Observation of Curative Effect of Surgical Nursing in Patients with Grade III Hand-Foot Syndrome

Objective: To investigate the effect of surgical nursing on grade III Hand-Foot Syndrome (HFS) induced by Doxorubicin hydrochloride liposome chemotherapy after breast cancer surgery. Method: From January 2019 to December 2019, 10 patients with HFS grade III caused by Doxorubicin hydrochloride liposome chemotherapy after breast cancer surgery in the Breast Department of Cancer Prevention and Treatment Center of Sun Yat-sen University were selected, and surgical nursing methods were used to intervene and observe the therapeutic effects of the patients. Results: One patient was cured within 7 days, the cure rate was 10% in 7 days, 8 patients were cured within 10 days, the cure rate was 80% in 10 days, 10 patients were cured within 15 days, the cure rate was 100% in 15 days. Conclusion: The surgical nursing method is effective for patients with grade III HFS caused by Doxorubicin hydrochloride liposome chemotherapy after breast cancer surgery, shortening the treatment time of HFS, and is worthy of clinical promotion.

Relationship between neonatal respiratory distress syndrome pulmonary ultrasonography and respiratory distress score,oxygenation index,and chest radiography grading

BACKGROUND Accurate condition assessment is critical for improving the prognosis of neonatal respiratory distress syndrome(RDS),but current assessment methods for RDS pose a cumulative risk of harm to neonates.Thus,a less harmful method for assessing the health of neonates with RDS is needed.AIM To analyze the relationships between pulmonary ultrasonography and respiratory distress scores,oxygenation index,and chest X-ray grade of neonatal RDS to identify predictors of neonatal RDS severity.METHODS This retrospective study analyzed the medical information of 73 neonates with RDS admitted to the neonatal intensive care unit of Liupanshui Maternal and Child Care Service Center between April and December 2022.The pulmonary ultrasonography score,respiratory distress score,oxygenation index,and chest Xray grade of each newborn before and after treatment were collected.Spearman correlation analysis was performed to determine the relationships among these values and neonatal RDS severity.RESULTS The pulmonary ultrasonography score,respiratory distress score,oxygenation index,and chest X-ray RDS grade of the neonates were significantly lower after treatment than before treatment(P<0.05).Spearman correlation analysis showed that before and after treatment,the pulmonary ultrasonography score of neonates with RDS was positively correlated with the respiratory distress score,oxygenation index,and chest X-ray grade(ρ=0.429–0.859,P<0.05).Receiver operating characteristic curve analysis indicated that pulmonary ultrasonography screening effectively predicted the severity of neonatal RDS(area under the curve=0.805–1.000,P<0.05).CONCLUSION The pulmonary ultrasonography score was significantly associated with the neonatal RDS score,oxygenation index,and chest X-ray grade.The pulmonary ultrasonography score was an effective predictor of neonatal RDS severity.

New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

Irritable bowel syndrome(IBS)is a chronic,recurring,and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain,distention,and changes in bowel habits.Although there are several drugs for IBS,effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed.Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism,neurohormonal regulation,immune dysfunction,the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS.With regards to therapies for restoring intestinal permeability,multiple studies with prebiotics and probiotics are ongoing,even if to date their efficacy has been limited.In parallel,much progress has been made in targeting low-grade inflammation,especially through the introduction of drugs such as mesalazine and rifaximin,even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs.This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS,most recently developed in preclinical as well as Phase 1 and Phase 2clinical studies.

