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 effect of indigo on inflammatory factors and the aryl hydrocarbon receptor(AhR)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in lipopolysaccharide(LPS)-induced keratinocytes(HaCaT cells).Methods An LPS-induced HaCaT cell model was established,and experimental groups were set as follows:blank group,model group,indigo group,AhR agonist(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)group,AhR inhibitor(CH-223191)group,and indigo+AhR inhibitor group.The Cell Counting Kit-8(CCK-8)assay was used to detect the effects of different concentrations of indigo,TCDD,and CH-223191 on HaCaT cell viability after 24 hours of intervention.Quantitative real-time PCR(qPCR)was employed to measure the mRNA expression levels of interleukin-1β(IL-1β),nuclear factor kappa B(NF-κB),tumor necrosis factor-α(TNF-α),AhR,cytochrome P450 family 1 subfamily A member 1(CYP1A1),NLRP3,Caspase-1,and apoptosis-associated speck-like protein(ASC)in each group.Western Blot analysis was used to assess changes in the cellular localization of AhR protein expression.Results(1)The IC50 of indigo intervention in HaCaT cells was 118.7 μmol·L-1.Treatment with different concentrations of CH-223191 and TCDD for 24 hours had no significant effect on HaCaT cell viability.(2)Compared with the model group,the indigo group showed decreased mRNA expression levels of IL-1β,NF-κB,NLRP3,and Caspase-1(P＜0.05 or P＜0.000 1),while the mRNA expression levels of AhR and CYP1A1 were significantly increased(P＜0.05 or P＜0.000 1).(3)Compared with the blank group,the indigo group reduced cytoplasmic AhR protein expression and increased nuclear AhR protein expression(P＜0.001 or P＜0.000 1).(4)Compared with the model group,both the indigo group and the AhR agonist group significantly increased AhR mRNA expression levels(P＜0.05),while the AhR inhibitor group decreased AhR and CYP1A1 mRNA expression levels(P＜0.05)and increased IL-1β and NLRP3 mRNA expression levels(P＜0.05).(5)Compared with the AhR inhibitor group,the indigo+AhR inhibitor group showed increased mRNA expression levels of AhR and CYP1A1(P＜0.05)and decreased mRNA expression levels of NLRP3,Caspase-1,and IL-1β(P＜0.05).Conclusion Indigo reduces inflammatory factors in LPS-induced HaCaT cells and participates in inhibiting the occurrence and development of psoriasis by activating AhR to negatively regulate the NLRP3 inflammasome.

Objective:To explore the related factors affecting the prognosis of primary vulvar malignant tumors after initial treatment.Methods:The clinical and follow-up data of 228 patients with primary malignant tumor of the vulvar who received initial treatment at Liaoning Cancer Hospital from January 1,2005 to September 30,2018 were collected.Univariate and multivariate Cox regression analysis were used to identify factors affecting the overall survival rate(OS)of primary vulvar malignancies.Results:The median age of 228 patients of primary vulvar ma-lignant tumors was 55(15-80),with a median follow-up time of 78 months.The 3-year progression free survival(PFS)rate was 72.8％,the 3-year OS rate was 76.4％,the 5-year OS was 70.7％.The results of univariate anal-ysis showed that age,tumor diameter,lymph node metastasis,clinical stage and treatment method were all related to 5-year OS(P＜0.05),Multivariate COX regression analysis showed that age＞60 years(OR 3.96,95％CI 1.90-6.01),tumor diameter＞4 cm(OR3.58,95％CI 2.02-6.37),and lymph node metastasis(OR 1.85,95％CI 1.28-3.00)were independent risk factors affecting 5-year OS after initial treatment(P＜0.05).Conclusions:Age,tumor diameter and inguinal lymph node status are related factors that affect the prognosis of primary vulvar malignant tumors after initial treatment.If high-risk factors exist,such as lymph node metastasis after operation or large tumor lesions,it is recommended to supplement radiotherapy and chemotherapy to improve survival progno-sis.

