Accumulating evidence has indicated that the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis plays a crucial role in the recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) into lesion sites in animal models. The aim of this study was to investigate the effects of the SDF-1/CXCR4 axis on the migration of transplanted BMSCs mobilized by erythropoietin (EPO) toward the lesion site following spinal cord injury (SCI). A model of SCI was established in rats using the modified Allen's test. In the EPO group, EPO was administered at a distance of 2 mm cranially and then 2 mm caudally from the site of injury. In the BMSC group, 10 µl of BMSC suspension was administered in the same manner. In the BMSC + EPO group, both BMSCs and EPO were administered as described above. In the BMSC + EPO + AMD3100 group, in addition to the injection of BMSCs and EPO, AMD3100 (a chemokine receptor antagonist) was administered. The Basso-Beattie-Bresnahan (BBB) Locomotor Rating Scale and a grid walk test were used to estimate the neurological recovery following SCI. Enzyme-linked immunosorbent assay (ELISA) was performed to assess the tumor necrosis factor-α (TNF-α) and SDF-1 expression levels. An immunofluorescence assay was performed to identify the distribution of the BMSCs in the injured spinal cord. A Transwell migration assay was performed to examine BMSC migration. A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was performed to detect the apoptotic index (AI). Western blot analysis was performed to measure the expression levels of erythropoietin receptor (EPOR) and CXCR4. Significant improvements in locomotor function were detected in the BMSC + EPO group compared with the BMSC group (P<0.05). GFP-labeled BMSCs were observed and were located at the lesion sites. Additionally, EPO significantly decreased the TNF-α levels and increased the SDF-1 levels in the injured spinal cord (P<0.05).The AI in the BMSC + EPO group was significantly lower compared with that in the other groups (P<0.05). Furthermore, EPO significantly upregulated the protein expression of CXCR4 in the BMSCs and promoted the migration of the BMSCs, whereas these effects were markedly inhibited when the BMSCs were co-transplanted with AMD3100. The findings of the present study confirm that EPO mobilizes BMSCs to the lesion site following SCI and enhances the anti-apoptotic effects of the BMSCs by upregulating the expression of SDF-1/CXCR4 axis.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck region. Plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA (lncRNA), has been found to be overexpressed in multiple cancers, including OSCC. However, the upstream and downstream regulatory mechanisms through which PVT1 influences the malignant progression of OSCC remain to be further explored. In this study, PVT1 was confirmed to be overexpressed in OSCC tissues, and its roles in promoting OSCC cell proliferation, migration and invasion were identified. RNA-sequencing was used to screen the candidate target genes of PVT1, among which serpin family B member 4 (SERPINB4) was the most downregulated. SERPINB4 promoted OSCC cell proliferation, migration and invasion. In addition, mechanistic investigations demonstrated that PVT1 regulates SERPINB4 by sponging miR-185-5p in OSCC cells. Furthermore, SERPINB4 overexpression or miR-185-5p knockdown partly restores the decrease of OSCC cell proliferation and metastasis induced by PVT1 knockdown. Additional studies revealed that methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification induced the upregulation of PVT1 by stabilizing its RNA transcript. In conclusion, elevated expression of PVT1 in OSCC is associated with poor prognosis and promotes tumor development. METTL3 promotes PVT1 stability through m6A deposition and upregulates its expression in OSCC, which could upregulate SERPINB4 by sponging miR-185-5p, and ultimately promoting OSCC growth and metastasis. These findings suggest that PVT1 could serve as a potential biomarker and therapeutic target for OSCC.

