Derived from healthy human blood， human albumin is widely applied for treating critically and seriously ill patients. However， inappropriate off-label and irrational use of human albumin has remained prevalent， resulting in significant wasting of valuable drug resources. Currently， there is an acute dearth of authoritative guidelines or consensus on clinical application management of human albumin in China. To address this wide gap， a multidisciplinary panel of experts， under the auspices of Committee of Hospital Pharmacy of Chinese Pharmaceutical Association， has collaborated on developing a comprehensive consensus for standardizing management measures and providing guidance for rational utilization of human albumin. This consensus focused upon eight major aspects of clinical application management， including supply management， formulating clinical application standards， management of off-label drug use， training in rational usage， management of prescription sessions， prescription review processes， informatization management and patient education regarding medication usage.
OBJECTIVE To conduct pharmacodynamic evaluations of quaternized amphiphilic carbonaceous particles topical antimicrobial gel （TAG/QACPs） for its potential application for skin wound. METHODS The effects of TAG/QACPs on the activities of Staphylococcus aureus， Escherichia coli and Candida albicans were examined by spread plating. And the effects of TAG/QACPs on the wounds of the injured mice models were assessed. The safety of TAG/QACPs was analyzed by skin irritation and skin allergy tests in rabbits. RESULTS The bactericidal rate of TAG/QACPs for the tested microorganism was 99.9% at an addition volume of 0.3 mg∙g–1 QACPs. Wound healing rate of injured mice models within 14 days was 98.86% after using this agent. No irritation or allergic reaction occurred after plating this agent onto the skin of rabbits. CONCLUSION TAG/QACPs is a safe and effective antibacterial agent capable of promoting skin wound healing.
OBJECTIVE To explore the correlation between fingerprint spectrum of deer bone and its immunomodulatory function and identify the active components contributing to its immunomodulatory effect. METHODS Ten groups of deer bone samples were prepared at different extraction temperatures and their fingerprint spectra detected. Multivariate statistical analysis was performed for common peaks in fingerprint spectra. Liquid chromatography-mass spectrometry （LC-MS） and standard product comparisons were employed for identification. Immunomodulatory function of deer bone was evaluated by measuring cellular viability and nitric oxide （NO） concentration of RAW264.7 injury model with ten groups of deer bone extracts. Spectrum-effect relationship of deer bone was established through grey relational analysis. RESULTS The fingerprint spectrum of deer bone had ten common peaks. The structures of these ten peaks were identified by LC-MS and six compounds detected through standard product comparisons. The similarity of deer bone fingerprint spectrum was greater than 0.9. Cluster analysis and principal component analysis yielded the same results， classifying deer bone into six categories. Orthogonal partial least squares discriminant analysis （OPLS-DA） revealed five chromatographic peaks with variable importance in projection （VIP） greater than 1， namely peaks 4， 7 （uridine）， 10 （guanosine）， 5 and 9 （inosine）. Grey relational analysis indicated that all ten chromatographic peaks had a correlation greater than 0.6， suggesting that deer bone might exert its immunomodulatory function through multiple components. Nine chromatographic peaks had a correlation greater than 0.7， indicating a strong correlation. The first six chromatographic peaks were 7 （uridine）， 10 （guanosine）， 9 （inosine）， 2 （cytidine）， 3 （uracil） and 6 （hypoxanthine）. In summary， three nucleoside components of uridine， guanosine and inosine might be the major immunomodulatory components in deer bone. CONCLUSION Immunomodulatory function of deer bone may be the result of synergistic action of multiple nucleoside components. And uridine， guanosine and inosine are probably the major active components contributing to immunomodulatory effect of deer bone.
