Objective:To evaluate the efficacy and safety of eculizumab in treating acute attacks of aquaporin-4 antibody(AQP4-IgG)positive neuromyelitis optica spectrum disorder(NMOSD).Methods:Six patients with AQP4-IgG-positive NMOSD treated with eculizumab at the Affiliated Hospital of Qingdao University from August 2023 to April 2024 were included.The patients' clinical characteristics, changes in scores of neurological function, pain and spasm before and after eculizumab treatment, and adverse drug reactions during the treatment period were described, and the data were subjected to Friedman test using SPSS 25.0.Results:The median score of expanded disability status scale in the six patients decreased from 3.25 before treatment to 1.25 after treatment, and the difference was statistically significant ( F=44.77, P<0.01).The functional status score showed noticeable improvement as early as week 1, demonstrating greater sensitivity to treatment response.Three patients experienced moderate to severe pain before treatment, with a mean pain score of 6, which reduced to 4.67 and 1.33 at week 2 and 6, respectively( F=29.17, P<0.05).Two patients reported spasms before treatment, with a mean score of 3.00, which decreased to 2.00, 1.50, and 1.00 at week 2, 3, and 6 after treatment, respectively( F=18.00, P>0.05).No serious adverse reactions were reported during the treatment. Conclusion:Eculizumab can effectively improve the neurological function and alleviate pain in patients with AQP4-IgG-positive NMOSD during acute attacks, and demonstrate good safety.

Objective:To evaluate the efficacy and safety of eculizumab in treating acute attacks of aquaporin-4 antibody(AQP4-IgG)positive neuromyelitis optica spectrum disorder(NMOSD).Methods:Six patients with AQP4-IgG-positive NMOSD treated with eculizumab at the Affiliated Hospital of Qingdao University from August 2023 to April 2024 were included.The patients' clinical characteristics, changes in scores of neurological function, pain and spasm before and after eculizumab treatment, and adverse drug reactions during the treatment period were described, and the data were subjected to Friedman test using SPSS 25.0.Results:The median score of expanded disability status scale in the six patients decreased from 3.25 before treatment to 1.25 after treatment, and the difference was statistically significant ( F=44.77, P<0.01).The functional status score showed noticeable improvement as early as week 1, demonstrating greater sensitivity to treatment response.Three patients experienced moderate to severe pain before treatment, with a mean pain score of 6, which reduced to 4.67 and 1.33 at week 2 and 6, respectively( F=29.17, P<0.05).Two patients reported spasms before treatment, with a mean score of 3.00, which decreased to 2.00, 1.50, and 1.00 at week 2, 3, and 6 after treatment, respectively( F=18.00, P>0.05).No serious adverse reactions were reported during the treatment. Conclusion:Eculizumab can effectively improve the neurological function and alleviate pain in patients with AQP4-IgG-positive NMOSD during acute attacks, and demonstrate good safety.

The emergence of high virulent mutant strains of infectious bursal disease virus(IBDV)becomes a serious threat to the poultry industry.However,the live attenuated IBDV vaccine can potentially revert to a virulent strain.Therefore,it is a necessary to develop safe and effective IB-DV-associated vaccines.The construction of a recombinant Marek's disease(MD)vaccine strain,CVI988,expressing the IBDV VP2 protein,can protect against disease induced by both IBDV and Marek's disease virus(MDV).Here,the IBDV-VP2 gene was integrated into the UL55 locus of CVI988 by bacterial artificial chromosome(BAC)technique,resulting in the recombinant virus CVI988 BAC-VP2.The recombinant virus was characterized by PCR,IFA and subsequently the bi-ological properties of the recombinant virus were investigated.The results showed that the recom-binant virus CVI988 BAC-VP2 was successfully rescued.The VP2 protein stably expressed in chick-en embryo fibroblasts(CEF).The growth kinetics and plague size assays showed that there was comparable replication ability between recombinant virus and parental virus.This study provides the basis for the development of a low-cost vaccine against both IBDV and MDV infections.

