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*

Objective:To investigate the tumor suppressing effect of Shenqi Yiliu decoction combined with cisplatin via ERK-mediated C-Myc/PD-L1 phase-coordinated pathway on H22 hepatocellular carcinoma tumor-bearing mice and its mechanism.Meth-ods:In 60 SPF-grade male Kunming mice,10 mice were taken as blank group by random number table method,and the other 50 mice were replicated as H22 hepatocellular carcinoma tumor-bearing mouse model.After successful replication of the model,the model mice were randomly divided into model group,cisplatin group[2.5×10-3 g/(kg·3 d)],Shenqi Yiliu decoction low[13.515 g/(kg·d)],me-dium[27.03 g/(kg·d-1)],and high dose[27.030 g/(kg·d)]combined with cisplatin group[2.5×10-3 g/(kg·3 d)],10 mice in each group were treated for 13 d.After 24 h of the last dose,the mice were anesthetized and sacrificed,and the tumor inhibition rate,spleen index and thymus index of each drug group were determined;HE staining was performed to observe the histopathological changes of tumor in mice;ELISA kit was used to detect the contents of EGF and IFN-γ in tumor tissue homogenate;p-ERK1/2,C-Myc and PD-L1 protein expression in tumor tissue were detected by IHC and Western blot;ERK,C-Myc and PD-L1 mRNA expression levels in tumor tissue were detected by RT-PCR.Results:Compared with blank group,the average body mass and spleen index of mice in model group were decreased(P<0.05).Compared with model group,the tumor inhibition effect of each treatment group was obvious,and Shenqi Yiliu decoction combined with cisplatin group inhibited tumor growth in liver cancer mice in a dose-dependent way,im-proved the average body mass,spleen index and thymus index of mice,promoted the necrosis of tumor cells and increased the necrotic area.EGF and IFN-γ contents,P-ERK1/2,C-Myc,PD-L1 protein expressions and ERK,C-Myc,PD-L1 mRNA expression levels were decreased in tumor tissues(P<0.05).Compared with cisplatin group,the therapeutic effect of Shenqi decoction combined with cisplatin in medium and high dose groups was significant,and the difference was statistically significant(P<0.05).Conclusion:Shenqi Yiliu decoction combined with cisplatin effectively inhibited the tumor growth of H22 liver cancer tumor-bearing mice and significantly reduces the expression of C-Myc and PD-L1 proteins in the tumor tissues,which may be through the regulation of ERK signaling path-way-related protein expression to exert tumor suppressive effect.

Objective:To investigate the efficacy of fixation through dual minimally invasive incisions and dual osseous channels with a loop titanium plate combined with a Dog-Bone titanium plate for acute Rockwood Ⅲ acromioclavicular dislocation in comparison with open reduction and fixation with a clavicular hook plate.Methods:A retrospective study was conducted to analyze the data of the 60 patients with acute type Ⅲ acromioclavicular dislocation who had been treated at Department of Orthopedics, Liaocheng People's Hospital from February 2019 to May 2022. There were 35 males and 25 females with an age of (43.2±8.0) years, and 34 left sides and 26 right sides affected. According to different surgical methods, they were divided into a double titanium plates group of 32 cases who had been treated by fixation through dual minimally invasive incisions and dual osseous channels with a loop titanium plate combined with a Dog Bone titanium plate and a hook plate group of 28 cases who had been treated by open reduction and internal fixation with a clavicle hook plate. The time from injury to operation was (2.1±1.3) d. The 2 groups were compared in terms of incision length, operation time, intraoperative bleeding, and visual analogue scale (VAS) pain score, Constant-Murley shoulder function score and the coracoclavicular distance on the affected side which were recorded preoperatively and at the last follow-up. Complications such as infection, loosening of internal fixation or secondary fracture were observed.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P > 0.05). All patients were followed up for (11.2±2.1) months. The incision length in the double titanium plates group [(3.5±0.3) cm] was significantly shorter than that in the hook plate group [(6.2±0.7) cm], and the intraoperative bleeding [(45.3±7.5) mL] in the former was significantly less than that in the latter [(64.1±6.2) mL] ( P < 0.05). However, there was no statistically significant difference in the operation time between the 2 groups ( P > 0.05). The VAS score [0.5 (0, 1.0) points] and Constant-Murley shoulder function score [(95.1±2.1) points] in the double titanium plates group were significantly better than those in the hook plate group [0.8 (0, 1.0) points, (86.0±4.4) points] at the last follow-up ( P < 0.05). However, there was no statistically significant difference between the 2 groups in the coracoclavicular distance on the affected side ( P > 0.05). Good acromioclavicular joint repositioning and fixation were achieved in all patients. There were no surgery-related complications except for sinus tract formation in one patient in the double titanium plates group. Conclusion:In the treatment of acute Rockwood Ⅲ acromioclavicular dislocation, fixation through dual minimally invasive incisions and dual osseous channels with a loop titanium plate combined with a Dog-Bone titanium plate is superior to open reduction and internal fixation with a clavicular hook plate, showing advantages of minimal invasion, better safety, less intraoperative bleeding, and faster joint function recovery.