OBJECTIVE To optimize the fermentation technique of Panax notoginseng saponins and compare the immune activity of saponins before and after fermentation. METHODS Fermentation process of saponins was optimized with a response surface methodology based upon a single factor experiment where medium pH value， fermentation time， fermentation temperature and amount of inoculation of Lactobacillus plantarum were influencing factors. And total contents of ginsenosides Rh1， Rg3 and Compound K（CK） were response values. An immunosuppressive model was established by an intradermal injection of acetylphenylhydrazine and cyclophosphamide. Thymic and splenic indices were calculated by weighting body， thymus and spleen. Serum levels of tumor necrosis factor-alpha （TNF-α）， interferon-gamma （IFN-γ）， interferon-6 （IL-6） and interferon-10 （IL-10） were detected by enzyme-linked immunosorbent assay （ELISA）. And improvement effects of saponins before and after fermentation on immunosuppressed rats were evaluated with the above indices. RESULTS The optimal fermentation conditions were as follows： pH 7.0， fermentation time 3.2 days， fermentation temperature 37.6 ℃ and inoculation amount of L. plantarum liquid 3.1%. Three parallel experiments were performed under optimal conditions with a total saponin level of 2.42 mg·g–1. PNS before and after fermentation could boost thymic index and splenic index of immunosuppressed rats and elevate the serum levels of TNF-α， IFN-γ， IL-6 and IL-10. Also immune activity of PNS post-fermentation was higher than that of PNS pre-fermentation. CONCLUSION The levels of ginsenoside Rh1， Rg3 and CK spike markedly in fermented saponins and immunomodulatory effects are significantly enhanced.
OBJECTIVE To predict and verify the methylation regulatory sites of Shenzhu Baihu Granules （Shenzhu） and explore its mechanism of action in treating gastric cancer （GC）. METHODS Anti-tumor effect of Shenshu was verified by a NOD scid gamma （NSG） nude murine model of GC. The effective chemical components and surgical targets were mined by searching the databases of Traditional Chinese Medicine Systems Pharmacology Database & Analysis Platform （TCMSP）， DrugBank， UniProt and PubChem and the differentially expressed genes of GC retrieved from the databases of GeneCards， MalaCards and GEO. The potential surgical targets for GC were obtained by intersection of both with Venny 2.1.0. A protein interaction network diagram was constructed in the database of STRING 11.5. GO functional and KEGG pathway enrichment analyses were performed with the database of DAVID. And a “drug component target disease pathway” network diagram was constructed with Cytoscape software for screening out key pathways and core targets for treating GC. Molecular docking verification of active ingredients and core targets was performed by AutoDockTools 1.1.2 software. And visualization of mapping results was enabled by Pymol software. Finally real-time quantitative polymerase cahin reaction （RT-qPCR）， Western blot and immunohistochemistry were utilized for verifying target genes. RESULTS After 12-day dosing， tumor volume and weight of treatment group were significantly smaller than those of control group （P<0.05）. A total of 42 effective drug ingredients were screened through network pharmacology with 664 potential target genes. After intersecting with 71 differentially expressed genes in GC， 15 target genes were obtained. GO/KEGG analysis revealed 11 pathways and two major genes for methylation modification-DNMT1 and EZH2. There was a significant marked down-regulation of DNMT1/EZH2 in tumor tissue of treatment group （P<0.05）. Molecular docking revealed that 7 active drug ingredients possessed docking activity with DNMT1/EZH2. CONCLUSION Seven key active ingredients in Shenshu， including acacia， luteolin and quercetin， may act on DNMT1/EZH2 core target proteins， reverse DNA/histone methylation modification and exert inhibitory effects on GC growth.
OBJECTIVE To establish the high performance liquid chromatography （HPLC） fingerprint of Qiangxin Mixture （QM） and determine the multi-component content and examine the effects of extraction， concentration， centrifugation and sterilization on the quality of QM during preparation process. METHODS Extract， concentrate， centrifuge and mixture （after sterilization） of QM were used as test products. And the fingerprints of four different process stages of preparation process of QM were established by HPLC and similarity evaluation and chromatographic peak identification performed. The contents of six components of quercetin-3-O-β-D glucose 7-O-β-D gentiandiglycoside， glucosine thiocyanate， glucosinoic acid， psyllin， isoflavone glucoside and psyllin D were determined. RESULTS As compared with control fingerprint， the similarity of different process stages in the preparation of 10 batches of QM was greater than 0.90. It indicated that the production process was relatively stable and 18 common peaks in the extract increased to 21 after concentration， centrifugation and sterilization. The content determination results showed that different process stages of preparation process had varying degrees of influence on the quality of QM and concentration process had the greatest impact. CONCLUSION This study examined the effects of different preparation processes on the quality of QM and provided data and theoretical rationales for common techniques of overall quality evaluation during preparation processes of traditional Chinese medicines.
