Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objective:To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis.Methods:C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×10 6 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson′s trichrome to assess the extent of renal fibrosis. Results:Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×10 6 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group ( P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group ( P<0.05), but increased again upon addition of SC79. Conclusion:Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

OBJECTIVE: To analyze the clinical features and genetic basis for a Chinese pedigree affected with hereditary dyschromatosis symmetrica hereditaria (DSH). METHODS: Peripheral blood samples of the proband and his mother were collected and subjected to PCR and Sanger sequencing. RESULTS: The patient has conformed to the typical pattern of DSH and manifested with hyperpigmentation, hypo- and hyperpigmentation spots on the back of hands, feet and face. Sanger sequencing confirmed that the proband and his mother have both harbored heterozygous splicing variant c.2762+1G>T in exon 9 of the ADAR gene, which was unreported previously. The same variant was not detected among 100 healthy controls. According to the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PM2+PP4). CONCLUSION The c.2762+1G>T variant of the ADAR gene probably underlay the DSH in this pedigree. Above finding has enriched the spectrum of ADAR gene mutations.
Adenosine Deaminase/genetics* ; China ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

Objective:To compare the efficacy and safety of triamcinolone acetonide (TA) alone and in combination with 5-fluorouracil (5-FU) for treating keloids using meta-analysis.Methods:Databases including PubMed, Embase, and Cochrane Library were retrieved with the search terms of " triamcinolone acetonide, 5-fluorouracil, glucocorticoid, fluorouracil, keloid, scar, TAC, 5-FU, hypertrophic scar " and databases including Chinese Journal Full- Text Database, Chinese Biomedical Database, and Wanfang Data were retrieved with the search terms of "曲安奈德,瘢痕疙瘩, 5-氟尿嘧啶,糖皮质激素,增生性瘢痕" in Chinese to obtain the publicly published randomized controlled trials about the effects of TA alone and in combination with 5-fluorouracil for treating keloids from the establishment of each database to august 2019. The outcome indexes included effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion of keloids. RevMan 5.3 and Stata 14.0 statistical software were used to conduct a meta-analysis of eligible studies. Results:A total of 1 326 patients with keloids were included in 14 studies, including 668 patients in TA+ 5-fluorouracil group whose keloids were injected with TA and 5-fluorouracil and 658 patients in TA alone group whose keloids were injected with TA alone. A total of 7 articles achieved 1 to 3 points in modified Jadad score, while 7 articles achieved 4 to 7 points in modified Jadad score. Patients in TA+ 5-fluorouracil group had a higher effective proportion of treatment than that of TA alone group (relative risk=1.28, 95% confidence interval=1.16-1.41, P<0.01). Subgroup analysis showed that the quality of the included literature and ethnic factors might be the source of heterogeneity in effective proportion of treatment. Patients in TA+ 5-fluorouracil group had a lower incidence proportion of adverse reactions than that of TA alone group (relative risk=0.44, 95% confidence interval=0.25-0.75, P<0.01). Patients in TA+ 5-fluorouracil group had a lower recurrence proportion of keloids than that of TA alone group (relative risk=0.25, 95% confidence interval=0.14-0.44, P<0.01). There was no publication bias in incidence proportion of adverse reactions ( P>0.05), while the effective proportion of treatment and recurrence proportion of keloids had publication bias ( P<0.05). Conclusions:TA combined with 5-fluorouracil is more effective than TA alone for treating keloids, with less incidence of adverse reactions and recurrence.

