简介：AbstractBackground:Taxanes are an essential class of antineoplastic agents used to treat various cancers and are a fundamental cause of hypersensitivity reactions. In addition, other adverse events, such as bone marrow toxicity and peripheral neuropathy, can lead to chemotherapy discontinuation. This study aimed to evaluate the safety of taxanes in the real world.Methods:Taxane-associated adverse events were identified by the Medical Dictionary for Regulatory Activities Preferred Terms and analyzed and compared by mining the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database from January 2004 to December 2019. Reported adverse events, such as hypersensitivity reaction, bone marrow toxicity, and peripheral neuropathy, were analyzed with the following signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), Bayesian confidence propagation neural network (BCPNN), and logistic regression methods. Adverse outcome events and death outcome rates were compared between different taxane groups using Pearson’s χ2 test, whereas significance was determined at P < 0.05 with a 95% confidence interval (CI).Results:A total of 966 reports of hypersensitivity reactions, 1109 reports of bone marrow toxicity, and 1374 reports of peripheral neuropathy were analyzed. Compared with paclitaxel and docetaxel, bone marrow toxicity following the use of nab-paclitaxel had the highest ROR of 6.45 (95% two-sided CI, 6.05-6.88), PRR of 5.66, (χ2 = 4342.98), information component of 2.50 (95% one-sided CI = 2.34), and empirical Bayes geometric mean of 5.64 (95% one-sided CI = 5.34). Peripheral neuropathy following the use of nab-paclitaxel showed a higher ROR of 12.78 (95% two-sided CI, 11.55-14.14), PRR of 12.16 (χ2 = 4060.88), information component of 3.59 (95% one-sided CI = 3.25), and empirical Bayes geometric mean of 12.07 (95% one-sided CI = 11.09).Conclusions:The results showed that bone marrow toxicity and peripheral neuropathy were the major adverse events induced by taxanes. Nab-paclitaxel exhibited the highest potential for taxane-associated adverse events. Further research in the future is warranted to explain taxane-associated adverse effects in real-world circumstances.

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简介：AIM:Toestimatethepotentialsystemiceventsduringandafterretinopathyofprematurity（ROP）screening.METHODS:Aprospectiveanddescriptivedesignedstudywasconductedtodetectthephysiologicandpathologicalchanges24hbefore,during,and72hafterROPscreening.Controlbloodpressure（BP）,saturation,pulserate,andbodytemperaturewereroutinelytakenatvarioustimeinternalsbeforeandafterscreening.Adverseeffectspertaintocardiovascularsystem,respiratorysystem,gastricsystem,urinarysystemandnervoussystemwereretrospect0-72hafterROPscreeningata24-hourinterval.RESULTS:Totally1254prematuritybabiesreceivingROPscreeningduringJan.1st2013toDec.31th2013wereenrolledinoursurvey.Comparedtocontrolvitalsigndatatakenbeforetheexamination,therewasafluctuationinthediastolicBPwiththeincreased3.03mmHg（P=0.04）after3dosesofmydriaticdrops.Immediatelyaftertheexamination,therewasafurther12.64mmHg（P<0.01）increaseinsystolicBPanda7.24mmHg（P<0.01）indiastolicBP.Themeanpulserateduringexaminationwas22.4bpm（P<0.01）higherthanthe133.3±9.0bpmcontrollevel.Theoxygensaturationsharedanaveragedropof5%（P<0.01）duringscreening.Inprematuritywithpostconceptionalagelessthan31wk,theincidenceofapnea（23.5%）,necrotizingenterocolitis（NEC）（8.7%）,gastricresidual（25.4%）andupperdigestivetracthemorrhage（6.4%）alsodemonstratedasignificantrise（P<0.01）.CONCLUSION:Inourstudysample,ROPscreeningwasassociatedwithNEC,gastricresidualandupperdigestivetracthemorrhage.Thesegastrointestinalsideeffects,alongwithbreathactivitypatternchangeandvitalsignsindicatorsfluctuation,mayberesultsofadditionalstressresponses.

