Objective : To screen and analyze mutations in two families with non-syndromic tooth agenesis, providing a theoretical basis for the diagnosis and treatment of tooth agenesis Methods: This study was reviewed and approved by the Medical Ethics Committee, and informed consent was obtained from patients. Information and blood samples from two core families with non-syndromic congenital tooth agenesis were collected, along with blood samples from 100 normal controls. Pathogenic gene mutations were explored through whole exome sequencing and Sanger sequencing. The pathogenicity of the identified mutations was analyzed using prediction software Polyphen-2, CADD, and FAMMTH. The impact of the mutations on protein stability was predicted using Mupro, DUET, and I-Mutant software. Conservation analysis and protein 2D/3D structure analysis were used to predict the impact of mutations on protein function. The impact of the mutant proteins on subcellular localization was predicted using DeepLoc 2.1 software. Results: We identified two novel mutations in the muscle segment homeobox 1 (MSX1) gene: c.547C>A (p.Gln183Lys) and c.854T>C(p.Val285Ala) in the two families. Polyphen-2, CADD, and FATHMM predicted these mutations to be pathogenic, and ACMG classified these mutations as likely pathogenic. Conservation analysis showed that the two mutation sites (Gln183 and Val285) are located in highly conserved regions during evolution. Protein stability predictions indicated that these mutations influence protein stability. Protein 2D structure analysis indicated that these two mutations affect the 2D structure of the protein. 3D structure analysis showed that these two mutations can cause changes in the 3D structure. Software predictions indicated that these mutations do not affect the subcellular localization of the protein. Conclusion This study is the first to report two novel mutations in the MSX1 gene (c.547C>A and c.854T>C) associated with tooth agenesis, providing a basis for clinical diagnosis and treatment of congenital tooth loss.

[摘 要] 目的：探讨积雪草苷（ASI）是否通过环磷酸腺苷/蛋白激酶A/环磷酸腺苷反应成分结合蛋白(cAMP/PKA/CREB)信号通路调节肝细胞癌Huh7细胞的恶性生物学行为。方法：MTT筛选合适的ASI及时间后，将Huh7细胞分为对照组、ASI低剂量组（ASI-L组，20 μmol/L ASI）、ASI中剂量组（ASI-M组，40 μmol/L ASI）、ASI高剂量组（ASI-H组，80 μmol/L ASI）及ASI-H+Forskolin组（80 μmol/L ASI+100 μmol/L cAMP激活剂-Forskolin），按照上述分组处理48 h后，MTT及细胞克隆实验检测Huh7细胞增殖；Transwell实验分析Huh7细胞迁移、侵袭变化；膜联蛋白V-FITC凋亡试剂盒检测细胞凋亡变化；ELISA实验、WB法检测Huh7细胞的cAMP分泌水平及p-PKA、p-CREB蛋白的表达水平；将Huh7细胞经皮下注射于裸鼠右腹部，建立肝癌异种移植模型，以5、15和45 mg/kg的ASI灌胃干预4周，分离肿瘤组织并称质量。结果：以接近IC50的40 μmol/L ASI处理48 h为合适的浓度和时间。ASI-L组、ASI-M组、ASI-H组Huh7细胞增殖及克隆数、迁移数、侵袭数、cAMP水平、p-PKA/PKA和p-CREB/CREB表达均显著低于对照组（均P < 0.05），而凋亡率均显著高于对照组（均P < 0.05）；ASI-H+Forskolin组Huh7细胞增殖及克隆数、迁移数、侵袭数、cAMP水平、p-PKA/PKA、p-CREB/CREB表达均显著高于ASI-H组（均P < 0.05），而Huh7细胞凋亡率显著低于ASI-H组（P < 0.05）；在裸鼠移植瘤实验中，5、15和45 mg/kg ASI处理组的移植瘤质量均显著低于对照组（均P < 0.05）。结论：ASI可通过下调cAMP/PKA/CREB信号通路蛋白表达抑制Huh7细胞的恶性生物学行为、促进其凋亡，以及抑制裸鼠移植瘤的生长。

