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Diabetic retinopathy (DR), one of the common complications of diabetes, is the main cause of blindness. Due to the limitations of the existing clinical treatment methods, it is urgent to develop new targets or/and new therapeutic drugs. This review summarizes the clinical trials of anti-DR drugs in recent years, and we note that gene therapy is a potential direction for DR treatment development. Due to the characteristics of ocular structure, including small size, a relatively independent organ, immune privilege and the opportunity for local administration, gene therapy could well be advantageous in the treatment of DR. Furthermore, the long-term therapeutic effects of gene therapy also improve compliance by DR patients. All these indicate that gene therapy is likely a future direction for development of DR therapies.
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Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.
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Objective: To analyze the clinical characteristics of adenosquamous carcinoma of the pancreas (ACP) and pancreatic ductal adenocarcinoma (PDA), and to explore the differences in prognosis between the two types. Methods: The clinical and pathological characteristics of 26 cases with ACP (Group A) and another 26 with PDA (Group B), both of whom underwent radical surgery at Tianjin Medical University Cancer Hospital from August 2014 to April 2019, were retrospectively analyzed, and were matched according to the ratio of one to one. In our study, the characteristics of each pair included preoperative ECOG score, age, gender, the location and size of the tumors, TNM staging, CA19-9, CEA. The prognostic differences between the two groups were compared and analyzed. Results: There were 7 females and 19 males in both groups, among which 12 had lesions in the head of the pancreas and 14 in the tail of the pancreas; TNM staging: 13 in stageb, 6 in stage Ⅱa, 6 in stage Ⅱb, and 1 in stage III. The average tumor size was 3.9 cm in the Group B, and 4.4 cm in the Group A. Radical surgery was performed in the patients of both groups, and among them 7 patients in Group A received combined organ resections. Survival analysis showed that the median survival time was 8.5 months in Group A and 19 moths in Group B (HR: 0.442; 95% CI: 0.224-0.872; P=0.019). Conclusions: ACP is more common in the males and its The prognosis is worse compared with PDA, but it has no specific clinical manifestations.
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Objective:To prepare magnetic solid lipid nanoparticles co-loaded quercetin and resveratrol(QR-MSLN),develop the reasonable characterization method,and investigate its inhibitory effect on transplanted hepatocarcinoma H22 tumor in mice. Method:Magnetic Fe3O4 particles coated with oleic acid(OA-Fe3O4) were synthesized and its structure was confirmed by Fourier transform infrared spectrometer(FT-IR).QR-MSLN was prepared by emulsion ultrasonic dispersion method,its morphology was examined by transmission electron microscopy,its particle size was determined by laser particle sizer.Concentration of Fe in the preparation was determined by phenanthroline spectrophotometry.The entrapment efficiency,saturation magnetization,in vitro release behavior were investigated by ultrafiltration centrifugation,vibrating sample magnetometer(VSM) and dialysis method,respectively.Mouse tumor model transplanted with hepatoma H22 ascites tumor was established and antitumor effect of QR-MSLN on H22 bearing mice were observed in the presence of an applied magnetic field. Result:Morphology of QR-MSLN was round,and black magnetic particles could be observed inside it,its particle size was (171.9±2.2) nm,the concentration of Fe was (1.40±0.46) g·L-1.The preparation exhibited apparent superparamagnetism and the saturation magnetization was 7.75 A·m2·kg-1.The entrapment efficiencies of quercetin and resveratrol in QR-MSLN were 99.10% and 80.83%,respectively.QR-MSLN had a significantly higher effect of tumor inhibition than SLN(containing quercetin and resveratrol) and free drug(PConclusion:QR-MSLN has uniform particle size and good magnetic response,and shows remarkable antitumor effect on H22 bearing mice.