Utility of cooling patches to prevent hand-foot syndrome caused by pegylated liposomal doxorubicin in breast cancer patients

BACKGROUND Pegylated liposomal doxorubicin(PLD)uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands,producing toxic free radicals and oxidative damage,resulting in hand-foot syndrome(HFS).Regional cooling can induce vasoconstriction to reduce the release of drugs in the limbs and reduce the accumulation of drugs in sweat glands;thus,decreasing the incidence and severity of HFS.AIM To study the efficacy of cooling patches to prevent HFS caused by PLD in the short-term.METHODS This is a retrospective cohort study.Female breast cancer patients(n=101)who were treated with PLD in two breast wards at our department from February 2020 to February 2021 were enrolled in the study and were randomly divided into the cooling group(51 patients)and the control group(50 patients).Patients in the control group only received routine care,while the patients in the cooling group applied cooling patches,based on routine care,to the palm and back of the hands 15 min before chemotherapy infusion for 10 h.All patients took a corresponding dose of dexamethasone orally one day before chemotherapy,on the day of chemotherapy,and one day after chemotherapy.SPSS23.0 version was used to analyze the data in this study.The occurrence and severity of HFS was analyzed by the Mann-Whitney U test,and scores were analyzed by the Student’s t test or Wilcoxon rank-sum test.A P value<0.05 was regarded as statistically significant.RESULTS In this study,neither group of patients developed Grade 3 HFS.In the control group,the incidence of Grade 1 HFS and Grade 2 HFS was 38%and 2%,respectively.However,in the cooling group,only one person developed Grade 1 HFS(2%),and none of the patients developed Grade 2 HFS.These findings showed that cooling patches can effectively reduce the frequency and severity of HFS(P<0.0001)in the short-term.Before the fourth chemotherapy cycle,although general self-efficacy scale scores in the cooling group were low,they were still significantly higher than those in the control group(17.22±5.16 vs 19.63±6.42,P=0.041).Compared with the control group,the mean Hand-Foot Skin Reaction and Quality of Life Questionnaire score in the cooling group was significantly lower(18.08±7.01 vs 14.20±7.39,P=0.008).CONCLUSION Cooling patches can effectively reduce the frequency and severity of HFS caused by PLD in the short-term.In addition,it may help delay the decline in patients’self-efficacy.

Pazopanib Induced Hand-Foot Syndrome in a Patient Previously Treated with Sunitinib: A Possible Cumulative Skin Toxicity?

Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a skin toxicity that could be observed during target therapies such as with tyrosine-kinase inhibitors (TKI). It usually develops within the first 2 - 4 weeks of drug administration. We present a case of HFS induced by Pazopanib after 2 months of treatment, in patients previously treated with Sunitinib, suggesting a possible cumulative toxicity of two drugs. The clinical and therapeutic management of skin adverse reactions during TKI therapy usually requires 25% dose reduction and adequate local treatment. It is important for the clinicians to recognize clinical signs and symptoms of such skin toxicities. Attention should be paid especially when two or more drugs from the same class are used in combined treatment.

中医药治疗HIV/AIDS相关腹泻疗效和安全性的Meta分析与GRADE证据评价

目的:系统评价中医药治疗人类免疫缺陷病毒感染或获得性免疫缺陷综合征(HIV/AIDS)相关腹泻(HRD)的临床疗效和安全性,并进行GRADE证据质量评价。方法:检索中国知网(CNKI)、PubMed等中英文数据库和临床试验注册平台,检索中医药治疗HRD的随机对照试验(检索时间从各个数据库建库至2023年3月31日),由2名研究人员独立进行数据检索、数据提取、偏倚风险评价和Meta分析。结果:最终纳入31篇文献和1项临床研究,共计3474例患者,其中试验组1830例,对照组1644例。Meta分析结果显示,中医药治疗能显著提高HRD患者的临床疗效有效率,降低大便次数积分、中医症状积分、腹泻量表积分、腹痛积分,加快腹泻消失时间,增加体质量。临床疗效有效率和中医症状积分均未发现发表偏倚。GRADE证据质量评价结果显示:中医症状积分、大便次数积分、CD4+T细胞绝对数量为高级质量证据;临床疗效有效率、腹泻恢复时间、腹泻量表积分、腹痛积分、不良反应发生率和体质量为中级质量证据;中医证候临床疗效有效率为低级质量证据。结论:中医药能提高HRD患者的临床疗效有效率,改善腹泻临床症状,且安全性较好,推荐使用于HRD的治疗。但由于所纳入的研究方法质量较低和部分结局指标证据质量较低,尚需更多设计严谨的多中心随机对照试验增加证据强度。

