1.Exploring Therapeutic Mechanism of Xihuang Wan for Hyperplasia of Mammary Glands Based on Network Pharmacology, Molecular Docking, and Cell Experiments
Junliang WANG ; Peihua LIANG ; Xueli MA ; Juanxia SUN ; Tao HAN ; Yongmei LAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):41-49
ObjectiveTo study the therapeutic mechanism of Xihuang Wan for hyperplasia of mammary glands based on network pharmacology, molecular docking, and cell experiments. MethodsThe active ingredients and targets of Xihuang Wan were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and A Bioinformatics Annotation daTabase for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) and supplemented by searching against PubChem and Swiss Target Prediction. The targets of differential metabolites in tissues and urine were obtained from previous metabolomics studies through PubChem and Swiss Target Prediction. GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGKB, Therapeutic Target Database (TTD), Drunbank were searched for the targets of hyperplasia of mammary glands. After the common targets were obtained via Veeny2.1.0, the STRING database was used to analyze the protein-protein interactions, and Cytoscape was used for the core target analysis and visualization. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed for enrichment analysis. Molecular docking was carried out in Autodock, and cell experiments were conducted to verify the prediction results. In the cell experiments, estradiol and progesterone (E2+P) were used to intervene in human mammary epithelial/MCF-10A cells, and thus the MCF-10A cell proliferation model was established. The cells were then treated with Xihuang Wan-medicated serum. The cell counting kit-8 (CCK-8) was used to measure the cell proliferation, and flow cytometry was used to detect apoptosis. The mRNA and protein levels of key factors in MCF-10A cells were determined by real-time PCR and Western blot, respectively. ResultsThe results of network pharmacology showed that 90 active ingredients and 316 common targets were obtained, from which 20 core targets and 38 corresponding active ingredients were screened out. The results of GO and KEGG enrichment analyses showed that Xihuang Wan exerted effect against hyperplasia of mammary glands by regulating a variety of biological processes, which may be related to protein kinase B (Akt)-related molecular functions, estrogen signaling pathway, prolactin signaling pathway and other biological processes. The results of molecular docking showed that estrogen receptor 1 (ESR1), serine/threonine kinase 1 (Akt1), non-receptor tyrosine kinase (SRC), and signal transducer and activator of transcription 3 (STAT3) all had strong binding activity with the nine active ingredients, suggesting that Xihuang Wan exert the effect through the ESR1/SRC/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and the Janus kinase (JAK)/STAT3 signaling pathway. The results of cell experiments showed that E2+P intervention in MCF-10A cells promoted the proliferation of MCF-10A cells (P<0.05), while the Xihuang Wan-medicated serum inhibited the proliferation of MCF-10A cells exposed to E2+P (P<0.05). Flow cytometry showed that the Xihuang Wan-medicated serum promoted the apoptosis of MCF-10A cells exposed to E2+P (P<0.01). The results of Real-time PCR showed that the Xihuang Wan-medicated serum down-regulated the mRNA levels of PI3K, Akt, JAK2, and STAT3 in MCF-10A cells treated with E2+P (P<0.01). The results of Western blot showed that the Xihuang Wan-medicated serum inhibited the expression of p-PI3K/PI3K, p-Akt/Akt, p-JAK2/JAK2, and p-STAT3/STAT3 in MCF-10A cells treated with E2+P (P<0.05). ConclusionXihuang Wan may exert the effect against hyperplasia of mammary glands by inhibiting the proliferation and promoting the apoptosis of MCF-10A cells, which may related to the inhibition of the activation of PI3K/Akt and JAK2/STAT3 signaling pathways.