Background: Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory disease which predominantly affects the spine and sacroiliac joints (SIJ) [1]. Ixekizumab, a high-affinity interleukin 17A (IL-17A) inhibitor, demonstrated efficacy (Assessment of SpondyloArthritis International Society 40 [ASAS40] response at Week 16) irrespective of elevated or normal/low inflammation at baseline [2]. The association of baseline inflammation status with efficacy endpoints in Chinese r-axSpA population has not been investigated. Objectives: To evaluate the association of the efficacy of ixekizumab in disease activity through Week 52 with the objective baseline inflammation status (measured by baseline c-reactive protein [CRP] level, Spondyloarthritis Research Consortium of Canada [SPARCC] magnetic resonance imaging [MRI] spine or SIJ inflammation score) in Chinese patients with r-axSpA. Methods: Chinese patients with r-axSpA, biologic-naive or tumor necrosis factor inhibitor (TNFi)-experienced, were enrolled in a phase 3, randomized, double-blind, placebo-controlled study (NCT04285229) and randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or placebo (PBO) for 16 weeks. At Week 16, patients receiving PBO were switched to IXEQ4W, and those receiving IXEQ4W continued, until Week 52. Subgroup analyses were performed through Week 52 for the intent-to-treat population by baseline CRP level (normal/low [≤5 mg/L] or elevated [>5 mg/L]), SPARCC MRI spine or SIJ inflammation score(<2 or ≥2). Baseline MRI was available in 98.6% of patients by central reading. Endpoints included response rates of ASAS40, Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50), Ankylosing Spondylitis Disease Activity Score (ASDAS)< 2.1. Non-responder imputation (NRI) was used for imputing missing responses. p-values for treatment comparison were based on Fisher's exact test for Week 0 - 16 data. p < 0.05 was considered statistically significant. Week 20-52 data were summarized descriptively. Results: Baseline characteristics were balanced between IXEQ4W and PBO groups [3]. Analyses results demonstrated that IXEQ4W provided significant improvement in ASAS40, BASDAI50, and ASDAS < 2.1 response rates compared with PBO at Week 16 within subgroups (except for ASAS40,BASDAI50, and ASDAS < 2.1 response rates within baseline SPARCC MRI spine score <2 subgroup [p=0.088, 0.104, and 0.203, respectively]) and efficacy sustained through Week 52, irrespective of the baseline CRP level, SPARCC MRI spine or SIJ score (Table 1 and Figure 1). Significant differences between IXEQ4W and PBO in the ASDAS < 2.1 response rates were observed as early as Week 1 across most of the subgroups (except for baseline SPARCC MRI spine score <2). Regardless of the baseline CRP level, SPARCC MRI spine or SIJ score, patients who initially received IXEQ4W had sustained improvements in ASDAS<2.1 response through Week 52; patients randomized to receive PBO and switched to IXEQ4W at Week 16 reported a rapid and sustained improvement through Week 52 after switching (Figure 1). Conclusion: IXEQ4W demonstrated rapid and sustained improvement in disease activity in Chinese patients with r-axSpA through Week 52 irrespective of baseline elevated or normal/low inflammation measured by CRP level, SPARCC MRI spine or SIJ score. These subgroup analyses results were generally consistent with those from overall population. REFERENCES: [1] Navarro-Compán V, Sepriano A, El-Zorkany B, van der Heijde D. Axial spondyloarthritis. Ann Rheum Dis. 2021;80(12):1511-1521. doi:10.1136/annrheumdis-2021-221035 [2] Maksymowych WP, Bolce R, Gallo G, et al. Ixekizumab in radiographic axial spondyloarthritis with and without elevated C-reactive protein or positive magnetic resonance imaging. Rheumatology (Oxford). 2022;61(11):4324-4334. doi:10.1093/rheumatology/keac104 [3] Xue Y, Hu J, Liu D, et al. Ixekizumab for Active Radiographic Axial Spondyloarthritis in Chinese Patients: 16- and 52-Week Results from a Phase III, Randomized, Double-Blind, Placebo-Controlled Study. BioDrugs. Published online September 22, 2023. doi:10.1007/s40259-023-00625-2 Acknowledgements: NIL. Disclosure of Interests: Ning Kong: None declared, Jiankang Hu: None declared, Dongzhou Liu: None declared, Jingyang Li: None declared, Lingyun Sun: None declared, Lie Dai: None declared, Chunyu Tan: None declared, Zhijun Li: None declared, Zhengyu Xiao: None declared, Yongfu Wang: None declared, Lijun Wu: None declared, Yan Yan Eli Lilly and Company, Eli Lilly and Company, Hongying Li Eli Lilly and Company, Eli Lilly and Company, Hejian Zou Eli Lilly and Company.

