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*

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

This paper summarized professor WANG Shouchuan's experience in differentiating and treating children epistaxis from the perspective of "four excess and three deficiency". It is believed that the pathogenesis of children epistaxis is concluded as "four excess and three deficiency"， of which the four excess syndromes are exuberant heat in the lung channel， intense stomach fire， heart fire hyperactivity， and liver fire flaming upward， while the three deficiency syndromes include qi， yin and yang deficiency. Seven methods for treating children epistaxis are summarized. For exuberant heat in the lung channel syndrome， it is recommended to clear lung and direct qi downward， using self-made Xiebai Zhiniu Decoction （泻白止衄汤）. For intense stomach fire syndrome， the method of clearing stomach and draining fire can be used with self-made Qingwei Zhiniu Decoction （清胃止衄汤）. In terms of heart fire hyperactivity syndrome， it is better to clear heart and drain fire， using self-made Daochi Zhiniu Decoction （导赤止衄汤）. For liver fire flaming upward syndrome， it is advised to clear liver and drain fire， using self-made Yimu Zhiniu Decoction （抑木止衄汤）. In terms of qi deficiency syndrome， the method of fortifying spleen and boosting qi and containing blood should be used with self-made Futu Zhiniu Decoction （扶土止衄汤）. If there is yin deficiency syndrome， it is advised to supplement kidney， enrich yin and clear heat， using self-made Zishui Zhiniu Decoction （滋水止衄汤）. If there is yang deficiency syndrome， the method of boosting qi， warming yang and nourishing blood can be used， using self-made Wenpi Zhiniu Decoction （温脾止衄汤）.

Objective:To investigate the clinicopathological characteristics of gastrointestinal tumors with SWI/SNF complex deficiency and to perform a prognostic analysis of the patients.Methods:Gastrointestinal tumor cases with SWI/SNF complex deficiency expression diagnosed at the Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China from August 2021 to May 2023 were collected. Hematoxylin and eosin (HE) stained slides were reviewed, and immunohistochemical results were analyzed. Clinical and pathological information was recorded, and relevant literature was reviewed.Results:A total of 36 cases of gastrointestinal tumor with loss of SWI/SNF complex expression were identified, including 28 males (77.8%) and 8 females (22.2%). The average age at diagnosis was 70 years (range 48-85 years). Clinical staging showed 3 cases in stage Ⅰ (8.3%), 12 cases in stage Ⅱ (33.3%), 19 cases in stage Ⅲ (52.8%), and 2 cases in stage Ⅳ (5.6%). Complete or partial loss of ARID1A expression was observed in 20 cases (55.6%); complete or partial loss of SMARCA2 expression was observed in 24 cases (66.7%). SMARCA4 exhibited complete loss of expression in 4 cases (11.1%). Eleven cases (30.6%) showed concurrent complete or partial losses of both ARID1A and SMARCA2 expression. Twelve cases (33.3%) had mismatch repair protein deficiency, all of which were characterized by MLH1/PMS2 absence. Mismatch repair protein deficiency was associated with loss of ARID1A expression ( P<0.01). Patients with mismatch repair protein deficiency were also associated with earlier clinical stage and a lower risk of lymph node metastasis compared to the ones with intact mismatch repair proteins ( P<0.05). Conclusions:SWI/SNF complex deficiency in gastrointestinal tumors is associated with dedifferentiation and often accompanied by mismatch repair protein deficiency. Compared to the cases with intact mismatch repair proteins, the cases with defective mismatch repair protein have an earlier clinical stage and a lower risk of lymph node metastasis.

