目的 通过分析奥氮平的群体药代动力学研究,探讨影响奥氮平药动学参数的因素,为临床制定个体化给药方案提供依据。方法 在中国知网、万方、维普、迈特思创、PubMed和Embase等中英文数据库,以“奥氮平”“群体药代动力学”“模型”“非线性混合效应模型”及“olanzapine pamoate”“olanzapine”“population pharmacokinetic”“pharmacokinetic model”“nonlinear mixed effect”“NONMEM”为检索策略,检索建库至2023年5月所有关于奥氮平群体药代动力学的研究。结果 共纳入14篇奥氮平的群体药代动力学研究,大多数研究将奥氮平的药代动力学描述为一个单室模型。成人群体药代动力学模型群体典型值吸收速率常数：（0.3~2.85）/h;表观分布清除率：（10.4~25.4）L/h;表观分布容积：（223~2 390）L。儿童青少年模型群体典型值吸收速率常数：（0.142~0.758）/h;表观分布清除率：（13.6~16.8）L/h;表观分布容积：（322~899）L。年龄、体质量、性别、种族、吸烟状况、合并用药是影响奥氮平药动学参数的显著协变量。结论 奥氮平药动学参数估计值存在差异且有不同程度的个体间变异,未来应侧重于对特殊人群的研究。有必要对先前发表的模型进行外部验证,以便更准地的描述模型的适用性。

Objective By analyzing the population pharmacokinetics of olanzapine,the factors affecting the pharmacokinetic parameters of olanzapine were discussed,so as to provide a basis for the clinical formulation of individualized dosing regimens．Methods In Chinese and English databases such as CNKI,Wanfang,Wipro database,FMRS,PubMed and Embase,all studies on population pharmacokinetics of olanzapine from the establishment of the database to May 2023 were searched with “olanzapine pamoate”“olanzapine”,“population pharmacokinetics”,“pharmacokinetic model”,“nonlinear mixed-effect” and “NONMEM” as key words．Results A total of 14 population pharmacokinetic studies of olanzapine were included．Most studies described the pharmacokinetics of olanzapine as a single-chamber model．Adult pharmacokinetic model population typical values absorption rate constant was（0.3-2.85）/h;apparent distribution clearance was（10.4-25.4）L/h;apparent volume of distribution was（223-2390）L．absorption rate constants of the population of children and adolescents was（0.142-0.758）/h,apparent distribution clearance was（13.6-16.8）L/h,apparent volume of distribution was（322-899）L．Age,weight,gender,ethnicity,smoking status and concomitant medication were significant covariates affecting the pharmacokinetic parameters of olanzapine．Conclusions Estimates of pharmacokinetic parameters of olanzapine vary and have varying degrees of inter-individual variation．In the future,research should focus on special populations．Externally validation of previously published models should also be performed to more accurately describe the applicability of the models．

目的 检测微小RNA（miR）在人黑色素瘤中的表达情况,研究miR-412通过抑制性别确定区Y框转录因子6（SOX6）的表达影响黑色素瘤细胞增殖及侵袭能力的变化。方法 癌症基因组图谱（TCGA）数据库分析发现miR-412在黑色素瘤中异常表达,为研究其表达与肿瘤的相关性,采用Transwell小室,非锚定独立生长实验分析miR-412对黑色素瘤细胞增殖及侵袭能力的影响。软件预测SOX6可能为其靶向基因,采用荧光素酶报告分析及Western blot实验检测SOX6与miR-412的靶向调节情况。结果 TCGA数据库分析黑色素瘤组织中miR-412表达水平高于正常对照组,表达越高,生存时间越短。Transwell小室,非锚定独立生长实验显示miR-412过表达后促进细胞增殖及侵袭能力,而下调miR-412后抑制黑色素瘤细胞增殖及侵袭能力;通过靶点预测miR-412结合SOX6基因3’-非翻译区（UTR）,导致SOX6蛋白因miR-412表达增高而下调;同时在miR-412下调的细胞中抑制SOX6表达可恢复黑色素瘤细胞的增殖及侵袭能力。结论 miR-412过表达后促进黑色素瘤细胞增殖及侵袭能力,反之则抑制黑色素瘤细胞增殖及侵袭能力。 miR-412通过靶向调控SOX6影响黑色素瘤细胞增殖及侵袭,提示miR-412在黑色素瘤的发病过程中起重要作用,是潜在的治疗靶点。