In recent years, the prevalence of metabolic diseases, including obesity, diabetes, nonalcoholic fatty liver disease, and metabolic syndrome, increased significantly. Fatigue is common in metabolic diseases and may lead to functional disability. This complicated feeling imposes a huge influence on patients with metabolic diseases physically and psychologically, which seriously affects the quality of life and brings serious burden to the social economy. There were an increasing number of researches on fatigue and metabolic diseases. This article reviews the evidences of the linkages between fatigue and metabolic diseases.

Objective: To investigate neglect among preschool children in two-child families in southwest Shandong Province, and to provide reference is for improving nursing parenting quality of two-child families. Methods: A questionnaire survey was conducted among 2 646 parents of two-child families and 2 074 parents of one-child families from 16 kindergartens in southwest Shandong Province. Results: The total neglect rate of two-child family preschool children in southwest Shandong Province was 27.37%, and the degree score of neglect was(40.15±5.51). The physical neglect rate(10.39%), emotional neglect rate(40.15±5.51), total neglect (38.15±4.88) and emotional neglect (46.12±6.91) of boys were higher than those of girls, and the difference was statistically significant(χ2/t=4.57, 6.65, 4.58, 4.72, P<0.05); No significant frequencies were found in total neglect rate, total neglect, neglect rate and neglect at all levels among all age groups(P>0.05); Among preschool children with siblings aged 7-<13, ≥13, total neglect rate(30.44%, 32.77%), emotional neglect rate(10.20%,12.00%), total neglect degree (44.71±5.98, 45.33±5.20) and emotional neglect degree (45.95±7.12, 48.86±4.97) of preschool children in two-child families have higher than those in onechild families, and the differences were of statistical significance(χ2/t=31.10, 4.55, 27.92, 24.13, 19.83, P<0.05); the total neglect rate(27.37%), emotional neglect rate(23.47%), emotional neglect (43.68±6.83) of twochild families and the total neglect (40.15±5.51) were higher than those of one-child families, and the differences were of statistical significance(χ2/t=4.98, 4.96, 3.76, 8.53, P<0.05). The age of siblings(OR=0.58), the education level of mothers(OR=0.64), and the main executor of family education (OR=1.54) were main factors to influence the child neglect of preschool children in two-child families(P<0.05). Conclusion Neglect of preschool children in two-child families is higher than that in one-child families in southwest Shandong, especially among those preschool boys and preschool children whose siblings were of school age.

In the original publication the grant number is incorrectly published. The correct grant number should be read as "17140901600". The corrected contents are provided in this correction article. This work was partially supported by grants from the National Natural Science Foundation of China (Nos. 81670470 and 81600149), a grant from the Shanghai Municipal Commission for Science and Technology (17140901600, 18411953500 and 15JC1400201) and a grant from National Key Research and Development Program (2016YFC0905100).

Adenosine ; genetics ; Adenosine Deaminase ; genetics ; metabolism ; Animals ; CRISPR-Associated Protein 9 ; genetics ; metabolism ; CRISPR-Cas Systems ; genetics ; Embryo, Mammalian ; metabolism ; Gene Editing ; Genetic Variation ; genetics ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Sprague-Dawley