2.A systematic review on the integrated application of evidence-based narrative education and undergraduate nursing teaching
Nannan BAI ; Meng LI ; Qian LIANG ; Chou YAO ; Yan WANG ; Ju HAN ; Chenyang HOU ; Nana XING
Chinese Medical Ethics 2026;39(2):229-237
ObjectiveTo systematically evaluate the application of narrative education in undergraduate nursing teaching, to understand the current application status of narrative education, and to provide a theoretical basis for the subsequent establishment of a sound narrative education system. MethodsA systematic search was conducted for studies published in Chinese and English databases on applying narrative education to undergraduate nursing teaching, with the search period ranging from database inception to February 23, 2025. Literature was screened, and relevant information was extracted. A rigorous quality evaluation was conducted on the included studies, and a descriptive analysis was performed on their content. ResultsA total of 20 papers were included, involving 3,180 research subjects, all of whom were undergraduate nursing students. The results of descriptive analysis showed that the teaching model of narrative education primarily encompassed reading narrative works, watching films and videos, performing narrative scenarios, and writing reflective journals. The course setting and content covered pre-teaching preparation and in-teaching implementation. The evaluation of teaching effectiveness included the evaluation of teachers’ teaching methods (student evaluation/self-evaluation) and the evaluation of students’ learning effectiveness (course grade evaluation/humanistic care scale/empathy scale assessment, and others). ConclusionNarrative education combines abstract concepts with concrete clinical situations, which not only enriches students’ learning experiences but also enhances their humanistic literacy. Meanwhile, it provides teachers with opportunities to develop their narrative teaching skills, which requires them to possess profound professional knowledge and employ narrative techniques to guide students in reflection and critical thinking, thereby improving teaching quality and learning outcomes. Future efforts should consistently deepen the connotation research of narrative education and build a systematic nursing education system.
3.Expert consensus on clinical application of parenteral direct thrombin inhibitors in perioperative period
Mingyu JIANG ; Yuan BIAN ; Lizhu HAN ; Qinan YIN ; Fengjiao KANG ; Anhua WEI ; Danjie ZHAO ; Lin WANG ; Ying SHAO ; Li TANG ; Yi WANG ; Shuhong LIANG ; Huijuan LIU ; Guirong XIAO ; Yue LI
China Pharmacy 2026;37(6):689-699
OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors (DTIs) in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (the Affiliated Hospital of UESTC), a multidisciplinary working group was established. Through literature review and the Delphi method, clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework; systematic searches were conducted in CNKI, Medline, Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment,Development and Evaluation (GRADE) approach, and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations (each with an expert consensus rate exceeding 90%) on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection, dosing ranges, key monitoring points, and safety management strategies for parenteral DTIs in various scenarios, including the perioperative period of ventricular assist device implantation, the perioperative period of cardiac surgery, perioperative patients with lower-extremity atherosclerotic disease, the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome, the perioperative period of carotid artery stenting in patients with carotid stenosis, the perioperative period of patients with right heart thrombosis, and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition, warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus, which is formulated based on the best available evidence, provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.
4.Effects of transcutaneous auricular vagus nerve stimulation on functional brain activity in patients with prolonged disorders of consciousness: A randomized controlled trial protocol using functional near-infrared spectroscopy and electroencephalography
Huan OUYANG ; Yifei WANG ; Ying HAN ; Jinling ZHANG ; Liang LI ; Chen XIN ; Jianghong HE ; Peijing RONG
Science of Traditional Chinese Medicine 2026;4(2):181-187
Background: Advances in intensive care have markedly improved survival after severe brain injury, leading to a growing population of patients with prolonged disorders of consciousness (pDOC). Current management of pDOC remains largely supportive, and evidence-based neuromodulatory interventions are limited; moreover, existing guidelines provide insufficiently explicit recommendations regarding mechanisms of action and objective biomarkers of treatment response. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a potential noninvasive intervention; however, its modulatory effects on brain function in pDOC are not yet well characterized, and the paucity of integrative mechanistic evidence has constrained its translation into routine clinical practice. Objectives: Within a multimodal assessment framework, this study aims to systematically elucidate the neurobiological mechanisms by which taVNS modulates brain function and autonomic activity in patients with pDOC, and to evaluate its clinical potential to enhance levels of consciousness. Methods: In this randomized controlled trial, 60 patients with vegetative state/minimally conscious state will be enrolled and randomly allocated to a taVNS group, a transcutaneous nonauricular vagus nerve stimulation group (sham), or a control group (n = 20 per group) for a 4-week intervention. The primary outcome will be changes in the Coma Recovery Scale-Revised scores from baseline to weeks 1, 2, and 4 of treatment. Secondary outcomes will include functional brain activity assessed by electroencephalography and functional near-infrared spectroscopy, as well as autonomic modulation indexed by heart rate variability. Functional prognosis will be evaluated using the Glasgow Outcome Scale-Extended at the end of treatment and at a 6-month follow-up. Safety will be assessed by continuous monitoring and documentation of adverse events throughout the study period. Results and discussion: By integrating electroencephalography–functional near-infrared spectroscopy with heart rate variability, this study will characterize the effects of taVNS on functional brain networks and consciousness recovery in pDOC across complementary behavioral, electrophysiological, hemodynamic, and autonomic domains, while interrogating potential sources of clinical and neurobiological heterogeneity. The findings are expected to provide a mechanistic and evidence-based foundation for the mechanism-driven clinical implementation of taVNS and the optimization of stimulation protocols in pDOC. Clinical trial registration: International Traditional Medicine Clinical Trial Registry, ITMCTR20250021041, https://itmctr.ccebtcm.org.cn.