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简介：在这份报纸，在骚乱边界层与的流动的数字研究不利并且压力坡度(APG)被使用平均Reynolds的海军司烧(RANS)进行方程。这研究选六为典型骚乱模型，它对计算精确，并且到评估APG的问题批评。本地摩擦抵抗系数在数字、试验性的结果之间被比较。无尺寸的平均速度侧面的一样的比较也被执行。威尔科克斯(2006)k-w产生的结果离试验性的数据很靠近，这被发现。同时，象狂暴的动能和Reynolds压力那样的狂暴的数量也被学习。

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简介：Lipoxygenase3(LOX3)isamajorcomponentoftheLOXisozymesinmaturericeseeds.ToinvestigatetheroleofLOX3geneunderstresses,aplantexpressionvectorcontainingantisensecDNAofLOX3wasconstructed.RicevarietiesWuyunjing7andKasalathweretransformedbytheAgrobacterium-mediatedmethodandtransgenicriceplantsweregenerated.PCRandSouthernblotresultsshowedthattheantisenseLOX3genewasintegratedintothericegenome.AnalysesofembryoLOX3deletionandsemi-quantitativeRT-PCRconfirmedtheantisensesuppressionofLOX3geneintransgenicplants.TheT2antisenseplantsofLOX3weresensitivetodroughtstress,riceblastandbacterialblightcomparedwithnon-transgenicplants.TheseresultssuggestthattheLOX3genemightfunctioninresponsetostresses.

简介：Itiswidelyacceptedthatinaturbulentboundarylayer(TBL)withadversepressuregradient(APG)anouterpeakusuallyappearsintheprofileofstreamwiseReynoldsstress.However,theeffectofAPGonthisouterpeakisnotclearlyunderstood.Inthispaper,theeffectofAPGisanalysedusingthenumericalandexperimentalresultsintheliterature.BecausetheeffectofupstreamflowisinherentintheTBL,wefirstanalysethiseffectinTBLswithzeropressuregradientonflatplates.Undertheindividualeffectofupstreamflow,anouterpeakalreadyappearsintheprofileofstreamwiseReynoldsstresswhentheTBLcontinuesdevelopinginthestreamwisedirection.TheAPGacceleratestheappearanceoftheouterpeak,insteadofbeingatrigger.

简介：AbstractImmune checkpoint inhibitors (ICIs) are widely used in lung cancer therapy due to their effectiveness and minimal side effects. However, only a few lung cancer patients benefit from ICI therapy, driving the need to develop alternative biomarkers. Programmed death-ligand 1 (PD-L1) molecules expressed in tumor cells and immune cells play a key role in the immune checkpoint pathway. Therefore, PD-L1 expression is a prognostic biomarker in evaluating the effectiveness of programmed death-1 (PD-1)/PD-L1 inhibitors. Nevertheless, adverse predictive outcomes suggest that other factors are implicated in the response. In this review, we present a detailed introduction of existing biomarkers concerning tumor abnormality and host immunity. PD-L1 expression, tumor mutation burden, neoantigens, specific gene mutations, circulating tumor DNA, human leukocyte antigen class I, tumor microenvironment, peripheral inflammatory cells, and microbiome are discussed in detail. To sum up, this review provides information on the current application and future prospects of ICI biomarkers.

简介：AbstractObjective:The aim of the study is to investigate the relationship between antenatal depression and adverse perinatal outcomes.Methods:This prospective cohort study enrolled pregnant women between gestational ages of 12-20 weeks to complete the Chinese version of the Zung Self-Rating Depression Scale (SDS) and followed them for delivery from September 2015 to September 2016. Participants were classified into mild, moderate, and severe depression groups according to the SDS scores. Logistic regression was performed to assess the association between antenatal depression and perinatal outcomes including preterm birth (PTB), cesarean section use, hypertension disorders, gestational diabetes, and thyroid diseases during pregnancy. An age-stratified analysis was performed.Results:A total of 4,663 pregnant women were analyzed. As a result, 13.8%, 1.7%, and 0.2% of women were classified as mild, moderate, and severe depression, respectively. Severely depressed mothers were at higher risk for PTB (adjusted odds ratio [OR] =11.31, 95% confidence interval [CI] 2.13-60.03), especially spontaneous PTB. Moderate-depressed women were at higher risk for hyperthyroidism during pregnancy (adjusted OR = 3.67, 95% CI 1.10-12.27), while women with mild depression tended to choose cesarean sections (OR = 1.24, 95% CI = 1.04-1.49). Age-stratified analysis indicated an elevated risk of adverse outcomes associated with depression in women aged <25 years, but the association was not significant.Conclusions:Antenatal depression was associated with PTB, hyperthyroidism, and cesarean use. Studies with large sample sizes should verify the relationship between PTB and antenatal depression to avoid casual events.

