血友病是一种由于X染色体上凝血因子基因突变所致的遗传性出血性疾病,目前主要的治疗方法是凝血因子替代疗法。但长期频繁的注射用药往往导致患者依从性差,容易产生抑制性抗体,从而影响治疗效果。虽然现在延长半衰期的新型凝血因子药物、人源化双特异性抗体以及抗组织因子途径抑制剂单克隆抗体等用于疾病治疗,在给药方式和作用持续时间上已有很大进步,但它们仍无法治愈血友病。因此,以疾病根治为重要目标的基因治疗被设计出来,近年来受到了广泛的关注。该文介绍了血友病基因治疗的原理、基因治疗载体的选择、基因治疗预处理方案,总结了现阶段基因治疗临床应用的安全性和有效性;最后讨论基因治疗目前存在的问题以及未来发展方向。

Hemophilia is a genetic bleeding disorder resulting from mutations in coagulation factor genes on the X chromosome．The mainstay of current treatment is coagulation factor replacement therapy．However,frequent and long-term injections often lead to poor patient compliance,easy inhibitor development,and compromised therapeutic efficacy．Despite advancements in delivery methods and prolonged action of novel agents such as extended half-life coagulation factor concentrates,humanized bispecific antibodies,and anti-tissue factor pathway inhibitor monoclonal antibodies,these approaches still fall short of curing hemophilia．Consequently,gene therapy,aiming for disease eradication,has garnered significant attention in recent years．This review delves into the principles of gene therapy,the selection of gene therapy vectors,and gene therapy preconditioning regimens．It summarizes the safety and efficacy of gene therapy in current clinical applications and discusses challenges and future directions in this field．

目的 探讨富血小板血浆（PRP）联合关节镜治疗Ⅲ度半月板损伤患者的临床疗效,及其对膝关节功能恢复时间的影响。方法 选取2021年2月—2022年2月南方医科大学南方医院增城院区骨科收治的Ⅲ度半月板损伤患者45例,采用随机数字法分为观察组22例与对照组23例,对照组患者在关节镜下行半月板成形术,观察组在对照组基础上给予PRP治疗。观察两组患者术后恢复时间、治疗效果及并发症发生情况;比较两组治疗前和治疗后1、3、6个月膝关节功能、疼痛情况。结果 利用观察组患者自体全血制备的PRP,其血小板的回收率、红细胞留存率、白细胞留存率分别为（91.00±9.27）%、（0.29±0.12）%、（29.98±6.68）%,PRP制备质量稳定、可控。观察组联合PRP治疗术与关节镜手术治疗后恢复时间均短于对照组,观察组治疗有效率高于对照组（P<0.05）。经重复方差测量分析,两组美国特种外科医院膝关节评分系统（HSS）评分、西安大略大学和麦克马斯特大学骨关节炎指数（WOMAC）评分、视觉模拟疼痛评分法（VAS）交互（F_交互=1.869、F_交互=1.482、F_交互=2.193）比较差异均有统计学意义（P<0.05）;与对照组治疗后1、3、6个月比较,观察组HSS评分升高,WOMAC评分、VAS评分下降（P<0.05）;观察组并发症总发生率4.55%低于对照组30.43%（χ²=5.156、P=0.023）。结论 对于Ⅲ度半月板损伤患者,采用PRP联合关节镜手术治疗可帮助患者消炎止痛、加快疗效、加快膝关节功能的恢复,缩短其恢复的时间,效果良好,且安全性较高。

