目的 评估调脂药物靶点所介导的脂质表型（HMGCR、PCSK9和NPC1L1）与高血压肾病风险之间潜在的因果相关性。方法 使用来自欧洲人群公开可获得的全基因组关联研究（GWAS）汇总数据进行孟德尔随机化（MR）分析。采用与低密度脂蛋白胆固醇（LDL-C）相关的遗传变异,根据选定的调脂药物靶基因筛选工具变量,使用逆方差加权法作为主要MR分析方法,并进行敏感性分析确保结果的稳健性。结果 基因预测的LDL-C水平与较高的高血压肾病风险相关（OR=1.19,95% CI：1.03~1.38,P=0.021）。较高的HMGCR介导的LDL-C水平与高血压肾病风险存在正向因果相关性（OR=4.08,95% CI：2.86~5.81;P<0.001）。然而,PCSK9和NPC1L1介导的LDL-C水平与高血压肾病风险无相关性。Cochran Q检验、MR-PRESSO检测和MR-Egger截距测试显示工具变量之间不存在异质性或水平多效性。结论 HMGCR介导的LDL-C与高血压肾病的发病风险存在因果相关性,针对HMGCR基因的他汀类药物在高血压肾病的防治中可能具有潜在益处。

Objective To assess the potential causal relationship between lipid phenotypes mediated by lipid-lowering drug targets（HMGCR,PCSK9 and NPC1L1）and the risk of hypertensive nephropathy．Methods Mendelian randomization（MR）analysis was conducted using summary data from publicly available European ancestry genome-wide association studies（GWAS）．Genetic variants associated with low-density lipoprotein cholesterol（LDL-C）were used as instrumental variables based on selected lipid-lowering drug target genes screening tools．Inverse variance weighting was selected as the main MR analysis method,with sensitivity analyses conducted to ensure the robustness of the results．Results Genetically predicted LDL-C levels were associated with a higher risk of hypertensive nephropathy（OR=1.19,95% CI：1.03~1.38,P=0.021）．Higher LDL-C levels mediated by HMGCR were positively causally related to increased risk of hypertensive nephropathy（OR=4.08,95% CI：2.86~5.81;P<0.001）．However,LDL-C levels mediated by PCSK9 and NPC1L1 showed no significant association with the risk of hypertensive nephropathy．Cochran’s Q test,MR-PRESSO,and MR-Egger intercept tests showed no heterogeneity or horizontal pleiotropy among instrumental variables．Conclusions The findings of this study support the causal relationship between LDL-C mediated by HMGCR and increased risk of hypertensive nephropathy,suggesting potential benefits of statin therapy for hypertensive nephropathy．

目的 研究靶向NKG2A抑制剂抗头颈部鳞状细胞癌（HNSCC）的作用。方法 应用GEO和TCGA数据库分析NKG2A及其配体HLA-E单细胞表达情况、与患者预后以及免疫微环境的相关性。构建HNSCC皮下抑制瘤模型,流式细胞技术检测化学治疗（化疗）对免疫检测点NKG2A表达的影响。动物实验验证NKG2A抑制剂以及NKG2A抑制剂联合多西他赛化疗的抗肿瘤作用。结果 NKG2A（KLRC1）主要表达在NK细胞,少量表达在T淋巴细胞。HNSCC肿瘤高表达NKG2A/HLA-E（P<0.01）,与患者不良预后密切相关;肿瘤微环境中NKG2A/HLA-E与多个免疫细胞浸润以及免疫检测点表达密切相关（P<0.01）。动物实验显示化疗能上调T、B淋巴细胞表达免疫检查点NKG2A的表达水平（P<0.01）;化疗的基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用（P=0.013）。结论 化疗基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用,为探索HNSCC临床新策略提供实验和理论基础。

