Objective:To explore the dynamic temporal variability of brain functional networks in individuals with internet gaming disorder(IGD)using dynamic functional connectivity density(dFCD).Methods:From January 2019 to December 2021, resting-state functional magnetic resonance imaging data were recruited from 55 patients with IGD and demographically matched 50 healthy controls.Data analysis was performed by IBM SPSS 21.0 software. The functional connectivity density(FCD) combined with sliding window analysis was employed to calculate the temporal variability of global functional connectivity.FCD in whole brain was further devided into ipsilateral and cotralateral parts.The temporal variability of dFCD was further quantified utilizing the standard deviations of whole brain, intra-, and inter-hemispheric FCD. Finally, Pearson correlation analysis was performed between dFCD variance in differential brain regions and clinical behaviors.Results:The inter-hemispheric dFCD in the left posterior cingulate cortex(-0.16±0.24) and the left precuneus(-0.08±0.23) in patients with IGD were lower that those in healthy controls(0.002±0.260, 0.12±0.36)( t=-3.502, -4.160, both P<0.05).And the intra-hemispheric dFCD in the left calcarine, the left precuneus, and the left posterior cingulate cortex in patients with IGD were lower that those in healthy controls( t=-3.809, -4.360, -3.561, all P<0.05).Moreover, abnormal global dFCD variability of the calcarine and ipsilateral dFCD variability of the PCC negatively correlated with the severity of IGD( r=-0.380, -0.413, both P<0.05). Conclusion:Patients with IGD show intra-and inter-hemispheric dFCD differences in the visual attention network and default mode network, which may respond to the underlying neurobiological basis for the presence of cognitive dysfunction and impaired concentration.

Objective:To analyze the clinical features and immunotherapy responsiveness of patients with myelin oligodendrocyte glycoprotein immunoglobulin G-antibody associated disease (MOGAD) with epilepsy, and display the risk factors of epilepsy in MOGAD.Methods:Eighty-nine patients with MOGAD diagnosed at the First Affiliated Hospital of Zhengzhou University between October 2019 and May 2023 were enrolled and classified into 2 groups upon MOGAD with ( n=29) or without epilepsy ( n=60). The Expanded Disability Status Scale (EDSS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) were used for evaluation of severity, and EDSS or CASE scores on the 30th day after first-line immunotherapy initiation lower than that on admission were defined as well treatment responsiveness. The differences of general data, clinical manifestations, cerebrospinal fluid (CSF) and peripheral blood biochemical examination results, and immunotherapy reactivity between the 2 groups were thoroughly explicated. In addition, the risk factors of epilepsy in MOGAD were analyzed by univariate and multivariate Logistic regression analysis. Results:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy were characterized by lower age of onset [24.5(10.3, 34.0) years vs 11.0(6.5, 20.0) years, Z=-2.348, P=0.019], higher percentage of male patients [43.3%(26/60) vs 75.9%(22/29), χ 2=8.326, P=0.004], higher virus infection rate [28.3%(17/60) vs 51.7%(15/29), χ 2=4.645, P=0.031], higher incidence of prodromal symptoms [11.7%(7/60) vs 34.5%(10/29), χ 2=6.586, P=0.010], higher blood-brain barrier breakdown rate [35.0%(21/60) vs 58.6%(17/29), χ 2=4.458, P=0.035], higher percentage of CSF albumin level>450 mg/L [48.3%(29/60) vs 75.9%(22/29), χ 2=6.056, P=0.014] and higher creatine kinase level [45.50(28.50, 69.75) U/L vs 57.50(41.75, 97.25) U/L, Z=-2.349, P=0.019]; more epilepsy [0(0) vs 29/29 (100.0%), χ 2=89.000, P<0.001] and disturbance of consciousness [0(0) vs 6/29(20.7%), χ 2=10.224, P=0.001] as clinical manifestations, and more cerebral cortex lesions [30/60(50.0%) vs 25/29(86.2%), χ 2=10.856, P=0.001] on magnetic resonance imaging. Nevertheless, the patients with MOGAD without epilepsy were featured with more visual impairment [23/60(38.3%) vs 3/29(10.3%), χ 2=7.406, P=0.007], limb weakness [18/60(30.0%) vs 1/29(3.4%), χ 2=8.209, P=0.004], sensory disturbance [15/60(25.0%) vs 0(0), Fisher exact probability test, P=0.002] and more cervical cord lesions [22/60(36.7%) vs 4/29(13.8%), χ 2=4.946, P=0.026] on magnetic resonance imaging. Immunotherapy responsiveness was relatively poor in the MOGAD with epilepsy group [EDSS score lower than that on admission: 15/29(51.7%) vs 46/60(76.7%), χ 2=5.641, P=0.018; CASE score lower than that on admission: 16/29(55.2%) vs 47/60(78.3%), χ 2=5.072, P=0.024] compared with the MOGAD without epilepsy group. Male was the independent risk factor of epilepsy in MOGAD ( OR=7.078, 95% CI 1.709-29.326, P=0.007). Conclusions:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy reported more male patients, lower age of onset and higher incidence of prodromal symptoms, blood-brain barrier dysfunction rate, virus infection rate, CSF albumin level and creatine kinase level; clinical phenotypes were mainly meningoencephalitis and more cerebral cortex lesions were shown on magnetic resonance imaging. MOGAD with epilepsy was closely related to poor immunotherapy responsiveness, and gender was found to be the independent risk factor for epilepsy in MOGAD.

