1.Signal mining of adverse reactions associated with macrolide antibiotics in pediatric patients based on the FAERS database
Zhenpo ZHANG ; Jiaxin HE ; Jingping ZHENG ; Yuting WANG ; Lin MA ; Ling SU
Journal of Pharmaceutical Practice and Service 2026;44(3):160-166
Objective To explore the adverse event signals of children using macrolide drugs (azithromycin, clarithromycin, and erythromycin), and provide reference for rational medicine use in clinical practice. Methods Data from children under 12 years old were extracted from the US FAERS database spanning from the first quarter of 2004 to the second quarter of 2023. The adverse drug reaction (ADR) signal mining for three macrolide antibiotics was conducted using the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) methods. Special emphasis was placed on analyzing and contrasting the differences in adverse events among the three drugs. Results A total of 1 615 reports for children under 12 years old were retrieved from the FAERS database, including 1 024 reports of azithromycin, 460 reports of clarithromycin, and 131 reports of erythromycin. Among azithromycin and erythromycin, there were more reports from boys than girls, while for clarithromycin, there were more reports from girls than boys. Oral administration was the most common route of administration for all three drugs. Regarding the outcome of adverse events reported, azithromycin and clarithromycin were primarily associated with other serious adverse events, whereas erythromycin was mainly associated with hospitalization and other serious adverse events. The number of adverse events reported decreased with increasing age, with a higher number of reports in the 0-3 age group. Using the ROR and BCPNN methods for signal detection, 86 signals were identified for azithromycin, 91 for clarithromycin, and 34 for erythromycin. These signals involved 22 System Organ Classes (SOCs), with azithromycin mainly concentrated in skin and subcutaneous tissue disorders (n=21), clarithromycin in gastrointestinal disorders (n=15), and erythromycin in gastrointestinal disorders (n=8). Twenty-four signals of moderate to high risk were detected, with 13 for azithromycin, 9 for clarithromycin, and 2 for erythromycin. Conclusion The adverse events induced by the three drugs with different risks in different systems. When clinically treating Mycoplasma pneumoniae pneumonia in children, the risk profiles of drugs in different systems should be considered, and personalized dosing should be implemented.
2.Eccentric Cycling Improves Cardiopulmonary Fitness, Respiratory Function, and Quality of Life in Chronic Kidney Disease: A Randomized Controlled Trial
Yu-Ting HUANG ; Hsin-Yeh LEE ; Hui-Ching CHENG ; Hsin-Lun YANG ; Ching-Hsia HUNG ; Chien-Chou SU ; Yu-Tzu CHANG ; Chien-Yao SUN ; Kun-Ling TSAI
Annals of Rehabilitation Medicine 2026;50(2):105-116
Objective:
To compare the effects of eccentric cycling (ECC), concentric cycling (CON), and standard care (CTL) on cardiopulmonary capacity, respiratory health, and quality of life (QoL) in patients with chronic kidney disease (CKD).
Methods:
Thirty-one CKD patients were divided into the CTL, CON, and ECC groups. The CON and ECC groups participated in 8-week, 24-session cycling programs. Outcomes were assessed through cardiopulmonary exercise tests, respiratory function tests, and the 36-Item Short Form Survey Instrument questionnaire.
Results:
The ECC group achieved significant improvements in maximal oxygen uptake, while the CTL group showed a decline. For oxygen uptake efficiency slope, significant changes were observed only in the ECC group, with a group-by-time interaction effect compared to CTL. Furthermore, the ECC group demonstrated the most significant increase in diaphragm movement and a significant increase in diaphragm thickness, with comparisons indicating that ECC outperformed both CTL and CON. Regarding QoL, the ECC group exhibited significantly greater improvements in Physical Component Summary and Mental Component Summary, with statistically significant differences compared with the CTL and CON groups.
Conclusion
ECC is a low-effort, high-benefit exercise modality that significantly enhances cardiopulmonary fitness, respiratory function, and QoL in patients with CKD.