Given the intricate situation of modelling gigapixel images, the usage of multiple instance learning (MIL) framework has recently increased to support clinical practice, encompassing cancer diagnosis, subtyping, survival prediction and other tasks. In current practice, most state-of-the-art MIL proposals typically apply a frozen pre-trained CNN or a pathological foundation model for feature extraction. While this paradigm lacks the capability for sequence feature fine-tuning within the downstream-specific tasks, which hinders the continuous performance promotion in Whole Slide Images (WSIs) Analysis. To address this issue, we propose a Sequence Feature Reconstruction Transformer (SeqFRT) for optimizing feature extraction of the foundation model, which can capture more discriminative features within pathological instance sequences. The proposed model comprises three main modules: 1) an offline foundation model as the pathological feature extractor; 2) a sequence position optimization architecture which aims at refining the correlations between instances in both sequential ordering and transpositional ordering; 3) a sequence sparsity enhancement strategy is designed to reconstruct the sequence feature and extract the latent representations instead of redundant information. Extensive experiments on six benchmark datasets for three computational pathology tasks demonstrated our model’s superiority over the state-of-the-art MIL methods. The source code is available at https://github.com/caicai2526/SeqFRT-MIL.

IntroductionHuman oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and has a poor survival rate. Cell-cell communication between OSCC cells and cancer-associated fibroblasts (CAFs) plays important roles in OSCC progression. We previously demonstrated that CAFs promote OSCC cell migration and invasion. However, how OSCC cells influence CAFs proliferation is unknown.MethodsKnockdown of PVT1 was confirmed using lentivirus infection technique. CAFs in tissues were identified by staining the cells with alpha-SMA using immunohistochemical technique. CCK-8 assay was used to evaluate cell proliferation. The mRNA level of a gene was measured by qRT-PCR. Secreted TGF-beta were detected using ELISA assay.ResultsWe found that knockdown of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was associated with a low density of CAFs in xenograft tumors in mice; further analysis revealed that PVT1 in OSCC cells induced CAF proliferation through transforming growth factor (TGF)-beta.DiscussionOur results demonstrate that lncRNA PVT1 in tumor cells participates in CAF development in OSCC by regulating TGF-beta. This study revealed a new mechanism by which PVT1 regulates OSCC progression and PVT1 is a potential therapeutic target in OSCC

To evaluate the effect of enhanced recovery after surgery (ERAS)‐optimized management system with nurse‐led multidisciplinary cooperation.

Circular RNAs (circRNAs) are closely associated with the progression of oral squamous cell carcinoma (OSCC). circRNA_0001971 has been proved to accelerate the OSCC development. Here, we aim to identify the new molecular mechanism of hsa_circRNA_0001971 (circRNA_0001971) in OSCC.

目的:研究经超声支气管镜针吸活检(EBUS-TBNA)在老年纵隔及肺门病变中的诊断价值和安全性.方法:回顾分析武汉大学中南医院2017年1月至2021年4月52例纵隔、肺门淋巴结肿大或肺部占位病变并行EBUS-TBNA的老年患者(年龄在70岁及70岁及以上)的临床资料,并选取同期的年龄小于70岁的248例患者作为对照,统计分析EBUS-TBNA在老年患者诊断中的诊断价值及安全性.结果:52例70岁及以上的患者中,平均年龄为(75.2±4.0)岁,男性占76.9％,高血压、冠心病、慢性阻塞性肺疾病(COPD)和糖尿病的合并症比例分别为17.3％、13.4％、30.8％和9.6％,其中COPD患者的比例明显高于70岁以下的患者(16/36 vs 31/248,P＜0.01).EBUS-TBNA在70岁及以上的老年患者诊断的的敏感度为95.3％、特异度为100％;在安全性方面,52例老年患者中,穿刺点出血2例,一过性低血压2例,一过性心律失常4例,一过性低氧血症10例,二氧化碳升高4例,与70岁以下的患者相比,差异无统计学意义.结论:经超声支气管镜针吸活检在老年纵隔及肺部疾病中,具有良好的诊断价值和安全性.

