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 analyze the clinical efficacy of low temperature plasma radiofrequency ablation(RFA)combined with nasal irrigation in the treatment of allergic rhinitis(AR)with nasal septal deviation.Methods A total of 120 AR patients with nasal septal deviation who were diagnosed and treated in Taikang Xianlin Drum Tower Hospital from August 2018 to December 2022 were selected as research objects.They were assigned to observation group or control group according to random number table method,with 60 cases in each group.The control group received nasal irrigation,and the observation group received low temperature plasma RFA and nasal irrigation.The efficacy,immunity,inflammation,quality of life,safety and prognosis were compared between the two groups.Results The observation group had better curative effect than the control group(P<0.05).The natural killer(NK)cells were increased,and the levels of immunoglobulin G(IgE),thymic stromal lymphopoietin(TSLP),hypoxia-inducible factor-1(HIF-1)and fractional exhaled nitric oxide(FeNO)were decreased in both groups after treatment.The level of NK cells in the observation group was higher than that in the control group after treatment,and the levels of IgE,TSLP,HIF-1,and FeNO in the observation group were lower than those in the control group(P<0.05).After treatment,the rhinoconjunctivitis quality of life questionnaire(RQLQ)scores decreased in both groups,and the scores in the observation group were lower than those in the control group(P<0.05).There was no significant difference in safety between the two groups(P>0.05).The control group had higher recurrence rate than the observation group(P<0.05).Conclusion Low temperature plasma RFA combined with nasal irrigation can effectively improve the immune function and inflammation of AR patients with nasal septal deviation,thereby improving the efficacy and quality of life,and reducing the recurrence rate,with high safety.

Objective To evaluate the influencing factors of aspiration in neurological critically ill patients by Meta-analysis.Methods PubMed,Embase,Web of Science,CNKI,and Wanfang Data were searched from inception to 1 October,2023,to obtain relevant studies on influencing fac-tors of aspiration in neurological critically ill patients.The literature screening,data extraction and quality evaluation were completed by two researchers.RevMan 5.4 and Stata 13.0 software were ap-plied for pooled Meta-analysisand assessed publication bias,respectively.Results A total of 8 arti-cles,including 1,315 neurocritical care patients,were included in this study.Nine influencing factors related to aspiration were extracted for Meta-analysis.The Meta-analysis results showed that the three influencing factors that caused aspiration in neurocritical care patients were stroke history(OR=5.03,95％CI,2.71 to 9.32,P＜0.000 01),National Institutes of Health Stroke Scale(NIHSS)score＞10(OR=3.35,95％CI,1.75 to 6.42,P=0.000 3),and gastric residual volume＞150mL(OR=7.13,95％CI,2.55 to 9.96,P=0.001).Conclusion This study provides a scientific basis for clinical healthcare professionals to early identify high-risk patients for aspiration,take targeted inter-vention measures,and prevent the occurrence of aspiration.

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.

OBJECTIVE To prepare Lanqin extract/cyclodextrin complexes for probing its effects of different kinds of cyclodextrins on the taste-masking. METHODS Bitter compounds in the extracts were performed on ion exchange resin adsorption combined with HPLC. The formulations of complexes were screened by human taste panel method. The complexes were prepared by spray-drying and characterized through scanning electron microscope, differential scanning calorimetry, and hygroscopicty test. Moreover, the in vitro bitter taste perception of complexes was evaluated by electronic tongue and further valuation the credibility of the results was conducted on human gustatory sensation tests. RESULTS The sulfobutylether-β-cyclodextrin-based combinational formulation with multiple cyclodextrins could significantly inhibit the bitter taste of the extract which mainly caused by its alkaline constituents at a lower dosage. The results of electron scanning microscopy, differential scanning calorimetry, and hygroscopicity indicated that the Lanqin extract and cyclodextrin in the complex may form inclusion complexes rather than physical mixtures. The results of electronic tongue and human gustatory sensation tests showed that, compared with the extract suggested the taste characteristics of the optimal complexes was similar to corresponding excipient while the bitterness significantly reduced. CONCLUSION The Lanqin extract/cyclodextrin complexes prepared in this study are suitable for industrial production for its good flavour, less total amount of cyclodextrins, and simple process. The present study has important significance for the development of related taste masking products of Lanqin.

In the context of high-quality development in medical institutions, the supply-processing-distribution(SPD) management mode has gradually been widely applied. The authors described in detail the procurement, supply, inventory, distribution, and settlement management of medical consumables and in vitro diagnostic reagents in a certain hospital under the SPD mode. It was found that SPD was conducive to strengthening the supervision of medical consumables and in vitro diagnostic reagents in the hospital, ensuring quality and safety of use, reducing hospital operating costs, and improving hospital′s competitiveness. However, attention should be paid to preventing data security risks, strengthening operational management, and improving the cost-benefit analysis of in vitro diagnostic reagents.