OBJECTIVE To optimize maintenance regimen of levetiracetam （LEV） in Chinese epileptic children based upon Monte Carlo simulation （MCS）. METHODS According to the published pharmacokinetic data of LEV population in Chinese epileptic children， MCS was utilized for predicting the steady-state blood concentration （Css） of LEV under different dosing regimens and the probability distribution of Css within the therapeutic concentration reference range of 10 to 40 mg·L–1. RESULTS For LEV dosing in epileptic children aged 0–17 years， the maximal PTA value （97.4%） of Css distributed in 10–40 mg·L–1 was obtained with a dose of Lev at 15 mg·kg–1 bid. At a target concentration of 0–10 mg·L–1， PTA value peaked （69.3%） at a dose of 5 mg·kg–1 bid； at a target concentration of 10–20 mg·L–1， maximal PTA value was 66% at a dose of 8 mg·kg–1 bid； at a target concentration of 20–30 mg·L–1， PTA value peaked （43.5%） with a dose of 12.5 mg·kg–1 bid； at a target concentration of 30–40 mg·L–1， PTA value peaked （31.1%） at a dose of 17.5 mg·kg–1 bid. CONCLUSION MCS simulation may predict the reaching probability of Css at different LEV maintenance doses and reveal its distribution in different reference concentration ranges in Chinese epileptic children. It provides references for optimizing LEV dosing regimen.
OBJECTIVE To optimize the formulation of berberine and magnolol co-loaded liposomes （Lip-MB） by Box-Behnken response surface method. METHODS The content of berberine and magnolol was determined by high performance liquid chromatography （HPLC）. Lip-MB was prepared by thin-film dispersion plus pH gradient method. Based upon the results of single factor experiment， Box-Behnken response surface method was employed for optimizing the formulation with berberine and magnolol encapsulation efficiency as dependent variables. Morphology， particle size， zeta potential and in vitro release of Lip-MB were evaluated. RESULTS The optimal formulation process was as follow： mass ratio of hydrogenated soybean phosphotidylcholine （HSPC） to cholesterol （CHOL） 3.6∶1， drug-to-lipid ratio 1∶23， pH value of external aqueous phase 8.4 and incubation temperature of 59°C. The encapsulation efficiencies of berberine and magnolol in Lip-MB were （91.74±1.91）% and （83.17±1.05）%. Average particle size of liposomes was （106.6±2.60） nm and Zeta potential （–9.88±2.33） mV. Cumulative release rates of berberine and magnolol were 98.41% and 81.83% within 84h respectively. CONCLUSION The model established by Box-Behnken design-response surface method may be employed for optimizing the formulation of Lip-MB. And optimized liposomes offer high encapsulation efficiency， small particle size， uniform distribution and slow release effect.
OBJECTIVE To explore the potential mechanism of Mongolian medicine Zhachong 13 Pills for ischemic stroke through network pharmacology and verify through molecular docking and animal experiments. METHODS The active chemical constituents of Zhachong 13 Pills were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and other databases for target prediction and collection. Online Mendelian Inheritance in Man （OMIM） and other databases were employed for obtaining disease targets， Venny was utilized for obtaining intersection targets and protein-protein interaction （PPI） network was constructed. GO function enrichment and KEGG path enrichment analyses were performed with the database of Metascape. Molecular docking was performed by Autodock Vina. A rat model of ischemic stroke was established by a ligation of bilateral common carotid artery. Five groups of sham operation， model， Zhachong 13 high-dose， Zhachong 13 low-dose and positive control were designated. High-dose and low-dose groups received a suspension of Zhachong 13 Pills by 0.324 g·kg–1 and 0.162 g·kg–1 respectively. Positive control group had a donepezil solution by 0.45 mg·kg–1. Nerve injury of rats was evaluated at Day 3/7/14/28 post-modeling according to stroke index. After 28-day continuous instillation， brain tissue was harvested for hematoxylin-eosin （HE） stain and serum contents of dopamine （DA） and 5-hydroxytryptamine （5-HT） in rats determined by enzyme-linked immunosorbent assay （ELISA）. And the results of network pharmacology were preliminatively verified. RESULTS There were 182 active components of Zhachong 13 Pills， 905 targets and 668 common targets for disease effects. Pathway enrichment analysis revealed that the major pathways were cAMP signaling， 5-HT-synapses， dopaminergic synapses and platelet activation. Nerve function injury score and HE stain indicated that Zhachong 13 Pills could improve brain injury of ischemic stroke. ELISA confirmed that Zhachong 13 Pills could lower the serum contents of DA and 5-HT in ischemic stroke rats. CONCLUSION The potential acting mechanism Zhachong 13 Pills in ischemic stroke rats has been preliminarily verified through network pharmacology and animal experiments. It shall provide rationales for further researches on pharmacodynamic materials and acting mechanisms of Zhachong 13 Pills for ischemic stroke.