Objective:To discuss the differential effects of apolipoprotein E(APOE)gene polymorphism in the neurotoxicity-reactive astrocytes,and to provide the theoretical basis for the study of the pathogenesis of Alzheimer's disease(AD).Methods:The primary cortical astrocytes from the APOE-knockout mice(APOE-/-)were isolated and cultured in vitro,and the purity of the cells was identified by immunofluorescence staining.The human APOE3 and APOE4 recombinant over-expression plasmids were constructed and separately transfected into the primary APOE-/-astrocytes,and the APOE-/-primary cells were regarded as control.Western blotting method was used to detect the expression levels of APOE and glial fibrillary acidic protein(GFAP)proteins in the cells;enzyme-linked immunosorbent assay(ELISA)method was used to detect the APOE level in the cellular culture supernatant.The inflammatory models were prepared with the primary astrocytes transfected with APOE3 and APOE4 and co-stimulated with interleukin-1α(IL-1α),tumor necrosis factor(TNF),and complement C1q.The cells were divided into APOE3+PBS group,APOE4+PBS group,APOE3+IL-1α+TNF+ C1q group,and APOE4+IL-1α+TNF+C1q group.Cell immunofluorescence staining method was used to observe the morphology of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of glypican 4(Gpc4),glypican 6(Gpc6),thrombospondin 1(Thbs1),thrombospondin 2(Thbs2),SPARC-like protein 1(Sparcl1)and glial cell line derived neurotrophic factor(GDNF),C3,and S100 calcium binding protein B(S100B)mRNA in the cells in various groups;microsphere phagocytosis assay was used to detect the phagocytic capacities of the cells in various groups;Western blotting was used to detect the protein expression levels of B-cell lymphoma 2(Bcl-2),and cysteinyl aspartate specific protease-3(Caspase-3)proteins in the cells in various groups.Results:Compared with APOE-/-group,the expression levels of APOE and GFAP proteins in the cells and the APOE level in the cellular culture supernatant in transfected APOE3 and transfected APOE4 groups were increased(P<0.01).The fluorescence microscope observation results showed that compared with APOE3+PBS and APOE4+PBS groups,the astrocytic processes in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α+TNF+Cq1 group became shorter and the cell bodies became larger;compared with APOE3+IL-1α +TNF+Cq1 group,the astrocytic processes in APOE4+IL-1α +TNF+Cq1 group were even shorter.Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.05 or P<0.01).Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of GDNF mRNA in the cells in APOE3+IL-1α+TNF+Cq1 group and APOE4+ IL-1α +TNF+Cq1 group were decreased(P<0.01),and the expression levels of C3 and S100B mRNA were increased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression level of GDNF mRNA in the cells in APOE4+IL-1α+TNF+Cq1 group was decreased(P<0.05),and the expression levels of C3 and S100B mRNA were increased(P<0.05).Compared with APOE3+ PBS group and APOE4+PBS group,the numbers of hagocytosis of microspheres in the cells in APOE3+ IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased;compared with APOE3+IL-1α+TNF+Cq1 group,the number of hagocytosis of microspheres in the cells in APOE4+IL-1α+TNF+Cq1 group was significantly decreased.Compared with APOE3+PBS group and APOE4+PBS group,the expression levels of Bcl-2 protein in the cells in APOE3+IL-1α+TNF+ Cq1 group and APOE4+IL-1α +TNF+Cq1 group were decreased(P<0.05 or P<0.01)and the expression levels of Caspase-3 protein were significantly increased(P<0.01);compared with APOE3+ IL-1α+TNF+Cq1 group,the expression level of Bcl-2 protein in the cells in APOE4+IL-1α+TNF+ Cq1 group was decreased(P<0.01),and the expression level of Caspase-3 protein was increased(P<0.05).Conclusion:The APOE4 genotype has a stronger ability to induce the inflammatory factors compared with APOE3;it can lead to a neurotoxicity-reactive astrocyte phenotype,increase the neurotoxicity,affect the astrocyte apoptosis,and aggravate the neuron damage.