Biologics are developing rapidly and have demonstrated their unique advantages in the treatment of many diseases. And with common administration, like oral and injection, biological products often have problems in instability, short half-life and poor utilization of the central nervous system, which limits the application scope and development of biological products. Intranasal biologics are promising strategy taking advantages in nasal administration that bypass the restrictions in vivo, like blood-brain-barrier, to improve the drug avalibility in the target site, which have potential to improve efficient delivery and the availability. According to published literature, clinical databases, industry guidelines around the world, this review highlighted the rescent progress in intranasal macromolecular drugs, intranasal vaccine and intranasal cell therapy, which were the main fields of intranasal biologics, offering perspectives suggestions for the further development of this field.

Objective:To evaluate the effect of long non-coding RNA PRMT5-AS1 on ferroptosis of hepatocellular carcinoma cell(HCC) after ionizing irradiation.Methods:The PRMT5-AS1 overexpression model was constructed in MHCC-97H cells and the PRMT5-AS1 knockdown model was constructed in HepG2 cells. X-ray irradiation(IR) was performed with an absorbed dose of 10 Gy and a dose rate of 3 Gy/min. Western blot and qRT-PCR were used to detect gene expression. The effect of PRMT5-AS1 expression on lipid peroxidation and ferroptosis of HCC after IR was detected by Trypan blue staining flow cytometry. The effect of PRMT5-AS1 expression on the death of HCC after IR was detected by CCK-8 assay. Dual luciferase assay to detect the binding of let-7c-5p to PRMT5-AS1 and SLC7A11.Results:Overexpression of PRMT5-AS1 in MHCC-97H cells could significantly reduce cell death induced by IR (Vector vs. PRMT5-AS1: 27.57% vs.18.30%, t=14.94, P<0.05). Knockdown of PRMT5-AS1 in HepG2 cells significantly increased cell death induced by IR (siNC vs. siPRMT5-AS1: 17.26% vs. 28.26%, t=13.63, P<0.05). Flow cytometry result show that overexpression of PRMT5-AS1 can significantly inhibit the increase of intracellular lipid ROS level induced by IR (Vector vs. PRMT5-AS1: 17.01% vs. 12.52%, t=12.80, P<0.05), and knockdown of PRMT5-AS1 significantly increases the lipid ROS level induced by IR (siNC vs. siPRMT5-AS1: 14.54% vs. 17.72%, t=5.93, P<0.05). The result of CCK-8 experiment showed that overexpression of PRMT5-AS1 could significantly inhibit Erastin induced cell activity reduction (Vector vs. PRMT5-AS1: 87.92% vs. 109.06%, t=2.87, P<0.05), and knockdown of PRMT5-AS1 could promote Erastin′s inhibitory effect on cell activity (siNC vs. siPRMT5-AS1: 82.56% vs. 60.58%, t=38.35, P<0.05). Western blot and fluorescent quantitative PCR result showed that the protein and mRNA levels of SLC7A11 were significantly increased after overexpression of PRMT5-AS1 ( t=26.24, P<0.05), and the protein and mRNA levels of SLC7A11 were significantly decreased after knockdown of PRMT5-AS1 ( t=5.60, P<0.05). The correlation between PRMT5-AS1 and let-7c-5p was confirmed by luciferase report gene experiment ( t=9.74, P<0.05). The result of luciferase reporter gene experiment showed that PRMT5-AS1 could form ceRNA network with let-7c-5p to regulate SLC7A11. Let-7c-5p was able to reverse the increase in SLC7A11 expression levels, decrease in Lipid-ROS levels and cell death induced by overexpression of PRMT5-AS1 ( t=3.01, 4.11, P<0.05). And knockdown of SLC7A11 reversed Lipid-ROS inhibition and reduced cell death caused by PRMT5-AS1( t=21.35, 7.15, P<0.05). Conclusions:LncRNA PRMT5-AS1 inhibits IR-induced ferroptosis in HCC through the PRMT5-AS1/let-7c-5p/SLC7A11 axis.

