Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

Lung cancer is one of the most prevalent and the highest mortality rate malignancies,and its treatment landscape has undergone a disruptive transformation with the discovery and clinical application of immune checkpoint inhibitors.However,there still exists a number of patients who acquire resistance or fail to respond to these treatments,posing new challenges for lung cancer therapy.In light of this,there is an urgent need to actively explore and develop novel targets and innovative therapeutic strategies.This article aims to review the cutting-edge advancements in the novel immune checkpoint inhibitors,agonists,bispecific antibodies,adoptive cellular immunotherapy,and combination therapies involving immune checkpoint inhibitors,as well as to revisit existing related clinical trials along with their limitations,with the goal of advancing lung cancer immunotherapy towards a more personalized and precise approach.

Objectives: . The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. Methods: . The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. Results: . miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Conclusion . Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

Lung cancer is one of the most prevalent and the highest mortality rate malignancies,and its treatment landscape has undergone a disruptive transformation with the discovery and clinical application of immune checkpoint inhibitors.However,there still exists a number of patients who acquire resistance or fail to respond to these treatments,posing new challenges for lung cancer therapy.In light of this,there is an urgent need to actively explore and develop novel targets and innovative therapeutic strategies.This article aims to review the cutting-edge advancements in the novel immune checkpoint inhibitors,agonists,bispecific antibodies,adoptive cellular immunotherapy,and combination therapies involving immune checkpoint inhibitors,as well as to revisit existing related clinical trials along with their limitations,with the goal of advancing lung cancer immunotherapy towards a more personalized and precise approach.

Objective:To evaluate the emergency iliosacral screw fixation assisted by TiRobot for unstable posterior pelvic ring fracture.Methods:The 26 patients with unstable pelvic fracture were analyzed retrospectively who had undergone emergency iliosacral screw fixation at Department of Orthopedics & Traumatology, Beijing Jishuitan Hospital from June 2018 to December 2020. They were divided into 2 groups depending on whether orthopaedic TiRobot was used to assist screw insertion. In the observation group of 14 cases subjected to TiRobot-assisted insertion of iliosacral screws, there were 10 males and 4 females with an age of (45.9 ± 10.1) years; in the control group of 12 cases subjected to conventional manual insertion of iliosacral screws, there were 9 males and 3 females with an age of (49.2 ± 11.3) years. All the surgeries were conducted within 24 hours after injury. The 2 groups were compared in terms of screw insertion time, pin insertion, intraoperative blood loss, fluoroscopy time, postoperative screw position, fracture reduction and Harris hip score at the final follow-up.Results:The 2 groups were comparable because there was no significant difference between them in their preoperative general clinical data or follow-up time ( P>0.05). The screw insertion time [(16.1 ± 3.4) min] and fluoroscopy time [(8.1 ± 3.3) s] in the observation group were significantly shorter than those in the control group [(26.4 ± 5.4) min and (25.2 ± 7.4) s], and the pin insertions [1 (1, 2) times] and intraoperative blood loss [(10.5 ± 6.4) mL] in the former were significantly less than those in the latter [6 (3, 8) times and (24.8 ± 6.7) mL] (all P<0.05). Postoperatively, the sacroiliac screw position was excellent in 18 cases and good in 2 in the observation group while excellent in 14 cases, good in 2 and poor in 2 in the control group; the fracture reduction was excellent in 12 cases, good in one and fair in one in the observation group while excellent in 10 cases, good in one and fair in one in the control group, showing insignificant differences in the above comparisons ( P>0.05). There was no significant difference either in the Harris hip score at the final follow-up between the 2 groups ( P>0.05). Conclusion:Compared with conventional manual insertion of iliosacral screws, emergency iliosacral screw fixation assisted by TiRobot can effectively decrease surgical time and reduce operative invasion due to a higher accuracy rate of screw insertion.

