Cerebral small vessel disease （CSVD） is a common cause of vascular dementia and has various etiologies， among which hypertension is the most common risk factor and can induce the disease by damaging the neurovascular glial unit. The process of CSVD leading to cognitive impairment is mainly associated with the disruption of cerebral network connections due to the destruction of cerebral white matter fibers， as well as secondary cortical atrophy and thinning； however， with the discovery of the glymphatic system in recent years， cognitive impairment associated with β-amyloid clearance dysfunction has been considered a new mechanism. The clearance function of the glymphatic system reaches the peak during sleep due to circadian rhythm. Previous studies on the association between CSVD and circadian rhythm have shown that CSVD patients often experience sleep disorders， which is a specific manifestation of circadian rhythm disorders. Such disorders are often neglected， which can lead to a reduction in the function of the glymphatic system in β-amyloid clearance， thereby aggravating cognitive impairment in patients. However， there is still a lack of in-depth studies on the association between the circadian rhythm disorders of the glymphatic system and cognitive impairment in CSVD. This article reviews the studies on sleep rhythm disorders， dysfunction of the glymphatic system， and their influence on cognitive impairment in CSVD.

OBJECTIVE: To explore the biomarkers of tinnitus in vestibular schwannoma patients using electroencephalographic (EEG) microstate technology. METHODS: The EEG and clinical data of 41 patients with vestibular schwannoma were collected. All the patients were evaluated by SAS, SDS, THI and VAS scales. The EEG acquisition time was 10-15 min, and the EEG data were preprocessed and analyzed using MATLAB and EEGLAB software package. RESULTS: Of the 41 patients with vestibular schwannoma, 29 patients had tinnitus and 12 did not have tinnitus, and their clinical parameters were comparable. The average global explanation variances of the non-tinnitus and tinnitus groups were 78.8% and 80.1%, respectively. The results of EEG microstate analysis showed that compared with those without tinnitus, the patients with tinnitus had an increased frequency (P=0.033) and contribution (P=0.028) of microstate C. Correlation analysis showed that THI scale scores of the patients were negatively correlated with the duration of microstate A (R=-0.435, P=0.018) and positively with the frequencies of microstate B (R=0.456, P=0.013) and microstate C (R=0.412, P=0.026). Syntax analysis showed that the probability of transition from microstate C to microstate B increased significantly in vestibular schwannoma patients with tinnitus (P=0.031). CONCLUSION EEG microstate features differ significantly between vestibular schwannoma patients with and without tinnitus. This abnormality in patients with tinnitus may reflect the potential abnormality in the allocation of neural resources and the transition of brain functional activity.
Humans ; Neuroma, Acoustic/complications* ; Electroencephalography ; Patients ; Probability

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective: To investigate the pyroptosis induced by different enteroviruses in human neuroblastoma cells SH-SY5Y and the differences among them. Methods: SH-SY5Y cells were infected with nine strains of enterovirus respectively, including enterovirus A71 (EV-A71), Coxsackievirus A (CA), Coxsackievirus B (CB), Echovirus (Echo). The cellular morphology of infected and control groups were observed and activity of Caspase-1 of infected and control groups were detected by flow cytometry at 48 h post infection. Results: The activity of Caspase-1 induced by EV-A71 was higher than control (P<0.001), and the activity of Caspase-1 induced by EV-A71 isolated from severe case was significantly higher than that induced by EV-A71 isolated from common case (P<0.001). The activity of Caspase-1 induced by CA was at a lower level. The activity of Caspase-1 induced by CB and Echo were both significantly higher than that induced by EV-A71 and control (P<0.001). Cytopathic effects (CPE) were found to be related with the activity of Caspase-1. Conclusions EV-A71, CB and Echo all could induce pyroptosis mediated by Caspase-1 in SH-SY5Y cells, but the ability of CA to induce pyroptosis was at a lower level, which may provide evidences for further study on mechanism of neuropathy caused by enterovirus.

Objective To explore the effects of quality control circle ( QCC ) on decreasing fraction defective of urine culture collecting. Methods QCC team was established. Followed the steps of QCC techniques, we analyzed the reasons of fraction defective of the urine culture, formulated countermeasures, and analyzed the results between before and after the implementation of countermeasures. Results The fraction defective of the urine culture declined from 10. 37% to 2. 46%, and objective achieved 111. 72% with the progress rate of 76. 28% after the implementation of countermeasures. Conclusions QCC program is a useful method to decrease fraction defective of the urine culture and regulate the standard of collecting. Meanwhile, the ability of the circle members was improved to resolve clinical problems.