3.Research progress on traditional Chinese medicine in treating cardiotoxicity induced by anticancer drugs
Linling SU ; Xianxia YUAN ; Wenyu JIANG ; Ling MO ; Jiaxue WU ; Min WANG ; Dongling LIU ; Yang HAI
Journal of China Pharmaceutical University 2026;57(3):393-400
Cardiotoxicity induced by antineoplastic agents is an important factor affecting the prognosis of cancer patients. This article systematically summarizes the clinical manifestations of cardiotoxicity caused by chemotherapeutic drugs, molecular targeted cancer therapies, and immunotherapeutic drugs, and identifies the core injury mechanisms, including cardiomyocyte apoptosis, oxidative stress, and mitochondrial dysfunction. In Traditional Chinese Medicine (TCM) theory, anticancer drug-induced cardiotoxicity falls under the category of “heat toxins” characterized by dual deficiency of qi and blood, upward flaming of heart heat, stagnation of the heart vessels, and meridian obstruction induced by phlegm-dampness. Therefore, by reviewing the preventive and therapeutic effects and the underlying mechanisms of tonic medicines, interior heat-clearing medicines, blood-circulating and stasis-resolving medicines, phlegm-transforming, cough-suppressing and panting-relieving medicines, and interior-warming medicines, this paper concludes that TCM prevention and treatment of this condition adheres to the formulation principle of “reinforcing healthy qi, removing toxins, and resolving blood stasis”. Its mechanisms of action—including antioxidation effects, regulation of autophagic balance, antagonism of inflammatory responses, and improvement of microcirculation—are highly consistent with modern medical treatment strategies (e.g., dexrazoxane for inhibiting iron-dependent oxidative stress, statins for anti-inflammatory effects). This study provides theoretical support and practical guidance for the collaborative and precise prevention and treatment of anticancer drug-induced cardiotoxicity through the integration of traditional Chinese and Western medicine.
4.Efficacy and safety of Chinese herbal compounds for pulmonary nodules: A systematic review and meta-analysis
Yanlong LI ; Xinze ZHENG ; Lingyan LAN ; Ying WANG ; Wei SU ; Jiahui CHEN ; Xiangjun QI ; Xuewei LI ; Bo AN ; Ling YU ; Lingling SUN ; Lizhu LIN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(07):1119-1128
Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.
5.Prevalence of Polypharmacy and Potentially Inappropriate Prescribing (PIP) among Older Adults Aged 65 Years and above in Brunei Darussalam
Sebastian Eng Chong KOH ; Maggie SIM ; Lina Maziyyah PG METUSSIN ; Pey Siaw LIM ; Su Ying YEO ; Yung Shin YEO ; Wai See WONG ; Shyh Poh TEO ; Li Ling CHAW
Brunei International Medical Journal 2026;22():97-104
Introduction: Polypharmacy and potentially inappropriate prescribing (PIP) are increasingly recognised as important contributors to medication -related harm among older adults. However, published national data on the prevalence of polypharmacy and PIP in Brunei Darussalam are unavailable. The objectives of this study was to determine the prevalence of polypharmacy and PIP among adults aged 65 years and above in Brunei Darussalam using Screening Tool of Older Persons ’ potentially inappropriate Prescriptions (STOPP) version 2 criteria. Materials and Methods: A retrospective cross -sectional study was conducted using data from the Brunei Healthcare Information Management System (Bru -HIMS). A stratified proportional random sample of 2,000 older adults with documented medical encounters in 2016 was selected. Polypharmacy was defined as the concurrent use of five or more medications. PIP was assessed using STOPP version 2 criteria. Descriptive statistics were used to summarise prescribing patterns. Results: Of the 2000 older adults included (mean age 73.0 ± 6.6 years), 1,181 (59.1%) had polypharmacy. Among those with polypharmacy, 1,057 (89.5%) could be assessed using STOPP criteria, and 206 (19.5%) had at least one PIP. The most frequently identified PIPs involved prolonged use of proton pump inhibitors for uncomplicated peptic ulcer disease at full therapeutic dosage for more than eight weeks, where dose reduction, discontinuation, or transition to maintenance therapy (e.g. H2 receptor antagonists) is indicated, prescribing without evidence -based indication, duplication of drug classes, use of ACE inhibitors or angiotensin receptor blockers in patients with hyperkalaemia, and use of first -generation antihistamines. Conclusion: Polypharmacy and PIP are common among older adults in Brunei Darussalam. The findings highlight the need for systematic medication review and deprescribing strategies to optimise pharmacotherapy and improve medication safety in older populations
6.Prevalence of Polypharmacy and Potentially Inappropriate Prescribing (PIP) among Older Adults Aged 65 Years and above in Brunei Darussalam
Sebastian Eng Chong KOH ; Maggie SIM ; Lina Maziyyah PG METUSSIN ; Pey Siaw LIM ; Su Ying YEO ; Yung Shin YEO ; Wai See WONG ; Shyh Poh TEO ; Li Ling CHAW
Brunei International Medical Journal 2026;22():97-104