BACKGROUND: The etiology of lumbar muscle strain is unclear, and it is a kind of specific disease. Lumbar muscles strain not only affects quality of life and work, but also causes heavy medical burden and indirect social costs. OBJECTIVE: To explore the effect of electropuncture and core strength training on lumbar muscle strain in college students. METHODS: The study was in accordance with the ethics requirements of Guangxi Normal University. Eighty college students with lumbar muscle strain were selected, and they signed the informed consents. The participants were randomized into control group (no intervention), electropuncture group, core strength training group, electropuncture with core strength training group. The intervention time was 7 weeks. The Visual Analogue Scale scores and pain system scores at baseline and after treatment were recorded. The recurrence was measured after 4 months of follow-up. RESULTSANDCONCLUSION: (1) The Visual Analogue Scale scores and pain system scores in the electropuncture, core strength training, and electropuncture with core strength training groups were significantly decreased compared with the baseline scores (P < 0.05). (2) The Visual Analogue Scale scores and pain system scores in the electropuncture, core strength training, and electropuncture with core strength training groups were significantly lower than those in the control group after intervention, and the scores in the electropuncture with core strength training group were significantly lower than those in the electropuncture and core strength training groups (P< 0.05). (3) The healing rate in the core strength training and electropuncture with core strength training groups was significantly higher than that in the electropuncture group, and the treatment efficacy in the core strength training and electropuncture with core strength training groups was significantly superior to the electropuncture group (P＜0.05). (4) The recurrence in the core strength training and electropuncture with core strength training groups was significantly lower than that in the electropuncture group (P＜0.05). (5) These results indicate that electropuncture and core strength training both have certain treatment efficacy for lumbar muscle strain in college students and core strength training is better than electropuncture, with lower recurrence. The synergistic effect of the combination of core strength training and electropuncture for lumbar muscle strain in college students is remarkable.

Objective To evaluate the clinical effect of early total care (ETC) for treatment of unstable pelvic fractures.Methods This retrospective case series study included eighteen patients with unstable pelvic fractures treated surgically from May 2013 to May 2015.There were 11 male and 7 female patients,aged (45.1 ± 13.1)years.Eleven patients were injured due to road traffic accidents and 7 due to fall from height.Tile B type pelvic fractures were seen in 8 patients and Tile C type in 10 patients.All patients were treated with ETC method and received open reduction and internal fixation within 24 to 48 hours after the primary treatment.Data were collected,such as operation time,intraoperative blood loss,hospital length of stay and perioperative complications.Majeed score and EuroQol 5 dimension (EQ-5D) were used for evaluation of clinical outcome and quality of life respectively.Excellent and good rate of operation was assessed using the Matta clinical evaluation standard.Results Three patients died and fifteen patients survived.Operation time was (120.1 ± 22.2)minutes,amount of intraoperative blood loss was (355.9 ± 56.4) ml,and hospitalization was (8.5 ± 1.6) days.Incidence of perioperative complications was 56％,including 3 patients with acute respiratory distress syndrome,1 pneumonia,2 acute lung injury,1 incisional wound infection,2 multiple organ failure and 1 diffuse intravascular coagulation.All patients were followed up for (15.1 ±2.4)months (range,12-21 months).Majeed score was decreased from preoperative (93.7 ± 6.1) points to final follow-up of (74.1 ± 9.2) points,and the EQ-5D index was decreased from preoperative 0.96 ± 0.04 to final follow-up of 0.74 ± 0.19 (both P ＜ 0.05).Excellent and good rate of operation was 80％.Conclusions ECT provides satisfactory short-term outcome for treatment of unstable pelvic fractures,but the incidence of complications is high.Doctors should choose reasonable treatment plan according to the surgical indications.