5.Clear cell renal cell carcinoma with parotid gland metastasis 10 years after radical nephrectomy: a case report and literature review
Hongjun LIU ; Chenxu MA ; Xueping ZHANG ; Feng HAN ; Yuan GAO ; Hongjun ZHAO ; Liang QIAO
Journal of Modern Urology 2026;31(1):42-45
Objective To analyze the diagnosis, treatment and clinical characteristics of a patient with parotid gland metastasis of clear cell renal cell carcinoma(ccRCC)following radical nephrectomy. Methods The clinical data and diagnostic/therapeutic course of the patient were reported, and the metastasis time and treatment methods of patients with parotid metastasis of renal cancer were summarized in combination with literature. Results The 63-year-old male patient sought medical help due to a mass behind the right ear persisting for 3 months. He had undergone a right radical nephrectomy for a renal tumor 10 years ago. Preoperative computed tomography(CT)with contrast of the parotid region revealed an approximately 2.5 cm×2.1 cm round soft-tissue density lesion in the right parotid gland with slightly irregular margins. Positron emission tomography/computed tomography(PET/CT)showed an enlarged left kidney with an irregular shape and multiple round, slightly hyperdense lesion(SUVmax=7.2), suggestive of malignancy. A round, slightly hyperdense lesion(diameter 2.6 cm, SUVmax=4.2)with well-defined borders and increased radiotracer uptake was noted in the right parotid gland, indicating a hypermetabolic mass where malignancy could not be excluded. The patient subsequently underwent partial parotidectomy, advancement flap transplantation, and facial nerve dissection. Postoperative pathology revealed tumor cells with clear/eosinophilic cytoplasm and nuclear atypia, exhibiting ill-defined borders with salivary gland tissue. Immunohistochemistry was positive for PAX-8, CAⅨ, and Ki-67. During the 12-month follow-up, the patient was in good condition with no evidence of tumor recurrence or metastasis. Conclusion Parotid gland metastasis following radical nephrectomy is exceedingly rare, with no specific imaging features and clinical manifestations, and definitive diagnosis relies on pathological examination. Currently, there is no standardized treatment protocol, but complete surgical excision remains the primary therapeutic option.
