Sleep disorders are common diseases with various dys-function during sleep-wake process, including difficulty falling or staying asleep, falling asleep at inappropriate times, excessive total sleep time, or abnormal behaviors associated with sleep. Sleep disorders can lead to the deposition of amyloid beta protein ( Aβ) by affecting the normal metabolism of amyloid beta protein in the brain. Patients with Alzheimer’s disease ( AD) often suffer from sleep disorders, and its pathology always results in more se-vere sleep disorders, which leads to a risk of cognitive impair-ment and hypofunction. Sleep disorders could interact closely with AD, forming a positive feedback loop, which causes serious damage to the body health. This review summarized the current research about sleep disorder in the onset of AD and the current status of medication.

This study is to investigate the sedative and hypnotic effects of a novel compound H1208. The sedative activity of H1208 was investigated by recording the spontaneous locomotor activity of mice. The hypnotic property was evaluated by the latency and duration of sleep (loss of righting reflex) in mice and the effect of hypnotics on sleep pattern of electroencephalogram were studied in conscious, freely moving mice with chronically implanted electrodes. The brain monoamine neurotransmitters levels in mice were measured by high performance liquid chromatography-electrochemical detection. The spontaneous locomotor activity was decreased by 56.7% and 80.2% in H1208 (5 and 25 mg x kg(-1), ip) treated mice, respectively. The loss of righting reflex was directly induced in mice after H1208 (60 mg x kg(-1), ip) administration. The non-rapid eye movement sleep increased significantly by 131% and 259%, respectively, within 3 hours after H1208 (30 and 60 mg x kg(-1), ip) administration. However, the rapid eye movement sleep decreased significantly. The contents of DA in the striatum and cortex and 5-HT in the cortex decreased significantly. These results demonstrated that H1208 has potent sedative and hypnotic effects, which may be closely related to the decreased contents of DA and 5-HT in mouse brain.

A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.

Objective To study the nutritional risks in elderly patients with prostate cancer and explore its related factors.Methods 346 elderly patients with prostate cancer in Wuhan area from May 2013 to May 2014 were chosen as the objects in this study.Nutritional risk screening 2002 was used to evaluate nutritional risk.The sleep quality,anxiety,lower urinary tract symptoms,differentiation and other data of patients were collected.The influencing factors for nutritional risk in the patients were analyzed.Results The ratio of nutritional risk in elderly advanced prostate cancer patients was 35.3％ (122/346).The nutritional risk was increased with age (P＜0.05).The prostate cancer patients with nutritional risk had a higher international prostate symptom score (IPSS) (P＜ 0.05).Monovariate factor analysis showed that sleep quality,operation,pathology staging,radiotherapy,chemotherapy,lower urinary tract symptoms (LUTS) were the impact factors for nutritional status in elderly patients with prostate cancer (P＜0.05).Logistic regression analysis showed that age (OR=0.29),sleep quality (OR=0.25) were the protective factors for the nutritional status,while surgery (OR=12.67),pathological staging (OR=1.65),radiotherapy (OR=2.65),SPSS (OR=1.55),chemotherapy (OR=1.85) were the risk factors for nutritional status (P＜ 0.05).Conclusions The incidence of nutritional risk is high in elderly prostate cancer patients.Age,sleep quality are the protective factors,and operation,pathology staging,SPSS,chemotherapy,and radiotherapy are the risk factors for nutritional status.

Objective:To describe the electroclinical features of the coexistence of epilepsy and narcolepsy.Methods:The electroencephalography database was searched using the terms “epilepsy” and “narcolepsy” over a four-year period from January 2016 to December 2019 in the Xijing Hospital. The clinical and electrophysiological characteristics of patients with coexistence of epilepsy and narcolepsy were studied.Results:Five patients with comorbidity for epilepsy and narcolepsy were found, of which three patients were female, two patients were male. The age at epilepsy onset and narcolepsy onset was 2-12 years and 8-17 years, respectively. There were two patients with juvenile myoclonic epilepsy, one with sleep-related hypermoter epilepsy, one with epilepsy with retardation of brain development, one with symptomatic epilepsy with cognitive decline. All the patients had narcolepsy with cataplexy, which followed the onset of epilepsy by three months to eight years. All the patients accepted 24 h video electroencephalography monitoring and multiple sleep latency test. Interictal epileptic discharges were found, mean sleep latency was<8 min, and two or more sleep onset rapid eye movement periods were recorded. Duloxetine hydrochloride can effectively improve the drowsiness and catalepsy symptoms of narcolepsy, and seizures did not worsen in patients using duloxetine hydrochloride.Conclusions:Both generalized and focal epilepsy can occur in narcolepsy with cataplexy. Duloxetine hydrochloride may be safe and effective in treating narcolepsy in patients with epilepsy.