[摘 要] 目的：探讨同源框蛋白C4（HOXC4）在胃癌组织和细胞中的表达及其对胃癌细胞增殖、迁移与侵袭的作用及其机制。方法：收集2020年5月至2021年4月期间在南阳市第一人民医院肿瘤科手术切除的16例进展期胃癌患者的癌及癌旁组织标本，以及人胃正常上皮细胞GES-1和胃癌细胞AGS、SGC-790和MGC-803，采用WB法检测胃癌组织和细胞中HOXC4的表达。通过RNA干扰技术对SGC-790及AGS细胞中HOXC4进行敲低或过表达，实验分为sh-HOXC4#1组、sh-HOXC4#2组、sh-Con组、sh-HOXC4 + pc-integrin β1组、pc-HOXC4组、pc-Con组、pc-HOXC4 + pc-integrin β1组。利用EdU、CCK-8、Transwell实验分别检测敲低或过表达HOXC4对各组细胞活力、增殖、侵袭、迁移和integrin β1表达的影响。用敲低HOXC4的胃癌AGS细胞构建荷瘤小鼠模型，观察敲低HOXC4对移植瘤体积及组织中Ki67和integrin β1蛋白表达的影响。结果：胃癌组织和细胞中HOXC4的表达均显著上调（均P < 0.01）。与sh-Con组相比，sh-HOXC4#1组和sh-HOXC4#2组SGC-790及AGS细胞中HOXC4、integrin β1蛋白表达水平，以及细胞的活力、增殖、迁移及侵袭能力均显著降低（均P < 0.01）。与sh-HOXC4组相比，sh-HOXC4 + pc-integrin β1组细胞活力、增殖、迁移及侵袭能力均显著增加（均P < 0.01）；与pc-Con组相比，pc-HOXC4组细胞活力、侵袭及迁移能力均显著增加（均P < 0.01）；与pc-HOXC4组相比，pc-HOXC4 + pc-integrin β1组细胞活力、迁移及侵袭能力均显著降低（均P < 0.01）。与sh-Con组相比，sh-HOXC4#1组和sh-HOXC4#2组小鼠移植瘤生长缓慢、体积变小，组织中Ki67和integrin β1表达均显著降低（均P < 0.01）。结论：HOXC4在胃癌组织与细胞中表达上调，其通过激活integrin β1信号促进胃癌细胞的增殖、迁移与侵袭。

[摘 要] 目的：探讨环状RNA hsa_circ_0046701在胶质瘤组织中的表达及其对胶质瘤U251细胞增殖、迁移与侵袭的影响。方法：收集2022年6月至2023年3月期间在同济大学附属普陀人民医院接受手术治疗的52例胶质瘤患者的瘤组织标本及临床资料，另收集30例正常脑组织标本作为对照。通过qPCR法检测胶质瘤组织中hsa_circ_0046701表达水平，分析其与患者临床特征间的关系，通过Kaplan-Meier法分析hsa_circ_0046701水平与生存预后的关系。利用RNA干扰技术，分别将circ_0046701过表达及空载体（vector）、siRNA-circ_0046701及阴性对照（si-NC）质粒转染到胶质瘤U251细胞中，实验分为si-circ_0046701组、si-NC组、circ_0046701 OE组、Vector组。应用CCK-8法、Transwell小室实验检测各组细胞的增殖、迁移及侵袭能力，WB法检测各组细胞中vimentin、Snail、E-cadherin和cyclin D1蛋白的表达。结果：胶质瘤组织中hsa_circ_0046701表达显著高于正常脑组织（P < 0.01）。hsa_circ_0046701高表达组患者WHO脑胶质瘤分级（Ⅲ~Ⅳ级）占比显著高于低表达组（P < 0.01），其高表达组患者术后生存期显著短于低表达组。与si-NC组相比，si-circ_0046701组U251细胞的增殖能力显著降低（P < 0.05或P < 0.01）、迁移及侵袭细胞数均显著减少（均P < 0.01），细胞中vimentin、Snail、cyclin D1蛋白表达均明显降低（均P < 0.01）、E-cadherin蛋白表达明显增高（P < 0.01）；与Vector组相比，circ_0046701 OE组U251细胞的增殖能力显著升高（P < 0.01）、迁移及侵袭细胞数均显著增多（均P < 0.01），细胞中vimentin、Snail、cyclin D1蛋白表达均显著增高（均P < 0.01）、E-cadherin蛋白表达明显降低（P < 0.01）。结论：环状RNA hsa_circ_0046701在胶质瘤组织中呈高表达，并与患者的不良预后密切相关；敲低hsa_circ_0046701表达能够抑制脑胶质瘤U251细胞的增殖、迁移及侵袭能力。