简介：AbstractBackground:Fever is the most common chief complaint of emergency patients. Early identification of patients at an increasing risk of death may avert adverse outcomes. The aim of this study was to establish an early prediction model of fatal adverse prognosis of fever patients by extracting key indicators using big data technology.Methods:A retrospective study of patients’ data was conducted using the Emergency Rescue Database of Chinese People’s Liberation Army General Hospital. Patients were divided into the fatal adverse prognosis group and the good prognosis group. The commonly used clinical indicators were compared. Recursive feature elimination method was used to determine the optimal number of the included variables. In the training model, logistic regression, random forest, adaboost, and bagging were selected. We also collected the emergency room data from December 2018 to December 2019 with the same inclusion and exclusion criterion. The performance of the model was evaluated by accuracy, F1-score, precision, sensitivity, and the areas under receiver operator characteristic curves (ROC-AUC).Results:The accuracy of logistic regression, decision tree, adaboost and bagging was 0.951, 0.928, 0.924, and 0.924, F1-scores were 0.938, 0.933, 0.930, and 0.930, the precision was 0.943, 0.938, 0.937, and 0.937, ROC-AUC were 0.808, 0.738, 0.736, and 0.885, respectively. ROC-AUC of ten-fold cross-validation in logistic and bagging models were 0.80 and 0.87, respectively. The top six coefficients and odds ratio (OR) values of the variables in the logistic regression were cardiac troponin T (CTnT) (coefficient = 0.346, OR = 1.413), temperature (T) (coefficient = 0.235, OR = 1.265), respiratory rate (RR) (coefficient= –0.206, OR = 0.814), serum kalium (K) (coefficient = 0.137, OR = 1.146), pulse oxygen saturation (SPO2) (coefficient = –0.101, OR = 0.904), and albumin (ALB) (coefficient = –0.043, OR = 0.958). The weights of the top six variables in the bagging model were: CTnT, RR, lactate dehydrogenase, serum amylase, heart rate, and systolic blood pressure.Conclusions:The main clinical indicators of concern included CTnT, RR, SPO2, T, ALB, and K. The bagging model and logistic regression model had better diagnostic performance comprehesively. Those may be conducive to the early identification of critical patients with fever by physicians.

简介：AbstractBackground:China’s two-child policy has led to a trend of aging in pregnancy which was associated with adverse outcomes. This study aimed to identify the clinically cutoff maternal age for adverse obstetric outcomes in China.Methods:This secondary analysis of a multicenter retrospective cohort study included data of childbearing women from 39 hospitals collected in urban China during 2011 to 2012. Logistic regression was used to assess the adjusted odds ratios (aOR) of adverse outcomes in different age groups in comparison to women aged 20 to 24 years. The adjustments included the location of the hospital, educational level, and residence status. Clinically cutoff age was defined as the age above which the aOR continuously become both statistically (P < 0.05) and clinically (aOR > 2) significant.Results:Overall, 108,059 women were recruited. In primiparae, clinically cutoff maternal ages for gestational diabetes (aOR: 2.136, 95% confidence interval [CI]: 1.856-2.458, P < 0.001), placenta previa (aOR: 2.400, 95% CI: 1.863-3.090, P < 0.001), cesarean section (aOR: 2.511, 95% CI: 2.341-2.694, P < 0.001), hypertensive disorder (aOR: 2.122, 95% CI: 1.753-2.569, P < 0.001), post-partum hemorrhage (aOR: 2.129, 95% CI: 1.334-3.397, P < 0.001), and low birth weight (aOR: 2.174, 95% CI: 1.615-2.927, P < 0.001) were 27, 31, 33, 37, 41, and 41 years, respectively. In multiparae, clinically cutoff ages for gestational diabetes (aOR: 2.977, 95%CI: 1.808-4.904, P < 0.001), hypertensive disorder (aOR: 2.555, 95% CI: 1.836-3.554, P < 0.001), cesarean section (aOR: 2.224, 95% CI: 1.952-2.534, P < 0.001), post-partum hemorrhage (aOR: 2.140, 95% CI: 1.472-3.110, P < 0.001), placenta previa (aOR: 2.272, 95% CI: 1.375-3.756, P < 0.001), macrosomia (aOR: 2.215, 95% CI: 1.552-3.161, P < 0.001), and neonatal asphyxia (aOR: 2.132, 95% CI: 1.461-3.110, P < 0.001) were 29, 31, 33, 35, 35, 41, and 41 years, respectively.Conclusions:Early cutoff ages for gestational diabetes and cesarean section highlight a reasonable childbearing age in urban China. The various optimized cutoff ages for different adverse pregnancy outcomes should be carefully considered in childbearing women.

