[摘 要] 目的：探讨多结节非小细胞肺癌（NSCLC）组织中的驱动基因突变情况与临床病理特征的关系，为多结节NSCLC患者治疗提供分子诊断依据。方法：本研究共纳入2018年1月至2023年10月间云南省肿瘤医院分子诊断中心检测的121例多结节NSCLC患者的253个肺结节肿瘤组织标本，以第二代测序（NGS）技术或扩增阻滞突变系统PCR（ARMS-PCR）技术检测多结节NSCLC 组织中驱动基因突变情况，分析其与患者临床病理特征的关系，比较不同结节间肺癌驱动基因的突变异质性。结果：与非“宣威”NSCLC相比，“宣威”多结节NSCLC患者驱动基因突变具有显著的地域特点，表现在“宣威”患者具有较低（20%）的EGFR敏感突变（L858R、19-del）及较高（27.26%）的EGFR少见突变（主要为G719/S768I、G719）；“宣威”多结节NSCLC患者的KRAS突变率（27.27%）亦显著高于非“宣威”患者突变率（12.59%）（P<0.05）。此外，“宣威”多结节NSCLC患者驱动基因突变不一致率高达69.23%，远高于非“宣威”患者驱动基因突变不一致率（55.07%）（P<0.05）。结论：“宣威”多结节NSCLC患者具有较高的EGFR少见突变及KRAS突变率，同一患者不同病灶之间存在更高的驱动基因突变异质性，本研究将为“宣威”多结节NSCLC的诊疗策略提供更多的选择。

[摘 要] 目的：探究SOX9通过上调长链非编码RNA LINC01503的表达对喉鳞状细胞癌（LSCC）细胞的增殖、迁移、侵袭及肿瘤干细胞干性的影响。方法： 常规培养人LSCC细胞AMC-HN-8、TU177、TU212和TU686，用转染试剂将敲减序列及其对照核酸（si-SOX9-NC、si-SOX9#1、 si-SOX9#2、si-LINC01503-NC、si-LINC01503#1、si-LINC01503#2）或过表达质粒及其对照核酸（pcDNA3.1-SOX-NC、pcDNA3.1-SOX-oe、pcDNA3.1-LIN01503-NC和pcDNA3.1-LIN01503-oe）分别转染至TU177细胞或TU686细胞，记为si-SOX9-NC组、si-SOX9#1组、si-SOX9#2组、si-LINC01503-NC组、si-LINC01503#1组、si-LINC01503#2组；pcDNA3.1-SOX9-NC组、pcDNA3.1-SOX9-oe组、pcDNA3.1-LINC01503-NC组、pcDNA3.1-LINC01503-oe组、si-SOX9-NC + pcDNA3.1-LINC01503-NC组和si-SOX9 + pcDNA3.1-LINC01503-oe组。qPCR法检测SOX9 mRNA和LINC01503 在各组细胞中的表达，生物信息学分析SOX9与LINC0503启动子区的结合位点，双萤光素酶报告基因实验和染色质免疫共沉淀实验验证SOX9与LINC01503启动子区是否直接结合，WB法检测SOX9的敲减效率及LINC01503对TU177和TU686细胞干性标志物表达的影响，MTS法检测各组细胞的增殖活力，划痕愈合和Transwell小室实验检测各组细胞的迁移能力，克隆形成实验检测各组细胞的克隆形成能力。结果：SOX9在各种LSCC细胞中呈高表达（均P < 0.05），数据库数据分析显示，在头颈部鳞状细胞癌中，SOX9与LINC01503表达呈正相关（R = 0.12，P = 0.005 9）；SOX9可与LINC01503启动子区直接结合并促进其转录表达（均P < 0.05）；敲减LINC01503可明显抑制TU177细胞的增殖、迁移、侵袭（均P < 0.05），过表达LINC01503明显促进TU686细胞增殖、迁移、侵袭的能力（均P < 0.05），提高TU686细胞克隆形成能力和细胞干性标志物分子CD133、OCT4、SOX2的mRNA和蛋白水平表达（均P < 0.05），敲减LINC01503则均可抑制TU686细胞的克隆形成和细胞干性标志物的表达（均P < 0.05）；敲减SOX9均可明显抑制TU177细胞的增殖、迁移和侵袭能力，降低其干性细胞标志物的表达（均P < 0.05），同时过表达LINC01503则可部分逆转敲减SOX9对TU177细胞恶性生物学行为和干性标志物表达的抑制作用（均P < 0.05）。结论：SOX9和LINC01503在LSCC细胞中呈高表达，SOX9可能通过上调LINC01503表达提高LSCC细胞增殖、转移和侵袭能力和肿瘤干细胞干性。

