1.New perspectives on microbiome-dependent gut-brain pathways for the treatment of depression with gastrointestinal symptoms: from bench to bedside.
Menglin LIU ; Genhao FAN ; Lingkai MENG ; Kuo YANG ; Huayi LIU
Journal of Zhejiang University. Science. B 2025;26(1):1-25
Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.
Humans
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Gastrointestinal Microbiome/physiology*
;
Depression/microbiology*
;
Gastrointestinal Diseases/physiopathology*
;
Brain
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Animals
;
Brain-Gut Axis
;
Gastrointestinal Tract/microbiology*
2.Effects of Jieyu Huatan Xiaoyu Formula on Clinical Efficacy and Nrf2-Keap Signaling Pathway in Patients with Gastric Precancerous Lesions of Liver-Stomach Disharmony Type
Yuxin CHEN ; Kuo YANG ; Huayi LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(11):2697-2704
Objective To investigate the clinical efficacy of Jieyu Huatan Xiaoyu Formula(JYHTXYF)in patients with gastric precancerous lesions(GPL)of liver-stomach disharmony type and to observe its effects on the nuclear factor erythroid 2-related factor 2(Nrf2)-Kelch-like ECH-associated protein 1(Keap1)signaling pathway.Methods A prospective study enrolled 100 GPL patients with liver-stomach disharmony syndrome treated at the Department of Gastroenterology,Affiliated Hospital of Tianjin Academy of Chinese Medicine from August 2023 to August 2024.Participants were randomized into control group(n=50,treated with Moluodan Pills)and trial group(n=50,treated with JYHTXYF decoction)for 6 months.Traditional Chinese medicine(TCM)syndrome scores,gastroscopic pathological scores,serum superoxide dismutase(SOD)and malondialdehyde(MDA)levels,along with Nrf2-Keap pathway-related gene/protein expressions were assessed before and after treatment.Results(1)Regarding clinical efficacy,after 6 months of treatment,the total effective rate was 94.00%(47/50)in the trial group and 76.00%(38/50)in the control group.Intergroup comparison(by chi-square test)showed that the efficacy of the trial group was significantly superior to that of the control group(P<0.05).(2)In terms of traditional Chinese medicine(TCM)syndrome scores,after treatment,the scores for TCM syndromes such as epigastric pain,gastric distension,belching,and poor appetite decreased in both groups compared to those before treatment(P<0.05),and the reduction in the trial group was significantly superior to that in the control group(P<0.01).(3)Regarding gastroscopic pathological scores,after treatment,the scores for gastric mucosal atrophy,intestinal metaplasia,dysplasia,and chronic inflammation decreased in both groups compared to those before treatment(P<0.05),and the reduction in the trial group was significantly greater than that in the control group(P<0.01).(4)In terms of oxidative stress indicators,after treatment,SOD levels increased in both groups compared to before treatment(P<0.05),while serum MDA levels decreased(P<0.05).The magnitude of increase in serum SOD levels and the magnitude of decrease in serum MDA levels in the trial group were significantly greater than those in the control group(P<0.05 or P<0.01).(5)Regarding the expression levels of genes related to the Nrf2-Keap signaling pathway,after treatment,the relative mRNA expression levels of Nrf2,NAD(P)H quinone dehydrogenase 1(NQO1),and heme oxygenase-1(HO-1)in gastric mucosal tissue increased in both groups compared to those before treatment(P<0.05),and the increase in the trial group was significantly greater than that in the control group(P<0.01).(6)Regarding the expression levels of proteins related to the Nrf2-Keap signaling pathway,after treatment,the relative protein expression levels of Nrf2,HO-1,and mitochondrial superoxide dismutase(SOD2)in gastric mucosal tissue increased in both groups compared to those before treatment(P<0.05),and the increase in the trial group was significantly greater than that in the control group(P<0.01).Conclusion JYHTXYF effectively improves TCM syndromes and gastroscopic pathology in GPL patients of liver-stomach disharmony type,elevates serum antioxidant enzyme levels,and upregulates the expression of genes and proteins associated with the Nrf2-Keap1 signaling pathway,thereby enhancing clinical efficacy.The study will provide novel insights and approaches for the treatment of gastric precancerous lesions.