简介：AbstractBackground:B-cell activating factor (BAFF) is vital for B cell survival. Serum BAFF levels are elevated in thrombotic antiphospholipid syndrome, but little is known about levels in patients with positive antiphospholipid antibodies (aPLs) and previous adverse pregnancy outcomes (APOs). We aimed to analyze serum BAFF concentrations of these patients in early pregnancy along with different pregnancy outcomes.Methods:Thirty-six pregnant patients positive for aPLs and previous APOs (patient group), 25 healthy pregnant females (HP group) and 35 healthy non-pregnant females (HNP group) from the Peking University Third Hospital, between October 2018 and March 2019, were enrolled in this study. Serum of HNP and serum of patients as well as HP in the first gestational trimester were collected. Enzyme-linked immunosorbent assay kits were used to measure serum BAFF and interferon-alpha (IFN-α) concentrations. Cytometric bead array analysis was used to measure serum concentrations of cytokines. The patient group was further divided into APOs and non-APOs (NAPOs) group, fetal loss and live birth group according to pregnancy outcomes. The Mann-Whitney U-test was used to assess significance between and within groups. Spearman rank-order was used to evaluate correlation coefficients between BAFF and related cytokines.Results:The serum BAFF level in HP group was significantly lower than HNP group (245.24 [218.80, 265.90] vs. 326.94 [267.31, 414.80] pg/mL, Z = -3.966, P < 0.001). The BAFF level was obviously elevated in patient group compared to that in HP group (307.77 [219.86, 415.65] vs. 245.24 [218.80, 265.90] pg/mL, Z = -2.464, P = 0.013). BAFF levels in APOs group tended to be higher than that in NAPOs group (416.52 [307.07, 511.12] vs. 259.37 [203.59, 375.81] pg/mL, Z = -2.718, P = 0.006). Compared to HP group, concentrations of IFN-α, interleukin (IL-6) and tumor necrosis factor were higher in patient group (33.37 [18.85, 48.12] vs. 13.10 [6.85, 25.47] pg/mL, Z = -2.023, P = 0.043; 39.16 [4.41, 195.87] vs. 3.37 [2.92, 3.90] pg/mL, Z = -3.650, P < 0.001; 8.23 [2.27, 64.46] vs. 1.53 [1.25, 2.31] pg/mL, Z = -3.604, P < 0.001, respectively). Serum BAFF levels had a positive correlation with the concentrations of both IL-6 and IL-10 (IL-6: r = 0.525, P = 0.002; IL-10: r = 0.438, P = 0.012).Conclusions:Serum BAFF levels are increased in patients with positive aPLs and previous APOs as compared to healthy pregnant females and tend to be higher in individuals with current APOs. The BAFF levels have a positive correlation with serum IL-6 and IL-10.