OBJECTICE To establish the drug use evaluation （DUE） criteria for ziprasidone for injection based upon technique for order preference by similarity to an ideal solution （TOPSIS） method for evaluating the rationality of its clinical use. METHODS Based upon the drug instructions of Ziprasidone for injection， the DUE standard for ziprasidone for injection was established by referring to the relevant guidelines and expert consensus through consultations. Also weighted TOPSIS method was employed for retrospectively reviewing the archived cases of ziprasidone for injection at Anhui Mental Health Center from January to December 2022 for rationality evaluation. RESULTS A total of 269 cases were included and only 31 （11.52%） fully fulfilled the evaluation criteria. Irrational use of ziprasidone for injection was common in off-label （46.47%）， contraindications （0.37%）， dosing course （9.29%）， auxiliary and laboratory examinations （32.71%）， drug interaction （13.01%）， special population （2.97%） and drug sequence （7.06%）. CONCLUSION The established ziprasidone for injection DUE standard may be used for clinical use of ziprasidone for injection.
OBJECTIVE Durvalumab/atezolizumab coupled with standard chemotherapy are currently only first-line immunotherapies as recommended by domestic and foreign guidelines for extensive-stage small cell lung cancer （ES-SCLC）. However， the economics of these two immunotherapies have remained ill-defined. Thus this study was intended to evaluate the cost-effectiveness of two immunotherapies for ES-SCLC from the perspective of Chinese healthcare system. METHODS Based upon Kaplan-Meier curves in clinical trials， a triple-state Markov model was constructed for simulating clinical output and cost consumption. Only direct medical expenses were calculated in the model and utility values obtained from the literature. Incremental cost-effectiveness ratio （ICER） was utilized as an outcome index. Sensitivity analysis was performed for determining the impact of parametric uncertainty on model stability. RESULTS Basic analysis revealed that， as compared with atezolizumab group， expense of durvalumab group was higher （292 619 vs. 436 738 yuan）. However， more quality adjusted life years （QALYs） were obtained （0.79 vs. 0.88） and ICER was 1 595 446 yuan/QALY. Sensitivity analysis indicated that utility value in progression-free survival （PFS） stage， price of durvalumab/atezolizumab and discount rate had the greatest impact on the model. CONCLUSION From the perspective of Chinese healthcare system， durvalumab regimen is not cost-effective as a first-line treatment of ES-SCLC as compared with atezolizumab regimen.
OBJECTIVE To explore the efficacy and safety of vancomycin versus linezolid for central nervous system infections （CNSIs） and provide a practical reference of real-world data for clinical treatment. METHODS For this retrospective cohort study， the relevant clinical data were reviewed for 155 CNSIs patients. They were divided into two groups of vancomycin （n=76） and linezolid （n=79）. The inter-group differences in efficacy （in-hospital mortality， abandoning therapy incidence & clinical effective rate） and safety （total adverse reaction， renal dysfunction， liver dysfunction & hematologic disorder） were compared. RESULTS The abandoning therapy incidence of linezolid group was significantly higher than that of vancomycin group （27.8% vs 10.5%， P=0.006）. Clinical effective rate of vancomycin group was significantly higher than that of linezolid group （81.6% vs 63.3%， P=0.011）. All outcomes of safety between two groups was not statistically significant （P>0.05）. Univariate and multivariate Logistic regression analyses revealed that use of vancomycin （OR=2.274， P=0.036） and a combined dosing of meropenem （OR=2.949， P=0.030） or cefoperazone-sulbactam （OR=4.403， P=0.010） were associated independently with clinical efficacy. CONCLUSION As compared with linezolid， vancomycin offers superior efficacy and comparable safety for CNSIs. Use of vancomycin and a combined dosing of meropenem or cefoperazone-sulbactam are favorable factors of clinical efficacy.