Introduction: Polypharmacy and potentially inappropriate prescribing (PIP) are increasingly recognised as important contributors to medication -related harm among older adults. However, published national data on the prevalence of polypharmacy and PIP in Brunei Darussalam are unavailable. The objectives of this study was to determine the prevalence of polypharmacy and PIP among adults aged 65 years and above in Brunei Darussalam using Screening Tool of Older Persons ’ potentially inappropriate Prescriptions (STOPP) version 2 criteria. Materials and Methods: A retrospective cross -sectional study was conducted using data from the Brunei Healthcare Information Management System (Bru -HIMS). A stratified proportional random sample of 2,000 older adults with documented medical encounters in 2016 was selected. Polypharmacy was defined as the concurrent use of five or more medications. PIP was assessed using STOPP version 2 criteria. Descriptive statistics were used to summarise prescribing patterns. Results: Of the 2000 older adults included (mean age 73.0 ± 6.6 years), 1,181 (59.1%) had polypharmacy. Among those with polypharmacy, 1,057 (89.5%) could be assessed using STOPP criteria, and 206 (19.5%) had at least one PIP. The most frequently identified PIPs involved prolonged use of proton pump inhibitors for uncomplicated peptic ulcer disease at full therapeutic dosage for more than eight weeks, where dose reduction, discontinuation, or transition to maintenance therapy (e.g. H2 receptor antagonists) is indicated, prescribing without evidence -based indication, duplication of drug classes, use of ACE inhibitors or angiotensin receptor blockers in patients with hyperkalaemia, and use of first -generation antihistamines. Conclusion: Polypharmacy and PIP are common among older adults in Brunei Darussalam. The findings highlight the need for systematic medication review and deprescribing strategies to optimise pharmacotherapy and improve medication safety in older populations
7.Analysis of soil-borne nematode infection status among rural communities in Yubei, Chongqing
Dan JIANG ; Yong-dong HAO ; Sen-ping YANG ; Xiao-yuan SU ; Hua-jun BAI ; Bo LYU ; Ya-ling RAN ; He-yi GUAN ; Ling HU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):85-89
Objective To analyze the infection status and epidemic trends of soil-borne nematode infections in Yubei, Chongqing City, in 2010,2021, and 2022. Methods The local populations from four survey sites of four towns in 2010 and five sites of five towns in 2021 and 2022 were surveyed regarding their basic information using a unified form. Fecal samples of the participants were collected and tested for soil-borne nematode infections using the modified Kato-Katz thick smear method. Results In 2010, 2 049 participants were surveyed, followed by 1 000 participants in 2021 and 2022. The overall prevalence of parasitic infections declined significantly from 3.86% to 0.20%. In 2010, soil-transmitted nematode included hookworms(3.81%) and roundworms(0.29%). In 2021, the infection rates of roundworms and hookworms were 1.70% and 0.10% respectively. Notably, only Ascaris was identified in 2022(0.20%). The≥60 age group consistently exhibited the highest infection rates across all surveys, followed by the 40-59 age group. The infection rates of males in the three surveys were 3.31%,1.92%, and 0.20% respectively, and those of females were 4.37%, 1.46%, and 0.20% respectively. There was no statistically significant difference in the infection rates between males and females. Educational attainment was inversely associated with infection; in 2010, the highest prevalence was observed among those with primary education or below, whereas in 2021, illiterate or semi-literate individuals showed the highest susceptibility. The occupational distribution of infections in 2010 indicated that retirees (8.33%), farmers(4.86%), and homemakers or unemployed individuals(3.45%)were the most affected. However, in 2021 and 2022, farmers emerged as the predominant occupational group with soil-transmitted nematode infections. Conclusions The infection rate of soil-borne nematodes showed a decreasing trend in Yubei, and the infection species changed from hookworms in 2010 to Ascaris in 2022. Farmers, the elderly, and people with low education levels should continue to be the focus of preventive and control efforts.
8.Accuracy of multivariate discriminant analysis versus fibrosis-4 in evaluating the liver fibrosis degree in patients with chronic HBV infection
Hongyu LIU ; Xiaoting LI ; Jianning JIANG ; Chao JIN ; Cailian CAI ; Keshan WANG ; Fangpeng LING ; Bingling FAN ; Minghua SU
Journal of Clinical Hepatology 2025;41(4):677-683
ObjectiveTo investigate the accuracy of multiple discriminant analysis (MDA) versus fibrosis-4 (FIB-4) in assessing liver fibrosis degree in patients with HBV infection, as well as the possibility of MDA as an indicator for disease progression. MethodsA total of 263 patients with HBV infection who underwent liver biopsy in The First Affiliated Hospital of Guangxi Medical University from April 2010 to April 2024 were included, and their clinical data were collected. According to the results of pathological examination, they were divided into non-significant fibrosis group (F<2) with 126 patients and significant fibrosis group (F≥2) with 137 patients. The correlation of MDA and FIB-4 with liver fibrosis degree was analyzed, and MDA and FIB-4 were compared in terms of their accuracy in assessing significant liver fibrosis. A total of 62 patients completed follow-up, and according to the presence or absence of progression to liver cirrhosis at the last follow-up visit, they were divided into progressive group with 21 patients and non-progressive group with 41 patients; the efficacy of MDA and FIB-4 in diagnosing disease progression was analyzed and compared. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the Kruskal-Wallis H test was used for comparison between multiple groups, and the Bonferroni method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data. The Spearman’s correlation coefficient was used for correlation analysis. The Wilcoxon signed rank sum test was used for the analysis of baseline data and data at the end of follow-up, and the binary Logistic regression analysis was used to investigate the influencing factors for progression to liver cirrhosis. The receiver operating characteristic (ROC) curve was used to investigate the diagnostic efficacy of indicators, the Z-test was used for comparison of the area under the ROC curve (AUC), and the paired chi-square test was used for comparison of the sensitivity, specificity, and accuracy of the two indicators. ResultsThe correlation coefficient between FIB-4 and liver fibrosis degree was 0.378, while the correlation coefficient between MDA and liver fibrosis degree was -0.325 (both P<0.001). FIB-4 had an AUC of 0.688, a sensitivity of 64.96%, a specificity of 68.87%, a positive predictive value of 67.42%, a negative predictive value of 63.36%, an accuracy of 65.40%, and a cut-off value of 1.01, while MDA had an AUC of 0.653, a sensitivity of 52.55%, a specificity of 78.57%, a positive predictive value of 72.73%, a negative predictive value of 60.37%, an accuracy of 65.02%, and a cut-off value of 0.29, suggesting that compared with FIB-4, MDA had a lower sensitivity (P=0.004) and a higher specificity (P=0.001). The progressive group had a significantly higher age than the non-progressive group at baseline (t=2.611, P=0.011). For the progressive group, there was an increase in FIB-4 and a reduction in MDA from baseline to the end of follow-up (both P<0.001), while the non-progressive group showed no significant changes (both P>0.05). The multivariate Logistic regression analysis showed that aspartate aminotransferase (odds ratio [OR]=0.940, 95% confidence interval [CI]: 0.885 — 0.998, P<0.05) and MDA (OR=0.445, 95%CI: 0.279 — 0.710, P<0.001) were independent influencing factors for disease progression. MDA had an AUC of 0.893 and an optimal cut-off value of -0.01 in diagnosing the disease progression of liver cirrhosis. ConclusionMDA has a comparable accuracy to FIB-4 in the diagnosis of significant liver fibrosis, and MDA<-0.01 has a high accuracy in diagnosing the progression of liver fibrosis to liver cirrhosis, which can help to reduce the need for liver biopsy in clinical practice.
9.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.
10.Establishment of Psoriasis Rat Model with Spleen Deficiency and Dampness Obstruction Syndrome Induced by External Dampness Factors
Yating ZHANG ; Haojie SU ; Fanlu LIU ; Panyu ZHOU ; Qing WANG ; Junhong ZHANG ; Jingjing WU ; Ling HAN
Journal of Traditional Chinese Medicine 2025;66(13):1369-1377
ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type), and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group (n=3), common psoriasis group (n=5), spleen deficiency and dampness obstruction syndrome (external dampness type) group (n=7), and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group (n=7). The spleen deficiency and dampness obstruction syndrome (external dampness type) rat model was established through 32-week exposure to an artificially simulated high-humidity environment, while the common psoriasis model was developed via 7-day topical application of imiquimod cream, and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type). Rats in the normal group were housed under normal humidity conditions. The general state, tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations; the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes; the severity of psoriasis in rats was evaluated through skin pathological changes, psoriasis area and severity index (PASI), proliferating cell nuclear antigen (PCNA) expression and spleen tissue changes; changes in rat CD4+ interferon-γ+ cells (CD4+IFN-γ+ cells), CD4+ tumour necrosis factor-α+ cells (CD4+ TNF-α+ cells), and forkhead framing protein P3+ regulatory T cells (CD3+CD4+FoxP3+ Treg cells) were detected by flow cytometry. ResultsMacroscopically, both the spleen deficiency and dampness obstruction syndrome (external dampness type) group and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group exhibited manifestations of spleen deficiency and dampness obstruction, including lethargy, huddling behavior, dull and disheveled fur, as well as soft or loose stools and perianal soiling in some individuals; both these two groups displayed enlarged tongue, swollen, and moist tongue texture, accompanied by slippery tongue surface. Microscopically, compared to the common psoriasis group, the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group showed increased epididymal fat index (P<0.05); compared to the normal group and spleen deficiency and dampness obstruction syndrome (external dampness type) group, the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group demonstrated significantly elevated spleen mass (P<0.05), while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group exhibited significantly higher erythema scores, scaling scores, infiltration scores, PASI total scores, and proportions of CD3+CD4+FoxP3+Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome (external dampness type) group (P<0.05), with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis; the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group displayed significantly increased proportions of CD4+TNF-α+cells compared to the spleen deficiency and dampness obstruction syndrome (external dampness type) group (P<0.05); whereas no significant differences were detected in CD4+IFN-γ+cell proportions among groups (P>0.05). ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.


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