The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Objective Evaluation of the effect and mechanism research of Qi-Shen-Yi-Zhi formula on improving learning and memory ability in mice injected with Aβ1-42 in hippocampus.Methods Alzheimer's disease model mice were constructed by injecting β amyloid peptide 1-42 into hippocampus and treated with water extracts of Qi-Shen-Yi-Zhi formula.The cognitive abilities of mice were assessed using Morris water maze and Y maze tests,which measure learning and memory capabilities.HE staining was used to observe the damage and TUNEL method was used to determine apoptosis of hippocampus.Detection of the expression of oxidative factors,inflammatory factors,and related antioxidant proteins and apoptotic proteins in the hippocampal tissue of a mouse model of dementia.Results Both high-dose and low-dose groups of Qi-Shen-Yi-Zhi formula significantly improved cognitive dysfunction in mice injected with Aβ1-42 in hippocampus,and attenuated the damage and apoptosis of the hippocampus.It also inhibited oxidative stress and downregulated the expressions of inflammatory factors IL-6,IL-1β and TNF-a,increased the expression of antioxidant proteins Nrf2 and HO-1,and regulated the expressions of apoptotic proteins Caspase-9,Caspase-3,Bax and Bcl-2.Conclusion Qi-Shen-Yi-Zhi formula improves the learning and memory abilities of mice injected with Aβ1-42 in hippocampus,which might be related to the attenuation of oxidative stress and neuronal inflammation of hippocampus.

OBJECTIVE To evaluate the effect of Qishen Yizhi formula on improving learning and memory ability in D-galactose subcutaneous injection induced subacute aging mice.METHODS Subacute aging mice model mice were developed by D-galactose subcutaneous injection and then treated with positive drug donepezil(2 mg·kg-1·d-1)and Qishen Yizhi formula water extracts in low(1.33 g·kg-1·d-1)and high dose group(2.67 g·kg-1·d-1).The learning and memory abilities of mice were evaluated using Morris water maze and Y maze tests;HE staining was used to examine hippocampal damage in model mice;TUNEL was used to detect apoptosis of mouse hippocampal tissue;ELISA was used to detect the expression levels of oxidative stress factors and inflammatory fac-tors in the mouse hippocampus tissue;Western blot was used to detect the expression of signaling pathway proteins related to apoptosis,oxidative stress and inflammatory stress in the hippocampus of mice.RESULTS The water extract of Qishen Yizhi formula signifi-cantly shortened the latency and distance of model mice for reaching the platform in the water maze test(P<0.01),and significantly increased the number of crossing the platform(P<0.01);increased the exploration time and number of the Y maze new arm in model mice(P<0.05);inhibited the TUNEL fluorescence expression in the hippocampus of model mice(P<0.01);upregulated the activity of the oxidative stress factor superoxide dismutase(SOD)(P<0.05)and glutathione(GSH)content(P<0.05),and downregulated malondialdehyde(MDA)content(P<0.05);reduced interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF-α)expression levels(P<0.05,P<0.01);decreased the expression of apoptosis signaling pathway proteins Cleaved Caspase-3 and Caspase-3(P<0.05),upregulated the expression of oxidative stress signaling pathway proteins Nrf2 and HO-1(P<0.05),and downregulated the expression of inflammatory stress signaling pathway proteins p-NF-κB and NF-κB(P<0.05).CONCLUSION Qishen Yizhi for-mula can improve the learning and memory ability of subacute aging model mice injected with D-galactose,which may be related to its inhibitory effect on hippocampal oxidative stress and inflammatory stress.

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.

As one of the imaging features of cerebral small vessel disease, white matter hyperintensity (WMH) of presumed vascular origin is quite common in the elderly. The burden of WMH is thought to progress slowly over time and is significantly associated with cognitive decline. However, the pathogenesis of WMH remains unclear and there is no effective treatment available. Recent studies have reported that some WMH lesions can regress during follow-up, along with progression and regression occurring alternately, suggesting that longitudinal changes in WMH are not unidirectional. This article presents a systematic review of current neuroimaging studies on WMH regression to enhance the understanding of dynamic changes in WMH and to provide new theoretical evidence for WMH intervention.