OBJECTIVE To compare three kinds of periodontitis care schemes through cost-effectiveness and cost-utility to provide rationales for a proper treatment of periodontitis. METHODS A total of 106 patients with periodontitis were randomized into 3 groups to receive basic periodontal treatment plus compound chlorhexidine gargle （n=38）， compound chlorhexidine gargle plus Sipaii gingival consolidation solution （n=35） and compound chlorhexidine gargle plus Kangfuxin gargle （n=33）. Baseline profiles， treatment expenses， effective rate and EQ-5D-3L scale score were recorded. Cost-effectiveness and cost-utility analyses were performed. Cost-effectiveness ratio （CER） was based upon total cost （C）/efficiency （E） and cost-utility. Health utility values were converted by EQ-5D-3L China effect value score system. Quality-adjusted life years （QALYs） = reported survival time × health utility value. And cost-utility ratio （CUR） = total cost （C）/QALYs. RESULTS The effective rates before and after treatment were compared among three groups. After treatment， the effective rates of three groups were 78.95%， 91.43% and 87.88% （H=6.753， P=0.034）. There were significant differences. Cost-effectiveness ratio was 1629.98， 1486.94 and 1516.52； Before treatment， utility values of three groups were 0.92， 0.89 and 0.90； After rehabilitation， utility values were 0.98， 0.98 and 0.97， respectively. Cost-utility ratio of three groups was 270.18， 190.41 and 240.13. Treatment expense was lower than per capita GDP of Jiangsu Province for each increment of one effective rate and one QALYs. It indicated that treatment cost was completely worthwhile. The ratios of cost-effectiveness and cost-utility were similar. Both were the lowest in compound chlorhexidine plus Xipayi gingival consolidation fluid group. It indicated that compound chlorhexidine plus Xipayi gingival consolidation fluid group achieved the same therapeutic effect with a minimal expense. CONCLUSION For periodontitis patients receiving basic periodontal basic care， a combination of compound chlorhexidine gargle and Xipayi gingival solidifying solution may significantly improve the efficiency and economy of periodontal treatment.
OBJECTIVE To evaluate the efficacy and safety of five commonly used oral iron agents for iron deficiency anemia （IDA） during pregnancy to provide evidence-based rationales for rational use of these drugs in clinical practices. METHODS The databases of China National Knowledge Infrastructure （CNKI）， WANFANG， VIP， SinoMed， PubMed， Cochrane library， Embase and Web of Science were searched for randomized controlled trials （RCT） of polysaccharide iron complex capsules， ferrous succinate sustained-release tablets， ferrous succinate tablets， ferrous dextran oral solution， compound ferrous sulfate and folic acid tablets for IDA during pregnancy. The retrieval period started from October 31， 2022. Two researchers independently screened the literature， extracted the data and applied Cochrane risk bias assessment tools for evaluating the quality of the included literature. Revman5.3 and Stata16.0 were utilized for network Meta-analysis. RESULTS A total of 21 studies involving 3 123 patients were retrieved. The results of network Meta-analysis indicated that， in terms of total effective rate， ferrous succinate sustained-release tablets > polysaccharide iron complex capsules > compound ferrous sulfate plus folic acid tablets > iron dextran oral solution > ferrous succinate tablets. In terms of cure rate， ferrous succinate sustained-release tablets > polysaccharide iron complex capsules > compound ferrous sulfate & folic acid tablets > iron dextran oral solution>ferrous succinate tablets； In terms of the incidence of gastrointestinal reactions， ferrous succinate tablets > compound ferrous sulfate & folic acid tablets > iron dextran oral solution > polysaccharide iron complex capsules > ferrous succinate sustained-release tablets. CONCLUSION Ferrous succinate sustained-release tablets and polysaccharide iron complex capsules offer better efficacies as judged by the above three outcome parameters.