What does irritable bowel syndrome share with non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease(NAFLD)and irritable bowel syndrome(IBS)are two very common diseases in the general population.To date,there are no studies that highlight a direct link between NAFLD and IBS,but some recent reports have found an interesting correlation between obesity and IBS.A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD,leading to an increased cardiovascular risk,and IBS,leading to microbial dysbiosis,impaired intestinal barrier and altered intestinal motility.It is not known when considering local and systemic inflammation/immune system activation,which one has greater importance in NAFLD and IBS pathogenesis.Also,the nervous system is implicated.In fact,inflammation participates in the development of mood disorders,such as anxiety and depression,characteristics of obesity and consequently of NAFLD and,on the other hand,in intestinal hypersensitivity and dysmotility.

Stevens-Johnson syndrome and concurrent hand foot syndrome during treatment with capecitabine:A case report

BACKGROUND Capecitabine is used in combination with lapatinib as palliative treatment for human epidermal growth factor receptor 2-positive metastatic breast cancer.The most frequently reported adverse events attributed to capecitabine include diarrhea,hyperbilirubinemia,and hand-foot syndrome(HFS).A number of cutaneous adverse events have been attributed to capecitabine,including Stevens-Johnson syndrome(SJS)as a rare and potentially life-threatening mucocutaneous condition.We report the first case involving concurrent SJS and HFS after capecitabine and lapatinib treatment.CASE SUMMARY A 70-year-old woman with a history of breast cancer treatment visited our hospital for evaluation of painful skin lesions.Six weeks earlier,she had been prescribed capecitabine plus lapatinib as treatment for metastatic breast cancer.She subsequently developed worsening erythema and bullae on her palms and soles,as well as reddish macules on her back and chest wall.Histopathological evaluation of the chest wall lesions revealed extensive eosinophilic epidermal necrosis and separation of the epidermis from the dermis.The capecitabine plus lapatinib treatment was discontinued immediately and treatment was started using systemic steroids.This treatment resolved most lesions,although the lesions on her palms and soles required Vaseline gauze dressings,which resulted in reepithelialization.Therefore,we determined that the patient had concurrent SJS and HFS.Although the dermatological problems resolved,the patient ultimately died because of multiple organ failure.CONCLUSION Oral capecitabine treatment carries a risk of both HFS and also life-threatening adverse cutaneous drug reactions,such as SJS.

Common traditional Chinese medicine therapies for diarrhea-predominant irritable bowel syndrome: An overview of systematic reviews

Objective: To critically evaluate and summarize the methodological quality of systematic reviews(SRs)and present objective and important outcomes on the effectiveness of traditional Chinese medicine(TCM) therapies, including Chinese herbal medicine(CHM), acupuncture, and moxibustion, for diarrheapredominant irritable bowel syndrome(IBS-D).Methods: We conducted a comprehensive literature search for SRs in 7 databases until April 16, 2022.Two reviewers independently extracted data and assessed the methodological quality of the reviews according to the Assessing the Methodological Quality of Systematic Reviews 2(AMSTAR-2), the Risk of Bias in Systematic reviews(ROBIS) tool, and the Preferred Reporting Item for Systematic Review and Meta-analysis(PRISMA) statement. The Grading of Recommendations, Assessment, Development, and Evaluation(GRADE) was used to rate the quality of evidence.Results: IBS-D patients included in 12 reviews were diagnosed in accordance with the Rome criteria, 9 reviews focused on CHM, 2 articles observed moxibustion and heat-sensitive moxibustion, 1 article studied acupuncture and CHM. The outcomes of the SRs were the effectiveness rate, the total effectiveness rate,global symptom improvement, and adverse effects. Based on AMSTAR-2, which measures the quality of methodology, all of the included studies were of low or critically low quality. According to the ROBIS tool, 10 SRs(83.33%) had a high risk of bias. With the PRISMA checklist, only 3 SRs reached over 90% compliance.Based on GRADE, most evidence was of low quality, and there was a moderate quality of evidence that the effectiveness rate of modified-Tongxie Yaofang was superior to Western medicine in the treatment of IBS-D.Conclusion: Given the suboptimal reporting and methodological quality of existing SRs, more studies are needed to clarify whether TCM therapies are more effective or safe than pharmacological medicine.Future studies should combine evidence-based medicine with TCM research according to the characteristics of TCM.

