ABSTRACTObjectiveWood dust is a human carcinogen. However, studies examining the relationship between wood dust exposure and laryngeal cancer have yielded inconsistent findings. Therefore, we systematically reviewed relevant studies examining the relationship between wood dust exposure and laryngeal cancer development, followed by a meta‐analysis.MethodsPublications in the following databases were searched: PubMed, Medline, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI). The Newcastle–Ottawa scale was used to evaluate the study quality. A random‐effects model was used for the meta‐analysis.ResultsEighteen case–control studies and one cohort study, involving a total of 4426 patients with laryngeal cancer and 319,129 control participants, were identified. The association between occupational/environmental exposure to wood dust and laryngeal cancer, if any, was unclear (adjusted combined OR: 1.11; 95% CI: 0.94–1.31). However, subgroup analyses according to the number of cases, geographic region, publication year, and follow‐up duration revealed correlations between wood dust exposure correlated and laryngeal cancer, as follows: number of cases > 200 (OR: 1.14; 95% CI: 1.01–1.25 [n = 10]); studies conducted in the US (OR: 1.21; 95% CI: 1.07–1.37 [n = 5]); follow‐up time > 5 years (OR: 1.19; 95% CI: 1.07–1.32 [n = 10]); and publication after the year 2000 (OR: 1.15; 95% CI: 1.04–1.28 [n = 8]). A high heterogeneity in the results was observed (I2 = 42.5%, p = 0.024). The results were stable, and no publication bias existed, according to sensitivity analysis.ConclusionsThis meta‐analysis suggests that wood dust exposure is associated with laryngeal cancer. Additional large‐scale studies are warranted to clarify the relationship between wood dust exposure and laryngeal cancer.

目的 探讨职业接触电焊烟尘与慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的关系.方法 检索从建库到2022年有关电焊烟尘和COPD的文献,数据库包括PubMed、Springer、中国知网和万方等.采用美国医疗保健研究和质量局(AHRQ)量表对符合标准的文章进行质量评估.根据I2和P值对文章进行异质性判断,并选用相应的效应模型.通过敏感性分析检验研究结果的稳定性;通过Begg's和Egger's检验评估发表偏倚.结果 共检索到相关文献108篇,最终有2项队列研究和6项横断面研究共11项研究纳入本次meta分析,未接触电焊烟尘的有3 425例COPD患者,接触电焊烟尘的有193.例COPD患者.文献质量评分均在5分以上.各研究间异质性较低(I2=11.8％),采用固定效应模型对合并优势比(OR)进行分析.合并OR值表明接触电焊烟尘会增加COPD的发病风险(OR=1.39,95％CI=1.15～1.69),在控制了吸烟因素后依旧显示接触电焊烟尘会增加COPD的发病风险(OR=1.34,95％CI:1.10～1.63).敏感性分析证实本次研究结果稳定.结论 劳动过程中接触电焊烟尘可增加职业人群患COPD的风险,应重视电焊烟尘工作人员的健康监护,及早控制可能的病情,在脱离岗位后要保持定期随访.

目的 探究职业接触石棉与患肾癌风险的关系.方法 检索有关职业接触石棉与患肾癌的电子文献数据库(中国知网、维普、万方、PubMed、EBSCO、Elsevier Science direct、Medical、Cochrane Library),根据 Newcastle-Ottawa scale(NOS)量表评价纳入文献的质量,对评价低于6分的文献不予纳入.用STATA12.0软件对文献的OR值及其95％置信区间进行合并.通过I2及P值对合并后的数据进行异质性检验.使用敏感性分析判定结果的稳定性,并做亚组分析.结果 共检索到文献248篇,最终纳入8篇文章、10个病例-对照研究,病例组3 725例,对照组6 970例.10项研究之间存在较低的异质性(I2＜0.1％,P=0.585).合并的效应值表明工作场所接触石棉会增加患肾癌的风险(OR=1.30,95％CI:1.17～1.45,P＜0.01).敏感性分析和亚组分析均证实了本次结果较稳定,并且未见明显的发表偏倚.结论 工作场所接触石棉会增加患肾癌的风险.