Objective To explore the management of postoperative infection following open reduction and internal fixation for acetabular fractures.Methods Ten patients were treated and completely followed up in Beijing Jishuitan Hospital from February 2012 to December 2016 for postoperative infection after open reduction and internal fixation for acetabular fracture.They were 9 males and one female,aged from 14 to 64 years(mean,40.6 years).According to Letournel classification,there were 2 double-column fractures,2 anterior descending transverse fractures,2 anterior column fractures,one posterior wall fracture,and one posterior wall fracture.Eight cases developed surgical regional infection within 2 weeks after internal fixation,and 2 presented with symptoms of infection more than 3 months after fracture fixation.Vacuum sealing drainage (VSD) was used to treat one case of acute superficial infection;open debridement surgery,carrier with sensitive antibiotics and intravenous antibiotics were used to treat 7 cases of acute deep infection and 2 cases of chronic deep infection.Results The infection symptoms disappeared 9 days after removal of VSD device in the one case of acute superficial infection.Normal fracture union was achieved in 6 cases after their infection was controlled;4 cases had to undergo total hip arthroplasty because their articular structure was damaged after control of infection.The 10 patients were followed up for 6 to 54 months (mean,25.7 months).Their Harris scores at the last follow-up averaged 74.8 (from 32 to 92).Conclusions Negative-pressure wound therapy is an effective management for acute superficial infection after acetabular fracture.Deep acute infection needs early repeated debridement combined with sensitive antibiotic carrier to protect joint function.For infection which is difficult to control or chronic infection associated with structural damage,repeated debridement combined with sensitive antibiotic spacer is effective for infection control at the first stage and artificial total hip arthroplasty can be carried out at the second stage when the infection is controlled.

Objective To present study was to investigate the effects of insulin-like growth factor binding protein 7 (IGFBP7)on the proliferation of human hepatocellular carcinoma HepG2 cells.Methods Human hepatocellular carcinoma HepG2 cells was cultured,and plasmid pIRES2-ZsGreen1-IGFBP7 or empty plasmid was transfected into HepG2 cells and the cell transfection efficiency was examined by fluores-cence microscopy;MTT was performed to evaluate the effect of IGFBP7 on proliferation and apoptosis of HepG2 cells in 48 hours after transfection.Results IGFBP7 transfected group decreased cell proliferation noticeably.Conclusions Overexpression of IGFBP7 can down-regulte the proliferation of human hepatocel-lular carcinoma HepG2 cells.

Objective:To evaluate the clinical significance of pattern visual evoked potential (P-VEP) parameters on amblyopic patients with normal-vision atfer pleoptic therapy. Methods:We investigated 60 amblyopic children (8-12 years old) who gained normal-vision atfer pleoptic therapy. hTese patients were assigned to a unilateral amblyopia group (40 patients)and a bilateral amblyopia group (20 patients). Another 20 healthy children served as a control group. All patients underwent a full initial ophthalmologic and orthoptic evaluation. P-VEP test was performed in all. Amplitude and latencies were analyzed and compared among groups. The latencies of P100 waves in the amblyopic eyes were used to generate a multiple linear regression formula from sex, ifrst treatment age, baseline visual acuity, and cycloplegic refraction. Results:hTere was no signiifcant difference in the mean levels of best-corrected visual acuity among groups (P>0.05). A signiifcant prolongation of the latency and a decrease of amplitude of P100 waves were observed in the unilateral amblyopia group and the bilateral amblyopia group compared with the healthy control group (P<0.05). Amplitude and latencies of the fellow eyes in the unilateral amblyopia group were abnormal compared with the healthy control group (P<0.05). Multiple linear regression analysis revealed that the latencies of P100 waves were signiifcantly correlated with the ifrst treatment age, baseline visual acuity, and cycloplegic refraction (R2=0.52, P<0.05). Conclusion:Deifcits exist in the fellow eyes and in normal-vision eyes atfer pleoptic therapy. hTe delayed P100 latency is affected by the ifrst treatment age, baseline visual acuity, and cycloplegic refraction. Traditional amblyopic therapy may be not enough for vision function recovery.