Relationship between Self-Care and Hand Foot Syndrome Specific Quality of Life in Cancer Patients

Purpose: The purpose of this study was to describe adherence to self-care for hand-foot syndrome (HFS) and the relationship between self-care and health-related quality of life (QOL). Methods: A cross-sectional study was conducted on 105 consecutive outpatients with HFS. To assess self-care for HFS and QOL, the participants were asked to complete self-care and HFS-14 (hand-foot syndrome specific QOL) questionnaires, respectively. Multiple regression models were used to identify the relationship between self-care and QOL. Results: Adherence to self-care for HFS was low, less than 50% for most of the items. Multivariate analysis revealed that poorer self-care (βs = -0.19;P = 0.03), depressive symptoms (βs = 0.43;P βs = 0.20;P = 0.04) were independent predictors of poorer QOL scores. Conclusions: We have identified a need for further research to develop effective programs of self-care in HFS.

Evaluation of the Preventive Effect of Regional Cooling Nursing on Hand Foot Syndrome Caused by Doxorubicin Hydrochloride Liposome

Purpose: To explore the preventive effect of Regional cooling comprehensive nursing on hand foot syndrome caused by pegylated liposomal doxorubicin (PLD). Method: Adopt overall sampling method. Patients who used the same adjuvant drugs from January to December 2020 were randomly divided into an intervention group and a control group. The patients in the two groups received routine nursing guidance and drug prevention for the use of amygdalin. The patients in the intervention group were required to take protective measures of Regional cooling during chemotherapy. The occurrence of hand foot syndrome during adriamycin liposome administration was compared between the two groups. Results: By comparing the adverse reactions of cases during Adriamycin Administration, the incidence rates of grade I, II and III hand foot syndrome in the control group were 28.8%, 7.6% and 27.5% respectively, and the incidence rates of grade I, II and III hand foot syndrome in the intervention group were 42.1%, 12.3% and 7.0% respectively, with statistical significance (P Conclusion: Regional cooling nursing and preventive behavior guidance can effectively reduce the severity of hand foot syndrome caused by adriamycin.

膝骨关节炎五种中医证候程度与膝关节Kellgren-Lawrence的X线分级、磁共振Recht分级的相关性研究

目的:研究膝骨关节炎五种中医证候程度与膝关节Kellgren-Lawrence的X线分级、磁共振Recht分级的相关性。方法:选取160例膝骨关节炎不同证候患者的中医证候评分量表量化证候程度,膝关节Kellgren-Lawrence的X线分级,软骨退变的磁共振成像(magnetic resonance imaging, MRI)Recht分级并统计分析各组间的相关性。结果:将膝骨关节炎五种中医证候患者的中医证候评分量表量化证候程度与膝关节Kellgren-Lawrence的X线分级、MRI下软骨退变的Recht分级绘制散点图。五种中医证候程度与膝关节Kellgren-Lawrence的X线分级的相关性分析:肝肾亏虚型(r=0.895,P<0.01),痰瘀互结型(r=0.545,P<0.05),气血两虚型(r=0.748,P<0.01,)两者相关性具有统计学意义。五种中医证候程度与MRI下软骨退变的Recht分级的相关性分析:肝肾亏虚型(r=0.839,P<0.01),痰瘀互结型(r=0.572,P<0.01),气血两虚型(r=0.898,P<0.01)两者相关性具有统计学意义。结论:膝骨关节炎不同证候患者膝关节Kellgren-Lawrence的X线分级,软骨退变的磁共振成像(magnetic resonance imaging, MRI) Recht分级呈现不同相关程度,其中肝肾亏虚、痰瘀互结、气血两虚型患者的证候程度能反映的膝关节Kellgren-Lawrence的X线分级、MRI下软骨损伤的分级的严重程度,通过研究我们可以发现,中医的辨证分型和西医的影像学分级在某些方面存在一定的相关性,这可能意味着中医和西医在治疗膝骨关节炎方面有共同的目标和策略。