Objective To investigate the anti-tumor effects of NKG2A inhibitor on head and neck squamous cell carcinoma（HNSCC）．Methods The single-cell expression of NKG2A ,its ligand HLA-E and their correlations with patient prognosis and immune microenvironment were analyzed in GEO and TCGA databases．The subcutaneous tumor model of HNSCC was constructed,and the effects of chemotherapy on the expression of NKG2A on T and B lymphocytes were detected by flow cytometry．Animal experiments were used to confirmed the anti-tumor effects of NKG2A inhibitor and NKG2A inhibitors combined with docetaxel．Results NKG2A（KLRC1）was mainly expressed in NK cells,and a small amount was expressed in T lymphocytes．The high expression of NKG2A/HLA-E in HNSCC tumors（P<0.01）were closely related to poor prognosis．NKG2A/HLA-E in tumor microenvironment were closely related to the infiltration of multiple immune cells and the expression of immune checkpoints（P<0.01）．Animal experiments showed that chemotherapy could up-regulate the expression of NKG2A in T and B lymphocytes（P<0.01）．Chemotherapy in combination with NKG2A inhibitor could mediate more effective antitumor effects in HNSCC（P=0.013）．Conclusions Combined with NKG2A inhibitor on the basis of chemotherapy can mediate more effective anti-tumor effects,and this study may provide experimental and theoretical basis for exploring new clinical strategies of HNSCC．

全膝关节置换术（TKA）是目前治疗终末期膝关节疾病的首选方法,它能够缓解疼痛、改善畸形、恢复力线、增加膝关节活动度及提高患者生活质量。目前,关于胫骨假体旋转对线的方法很多,主要包括胫骨结节、胫骨前后轴、胫骨前皮质、自我形合技术、计算机辅助导航技术、个性化截骨技术等,它们各有优缺点,但在临床上并没有达成共识。该文主要对胫骨近端的解剖学特点和TKA中胫骨假体旋转定位的方法等方面进行综述。旨在为临床骨科医生在行TKA时,选择合适的胫骨假体旋转对线方法提供一些参考。

Total knee replacement（TKA） is currently the preferred treatment for end-stage knee disease,and it can relieve pain,improve deformity,restore strength lines,increase knee range of motion,and improve patients’ quality of life．At present,there are many methods for the rotation of alignment of tibial prosthesis,mainly including tibial tubercles,tibial anteroposterior axes,anterior tibial cortex,self-morphing technology,computer-aided navigation technology,personalized osteotomy technology,etc．Each of the methods above has its advantages and disadvantages,but there is no clinical consensus at present．This article mainly reviews the anatomical characteristics of the proximal tibia and the method of rotational positioning of tibial prosthesis in TKA,which aims to provide some reference for clinical orthopedic surgeons to select the appropriate tibial prosthesis rotation alignment method when performing TKA．

目的 总结GuideLiner^®延长导管在复杂经皮冠状动脉介入治疗(PCI)中的初步经验,探讨其有效性及安全性。方法 选择2015年3月—2017年3月因冠心病于广州市第一人民医院行PCI的患者13例,因复杂病变需要更强支撑力而使用GuideLiner^®延长导管完成手术,总结手术成功率、并发症以及6个月随访主要不良心脏事件的发生情况。结果 13例患者在GuideLiner^®延长导管应用下均成功完成手术。使用延长导管的目的2例手术为辅助球囊通过,7例为辅助支架通过,4例为辅助支架及球囊通过。全部患者均未发生术中及住院期间死亡、急性心肌梗死,未发生急性支架内血栓形成、目标冠脉夹层或穿孔、心包填塞等并发症,6 个月随访均无不良心脏事件发生。结论 应用延长导管可提高支撑力,有效辅助球囊和/或支架到达冠状动脉病变部位,提高手术成功率,安全性较高。

Objective To evaluate the clinical efficacy and safety of GuideLiner^® guide extension catheter during complex coronary percutaneous coronary intervention(PCI) procedures. Methods Thirteen patients with coronary heart diseases performed PCI procedures were included in this study from March 2015 to March 2017. GuideLiner^® guide extension catheters were used in these complex cases. The PCI success rate,incidence of complications and 6-month follow up data were observed. Results Benefited from the stronger support produced by GuideLiner^®, PCI success rate was 100%. The guide extension catheters were used for the delivery of balloons in 2 cases, while 7 cases for stents, and 4 cases for both balloons and stents. No death were observed during the procedure or in hospital, and there were no dissection or acute myocardial infarction. During 6 months of follow-up,there was no major adverse cardiac events (MACE). Conclusion GuideLiner^® guide extension catheter may improve procedure success rate by ensuring the delivery of balloons and stents in complex PCI.