Objective To investigate the clinical effect of platelet rich plasma（PRP）combined with arthroscopy treatment on patients with third degree meniscus injury,and its impact on the recovery time of knee joint function．Methods From February 2021 to February 2022,45 patients with III-degree meniscal injuries admitted to the Department of Orthopedics,Zengcheng district,Nanfang Hospital of Southern Medical University were selected and divided into an observation group of 22 cases and a control group of 23 cases using the random number method．Patients in the control group received menisplasty under arthroscopy,and the observation group was given PRP treatment on the basis of the control group．The postoperative recovery time,treatment effects and complications of the two groups of patients were observed;the knee joint function and pain of the two groups before treatment and 1,3,and 6 months after treatment were compared．Results The platelet recovery rate,red blood cell retention rate,and white blood cell retention rate of PRP prepared from the autologous whole blood of patients in the observation group were（91.00±9.27）%,（0.29±0.12）%,and（29.98±6.68）% respectively．The PRP preparation quality is stable and controllable．The recovery time after combined PRP treatment and arthroscopic surgery in the observation group was shorter than that in the control group,and the treatment effectiveness of the observation group was higher than that of the control group（P<0.05）．After repeated measures of variance analysis,the comparison of American Hospital for Special Surgery（HSS）Knee Scoring System,Western Ontario and McMaster Universities Osteoarthritis Index（WOMAC）,and visual analogue pain scales（VAS）interacted(F_Interaction=1.869,F_interaction=1.482,F_interaction=2.193),the differences were statistically significant（P<0.05）．Compared with the control group 1,3,and 6 months after treatment,the HSS score of the observation group increased,and the WOMAC score,VAS score decreased（P<0.05）;the total incidence of complications in the observation group was 4.55%,lower than that in the control group（30.43%,χ²=5.156,P=0.023）．Conclusions For patients with III-degree meniscal injuries,PRP combined with arthroscopic surgery can help reduce inflammation and pain,speed up the curative effect,accelerate the recovery of knee joint function,and shorten the recovery time．It has good effects and is relatively safe．

目的 观察营养指导联合预防护理在小儿癫痫意外预防中作用。方法 抽取焦作市妇幼保健院2021年1月—2023年1月收治的116例小儿癫痫患儿,按照护理方法分为两组,每组各58例。对照组行常规护理,联合组患儿在常规护理基础上给予营养指导联合预防护理干预,对比两组家属满意度、患儿依从率、蒙特利尔认知评估量表（MoCA）评分。结果 经过护理干预,联合组家属满意率98.28%,依从率96.55%,比对照组87.93%、82.76%高（P<0.05）;住院至出院居家三个月内,相较于对照组,联合组患儿外伤发生次数、发病持续时间、癫痫发作次数较少（P<0.05）;护理后,联合组MoCA评分高于对照组（P<0.05）。结论 在小儿癫痫意外预防中联合应用营养指导和预防护理可改善患儿遵医行为,优化小儿癫痫意外预防效果,减少患儿外伤、癫痫发生次数,缩短患儿发病持续时间,提升患儿生活质量和家属满意度。

Objective To observe the effect of nutritional guidance combined with preventive nursing on the prevention of epilepsy accidents in children．Methods A total of 116 cases of pediatric epilepsy admitted in Jiaozuo Maternal and Child Health Care Hospital from January 2021 to January 2023 were selected．They were divided into two groups according to the nursing method,with 58 cases in each group．The control group was given usual care,while the combined group was given nutritional guidance combined preventive nursing intervention．The satisfaction,the compliance rate and MoCA score were compared between two groups．Results After nursing intervention,the satisfaction rate of the combined group was 98.28%,and the compliance rate of the combined group was 96.55%,which were higher than 87.93% and 82.76% in the control group（P<0.05）．Within three months from hospitalization to discharge,compared with the control group,number of injuries,duration and frequency of seizures were less in the combined group（P<0.05）．After nursing,the MoCA score of the combined group was higher than that of the control group（P<0.05）．Conclusions The combined application of nutritional guidance and preventive nursing in the prevention of pediatric epileptic accidents can improve the compliance behavior of children,optimize the prevention effect of pediatric epileptic accidents,reduce the incidence of trauma and epilepsy in children,shorten the duration of illness,and improve the quality of life of children and family satisfaction．