Objective: This study aimed to explore the efficacy of oral implant restoration in dentition defects and the factors that influence the efficacy. Methods: 98 patients with dentition defects in our hospital were enrolled in this study. They were randomized into group A and group B. Group A received oral implant restoration treatment and Group B received denture restoration treatment. The efficacy and functions of language and chewing in the two groups before and after treatment were observed. The levels of TNF-alpha and IL-6 in gingival crevicular fluid were measured by enzyme-linked immunosorbent assay (ELISA). Results: After treatment, the scores of chewing and language functions of group A and group B increased significantly (P<0.001), and were higher in group A than in group B (P<0.001). Meanwhile, Group A showed lower TNF-alpha and IL-6 levels of gingival crevicular fluid than those of group B (P<0.001). The univariate analysis of logistic regression suggested that the course of disease, number of defects, treatment, TNF-alpha and IL-6 levels might affect the efficacy (P<0.05). Further multivariate analysis of logistic regression suggested that the course of disease, number of defects, treatment, TNF-alpha and IL-6 levels were the factors that influenced the efficacy (P<0.05). Conclusion: Oral implant restoration showed good outcomes in dentition defects. Chewing and language functions were improved and the inflammatory factors in the gingival crevicular fluid were down-regulated. The course of disease, the number of defects, the treatment of oral implant restoration and the levels of TNF-alpha and IL-8 are the factors that influence the efficacy of dentition defects.

目的 探讨阻塞型睡眠呼吸暂停低通气综合征(OSAHS)患者血中性粒细胞/淋巴细胞比值(NLR)水平与认知功能的关系.方法 将66例OSAHS患者分为轻度组(n=16)、中度组(n=15)和重度组(n=35),选择25例健康者作对照组.用多导睡眠监测仪(PSG)监测患者夜间睡眠呼吸暂停低通气指数(AHI)和最低血氧饱和度(LSaO2),采用MMSE和MoCA量表评判患者认知功能,检测4组NLR水平.分析认知功能量表评分、AHI、LSaO2与NLR之间相关性.结果 与对照组比较,中、重度组MMSE、MoCA评分降低;与轻度组比较,重度组MMSE、MoCA评分降低(P＜0.05);OSAHS患者MMSE、MoCA评分与AHI呈负相关(r=-0.472和-0.768,P＜0.05),与LSaO2呈正相关(r=0.672和0.741,P＜0.05).与对照组、轻度组比较,重度组NLR水平升高(P＜0.05).OSAHS患者NLR水平与AHI呈正相关(r=0.2594,P＜0.05),与LSaO2呈负相关(r=-0.2423,P＜0.05);OSAHS患者MMSE、MoCA评分与NLR呈负相关(r=-0.3225和-0.3299,P＜0.05).结论 OSAHS患者NLR水平随着AHI增加和缺氧程度加重而升高,NLR升高与认知功能下降具有相关性,早期对OSAHS患者NLR进行筛查,对病情评估具有一定参考价值.

•Circulating exosomal microRNAs provide new opportunities to unlock the secrets of hepatocellular carcinoma.•Both serum exosomes-encapsulated microRNAs and combined with traditional biomarkers improve diagnosis methods.•Strategies target exosomal microRNAs offer new tactics for treatment of hepatocellular carcinoma.

[目的]探讨建立集束化依从性表格对哮喘雾化吸入病人治疗依从性及预后的影响.[方法]选取本院收治的哮喘雾化吸入治疗病人92例,根据随机数字表法将病人分为观察组及对照组各46例,对照组实施常规护理,观察组建立集束化依从性表格对病人实施干预,比较两组病人治疗依从性、不良事件及预后情况.[结果]观察组病人治疗依从率、总有效率、治疗满意率高于对照组(P<0.05),而病人雾化吸入不良反应、意外事件、医疗纠纷发生率低于对照组(P<0.05).观察组病人喘息缓解时间、肺部哮鸣音消失时间、咳嗽消失时间、雾化吸入治疗时间及住院时间均短于对照组(P<0.05).[结论]集束化依从性表格的应用将有助于提高哮喘雾化吸入病人治疗依从性,降低病人治疗不良事件的发生,改善病人预后,提高病人治疗满意度.