目的 分析谷草转氨酶（AST）、胆碱酯酶（CHE）、糖类抗原125（CA125）以及甲胎蛋白（AFP）对肝硬化患者的诊断效能。方法 选择70例肝硬化患者为观察组研究对象,另取70例同期健康体检者为对照组。两组研究对象均接受生化检验、肿瘤标志物检验。对比两组研究对象的AST、CHE、CA125、AFP检测结果,分析上述指标对肝硬化患者的诊断效能。结果 观察组肝硬化患者的CHE低于对照组,AST、CA125与AFP高于对照组（P<0.05）;AST与CHE在肝硬化诊断中具有良好的灵敏度、特异度;CA125联合AFP的灵敏度、特异度、符合率均高于CA125或AFP单独检验（P<0.05）。结论 AST、CHE、CA125、AFP在肝硬化患者临床诊断中具有良好的应用表现,是反映患者肝硬化病情进展的重要参考指标。

Objective To analyze the diagnostic efficacy of aspartate aminotransferase（AST）,cholinesterase（CHE）,carbohydrate antigen 125（CA125）,and alpha fetoprotein（AFP）in patients with liver cirrhosis．Methods A total of 70 patients with liver cirrhosis were included in the observation group as the study subjects,and 70 healthy individuals who underwent physical examinations during the same period were selected as the control group．Both groups of research subjects underwent biochemical testing and tumor marker testing．The AST,CHE,CA125,and AFP detection results of two groups of research subjects were compared,and the diagnostic effect of the above indicators on patients with liver cirrhosis were analyzed．Results The CHE test results of patients with liver cirrhosis in the observation group were significantly lower than those of healthy individuals undergoing physical examination,and the AST,CA125,and AFP test results were higher（P<0.05）．AST and CHE had good sensitivity and specificity in the diagnosis of liver cirrhosis．The sensitivity,specificity and coincidence rate of CA125 combined with AFP were higher than those of CA125 or AFP alone．Conclusions AST,CHE,CA125,and AFP have good clinical application performance in the diagnosis of liver cirrhosis patients,and are important reference indicators reflecting the progression of liver cirrhosis in patients．

目的 挖掘使用美托洛尔后的药物不良事件（ADE）,为临床合理用药提供参考意见。方法 对美国食品药品管理局（FDA）FDA药物ADE报告系统（FAERS）数据库进行信号挖掘,采用报告比值比法和比例报告比值法,分析FAERS数据库中2004年第1季度至2023年第2季度关于美托洛尔的ADE报告。结果 在FAERS数据库中收集到美托洛尔相关ADE共24 184例、667个阳性信号,共涉及27个系统器官分类。ADE严重报告共16 766（占69.33%）,ADE报告频次排名前3的分别是头晕、心动过缓、呼吸困难。结论 美托洛尔的不良反应主要集中在全身性疾病及给药部位各种反应、心脏器官疾病和各类损伤。在使用美托洛尔过程中发生ADE时,应该及时采取相应的干预措施。

Objective To explore the adverse drug events（ADEs）after the use of metoprolol and provide reference opinions for clinical rational drug use．Methods Signal mining was conducted on the FDA Adverse Event Reporting System（FAERS）database in the United States．The reporting ratio method and proportional reporting ratio method were used to analyze ADEs reports related to metoprolol in the FAERS database from the first quarter of 2019 to the second quarter of 2023．Results A total of 24 184 cases of metoprolol related ADEs were collected in the FAERS database,with 667 positive signals and a total of 27 system organ class involved．Conclusions The adverse reactions of metoprolol mainly focus on systemic diseases,various reactions at the administration site,heart organ diseases,and various injuries．It is recommended that timely intervention measures should be taken when ADE occurs during the use of metoprolol．