[摘 要] 目的：探索预后营养指数（PNI）在接受诱导化疗联合免疫（化免）序贯放疗的局部晚期食管鳞状细胞癌（ESCC）中的疗效预测价值及预后影响。方法: 回顾性分析浙江省肿瘤医院2019年5月至2023年8月期间收治的126例行诱导化免序贯放疗的局部晚期ESCC患者的临床资料。绘制受试者工作特征曲线（ROC曲线），确定患者诱导化免前1周内、放疗前1周内、放疗开始后4 ± 1周的PNI最佳临界值并对患者进行分组。采用Kaplan-Meier法绘制生存曲线，并用Log-Rank法比较组间患者的总生存期（OS）及无进展生存期（PFS），采用Cox回归分析探讨诱导化免序贯放疗的局部晚期ESCC患者的预后影响因素。结果: 共纳入126例局部晚期ESCC患者，男性118例，女性8例，中位年龄65岁（44~78岁）。运用ROC曲线确认的患者诱导化免前、放疗前和放疗中PNI最佳临界值为46.2、48.3和37.9。放疗前PNI ≥ 48.3组中位OS、PFS分别为47.3、28.2个月，放疗前PNI < 48.3组中位OS、PFS分别为18.7、15.2个月（P < 0.01，P < 0.05）。放疗中PNI ≥ 37.9组中位OS未达到，中位PFS为25.7个月，放疗中PNI < 37.9组中位OS、PFS分别为17.0、12.5个月（P < 0.01，P < 0.05）。诱导化免后PNI升高组中位OS未达到，中位PFS为28.4个月；PNI降低组中位OS、PFS分别为20.4、16.0个月（P < 0.01，P < 0.05）。多因素分析显示，放疗中PNI[HR = 2.292，95% CI（1.264,4.159），P < 0.05]、诱导化免后PNI变化[HR = 2.120, 95% CI（1.007, 4.463），P < 0.05]为影响OS因素。结论: 放疗中PNI、诱导化免后PNI变化与患者治疗疗效及预后有一定相关性，可作为预测ESCC化免序贯放疗获益的重要指标。

Severe trauma has high morbidity and mortality rates, being the leading cause of death in young adults. Among all traumas, traffic injuries are particularly lethal.[1-2] The injury severity score (ISS) can be used to assess trauma severity, with ISS of <9, 9-15, 16-24, and ≥25 indicating minor, moderate, severe, and critical trauma, respectively. The ISS is correlated with mortality, morbidity, and hospitalization duration after injury.[3-4] Here, we report one patient who was admitted to our emergency intensive care unit (EICU) due to traumatic liver rupture and traumatic myocardial infarction complicated with inferior vena cava (IVC) thrombosis.

[摘 要] 目的：探究β-半乳糖苷α-2-6唾液酸转移酶1（ST6GAL1）对结直肠癌（CRC）HCT116细胞糖酵解和迁移、侵袭的作用及可能的分子机制。方法：通过检索GEPIA2数据库，分析ST6GAL1在CRC患者和健康人群中的表达差异；WB法检测ST6GAL1在CRC细胞HCT116、SW480、Caco-2、HT29、LoVo和人正常结肠上皮细胞NCM460细胞中的表达差异；免疫组织化学法分析ST6GAL1在CRC组织和对应癌旁组织中的表达差异。通过慢病毒转染细胞的方法构建稳定敲低或过表达ST6GAL1的HCT116细胞，通过划痕愈合实验检测细胞迁移能力，Transwell实验检测细胞侵袭能力，WB法检测细胞糖酵解相关蛋白、Notch1受体胞内段（Notch1 ICD）以及PI3K/AKT/mTOR通路磷酸化水平，细胞免疫荧光实验观察Notch1 ICD表达水平和进入细胞核情况；加入Notch1受体激动剂Jagged1处理HCT116细胞，通过WB法检测糖酵解相关蛋白、Notch1 ICD表达水平以及PI3K/AKT/mTOR通路磷酸化水平。结果：ST6GAL1在CRC组织和细胞中均表达上调（均P < 0.05）。与对照组和过表达组相比，敲低ST6GAL1导致HCT116细胞内Notch1 ICD表达水平和PI3K/AKT/mTORC1磷酸化水平显著降低，细胞糖酵解相关蛋白表达水平降低，细胞迁移和侵袭能力减弱（均P < 0.05）；过表达ST6GAL1增加了HCT116细胞内Notch1 ICD表达水平并促进其进入细胞核，细胞糖酵解相关蛋白表达水平升高，细胞迁移和侵袭能力增强（均P < 0.05）。结论：ST6GAL1通过活化Notch1受体进而磷酸化激活PI3K/AKT/mTORC1通路，并增强CRC细胞糖酵解水平和迁移、侵袭能力。