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Objective To learn the command of basic theories, basic knowledge and basic skills, as well as strict requirement, strict attitude and strict behavior(three basics and three strictness)of clinicians at secondary and above public hospitals in Chongqing. Methods In this study, the examination scores of 1 650 clinicians from 55 such hospitals were assessed in terms of their three basics and three strictness performance during November 9-11 of 2016. The data were analyzed with t test and descriptive statistics. Results The theory scoring and skill scoring of all the clinicians averaged 61.25 ± 0.72 and 68.19 ± 21.12 respectively. Theory scoring and skill scoring of tertiary hospital clinicians were significantly higher than those at secondary(P<0.05). The skill scoring of teaching hospital clinicians averaged 74.87 ± 20.67, higher than those at non-teaching hospitals(67.38 ± 21.07, P=0.045). Conclusions The basic medical quality lacks due attention by medical institutions at all levels, and the training and assessment of clinicians on three basics and three strictness fall far behind. The clinicians rely heavily on large medical equipments for their diagnoses, neglecting most basic diagnostic skills. Basic medical quality of the city can only be enhanced by strengthening the training and assessment of three basics and three strictness for clinicians.
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Objective To investigate the associations between expression of Tensin1 protein and clinicpathological characteristics and prognoses of gastric cancer (GC) patients.Methods The retrospective casecontrol study was conducted.The clinicopathological data of 163 GC patients who were admitted to the Affiliated Hospital of Jiangsu University between July 31,2011 and December 31,2013 were collected.The GC tissues and adjacent normal tissues were taken to paraffin imbedding,and then were detected by immunohistochemistry.Observation indicator:(1) expressions of Tensinl protein in GC tissues and adjacent normal tissues;(2) association between expression of Tensinl protein in GC tissues and clinicopathological characteristics;(3) followup and survival situations;(4) prognostic factors analysis.Follow-up using telephone interview was performed to detect survival up to January 1,2017.Measurement data with skewed distribution were described as M (range).Count data were analyzed using the chi-square test or pairing chi-square test.The survival curve and rate were respectively drawn and calculated using the Kaplan-Meier method,and Log-rank test was used for survival analysis.The univariate analysis and multivariate analysis were done using the COX roportional hazard model.Results (1) Expressions of Tensinl protein in GC tissues and adjacent normal tissues:immunohistochemistry showed that Tensinl protein in GC tissues and adjacent normal tissues mainly expressed in cytoplasm.Of 163 patients,154 (66 with high expression and 88 with low expression) and 9 had respectively positive and negative expressions of Tensinl protein in GC tissues;79 (37 with high expression and 42 with low expression) and 84 had respectively positive and negative expressions of Tensinl protein in adjacent normal tissues,with statistically significant differences in positive expression ratio and expression levels (x2=64.65,12.93,P<0.05).(2) Association between expression of Tensinl protein in GC tissues and clinicopathological characteristics:high expression rate of Tensinl protein in GC tissues were respectively 31.34% (21/67) in GC patients with tumor metastases and 46.88% (45/96) in GC patients without tumor metastasis,with a statistically significant difference (x2 =3.95,P<0.05).(3) Follow-up and survival situations:all the 163 patients were followed up for 3.3-64.7 months,with a median time of 28.7 months.The 3-year cumulative disease-free survival rate and cumulative overall survival rate in GC tissues were 63.12%,74.22% in 66 patients with high expression of Tensinl protein and 47.30%,55.74% in 97 patients with low and negative expressions of Tensin1 protein,showing statistically significant differences in above indicators (x2 =4.58,4.11,P<0.05).Survival analysis of subgroups showed that 3-year cumulative disease-free survival rate in GC tissues of patients with maximum tumor dimension ≥ 5 cm,nerve and / or vascular invasions and stage Ⅲ of TNM staging were 45.98%,62.79%,52.75% in patients with high expression of Tensin1 protein and 18.11%,31.10%,32.80% in patients with low and negative expressions of Tensin1 protein,with a statistically significant difference (x2 =5.85,7.89,4.96,P<0.05).The 3-year cumulative overall survival rate was respectively 66.00%,75.75%,67.93% in patients with high expression of Tensin1 protein and 30.74%,40.15%,44.67% in patients with low and negative expressions of Tensinl protein,with statistically significant differences (x2 =7.59,9.62,4.32,P < 0.05).