OBJECTIVE To explore the clinical characteristics and occurrence patterns of drug-induced kidney injury （DIKI） in Wuhan Municipality and identify the risk signals of kidney injury caused by high-frequency agents to provide references for rational use of drugs in clinical practices. METHODS For this retrospective study， all DIKI-related reports were collected from Wuhan ADR spontaneous reporting system database during 2012 to 2022. Demographic profiles， distribution/type of drugs and clinical manifestations were recorded with descriptive statistics. Risk signal mining was further conducted with reporting odds ratio （ROR） and proportional reporting ratio （PRR） through the databases of Medicines and Healthcare Products Regulatory Agency （MHRA） and Bayesian Confidence Propagation Neural Network （BCPNN）. RESULTS A total of 1 504 DIKI cases were obtained with an annual increase in the number of cases. The degree of DIKI was mostly "general" and "serious" accounted for 38.43%. The subjects predominated in 60–79 age group with a male-to-female ratio of 1.58∶1. A large majority of DIKI reports occurred at Days 2-7 post-dosing. A total of 19 categories and 417 types of drugs were involved. The most frequently reported drugs were antibiotics （27.73%）， hematological agents （12.50%） and urinary system drugs （8.31%）. Top three drugs were scopolamine， mannitol and vancomycin. Further data mining revealed eight drugs with strong positive risk signals for kidney injury. CONCLUSION DIKI is associated with a large variety of drugs. Antibiotics are the most frequent. Due to diverse clinical manifestations of DIKI， high-risk senior males should be closely monitored. Drugs should be dosed strictly according to the indications and doses of package insert. And kidney functions shall be watched for minimizing the occurrence of DIKI in high-risk populations.
OBJECTIVE To explore the construction and effects of unattended and intelligent management model in surgical pharmacy. METHODS According to the flows of PDCA （Plan， Do， Check & Act） cycle， existing problems in surgical pharmacy were discussed， key points were determined and the corresponding countermeasures were formulated. Time for accessing medicine cabinets pre-operation， time for temporary treatment during operation and frequency of adverse events before and after implementation were recorded. RESULTS Time for accessing medicine cabinets pre-operation declined from 10.7 to 2.8 min. And time for temporary treatment during operation dropped significantly from 30.2 to 5.6 min. Further， the frequency of adverse events decreased from 56 to 24 cases， indicating a distinct downward trend. CONCLUSION Constructing a management model of unattended intelligent pharmacy in operating room not only can ensure the safety， effectiveness and timeliness of drug dosing during operation， but also enable a refined and scientific management of drugs. It provides references for advancing traditional pharmacy towards intelligence.
Gene therapy has demonstrated great therapeutic potentials for such major refractory diseases as malignant tumors， infectious， autoimmune and rare disease， etc. Gene delivery vectors are essential for a successful implementation of gene therapy. Polythylenimine （PEI） is a widely studied cationic gene delivery vector， showing stable and efficient gene transfection in numerous cell lines and transfection conditions. PEI25k is regarded as a "gold standard" for gene transfection. Although PEI has broad application prospects in the field of gene delivery， there are still urgent problems to be tackled， including low transfection efficiency in vivo， high cytotoxicity， low targeting capability and lysosomal degradation of loaded gene. This review summarized the latest advances of designing novel polyethylenimine-based nanosystems for gene therapy， including high molecular weight linear PEI， PEI modified with polysaccharides， hydrophilic polymers or dextran， crosslinked low molecular weight branched PEI， PEI-based inorganic nanoparticles and co-delivery vectors of drug/gene based upon PEI. It was intended to provide theoretical rationales for further constructing gene delivery carriers with high efficiency and low toxicity.
Anaplastic lymphoma kinase-tyrosine kinase inhibitors （ALK-TKIs） have been a first-line option for ALK-positive advanced non-small cell lung cancer. A large series of adverse reactions occur while benefiting patients. This review summarized the pharmaceutical cares for intolerable nausea and vomiting after crizotinib dosing in one patient of ALK-positive lung cancer. After switching to ensartinib， there was diffuse epidermal peeling of whole body. A clinical pharmacist assisted physicians in handling adverse reactions and implementing pharmaceutical monitoring. Follow-up intervention was both efficacious and well-tolerated. It fully exemplified the role of clinical pharmacists in individualized treatment of tumor patients. It provided practical references for a proper management of such adverse drug reactions.
Drug-induced hypersensitivity syndrome （DIHS） is an under-recognized and potentially life-threatening hypersensitivity reaction. One patient successively presented with fever， rash， lymphadenopathy and elevated liver enzymes after a 10-day regimen of piperacillin tazobactam and moxifloxacin. Improvements occurred after a discontinuation of all previous medications and systemic corticosteroid therapy. For patients presenting with skin rash and systemic abnormalities after medications， physicians should consider a possible diagnosis of DIHS and adopt aggressive measures.