目的 分析以信息-动机-行为技巧（IMB）模型为基础延续护理平台在帕金森病患者中的应用效果。方法 纳入河南省人民医院在2019年1月至2022年1月期收治的帕金森病患者96例进行研究,将其依据随机数表法分为对照组和观察组,均为48例,对照组均给予常规护理干预,观察组均给予以IMB模型为基础延续护理平台干预。比较两组主要照顾者干预前24 h（T0）和完成干预24 h（T1）内的心理状态评分、自我效能、希望水平、运动能力、肌张力、认知功能,并评估T1时刻的Barthel指数。结果 观察组患者T1时的汉密尔顿焦虑量表（HAMA）（16.64±2.57）分、汉密尔顿抑郁量表（HAMD）（16.38±1.69）分均低于对照组（20.65±1.68）（19.57±2.65）分（t=10.116、5.407,P<0.001）,观察组患者T1时的自我效能（7.24±1.48）分、希望水平（44.51±4.07分）均高于对照组（6.02±1.74）（38.95±4.54）分（t=3.357、3.311,P<0.001）,观察组患者T1时的运动能力评分（43.62±4.01）分高于对照组（39.17±5.25）分（t=4.715,P<0.001）,肌张力评分（0.72±0.21）分低于对照组（1.13±0.52）分（t=5.118,P<0.001）,观察组患者T1时刻的Barthel指数评估依靠帮助完成率（6.25%）、部分完成率（10.42%）低于对照组（25.00%）、（27.08%）（χ²=6.353、5.263,P<0.05）,观察组患者T1时刻的命名能力（3.46±0.51）、延迟回忆（3.78±0.21）分、语言能力（3.29±0.48）分、注意力评分（3.95±0.10）分均高于对照组（2.91±0.98 ）（3.21±0.96）（2.87±0.82）（3.76±0.05）分（t=3.698、3.675、3.846、4.305,P<0.001）。结论 以IMB模型为基础延续护理平台干预能够改善帕金森病患者的负性情绪,提升自我效能、希望水平,改善运动能力、肌张力、日常生活能力、认知水平。

Objective To analyze the application effect of the information motivation behavioral skills（IMB）model as a continuous care platform in Parkinson's patients. Methods A study was conducted on 96 Parkinson's patients enrolled in our hospital from January 2019 to January 2022．They were divided into a control group and an observation group based on a random number table method,with 48 patients in each group．The control group received routine nursing intervention,while the observation group received continuous nursing platform intervention based on the IMB model．The psychological state scores,self-efficacy,hope level,motor ability,muscle tone,cognitive function of the two main caregivers 24 hours before intervention（T0）and 24 hours after completion of intervention（T1）,and evaluate the Barthel index at T1 time were compared. Results The Hamilton Anxiety Scale（HAMA）[（16.64±2.57）points] and Hamilton Depression Scale（HAMD）[（16.38±1.69 points）scores] of patients in the observation group at T1 were lower than those in the control group [（20.65±1.68）points,（19.57±2.65）points]（t=10.116,5.407,P<0.001）．The self-efficacy of patients in the observation group at T1 was（7.24±1.48）points．The hope level [（44.51±4.07）points] was higher than that of the control group [（6.02±1.74）points,（38.95±4.54）points]（t=3.357,3.311,P<0.001）．The motor ability score at T1 time in the observation group [（43.62±4.01）points] was higher than that in the control group [（39.17±5.25）points]（t=4.715,P<0.001）,and the muscle tone score [（0.72±0.21）points] was lower than that in the control group [（1.13±0.52）points]（t=5.118,P<0.001）．The Barthel index evaluation of patients in the observation group at T1 time relied on help completion rate（6.25%）and partial completion rate（10.42%）,which were lower than those in the control group（25.00%）and（27.08%）（χ²=6.353,5.263,P=0.012,0.022）．The naming ability [（3.46±0.51）points],delayed recall [（3.78±0.21）points],language ability [（3.29±0.48）points],attention scores [（3.95±0.10）points] were higher than the control group [（2.91±0.98）points,（3.21±0.96）points,（2.87±0.82）points,（3.76±0.05）points]（t=3.698,3.675,3.846,4.305,P=<0.001,<0.001,<0.001）. Conclusions Continuing nursing platform intervention based on the IMB model can improve the negative emotions,self-efficacy,hope level,motor ability,muscle tone,daily living ability,and cognitive level of Parkinson's patients．