Objective:To clarify the M protein ( emm gene) types and drug susceptibility characteristic variations of Group A Streptococcus (GAS) in children in Beijing. Methods:The GAS strains isolated from throat swab samples of children diagnosed with scarlet fever and pharyngeal infection in scarlet fever etiology surveillance sentinel hospitals in 16 districts of Beijing in 2018, 2019 and 2021 were analyzed retrospectively.PCR amplification and sequencing were used for emm genotyping, and the minimum inhibitory concentrations (MIC) of 10 antibiotics were determined by the broth microdilution method.The data were analyzed using χ2 test and Fisher′ s exact method between groups. Results:A total of 557 GAS strains were collected, and 11 emm genotypes ( emm1, emm3, emm4, emm6, emm11, emm12, emm22, emm75, emm89, emm128, and emm212) were detected.Of 557 strains, 238 trains were of emm1 type (42.73%), 271 strains were of emm12 type (48.65%) and 48 strains were of other emm types (8.62%). The detection rates of emm1, emm12 and other emm type genes in 2018, 2019, and 2021 were [37.50% (105/280 strains), 57.14% (160/280 strains), 5.36% (15/280 strains)], [49.05% (129/263 strains), 39.54% (104/263 strains), 11.41% (30/263 strains)], and [28.57% (4/14 strains), 50.00% (7/14 strains), 21.43% (3/14 strains)], respectively.In children infected with emm12 in 2018 and 2019, there were more children under 6 years old than children over 6 years old (62.50% vs.46.88%, 46.36% vs.30.36%) (χ 2=7.182, 6.973; all P<0.05). Drug susceptibility testing results suggested that 225 randomly selected GAS strains were all 100.00% sensitive to 7 antibiotics including Penicillin, Levofloxacin, Meropenem, Linezolid, Cefotaxime, Cefepime and Vancomycin.The rates of resistance to Erythromycin, Tetracycline and Clindamycin were [88.57% (93/105 strains), 87.62% (92/105 strains), 86.67% (91/105 strains)], and [94.34% (100/106 strains), 94.34% (100/106 strains), 87.74% (93/106 strains)] in 2018 and 2019, respectively.The test strains were 100.00% (14/14 strains) resistant to the above 3 antibiotics in 2021.MIC 50 and MIC 90 values of Penicillin in 2018, 2019, and 2021 were (0.03 mg/L, 0.03 mg/L), (0.03 mg/L, 0.06 mg/L), and (0.06 mg/L, 0.06 mg/L), respectively.Among 225 GAS strains, 207 strains had drug resistance and were resistant to more than one drug.Specifically, 94.69% (196/207 strains) were resistant to Erythromycin, Tetracycline and Clindamycin.About 4.35% (9/207 strains) were resistant to both Erythromycin and Clindamycin.A total of 0.97% (2/207 strains) were resistant to Erythromycin and Tetracycline. Conclusions:The emm genotypes of GAS in children in Beijing are diverse in 2018, 2019 and 2021.The dominant genotypes are emm12 and emm1, and emm12 is the main epidemiological type.GAS strains maintain highly resistant to Erythromycin, Clindamycin and Tetracycline, and sensitive to Penicillin and other antibiotics.However, MIC 50 and MIC 90 of Penicillin shows an ascending trend.