Based on the traditional Chinese medicine theory of"form,qi,and spirit"deeply explores the application mechanism of meridian guided lung function training in the treatment of post-stroke shoulder pain.Post stroke shoulder pain,as one of the common complications in stroke patients,not only brings great distress to their physical health,but also seriously affects their daily quality of life and rehabilitation process.This study reveals the multiple effects of meridian guided lung function training through theoretical analysis and practical verification.The research results indicating that this training method can not only effectively improve lung function,but also achieve the effect of reducing shoulder pain symptoms and accelerating the rehabilitation process by regulating qi and blood circulation,strengthening organ function,and promoting harmonious unity of mental will.The study elaborated on the implementation steps of the training method,including specific breathing techniques,posture adjustment,and mind guidance.In addition,the study theoretically explained the role of shape adjustment,qi adjustment,and spirit adjustment in treatment,such as optimizing shoulder structure,regulating breathing,promoting qi and blood circulation,and relieving mental stress.By combining specific case studies,the actual effect of this therapy in clinical treatment was demonstrated.Finally,the study not only summarized the unique advantages of this therapy,but also pointed out potential directions for future research,providing valuable references experience for subsequent medical exploration.The results of this study not only bring hope to patients with post-stroke shoulder pain,but also provide new ideas and methods for integrated traditional Chinese and Western medicine treatment,demonstrating the enormous potential of combining traditional medicine with modern science.

Based on the traditional Chinese medicine theory of"form,qi,and spirit"deeply explores the application mechanism of meridian guided lung function training in the treatment of post-stroke shoulder pain.Post stroke shoulder pain,as one of the common complications in stroke patients,not only brings great distress to their physical health,but also seriously affects their daily quality of life and rehabilitation process.This study reveals the multiple effects of meridian guided lung function training through theoretical analysis and practical verification.The research results indicating that this training method can not only effectively improve lung function,but also achieve the effect of reducing shoulder pain symptoms and accelerating the rehabilitation process by regulating qi and blood circulation,strengthening organ function,and promoting harmonious unity of mental will.The study elaborated on the implementation steps of the training method,including specific breathing techniques,posture adjustment,and mind guidance.In addition,the study theoretically explained the role of shape adjustment,qi adjustment,and spirit adjustment in treatment,such as optimizing shoulder structure,regulating breathing,promoting qi and blood circulation,and relieving mental stress.By combining specific case studies,the actual effect of this therapy in clinical treatment was demonstrated.Finally,the study not only summarized the unique advantages of this therapy,but also pointed out potential directions for future research,providing valuable references experience for subsequent medical exploration.The results of this study not only bring hope to patients with post-stroke shoulder pain,but also provide new ideas and methods for integrated traditional Chinese and Western medicine treatment,demonstrating the enormous potential of combining traditional medicine with modern science.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Background: The incidence rate and mortality of colorectal cancer (CRC) in China are increasing, and the age of onset is tending to be younger. Aims: To analyze the results of colonoscopy in patients positive for CRC screening, and to explore the significance of a CRC screening protocol that combines risk assessment questionnaire with fecal occult blood test (FOBT) in early diagnosis of colorectal neoplasms. Methods: Individuals who were positive for the first stage of screening (questionnaire + FOBT) in a community CRC screening program in Shanghai Huangpu District from May 2013 to October 2019 and then received the second stage of screening (colonoscopy) in Ruijin Hospital Luwan Branch were enrolled consecutively. Biopsy or polypectomy specimens were taken for pathological examination if any lesions were found endoscopically. Patients who underwent colonoscopy due to changes in bowel habits in the same period were served as controls. The detection rates of colorectal neoplasms in these two groups and the disease characteristics in the screening positive group were analyzed. Results: The screening positive group included 1 329 residents positive for the first stage of screening. The overall detection rate of colorectal lesions was 63.3%, and the detection rates of CRC, colorectal polyps and adenomatous polyps were 2.6% (34 cases), 60.7% (807 cases) and 35.2% (468 cases), respectively. While in control group (n=22 438), the rates were 43.6%, 1.8%, 41.5%, and 21.6%, respectively, all were significantly lower than those in screening positive group (all P<0.05). In screening positive group, the overall detection rate of colorectal lesions was higher in male than in female (73.7% vs. 54.2%, P<0.05) and increased with aging (P<0.05). Most of the CRC cases were in 60-79 years old age group with no gender difference. All CRC and most of the adenomas with dysplasia were greater than or equal to 1 cm in diameter, while most of the adenomas without dysplasia, hyperplastic polyps and inflammatory polyps were less than 1 cm in diameter. Conclusions: The community CRC screening program practiced in China can increase the detection rates of CRC and precancerous lesions effectively.