Objective: To explore the imaging characteristics and related influencing factors of in-stent neoatherosclerosis (ISNA) in patients with restenosis after drug-eluting stent(DES) implantation with optical coherence tomography(OCT). Methods: A total of 25 cases of coronary heart disease patients(DES placement time ≥8 months) with coronary artery angiography showing DES in-stent restenosis (ISR) in Zunyi medical college affiliated hospital from July 2013 to December 2015 were included in this study and patient's data were retrospectively analyzed.In these patients with ISR, OCT images were acquired before percutaneous coronary intervention. Patients were divided into the ISNA group (12 patients and 12 lesions) and non-ISNA group(13 patients and 13 lesions) according to the result of OCT. ISNA on OCT was defined as neointima formation with the presence of lipids or calcification. Results: (1) The incidence of chronic kidney disease and increased low-density lipoprotein cholesterol level in ISNA group were significant higher than that in non-ISNA group(all P<0.05). The stent implantation time in ISNA group was longer than that in the non-ISNA group(53.0(14.0, 81.0) months vs. 15.0(8.5, 32.5) months, P<0.01). In addition, clinical manifestation of acute coronary syndrome was present in 8 out of 12 patientsin ISNA group, and stable angina pectoris was found in 10 out of 13 casesin non-ISNA group(P<0.01). (2) Quantitative analysis of OCT showed that the lumen area was less in ISNA group than in non-ISNA group((3.45±1.82)mm² vs. (4.17±1.68)mm², P<0.01), and neointimal area(3.89(2.26, 5.52)mm² vs. 2.96(1.99, 4.22)mm², P<0.01), neointimal load (53.15(40.18, 67.30)% vs. 41.54(32.08, 56.91)%, P<0.01), neointimal thickness(0.98(0.63, 1.36)μm vs. 0.72(0.51, 1.03)μm, P<0.01) were higher in ISNA group than in non-ISNA group.(3)Qualitative analysis of OCT showed that the prevalence of homogeneous intima was less in the ISNA group than in the non-ISNA group ((41.42±22.56)% vs.(72.06±18.68)%, P<0.05), on the contrary, the heterogeneous intima was more common in the ISNA group ((58.57±22.56)% vs. (27.94±18.68)%, P<0.05). There was no significant difference between two groups in the peri-stentmicrovessels (9/12 vs. 5/13,P>0.05), and prevalence of intraintimalmicrovessels was higher in the ISNA group than in non-ISNA group (7/12 vs. 2/13, P<0.05). In addition, thin cap fibrous plaque(7/12 vs. 0, P<0.01), disrupted intima with visible cavity (7/12 vs. 1/13, P<0.05),andintraluminal red thrombus(7/12 vs. 1/13, P<0.05) were significantly higher in ISNA group than in non-ISNA group. Conclusions Results of OCT show that ISNA occurs frequently in patients with ISR after DES implantation. The stent implantation time, incidence of chronic kidney disease and higher low-density lipoprotein cholesterol level are associated with the formation of ISNA in these patients.