不同NYHA心功能分级心力衰竭病人中医证候、证素演变规律的文献分析

目的:通过分析心力衰竭的中医临床研究文献,总结不同纽约心脏病协会(NYHA)心功能分级心力衰竭病人的中医证型、证素演变规律。方法:以中国知网数据库(CNKI)、万方数据库、维普中文期刊数据库(VIP)、PubMed、Web of Science(WOS)为数据来源,检索有关心力衰竭中医证候、证素相关文献,检索时限为建库至2022年9月1日。采用SPSS 27.0统计不同NYHA心功能分级病人证候的例数及证素的频次等信息,按出现频次统计构成比,分析证型分布情况。结果:共纳入48篇文献,累计病例10058例。将频率≥3.00%的证候作为常见证候,包括气虚血瘀、气阴两虚、痰浊阻肺、阳虚水泛、心肾阳虚、心肺气虚、心气阴两虚血瘀、气虚血瘀痰饮、心血瘀阻9种证候。将频率≥3.00%的证素作为常见证素,常见病性证素包括气虚、血瘀、阳虚、阴虚、水饮、痰浊6种,常见病位证素包括心、肺、肾、脾。结论:心力衰竭病位主要在心,与肺、肾、脾等均有密切关联。在不同NYHA心功能分级病人中,Ⅰ级主要证候以气虚血瘀痰饮证最突出,其次为心肺气虚证、心气(亏)虚证,病性证素主要为气虚、血瘀;Ⅱ级主要证候为气虚血瘀证、心气阴两虚证、心肺气虚证、心气阴两虚血瘀证,病性证素以气虚表现最突出,其次为血瘀、阴虚;Ⅲ级主要证候依次为气虚血瘀证、气阴两虚证、阳虚水泛证、心肺气虚证,病性证素依次为气虚、血瘀、阳虚;Ⅳ级主要证候依次为阳虚水泛证、气虚血瘀证、痰浊阻肺证,病性证素依次为气虚、阳虚、血瘀、水饮。

维生素B_6用于预防卡培他滨所致手足综合征的Meta分析与GRADE评价

目的评价维生素B_6(Vitamin B_6,VitB_6)用于预防卡培他滨(Capecitabine,Cape)所致手足综合征(Hand-foot syndrome,HFS)的有效性。方法以"维生素B_6"、"卡培他滨"、"手足综合征"为关键词检索Pub Med、EMbase、Cochrane Library、知网、万方、维普等数据库。以总HFS事件为主要结局,2/3级HFS事件为次要结局,采用Rev Man 5.3软件对数据进行处理,采用GRADE profiler 3.6软件对结果证据质量进行评级。结果纳入5项随机对照研究,共计809例患者。Meta分析结果表明,两组的总HFS事件(OR=0.85,95%CI:0.63～1.16,P=0.31)和2/3级HFS事件(OR=0.87,95%CI:0.63～1.18,P=0.37)差异均无统计学意义;总HFS事件和2/3级HFS事件的GRADE证据评级为中级和高级。结论 VitB_6不能有效预防Cape所致的手足综合征。