Objective:This study uses two markers of resting-state functional MRI (r-fMRI) to investigate changes in spontaneous neural activity and their correlation with postpartum depression (PPD) severity.Methods:A total of 15 individuals with PPD, who met the diagnostic criteria for DSM-5 unipolar depression, 24-Item Hamilton Depression Scale (HAMD 24) scores greater than 20, Edinburgh Postnatal Depression Scale (EPDS) score≥12, and 16 postpartum healthy mothers (control group) matched with age and education were examined using r-fMRI. Two-sample t-test was used to compare the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values between groups. Pearson correlation analysis was used to determine the correlation between the ALFF and ReHo of the abnormal brain region and the HAMD 24 and EPDS scores. Results:Compared with the healthy control (HC), PPD showed increased ALFF in the right cerebellum anterior lobe culmen and the left dorsolateral prefrontal cortex (DLPFC), and decreased ALFF in the right parietal lobe (individual voxel P<0.005, cluster size >10 voxels, Alphasim correction). PPD had increased ReHo values in the left superior?frontal?gyrus,?orbital?part, inferior?frontal?gyrus,?orbital?part, middle?frontal?gyrus, precuneus, inferior?parietal lobule than HC. Decreased ReHo values were found in the right inferior?occipital?gyrus, inferior?frontal?gyrus, frontal lobule and left cerebellum inferior semi-lunar lobule (individual voxel P<0.005, cluster size>10 voxels, Alphasim correction). The ALFF value of the left DLPFC was positively correlated with the HAMD 24 score in PPD ( r=0.585, P=0.022). Age, body mass index and education years of each subject was included as covariates, partial correlation coefficient was still statistically significant ( r = 0.561, P = 0.046). Conclusion:This r-fMRI study suggested that changes in the spontaneous neural activity of these regions were related to emotional responses. PPD cases with high ALFF values in the left DLPFC had severe depression.

Objective:This study uses two markers of resting-state functional MRI (r-fMRI) to investigate changes in spontaneous neural activity and their correlation with postpartum depression (PPD) severity.Methods:A total of 15 individuals with PPD, who met the diagnostic criteria for DSM-5 unipolar depression, 24-Item Hamilton Depression Scale (HAMD 24) scores greater than 20, Edinburgh Postnatal Depression Scale (EPDS) score≥12, and 16 postpartum healthy mothers (control group) matched with age and education were examined using r-fMRI. Two-sample t-test was used to compare the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values between groups. Pearson correlation analysis was used to determine the correlation between the ALFF and ReHo of the abnormal brain region and the HAMD 24 and EPDS scores. Results:Compared with the healthy control (HC), PPD showed increased ALFF in the right cerebellum anterior lobe culmen and the left dorsolateral prefrontal cortex (DLPFC), and decreased ALFF in the right parietal lobe (individual voxel P<0.005, cluster size >10 voxels, Alphasim correction). PPD had increased ReHo values in the left superior?frontal?gyrus,?orbital?part, inferior?frontal?gyrus,?orbital?part, middle?frontal?gyrus, precuneus, inferior?parietal lobule than HC. Decreased ReHo values were found in the right inferior?occipital?gyrus, inferior?frontal?gyrus, frontal lobule and left cerebellum inferior semi-lunar lobule (individual voxel P<0.005, cluster size>10 voxels, Alphasim correction). The ALFF value of the left DLPFC was positively correlated with the HAMD 24 score in PPD ( r=0.585, P=0.022). Age, body mass index and education years of each subject was included as covariates, partial correlation coefficient was still statistically significant ( r = 0.561, P = 0.046). Conclusion:This r-fMRI study suggested that changes in the spontaneous neural activity of these regions were related to emotional responses. PPD cases with high ALFF values in the left DLPFC had severe depression.

Objective The aim of this study was to investigate the effects of hesperidin ( HDN) on antioxidant ac-tivity in mice.Methods HDN scavenging free radicals was detected by spectrophotometry, inhibition of mitochondrial swelling was detected by pyrogallol autoxidation, and erythrocyte hemolysis was detected by Fe2+phenanthroline.The mice were fed with HDN at different concentrations (0, 80, 160, 320 mg/kg) by gastric gavage for 12 days.ELISA and spec-trophotometric methods were used to assay the amount of MDA in mouse liver and kidney tissues and the activity of antioxi-dant enzymes ( SOD, CAT, GSH-PX) , and the antioxidant enzyme gene mRNA expression was analyzed by RT-PCR.Re-sults Compared with the control group, the radical (· OH, O2 -· , DPPH· ) clearance rate was significantly increased in the HDN groups.There was a significant decrease of oxidative hemolysis of erythrocytes and mitochondrial swelling in vitro. MDA content in the mouse liver and kidney tissues and serum showed a decrease, and the activity of antioxidant enzymes ( SOD, CAT, GSH-PX) in the HDN group was significantly higher than that in the control group.There was an up-regula-tion of mRNA expression of antioxidant enzyme in mouse liver and kidney tissues.Conclusions The results showed that HDN can eliminate free radicals, reduce cell oxidative damage caused by free radicals, inhibit superoxide production, up-regulate antioxidant enzyme gene expression and enhance their enzyme activity, thus showing a good antioxidant effect.