[摘 要] 目的：探究长链非编码RNA葡萄糖醛酸酶β假基因11（GUSBP11）调节miR-339-5p/小鼠双分钟同源物2（MDM2）轴对胃癌细胞AGS增殖、迁移和侵袭的影响。方法：收集2023年12月至2024年6月期间在广州中医药大学附属佛山中医院手术治疗的25例胃癌患者的癌旁组织及癌组织。常规培养胃癌细胞AGS和正常胃黏膜上皮细胞GES-1，用转染试剂将对照质粒和敲减质粒转染AGS细胞，分为Ctrl组、sh-NC、sh-GUSBP11、sh-GUSBP11 + anti-NC、sh-GUSBP11 + anti-miR-339-5p。qPCR法检测胃癌组织及各组细胞中GUSBP11、miR-339-5p和MDM2 mRNA的表达；双萤光素酶报告基因实验检测GUSBP11或MDM2与miR-339-5p间的靶向关系；EdU法检、Transwell小室实验、划痕愈合实验和WB法分别检测各组AGS的增殖、迁移和侵袭能力和细胞中CDK1、MMP-2、MMP-9蛋白的表达；AGS细胞移植瘤实验检测敲减GUSBP11对移植瘤生长的影响。结果：胃癌组织和细胞中GUSBP11、MDM2 mRNA均呈高表达（均P < 0.05），miR-339-5p呈低表达（P < 0.05）。GUSBP11与miR-339-5p和MDM2与miR-339-5p间存在靶向关系。在AGS细胞中敲减GUSBP11可明显抑制MDM2蛋白、促进miR-339-5p的表达而抑制miR-339-5p则可促进MDM2蛋白表达。敲减GUSBP11可抑制AGS细胞的增殖、迁移和侵袭能力而抑制miR-339-5p则可逆转此作用。敲减GUSBP11可明显抑制CDK1、MMP-2和MMP-9蛋白的表达而抑制miR-339-5p则可逆转此作用。敲减GUSBP11可明显抑制AGS细胞移植瘤的生长。结论：GUSBP11在胃癌组织和细胞中呈高表达，敲减GUSBP11表达可能通过调控miR-339-5p/MDM2轴抑制胃癌细胞的恶性生物学行为。

Objective To compare the mid- and long-term clinical results of mitral valve plasty (MVP) and mitral valve replacement (MVR) in the treatment of functional mitral regurgitation (FMR). Methods Patients with FMR who underwent surgical treatment in the Department of Cardiovascular Surgery of the General Hospital of Northern Theater Command from 2012 to 2021 were collected. The patients who underwent MVP were divided into a MVP group, and those who underwent MVR into a MVR group. The clinical data and mid-term follow-up efficacy of two groups were compared. Results Finally 236 patients were included. There were 100 patients in the MVP group, including 53 males and 47 females, with an average age of (61.80±8.03) years. There were 136 patients in the MVR group, including 72 males and 64 females, with an average age of (61.29±8.97) years. There was no statistical difference in baseline data between the two groups (P＞0.05). There was no statistical difference between the two groups in the extracorporeal circulation time, aortic occlusion time, postoperative hospital and ICU stay, intraoperative blood loss, or hospitalization death (P＞0.05), but the time of mechanical ventilation in the MVP group was significantly shorter than that in the MVR group (P=0.022). The total follow-up rate was 100.0%, the longest follow-up was 10 years, and the average follow-up time was (3.60±2.55) years. There were statistical differences in the left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac function between the two groups compared with those before surgery (P<0.05). The postoperative left ventricular ejection fraction in the MVP group was statistically higher than that before surgery (P=0.002), but there was no statistical difference in the MVR group before and after surgery (P=0.658). The left atrial diameter in the MVP group was reduced compared with the MVR group (P=0.026). The recurrence rate of mitral regurgitation in the MVP group was higher than that in the MVR group, and the difference was statistically significant (10.0% vs. 1.5%, P=0.003). There were 14 deaths in the MVP group and 19 in the MVR group. The cumulative survival rate (P=0.605) and cardiovascular events-free survival rate (P=0.875) were not statistically significant between the two groups by Kaplan-Meier survival analysis. Conclusion The safety, and mid- and long-term clinical efficacy of MVP in the treatment of FMR patients are better than MVR, and the left atrial and left ventricular diameters are statistically reduced, and cardiac function is statistically improved. However, the surgeon needs to be well aware of the indications for the MVP procedure to reduce the rate of mitral regurgitation recurrence.

With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient&#39;s lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.