Objective:To prepare the modified hyaluronic acid viscous hydrogel loaded with sliver particles and to explore the roles and mechanism of the hydrogel in healing of full-thickness skin defect wounds with bacterial colonization in mice.Methods:The experimental research method was adopted. Dopamine modified hyaluronic acid (HA-DA) and phenylboric acid modified hyaluronic acid (HA-PBA) were prepared, and their characteristic peaks were detected by Fourier-transform infrared spectroscopy. Different mass of acrylamides was added to HA-DA and HA-PBA to prepare the viscous hydrogel with mass fraction of acrylamide in 10%, 15%, and 20%. The gelation of the viscous hydrogel with mass fraction of acrylamide in 20% was observed in the state of tilt and inversion at 37 ℃, and the storage modulus and loss modulus of the above 3 kinds of viscous hydrogels were detected by rotational rheometer. The sliver-loaded viscous hydrogel was prepared by adding nano silver ions to the viscous hydrogel with mass fraction of acrylamide in 20%. The concentration of silver ions released by sliver-loaded viscous hydrogel was measured by inductively coupled plasma mass spectrometer, and the cumulative release rate of silver ion was calculated ( n=5). The mouse fibroblasts L929 were divided into phosphate buffered saline (PBS) group, viscous hydrogel group, and sliver-loaded viscous hydrogel group, which were dealt correspondingly, and the cell survival was detected by cell counting kit 8 method after 1, 2, and 3 d of culture ( n=5). Twenty-four male C57BL/6 mice aged 6-8 weeks were selected, and forty-eight full-thickness skin defect wounds were inflicted and inoculated with the mixture of Escherichia coli and Staphylococcus aureus in the back of the mice, with two wounds in each mouse. The wounds were divided into normal saline group, viscous hydrogel group, and sliver-loaded viscous hydrogel group, which were dealt correspondingly, with 16 wounds in each group, and two wounds in each mouse were divided into different groups. On post injury day (PID) 3, 7, 10, and 14, the wound healing was observed and the wound healing rate was calculated. On PID 3, the colony forming units of Escherichia coli and Staphylococcus aureus in wounds were observed and counted. On PID 14, the epithelized epidermal thickness and the optical density of collagen fiber in wounds were observed and analyzed after hematoxylin eosin staining and Masson staining, respectively. On PID 3, 7, and 10, the expressions of tumor necrosis factor α (TNF-α), transforming growth factor β 1 (TGF-β 1), and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry. The number of wounds in each index detecting at each time point was four. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and Bonferroni correction. Results:The characteristic peaks of HA-PBA were detected at the wave numbers of 1 369 and 1 425 cm -1, indicating that phenylboric acid had been successfully grafted on hyaluronic acid, and the characteristic peaks of HA-DA were detected at the wave numbers of 1 516 and 1 431 cm -1, indicating that dopamine had been successfully grafted on hyaluronic acid. The viscous hydrogel with mass fraction of acrylamide in 20% maintained the stable and no-flow condition of gelation in the state of tilt and inversion at 37 ℃. The storage modulus and loss modulus of the viscous hydrogel increased with the increase of acrylamide content, the storage modulus and loss modulus of the 3 kinds of viscous hydrogels had no obvious changes with the increase of the oscillation frequency or time, and the storage modulus of the 3 kinds of acrylamide