Objective To analyze the constituent of the 32 kD protein band and its expression in schizophrenia se?rum. Methods Sixty schizophrenia patients and 58 health controls were recruited. The serum samples were collected and precipitated with 7%PEG. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was used to ob?tain the abnormal 32 kD proteins band in patients. This protein band was cut and then analyzed using mass spectrometric technique. Results The 32 kD protein band was present in 38 schizophrenia patients but not in control and positive rate was 63.33%. The mass spectrometric analysis showed that 32 kD protein band contained 14 proteins ranging from 30 kD to 35 kD, including 6 high-frequency proteins (cDNA coded protein 1 and 2, Apolin protein A-1, Isoform 2 of ficolin-2, Complement factor H and clusterin) and 8 low-frequency proteins (IgG H chain, zinc-alphg-2-glycoprotein, fermitin,family apolin protein L-1, isoform 10 of collectin-1, purine nucleoside, anne xin and cDNA coded protein 3). Three cD?NA coded unknown proteins were highly similar to complement C4-B, β2-glycoprotein and erythrocyte band 7 integral membrane protein. Conclusion There is a unknown specific 32 kD protein that is consisted mainly of fourteen proteins in serum of schizophrenia.

OBJECTIVETo investigate the correlation between Shigella flexneri multi-drug resistance and drug resistance gene cassette of integrons.

METHODAll 79 strains of Shigella flexneri were isolated from the feces of children ranged in age from 6 months to 14 years in some hospitals of Jinan, between May 2009 and April 2012.The resistance was detected by Kirby Bauer agar diffusion method, 1, 2 and 3 integron gene was amplified by PCR, the variable region of positive strains treated with enzyme digestion and determined by Series Analysis.

RESULTAmong 79 Shigella flexneri strains, the resistance rate was 91% (72/79) to ampicillin, chloramphenicol, tetracycline, streptomycin, 70% (55/79) to sulfamethoxazole/trimethoprim, 30% (24/79), 23% (18/79), 33% (26/79) and 32% (25/79) to cefotaxime, ceftazidime, ciprofloxacin and levofloxacin.All 79 strains were susceptible to cefoxitin, imipenem, cefoperazone/sulbactam. The common drug resistance pattern is ampicillin tetracycline-chloramphenicol-streptomycin, accounted for 91% (72/79); 91% (72/79) strains carried integrons of class 1, 86% (68/79) strains carried integrons of class 2, No intI3 was detected. The resistance to ampicillin, streptomycin, tetracycline, chloramphenicol of atypical class 1 integron positive strains was significantly higher than the negative strains (χ² = 35.96, P<0.01). The sequencing results:dfrV was detected in class 1 integron variable regions of 9 strains, dfrA17-aadA5 in 2 strains, blaOXA-30-aadA1 in 70 strains, 2 strains were not detected resistance gene cassette, all resistance gene cassettes were dfrA1-sat1-aadA1 in class 2 integron variable regions.

CONCLUSIONThe muti-drug resistance of Shigella flexneri in Jinan was closely associated with integrons.

Adolescent ; Anti-Bacterial Agents ; pharmacology ; Child ; Child, Preschool ; Drug Resistance, Multiple, Bacterial ; genetics ; Dysentery, Bacillary ; microbiology ; Feces ; microbiology ; Humans ; Infant ; Integrons ; Polymerase Chain Reaction ; Shigella flexneri ; drug effects ; genetics

Objective: To analyze variations of TYR and P genes among 14 patients with clinically diagnosed oculocutaneous albinism. Methods: Potential variations of the TYR and P genes were detected by Sanger sequencing. Novel variations were predicted with bioinformatics software including SIFT and PolyPhen-2. Results: No variation was found in the TYR gene, while 9 types of variations were found in the P gene among the 14 patients, which included c. 803-3C>G (7/26), c. 1327G>A (p.Val443Ile) (5/26), c. 632C>T (p.Pro211Leu) (4/26), c. 1832T>C (p.Leu611Pro) (3/26), c. 1349C>A (p.Thr450Lys) (2/26), c. 2363C>T (p.Ser788Leu) (2/26), c. 2228C>T (p.Pro743Leu) (1/26), c. 1525A>G(p.Thr509Ala) (1/26), and c. 1349C>T(p.Thr450Met) (1/26). Only 1 heterozygous variation was detected in 2 families. c. 2363C>T (p.Ser788Leu), c. 1832T>C (p.Leu611Pro) and c. 1525A>G (p.Thr509Ala) were not reported previously and predicted as "harmful" to the protein function. Conclusion The main type of ocular albinism is oculocutaneous albinism type Ⅱ in Liuzhou region, where the most common variations of the P gene were c. 803-3C>G and c. 1327G>A (p.Val443Ile). Above finding has enriched the variation spectrum of the P gene.