Objective To investigate the prognostic value of American Joint Committee on Cancer-tumor regression grading ( AJCC-TRG) combined with ypTN stage in patients with locally advanced rectal cancer (LARC),who were treated with neoadjuvant chemoradiotherapy,and to identify the subgroups with the worst prognosis. Methods A total of 263 patients with LARC,including 176 males and 87 females,with a median age of 55 years,were admitted to Sun Yat-sen University Cancer Center from 2004 to 2012.All the patients received neoadjuvant chemoradiotherapy before surgery and underwent total mesorectal excision at 6 to 8 weeks after radiotherapy. All the surgical specimens were reevaluated according to the AJCC ( 7th edition)-TRG system and ypTN staging criteria. The prognostic prediction by TRG combined with ypTN was evaluated using survival analysis. The Kaplan-Meier method was used to calculate the rates of overall survival ( OS ) , disease-free survival ( DFS ) , local recurrence-free survival ( LRFS ) , and distant metastasis-free survival ( DMFS ) . The log-rank test was used for survival comparison and univariate prognostic analysis. Results The median follow-up was 601 months. The 5-year rates of OS, DFS, LRFS, and DMFS for all patients were 800%,750%,970%,and 810%,respectively. There were significant differences in OS, DFS,and DMFS between different ypT/TRG subgroups and different ypN/TRG subgroups (all P<005). ypT3-4/TRG 2-3 and ypN1-2/TRG 2-3 subgroups showed the worst prognosis. The 5-year rates of OS,DFS, and DMFS of the two subgroups were 669%/560%, 522%/414%, and 609%/460%, respectively. Conclusions A combination of AJCC-TRG system and ypTN staging can better predict the prognosis of LARC and identify the subgroups with the worst prognosis, which may provide a clinical guidance for postoperative individualized decision on adjuvant therapy for LARC.

Objective To investigate the efficacy and toxicities of neoadjuvant chemoradiotherapy (neoCRT) in the management of unresectable locally advanced adherent colon cancer (LAACC).Methods A retrospective analysis was performed on the clinical records of 40 patients with initially diagnosed unresectable LAACC who received preoperative neoCRT in our center from October 2010 to December 2015.Results Thirty-nine patients completed the preoperative neoCRT.Thirty-four patients underwent radical resection after neoCRT, and the R0 resection rate, pathological complete response rate (pCR), tumor downstaging rate, nodal downstaging rate, and clinical downstaging rate were 91%, 24%(8/34patients), 76%(26/34patients),100%(32/32patients), and 94%(32/34patients), respectively.Among the 21 patients with bladder invasion, the full bladder was preserved in 7 patients (33%) and partial cystectomy was performed in 11 patients (52%).During the course of neoCRT, the grade 3-4 hematologic toxicity rate, grade 3 hand-foot syndrome rate, grade 3 radiodermatitis, and incomplete intestinal obstruction rate were 23%, 3%, 3%, and 5%, respectively.The 3-year sample size was 25 patients.For all the patients, the 3-year overall survival (OS) and progression-free survival (PFS) rates were 75% and 80%, respectively.Of the 34 patients who received surgical radical resection, the 3-year OS and disease-free survival (DFS) rates were 87% and 81%, respectively.In addition, local tumor recurrence was identified in 3 patients, and distant metastasis was identified in 6 patients.Conclusions NeoCRT is an effective treatment for unresectable LAACC that results in significant tumor downstaging and enhanced R0 resection rate without an increase in surgical complications.The patients treated with radical surgical resection after neoCRT show a satisfactory short-term outcome.Further studies will be required to determine the clinical value of neoCRT in treating LAACC.

Objective To systematically evaluate maternal perinatal complications and neonatal outcomes after in vitro fertili zation and embryo transplantation(IVF-ET).Methods The computer retrieval was performed on the databases of PubMed,Cochrane library,EMbase,CNKI,Wanfang and Chinese biomedical literature database.The articles on the comparison between IVF and natural pregnancy were included.The RevMan5.3 software was adopted to conduct the meta analysis.Results Twenty-three articles conforming to the requirements were included,including 1 312 651 cases,among them 113 044 cases were IVF and 1 199 607 cases were naturalpregnancy.IVF mother's age was larger than that of natural pregnancy,while the gestational weeks were smaller than those of natural pregnancy,the newborn birth weight was lighter than that of natural pregnancy(P＜0.05);the probability of pregnancy-induced hypertension (PIH),placenta previa,postpartum hemorrhage and gestational diabetes mellitus (GDM) occurrence in IVF mother were higher than that of natural pregnancy (P＜0.05);the rate of multiple and cesarean section in IVF mothers were higher than that of natural pregnancy (P＜0.05);the occurrence rates of small for gestational age(SGA),low birth weight infants,stillbirth and premature in IVF were higher than those of natural pregnancy (P＜0.05).Conclusion The maternal perinatal complications in IVF are higher than those of natural pregnancy,and the birth outcomes in IVF are worse than those of natural pregnancy.