慢性低度炎症在多囊卵巢综合征排卵障碍中的作用机制

目的 验证多囊卵巢综合征(PCOS)小鼠卵巢颗粒细胞炎症状态,并探索慢性低度炎症状态对PCOS排卵障碍的作用机制。方法 选取SPF级健康雌性C57BL/6小鼠10只,21~25 d,14~16 g,按照随机数字表法将其分为CONTROL组和PCOS组,每组5只。PCOS组每日皮下注射脱氢表雄酮(6 mg/100 g,溶剂:玉米油与DMSO混合液),CONTROL组小鼠每日皮下注射等体积溶剂,连续给药21 d。苏木精-伊红染色观察两组小鼠卵巢组织形态,免疫组织化学染色法检测两组小鼠卵巢颗粒细胞中肿瘤坏死因子-α(TNF-α)表达水平。向KGN细胞中加入脂多糖(LPS)0.1μg/ml(LPS 0.1组)、0.2μg/ml(LPS 0.2组)、0.5μg/ml(LPS 0.5组)、1.0μg/ml(LPS 1.0组)、5.0μg/ml(LPS 5.0组)构建颗粒细胞炎症模型,以KGN细胞作为对照组。Western blot法检测KGN细胞中TNF-α、SMAD4表达水平;免疫荧光检测对照组及LPS 0.2组KGN细胞中YTHDF2表达水平。转染PC3.1-YTHDF2质粒构建YTHDF2过表达颗粒细胞模型(PC3.1-YTHDF2组),转染PC3.1质粒作为对照(PC3.1组)。Western blot法检测PC3.1组和PC3.1-YTHDF2组KGN细胞中SMAD4表达水平。结果 CONTROL组小鼠卵巢中各时期卵泡均存在。与CONTROL组比较,PCOS组小鼠卵巢中存在大量未成熟卵泡。与CONTROL组比较,PCOS组小鼠卵巢颗粒细胞中TNF-α表达水平升高(P<0.05)。与对照组比较,LPS 0.2组、LPS 0.5组、LPS 1.0组、LPS 5.0组KGN细胞中TNF-α表达水平升高(P<0.05);LPS 0.1组、LPS 0.2组、LPS 0.5组、LPS 1.0组、LPS 5.0组KGN细胞中SMAD4表达水平降低(P<0.05)。与对照组比较,LPS 0.2组KGN细胞中YTHDF2表达水平升高(P<0.05)。与PC3.1组比较,PC3.1-YTHDF2组KGN细胞中SMAD4表达水平降低(P<0.05)。结论 PCOS小鼠颗粒细胞中存在炎症状态,PCOS颗粒细胞的炎症状态可影响其排卵功能,PCOS颗粒细胞炎症状态可能通过调控YTHDF2影响SMAD4的表达从而造成PCOS排卵障碍。

基于集束化理念的气道分级管理在新生儿呼吸窘迫综合征机械通气患儿中的应用

目的:探讨基于集束化理念的气道分级管理在新生儿呼吸窘迫综合征(neonatal respiratory distress syndrome,NRDS)机械通气患儿中的应用。方法:选取2018年10月—2022年10月鄂州市中心医院收治的96例NRDS机械通气患儿作为研究对象。根据随机数表法将其分为研究组与常规组,各48例。常规组实施常规气道管理护理,研究组实施基于集束化理念的气道分级管理。比较两组时间指标,护理前、出院时血气分析指标,不良事件。结果:研究组机械通气时间与住院时间均短于常规组,差异有统计学意义(P<0.05)。出院时,两组动脉血氧分压(partial pressure of oxygen in arterial blood,PaO_(2))、氧合指数(oxygenation index,OI)水平均升高,动脉血二氧化碳分压(partial pressure of carbon dioxide in arterial blood,PaCO_(2))降低,研究组PaO_(2)、OI水平均高于常规组,PaCO_(2)低于常规组,差异有统计学意义(P<0.05)。研究组呼吸机相关性肺炎、痰液堵塞发生率均低于常规组,差异有统计学意义(P<0.05)。结论:基于集束化理念的气道分级管理应用于NRDS机械通气患儿中,可缩短其机械通气时间与住院时间、改善血气指标、降低呼吸机相关性肺炎与痰液堵塞发生率。