Objective To assess the expression of miR-412 in human melanoma and investigate how miR-412 modulates melanoma cell proliferation and invasive capacity by inhibiting SRY-Box Transcription Factor 6,（SOX6） expression．Methods Analysis of the TCGA（The Cancer Genome Atlas）database identified aberrant miR-412 expression in melanoma．To explore its relevance to tumorigenesis,we conducted Transwell chamber and non-adherent independent growth assays to examine the effects of miR-412 on melanoma cell proliferation and invasion．Software predictions highlighted SOX6 as a potential target gene．We performed luciferase reporter assays and Western blot experiments to elucidate the regulatory interactions between SOX6 and miR-412．Results TCGA database analysis revealed significantly elevated miR-412 expression levels in melanoma tissues compared to the normal control group．Moreover,higher miR-412 expression correlated with shorter survival times．Functional assays using Transwell chambers and non-adherent independent growth assays demonstrated that overexpressing miR-412 enhanced cell proliferation and invasive capabilities．Conversely,reducing miR-412 expression restrained these attributes in melanoma cells． Target prediction analysis indicated that miR-412 binds to the 3’-UTR region of SOX6,resulting in decreased SOX6 protein levels due to increased miR-412 expression．Intriguingly,inhibiting SOX6 expression concurrently amplified the proliferation and invasive potential of melanoma cells,which was initially dampened by miR-412 downregulation．Conclusions Elevated miR-412 expression augments melanoma cell proliferation and invasive capabilities,while its suppression diminishes these traits．Through its targeted regulation of SOX6,miR-412 exerts a significant influence on melanoma cell proliferation and invasion．These findings underscore the pivotal role of miR-412 in melanoma pathogenesis and underscore its potential as a promising therapeutic target．

肝癌患者因食欲降低、进食减少导致不同程度的营养不良,引发厌食症,甚至恶病质,严重影响患者生存质量。食欲评估是降低营养风险的基础,医护人员可通过食欲症状的评估调整患者饮食及营养指导措施,以改善患者营养状态,提高生存质量。该文对食欲的评估工具、方法及干预在肝癌营养不良患者中的应用现状进行阐述,为肝癌患者的食欲干预提供科学依据。

Hepatocellular carcinoma patients suffer from different degrees of malnutrition due to decreased appetite and eating,which triggers anorexia and even cachexia,seriously affecting the quality of patient survival．Appetite assessment is the basis for reducing nutritional risk,and healthcare professionals can adjust patients’ diet and nutritional guidance measures through the assessment of appetite symptoms in order to improve patients’ nutritional status and survival quality．In this paper,the current status of the assessment tools,methods and interventions of appetite in malnutrition patients with hepatocellular carcinoma are described to provide a scientific basis for appetite interventions．

药物递送系统对于各类疾病意义非凡,但传统药物载体面临细胞毒性强、组织相容性低、半衰期短和靶向性弱等诸多挑战。血小板及其相关衍生物作为新型药物载体具有更为显著的优势。由于血小板自身的生理特点,以及在肿瘤、心血管疾病、血栓性疾病、感染等多种疾病中发挥的病理生理作用,血小板能够弥补传统药物载体的缺陷,具有极大的临床转化意义。该文总结了血小板相关药物递送系统目前的研究进展,以期为新型药物载体研究提供参考。

Drug delivery systems are important for various diseases,but conventional therapeutic drug have many shortcomings,such as high cytotoxicity,low histocompatibility,short half-life and weak targeting．Platelets and their derivatives have more significant advantages as novel drug carriers．Platelets play an important role in the pathophysiology of a wide range of diseases including oncology,cardiovascular diseases,thrombosis and infection．In this paper,we summarized the current research progress of platelet-related drug delivery systems to provide a reference for the research of novel drug delivery systems．