目的 探讨特发性间质性肺炎（IIPs）[非特发性肺间质性纤维化（IPF）型]合并弥漫性肺部出血综合征患者治疗方案以及应用价值。方法 报道1例IIPs（非IPF型）合并弥漫性肺部出血综合征患者的治疗经过以及结果,结合文献分析治疗IIPs（非IPF型）合并弥漫性肺部出血综合症临床应用价值。结果 该文报道 l 例特发性肺间质肺炎（非IPF型）伴弥漫性肺泡出血综合征的老年男性患者,合并呼吸、循环衰竭,启用静脉-静脉体外膜肺氧合（VV-ECMO）抢救并成功撤机,病情好转出院。结论 IIPs作为病因以及发病机制未明、临床表现多样的一类肺间质性疾病,需临床多学科协作,及早诊断、治疗,才能成功挽救患者。

Objective To explore the treatment plan and application value of idiopathic interstitial pneumonia（non IPF）complicated with diffuse alveolar hemorrhage syndrome．Methods A case of idiopathic interstitial pneumonia（non IPF）complicated with diffuse alveolar hemorrhage syndrome was reported．The clinical application value of treatment of idiopathic interstitial pneumonia（non IPF）complicated with diffuse alveolar hemorrhage syndrome was analyzed combined with the literature．Results A case of idiopathic interstitial pneumonia（non IPF type）with diffuse alveolar hemorrhage syndrome was reported in this paper． Combined with respiratory and circulatory failure,veno-venous extracorporeal membrane oxygenation was used to rescue and successfully wean,and the condition improved and discharged．Conclusions Through the curative effect evaluation of this patient,it is believed that idiopathic interstitial pneumonia,as a kind of pulmonary interstitial disease with unknown etiology and pathogenesis and diverse clinical manifestations,need clinical multidisciplinary cooperation,early diagnosis and treatment,in order to successfully save the patient．

本文探讨临床药师对口服靶向药物的非小细胞肺癌患者开展药学服务的要点,以案例为依据,通过查阅药品说明书、指南及文献等,分析药学服务的内容和方向。临床药师在安全性评估、剂量调整、个体化治疗方案选择、用药教育和健康宣教等方面为患者和临床医生提供专业、全面的药学服务。临床药师通过全程参与患者的治疗过程,指导患者正确用药、优化治疗方案,利用专业优势解决临床实际问题,提升药学服务质量的同时体现了药师的职业价值。

To explore the key points of pharmaceutical care for non-small cell lung cancer patients with oral targeted drugs．Based on clinical cases,the content and direction of pharmaceutical care were analyzed with drug instructions,guidelines and literature．Clinical pharmacists provided professional and comprehensive pharmaceutical services for patients and clinicians in safety assessment,dose adjustment,individualized treatment plan selection,medication education and health education．Clinical pharmacists participate in the whole treatment process,guide patients to use drugs correctly,optimize treatment plans,use professional advantages to solve clinical practical problems,improve the quality of pharmaceutical care and reflect the professional value of pharmacists．

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．

目的 探讨俯卧位通气在脓毒症合并急性肺损伤患儿的应用效果。方法 选取泉州市儿童医院2020年9月—2023年9月收治的72例脓毒症合并急性肺损伤患儿,应用抽签法将其分为观察组与对照组,均为36例。对照组患儿实施常规仰卧位机械通气与对应护理,观察组患儿在常规护理基础上增加俯卧位通气与对应护理。对比两组患儿机械通气时间,干预前和干预3 d后气道平台压和心率水平,动脉血二氧化碳分压（PaCO₂）、动脉血氧分压（PaO₂）,并计算动脉血氧分压与吸入气中的氧浓度分数比值（PaO₂/FiO₂）,评价两组患儿预后及不良事件发生情况。结果 观察组机械通气时间明显低于对照组（P<0.05）,干预后两组患儿气道平台压、心率均降低,且观察组低于对照组（P<0.05）;干预后两组患儿PaO₂/FiO₂、PaO₂水平升高,观察组高于对照组,PaCO₂降低,观察组低于对照组（P<0.05）;干预后两组患儿全身性感染相关性器官功能衰竭评分（SOFA）、急性生理和慢性健康状况评分Ⅱ（APACHEⅡ）评分均降低,观察组低于对照组（P<0.05）;两组患儿呼吸机管路折管、管路滑脱、压力性损伤等不良事件发生率对比差异无统计学意义（P>0.05）。结论 俯卧位通气在脓毒症合并急性肺损伤患儿的应用效果显著,可降低患儿气道平台压及心率,缩短机械通气时间,改善患儿通气功能,有助提升预后水平。