6.Mechanism of Rehmannia glutinosa-medicated serum regulating BV2 microglia polarization to interfere with neuroinflammation
Ping TIAN ; Hongzhi AN ; Qian FEI ; Ruifeng LIANG ; Dan YANG ; Xuexia ZHANG ; Wenjing GE ; Yifei LIU ; Hongwei LI ; Deen HAN
China Pharmacy 2026;37(15):1979-1985
OBJECTIVE To study the mechanism of action of Rehmannia glutinosa-medicated serum (RG) in regulating lipopolysaccharide (LPS)-induced polarization of BV2 microglia to interfere with neuroinflammation. METHODS An in vitro neuroinflammation model of BV2 cells induced by LPS was established. Cells were divided into control group, LPS group, 10%RG group, 20%RG group, BAY 11-7082 [nuclear factor kappa B (NF-κB) inhibitor] group, and 20%RG+BAY 11-7082 group. Except for the control group, cells in all other groups were pretreated with corresponding drugs for 12 h and then stimulated with LPS for 24 h. The morphology of cells in each group was observed, and the fluorescence intensity of ionized calcium binding adaptor molecule 1 (Iba-1), inducible nitric oxide synthase (iNOS), CD206, the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, iNOS, IL-4, IL-10, transforming growth factor-β (TGF-β), arginase-1 (Arg-1), and the Toll-like receptor 4 (TLR4)/NF-κB/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathway-related protein expression were detected. RESULTS Compared with the control group, the LPS group showed significant changes in cell morphology, exhibiting a typical M1 activated morphology. The fluorescence intensity of Iba-1 and iNOS, the relative expression levels of TNF-α, IL-6, IL-1β, iNOS mRNA, the relative expression levels of TLR4, NLRP3, caspase-1 p20, IL-1β p17 protein, and the phosphorylation levels of NF-κB p65 and inhibitor of nuclear factor kappa B α were significantly increased (P<0.05). The fluorescence intensity of CD206 and the relative expression levels of IL-4, IL-10, TGF-β, and Arg-1 mRNA were significantly reduced (P<0.05). Compared with the LPS group, the changes in the above indicators in the cells of the 10%RG group, 20%RG group, BAY 11-7082 group, and 20%RG+BAY 11-7082 group were significantly reversed (P<0.05), and there was no statistically significant difference in the comparison of the last three groups (P>0.05). CONCLUSIONS RG can effectively inhibit the overall activation of microglia and correct their M1/M2 polarization imbalance, and its mechanism may be closely related to the inhibition of excessive activation of the TLR4/NF-κB/NLRP3 signaling pathway.
7.Clinical Efficacy of Acupuncture in the Treatment of Adolescent Depression and Its Mechanism Revealed by Functional Magnetic Resonance Imaging and Serum Proteomics:A Multicenter,Double-Blind,Randomized Controlled Trial
Lihong LI ; Peiyun ZHANG ; Xingyu CHEN ; Lu HAN ; Fengling LIANG ; Jesús M. CORTÉS
Journal of Traditional Chinese Medicine 2026;67(17):1858-1867
ObjectiveTo evaluate the clinical efficacy of acupuncture in the treatment of adolescent depression and to explore its potential mechanisms based on functional magnetic resonance imaging (fMRI) and serum proteomics. MethodsA randomized, double-blind, sham acupuncture-controlled trial design was conducted. A total of 100 adolescents with depression were enrolled and randomly assigned to an acupuncture group and a sham acupuncture group, with 50 participants in each group. In addition, 20 healthy subjects were recruited as healthy controls. Participants in the acupuncture group received acupuncture at Baihui (GV 20), Yintang (GV 29), Zhongwan (CV 12), Qihai (CV 6), bilateral Tianshu (ST 25), bilateral Neiguan (PC 6), bilateral Zusanli (ST 36), and bilateral Taichong (LR3). The sham acupuncture group received intervention using a blunt placebo needle without skin penetration. Both groups received 30-min treatments three times per week for 4 weeks. The primary outcome was the reduction rate of the 24-item Hamilton Depression Rating Scale (HAMD-24) score. Secondary outcomes included changes in HAMD-24 scores before and after treatment, covering nine factors (anxiety/somatization, cognitive impairment, sleep disturbance, psychomotor retardation, hopelessness, fatigue, weight change, diurnal mood variation, and suicidal ideation), response rate and remission rate after treatment, and symptom severity before and after treatment. Subgroup analyses of total HAMD-24 scores were performed according to concomitant medication use and the number of medications taken. During the study period, all adverse events were monitored and recorded to evaluate safety. Patients who volunteered and met the eligibility criteria for imaging examinations were selected to undergo brain fMRI scanning and serum proteomic analysis to investigate changes in functional connectivity among brain regions and differential proteins. ResultsA total of 49 participants in the acupuncture group and 50 participants in the sham acupuncture group were included in the efficacy analysis. Among them, 20 participants in the acupuncture group and 21 in the sham acupuncture group completed fMRI scans, while 19 participants in the acupuncture group and 21 in the sham acupuncture group completed serum proteomic analyses. After 4 weeks of treatment, the mean reduction rate of HAMD-24 score in the acupuncture group was significantly higher than that in the sham acupuncture group [(58±24)% vs.