目的 分析音乐治疗焦虑领域研究热点的演变与趋势。方法 利用文献计量学方法对近20年（2003——2023）发表音乐治疗焦虑方面的研究与文献进行了可视化分析：对中国知网（CNKI）及Web of Science（WOS）文献库中收录的文献进行关键词（中文关键词：音乐治疗、焦虑;英文关键词：Music therapy、Anxiety）检索,利用CiteSpace 6.3 R2软件绘制知识图谱进行可视化分析。结果 通过文献的检索与筛选最终纳入中文文献506篇及英文文献1 782篇,其中国内外主要发文者为刘月芳、刘春艳、Bradt、Cold、Silverman等研究者团队,国内外主要研究机构均为高校,但国内高校相对于国外相关研究开展较为独立且合作联系较少;发文国家主要为美国、中国以及土耳其,西方国家之间的合作联系较为密切,我国开展相关跨地域研究主要是与亚洲国家进行多中心合作。国内研究热点为“音乐疗法”“心理干预”“五行音乐”等,国外研究热点为“Pain”“Depression”“Quality of life”等。结论 本文通过CiteSpace软件进行文献计量学分析发现,音乐治疗与焦虑结合是国内外研究的热点,国内研究聚焦于焦虑,而国外研究更关注音乐治疗在广泛心理问题中的应用。尽管该研究领域发展迅速,但国内外合作交流较少,国际研究团队间合作不够紧密。未来研究需进一步探索音乐治疗的机制和最佳实践方法,加强跨学科合作,利用科技创新,结合中国文化特色,以期实现音乐治疗在焦虑治疗中的更广泛应用,并提升患者的生活质量。同时,未来相关研究方法需多样化,以全面掌握研究趋势,为音乐治疗焦虑提供更有力的证据支持。

Objective To explore the evolution and trends of research hotspots in the field of music therapy for anxiety and provide reference and basis for related research．Methods Bibliometric analysis method was used to visualize and analyze the research and literature on music therapy for anxiety in the past 20 years（2003-2023）．Keyword searches were conducted in Chinese National Knowledge Infrastructure（CNKI）and Web of Science（WOS）databases,and a knowledge map was drawn using CiteSpace 6.3 R2 software for visualization analysis．Results Through the literature search and screening,506 Chinese and 1782 English literatures were included,and the main authors at home and abroad were researcher teams such as Liu Yuefang,Liu Chunyan,Bradt,Cold and Silverman．The main research institutions at home and abroad were universities,but domestic universities were more independent and had fewer collaborative relationships than foreign ones．The main publishing countries were the United States,China and Turkey,and there was closer cooperation between western countries．Multicenter cooperation with Asian countries was the main form of cross-region research in China．The research hotspots at home were “music therapy”,“psychological intervention”,“five elements music”,while the foreign research hotspots were “pain”,“depression”,and “quality of life”．Conclusions The combination of “music therapy” and “anxiety” is the main research hotspot at home and abroad in recent years．Among them,foreign scholars mainly use anxiety and other psychological problems as research topics to explore the application of music therapy to these issues,while domestic scholars focus on the research of anxiety and propose many music therapy programs for anxiety．In addition,there is relatively little cooperation and communication between domestic and foreign research sectors,and the degree of coincidence among international research teams is not high．Therefore,research teams at home and abroad should strengthen cooperation and communication．Based on the analysis of research hotspots in music therapy for anxiety in the past 20 years,this field has received considerable attention and has developed rapidly,but there are still many aspects that need to be explored and improved through continuous efforts and innovation．