Objective To study the differences in the blood cell analysis of male officers and soldiers be-tween in the high altitude area station and low altitude area station in summer.Methods A total of 239 male officers and soldiers in the high altitude area(Amdo Xizang,average altitude 4 800 m)and 336 male officers and soldiers in the low altitude area(Nanjing,Jiangsu,average altitude 30 m)from July 18 to 24,2022 were selected as the study subjects and the differences in blood cell analysis parameters of male officers and soldiers stationed between at high altitude and low altitude areas were retrospectively analyzed.Results The eosino-phils percentage(EDS％),eosinophils count(EOS)in the high altitude group were significantly lower than thosein the low altitude group(P＜0.05),and the basophillic granulocyte percentage(BASO％),basophillic granulo-cyte count(BASO)and monocyte percentage(MONO％)were significantly higher than those in the low alti-tude group,and the differences were statistically significant(P＜0.05),but which in the both groups were in the normal reference ranges.The red blood cell count(RBC)hemoglobin(Hb)and hematocrit(HCT)in the high altitude group were significantly higher than those in the low altitude group(P＜0.05),moreover Hb and HCT in the high altitude group were in the upper limit of the medical reference range.The mean corpus-cular volume(MCV),mean corpuscular hemoglobin(MCH),mean corpuscular hemoglobin concentration(MCHC)and red blood cell distribution width-standard diviation(RDW-SD)in the high altitude group were lower than those in the low-altitude group(P＜0.05),but the both groups were in the normal reference ran-ges;there was no statistically significant difference in the erythrocyte distribution width coefficient of variation(RDW-CV)between the two groups(P＞0.05).The platelet(PLT)and thrombocytocrit(PCT)in the high altitude group were higher than those in the low altitude group,the platelet distribution width(PDW),mean platelet volume(MPV)and platelet large cell ratio(P-LCR)were lower than those in the low altitude group,and the differences were statistically significant(P＜0.05);PDW in the low-altitude group was at the upper limit of the medical reference range,and the other platelet-related indexes were in the normal range.Conclusion There are obvious differences in the blood cell analysis indicators of male officers and soldiers be-tween the high altitude area and low altitude area.

Objective To evaluate the value of red cell volume distribution width(RDW)in the prognosis of patients with cardiac arrest(CA).Methods Clinical data of 146 CA patients admitted to intensive care unit(ICU)of Huzhou Central Hospital from January 2018 to October 2022 were retrospectively analyzed,and the patients were divided into survival group and death group according to the prognosis during ICU stay.The clinical data of two groups were compared,and the risk factors affecting the prognosis of CA patients were analyzed by multivariate Logistic regression.Receiver operating characteristic(ROC)curve was used to evaluate the predictive efficacy of RDW in CA patients.The survival curve was plotted by Kaplan-Meier method.Results A total of 146 CA patients were included in the analysis,among which 49 patients survived and 97 patients died,the mortality rate of CA patients in ICU was 66.44%.The scores of acute physiology and chronic health evaluation Ⅱ,RDW,blood sodium and alanine aminotransferase in death group were significantly higher than those in survival group,the time of cardiopulmonary resuscitation was significantly longer than that in survival group,and the length of ICU stay was significantly shorter than that in survival group(P<0.05).Multivariate Logistic regression analysis showed that RDW and time of cardiopulmonary resuscitation were independent risk factors for predicting death during ICU stay in CA patients(P<0.05).ROC curve results showed that RDW predicted death in CA patients with the area under curve of 0.742,the best cut-off value was 13.95%,the sensitivity was 59.8%,and the specificity was 85.7%.Patients with low RDW had significantly higher one-year cumulative survival rate than those with high RDW(χ2=18.757,P<0.001).Conclusion RDW was an independent risk factor for predicting death during ICU stay in CA patients.

Objective: To explore the relationship between air pollutants and pediatric outpatient volumes in Baoshan District, Shanghai Municipality. Methods: Data of meteorological factors, air pollutants and pediatric outpatient volumes in four general hospitals were collected in Baoshan District from 2015 to 2019, and a generalized additive model was used to fit the Poisson-like distribution. The exposure-response relationship between fine particulate matter (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and total pediatric outpatient volumes and pediatric respiratory outpatients. Results: The median of the average daily temperature and relative humidity were 18.7 (interquartile range, 14.4) ℃ and 74.5% (interquartile range, 18.0%) in Baoshan District from 2015 to 2019, respectively. The median of the average daily concentrations of PM2.5, SO2, NO2 and O3 were 35.0 (interquartile range, 35.0), 11.0 (interquartile range, 7.0), 45.0 (interquartile range, 31.8) and 84.5 (interquartile range, 50.0) μg/m3, respectively. The median of the average daily total and respiratory pediatric outpatient volumes were 680 (interquartile range, 246) and 392 (interquartile range, 253). Spearman rank correlation analysis showed that temperature, relative humidity, PM2.5, SO2, NO2 and O3 were associated with total and respiratory pediatric outpatient volume (all P<0.05). Under the single pollutant model, the excess risk of total and respiratory pediatric outpatient volume due to PM2.5 (ER=0.318, 0.257), SO2 (ER=1.610, 2.546), and NO2 (ER=0.808, 0.839) reached the maximum effect on the same day, and the effect of O3 (ER=0.102, 0.222) reached its maximum at the first day of lag. Under the multi-pollutant model, after O3, SO2, NO2 and PM2.5 were introduced, a exposure-response relationship between air pollutants and total pediatric outpatient volumes was the largest on the sixth day after the lag (ER=0.419). There was no exposure-response relationship between air pollutants and respiratory pediatric outpatient volumes. Conclusion PM2.5, SO2, NO2 and O3 are associated with total and respiratory pediatric outpatient volumes, and the lag effects due to different air pollutants are different.