(26±19)%, P<0.01]. Compared to baseline, scores for anxiety/somatization, cognitive impairment, psychomotor retardation, and hopelessness, and the total HAMD-24 score significantly decreased in both groups. In addition, the acupuncture group showed significant reductions in sleep disturbance, fatigue, and suicidal ideation scores (P<0.01). After treatment, the response rate and remission rate were 67.35% (33/49) and 24.48% (12/49) in the acupuncture group, respectively, significantly higher than 6.00% (3/50) and 0 in the sham acupuncture group (P<0.01). The proportion of participants with moderate symptoms was lower, whereas the proportion with mild symptoms was higher in the acupuncture group than the sham acupuncture group (P<0.01). Among those receiving acupuncture alone, acupuncture combined with medication, or fewer than three medications, the total HAMD-24 scores decreased after treatment in both the acupuncture subgroup and the sham acupuncture subgroup, with significantly lower scores in the acupuncture subgroup (P<0.01). During the study period, four mild adverse events were reported, including one case in the acupuncture group and three cases in the sham acupuncture group; none of these events affected the continuation of treatment. fMRI results showed that acupuncture enhanced functional connectivity between the prefrontal cortex and cerebellar-limbic system-related brain regions. Proteomic analysis identified 24 differentially expressed proteins associated with acupuncture treatment, mainly enriched in pathways related to neuroinflammation and energy metabolism. ConclusionAcupuncture can significantly improve depressive symptoms in adolescents with depression. Its therapeutic effects may be achieved by modulating emotion-related brain networks and regulating pathways associated with neuroinflammation and energy metabolism.
8.Analysis of knowledge, attitude, and practice levels regarding health protection against air pollution and related factors among Chinese primary school students
Chinese Journal of School Health 2026;47(7):958-961
Objective:
To assess the current status of knowledge, attitude, and practice (KAP) regarding health protection against air pollution among primary school students in China, and to analyze the impacts of fine particulate matter (PM 2.5 ) exposure, family, and individual factors on KAP levels, so as to provide empirical basis for implementing targeted interventions.
Methods:
Using stratified cluster random sampling method, a questionnaire survey was conducted among 19 297 primary school students from third to fifth grade across 30 provinces (autonomous regions and municipalities directly under the central government) in China in 2024. The questionnaire was developed based on the Technical Guidelines for the Assessment of Civic Environmental and Health Literacy (Trial), and encompasses three dimensions:knowledge, attitude, and practice. Spearman correlation analysis, Chi-square test, multivariate Logistic regression, and Bootstrap mediation effect test was applied for data analysis.
Results:
The overall mean KAP score for health protection against air pollution among primary school students was (79.73±13.53), with an adequacy rate of 80.47% ( n =15 528). The dimension scores for knowledge, attitude, and practice were (41.34±8.01, 16.43± 2.61 ), and (21.97±5.71), respectively. Knowledge was positively correlated with attitude and practice, and attitude was positively correlated with practice ( r =0.51, 0.35, 0.32, all P <0.01). Multivariate Logistic regression showed that the northeast region ( OR =2.36, 95% CI =2.02-2.75), having parents with a bachelor s degree or higher ( OR =4.76, 95% CI =2.71-8.37), living with both parents ( OR =1.33, 95% CI =1.15-1.55), being in the fifth grade ( OR =1.22, 95% CI =1.11-1.33), outdoor PM 2.5 level exceeding standard limits at the survey site ( OR =1.25, 95% CI =1.16-1.34), history of allergy ( OR =1.47, 95% CI =1.31-1.64), and wearing masks during heavily polluted weather ( OR =1.19, 95% CI =1.07-1.31) were promoting factors for KAP adequacy rate (all P <0.05). Conversely, obesity was a detrimental factor ( OR =0.78, 95% CI =0.69-0.88, all P <0.05).