(4) Prognostic factors analysis:results of univariate analysis showed that maximum tumor dimension,histological grade,nerve and / or vascular invasions,postoperative TNM staging,postoperative adjuvant chemotherapy and expression of Tensin1 protein were related factors affecting prognoses of GC patients [hazard ratio (HR) =3.66,2.45,2.17,3.36,0.41,0.54,95% confidence interval (CI):2.09-6.41,1.43-4.19,1.17-4.04,1.52-7.41,0.23-0.72,0.31-0.96,P<0.05].Results of multivariate analysis showed that maximum tumor dimension ≥ 5 cm and grade Ⅲ of histological grade were independent risk factors affecting prognoses of GC patients (HR=3.21,2.17,95%CI:1.63-6.32,1.18-3.99,P<0.05),and postoperative adjuvant chemotherapy and high expression of Tensin1 protein were independent protective factors affecting prognoses of GC patients (HR=0.50,0.44,95%CI:0.28-0.90,0.24-0.82,P<0.05).Conclusion High expression of Tensin1 protein may inhibit GC metastasis,and it is also an independent protective factor affecting prognoses of GC patients.
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@#AIM: To study the effects between low concentration atropine and orthokeratology on myopia prevention and control.<p>METHODS: Totally 150 cases of juvenile outpatients with myopia were chosen in our hospital. They were divided into 3 groups randomly. Group A(50 cases)were treated with low concentration atropine. Group B(50 cases)were treated with orthokeratology. Group C(50 cases)were treated with spectacles. Refractive degree and ocular axial length had no statistically significant differences between three groups before treatment. After 1a follow-up, refractive degree and ocular axial length of three groups were statistically analyzed. <p>RESULTS: After 1a, the refractive degree changes of each group before and after treatment were statistically significant(<i>P</i><0.01). The results of refractive degree changes among the groups were as follows: there was no significant differences between low concentration atropine group and orthokeratology group(<i>P</i>>0.05); compared with orthokeratology and low concentration atropine group, that of spectacles group was significantly different(<i>P</i>>0.05). After 1a follow up, the ocular axial length changes of each group before and after treatment were statistically significant(<i>P</i><0.01). The results of ocular axial length changes among the groups were as follows: there was no significant differences between low concentration atropine group and orthokeratology group(<i>P</i>>0.05); compared with orthokeratology and low concentration atropine group, that of spectacles group was significantly different(<i>P</i><0.05). <p>CONCLUSION: The effects of low concentration atropine and orthokeratology on controlling juvenile myopia and ocular axial length have no significant difference. They are superior to spectacles on controlling juvenile myopia.
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According to the technology requirements of the fourth national survey of Chinese Materia Medica resources (pilot), suitable investigation method of exploration and suggestions for investigating Chinese Materia Medica resources was proposed based on the type of wetland and artificial water of Hongze Lake region. Environment of Hongze Lake and overview of wetland, present situation of ecology and vegetation and vegetation distribution were analyzed. Establishment of survey plan, selection of sample area and sample square and confirmation of representative water area survey plan were all suggested. The present study provide references for improving Chinese materia medica resources survey around Hongze Lake, and improving the technical specifications. It also provide references for investigating Chinese Materia Medica resources survey on similar ecological environment under the condition of artificial intervention.