Objective: To investigate the characteristics and trend of stroke incidence in Jining City, Shangdong Province from 2015 to 2022, so as to provide the reference for formulating prevention and control strategies of stroke. Methods: Data of stroke incidence in Jining City from 2015 to 2022 were collected from Shandong Provincial Chronic Disease Surveillance Information Management System. The crude incidence was estimated, standardized using the data of the sixth national population census in 2010, and analyzed by age, gender and subtype. The trend in incidence of stroke was analyzed using annual percent change (APC). Results: A total of 316 267 cases of stroke were reported in Jining City from 2015 to 2022, with a crude incidence of 474.17/105 and a standardized incidence of 371.43/105. The incidence of stroke peaked from March to May (90 409 cases, 28.59%). There were 278 901 cases of ischemic stroke (88.19%) and 37 366 cases of hemorrhagic stroke (11.81%). The crude incidence of stroke was higher in males than in females (525.45/105 vs. 420.16/105, P<0.05). The crude incidence of stroke increased with age (P<0.05), reaching a peak in the age group of 80 years and above (2 764.92/105). From 2015 to 2022, the crude incidence of stroke in the overall population, males, females, the age groups of 0-<30 years and 40-<50 years showed increasing trends (APC=6.142%, 6.992%, 5.054%, 3.693% and 6.587%, all P<0.05); the crude incidence of ischemic stroke in the overall population, males and females showed increasing trends (APC=7.489%, 6.593% and 5.456%, all P<0.05), while the crude incidence rates of hemorrhagic stroke did not show significant trends (APC=3.455%, 2.804% and 1.919%, all P>0.05). Conclusions The crude incidence of stroke increased in Jining City from 2015 to 2022, with ischemic stroke as the predominant subtype. March to May was the peak period for disease onset, and young and middle-aged men should be focused on.

Objective:To investigate the correlation of the emm genotypes and virulence genes with the isolation sites of Group A Streptococcus (GAS). Methods:It was a retrospective study.The specimens were collected from children with impetigo in Beijing Children′s Hospital, Capital Medical University from 2006 to 2008 for GAS isolation and identification.A total of 24 GAS strains were isolated from 16 children with impetigo, among which 7 pairs of strains were isolated from the throat and skin of 7 children, and 1 pair of strains was isolated from the vulva and skin of one child, and the remaining 8 GAS strains were isolated from the skin pus samples of 8 children.Polymerase chain reaction was applied to detect the emm genotypes and 13 virulence genes ( speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa). The correlation of the emm genotypes and virulence genes with the isolation sites of GAS strains was analyzed. Results:In this study, four emm genotypes were detected, including emm1.0 (15/24), emm12.0 (4/24), emm22.0 (2/24) and emm160.0 (1/24), and one subtype emm12.19 (2/24) was detected as well.The carrying rates of 13 virulence genes speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa were 58.3%, 100%, 91.7%, 100%, 50.0%, 12.5%, 54.2%, 66.7%, 16.7%, 25.0%, 12.5%, 100% and 91.7%, respectively.All strains carried 5 to 11 virulence genes and they all carried speB, speF and smeZ.There were significant differences in the carrying rate of speA and speJ among the strains with different emm genotypes (all P<0.05). There was no significant difference in the distribution of virulence genes between skin isolates and pharyngeal isolates, including the 5 pairs of strains carrying the emm1.0 genotype (all P>0.05). Conclusions:The distribution of virulence gene of GAS in children with impetigo is significantly correlated with the emm genotype, rather than the isolation site.