CR) rate of the 21 AML patients was 66.7% (14/21). The CR rates was 87.5% (7/8) in patients older than 60 yrs,60.0% (9/15) in the refractory or relapsed patients,83.3% (5/6) in the MDS transformed AML patients. The CR rates for patients with hyperprolif-erative BM and median to poor proliferative BM were 33.3% and 91.7% ,respectively(P =0.009). The median o-verall survival (OS) time of the 21 AML patients was 450 days. Two-year survival rate estimated by Kaplan-Meier Method was 30.6%. The overall median disease free survival (DFS) was 165 days. The median OS time for those refractory or relapsed was 435 days. The median OS time for those with poor cytogenetic state or standard or good cytogenetic state was 140 days and 620 days, respectively (P = 0.001). The median OS time for patients with hyperproliferative BM and median to poor proliferative BM was 321 days and 620 days, respectively (P = 0.05). The median recovery time of granulocytes above 1.0×10~9/L was 8 days. The median duration of fever was 3.5 days. The rate of infections exceeding WHO grade Ⅱ was 42.9%. No early death occurred. Conclusions The CAG induction therapy may have a higher CR rate in patients with refractory or relapsed AML, elderly AML and secondary AML from MDS transformation, and extend the median overall survival time in refractory or relapsed patients. CAG therapy can not improve the outcome of patients whose BM was in high grade proliferation state or whose cytogenetic state was poor. CAG therapy can shorten the duration of agranulocytosis and decrease the inci-dence of serious infection. Therefore, CAG therapy is worth recommending to patients who can not endure the rou-tine intensive chemotherapy.

BACKGROUND: Electrical impedance tomography (EIT) uses non-invasive signals to probe the human body and then detect the responses on the boundary of the body in order to reconstruct an impedance distribution inside the body. Compared to CT and MRI, EIT takes the advantages of realtime technique, lower cost and easiness for both continuous monitoring and functional imaging.OBJECTIVE: This study was designed to perform the in vivo measurement of the rabbit brain impedance frequency response before and after ischemia. And it was to verify the feasibility of EIT in brain functional imaging by ischemia brain functional imaging using EIT.DESIGN: It was a single-sample experiment.SETTING: It was conducted at the Department of Medical Electronic Engineering, Faculty of Biomedical Engineering, Fourth Military Medical University of Chinese PLA.MATERIALS: This study was conducted at the Department of Medical Electronic Engineering, Faculty of Biomedical Engineering, Fourth Military Medical University of Chinese PLA from August to September 2001 and 10 healthy rabbits were selected.METHODS: Cerebral ischemia animal model was made using carotid artery ligation. Then the in vivo measurement of the rabbit brain impedance frequency response before and after ischemia was performed.Dynamic unilateral brain blood supply was recorded using EIT imaging.curves were plot before and after ischemia in the frequency range from 0.1 Hz EIT imagingRESULTS: Nine rabbits entered the statistical analysis and one was omitimpedance increased significantly. The ratio of increasing impedance can be up to 75% at frequencies lower than 10 Hz. And in the range from 1 kHz namic imaging showed that the changes in unilateral brain blood supply is accordant with the corresponding regions having a changing impedance.CONCLUSION: The changes in brain tissue impedance before and after ischemia can be imaged and it could be used as a variable for EIT imaging.

BACKGROUND:The electrical impedance tomography (EIT) is a kind of examination that is used to non-invasively measure the change and distribution of electrical bio-impedance by reconstructing the frequency response obtained by electrical stimuli applied onto the human body. The characteristics of impedance of any tissues are of great importance to the imaging of EIT and locating and monitoring the lesion focus.OBJECTIVE: To measure the human brain impedance in the frequency range from 0.1 Hz to 1 MHz and to compare these with those of other human tissues and the rabbit brain tissues.DESIGN: An observational experiment.SETTING:The Department of Medical Electric Engineering of the Biomedical Engineering College of the Fourth Military Medical University of Chinese PLA.MATERIALS:The experiment was conducted at the Otolaryngology Laboratory, Department of Medical Electric Engineering of Biomedical Engineering College, Fourth Military Medical University of Chinese PLA from April, 2000 to June, 2000. Two brains were harvested from two cadavers of adult men who died in less than 12 hours before the brains were taken.INTERVENTIONS :The brains were divided into 15 samples and the Solartron 1255B frequency resoonse analyzer was used to measure the complex impedance of human brain in vitro with four-electrode measurement method in the frequency range from 0.1 Hz to 1 MHz.There were also impedance interface (1294)and self-made experimental measurement box.MAIN OUTCOME MEASURES:The resistivity frequency response,curves of real part and imaginary part of complex impedance as well as the equivalent circuit model of the complex impedance.RESULTS:The resistivity of human brain tissues was about 1 200 Ω·cm in the frequency range of 0.1-100 Hz.But it decreased to 650 Ω·cm in the frequency range of 100-1×106 Hz. The real part of complex impedance remained steady in the frequency range of 0.1-100 Hz and it decreased along with the increase of frequency in the range of 100-1×106 Hz. The absolute value of frequency response curves of the imaginary part of human brain's complex impedance presented a tendency of monotonic increase.CONCLUSION: The resistivity and the real part of complex impedance curve of human brain were in accordance with those of other tissues such as muscles, the liver, kidney and lungs. The frequency response curve of the imaginary part of human brain's complex impedance was different from that of other animal tissues (such as muscles, the liver and kidney) but was in accordance with that of rabbit brain tissues in vitro. The construction of the equivalent circuit model obtained was more complex than other models known.