3.Effects of 8-week aerobic,resistance and combined exercise on hemodynamic and arterial stiffness in young obese women
Huayi ZHOU ; Hongbo LIU ; Chengzhu ZHANG
Chinese Journal of Rehabilitation Medicine 2025;40(10):1519-1527
Objective:To compare the effects of 8 weeks of aerobic exercise(AE),resistance exercise(RE)and com-bined exercise(CE)on cardiac function,hemodynamics and vascular stiffness in young women with obesity,and to provide theoretical and practical basis for exercise prescription in this population.Method:Forty-seven women with obesity(body fat percentage≥30%)were screened and randomly divided in-to AE,RE and CE group.Exercise intervention consisted of 8 weeks,60 min per session,3 sessions per week.The AE group exercised on a running platform at 70%—75%of the heart rate reserve for 50 min.The RE group completed squats,bench presses and pull-ups sequentially at 75%of the 1 repetition maximum for 10 reps per set,with a 2 min break between sets and 2 min for the change of the movement interval.The CE group performed 25min of resistance training followed by 25min of aerobic training with the same content and intensity as the AE and RE exercise group.Changes in body composition,cardiac function,hemodynam-ics and vascular stiffness were detected before,during and after exercise using a dual-energy X-ray detector,color Doppler ultrasound and arterial stiffness detector.Result:Body fat percentage decreased significantly in all three groups after 8 weeks of exercise compared to pre-exercise(P<0.05).Lean mass significantly decreased in the AE group(P=0.02)at week 4,whereas in-creased significantly in the RE and CE groups at week 8 compared to baseline and exercise(P<0.05).Left ventricular end-diastolic volume(P<0.01),stroke volume(P<0.01),and short-axis foreshortening rate(AE:P<0.01,RE:P=0.01,CE:P=0.047)increased significantly in all three groups after exercise compared to pre-exer-cise.Peak blood flow velocity(AE:P=0.04,CE:P<0.01)and blood flow shear(AE:P=0.01,CE:P<0.01)were significantly higher in the AE and CE groups than in the pre-exercise period,and only the increase in Wall shear stress was statistically significant in the RE group(P=0.02).The left and right brachial-ankle pulse wave conduction velocity(baPWV)of the AE group decreased significantly after 8 weeks of exercise(P<0.05).BaPWV of the RE group did not change significantly(P>0.05).The right baPWV of the CE group de-creased gradually with the increase of the duration of exercise,and the decrease appeared to be statistically significant in the 8 weeks(P=0.03).Conclusion:Eight weeks of aerobic,resistance and combined exercise all improved body composition,cardiac function and hemodynamic indices in young women with obesity.Aerobic and combined exercise not only re-duced body fat but also baPWV.Both combined and resistance exercise increased muscle mass,and resistance exercise had no effect on baPWV in young women with obesity.
4.Barriers and facilitator analysis of the clinical application of evidence to promote the initiation and establishment of maternal lactation
Suhang LI ; Liqun ZHU ; Fang XU ; Huayi JIN ; Jun ZHU ; Qing XIA ; Dandan YONG ; Lanping LIU
Chinese Journal of Practical Nursing 2025;41(18):1376-1383
Objective:Based on the best evidence, formulate the review indicators to promote the initiation and establishment of maternal lactation and carry out clinical review, analyze the barriers and promoting factors of the clinical application of evidence, and formulate countermeasures.Methods:Evidence-based nursing research was used to identify clinical problems, build evidence-based group, systematically search, evaluate and synthesize evidence. On September 1,2023 to December 31 in Affiliated Hospital of Jiangsu University document and delivery of maternal investigation, in Ottawa research application mode as a guide, based on the evidence to review indicators and review method, clear clinical status and evidence gap, combined with the stakeholders interview, using content analysis to analyze barriers and promoting factors, to formulate action countermeasures.Results:In this study, 140 pregnant women were finally included for clinical review, aged from 22 to 42 (30.13 ± 3.69) years. A total of 23 pieces of best evidence were incorporated, leading to the establishment of 29 review indicators. Among these, 20 review indicators showed compliance rates below 60%. The main obstacles based on the results of review and interviews with stakeholders: the evidence content covered perinatal stages but lacked specificity and practical applicability; nurses had insufficient knowledge and faced increased workloads; pregnant/postpartum women lacked essential knowledge and skills, with delayed resolution of lactation issues; the practice environment lacked evidence-based implementation protocols, specialized assessment tools, and professional lactation consultant teams, etc. Promoting factors: the project team had rich experience in evidence transformation; the reform aligned with national policies, high engagement from departmental leaders, and standardized management systems for evidence-based projects in the nursing department; strong motivation among pregnant/postpartum women; the hospital was an infant-friendly hospital with talents needed for evidence transformation.Conclusions:There is a big gap between the clinical status and the evidence of promoting the initiation and establishment of lactation, so nursing staff should make full use of the promoting factors and formulate countermeasures according to the obstacle factors, so as to provide reference for promoting the initiation of lactation and the establishment of relevant evidence to clinical transformation.