目的 进一步理清人体内镁离子和高尿酸血症之间的关系.方法 以关键词血镁、饮食摄入、重金属和高尿酸血症,在PubMed、Web of Knowledge、Elsevier ScienceDirect和Springer databases数据库进行文献检索,参考美国医疗保健研究与质量局(Agency for Healthcare Research and Quality,AHRQ)的标准对文章进行质量评价,最终纳入6篇文章,包含10项研究,根据异质性采用随机效应模型进行Meta分析.结果 多项横断面研究表明,血浆镁离子与高尿酸血症存在一定的关联,人体内镁离子水平与高尿酸血症患病率呈负相关(OR=0.72,95％CI:0.57～0.89),但存在一定的异质性(I2=68.5％,P=0.001).逐个排除1篇文章后合并的OR值为0.67(95％CI:0.57～0.79)～0.75(95％CI:0.61～0.94),敏感性分析证实了结果的稳定性;未见明显发表偏倚(Begg检验,P=0.588;Egger检验,P=0.721).结论 人体内镁离子与高尿酸血症间存在一定的负关联,一定浓度的镁离子摄入可以降低高尿酸血症发生的风险.

BACKGROUNDWood dust has been confirmed as one kind of human carcinogen. However, there are inconsistent study results of exploring the relationship of exposure to wood dust and occurrence of nasopharyngeal cancer (NPC). For a greater clarification, the authors systemically reviewed the relevant published articles on the relationship of exposure to wood dust and occurrence of NPC. And meta-analysis was conducted.METHODSThe databases of PubMed, U.S. National Library of Medicine (MEDLINE), Embase and Science Direct were searched for the relevant publications. And Newcastle-Ottawa scale was employed for judging the quality of articles. Random-effect model was utilized for meta-analysis.RESULTSAmong a total of 583 retrieved items, 10 case-control studies and 1 cohort study were selected. The ratio of maximal/minimal exposure concentration of wood dust yielded a pooled odd ratio (OR) of 2.18 (95% CI = 1.62-2.93, P = 0.063) with a moderate heterogeneity (I2: 43.0%; P = 0.001). And subgroup analysis was performed for such factors as exposure status, exposure population and geographic region. No publishing bias was noted. Exposing to a high concentration of wood dust was positively proportional to occurring risk of NPC.CONCLUSIONIt hints at the contributing effect of wood dust upon NPC. For eliminating the effects of other confounding factors, larger prospective cohort studies are required for further elucidating the relationship of exposure to wood dust and occurrence of NPC.

Lead is a known risk factor for amyotrophic lateral sclerosis (ALS). However, the results of studies exploring the relationship between lead exposure and the occurrence of ALS are inconsistent. To clarify this issue, we conducted a systematic review and meta-analysis of relevant published articles on the relationship between lead exposure and the occurrence of ALS. We searched the PubMed, MEDLINE, Embase, and Science Direct databases for relevant publications. The quality of the articles was judged according to the Newcastle-Ottawa scale, and the meta-analysis was conducted using a random effect model. A total of 583 items were retrieved of which 11 case-control studies were selected. The ratio of maximal/minimal lead exposure yielded a pooled odds ratio (OR) of 1.46 (95% confidence interval (CI) 1.16–1.83) with moderate heterogeneity (I2 = 51.8%; p = 0.019). Subgroup and sensitivity analyses showed stable results. There was evidence of publication bias, but the recalculated OR after employing the “fill and trim” method was 1.28 (95% CI 1.02–1.63). These results indicated that environmental/occupational lead exposure was positively proportional to the risk of ALS.

目的 探讨扬州市大气污染状况及其对儿童门诊就诊的影响.方法 收集扬州市2016-2018年大气污染物资料、气象数据及儿科门诊资料,采用广义相加模型分析大气污染物对儿童总门诊量及呼吸系统疾病门诊量的影响.结果 与《环境空气质量标准》(GB 3095-2012)二级标准相比,2016-2018年扬州市大气PM2.5和PM10日均浓度的超标率分别为16.07％和9.86％;1、2月PM25月均浓度最高,8月月均浓度最低.2017-2018年O3、NO2日均浓度的超标率分别为8.36％和0.82％.大气PM25浓度每增加10 μg/m3,当日及滞后4d的儿科总门诊量ER值分别为0.286％(95％CI:0.137％～0.434％)和0.211％(95％CI: 0.075％～0.347％);当日、滞后4d及5d的儿童呼吸系统门诊量ER值分别为0.255％(95％CI:0.071％～0.438％),0.259％(95％CI:0.091％～0.427％),0.183％ (95％ CI: 0.017％ ～0.349％).引入其他污染物(SO2、NO2、CO、O3)后,PM2.5浓度对儿科总门诊量及呼吸系统门诊量的影响消失(P＞0.05).结论 扬州市大气污染物以PM2.5和PM10为主,且冬季污染最严重.大气PM2.5浓度增加对儿童总门诊量及呼吸系统疾病门诊量的增加均有明显影响,且存在滞后效应.