创伤性肺脂肪栓塞的法医病理学研究进展及其鉴定应用

肺脂肪栓塞(pulmonary fat embolism,PFE)是骨折、广泛脂肪组织损伤后常见的继发性病理形态学改变,骨折等创伤后总发生率可达82%~93%。临床常规检查仍无法特异性诊断,加之起病隐匿急骤,因此目前仍以死后组织病理学检查为金标准。创伤性肺脂肪栓塞是否参与死亡、与死亡间的因果关系及伤病关系等均是法医实际工作中常面临的问题。以创伤性PFE的严重程度评估、死后诊断原则为主要综述内容,并总结了其检查方法、骨科手术及心肺复苏的影响等常见问题,以期为创伤性肺脂肪栓塞的法医学鉴定及研究提供参考。

塞来昔布预防卡培他滨所致手足综合征的Meta分析及GRADE证据质量评价

目的:系统评价塞来昔布防治卡培他滨所致手足综合征(HFS)的有效性和安全性,并评价结局指标的证据质量,为临床治疗提供参考。方法:计算机检索PubMed、Embase、the Cochrane Library、VIP、Wan Fang Data和CNKI数据库,搜集加用塞来昔布(试验组)对比安慰剂或维生素B6(对照组)预防卡培他滨相关HFS的随机对照试验(RCT),检索时限均为建库至2019年5月。两名研究者独立进行文献筛选、数据提取和偏倚风险评价后,采用Rev Man 5.3软件进行Meta分析,并采用GRADE profile 3.6软件对结果证据质量进行评价。结果:共纳入9个RCT,共计592例患者。Meta分析结果显示,试验组HFS的总发生率[OR=0.41,95%CI(0.29,0.60),P<0.00001]、2级HFS发生率[OR=0.53,95%CI(0.32,0.88),P=0.01]、3级HFS发生率[OR=0.27,95%CI(0.11,0.68),P=0.005]均低于对照组,差异均有统计学意义。试验组的1级HFS发生率与对照组比较降低不明显,两组的差异无统计学意义[OR=0.66,95%CI(0.44,1.00),P=0.05]。GRADE证据质量评价结果显示,HFS总发生率,1、2级HFS发生率均为高级证据质量,3级HFS发生率为中级证据质量。结论:当前证据显示,塞来昔布能有效预防卡培他滨相关HFS,可降低HFS的总发生率和2级、3级HFS发生率。

DNA damage-mediated cellular senescence promotes hand-foot syndrome that can be relieved by thymidine prodrug

Hand-foot syndrome(HFS)is a widely recognized dose-limiting cutaneous toxicity effect of fluoropyrimidine chemotherapy agents that impairs clinical benefits and treatment outcomes.Even though the cause and pathophysiology of HFS are relatively widely reported,how the toxicity of fluoropyrimidine translates into persistent inflammation has not been studied.Additionally,prevention and treatment strategies for HFS based on its mechanistic occurrence and development are scarce.In our study,we demonstrated that cGAS-STING signaling pathway-mediated cellular senescence played a critical role in the inflammatory reaction and provided a therapeutic solution for HFS.Mechanistically,DNA damage,as the primary cytotoxic cause,in keratinocytes induces cell cycle arrest,activates the cGAS-STING signaling pathway,and subsequently mediates cellular senescence,ultimately fueling a robust secondary inflammatory response that results in HFS.More importantly,the thymidine prodrug thymidine diacetate was proven to be effective in preventing HFS by compensating for thymidylate deficiency to facilitate the replication and repair of DNA and thus causing the escape from cellular senescence.These data highlight the importance of DNA damage-mediated cellular senescence in the etiology of HFS and provide a potential therapeutic anchor point for fluoropyrimidine-induced HFS.