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

Objective To demonstrate the changes in flexor digitorum and extensor digitorum tension in the affected hands with shear-wave elastography (SWE) before and after manual digitorum sensory stimulation (MDSS) in hemiplegic patients with stroke. Methods A total of 51 hemiplegic post-stroke inpatients in the Department of Rehabilitation Medicine in Second Hospital of Anhui Medical University from April to June, 2020, underwent MDSS completed by a researcher who used a bare thumb and index finger to squeeze each nail bed as well as the sides of each fingertip in the affected hand. The stimulation intensity was the minimum that could cause finger extension without obvious pain, and the interval between two stimulations was five to ten seconds. Muscular tension of the flexor digitorum superficialis, flexor digitorum profundus, flexor pollicis longus and extensor digitorum were assessed with modified Ashworth Scale (MAS) and shear-wave velocity (SWV) of SWE on the affected side before and immediately after MDSS. MAS score was -1 as low muscular tension. Results The MAS scores of all the muscles significantly reduced after MDSS (|Z| > 2.843, P < 0.001); while the changes of SWV were not significantly in all the muscles with initially MAS score of 0 or -1 (t < 1.052, P > 0.05), and it reduced in those muscles with initial MAS scores of one to three (t > 2.672, P < 0.05). The SWV were positively correlated with the MAS scores both before and after MDSS (r > 0.334, P < 0.05). Conclusion MDSS can effectively, immediately, and safely relieves muscle spasms of the flexor digitorum and facilitate active finger extension in the affected hand for hemiplegic patients with stroke. SWE is useful for quantitatively and objectively evaluating muscular tension in the affected hand for hemiplegic patients with stroke.

Objective To summarize the cardiac rehabilitation referral system.Methods The literatures about the construction of cardiac rehabilitation referral systems were retrieved from the databases of CNKI, Wanfang Date, PubMed and Web of Science, and cardiac rehabilitation websites.Results For some foreign countries, the referrals of cardiac rehabilitation mainly based on electronic medical record management system, internet platform, chronic care model, and hospitals and communities. For China, referral system is trying to build based on the medical conjoined system.Conclusion Referral, as the first step, plays an important role in participating in cardiac rehabilitation for patients. The cardiac rehabilitation referral system needs to be improved in China, referred the ways of developed countries.

<b>Backgroundb> In the context of global warming, the impact of meteorological factors on human health has gradually become a research hotspot at home and abroad. <b>Objectiveb> To describe the distribution of children's bronchopneumonia in Huzhou City, and explore the influence of diurnal temperature range (DTR) on children with bronchopneumonia, so as to provide guidance for identifying vulnerable populations and developing targeted measures. <b>Methodsb> A distributed lag nonlinear model (DLNM) was used to explore the potential nonlinear lag effect of DTR on admission of children with bronchopneumonia in Huzhou City from 2014 to 2019. Then a generalized additive model (GAM) was used to calculate the hospital admission risk of exposure to DTR in total population and sex-, age-, season-stratified populations. <b>Resultsb> A total of 17658 hospitalized children with bronchopneumonia were included in the study. When DTR exceeded 7.5 ℃, the relative risk rose abruptly. When DTR reached 17 ℃, the risk of admission to hospital of children with bronchopneumonia was the greatest. In terms of the single-day lag effect, the admission risk of DTR for bronchopneumonia in children began on the same day and persisted until lag day 2; it peaked on the same day, and RR was 1.353 (95%CI: 1.220-1.502). The cumulative lag effect occurred from lag0 to lag0-6, and the highest RR value was at lag0-3, which was 1.938 (95%CI:1.483-2.533). The results of stratified analysis showed that the maximum effect values for boys and girls appeared at lag0-3 (RR_boys=2.301, 95%CI: 1.671-3.169) and lag0-2(RR_girls=1.566, 95%CI: 1.152-2.129) respectively, and the effect value and duration of DTR in boys were higher and longer than those in girls. Among different age groups, both children of 0-3 years old and 4-14 years old had the maximum effect value at lag 0-3, the RR values were 1.734 (95%CI: 1.454-2.572) and 1.998 (95%CI: 1.226-2.254) respectively, and the effect value and duration of DTR on the children of 4-14 years old were higher and longer than those of the children of 0-3 years old. As to seasons, no significant increase was found in cumulative effect in summer and autumn (P>0.05); in winter and spring, the maximum effect value appeared at lag0-10, and the RR value was 4.164 (95%CI:1.191-14.561). <b>Conclusionb> The impact of DTR on bronchopneumonia in children is acute. Boys and children aged 4-14 years old are more sensitive to DTR changes. Therefore, we should be alert to severe DTR changes and take protective measures in advance