Objective:To explore the related factors affecting the prognosis of primary vulvar malignant tumors after initial treatment.Methods:The clinical and follow-up data of 228 patients with primary malignant tumor of the vulvar who received initial treatment at Liaoning Cancer Hospital from January 1,2005 to September 30,2018 were collected.Univariate and multivariate Cox regression analysis were used to identify factors affecting the overall survival rate(OS)of primary vulvar malignancies.Results:The median age of 228 patients of primary vulvar ma-lignant tumors was 55(15-80),with a median follow-up time of 78 months.The 3-year progression free survival(PFS)rate was 72.8％,the 3-year OS rate was 76.4％,the 5-year OS was 70.7％.The results of univariate anal-ysis showed that age,tumor diameter,lymph node metastasis,clinical stage and treatment method were all related to 5-year OS(P＜0.05),Multivariate COX regression analysis showed that age＞60 years(OR 3.96,95％CI 1.90-6.01),tumor diameter＞4 cm(OR3.58,95％CI 2.02-6.37),and lymph node metastasis(OR 1.85,95％CI 1.28-3.00)were independent risk factors affecting 5-year OS after initial treatment(P＜0.05).Conclusions:Age,tumor diameter and inguinal lymph node status are related factors that affect the prognosis of primary vulvar malignant tumors after initial treatment.If high-risk factors exist,such as lymph node metastasis after operation or large tumor lesions,it is recommended to supplement radiotherapy and chemotherapy to improve survival progno-sis.

AIM: To investigate the efficacy of lacrimal duct laser dacryoplasty combined with intubation and postoperative meibomian gland treatment in patients with chronic dacryocystitis complicated by meibomian gland dysfunction.METHODS: Data were collected from 128 patients with chronic dacryocystitis complicated by meibomian gland dysfunction treated at Xi'an No.1 Hospital from March 2021 to December 2022. All patients underwent lacrimal duct laser dacryoplasty combined with intubation. Postoperatively, those patients were randomly divided into two groups: group A(64 cases, without meibomian gland treatment)and group B(64 cases, with meibomian gland treatment). The lacrimal intubation was removed at 3 mo after surgery to evaluate the patency rate of lacrimal irrigation. Additionally, changes in the ocular surface disease index(OSDI)score, non-invasive tear film break-up time, tear meniscus height, conjunctival hyperemia analysis, meibomian gland analysis, tear lipid layer thickness, tear ferning test, and conjunctival impression cytology were compared between the two groups.RESULTS: The lacrimal irrigation patency rates in the group A and group B were 78.1% and 81.2% respectively, with no statistically significant difference between the two groups(P>0.05); compared with the group A, group B showed a significant extension in non-invasive tear breakup time at 3 mo after surgery, and the OSDI score, conjunctival hyperemia analysis, tear ferning test and conjunctival impression cytology grading were all significantly decreased(all P<0.05), while there was no significant difference in tear meniscus height, tear lipid layer thickness and meibomian gland loss score between the two groups(all P>0.05).CONCLUSION: Comprehensive treatment for patients with chronic dacryocystitis combined with meibomian gland dysfunction have improved patients' comfort, tear film stability, and reduces local inflammatory response. It is important to simultaneously address ocular surface microenvironment abnormalities during surgical treatment to achieve satisfactory efficacy.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Objective:To explore the incidence and severity of esophageal clearance impairment in stroke survivors with dysphagia, the clinical characteristics of patients with abnormal esophageal clearance, and their relationship with swallowing physiology, penetration and aspiration.Methods:Clinical data were collected describing 174 stroke survivors whose swallowing had been studied videofluoroscopically. In each selected case there was a good anterior-posterior view of esophageal clearance. Their anterior-posterior and lateral imaging results while swallowing 5ml of high-consistency food were analyzed. The esophageal clearance item of the modified barium swallow impairment profile was then used to rate each subject′s esophageal clearance and each physiological component of swallowing in the oral and pharyngeal phases. The Rosenbek penetration aspiration scale was employed evaluate the safety of their swallowing.Results:Seventy of the patients (40.2%) displayed abnormal esophageal clearance, and more than half of the 70 (43 patients, 24.7%) showed mid- to distal esophageal retention. Those with abnormal esophageal clearance had a higher average age and more severe overall impairment in the pharyngeal phase of swallowing. Esophageal clearance was not, however, significantly correlated with swallowing physiology in the oral phase or with penetration or aspiration grade. There were, however, significant positive correlations with laryngeal elevation, anterior hyoid excursion, pharyngeal stripping waves, pharynx contraction, upper esophageal sphincter opening, tongue base retraction and pharyx residue.Conclusion:Stroke survivors with dysphagia may display abnormal esophageal clearance. The risk is closely related to age and the severity of the dysphagia. Abnormal physiology during the pharyngeal phase of swallowing and reduced pharyngeal stripping may predict abnormal esophageal clearance. Swallowing assessment can be made more comprehensiveness and systematic by incorporating anterior-posterior videography in routine barium swallowing studies.