目的:研究扬州市大气污染物中细颗粒物(particulate matter,PM2.5)与居民每日死亡的相关性.方法:收集扬州市2015—2017年大气污染物PM2.5、二氧化硫(sulfur dioxide,SO2)、二氧化氮(nitrogen dioxide,NO2)和臭氧(ozone,O3)的日均浓度、气象因素(日平均气温、相对湿度)及每日死因别死亡人数,运用广义相加模型(generalized additive model,GAM)进行单污染物和多污染物分析,非意外总死亡年龄和性别的分层分析.结果:空气污染物PM2.5、SO2、NO2及O3年均浓度分别为53.16、23.36、29.87、91.54μg/m3,其中PM2.5浓度高于国家二级标准.单污染模型中,PM2.5浓度每增加10μg/m3,居民非意外总死亡率和循环系统死亡率增加0.685％(95％CI:0.334％～1.038％)和0.950％(95％CI:0.402％～1.501％),对呼吸系统死亡增加无统计学意义;多污染物模型中,当引入SO2和NO2时,PM2.5对非意外死亡和循环系统疾病死亡影响消失,引入O3时,非意外死亡和循环系统疾病死亡风险分别降至0.548％(95％CI:0.222％～0.875％)和0.588％(95％CI:0.065％～1.113％),引入所有污染物时,非意外死亡和循环系统疾病死亡风险分别降至0.640％(95％CI:0.311％～0.970％)和0.653％(95％CI:0.127％～1.182％);性别、年龄方面,PM2.5浓度增加使女性非意外死亡风险增加1.001％(95％CI:0.477％～1.527％),≥65岁风险增加0.758％(95％CI:0.369％～1.148％),男性及<65岁死亡风险无统计学意义.结论:大气污染物中PM2.5污染会增加居民非意外死亡率和循环系统死亡率,对≥65岁的老年人和女性人群影响最为明显.有必要开展针对性大气污染物治理,合理分配卫生资源.

[目的]分析扬州市职业性苯暴露工人的健康状况,为苯所致职业病的预防与控制提供依据.[方法]对2015-2017年扬州市职业性苯接触工人职业病监测数据进行描述与对比分析.[结果]截至2017年11月底,扬州市共申报涉苯企业510家,苯接触工人5 207人.苯作业场所和岗位超标率分别为4.44％、1.58％,2015-2017年涉苯工作场所苯超标率逐年降低(P＜0.05),超标场所主要位于江都区.3年间,收集到248家企业的11 444份职业健康检查资料.248家企业以小型(67.74％)为主,主要来自宝应县和邗江区(均为20.97％),高邮市最少,占3.63％;行业分布以化学原料和化学制品制造业(12.10％),皮革、毛皮、羽毛及其制品和制鞋业(1 1.69％)为主.3年间共检出疑似苯中毒病人490例,职业禁忌证83例,其中2015年分别为89例、2例,2016年分别为183例、37例,2017年分别为218例、44例.3年问,疑似苯中毒、职业禁忌证检出率均有逐年升高的趋势(P＜0.01).白细胞和中性粒细胞偏低检出率逐年降低(P＜0.05).2015-2017年扬州市仅3例职业性苯中毒报告病例,且于诊断后隔年落实工伤保险待遇.[结论]扬州市职业性苯暴露工人职业健康状况不容乐观,建议继续加强职业性苯暴露所致职业病的监测工作.