Objective To evaluate the clinical efficacy of three-dimensional conformal radiotherapy (3D-CRT) combined with thermochemotherapy in the treatment of locally advanced pancreatic cancer (LAPC).Methods From June 2008 to June 2011,70 patients with LAPC were divided into radiotherapy group (30 patients) and combination group (40 patients).Radiotherapy used 3D-CRT with a 90％ to 95％ isodose curve,a single dose of 1.8 to 2.OGy,and total radiation dose 50 ～ 70 Gy.The combination group patients received simultaneous thermotherapy at 41.5 ～43.5 ℃ (1 h/fraction,twice a week for 6 times),and hyperthermia given simultaneously injected using arsenic trioxide 20 mg,recombinant mutant human tumor necrosis factor(rmhTNF) intravenous infusion of 10 million U,4 to 6 times,or 3D-CRT at the same time and the treatment given after gemcitabine(0.6 ～ 1.0 g/m2) on Days dl and 8 and cisplatin (DDP) (20 ～ 30 mg/m2) on Days d1-3 intravenous infusion,repeated every 28 days for 3 ～ 6 cycles.Results At 3 months after treatment,the total response (complete remission and partial remission) rate was 70.0％ (49/70),the efficiency of radiotherapy combined with chemotherapy,and radiotherapy combined with thermo-chemotherapy were 56.5％ and 88.2％,and the radiotherapy alone group was 56.7％.There were significant difference in efficiency between radiotherapy combined with thermo-chemotherapy group compared to radiotherapy-chemotherapy group and radiotherapy group (x2 =4.68,4.98,P ＜ 0.05),the last two groups showed no significant difference (P ＞ 0.05).The 1-year and 2-year survival rate was 46.8％ and 20.3％,respectively.The 1-year and 2-year survival rates were 52.4％ and 26.7％ in combination group,and 42.5％ and 16.2％ in radiotherapy group (x2 =14.17,P ＜ 0.05 ; x2 =9.74,P ＜ 0.05).No serious complications such as perforation,bleeding,and high fever were seen during treatment and follow-up.Conclusions 3D-CRT combined with thermochemotherapy is well tolerated and is relatively effective for the LAPC patients.

ObjectiveTo determine the peripheral serum expressions and clinical value of carcinoembryonic antigen (CEA) and carbohydrate antigen CA19-9,CA242,CA72-4 and a single sialic acid ganglioside (CA50) antigen in advanced pancreatic cancer patients treated by three-dimensional conformal radiotherapy (3D-CRT) combined with endogenous field hyperthermia.Methods60 patients inoperable,advanced pancreatic cancer were treated by 3D-CRT combined with endogenous field hyperthermia.Radiation dose (DT) was 46 ～ 66 GY/23 ～ 33 F.Hyperthermia temperature was 41 ～ 43 ℃ 2 times/week,lasted 60 min each time.The expressions of CEA,CA19-9,CA242,CA72-4 and CA50 in peripheral serum were detected by Electrochemiluminescence immunoassay (ECLIA) every 2 weeks during treatment,and correlation were analyzed with tumor diameter,clinical stage,lymph node metastasis.Results From the 8th week,with 3D-CRT combined with endogenous field hyperthermia ongoing,CEA,CA19-9,CA50 andCA242 expression levels showed a gradual decline.CEA,CA19-9,CA50 and CA242 expression levels were (6.22 ± 2.71 ) μg/L,(43.44 ± 12.93 ) μg/L,(23.21 ± 7.71 )g/L and (24.26 ± 8.92) μg/L in 6 weeks,respectively.The difference was statistically significant among week 6 and week 0,week2,week 4 ( P ＜0.05),however there was no significant difference between week 6 and week 8 ( P ＞ 0.05 ).The CA724 expression did not change significantly ( P ＞ 0.05 ).There were positively correlation between CEA,CA199,CA50 and CA242 with pancreatic cancer tumor size,clinical stage and lymph node metastasis( respectively r =0.877,0.725,0.826,all P ＜ 0.01 ),however CA72-4 had no correlations ( P ＞ 0.05).ConclusionsCEA,CA19-9,CA50 and CA242 expressions in peripheral serum of pancreatic cancer patients were closely related to the treatment.Their joint detection can be served as independent objective evaluation reference information for the treatment efficacy and prognosis.

Objective To investigate the role of the expression of prostate stem cell antigen(PSCA)in the development of perineural invasion in pancreatic carcinoma.Methods The histopathologic and immunohis-tochemical(SABC)studies were performed on 80 patients with pancreatic carcinoma.The overall incidence of PSCA expression,perineural,lymphatic and vascular vessel invasion were counted to investigate the relationships among them.Results Perineurel invasion was positively correlated with lymphatic and vascular vessel invasion (P<0.01).A positive corelation Was found between tumor PSCA expressioa(53 cases)and the perineurel in-vasion(66 cases).A definite correlation Was also found between cancer differentiation and PSCA tyxplres-sion.Conclusion PSCA is one of the most important molecules and may play a role as a "navigating" and " docking" molecule in the developmeat of perineural invasion.

Objective: To investigate the effect of nerve growth factor-β(NGF-β) on the proliferation and cell cycle of human pancreatic cancer MIA PaCa-2 cells. Methods: MIA PaCa-2 cells were treated with different concentrations of NGF-β and K252a (inhibitor of NGF-β receptor TrKA) alone or in combination. Clone forming rate, proliferation, and cell cycle of MIA PaCa-2 cells treated with different strategies were examined by clone formation assay, MTT, and flow cytometry, respectively. Results: NGF-β significantly increased the clone formation and proliferation of MIA PaCa-2 cells (P<0.05, P<0.01). K252a significantly inhibited the proliferation of MIA PaCa-2 cells (P<0.05), while NGF-β combined with K252a had no significant effect on the proliferation of MIA PaCa-2 cells. NGF-β arrested MIA PaCa-2 cell cycle in S phase, K252a arrested cell cycle in G_0/ G_1 phase, and NGF-β combined with K252a arrested cell cycle in S phase. Conclusion: NGF-β can enhance the proliferation of pancreatic carcinoma MIA PaCa-2 cells.

pancreatic carcinoma by some signal transduction.