Objective To explore the application effect of prone position ventilation in children with sepsis complicated with acute lung injury．Methods From September 2020 to September 2023,72 children with sepsis and acute lung injury admitted to Quanzhou Children's Hospital were selected and divided into observation group and control group by drawing lots,both with 36 cases．The children in the control group received routine supine mechanical ventilation and corresponding nursing,and the children in the observation group added prone ventilation and corresponding nursing on the basis of routine nursing．By comparing the duration of mechanical ventilation,airway plateau pressure and heart rate level,PaCO₂,PaO₂,PaO₂/FiO₂,the prognosis and occurrence of adverse events in the two groups were evaluated．Results The mechanical ventilation time in the observation group was significantly shorter than that in the control group（P<0.05）．After intervention,the airway plateau pressure and heart rate levels of the two groups of children decreased,and the observation group was lower than the control group（P<0.05）．After the intervention,the levels of PaO₂/FiO₂ and PaO₂ in the two groups of children increased,with the observation group higher than the control group,while the level of PaCO₂ was lower,with the observation group lower than the control group（P<0.05）．After the intervention,the SOFA and APACHE II scores of the two groups of children decreased,and the observation group was lower than the control group（P<0.05）．There was no difference in the incidence of adverse events such as ventilator tube folding,tube slip and pressure injury between the two groups（P>0.05）．Conclusions The application of prone position ventilation in children with sepsis combined with acute lung injury has a significant effect,which can reduce airway plateau pressure,lower heart rate,shorten mechanical ventilation time,improve ventilation function,and assist in improving prognosis．

目的 对比分析在产程不同阶段对妊娠期高血压产妇给予分娩镇痛的效果差异。方法 选择2021年1月—2022年12月在福清市妇幼保健院接受无痛分娩治疗的240例妊娠期高血压产妇,随机分为在产程活跃期实施镇痛的对照组（n=120）和产程潜伏期实施镇痛的实验组（n=120）,比较两组产妇的产程时间、子宫动脉、胎儿脐动脉血流动力学参数、镇痛效果以及母婴结局。结果 实验组的第一、第二、第三产程时间分别为（389.71±35.05）（58.62±5.26）（8.71±0.69）min,略低于对照组的（403.72±42.19）（60.74±7.22）（8.91±1.62）min,但组间比较差异无统计学意义（P>0.05）;实验组镇痛前、活跃期、第二产程的疼痛评分分别为（9.18±0.13）（1.16±0.22）（2.83±1.16）分,与对照组的（9.22±0.16）（1.24±0.32）（2.72±1.09）分比较差异无统计学意义（P>0.05）,但在潜伏期,实验组产妇疼痛评分为（3.32±0.36）分,低于对照组的（8.11±0.32）分（P<0.05）;关闭镇痛泵后,实验组胎儿脐动脉阻力指数、搏动指数、收缩期峰值流速/舒张期流速分别为（0.58±0.09）（0.81±0.14）（2.31±0.29）,与对照组的（0.54±0.11）（0.79±0.13）（2.24±0.27）比较差异无统计学意义（P>0.05）,实验组产妇子宫动脉阻力指数、搏动指数、收缩期峰值流速/舒张期流速分别为（0.42±0.08）（0.64±0.08）（2.31±0.29）,均高于对照组的（0.39±0.06）（0.58±0.11）（1.65±0.08）（P<0.05）;实验组自然分娩、中转剖宫产、阴道助产例数及新生儿Apgar评分分别为87例、23例、10例、（8.88±0.15）分,与对照组的83例、28例、9例、（8.81±0.19）分比较差异无统计学意义（P>0.05）。结论 潜伏期与活跃期对妊娠期高血压产妇实施分娩镇痛对产程时间以及母婴结局的影响不大,但潜伏期镇痛可改善产妇潜伏期的疼痛,可尽早缓解产妇痛苦,且对产妇子宫动脉血流灌注的影响更小。