Objective To observe the effect of buccal needle therapy on perioperative analgesia in patients undergoing laparoscopic radical colon cancer surgery.Methods Sixty patients underwent dective laparoscopic radical of colon cancer surgery were selected,32 males and 28 females,aged 45-74 years,BMI 18.5-25.0 kg/m2 and ASA physical status Ⅱ or Ⅲ.The patients were divided into two groups using the randomized numerical table method:buccal needle group and control group,30 patients in each group.Before the induction of anesthesia,the buccal needle group was given buccal needle therapy once,and buc-cal needle therapy was performed once a day at 9 a.m.in the postoperative period,leaving the needle in place for 30 minutes each time,for 3 consecutive days of treatment,and the control group was not treated with buccal needle therapy.The amount of intraoperative propofol,remifentanil,sufentanil used in the 48 hours postoperative period and recorded.VAS pain scores were recorded at 1 hour,4,24,and 48 hours postoperatively.Venous blood was collected at the time of admission to the hand room and at 1 day,2,and 3 days postoperatively,respectively,and the concentrations of plasma C-reactive protein(CRP),interleu-kin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)were measured.The occurrence of adverse reactions within 48 hours after operation was recorded.Results Compared with the control group,intraop-erative propofol,remifentanil,the amount of sufentanil used and the number of analgesic pump presses with-in 48 hours after operation in the buccal needle group were significantly reduced in the buccal needle group(P＜0.05),VAS pain scores were significantly lower at 1 hour,4,24,and 48 hours postoperatively(P＜0.05),CRP,IL-6,and TNF-α concentrations were significantly lower at 1 day,2,and 3 days postopera-tively(P＜0.05),and nausea and vomiting,incidence of laryngospasm and laryngeal discomfort were sig-nificantly reduced(P＜0.05).Conclusion The perioperative use of buccal needle therapy in patients un-dergoing laparoscopic radical colon cancer surgery can effectively reduce pain,inhibit inflammatory respon-ses,and decrease the incidence of postoperative adverse reactions.

Objective:To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation (HSCT) model for patients with multiple myeloma.Methods:A total of 96 patients with newly diagnosed multiple myeloma (NDMM) between July 31, 2020, and December 31, 2022, were retrospectively analyzed, of which 41 patients in the observation group received integrated non-cryopreserved transplantation mode. After hematopoietic stem cells were mobilized and collected, melphalan was started immediately for pre-transplant conditioning, and non-cryopreserved grafts from the medical blood transfusion refrigerator were directly injected intravenously into the patient within 24-48 h after the melphalan conditioning. The control group consisted of 55 patients who received traditional transplantation mode. After hematopoietic stem cells were collected, stem cell cryopreservation was performed in liquid nitrogen, and then the transplant plans were started at the right time. All patients received mobilization of autologous hematopoietic stem cells using the G-CSF combined with the plerixafor.Results:① A total of 34 patients (82.9% ) with VGPR plus CR in the observation group were significantly higher than 33 patients (60.0% ) in the control group ( P=0.016). ②Compared with the control group, the incidence of grade 1 oral mucosal inflammation was higher in the observation group ( P<0.001) ; however, the incidence of grades 2 and 3 oral mucosal inflammation was lower ( P=0.004, P=0.048), and neither group experienced grade 4 or above oral mucosal inflammation. The incidence of grade 1 diarrhea was higher in the observation group ( P=0.002), whereas the incidence of grade 3 diarrhea was lower ( P=0.007). No statistically significant difference was observed in the incidence of grade 4 diarrhea ( P=0.506), and neither group experienced grade 5 diarrhea. ③ The incidence of bacterial infection in the observation group was lower than that in the control group (34.1% vs 65.5%, P=0.002), whereas no statistically significant difference was observed in the incidence of fungal infection (29.3% vs 31.4%, P=0.863) and viral infection (4.88% vs 3.64%, P=0.831). ④No statistically significant difference was observed in the implantation time of granulocytes and platelets between the observation and control groups [10 (8-20) days vs 11 (8-17) days, P=0.501; 13 (10-21) days vs 15 (10-20) days, P=0.245]. ⑤ All patients did not receive lenalidomide treatment 100 days post-transplantation. At 30 days post-transplantation, the CTL, NK, and Th cell counts in the observation group were lower than those in the control group ( P<0.001, P=0.002, P=0.049), and the NKT cell counts were higher than those in the control group ( P=0.024). At 100 days post-transplantation, the CTL, NKT, and Th cell counts in the observation group were higher than those in the control group ( P=0.025, P=0.011, P=0.007), and no statistically significant difference in NK cell counts was observed between the two groups ( P=0.396). ⑥ The median follow-up was 18 (4-33) months. The overall 2-year survival rates of the observation and control groups post-transplantation were 91.5% and 78.2%, respectively ( P=0.337). The recurrence-free survival rates were 85.3% and 77.6%, respectively ( P=0.386), and the cumulative recurrence rates were 9.8% and 16.9%, respectively ( P=0.373) . Conclusion:In NDMM, the cryopreservation-free integrated autologous HSCT model can achieve similar therapeutic effects as traditional transplantation models, with lower rates of severe mucosal inflammation and infection compared with traditional transplantation models.

[This corrects the article DOI: 10.1016/j.apsb.2021.03.043.].