目的 研究扬州市大气污染物中臭氧(O3)与居民每日死亡的相关性.方法 收集扬州市2015-2017年O3日均浓度 、气象因素(包括日平均气温 、相对湿度)及每日死因别死亡人数,运用广义相加模型(GAM),进行非意外总死亡年龄和性别的分层分析.结果 O3浓度每增加10μg/m 3,居民非意外死亡风险增加1.943％[95％ 可信区间(95％CI)1.570％ ～2.317％]、呼吸系统死亡风险增加2.182％(95％CI 1.014％ ～3.363％)、循环系统死亡风险增加2.507％(95％CI 1.903％ ～3.114％);其中男性非意外死亡风险增加1.555％(95％CI 1.054％ ～2.059％),女性增加2.426％(95％CI 1.868％ ～2.986％);<65岁人群增加0.916％(95％CI 0.088％ ～1.751％),≥65岁人群增加2.199％(95％CI 1.782％ ～2.618％).结论 扬州市O3的短期暴露能增加居民非意外死亡 、呼吸系统及循环系统死亡的风险,女性和年龄65岁及以上老年人群为暴露的敏感人群.有必要针对性地对大气污染物的治理采取措施,降低居民死亡风险.

目的:分析2000—2017年国内医务工作者抑郁症状检出率及三间分布特征.方法:检索CNKI、Wanfang Data、VIP、Pubmed及Web of Science,收集国内医务人员抑郁症状的相关文献.结果:共纳入28篇文献,医务人员抑郁症状合并检出率为27.7％(95％C I:18.9％～36.4％).东部医务人员抑郁检出率(30.7％)明显高于中部(26.8％)和西部(23.0％);抑郁检出率呈现下降趋势(2000—2005年:42.3％,2006—2010年:27.2％,2011—2017年:25.8％);女性、35岁以下、本科及以上学历、未婚/离婚/丧偶、医生抑郁检出率高于其他分组;县、市级(30.1％)、部队及专科医院(31.5％)抑郁检出率明显高于基层医院(23.0％).结论:国内医务人员抑郁症状检出率在性别、地区、年龄、医院级别分布不同,量表和抽样方法选择对检出率有影响.

Objective To explore the impact of welding work on human health and its relevant factors by the welders' pneumoconiosis sentinel surveillance.Methods 845 people were enrolled in the experimental group according to the " Key Occupational Disease Surveillance Technology Program",and 310 enterprises without occupational hazards were enrolled in the control group.They have conducted surveys and related health checks based on a unified questionnaire.The results were compared and conducted regression analysis.Results The prevalence of hypertension,abnormal hemoglobin,positive urinary protein and abnormal electrocardiogram was higher in the exposed group than in the control group (P ＜ 0.05).The rates of abnormal lung examination were significantly different between exposed group and control group (P ＜ 0.05).Multivariate logistic regression analysis showed that female (OR =1.89,95％ CI:1.16 ～ 3.08),age (30 ～) (OR =1.48,95％ CI:0.86 ～2.56),age ≥40 (OR =3.65,95％ CI:2.05 ～ 6.48) and not wearing protective equipment (OR =2.31,95％ CI:1.36 ～ 3.90) were risk factors.The length of service (5 ～) (OR =0.52,95 ％ CI:0.33 ～ 0.84),(≥ 10 years) (OR =0.34,95 ％ CI:0.17 ～ 0.65) were protective factors.Conclusion Welding operations can easily lead to cardiovascular damage in the working population,and female workers are more likely to cause damage to the lungs as they grow older.Regular wear of protective equipment is the key to prevent welders from pneumoconiosis.

Objective To understand the current status of social support among the elderly,aged ≥60 years,as well as to identify influencing factors and to provide a reference for relevant health care services.Methods Publications about social support of the elderly were collected by searching the database of CNKI,VIP,Wanfang Data,Pubmed,and Web of Science.A random effects model was employed according to the results of heterogeneity (I2＞50％) to pool the extracted data.Results Thirty-two articles were included,with a total sample of 21 763 articles.Total scores of social support and three dimensions were low,with social support of 34.047 (95％CI:32.532-35.563),subjective support of 19.218 (95％CI:17.589-20.846),objective support of 7.787 (95％CI:7.483-8.091),and support utilization of 7.075 (95％CI:6.884-7.266).Scores of elderly with character of high age (aged 80:30.907,95％CI:28.378-33.436),female (32.512,95％CI:30.723-34.300),low education (illiteracy:32.088,95％CI:30.944-33.231;primary school:32.709,95％CI:30.069-35.349),country side (33.780,95％CI:31.523-36.038),empty nest (32.301,95％CI:27.061-37.542) and incomplete marriage (discoverture:27.044,95％CI:24.652-29.437;divorced:29.159,95％CI:24.520-33.791) was lower than the others.Conclusions The current status of social support is not optimistic.Scores of social support and its dimensions were relatively low,and a significant difference was found between elderly of different character,indicating that health interventions should be implemented based on character.