Conclusions
Primary school students in China exhibit a favorable KAP level regarding health protection against air pollution, though regional, familial, and individual disparities persist. Exposure to PM 2.5 levels exceeding standard limits exerts a direct positive effect on enhancing health protection literacy. Future efforts should focus on the western region, families with lower educational attainment children to implement tailored, stratified interventions.
9.Guidelines for the perioperative diagnosis and treatment of oncogene-driven non-small cell lung cancer (2026)
Weidong WANG ; Yongbin LIN ; Hui TIAN ; Gaofeng LI ; Shun XU ; Yongde LIAO ; Haitao MA ; Junfeng LIU ; Chundong GU ; Xiaolong YAN ; Shumin WANG ; Daqiang SUN ; Jianyang LIU ; Tao XUE ; Shaohua MA ; Zhigang LI ; Shuanghu YUAN ; Gen LIN ; Ling CAI ; Jianping ZHOU ; Wenzhao ZHONG ; Naixin LIANG ; Yi HAN ; Junfeng WANG ; Weidong ZHANG ; Xin WANG ; Lianjuan CHEN ; Lunxu LIU ; Xiuyi ZHI ; Lanjun ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(09):1337-1353
Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.
10.Preventive Effect and Safety Evaluation of Xiaozhen Formula (消疹方) on Skin Toxicity Induced by Epidermal Growth Factor Receptor Inhibitors in the Treatment of Non-small Cell Lung Cancer:A Multicenter,Randomized,Double-Blind,Placebo-Controlled Trial
Ling LUO ; Xintian WANG ; Cheng CHENG ; Zitong HAN ; Chunru WANG ; Guoli WEI ; Jianyue LI ; Li WANG ; Jirong WANG ; Peng SHU ; Liang LI ; Fenglin LIU ; Ran SONG ; Jing BAI ; Haiyan XING
Journal of Traditional Chinese Medicine 2026;67(18):1987-1994
ObjectiveTo evaluate the clinical efficacy and safety of Xiaozhen Formula (消疹方) in preventing skin toxicity induced by epidermal growth factor receptor inhibitors (EGFRIs) in patients with EGFR-mutant non-small cell lung cancer (NSCLC). MethodsA randomized, double-blind, placebo-controlled, multicenter clinical study was conducted. A total of 120 patients with EGFR-mutant NSCLC from seven centers were enrolled and randomly assigned to a treatment group (60 cases) or a control group (60 cases). On the basis of EGFRI-targeted therapy, patients in the treatment group received Xiaozhen Formula granules, whereas those in the control group received Xiaozhen Formula placebo granules, both at 10 g twice daily for 4 consecutive weeks. The primary outcomes were the grading of skin toxicity evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 and the incidence of rash. Secondary outcomes included the time to onset and time to resolution of the highest-grade rash, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) scores, the Hospital Anxiety and Depression Scale (HADS) scores, and disease control rate, together with safety assessments. ResultsBased on the full analysis set (FAS), the incidence of skin toxicity in the treatment group was 18.33% (11/60), significantly lower than 45.00% (27/60) in the control group (P<0.01), with the highest severity of skin toxicity in both groups was grade 2. Among patients who developed rash, the resolution rate in the treatment group was 90.91% (10/11), higher than that 33.33% (9/27) in the control group. The median time to resolution was 15 days (95%CI: 8-17 days) in the treatment group and it was not reached in the control group; the distribution of time to resolution differed significantly between groups (P<0.001). After treatment, the treatment group had higher EORTC QLQ-C30 functional scale and global health status/quality-of-life scores, and lower symptom scale, single-item scores, as well as HADS-A, and HADS-D scores than the control group (P<0.05). In the FAS analysis, the disease control rate (DCR) was 85.0% (51/60) in the treatment group, lower than 100.0% (60/60) in the control group (P=0.003), whereas no significant between-group difference was observed in the per-protocol set (PPS) analysis (P=0.464). The incidence of adverse events did not differ significantly between the two groups (P>0.05), and no definite safety signals related to the investigational drug were observed. ConclusionXiaozhen Formula can reduce the incidence of EGFRI-induced skin toxicity, and improve the outcome of rash regression, the patients' quality of life and psychological status in EGFR-mutant NSCLC patients.


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