脊髓损伤是一种高致残性中枢神经系统疾病,目前缺乏有效的治疗措施。干细胞组织工程兴起和神经调控技术的发展,给脊髓损伤的治疗带来新的希望。目前,多项针对脊髓损伤的干细胞相关治疗项目的临床研究已在全球注册,干细胞疗法是脊髓损伤领域的研究热点,具有良好的应用前景。而神经调控技术一直在临床上脊髓损伤后的康复治疗中发挥着重要作用,特别是靶向神经调控技术近年在脊髓损伤治疗方面取得突破性进展。有研究尝试联合干细胞疗法和神经调控技术应用治疗脊髓损伤,试图取得更好的效果。本文综述了干细胞疗法和神经调控技术在脊髓损伤治疗中的研究进展,旨在探讨其作用效果、修复机制、应用前景以及面临的问题,进一步为脊髓损伤的基础研究和临床转化提供参考。

Spinal cord injury is a highly disabling disease of the central nervous system without effective treatment to date．With the rise of stem cell and tissue engineering,and the breakthrough of neuromodulation technology,it brings new hope to the treatment of spinal cord injury．At present,a number of clinical studies on stem cell-related treatment projects for spinal cord injury have been registered worldwide,which has become a research hotspot．Neuromodulation technology has been playing an important role in the clinical rehabilitation of spinal cord injury．Especially,breakthroughs have been made in the treatment of spinal cord injury by targeted neuromodulation technology in recent years,which is encouraging．Some studies have attempted to combine stem cell therapy and neuromodulation technology to treat spinal cord injuries in an attempt to achieve better effect．This review summarizes the research progress of stem cell therapy and neuromodulation technology in the treatment of spinal cord injury,with the aim of discussing their effect,repair mechanisms,application prospect and various problems to face,and providing further reference for the basic research and clinical transformation of spinal cord injury．

目的 以临床二级学院附属医院的管理为例,对当下医科类高校研究生校院二级管理存在问题进行探讨。方法 对某医科高校附属医院474名临床医学研究生及9名辅导员进行调查。结果 55.56%的研究生表示导师的约束力最大,但42.56%的学生与导师是不定期沟通;39.83%的学生不认可在培养方式上严格区分培养,其中学术型硕士二年级学生中44.3%认为有一定区别,但区别不大;学院配备的学生工作管理专职人员不足、学院层级的管理制度和机制不健全和二级学院权责不清运行机制不顺畅。结论 明确医科类高校与二级附属医院之间的关系、提高治理效能激活医科类高校二级附属医院人才培养的自主性和内生动力、医科类高校二级附属医院研究生施行差异化培养和整合资源,共同提升医科高校与附属医学院的整体水平。

Objective To discuss the existing problems of secondary management in medical colleges and universities,taking the management of secondary college of affiliated hospital as an example．Methods Through the investigation of 474 clinical medical graduate students and 9 counselors in the affiliated hospital of a medical university．Results There was 55.56% of the graduate students said that the supervisor was the most binding force,but 42.56% of the students communicated with the supervisor irregularly;39.83% of the students do not recognize the strict differentiation of training methods,44.3% of the students in the second year of study believed that there was a certain difference,but the difference was not big．The college was equipped with insufficient full-time staff for student work management,the management system and mechanism at the college level were not perfect,and the power and responsibility of the second-level college were not clear and the operation mechanism is not smooth．Conclusions Clarify the relationship between medical colleges and secondary affiliated hospitals,improve governance efficiency and activate the autonomy and endogenous motivation of talent training in secondary affiliated hospitals of medical colleges and universities,implement differentiated training the graduates of secondary affiliated hospitals of medical colleges and universities,integrate resources,so as to jointly improve the overall level of medical colleges and universities and affiliated medical schools．

目的 探讨护理目标执行理念护理在哮喘患儿治疗中的价值。方法 前瞻性选取泉州市妇幼保健院于2021年8月—2023年8月收治的100例支气管哮喘患儿,应用随机数字表法将其分为两组,每组均为50例。对照组采取常规护理,观察组在常规护理基础上给予护理目标执行理念护理。3个月后,对比两组家属对患儿的疾病管理能力、哮喘控制状况、生活质量。结果 护理后两组患儿家属相关家庭管理测量量表（FaMM）评分均升高,且观察组高于对照组（P<0.05）;观察组患儿哮喘控制率高于对照组（P<0.05）;护理后两组患儿情感、活动、症状相关标准儿童哮喘生活质量评分表（PAQLQ）评分均升高,且观察组高于对照组（P<0.05）。结论 护理目标执行理念护理可改善哮喘患儿家属对患儿疾病的管理能力,改善哮喘控制效果,提升患儿生活质量。