Objective: To evaluate the effectiveness of mumps prevention and control after implementation of two doses mumps-containing combined vaccine (MuCV) policy by analyzing epidemiological characteristics of mumps and mumps antibody levels in general population. Methods: We obtained data on cases of mumps reported during 2004-2015 from National Notifiable Diseases Reporting System (NNDRS). Descriptive analysis methods were used to describe the epidemiological characteristics of mumps during 2004-2015. MuCV immunization information from 2005 to 2015 was obtained from the immunization information management system in Shandong Province. Antibody data of mumps in healthy people were from a cross-sectional survey according to the principle of stratified random sampling from 0 to 60 years old healthy people in 2015. Commercial ELISA kits were used to detect and quantify human IgG antibodies against mumps virus in sera, and the results were analyzed statistically. Results: The average incidence of mumps from 2004 to 2015 was 11.43/100 000 in Shandong. The incidence of mumps in the central region (14.64/100 000) was higher than that in the eastern and western regions (11.14/100 000, 11.33/100 000). The incidence of mumps was still high in 2009-2013 (stage of one-dose MuCV free, 16.07/100 000) with the highest incidence of 25.33/100 000 and 24.45/100 000 occurred in 2012 and 2013 and the cases were mainly 6 to 9 years old group (172.67/100 000). Since the second dose MuCV was introduced into NIP for 6 years old children in May 2013 in Shandong, the incidence of mump decreased significantly in 2014-2015 (7.81/100 000), especially in children of 6-8 years old who were vaccinated with two doses of MuCV (2009-2013 was 114.02/100 000; 2014-2015 was 45.66/100 000) and lower than 3-5 years old vaccinated one doses of MuCV. A total of 1 785 serum samples were collected from the healthy population, the average seroprevalence was 80.62% and Geometric Mean Concentration (GMC) was 38.11 IU/ml (95%CI: 37.03-39.19 IU/ml) . There was no significant difference about seroprevalence in different regions, while the GMC in middle region was significantly higher compared to east and west region. The prevalence and GMC in children aged 19 months-2 years and 3-5 years old who received one dose of MuCV were significantly higher than those of <19 months old children. The GMC (46.88 IU/ml, 95%CI: 39.43-55.74 IU/ml) in children aged 6-9 years old who received the two doses MuCV was significantly higher than that of aged 3-5 years old children (31.71 IU/ml, 95%CI: 27.23-36.93 IU/ml). Conclusion The incidence of mumps in Shandong was still at a high level in spite of coverage one doses MuCV to children. Compared with the period of the 1 dose MuCV immunization strategy, the incidence the groups coverage two doses MuCV was significantly reduced and lower the groups coverage one dose MuCV, but the prevalence and GMC were higher than that of the groups coverage one dose MuCV.

Objective To investigate the effects and mechanisms of HMGB-1 combined with MSCs transplantation on the heart function in rat with acute myocardial infarction.Methods A total of 144 male SD rats were divided into the healthy control group,model control group,MSCs transplantation group,HMGB-1 injection group,HMGB-1 injection+ MSCs transplantation group,HMGB-1 BoxA injection+MSCs transplantation group.On the 28th day after surgery,the heart function,myocardial pathological section,myocardial infarction area and new vessel density in infarction area were detected.Andthe level of related serum cytokines were measured on the 3rd,7th and 28th days after surgery.Results On the 28th day after surgery,left ventricular end diastolic dimension (LVDd) and left ventricular iiaternal diameter at end-systole (LVDs) in the HMGB-1 injection+ MSCs transplantation group were significantly decreased and the fractional shortening (FS) and ejection fraction (EF) value were significantly increased compared with the other five groups (P＜0.05);the infarction area in the HMGB-1 injection+MSCs transplantation group was significantly decreased and the new vessels number in the infarction area was significantly increased compared with the other model groups (P＜0.05).On the 3rd and 7th days after surgery,serum TLR4 and VEGF levels in the HMGB-1 injection+MSCs transplantation group were the highest (P＜0.05).On the 7th and 28th days after surgery,the levels of serum IL-6,NF-κB and TNF-α in the HMGB-1 injection+MSCs transplantation group were the lowest among all groups (P＜0,05).Conclusion HMGB-1 injection combined with MSCs transplantation treatment can effectively improve the prognosis of myocardial infarction.

Objective To analyze risk factors and complication characteristics of healthcare-associated infection (HAI)in patients with lung cancer,and provide evidence for the formulation of HAI management strategy. Methods HAI-related articles were retrieved from China Biology Medicine (CBM),China National Knowledge Infrastructure (CNKI),Wanfang database,Vip database,PubMed,and Embase,all data were conducted Meta-analysis.Results A total of 19 articles involving 8 069 hospitalized patients with lung cancer (1 280 had HAI)were included.Meta-analysis on combined values of medical factors for HAI were as follows:OR(95%CI )of anti-tumor therapy(radiotherapy and chemotherapy),number of chemotherapy (≥ 2 times ),antimicrobial prophylaxis, immunosuppressant therapy,and invasive operation were 3.13 (1 .82,5.39),9.20 (3.04,27.87),3.23 (1 .77, 5.91),2.00(1 .56,2.57),and 2.28(1 .81 ,2.88),respectively;Meta-analysis on combined values of complication factors for HAI were as follows:OR (95% CI )of pulmonary diseases,chronic obstructive pulmonary disease (COPD),diabetes,renal dysfunction,malnutrition,hypoalbuminemia,neutropenia,and leukopenia were 2.65 (1 .74,4.02),2.40 (1 .76,3.27),2.25 (1 .85,2.73 ),2.56 (1 .18,5.52),5.51 (1 .70,17.89),2.05 (1 .56, 2.70),3.38(1 .40,8.18),and 2.10 (1 .22,3.62),respectively.Conclusion HAI-related factors of medical treat-ment and complications in patients with lung cancer are diversity,risk factors for HAI in patients with lung cancer are anti-tumor therapy,immunosuppressant therapy,antimicrobial prophylaxis,invasive operation,pulmonary dis-eases,COPD,diabetes,renal dysfunction,malnutrition,hypoalbuminemia,neutropenia,and leucopenia.