This study aimed to investigate the ameliorative effects of 60% ethanol elution fraction (ESMW) from Si Miao Wan on the hepatic lipid accumulation and its mechanism.TG kit, BODIPY fluorescence staining, QPCR, WB, oil red O staining, and AMPKα knockdown were used to detect the ability of ESMW to improve lipid accumulation in hepatocytes stimulated with free fatty acid.Furthermore, the effects of ESMW on the oral glucose tolerance, serum biochemical indexes, TG content in liver tissue, the expressions of mRNA and protein related to lipid metabolism in liver tissue were studied in mice fed with high fat diet to verify the mechanism of ESMW fraction on hepatic lipid accumulation.The results showed that ESMW inhibited lipid accumulation induced by free fatty acids by regulating AMPK signaling pathway, and that ESMW significantly improved the lipid metabolism of mice fed with high fat diet, with relation to AMPK signaling pathway.

Objective:To investigate the prenatal MRI diagnosis of fetal intracranial hemorrhage (ICH) and the pregnancy outcomes.Methods:This retrospective study included 49 cases of fetal ICH diagnosed by MRI in Obstetrics and Gynecology Hospital of Fudan University from July 2011 to November 2019. Two experts with more than five years of experience in obstetric radiology determined the location, number, area, stage and grade of the hemorrhage based on the MRI findings. Maternal age, gestational age at MRI, and the site, number, stage and grade of hemorrhage as well as other intracranial and extracranial abnormalities of the fetuses were compared between women with fetal germinal matrix-intraventricular hemorrhage (GM-IVH; GM-IVH group, n=39) and those without (non-GM-IVH group, n=10). MRI and ultrasound examination results of 37 cases who had MRI within three days after the ultrasound examination were compared. Postnatal and follow-up outcomes were summarized. Statistical analysis was performed using the independent sample t-test, Mann-Whitney U test and Chi-square test. Results:There was no significant difference in the maternal age, gestational age at MRI, or the site, number or stage of hemorrhage between the GM-IVH group and non-GM-IVH group (all P>0.05). The incidence of ventriculomegaly was higher in the GM-IVH group than that in the non-GM-IVH group [87% (34/39) vs 0/10, t=24.522, P<0.001]. There were 51% (19/37) of the lesions that were missed by ultrasound found by MRI, including GM-IVH in 17 cases, right cerebellar hemisphere hemorrhage in one case and corpus callosum hemorrhage in one case. Among the 49 cases, seven were lost to follow-up, 29 terminated the pregnancy (six in non-GM-IVH group and 23 in GM-IVH group), two experienced intrauterine fetal death in late pregnancy and 11 gave live birth. Ten live births had GM-IVH, among them a relatively good prognosis was noted in fetuses with grade Ⅰ (two cases), grade Ⅱ (four cases), and grade Ⅲ (three cases) GM-IVH, while one case with grade Ⅳ GM-IVH had mental retardation at eight years old; one non-GM-IVH infant had hearing loss at birth and a cochlear was implanted with no other anomalies reported during a three-year follow-up. Conclusions:MRI can provide a more direct view of the location and grade of fetal ICH and is more accurate than prenatal ultrasound in diagnosing fetal ICH, which is a beneficial supplement to ultrasound. The prognosis of cases with grade Ⅳ GM-IVH is not good.