目的:对确诊为颅骨锁骨发育不全(cleidocranial dysplasia,CCD)的先证者RUNX2基因测序,了解其序列特征,认识CCD分子生物学水平成因,扩充RUNX2基因序列大数据.方法:通过临床症状和X线检查,确诊了1例CCD先证者,抽取该先证者及其家庭成员的外周血进行基因分析.发现该先证者RUNX2基因转录过程中新的突变点,并针对该突变点,采用PCR方法进行基因扩增后,进行基因突变分析.结果:从这例先证者的基因中发现了1个新的突变点——7号外显子上有1种在正常家庭成员中的基因序列中并不存在的新的错义突变(c 895T>C,Y299H).此突变将导致密码子895(p Tyr 299 His)相对应的氨基酸发生变化,即从1个翻译成色氨酸的密码子(TAT)变成了1个翻译成组氨酸的密码子(CAT).结论:首次在1例中国CCD患者中发现7号外显子新的错义突变位点(c 895T>C),补充了CCD疾病相关基因RUNX2变异库.

Despite the successes of bone marrow mesenchymal stem cell (BMSC) transplantation for the treatment of spinal cord injuries, only a small fraction of grafted cells migrate to the target areas. Therefore, there remains a need for more efficient strategies of BMSC delivery. The present study was designed to explore this. Rat models of spinal cord injury (SCI) were established and exposed to phosphate buffered saline (control), BMSCs or BMSCs + erythropoietin (EPO). Basso, Beattie and Bresnahan (BBB) locomotor scale and grid walk tests were then utilized to estimate neurological rehabilitation. Additionally, the following assays were performed: Immunofluorescence localization of BMSCs to the site of SCI; the transwell migration assay to detect in vitro cellular migration; the terminal deoxynucleotidyl transferase dUTP nick end labeling assay to determine the apoptotic index of the lesion; and western blotting analysis to evaluate the expression of vascular endothelial growth factor (VEGF) and brain derived neurotrophic factor (BDNF) at the site of SCI. The BBB scores of the BMSC + EPO treated group were significantly increased compared with the BMSC treatment group (P<0.05). For example, BMSC + EPO treated rats had a significantly decreased number of hind limb slips compared with the BMSC treatment group (P<0.05). Furthermore, EPO significantly increased the migration capacity of BMSCs compared with the control group (P<0.001). In addition, the apoptotic index of the BMSC + EPO group was significantly decreased compared with the BMSC group (P<0.05). Green fluorescent protein-labeled BMSCs were detected at the site of SCI in the BMSC and BMSCs + EPO groups, with the signal being notably stronger in the latter. Moreover, the expression of VEGF and BDNF in the BMSCs + EPO group was significantly increased compared with the BMSC group (P<0.05). In conclusion, the results of the present study indicate that EPO can facilitate the recruitment of BMSCs to sites of SCI, increase expression of BDNF and VEGF, and accelerate recovery of neurological function following SCI.

objectiveto explore the clinical ffect on three oxide agglomeration treated tooth pulp disease.Methods to choose dental pulp disease96cases in our hospital from January2012 to December2012, they were divided into treatment group and control group according to different repair materials, the treatment group using the MTA to repair, the control group with light-cured glass ion cement, compared the two groups of patients with clinically repairing effect.Results the total effective rate of the treatment group was93.75%, the total effective rate of the control group was68.75%, to compare the two groups’ total effective rate, χ2=5.086, P<0.05, the difference of the total effective rate had statistically significant. review after1 week’srepair, the treatment group patients had no adverse reactions, and the control group found1swollen gums and had symptomatic improvement after treatment. Patient’s age, repair materials, perforation diameter and repair aesthetic effect into positive correlation.Conclu-sion the MTA has good biocompatibility, persistent closure, and good security, repair operation is simple, shorten the period of treatment, reducing patient’s pain, it is clinical operation is easy and can be good used tooth body perforation repair materials.