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Objective: To investigate the essential oil profile and terpenes accumulation in the roots of Gynura bicolor (Asteracese) treated by CO2 and LED lighting. Methods: G. bicolor herbs were treated by CO2 at the levels of 450 (control) and 1200 (elevated) μmol/mol and LED lighting with white light, RB20 (red/blue=8/2) and RB40 (red/blue=6/4). Headspace solid-phase micro-extraction-GC MS was employed to analyze terpenes from the essential oil of the roots. Results: In all treated-roots, the major components of terpenes were (E)-β-farnesene, α-, β-caryophyllene, δ-, β-, γ-elemene, and α-pinene. Increasing CO2 significantly decreased mono- and sesqui-terpenes in the roots under all light conditions, leading to the decreasing yields of the essential oils. Terpenes were at a higher level in RB20-treated roots than that in RB40-treated ones under both control and elevated CO2. Conclusion: CO2 (450 μmol/mol) and 20 % blue LED lights are more conducive to the accumulation of terpenes in the roots than 1200 μmol/mol CO2 and 40% blue LED lights. © 2014 Tianjin Press of Chinese Herbal Medicines.
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As an important ABC transporter, breast cancer re-sistance protein ( BCRP) plays an important role in tumor multi-drug resistance. Many laboratories are focusing on BCRP to re-verse multidrug resistance. We summarize in the paper the re-search progress on the regulation of BCRP expression, subcellu-lar localization, ATP-dependence, inhibition or modulation of its transport activity and potential clinical treatment strategies in or-der to provide theoretical support and some new research ideas for the reverse of multidrug resistance in clinic.
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To observe the clinical efficacy of Artisan iris-clip intraocular lens ( lOL) implantation on cataract with a wide range of lens dislocation. ●METHODS: Twenty-four hospital patients (28 eyes) of cataract with lens subluxation by trauma (20 patients, 20 eyes) and Marfan's syndrome (4 patients, 8 eyes) during May 2007 to December 2011 were selected. All of them underwent phacoemulsification or an anterior vitrectomy and Artisan iris - clip lOL implantation at stage Ⅰ. Postoperative visual acuity, corneal endothelial cell count, intraocular lens position and postoperative complications were observed. Follow-up time was 6mo. ●RESULTS: Compared with the preoperative, postoperative best corrected visual acuity improved to varying degrees, visual acuity of 0. 1-0. 5 was in 20 eyes, 0. 5-1. 0 in 8 eyes. After followed up 1-6mo, no artificial lens shift, iris inflammation, iris atrophy and corneal decompensation and other complications were observed. ●CONCLUSlON: Cataract surgery with a wide range of lens dislocation is difficult, but as long as surgeons who have a wealth of clinical experience and superb skills, still can carry out phacoemulsification surgery or anterior vitrectomy and Artisan iris - clip lOL implantation and obtain a better outcome.
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Cembranoid type diterpenes are important natural products which have novel structures and remarkable bioactivities. Cembranoid type diterpenes obtained now included isopropyl type, five, six, seven, eight membered lactone ring, open ring, reducing carbon types, etc, with cytotoxicity and antitumor activity. This paper reviews the structures and bioactivities of 193 cembranoid diterpenes which have been discovered since 2007, providing the scientific evidence for reasonable exploitation and application of cembranoid diterpenes.
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Safety on vaccine issues has been under greater concern.Epidemiologically,classical study designs on investigating the association between a rare adverse event and vaccine inoculation usually confronted with lower feasibility in practice.Self-controlled case series (SCCS) method was derived from cohort studies.The key advantage of this method is that it only uses data related to cases and trying to find relative incidence of events in the ‘ at risk' periods relative to the ‘ controlled' periods.A further benefit of this method is that all the fixed confounders are controlled implicitly,by self-control,thus provides high statistic powers.With these advantages,SCCS is suitable for the causality assessment on rare but severe adverse events caused by immunization,which has been widely used,abroad.However,the methodology of SCCS is still being developed,and the areas in use have been expanded to the studies related to the safety and effectiveness of drugs,efficacy of vaccines as well as risk factors of disease.