目的 评价不同间变性淋巴瘤激酶（ALK）抑制剂联合安罗替尼治疗非小细胞肺癌（NSCLC）的疗效。方法 收集ALK突变阳性NSCLC患者的临床资料,筛选服用ALK抑制剂疗效不佳再加用安罗替尼的病例。根据不同的用药方案分为阿来替尼+安罗替尼,塞瑞替尼+安罗替尼和克唑替尼+安罗替尼三个组别。记录患者联合用药前最近一次的影像学检查结果,并以此为基线按Recist1.1评价疗效,以病情进展、患者死亡、停药、改变治疗方案为终点计算各组患者的无事件生存期（EFS）,收集肿瘤标志物、血常规和肝功、心功能、肾功能生化检测等指标数据,统计分析患者联合用药前后各项指标的变化。结果 经筛选,共纳入49例患者的临床数据。阿来替尼+安罗替尼组有23例,疾病控制率（DCR）为86.96%;平均EFS为（10.8±3.6）个月,中位EFS为8.3个月;塞瑞替尼+安罗替尼组有14例,DCR为71.43%;平均EFS为（6.5±2.9）个月,中位EFS为5.6个月;克唑替尼+安罗替尼组有12列,DCR为66.67%;平均EFS为（7.7±3.2）个月,中位EFS为7.2个月。阿来替尼+安罗替尼组的平均EFS长于另外两组（P<0.05）。各研究组肿瘤标志物仅有CyFra21-1在克唑替尼+安罗替尼组在联合用药后升高（P<0.05）,生化检测和血常规指标在用药前后差异无统计学意义（P>0.05）。结论 ALK抑制剂与安罗替尼联用,疗效最好为阿来替尼,其次为塞瑞替尼,最后为克唑替尼。三种ALK抑制剂与安罗替尼联用后,均未导致心、肝、肾功能和血细胞损害。

Objective To evaluate the efficacy of different anaplastic lymphoma kinase（ALK）inhibitors combined with anlotinib in the treatment of non-small cell lung cancer（NSCLC）. Methods Clinical data of drug resistant NSCLC patients with ALK positive mutation was collected who were treated with ALK inhibitors and anlotinib synchronously．According to different regimens,three groups were set,alectinib+anlotinib,ceritinib+anlotinib,and crizotinib+anlotinib．The latest imageological examination results of the patient before the synchronous therapy was set as the baseline to evaluate the therapeutic effect according to Recist1.1．The event free survival（EFS）of each group was calculated with disease progression,patient death,treatment discontinuation and changing regimen as endpoints．Data of tumor markers,hematology test,liver function,cardiac function,renal function biochemical examination was collected and analyzed statistically before and after the combination therapy,with P<0.05 as the statistically significant difference. Results After screening,clinical data of 49 patients were collected．Twenty-three patients in the alectinib+anlotinib group,with a disease control rate（DCR） of 86.96%;mean EFS was（10.8±3.6）months,median EFS of 8.3 months;14 patients in the ceritinib+anlotinib group,with a DCR of 71.43%,mean EFS was（6.5±2.9）months,median EFS was 5.6 months;12 patients in the crizotinib+anlotinib group,with a DCR of 66.67%,mean EFS was（7.7±3.2）months,median EFS was 7.2 months．EFS of alectinib+anlotinib group was longer significantly than the other two groups（P<0.05）．Only CyFra21-1,increased significantly after the combination of crizotinib and anlotinib（P<0.05）．No statistically significant difference in biochemical test and hematology test before and after the treatment（P>0.05）． Conclusions The therapeutic effect of ALK inhibitors with anlotinib was ordered,alectinib being the most effective,followed by ceritinib and finally crizotinib．The combination of ALK inhibitors with anlotinib did not cause any abnormal results in the examination of heart,liver,kidney and blood cells．