简介：oseltamivir的使用，广泛地是的stockpiled为在可能的鸟的流行性感冒的使用的药之一流行，被报导了与neuropsychiatricdisorders和严重皮肤反应被联系，首先在日本。这里，我们在dbSNP数据库识别了非同义的SNP(单个核苷酸多型性)，R41Q在humancytosolicsialidase的酶的活跃地点附近，是oseltamivir的目标的病毒neuraminidase的一个相当或相同事物。在欧洲、非洲的美国人口的9.29%亚洲人口和没有的这SNPoccurred。Ourstructural分析和Ki大小使用试管内sialidase试金显示这SNPcould增加人的sialidase的非计划中的有约束力的亲密关系到oseltamivir羧化物，oseltamivir的活跃形式，因此减少sialidase活动。另外，这SNP自己与一项内在地更低的sialidase活动导致酶，由它的增加的Km证明Vmax珍视并且减少。理论上，到有这SNP的人的oseltamivir的管理可能进一步减少他们的sialidase活动。我们注意oseltamivir的reportedneuropsychiatric副酌和人的sialidase-relateddisorders的已知的症状的类似。我们建议这个充实亚洲人的sialidase变化由SNP引起了，在同型结合的形式可能，可以与对oseltamivir的某些严重不利反应被联系。

简介：AbstractBackground:The platelet to lymphocyte ratio (PLR) has recently emerged as a potential inflammatory biomarker and has been shown to be significantly associated with atherosclerotic coronary artery disease (CAD). Therefore, we aimed to explore the association of PLR with in-hospital major adverse cardiovascular events (MACEs) and the severity of CAD assessed by the Gensini score (GS) in patients with acute myocardial infarction (AMI) undergoing coronary angiography.Methods:A total of 502 patients with AMI consecutively treated at the Affiliated Hospital of Qingdao University (Qingdao, China) and underwent coronary angiography from August 2017 to December 2018 were recruited in this study. The demographic, clinical, angiographic characteristics, and laboratory parameters were collected. According to the presence of in-hospital MACEs, the included patients were divided into the MACE group (n = 81) and the non-MACE group (n = 421). Further, according to tertiles of the GS, the patients were classified into three groups: the low GS group (GS ≤32 points, n = 173), medium GS group (32 points < GS ≤ 60 points, n = 169), and high GS group (60 points < GS ≤ 180 points, n = 160). The main statistical methods included Chisquared test, non-parametric Mann-Whitney U test, Kruskal-Wallis H test, logistic regression, and receiver operating characteristic curves.Results:The PLR in the MACE group was significantly higher than that in the non-MACE group (179.43 [132.84, 239.74] vs. 116.11 [87.98, 145.45], Z = -8.109, P < 0.001). Further, there were significant differences in PLR among the tertiles of GS (110.05[84.57, 139.06] vs. 119.78 [98.44, 157.98] vs. 140.00 [102.27, 191.83], H= 19.524, P < 0.001). PLR was demonstrated to be an independent risk factor of in-hospital MACEs (odds ratio [OR]: 1.012, 95% confidential interval [CI]: 1.006-1.018, P < 0.001) and severe CAD assessed by the GS (OR: 1.004, 95% CI: 1.002-1.009, P= 0.042). The cutoff value of PLR for predicting the development of in-hospital MACEs was 151.28 with a sensitivity of 66.7% and a specificity of 78.1% (area under the curve [AUC]: 0.786, 95% CI: 0.730-0.842, P < 0.001), and a PLR of 139.31 was also identified to be an effective cutoff point for detecting a high GS (<60 points) with a sensitivity of 49.4% and a specificity of 69.6% (AUC: 0.611, 95% CI: 0.556-0.666, P < 0.001).Conclusions:PLR as a novel inflammatory marker is significantly and independently associated with the occurrence of in-hospital MACEs and the severity of CAD assessed by the GS in patients with AMI. As an easily available and inexpensive inflammatory indicator, PLR could be widely used as an efficient inflammatory biomarker for identifying high-risk patients and for individualizing targeted therapy to improve the prognosis of AMI.