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OBJECTIVE@#To investigate ultrastructural changes in pulmonary tissue of a rat model of pulmonary fibrosis following treatment with compound Carapax trionycis (C. trionycis; Biejia in Chinese) formula.@*METHODS@#Sixty male Sprague-Dawley rats were randomly divided into four groups (n=15): compound C. trionycis formula high-, middle-, and low-dose groups as well as model group. Pulmonary fibrosis was induced by bleomycin. Five rats from each group were sacrificed on day 7, 14 and 28 of the drug treatment, respectively. The pulmonary tissue was harvested followed by hematoxylin-eosin staining and subsequent transmission electron microscopy. The Szapiel's method was used to assess the degree of alveolitis and pulmonary fibrosis.@*RESULTS@#Compared with the model group, the compound C. trionycis formula groups had slighter pulmonary alveolitis after the 7-day treatment and also had alleviated alveolar inflammation and pulmonary fibrosis after the 14-day treatment. After the 28-day treatment, the compound C. trionycis formula groups showed deposition of a small amount of fibrous tissue and lesions occupying less than 21% of the whole lung area, while the model group showed focal or diffuse fibrous deposition, narrow alveolar cavity, disordered lung structure, and lesions in larger than 51% of the whole lung area.@*CONCLUSIONS@#The compound C. trionycis formula can inhibit the proliferation of collagen fibers and resist pulmonary fibrosis.
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Animales , Masculino , Ratas , Histocitoquímica , Pulmón , Patología , Medicina Tradicional China , Métodos , Fibrosis Pulmonar , Patología , Distribución Aleatoria , Ratas Sprague-Dawley , TortugasRESUMEN
<p><b>OBJECTIVE</b>forecast the epidemic trend and to evaluate the effect of outbreak control measures by investigation of a varicella outbreak event with a discrete time delay SEIR model.</p><p><b>METHODS</b>A discrete time delay model was formulated by discretization method based on a continuous SEIR model with the consideration of the time delay effect on latent period and communicable period. The epidemic trend forecast was carried out based on the number of expected cases. The theoretical effect evaluation was assessed by comparing the results from different emergency control measures.</p><p><b>RESULTS</b>Without any control measures, the theoretical attack rate was 30.16% (504/1671). The course of the epidemic lasted for 4 months and the peak epidemic time was 78 days after the onset of the first case. 'Generation' phenomenon had been observed in the course of the epidemic with the interval of two weeks. The actual number of cases was decreased by 89.48% (451/504) compared with the number of expected cases under no control measure scenario. With the rigorous quarantine measure for all cases on their onset day, when the measure was conducted on 0, 14, 28, 42 days after the onset of the first case, the total numbers of expected cases were 22, 59, 127 and 220 respectively. With the quarantine measure conducted on 14 days after the onset of the first case, when the proportion of quarantine was 30%, 50%, 70%, 90%, the total number of expected cases were 485, 457, 386 and 169, respectively. With the emergent vaccination for all persons, when the measure was conducted on 0, 14, 28, 42 days after the onset of the first case, the total numbers of expected cases were 7, 26, 81 and 202 respectively. With the emergent vaccination conducted on 14 days after the onset of the first case, when the immunization coverage rate was 30%, 50%, 70%, 90%, the total numbers of expected cases were 354, 246, 127 and 40, respectively.</p><p><b>CONCLUSION</b>The number of expected cases can be regarded as the reference to evaluate the effect of control measures. The simulation results suggest that it will get more benefits to conduct control measures earlier in varicella outbreak events, and the effect of emergent vaccination is better than that of quarantine measure under the same conditions.</p>
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Humanos , Varicela , Epidemiología , Control de Enfermedades Transmisibles , Métodos , Brotes de Enfermedades , Incidencia , Modelos TeóricosRESUMEN
For most variety of vaccines, two types of effects-direct and indirect, can result from immunization programs. Unimmunized individuals in the population that receive immunization program can benefit from the vaccines in addition to the protection from immunization.The classical vaccine trails allocate individuals into study and control arms with individual randomization, so the programs' cost-benefit is underestimated due to the impossible measurement on indirect effect. The objectives of the present work are to introduce the conceptual framework,developed by Halloran et al, for four types of study designs that differentiate and account for direct,indirect, total and overall effects of intervention programs, and to explain the relationships of these effects as well. With the examples of field trails of oral cholera vaccines in Bangladesh and Vi typhoid vaccine in India, further issues refer to the identification of indirect effect. The application in practice is also discussed.