5.Effects of 8-week aerobic,resistance and combined exercise on hemodynamic and arterial stiffness in young obese women
Huayi ZHOU ; Hongbo LIU ; Chengzhu ZHANG
Chinese Journal of Rehabilitation Medicine 2025;40(10):1519-1527
Objective:To compare the effects of 8 weeks of aerobic exercise(AE),resistance exercise(RE)and com-bined exercise(CE)on cardiac function,hemodynamics and vascular stiffness in young women with obesity,and to provide theoretical and practical basis for exercise prescription in this population.Method:Forty-seven women with obesity(body fat percentage≥30%)were screened and randomly divided in-to AE,RE and CE group.Exercise intervention consisted of 8 weeks,60 min per session,3 sessions per week.The AE group exercised on a running platform at 70%—75%of the heart rate reserve for 50 min.The RE group completed squats,bench presses and pull-ups sequentially at 75%of the 1 repetition maximum for 10 reps per set,with a 2 min break between sets and 2 min for the change of the movement interval.The CE group performed 25min of resistance training followed by 25min of aerobic training with the same content and intensity as the AE and RE exercise group.Changes in body composition,cardiac function,hemodynam-ics and vascular stiffness were detected before,during and after exercise using a dual-energy X-ray detector,color Doppler ultrasound and arterial stiffness detector.Result:Body fat percentage decreased significantly in all three groups after 8 weeks of exercise compared to pre-exercise(P<0.05).Lean mass significantly decreased in the AE group(P=0.02)at week 4,whereas in-creased significantly in the RE and CE groups at week 8 compared to baseline and exercise(P<0.05).Left ventricular end-diastolic volume(P<0.01),stroke volume(P<0.01),and short-axis foreshortening rate(AE:P<0.01,RE:P=0.01,CE:P=0.047)increased significantly in all three groups after exercise compared to pre-exer-cise.Peak blood flow velocity(AE:P=0.04,CE:P<0.01)and blood flow shear(AE:P=0.01,CE:P<0.01)were significantly higher in the AE and CE groups than in the pre-exercise period,and only the increase in Wall shear stress was statistically significant in the RE group(P=0.02).The left and right brachial-ankle pulse wave conduction velocity(baPWV)of the AE group decreased significantly after 8 weeks of exercise(P<0.05).BaPWV of the RE group did not change significantly(P>0.05).The right baPWV of the CE group de-creased gradually with the increase of the duration of exercise,and the decrease appeared to be statistically significant in the 8 weeks(P=0.03).Conclusion:Eight weeks of aerobic,resistance and combined exercise all improved body composition,cardiac function and hemodynamic indices in young women with obesity.Aerobic and combined exercise not only re-duced body fat but also baPWV.Both combined and resistance exercise increased muscle mass,and resistance exercise had no effect on baPWV in young women with obesity.