hydrogels were greater than the loss modulus. The release of silver ion in the sliver-loaded viscous hydrogel lasted for 7 days, and the cumulative release rate of silver ion was up to 65%. After 1, 2, and 3 d of culture, the cell survival rates in sliver-loaded viscous hydrogel group were significantly lower than those in PBS group and viscous hydrogel group ( P<0.05 or P<0.01), while after 1 d of culture, the cell survival rate in viscous hydrogel group was significantly lower than that in PBS group ( P<0.01). With extension of time after injury, the wounds of mice in the 3 groups shrank gradually. On PID 3, 7, 10, and 14, the wound healing rates in sliver-loaded viscous hydrogel group were (53.0±3.6)%, (75.3±6.9)%, (93.3±1.2)%, and (96.7±0.8)%, which were significantly higher than (21.8±6.4)%, (53.9±8.2)%, (72.0±7.8)%, and (92.5±0.4)% in normal saline group ( P<0.01). On PID 3 and 14, the wound healing rates in sliver-loaded viscous hydrogel group were significantly higher than (43.5±2.4)% and (94.1±1.5)% in viscous hydrogel group ( P<0.05). On PID 3 and 10, the wound healing rates in viscous hydrogel group were significantly higher than those in normal saline group ( P<0.01). On PID 3, the colony forming units of two bacteria in wound of sliver-loaded viscous hydrogel group were significantly less than those in normal saline group and viscous hydrogel group ( P<0.01), while the colony forming units of two bacteria in wound of viscous hydrogel group were significantly less than those in normal saline group ( P<0.05). On PID 14, the wounds were basically epithelialized and the epidermis was thicker, with collagen protein content being increased significantly and more orderly arranged collagen in sliver-loaded viscous hydrogel group compared with those in the other 2 groups. On PID 14, the epidermal thickness in wounds of sliver-loaded viscous hydrogel group was significantly increased compared with that in the other two groups ( P<0.05), and the optical density of collagen fiber was significantly increased compared with those in normal saline group ( P<0.05). On PID 3, the expressions of TGF-β 1 and VEGF in wounds of sliver-loaded viscous hydrogel group were significantly higher than those in normal saline group ( P<0.05 or P<0.01), while the expression of VEGF in wounds of viscous hydrogel group was significantly higher than that in normal saline group ( P<0.01). On PID 7, the expression of TGF-β 1 in wounds of sliver-loaded viscous hydrogel group was significantly higher than that in the other 2 groups ( P<0.01), and the expression of VEGF was significantly higher than that in normal saline group ( P<0.01). On PID 10, the expression of TNF-α in wounds of sliver-loaded viscous hydrogel group was significantly lower than that in normal saline group ( P<0.05), the expressions of TGF-β 1 and VEGF in wounds of sliver-loaded viscous hydrogel group were significantly higher than those in normal saline group ( P<0.05 or P<0.01), and the expression of VEGF in wounds of sliver-loaded viscous hydrogel group was significantly higher than that in viscous hydrogel group ( P<0.05). Conclusions:The sliver-loaded viscous hydrogel prepared in this study has good stability and elasticity, which can continuously release silver ions and help to accelerate the healing of full-thickness defect wounds with bacterial colonization in mice. Besides, the sliver-loaded viscous hydrogel has low biological toxicity and can promote re-epithelialization, collagen deposition as well as angiogenesis of wounds, which may be related to the infiltration and regression of inflammatory cells.