[Summary] SIRT3 is a member of the silent information regulator 2 ( Sir2) family, located in the inner mitochondrial membrane, with a strong effect of deacetylation. SIRT3 not only modulates energy metabolism, cell apoptosis, tumor growth, anti-aging etc. , but also plays an important role in the field of cardiovascular diseases. In this review, we summarize recent findings related to SIRT3 with metabolic syndrome and cardiac hypertrophy, to provide a theoretical basis for the further study on the potential role of SIRT3 in cardiovascular diseases.

BACKGROUND: Imatinib has a significant pro-apoptosis effect on chronic myelogenous leukemia (CML), but there are still some patients being resistant to it. Human umbilical cord mesenchymal stem cells (hUC-MSCs) affect the apoptosis of a variety of hematologic malignancies. However, the impacts of hUC-MSCs on the apoptosis of CML cells induced by imatinib remain unclear.OBJECTIVE: To investigate whether hUC-MSCs have an influence on the apoptosis of K562 cells induced by imatinib and to reveal the possible underlying mechanism.METHODS: K562 cells were cultured with hUC-MSCs or/and imatinib. Cellular apoptosis was measured with Annexin-V and PI staining by flow cytometry analysis. The protein expressions of Bax, Bcl-2, caspase-3, caspase-9 and cleaved-PARP in K562 cells were detected by western blot assay. Pan-caspase inhibitor Z-VAD-FMK was used to block apoptosis in each group, and during this process the effect of caspase apoptosis signaling pathway was detected.RESULTS AND CONCLUSION: The apoptosis of K562 cells was enhanced, when imatinib was combined with hUC-MSCs. Western blot analysis showed that the expression of pro-apoptotic protein Bax was enhenced and the expression of anti-apoptotic protein Bcl-2 was suppressed. Furthermore, the cleaved forms of caspase-9, caspase-3 and PARP in K562 cell were higher in the hUC-MSCs+imatinib group than in the imatinib group. The apoptosis of K562 cells induced by the hUC-MSCs combined with imatinib was significantly inhibited by Z-VAD-FMK. In conclusion, these findings indicate that hUC-MSCs can enhance imatinib-induced apoptosis of K562 cells by activating caspase apoptosis signaling pathway.

Objective To explore the correlation of positive psychological capital and time management disposition in medical college students.Methods A total of 880 students from medical university were surveyed by using positive psychological capital scale and time management disposition scale.Results For gender variables,the scores of hope and optimism of males were significantly lower than those of females(P ＜ 0.05);there was no significant difference in the scores of time value sense,time monitoring sense,time efficacy sense,self-confidence and toughness between males and females (P ＞ 0.05).For birthplace variables,the rural students' scores of time value sense,hope and optimism were significantly higher than those of urban students (P ＜ 0.05);there was no significant difference in the scores of time monitoring sense,time efficacy sense,self-confidence and toughness between rural students and urban students (P ＞ 0.05).For grade variables,the score of time value sense of seniors was significantly higher than that of freshman(P ＜ 0.05);the score of time value sense of the fifth grader students was significantly higher than that of freshmen and sophomore (P ＜ 0.05);the score of time efficacy sense of the fifth grader students was significantly higher than that of sophomore (P ＜ 0.05);the scores of hope and optimism of the fifth grader students were significantly higher than those of sophomore (P ＜ 0.05);the score of optimism of freshman was significantly higher than that of sophomore(P ＜ 0.05);there was no significant difference in the scores of another dimensions in the other grades (P ＞ 0.05).Positive psychological capital and its dimensions were positively correlated with time management disposition and its dimensions (P ＜ 0.01).Positive psychological capital has good positive predictive ability on the four dimensions of time management disposition.Conclusion There is a positive correlation between positive psychological capital and time management disposition.The improvement of the level of psychological capital of college students can help to improve the ability of time management.