[摘 要] 目的：探讨CD68+ 肿瘤相关巨噬细胞（TAM）、CD8+ T细胞、Foxp3+ Treg细胞等在肺腺癌（LUAD）组织中浸润分布及其与患者预后的关系。方法：收集2004年9月至2009年4月间在苏州大学附属第三医院手术切除的93例LUAD组织及78例癌旁组织，采用组织芯片（TMA）及多重免疫荧光（mIF）技术检测其中的免疫细胞浸润与分布，Wilcoxon秩和检验比较癌与癌旁组织、癌巢与间质中浸润水平的差异，χ2检验分析其浸润水平及CD8+/CD68+细胞比值与临床病理特征的关系，Kaplan-Meier法和COX模型分析影响患者OS的潜在危险因素。结果：与癌旁组织比较，癌组织中CD68+ TAM、CD8+ T细胞、Foxp3+ Treg细胞浸润水平均显著增加（均P<0.01），间质CD68+ TAM、CD8+ T细胞的浸润水平均显著高于癌巢（均P<0.01）。总CD68+ TAM、癌巢及间质CD68+ TAM浸润水平与淋巴结转移呈正向关联（均P<0.05），癌巢CD68+ TAM浸润水平与T分期呈正向关联（P<0.05），间质CD68+ TAM浸润水平与病理分级呈正向关联（P<0.05）；癌组织中CD8+/CD68+细胞比值与病理分级、淋巴结转移均呈负向关联（均P<0.05）。Kaplan-Meier生存分析显示，LUAD组织中总CD68+ TAM、癌巢及间质CD68+ TAM高浸润患者OS均短于低浸润患者（P<0.05或P<0.01）、癌组织中CD8+/CD68+细胞比值高患者OS显著长于低比值患者（P<0.05）。多因素COX模型分析示，LUAD患者年龄、TNM分期及癌组织中CD8+/CD68+ 细胞比值是影响患者预后的独立风险因素（P<0.05或P<0.01）。结论:高度浸润的CD68+ TAM与LUAD的进展、侵袭、转移和不良预后显著关联，而高CD8+/CD68+ 细胞比值是影响LUAD患者OS的独立保护因素。

This study compared the effects on bone metabolism and morphology of pathological obesity induced by excessive fat intake in a non-hibernator (mice) versus healthy obesity due to pre-hibernation fattening in a hibernator (ground squirrels). Kunming mice were fed a high-fat diet to provide a model of pathological obesity (OB group). Daurian ground squirrels fattened naturally in their pre-hibernation season (PRE group) were used as a healthy obesity model. Micro-computed tomography (micro-CT) and three-point bending tests were used to determine the microstructure and mechanical properties of bone. Western blots were used to analyze protein expression levels related to bone metabolism (Runt-related transcription factor 2 (RunX2), osteocalcin (OCN), alkaline phosphatase (ALP), osteoprotegerin (OPG), receptor activator of nuclear factor-‍κB ligand (RANKL), cathepsin K, matrix metallopeptidase 9 (MMP9), patched protein homolog 1 (Ptch1), phosphorylated β‍-‍catenin (P‍-‍β‍-‍catenin), and glycogen synthase kinase-3β (GSK-3β)). Compared with controls, there was no obvious bone loss in the OB mice, and the stiffness of the femur was increased significantly. Compared with summer active squirrels, bone formation was enhanced but the mechanical properties did not change in the PRE group squirrels. In OB mice, western blots showed significantly increased expression levels of all proteins except RunX2, OPG, and Ptch1. PRE ground squirrels showed significantly increased expression of most proteins except OCN and Ptch1, which decreased significantly, and P‍-‍β‍-‍catenin and OPG, which did not change. In conclusion, for non-hibernating mice, moderate obesity had a certain protective effect on bones, demonstrating two-way regulation, increasing both bone loss and bone formation. For pre-hibernating ground squirrels, the healthy obesity acquired before hibernation had a positive effect on the microstructure of bones, and also enhanced the expression levels of proteins related to bone formation, bone resorption, and Wnt signaling.
Mice ; Animals ; Hibernation ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Diet, High-Fat ; X-Ray Microtomography ; Sciuridae/metabolism* ; Obesity

Objective: To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD. Methods: A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD. Results: The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD. Conclusion There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.
Cross-Sectional Studies ; Diabetes Mellitus/epidemiology* ; Humans ; Hyperlipidemias/epidemiology* ; Hypertension/epidemiology* ; Macular Degeneration/etiology* ; Risk Factors

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Adenocarcinoma of Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Squamous Cell/genetics* ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/genetics* ; Polymorphism, Single Nucleotide