Objective To summarize the electrophysiological indexes and scales used for evaluation of post-stroke spasticity, for integration of clinical management of spasms. Methods Literatures on identification and evaluation of post-stroke spasticity from databases of Web of Science, PubMed, CNKI, and Wanfang Data up to May 15, 2021 were retrieved and the indicators related to post-stroke spasticity were extracted for a scoping review. Results The scales of modified Asworth Scale, Comprehensive Spasticity Scale and modified Tardieu Scale; the electrophysiological indexes of F wave, H reflex, motor evoked potentials, visual-startle reaction time and vestibular evoked myogenic potentials were used to identify and evaluate post-stroke spasticity. Conclusion More clinical researches are needed to explore earlier identification and evaluation of post-stroke spasticity more objectively and accurately.

Objective:To study the characteristics and related factors of neonatal intestinal necrosis caused by midgut volvulus.Methods:We retrospectively analyzed the clinical data of neonates with midgut volvulus who were admitted to Guangzhou Women and Children's Medical Center, from January 2009 to December 2019 and confirmed by surgery. The cases with intestinal necrosis belong to the intestinal necrosis group, and those without intestinal necrosis, the non-intestinal necrosis group which was randomly sampled at a ratio of about 4∶1 to the number of cases in the intestinal necrosis group. The two groups were compared in terms of personal history, age of onset, initial symptoms, vital signs within 2 h after admission, time from symptom onset to operation, clinical outcome, laboratory indicators within 2 h after admission, etc. Multivariate Logistic regression analysis was used to screen the related factors of intestinal necrosis in midgut volvulus. The effective warning indexes are screened by receiver operating characteristic (ROC) curve.Results:(1) Among 231 cases of midgut volvulus, 21 cases (9.1%, 21/231) had intestinal necrosis at the time of operation, 87 cases were included in the non-intestinal necrosis group. (2) The levels of heart rate within 2 h after admission, mean arterial pressure, WBC, C reactive protein (CRP), blood glucose and potassium in intestinal necrosis group were significantly higher than those in non-intestinal necrosis group ( P<0.05). Admission days of age, hemoglobin, serum albumin, serum sodium, pH and BE levels were significantly lower than those in the group without intestinal necrosis ( P<0.05). (3) In the multivariate analysis, increased heart rate, mean arterial pressure, serum CRP, and decreased serum sodium, serum albumin, and pH levels were predictors related to intestinal necrosis in patients with midgut volvulus. (4) The area under the ROC curve (AUC) of CRP was 0.883, the cutoff value was 9.88 mg/L, the sensitivity was 76.2%, and the specificity was 94.3%. The ROC curve of serum albumin was 0.792, the cut-off value was 36.65 g/L, the sensitivity was 70.1%, and the specificity was 94.3%. Conclusions:Heart rate, mean arterial pressure, increased CRP, decreased serum sodium, serum albumin and pH are helpful to predict whether intestinal necrosis occurs in midgut volvulus, and CRP > 9.88 mg/L and serum albumin < 36.65 g/L are likely warning indicators.

Objective:To explore the expression and clinical significance of miR-143 in papillary thyroid cancer (PTC) .Methods:Tumor samples and adjacent tissues from 52 patients with PTC were obtained from Jan. 1st, 2018 to Mar. 31st, 2018 in Thyroid Surgery Department of the Affiliated Yantai Yuhuangding Hospital of Qingdao University. Quantitative reverse-transcriptase PCR (RT-qPCR) was used to measure the expression of miR-143 in those subjects. In addition, the relationship between the expression levels of miR-143 and the clinicopathological characteristics was analyzed.Results:RT-qPCR indicated that the expression of miR-143 was down-regulated in PTC, which was significantly lower than that in adjacent tissues ( t=-21.39, 95% CI: 18.20-15.07, P<0.001) . Low expression of miR-143 was related to the number of lymph node metastasis ≥3 in central compartment ( t=10.13, P=0.012) and lateral neck lymph node metastasis ( t=-4.67, P<0.001) . Conclusion:Downregulation of miR-143 in PTC is linked to the metastasis of PTC and may be a potential target for therapeutic intervention.