Objective:To investigate the specificity and sensitivity of four methods including ultrafastreal-time fluorescence polymerase chain reaction (PCR), real-time fluorescence (RT)-PCR, enzyme-linked immunosorbent assay (ELISA) and gold immunochromatography assay (GICA) for the detection of novel Bunya virus, so as to provide experimental basis for the early diagnosis of severe fever with thrombocytopenia syndrome (SFTS).Methods:Serum samples from 86 clinically diagnosis SFTS patients admitted to the Jinan Infectious Diseases Hospital Affiliated to Shandoug University were tested by ultrafast real-time fluorescence PCR, RT-PCR, ELISA and GICA during June 1 to September 30, 2017. Chi-square test was used for statistical analysis.Results:Among 86 serum samples, the positive rate of novel Bunya virus of ultrafast real-time fluorescence PCR, RT-PCR, IgM-ELISA, IgG-ELISA, IgM-GICA and IgG-GICA were 82(95.34%), 79(91.86%), 41(47.67%), 8(9.3%), 19(22.09%) and 3(3.49%), respectively. The specificity of ultrafast real-time fluorescence PCR was 100%, and the sensitivity was 1×10 3 copies/mL.Repeated amplification test showed that the variation coefficient of the computed tomography value was <2%.During phases one, two and three, the positive rates of ultrafast real-time fluorescence PCR were 41(97.62%), 34(94.44%) and 7(87.50%), and RT-PCR were 39(92.86%), 33(91.67%) and 7(87.50%), respectively. During phases one and two, the positive rate of ultrafast real-time fluorescence PCR was slightly higher. The positive rate of anti-novel Bunya virus antibody (IgM) tested by ELISA had a significant increase from phase one (28.57%)to phase three (87.50%). There were statistical differences between phase two and phase, as well as between phase three and phase one ( χ2=8.347 and 7.561, respectively, both P<0.01). IgM-GICA also had an increase from phase one (14.29%) to phase two (33.33%)( χ2=3.962, P<0.01), while it was still lower than the other tests.In phase one, the positive rate of RT-PCR was higher than those of ELISA(both IgM and IgG)and GICA(both IgM and IgG)( χ2=33.740, 55.080, 49.010 and 64.340, respectively, all P<0.01). In phase two, the positive rate of RT-PCR was higher than those of ELISA(both IgM and IgG)and GICA(both IgM and IgG) ( χ2=7.700, 46.720, 23.700 and 50.630, respectively, all P<0.01). In phase three, the positive rates of ultrafast real-time fluorescence PCR, RT-PCR and IgM-ELISA were equivalent, which were all higher than those of IgG-ELISA and GICA (both IgM and IgG). The positive rates of RT-PCR and IgG-ELISA, IgM-GICA and IgG-GICA were significantly different (all χ2=6.250, all P<0.05). Conclusion:In the early detection of novel Bunya virus, ultrafast real-time fluorescence PCR has higher sensitivity, specificity, good repeatability and high stability, which greatly reduces the amplification time compared with the traditional RT-PCR, and is of great value in the early and rapid diagnosis of SFTS.

AIM: To investigate the effect of adalimumab combined with dexamethasone intravitreal implant in the treatment of refractory non-infectious uveitis macular edema(UME).METHODS: A total of 92 cases(131 eyes)of refractory non-infectious UME patients admitted to our hospital from January 2020 to January 2022 were selected and randomly divided into control group, with 46 cases(63 eyes)treated with dexamethasone intravitreal implant and observation group, with 46 cases(68 eyes)treated with adalimumab subcutaneous injection combined with dexamethasone intravitreal implant. The best corrected visual acuity(BCVA), central retinal thickness(CRT), vitreous opacity and Th17/Treg cytokines were measured before and after treatment, and the occurrence of adverse reactions was recorded.RESULTS: Totally 3 cases(4 eyes)were lost to follow-up. After treatment for 1, 3, 6 and 12 mo, BCVA was improved in both groups compared with that before treatment, and CRT, vitreous opacity score, serum interleukin(IL)-17 and IL-22 levels were decreased compared with those before treatment, and serum transforming growth factor-β(TGF-β)and IL-10 levels were increased compared with those before treatment. BCVA in the observation group was better than that in the control group, and CRT, vitreous opacity score, serum IL-17 and IL-22 levels were lower than those in the control group, and serum TGF-β and IL-10 levels were higher than those in the control group(all P<0.05). During treatment and follow-up, no serious adverse reactions occurred in both groups.CONCLUSION: Adalimumab combined with dexamethasone intravitreal implants in the treatment of refractory non-infectious UME can significantly subside the macular edema, reduce vitreous opacity and improve visual acuity.