Objective To investigate the variations of glomerular function in rabbits with partial unilateral ureteral obstruction (PUUO). Methods Thirty healty adult Japanese White Rabbits were randomly divided into the control group (6 rabbits) and the obstruction group (24 rabbits). The right PUUO model was established according to Cheng′s method. According to the PUUO duration, they were eaqually divided into four subgroups:the 7 day PUUO group, the 14 d PUUO group, the 28 d PUUO group and the 56 d PUUO group. The dynamic renal imaging was performed on all rabbits, and the glomerular filtration rate (GFR) was also calculated. The correlation between the renal function and PUUO duration was analyzed , and functional variations in the healthy kidneys were observed. Results (1)To the control group, no significant difference in the renal function was found between the left and the right kidneys (t = -0.145, P = 0.894). However, to the PUUO group, the right renal GFRs were significantly lower than the left renal GFRs (P < 0.05). (2) To the right renal GFR, significant difference was observed between the 7 day PUUO group and the control group (t = 5.066, P = 0.001),but not among the 7 day PUUO group, the 14 day PUUO group, the 28 day and the 56 day PUUO group (P > 0.05), (3)No significant differences were found in the left renal GFRs among the five groups. Conclusions The function of PUUO kidneys is characterized by an obvious decrease in the early stage, followed with a steady state. The basic function of the opposite healthy kidney does not present the compensation phenomenon.

Objective To provide the evidences for the management strategies of ventilator-associated pneumonia (VAP) in neonates,we systematically reviewed all related studies and analyzed the high-risk primary disease and medical factors of VAP in neonates.Methods We retrieved all related studies in CNKI,Wanfang,VIP,CBM,Pubmed and Embase and evaluated their quality by Newcastle-Ottawa Scale and analyzed all data by qualitative and Meta-analysis.Results There were 12 case-control studies with higher methodological quality and involving 1 994 neonates and with 708 VAP patients.Six studies involving 872 neonates were included,the odds ratio of respiratory distress syndrome(OR=2.81) and malnutrition(OR=5.18) had significant differences between VAP and non-VAP group.Seven studies involving 1 110 neonates were included and the odds ratio of patients with corticosteroids (OR=3.12),central inhibitors (OR=2.31),antacids (OR=4.35) and Gamma globulin with large doses (OR=2.35) had significant differences between VAP group and non VAP.Four studies involving 554 neonates were included and the odds ratio of patients with closed chest drainage (OR=1.81)and umbilical vein catheterization (OR=9.19) had significant differences between VAP group and non VAP.Six studies involving 1 139 neonates were included and the odds ratio of patients with parenteral nutrition (OR=1.82)and blood transfusions (OR=2.49) had significant differences between VAP group and non VAP.Conclusions Our study confirms that the respiratory distress syndrome and malnutrition corticosteroids,central inhibitors,antacids,Gamma globulin with large doses,closed chest drainage,umbilical vein catheterization,parenteral nutrition and blood transfusions are important risk and early-warning factors.