铅是用途十分广泛的一种重金属,在使用过程中会造成环境的污染及人体健康损害.我国铅中毒的机制研究已达到了分子和细胞水平,许多铅导致的疾病已经逐渐被认知.但是目前中国尚缺乏铅导致的肌萎缩侧索硬化症患病率的流行病学数据调查,为此,针对近年来国内外铅暴露的流行病学证据,对居民健康危害及铅暴露的生物标志物研究进展进行综述.

目的：评价顺酐生产过程中存在的职业病危害因素及其控制效果，提出针对性的防护措施。方法采用现场职业卫生调查的方法，对某化工企业顺酐生产项目进行职业病危害因素检测，调查该项目作业场所职业病防护措施，并结合职业健康检查的结果，对该项目的职业病危害控制效果进行评价。结果顺酐项目生产过程中存在的职业病危害因素主要有正丁烷、顺酐、邻苯二甲酸二丁酯、氨、一氧化碳、噪声和工频电场。经检测，各作业点化学有害因素和工频电场的浓（强）度均低于国家职业接触限值，6个工种噪声作业人员8 h等效声级符合相关限值要求。结论顺酐生产项目主要职业病危害因素为顺酐、邻苯二甲酸二丁酯、氨，采用国内先进安全的工艺技术，各项职业病防护措施有效可行，基本符合职业卫生要求。

目的 识别、评价、控制某古筝制品厂产生的职业病危害因素,保护劳动者的身体健康.方法 收集相关资料,开展现场职业卫生学调查、职业病危害因素检测及职业健康体检,结合职业病防护设施、个人职业防护水平对用人单位职业病危害现状进行定性与定量评价.结果 该企业生产过程中可能产生的职业病危害因素主要有苯、甲苯、二甲苯、木粉尘和噪声,压模点、磨灰点木粉尘浓度为5.08 mg/m3和4.25 mg/m3,下料点噪声强度87.7 dB(A),超过国家职业接触限值,其他岗位职业病危害因素均符合标准.职业健康检查发现1名工人存在职业禁忌证.结论 该企业职业卫生基本符合要求.