目的 研究核磁共振（MR）引导的海马保护技术应用于小细胞肺癌全脑放射治疗（放疗）的效果。方法 对确定行全脑放疗的30例小细胞肺癌脑转移患者,行常规放疗CT定位后以定位体位行全头颅MR平扫,将计算机断层扫描（CT）和MR的T1加权像在Monaco 5.1计划系统上进行精准融合,勾画全脑放疗及海马区域,在海马区域三维方向上分别外扩5、15 mm作为海马与计划靶区之间的剂量跌落,每一例患者在Monaco 5.1计划系统上按照不保护海马组织以及外扩5、15 mm进行保护设计3个容积旋转调强技术（VMAT）放疗计划,观察海马组织的平均及最大放疗剂量。结果 增加保护海马组织之后,3个放疗计划的D100均≥95%,每例的3个放疗计划间D100比较差异无统计学意义（P>0.05）;设置外扩5、15 mm的剂量跌落区后,左、右海马的平均剂量、最大剂量均明显降低,而且3个放疗计划的海马平均剂量、最大剂量之间对比差异有统计学意义。结论 小细胞肺癌脑转移患者进行全脑放疗时,利用MR引导的海马保护技术并设置外扩15 mm的剂量跌落区,能够显著降低海马的剂量,达到保护目的。

Objective To explore the application of MR guided hippocampal avoidant whole brain radiotherapy（WBRT）for small cell lung cancer（SCLC）．Methods Thirty SCLC patients with brain metastases who underwent WBRT were enrdled．After routine CT localization was performed,and a head MR was performed in a the same position．T1 weighted images of MR and CT images were accurately fused on the Monaco 5.1 planning system．The entire brain tissue and hippocampus region were delineated． The dose drop areas between the hippocampus and the planned target area were expanded 5mm and 15mm in the three-dimensional direction of the hippocampus,respectively．Three volumetric modulated arc therapy（VMAT）radiotherapy plans were designed for each patient on the Monaco 5.1 planning system based on whether the hippocampal tissue was avoid．The average and maximum doses of hippocampal tissue were observed．Results After the avoidance of hippocampal tissue,the D100 of the three radiotherapy plans reached ≥95%,and there was no significant difference in D100 between the three radiotherapy plans in each case．After setting dose drop areas of 5mm and 15mm for external expansion,the average and maximum doses of the left and right hippocampus were significantly reduced,and there was a significant difference in the comparison between the average and maximum doses in the hippocampus of the three radiotherapy plans．Conclusions MR guided hippocampal avoidant technology and the setting of a 15 mm dose drop area can significantly reduce the dose to the hippocampus in patients with SCLC undergo whole brain radiotherapy．

随着糖尿病发病率不断攀升,人们逐渐聚焦于糖尿病合并骨质疏松。围绕此疾病,国内外学者开展了广泛而深入的研究,临床实践聚焦于两点：糖尿病的精准治疗和骨质疏松的有效干预。在确保血糖稳定的基础上,致力于抑制骨吸收、促进骨形成。在此治疗理念指导下,临床医生应当更加全面了解血糖管理与抗骨质疏松药物的作用机制并合理应用,更大程度改善患者的临床症状及预后。然而,药物作用机制复杂,联合应用存在潜在药物相互作用问题。未来研究方向包括探索更安全有效的联合治疗方案,更加精确化地治疗以提高临床疗效。文章分析了降糖药物及抗骨质疏松药物对疾病的疗效,并展望未来的研究方向,旨在为临床实践提供更为深刻与全面的指导。

As the incidence of diabetes mellitus continues to rise,people are also gradually focusing on diabetes mellitus combined with osteoporosis,which puts patients at a higher risk of fragility fracture．Scholars at home and abroad have conducted extensive and in-depth research around this condition,and clinical practice has focused on two points：first,the precise treatment of diabetes,and second,the effective intervention of osteoporosis．On the basis of ensuring blood glucose stabilization,we are committed to inhibiting bone resorption and promoting bone formation．Under the guidance of this therapeutic concept,we should have a more comprehensive understanding of the mechanism of action of blood glucose management and anti-osteoporosis drugs and apply them rationally,aiming to improve the clinical symptoms and prognosis of patients to a greater extent through dual intervention． However,the mechanism of action of different drugs is complex,and there are potential drug-drug interactions and safety issues associated with their combined use．Future research directions should include exploring safer and more effective combination therapies,developing novel drugs,and more precise and individualized treatments to improve clinical efficacy．This article analyzes the efficacy of glucose-lowering drugs and anti-osteoporosis drugs on the disease and looks forward to future research directions,aiming to provide more profound and comprehensive guidance for clinical practice．