简介：AbstractObjective:Health-care workers (HCWs) in Indonesia have been participating in the war against the coronavirus disease-2019 since March 2020. Ever since HCWs were exposed to the regular use of personal protective equipment (PPE) with varying levels and maintain hand hygiene more as recommended by the World Health Organization. Adverse skin reactions to PPE in Indonesia has yet to be acknowledged. This study aimed to study the prevalence and characteristics-, possible risk factors-, and suggest possible solutions towards adverse skin reactions to PPE among HCWs in a multi-center setting of Indonesia.Methods:A cross-sectional survey was conducted online among HCWs in the Siloam Hospitals Group of Banten province. HCWs of Banten Province were surveyed from June 1 to August 31, 2020. The data was obtained using avalidated online survey questionnaire including (1) demographic characteristics; (2) occupational-related characteristics; (3) adverse skin reactions.Results:A response rate of 40.2% was obtained and 200 valid respondents were yielded. The mean age of respondents was (26.94 ± 7.23) years old. Adverse skin reactions (66.5%) were reported primarily in female (73.7%) working as doctors (82.7%) of a non-referral center for coronavirus disease-2019 (60.2%) wearing level 2 and 3 PPE (43.6% and 37.6%, respectively). The cheeks and chin was the most common site involved (69.9%) with dryness/tightness (63.9%) and acne (77.4%) as the highest symptoms and signs reported. Sex, age group classification, level of PPE worn, hand hygiene frequency, and duration of PPE worn daily were factors considerably associated with adverse skin reactions to PPE (P < 0.05).Conclusions:Adverse skin reactions to PPE are common among HCWs in Indonesia. Comprehensive strengthening of the skin condition and awareness on adverse skin reactions should be advocated.

简介：BackgroundItiswellknownthattherewasasignificantlinkbetweenpreproceduralbloodglucoselevelsandshort-termandlong-termadverseoutcomesinpatientsundergoingelectivePCI.However,theroleofpre-proceduralbloodglucoselevelsasapredictorofadverseeventsinCKDpatientswhounderwentPCIoutofestablisheddiabeteshasyettobeidentified.MethodsInourstudy,weconductedaprospectivestudyof331acutecoronarysyndrome(ACS)patientswithCKDwhounderwentPCIoutofestablisheddiabetes.Patientsweredividedintotwogroupsbasedonpre-proceduralglucoselevels(hypoglycemia<7.0mmol/L;hyperglycemia≥7.0mmol/L).Allpatientswerefollowedupprospectivelyformajoradversecardiovascularevents(MACEs)andmortalityfor6months.ResultsInourcohort,hyperglycemiapatientsreportedahigherincidenceofin-hospitalmortalitythanhypoglycemiapatients(7.5%vs.0%,P<0.001).Hyperglycemiapatientsreportedasignificantlyhigherrateof6-monthMACEs(10%vs.2.4%,P=0.007),allcausemortality(7.5%vs.1.6%,P=0.015),andcardiovascularmortality(6.2%vs1.6%,P=0.041)comparedwithhypoglycemiapatientswithpre-proceduralglucoselevels<7.0mmol/L.Multivariateanalysisdisclosedthatapre-proceduralglucoselevel≥7.0mmol/LwasasignificantindependentpredictorofMACEs(OR=2.53,95%CI1.68-17.15,P=0.004),allcausemortality(OR=4.6,95%CI1.10-18.84,P=0.036),andcardiovascularmortality(OR=6.2,95%CI1.53-24.94,P=0.011)at6monthsinpatientsafterPCI.ConclusionThestudysuggestedthatpre-proceduralglucoselevelsareassociatedwithshort-termcardiovascularoutcomeCKDpatientswhounderwentPCIwithoutestablisheddiabetesinthesettingofACS.

简介：[摘要]目的：探讨药学干预对2型糖尿病（T2DM）病患用药依从性及药品不良反应（ADR）产生的影响。方法：选择2020.1~2021.12收治的60例T2DM患者作为研究对象，分成甲、乙组，每组均30例，均进行常规管理，乙组进行药学干预，对比两组干预情况。结果：乙组用药依从性、ADR发生率分别是96.67%、10.00%，甲组为73.33%、33.33%，数据差异显著，有统计学意义（P＜0.05）。结论：对T2DM患者进行药学干预，有益于提升用药依从性，减少药物副作用，值得推广。

简介：【摘要】目的 对2型糖尿病患者药学干预的实施对患者用药依从性以及药品使用不良反应的影响展开研究。方法 研究对象为我院在2021年1月到2021年11月期间收治的66例2型糖尿病患者，分组后对照组33例不应用药学干预，观察组33例使用药学干预，对比两组患者用药情况。结果 对比发现观察组用药依从性更高，药品使用不良反应发生率更低。（P＜0.05）结论 药学干预在2型糖尿病中的应用可以优化患者用药行为与用药安全性，提高患者药用依从性，减少药用不良反应。