Objective:To evaluate the effect of mushroom-like pattern femtosecond laser enabled penetrating keratoplasty with different laser energies on the ring incision and corneal endothelial cells, and compare with conventional penetrating keratoplasty.Methods:According to the point/line separation and blasting energy, 48 porcine corneas were randomly divided into 6 groups by using a random number table.In group A, B, C, D and E, the point/line separation was 4/4, 4/4, 8/8, 8/8 and 4/2 μm, and the blasting energy was 1.5, 2.0, 1.5, 2.0 and 2.0 μJ; In group F, a negative pressure ring drill was used to make penetrating incisions.There were 8 porcine corneas in each group.Femtosecond laser of 200 kHz was used to make corresponding mushroom-shaped penetrating incisions on the porcine corneas, and compared with porcine corneas incisions with a ring drill.The optical and scanning electron microscope images were used to evaluate the glossiness of ring incisions.Four human corneas used femtosecond laser for mushroom-like penetrating incisions with point/line separation 8/8 μm, and blasting energy 2.0 μJ as the experimental group; three human corneas received a negative pressure ring drill for penetrating incisions as the control group.The loss rate of corneal endothelial cells was observed and compared between experimental group and control group.The donor guardians agreed to the acquisition and use of the donors' cornea and signed informed consents.This study protocol was approved by the Ethics Committee of Nanjing First Hospital.Results:Femtosecond laser mushroom penetrating ring incision completion rate was 100%.The corneal ring incision in each group was stepped, and sections of ring incisions in group A and group E were glossiest by the light microscope.Sections of ring incisions in group E were glossiest by the laser scanning electron microscope.The overall glossiness scores of the corneal ring incisions among various groups were statistically significantly different by the light microscopy ( F=22.75, P<0.01). Among them, the glossiness scores in the group A were higher than those in the group B, and the glossiness scores in the group C were higher than those in the group D, with statistically significant differences (both P<0.05). The overall glossiness scores of corneal ring incisions among various groups were statistically significantly different by laser scanning electron microscopey ( F=122.33, P<0.01). Among them, the glossiness scores in the group A were higher than those in the group B, and the the glossiness scores in the group C were higher than those in the group D, with statistically significant differences (both P<0.05). The corneal endothelial cells showed regular shape and tight arrangement in the experimental group, and irregular shape and loose connections were seen in the control group.The average corneal endothelial cell loss rate in the experimental group was (2.2±1.3)%, lower than (6.7±2.1)% of the control group, with a significant difference between them ( t=3.569, P<0.05). Conclusions:Femtosecond laser can produce perfect mushroom configuration, and the ring incision glossiness is better in comparison with trephine cutting.Femtosecond laser ring cut can lessen corneal endothelial loss.

Objective: To assess the effectiveness of seasonal influenza vaccine among children aged 6 to 72 months. Methods: The test-negative case control study was conducted based on available surveillance data which was from China Influenza Surveillance Information system (CSIS). From October 2016 to April 2017 and from October 2017 to April 2018,1 161 cases aged 6-72 months with influenza-like illness in Yongkang and Yiwu city, were selected as the study subjects, and the cases with influenza test-positive were selected as the case group (403 cases). Test-negative subjects were selected as control group (758 cases). The etiology and immunization data of the subjects were obtained from CSIS and Immune Information and Management System (IIMS) respectively. Vaccine effectiveness was estimated using multivariate logistic regression model,and the mixed effects of non-randomized control in TNCC study were equalized by using the propensity score (PS) method in the statistical analysis. Results: The age of the subjects was (2.44±1.60) years,and there were 681 boys (58.66%). The age of case group was (2.62±1.58) years, and there were 246 boys (61.04%). The case group was including of 237 cases (58.81%) of influenza A (H3N2), 92 cases (22.83%) of influenza A (H1N1) pmd09, 62 cases (15.38%) of influenza B(Victoria) lineage, 11 cases (2.73%) of influenza B (Yamagata) lineage and one case (0.25%) co-infection of influenza [A(H₃N₂)+B (Victoria)]. The mean age of the control group was (2.35±1.61) years,and there were 435 boys (57.39%). Overall vaccine effectiveness (VE) against all type influenza for two seasons combined was 58% (95%CI: 31%-74%). An analysis by age groups showed 68% (95%CI:41%-82%) of the VE estimate among children aged 36-72 months while it was 28%(95%CI:-80%-71%)of the VE estimate among children aged 6-35 months. The VE estimate value was 54% (95%CI:16%-75%) against all type influenza and 65% (95%CI:24%-83%) against influenza A (H₃N₂) during the 2016-2017 season. During the 2017-2018 season, the VE estimate value was 69% (95%CI:18%-88%) against all type influenza. Conclusion Influenza vaccine is effective in preventing influenza virus infection during the flu season,especially the effect among children aged 36-72 months is higher compared to that among children aged 6-35 months.