Objective To explore the value of nursing goal execution concept intervention in the treatment of children with asthma．Methods From August 2021 to August 2023,100 children with bronchial asthma admitted to Quanzhou Maternal and Child Health Hospital were Prospective selected．They were randomly divided into observation group and control group,with 50 cases in each group．The control group of children received routine care,while the observation group of children received intervention based on the nursing goals execution concept in addition to routine care．After 3 months of intervention,The disease management ability,compliance,asthma control and quality of life of the two groups were compared．Results Family-related FaMM scores were increased in all two groups after the intervention,and the observation group was higher than the control group（P<0.05）．The asthma control rate of the children in the observation group was higher than that in the control group（P<0.05）;after nursing,the PAQLQ score increased,and the observation group was higher than the control group（P<0.05）．Conclusions Intervention based on the nursing goals execution concept can improve the management ability of family members of asthma patients towards their diseases,and enhance their quality of life,which is worthy of clinical application and promotion．

目的 探讨早产儿语言-社会行为情况及其影响因素,研究语言-社会行为发育与智能发育之间的关系,为早产儿保健提供指导。方法 采用自制的一般情况问卷对125例早产儿开展随访、追踪,直至2岁时,采用盖泽尔发展量表（GDS）进行语言-社会行为及智能发育评估。结果 早产儿语言发育正常43例（34.4%）,社会行为发育正常40例（32%）。早产儿语言发育商平均为（67.99±25.75）,社会行为发育商平均为（67.75±23.98）,处于发育低下水平。性别、脑出血病史、定期随访史、康复干预史、家庭干预史在语言、社会行为方面比较差异均无统计学意义（P>0.05）。不同胎儿期安胎史、胎龄、出生体质量在语言、社会行为方面比较差异有统计学意义（P<0.05）;且胎儿期反复安胎,胎龄小,出生体质量低,语言及社会行为发育较差。与出生时无中-重度窒息史的患儿相比,出生时有中-重度窒息的患儿存在更多的语言发育异常,比较差异有统计学意义（P<0.05）;但在社会行为发育方面比较差异无统计学意义（P>0.05）。语言-社交行为发育落后的同时,早产儿的大运动、精细动作、适应性行为也存在落后,五大能区比较差异并均有统计学意义（P<0.05）。结论 多数早产儿存在语言-社会行为发育落后,其同时可能伴有更多的运动和适应行为发育问题;语言-社交行为发育落后的患儿在胎儿期存在反复安胎且胎龄较小、出生体质量更低或有中-重度窒息史。对早产儿的语言-社会行为要及时给予关注,早期发现并早期干预,改善预后。

Objective To explore the language-social behavior of preterm infants and its influencing factors,to study the relationship between language-social behavior development and intellectual development,and to provide guidance for preterm infants' health care．Methods A self-administered general questionnaire was used to follow up 125 preterm infants until the age of 2 years,and Gesell development scale（GDS）was used to assess their language-social behavior and intellectual development．Results Preterm infants had normal language development in 43 cases（34.4%）and normal social behavioral development in 40 cases（32%）．The mean language development quotient of preterm infants was（67.99±25.75）and the mean social behavioral development quotient was（67.75±23.98）,which was at the low developmental level．There were no significant differences in gender,history of cerebral hemorrhage,regular follow-up,rehabilitation intervention,family intervention and language or social behavior（P>0.05）．Infants with different fetal age history,gestational age,and birth weight varied significantly in language and social behavior（P<0.05）;and with repeated miscarriage,small gestational age,low birth weight,showed poor language and social behavior development．Compared the children with and without moderate to severe asphyxia at birth,there was statistically significant differences in language development（P<0.05）,but in social behavior there was no significant difference（P>0.05）．The backward development of language-social behavior was accompanied by backwardness in gross motor,fine motor,and adaptive behavior in preterm infants,and the differences in the five major domains were all present and statistically significant（P<0.05）．Conclusions A major of preterm infants have poor language-social behavior development,which may be accompanied by more motor and adaptive behavior development problems;children with poor language-social behavior development have repeated miscarriage prevention at younger gestational ages,lower birth weights,or a history of moderate-to-severe asphyxia during the fetal period．It is important to give timely attention to language-social behavior in preterm infants for early detection and early intervention to improve prognosis．