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To find anti-hypertensive lead drug, angiotensin converting enzyme (ACE) inhibitory peptides were synthesized and their effects on inhibiting ACE activity were investigated. ACE inhibitory peptides were synthesized via Fmoc solid-phase synthesis, isolated and purified through reversed phase high-performance liquid chromatography (RP-HPLC), and identified by mass spectrometry. A RP-HPLC analysis method was used to test ACE inhibitory activity in vitro of these ACE inhibitory peptides. Six octapeptides were successfully synthesized, and the analytical results of mass spectrum were consistent with their theoretically calculated data. Among these synthetic octapeptides, the anti-SARS (severe acute respiratory syndromes) octapeptide had the most obvious ACE inhibitory activity with an IC50 value of 3.4 x 10(-5) mol x L(-1). So octapeptide AVLQSGFR-OH (anti-SARS peptide) was found to be the strongest candidate for potential development as an anti-hypertensive drug and had the implication of further study.
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Inhibidores de la Enzima Convertidora de Angiotensina , Química , Farmacología , Antihipertensivos , Química , Farmacología , Cromatografía Líquida de Alta Presión , Métodos , Espectrometría de Masas , Estructura Molecular , Oligopéptidos , Química , Farmacología , Peptidil-Dipeptidasa A , Técnicas de Síntesis en Fase SólidaRESUMEN
To find anti-hypertensive lead drug, angiotensin converting enzyme (ACE) inhibitory peptides were synthesized and their effects on inhibiting ACE activity were investigated. ACE inhibitory peptides were synthesized via Fmoc solid-phase synthesis, isolated and purified through reversed phase high-performance liquid chromatography (RP-HPLC), and identified by mass spectrometry. A RP-HPLC analysis method was used to test ACE inhibitory activity in vitro of these ACE inhibitory peptides. Six octapeptides were successfully synthesized, and the analytical results of mass spectrum were consistent with their theoretically calculated data. Among these synthetic octapeptides, the anti-SARS (severe acute respiratory syndromes) octapeptide had the most obvious ACE inhibitory activity with an IC50 value of 3.4 x 10(-5) mol x L(-1). So octapeptide AVLQSGFR-OH (anti-SARS peptide) was found to be the strongest candidate for potential development as an anti-hypertensive drug and had the implication of further study.
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Interaction assessment is an important step in epidemiological analysis. When etiological study is carried out, the logarithmic models such as logistic model or Cox proportional hazard model are commonly used to estimate the independent effects of the risk factors. However,estimating interaction between risk factors by the regression coefficient of the product term is on multiplicative scale, and for public-health purposes, it is supposed to be on additive scale or departure from additivity. This paper illustrates with a example of cohort study by fitting Cox proportional hazard model to estimate three measures for additive interaction which presented by Rothman.Adopting the S-Plus application with a built-in Bootstrap function, it is convenient to estimate the confidence interval for additive interaction. Furthermore, this method can avoid the exaggerated estimation by using ORs in a cohort study to gain better precision. When using the complex combination models between additive interaction and multiplicative interaction, it is reasonable to choose the former one when the result is inconsistent.
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Drug-induced nephrotoxicity is very common in both new drug development and clinic practice. Various drugs can induce kidney injuries, including tubulointerstitial, glomerular and renal vascular disease. To investigate the mechanism of drug induced nephrotoxicity is important for risk reduction of new drug development, reasonable drug usage, early discovery and effective prevention/treatment of adverse effects in clinics.