6.Barriers and facilitator analysis of the clinical application of evidence to promote the initiation and establishment of maternal lactation
Suhang LI ; Liqun ZHU ; Fang XU ; Huayi JIN ; Jun ZHU ; Qing XIA ; Dandan YONG ; Lanping LIU
Chinese Journal of Practical Nursing 2025;41(18):1376-1383
Objective:Based on the best evidence, formulate the review indicators to promote the initiation and establishment of maternal lactation and carry out clinical review, analyze the barriers and promoting factors of the clinical application of evidence, and formulate countermeasures.Methods:Evidence-based nursing research was used to identify clinical problems, build evidence-based group, systematically search, evaluate and synthesize evidence. On September 1,2023 to December 31 in Affiliated Hospital of Jiangsu University document and delivery of maternal investigation, in Ottawa research application mode as a guide, based on the evidence to review indicators and review method, clear clinical status and evidence gap, combined with the stakeholders interview, using content analysis to analyze barriers and promoting factors, to formulate action countermeasures.Results:In this study, 140 pregnant women were finally included for clinical review, aged from 22 to 42 (30.13 ± 3.69) years. A total of 23 pieces of best evidence were incorporated, leading to the establishment of 29 review indicators. Among these, 20 review indicators showed compliance rates below 60%. The main obstacles based on the results of review and interviews with stakeholders: the evidence content covered perinatal stages but lacked specificity and practical applicability; nurses had insufficient knowledge and faced increased workloads; pregnant/postpartum women lacked essential knowledge and skills, with delayed resolution of lactation issues; the practice environment lacked evidence-based implementation protocols, specialized assessment tools, and professional lactation consultant teams, etc. Promoting factors: the project team had rich experience in evidence transformation; the reform aligned with national policies, high engagement from departmental leaders, and standardized management systems for evidence-based projects in the nursing department; strong motivation among pregnant/postpartum women; the hospital was an infant-friendly hospital with talents needed for evidence transformation.Conclusions:There is a big gap between the clinical status and the evidence of promoting the initiation and establishment of lactation, so nursing staff should make full use of the promoting factors and formulate countermeasures according to the obstacle factors, so as to provide reference for promoting the initiation of lactation and the establishment of relevant evidence to clinical transformation.
7.Neutrophil-to-lymphocyte ratio may help predict pediatric testicular torsion in chlidren with acute scrotal pain before surgery
Xianya HE ; Chen WANG ; Yongjun YANG ; Junjie CHEN ; Xuecheng WU ; Zhuo LI ; Zhe LIU ; Guangqing SONG ; Yili TENG ; Jia CHEN ; Hongwei WANG ; Huayi ZHENG ; Yuanwei LI ; Qiang LU
Journal of Modern Urology 2024;29(9):785-789
Objective To explore the feasibility and accuracy of neutrophil-to-lymphocyte ratio(NLR)in the prediction of testicular torsion(TT)in children with acute scrotal pain.Methods A retrospective case-control study was performed on 158 pediatric patients with ultrasound suspicion of TT who underwent surgical testicular examination during Jan.2017 and Jan.2024.The patients were divided into TT group and non-TT group.Clinical data and laboratory data at admission were analyzed.Sensitivity and specificity of NLR to TT were determined with the area under the curve(AUC)represented on the receiver operating characteristic(ROC)curves.Results There were with no statistically significant differences in clinical data between the two groups(P>0.05).The NLR was significantly higher in the TT group than in the non-TT group[(4.82±2.37)vs.(2.85±0.75),P<0.05].The optimal cut-off value of TT predicted by NLR was 2.07,the AUC was 0.809(95%CI:0.709-0.909),and the sensitivity and specificity were 97.9%and 93.3%,respectively,which were significantly higher than other factors.Conclusion For suspicious ultrasound diagnosis of pediatric acute scrotal pain cases,NLR can be used to predict the possibility of TT and may help to evaluate the urgent surgical treatment in these patients.
8.High-fat intake alleviates lung injury induced by Paragonimus proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues
Siqi LIU ; Qingqing WANG ; Weiqun WANG ; Lei WU ; Zhiqiang MA ; Lin WANG ; Guoji CHANG ; Jie DING ; Lijuan HUA ; Huayi CHEN ; Shenghao LI ; Wenlin WANG
Chinese Journal of Schistosomiasis Control 2023;35(2):171-176
Objective To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments. Methods SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high-fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays. Results Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1β [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1β: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1β: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). Conclusion High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.
9.NKD1 promotes glucose uptake in colon cancer cells by activating YWHAE transcription.
Qian LIU ; Yuyang DAI ; Huayi YU ; Ying SHEN ; Jianzhong DENG ; Wenbin LU ; Jianhua JIN
Journal of Southern Medical University 2023;43(4):585-589
OBJECTIVE:
Bo investigate the regulatory relationship between NKD1 and YWHAE and the mechanism of NKD1 for promoting tumor cell proliferation.