目的 探讨胆囊结石并发肝外胆管结石经腹腔镜胆囊切除术（LC）联合内窥镜逆行胰胆管造影术（ERCP）/内窥镜下括约肌切开术（EST）治疗的临床效果。方法 选取2020年1月—2023年6间就诊于南平市第一医院的86例胆囊结石合并肝外胆管结石患者,根据治疗方案不同分为对照组（n=40）和观察组（n=46）。对照组给予LC联合经腹腔镜胆总管切开取石术（LCBDE）治疗,观察组给予LC联合ERCP、EST在治疗,观察两组手术相关指标情况、血管紧张素水平、肝功能以及并发症发生情况。结果 观察组患者术中出血量少于对照组的（t=12.440,P<0.001）,观察组手术用时、肛门排气时间以及住院时间均短于对照组（均P<0.001）;观察组血管紧张素1-7（Ang1-7）、血管紧张素Ⅰ（AngⅠ）、血管紧张素Ⅱ（AngⅡ）水平低于对照组,组间比较差异均无统计学意义（均P>0.05）;观察组总胆红素（TBIL）、谷氨酸转氨酶（ALT）水平低于对照组水平,组间比较差异无统计学意义（均P>0.05）;观察组无患者发生胆漏、结石残留,对照组胆漏、结石残留发生率分别为5.00%、2.50 %,组间对比差异均无统计学意义（均P>0.05）,观察组出血、胆道感染生率分别为4.35 %、2.17 %低于对照组10.00%、5.00 %,组间对比差异均无统计学意义（均P>0.05。结论 LC联合ERCP/EST治疗胆囊结石合并肝外胆管结石可以减少术中出血,缩短手术用时和住院时间。

Objective This study aims to investigate the clinical efficacy of laparoscopic cholecystectomy（LC）combined with endoscopic retrograde cholangiopancreatography（ERCP）or endoscopic sphincterotomy（EST）in the treatment of gallbladder stones complicated by extrahepatic bile duct stones．Methods A total of 86 patients with gallbladder stones and extrahepatic bile duct stones treated at the First Hospital of Nanping from January 2020 to June 2023 were selected．According to different treatment regimens,they were divided into a control group（n=40）and an observation group（n=46）．The control group received LC combined with laparoscopic common bile duct exploration（LCBDE）,while the observation group received LC combined with ERCP and EST．Surgical-related indicators,angiotensin levels,liver function,and complications were observed in both groups．Results The observation group had less intraoperative bleeding than the control group（t=12.440,P<0.001）．The observation group had a shorter operation time,postoperative anal exhaust time,and hospital stay than the control group（all P<0.001）．The levels of angiotensin 1-7（Ang1-7）,angiotensin I（AngⅠ）,and angiotensin II（AngⅡ）in the observation group were lower than those in the control group,with no statistically significant differences between the groups（all P>0.05）．Total bilirubin（TBIL）and alanine aminotransferase（ALT）levels in the observation group were comparable to those in the control group（all P>0.05）．No patients in the observation group experienced bile leakage or residual stones,while the incidence rates in the control group were 5.00% and 2.50%,respectively,with no statistically significant differences between the groups（all P>0.05）．The observation group had lower rates of bleeding and biliary tract infection at 4.35% and 2.17%,respectively,compared to the control group at 10.00% and 5.00%,with no statistically significant differences between the groups（all P>0.05）．Conclusions LC combined with ERCP/EST in the treatment of gallbladder stones complicated by extrahepatic bile duct stones can reduce intraoperative bleeding,shorten operation time,and decrease hospital stay．