Aims: To assess passive smoking as a risk factor for developing type 2 Diabetes Mellitus (T2DM).Methods: A search of PubMed, Web of Knowledge, Elsevier ScienceDirect and Springer (up to March, 2014) databases were performed using subject and random words. Two authors independently extracted the data. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. The odds ratio (ORs) for the association was determined using a fix-effects model. Subgroup and sensitivity analyses were performed and publication bias was assessed.Result: 7 prospective studies were included in this meta-analysis which included a total of 162,001 subjects. The overall OR for developing T2DM for passive smoking was 1.33 (95% confidence interval (CI) 1.20-1.46), with no significant heterogeneity between studies. The result was stable in the subgroup and sensitivity analyses, however there was evidence of publication bias. After the "fill and trim'' method, the recalculated OR was 1.27 (95% CI 1.161.40).Conclusions: Passive smoking is a risk factor of T2DM even in those who were not themselves active smokers. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Acrylamide (ACR) is a vinyl monomer with established human neurotoxic effects, which is characterized by the accumulation of neurofilaments (NFs) in the distal swellings of large axons in peripheral and central nervous systems. However, the mechanisms of neurotoxicity remain unclear. The objective is to investigate the neuroprotective effect of calpeptin (CP) on ACR-induced neuropathy and its mechanism. Female adult Wistar rats were randomly divided into four groups (control, CP, ACR, and ACR + CP group). Control group received 0.9 % saline, ACR and ACR + CP groups received 30 mg/kg ACR by intraperitoneal injection. In addition, CP and ACR + CP groups also received 200 µg/kg CP. Gait analysis and hind limb splay were measured weekly to analyze neurobehavioral changes. The calpain activity and the changes of NFs protein levels in spinal cord are determined. Compared with control group, body weight of rats in ACR group decreased by 11.3 % (P < 0.01), while in ACR + CP group body weight increased significantly by 8.3 % (P < 0.01) compared with ACR group by the end of the 4th week; gait score of rats in both ACR and ACR + CP groups increased significantly by 167 % and 100 % (P < 0.01) compared with control group, while it decreased significantly by 25.1 % (P < 0.01) in ACR + CP group compared with ACR group; the distance of hind limb splay in both ACR and ACR + CP groups increased by 76.7 % and 49.5 % (P < 0.01) compared with control group, while it decreased by 15.4 % (P < 0.01) in ACR + CP group compared with ACR group; calpain activity of spinal cord at ACR and ACR + CP groups increased significantly by 14.9 % and 10.0 % (P < 0.01) compared with control group, while it decreased 4.2 % (P < 0.01) in ACR + CP group compared with ACR group; compared with control group, the levels of light NF (NF-L), medium NF (NF-M) and heavy NF (NF-H) subunits increased by 81.2 %, 263.6 % and 22.6 % (P < 0.01) in the supernatant of ACR group in spinal cord tissue and increased by 28.4 %, 96.6 % and 10.6 % (P < 0.01) in ACR + CP group, while the levels of NF-L, NF-M and NF-H subunits decreased by 29.1 %, 45.9 % and 9.8 % (P < 0.01) in ACR + CP group compared with ACR group. The present results suggested that CP can relieve ACR neuropathy by decrease calpain activity and NFs degradation. The changes of calpain activity and NFs may be one of the mechanisms of ACR-induced neuropathy.

目的 探讨钙蛋白酶抑制剂(calpeptin,CP)对丙烯酰胺(acrylamide,ACR)中毒大鼠神经毒性的拮抗作用.方法 将30只健康成年雌性Wistar大鼠随机分为对照组、ACR中毒组、CP干预组3组,每组10只.ACR中毒组腹腔注射ACR30 mg/kg,3次/周,共4周;对照组腹腔注射等体积生理盐水;CP干预组腹腔注射ACR后1h再腹腔注射CP 200 μg/kg,3次/周,共4周.测定体重、步态评分、后肢撑力和神经组织细胞内钙蛋白酶(calpain)活力.结果 与对照组相比,ACR中毒组大鼠体重增加缓慢(P＜0.05);与ACR中毒组相比,CP干预组大鼠体重在第2周显著升高(P＜0.05).ACR中毒组和CP干预组步态评分和后肢撑力明显高于对照组(P＜0.01),CP干预组明显高于ACR组(P＜0.05).ACR中毒组和CP干预组脊髓、坐骨神经细胞中calpain活力均明显高于对照组(CP干预组坐骨神经除外);CP干预组脊髓、坐骨神经细胞中calpain活力明显低于ACR组(P＜0.05).结论 CP可通过抑制钙蛋白酶的活力拮抗ACR诱导的神经毒作用.

Objective To establish the model of intervention effects of calpain inhibitor(MDL-28170) on neural stem cells(NSCs)injury induced by acrylamide.Methods The dorsal root ganglion of postnatal Wistar rats were collected for primary cellular culture.Specific protein nestin,neuron specific enolase(NSE) and glial fibrillary acidic protein(GFAP) in cells were identified by immunocytochemistry staining.The NSCs in logarithmic phase were divided into control group(culture),ACR-infected groups(140,350,560,700 μmol/L) and intervention groups(700 μmol/L ACR+65,130,195,260 μmol/L MDL-28170).The cells were cultured for 48 h in 5% CO2 and at 37 ℃.MTT method was used to determine the cell survival rate.Results Compared with the control group,the cell survival rate in 700 μmol/L ACR group and intervention group were significantly lower(P0.05).With the increase of ACR exposure doses,the survival rate of NSCs showed a declining curve.Compared with 700 μmol/L ACR group,the cell survival rates of 65,130 μmol/L intervention groups were significantly higher(P0.05),and the cell survival rate of 260 μmol/L intervention group was significantly lower(P0.05).Conclusion The model of the intervention effects of calpain inhibitor on NSCs injury induced by acrylamide is established successfully in the study.