s:Objective To observe the effect of Yinxingdamo combined with Batroxobin in treatment of sudden hearing loss.Methods 63 patients with sudden deafness were randomly divided into two groups, treatment group of 32 patients was given Yinxingdamo combined with Batroxobin, control group of 31 patients was given Batroxobin individually.Both groups were also adopted oral prednisone tablet after the on-set and intramuscular injection of B1 and B12 .While the course of treatment ended with 14 days, the curative effect of two groups was com-pared by review hearing .Results The effective rate of treatment group was 93.8% and control group was 70.9%, there was significant difference between two groups (P<0.05).Conclusion The effect of Yinxingdamo combined with Batroxobin in treatment of sudden hearing loss is better than Batroxobin individually.

目的：观察哌拉西林与他唑巴坦治疗急性脑卒中相关性肺炎的疗效及护理效果。方法选取我院2012-01-2013-01收治的52例经病原学证实的急性脑卒中相关性肺炎患者，均经验性选择哌拉西林/他唑巴坦4.5 g静滴，8 h一次，3次/d ，治疗14 d为一个疗程。治疗过程中及治疗后，所有患者均给予综合性的护理干预措施。复查痰培养，观察患者不良反应发生率及生存质量。结果经哌拉西林/他唑巴坦治疗及护理人员的综合护理干预，本组急性脑卒中相关性肺炎患者治疗有效率92.3％，细菌清除率88.5％，护理相关不良反应发生率3.8％，生存质量较高。结论哌拉西林/他唑巴坦治疗急性脑卒中相关性肺炎疗效显著，不良反应少，配合早期的综合性护理干预，可提高生存质量。

Objective:The purpose of this study was to investigate the biomechanics and clinical application of the asymmetry assistant expansion arch used in unilateral arch width deficiency. Method:Measure the force value in vitro when type Ⅰ、Ⅱ、Ⅲ asymmetric auxiliary expansion arch effect on arch wire respectively. Subsequently,to apply asymmetric auxiliary expansion arch to correct the posterior cross-bite and unilateral posterior scissors bite in clinic. Result:When asymmetric auxiliary expansion arch was used in unilateral arch width deficiency,different points of application may lead to different force. Different points of application could be chosen according to the condition. Conclusion:The asymmetric auxiliary expansion arch can correct the unilateral arch width deficiency effectively.

Objective: To observe the efficacy of dirithromycin long-term and low dose using in post-operative treatment of rhinosinusitis with nasal polyps.Methods: Sixty-three patients with chronic rhinosinusitis and nasal polyps were randomly divided into dirithromycin group and clarithromycin group(as control group),combining with saline nasal washing and nasal fluticasone spray.The surgery efficacy and visual analog scale(VAS) score was compared between the two groups.Results: After 12 weeks,the effective rates of dirithromycin and clarithromycin groups were 87.9% and 90%,respectively,and the difference was not statistically significant(P>0.05).Significant improvements were found in both groups,but the dirithromycin group showed better improvement of nasal congestion and rhinorrhea symptoms than control group(P<0.05).Conclusion: The dirithromycin or clarithromycin was useful to improve the clinical symptoms of post-operation patients with chronic rhinosinusitis with nasal polyps.Also the way of long-term and low-dose using showed no serious side effects but dirithromycin showed more advantages.

Objective To investigate the analgesia efficacy of parecoxib for uvulopalatopharyngoplasty(UPPP) postoperative patients.Methods Forty-two patients of obstructive sleep apnea hypopnea syndrome(OSAHS) undergoing UPPP were randomly assigned to treatment group and control group(n=21 of each).The treatment group patients were given a single dose of parecoxib 40 mg before extubation and 40 mg·d-1 during following 3 days.The control group patients were given normal saline as a placebo.Visual analog scale(VAS) was used to evaluate the degree of postoperative pain and the scores at 2 h,12 h,24 h,48 h post operation and the blood coagulation were recorded.Results Parecoxib showd significantly postoperative analgesia efficacy(P<0.05) but little impact on blood coagulation.Conclusion Parecoxib could be used safely as postoperative analgesia for OSAHS patients.