METHODS:
HCT116 cells transfected with pcDNA3.0-NKD1 plasmid, SW620 cells transfected with NKD1 siRNA, HCT116 cells with stable NKD1 overexpression (HCT116-NKD1 cells), SW620 cells with nkd1knockout (SW620-nkd1-/- cells), and SW620-nkd1-/- cells transfected with pcDNA3.0-YWHAE plasmid were examined for changes in mRNA and protein expression levels of YWHAE using qRT-PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assay was used to detect the binding of NKD1 to the promoter region of YWHAE gene. The regulatory effect of NKD1 on YWHAE gene promoter activity was analyzed by dual-luciferase reporter gene assay, and the interaction between NKD1 and YWHAE was analyzed with immunofluorescence assay. The regulatory effect of NKD1 on glucose uptake was examined in the tumor cells.
RESULTS:
In HCT116 cells, overexpression of NKD1 significantly enhanced the expression of YWHAE at both the mRNA and protein levels, while NKD1 knockout decreased its expression in SW620 cells (P < 0.001). ChIP assay showed that NKD1 protein was capable of binding to the YWHAE promoter sequence; dual luciferase reporter gene assay showed that NKD1 overexpression (or knockdown) in the colon cancer cells significantly enhanced (or reduced) the transcriptional activity of YWHAE promoter (P < 0.05). Immunofluorescence assay demonstrated the binding of NKD1 and YWHAE proteins in colon cancer cells. NKD1 knockout significantly reduced glucose uptake in colon cancer cells (P < 0.01), while YWHAE overexpression restored the glucose uptake in NKD1-knockout cells (P < 0.05).
CONCLUSION
NKD1 protein activates the transcriptional activity of YWHAE gene to promote glucose uptake in colon cancer cells.
Humans
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Colonic Neoplasms
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HCT116 Cells
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Cell Line, Tumor
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Cell Proliferation
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Gene Expression Regulation, Neoplastic
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RNA, Messenger
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Glucose
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Calcium-Binding Proteins/metabolism*
;
Adaptor Proteins, Signal Transducing/metabolism*
;
14-3-3 Proteins/metabolism*
10.Study on the efficacy and influencing factors of pyrotinib in treatment of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer
Xiaodong GU ; Chao LAN ; Huayi ZHANG ; Wenfu YANG ; Huijuan LIU ; Jia WANG ; Bo ZHANG ; Ruilin ZHENG ; Yu WANG
Cancer Research and Clinic 2023;35(3):200-204
Objective:To evaluate the efficacy of oral pyrotinib in treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in the real world, and to explore its influencing factors.Methods:The clinical data of 148 patients with HER2-positive metastatic breast cancer treated with oral pyrrolitinib in Shanxi Cancer Hospital from September 2018 to December 2020 were retrospectively analyzed. The efficacy was evaluated according to the efficacy evaluation criteria for solid tumors, version 1.1, and the adverse effects were graded according to the National Cancer Institute common terminology criteria of adverse effects, version 4.0. The Kaplan-Meier method was used to draw progression-free survival (PFS) curves, the patients were stratified by different clinical characteristics, and log-rank test was used for univariate analysis of PFS; the multivariate analysis of PFS was performed using Cox proportional hazards model.Results:The objective response rate (ORR) of 148 patients was 71.6% (106/148), and the disease control rate (DCR) was 89.2% (132/148). The overall median PFS time was 11.0 months (95% CI 10.1-11.9 months), and the median PFS of 19 patients with brain metastases was 10.0 months (95% CI 7.4-12.6 months). The differences in PFS between patients stratified by disease-free interval (DFI), the number of metastatic site and Eastern Cooperative Oncology Group (ECOG) score were statistically significant (all P < 0.05), but the difference in PFS between patients with negative and positive hormone receptor was not statistically significant ( P > 0.05). Multivariate Cox regression analysis showed that DFI (>1 year vs. ≤1 year: HR = 5.254, 95% CI 0.728-37.933, P = 0.046) and ECOG score (≥2 points vs. 0-1 point: HR = 2.454, 95% CI 1.261-4.788, P = 0.008) were independent influencing factors of PFS. The most common ≥grade 3 adverse effects were diarrhea (31 cases, 20.9%) and hand-foot syndrome (38 cases, 25.8%). Conclusions:The pyrotinib has definite efficacy and good safety in the treatment of HER2-positive metastatic breast cancer in the real world, especially for patients with DFI > 1 year and ECOG score 0-1 point, the efficacy and safety are particularly good.

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