Objective To assess the effectiveness of seasonal influenza vaccine among children aged 6 to 72 months. Methods The test?negative case control study was conducted based on available surveillance data which was from China Influenza Surveillance Information system (CSIS). From October 2016 to April 2017 and from October 2017 to April 2018,1 161 cases aged 6-72 months with influenza?like illness in Yongkang and Yiwu city, were selected as the study subjects, and the cases with influenza test?positive were selected as the case group (403 cases). Test?negative subjects were selected as control group (758 cases). The etiology and immunization data of the subjects were obtained from CSIS and Immune Information and Management System (IIMS) respectively. Vaccine effectiveness was estimated using multivariate logistic regression model,and the mixed effects of non?randomized control in TNCC study were equalized by using the propensity score (PS) method in the statistical analysis. Results The age of the subjects was (2.44±1.60) years,and there were 681 boys (58.66%). The age of case group was (2.62±1.58) years, and there were 246 boys (61.04%). The case group was including of 237 cases (58.81%) of influenza A (H3N2), 92 cases (22.83%) of influenza A (H1N1) pmd09, 62 cases (15.38%) of influenza B(Victoria) lineage, 11 cases (2.73%) of influenza B (Yamagata) lineage and one case (0.25%) co?infection of influenza [A(H3N2)+B (Victoria)]. The mean age of the control group was (2.35±1.61) years,and there were 435 boys (57.39%). Overall vaccine effectiveness (VE) against all type influenza for two seasons combined was 58% (95%CI: 31%-74%). An analysis by age groups showed 68% (95%CI:41%-82%) of the VE estimate among children aged 36-72 months while it was 28%(95%CI : -80%-71%)of the VE estimate among children aged 6-35 months. The VE estimate value was 54% (95%CI:16%-75%) against all type influenza and 65% (95%CI:24%-83%) against influenza A (H3N2) during the 2016-2017 season. During the 2017-2018 season, the VE estimate value was 69% (95%CI: 18%-88%) against all type influenza. Conclusion Influenza vaccine is effective in preventing influenza virus infection during the flu season,especially the effect among children aged 36-72 months is higher compared to that among children aged 6-35 months.

Objective To assess the effectiveness of seasonal influenza vaccine among children aged 6 to 72 months. Methods The test?negative case control study was conducted based on available surveillance data which was from China Influenza Surveillance Information system (CSIS). From October 2016 to April 2017 and from October 2017 to April 2018,1 161 cases aged 6-72 months with influenza?like illness in Yongkang and Yiwu city, were selected as the study subjects, and the cases with influenza test?positive were selected as the case group (403 cases). Test?negative subjects were selected as control group (758 cases). The etiology and immunization data of the subjects were obtained from CSIS and Immune Information and Management System (IIMS) respectively. Vaccine effectiveness was estimated using multivariate logistic regression model,and the mixed effects of non?randomized control in TNCC study were equalized by using the propensity score (PS) method in the statistical analysis. Results The age of the subjects was (2.44±1.60) years,and there were 681 boys (58.66%). The age of case group was (2.62±1.58) years, and there were 246 boys (61.04%). The case group was including of 237 cases (58.81%) of influenza A (H3N2), 92 cases (22.83%) of influenza A (H1N1) pmd09, 62 cases (15.38%) of influenza B(Victoria) lineage, 11 cases (2.73%) of influenza B (Yamagata) lineage and one case (0.25%) co?infection of influenza [A(H3N2)+B (Victoria)]. The mean age of the control group was (2.35±1.61) years,and there were 435 boys (57.39%). Overall vaccine effectiveness (VE) against all type influenza for two seasons combined was 58% (95%CI: 31%-74%). An analysis by age groups showed 68% (95%CI:41%-82%) of the VE estimate among children aged 36-72 months while it was 28%(95%CI : -80%-71%)of the VE estimate among children aged 6-35 months. The VE estimate value was 54% (95%CI:16%-75%) against all type influenza and 65% (95%CI:24%-83%) against influenza A (H3N2) during the 2016-2017 season. During the 2017-2018 season, the VE estimate value was 69% (95%CI: 18%-88%) against all type influenza. Conclusion Influenza vaccine is effective in preventing influenza virus infection during the flu season,especially the effect among children aged 36-72 months is higher compared to that among children aged 6-35 months.