1.Immunoregulation and Antitumor Effect of Yiqi Yangyin Jiedu Recipe on Lewis Lung Cancer Mice
Lianfang LIU ; Zihan LU ; Xia HU ; Qinfeng ZHOU ; Yin QIN ; Yubo MEI
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(1):95-101
OBJECTIVE To explore the anti-tumor effect of Yiqi Yangyin Jiedu Recipe on Lewis lung cancer mice and its influ-ence on immunomodulation.METHODS Lewis lung cancer mouse model was constructed by subcutaneous injection of Lewis lung cancer cells under the armpit and divided into model group,low dose group,medium dose group and high dose group.The tumor vol-ume,tumor inhibition rate and survival rate were calculated.The apoptosis and DNA damage of tumor cells were detected by HE stai-ning,TUNEL assay and comet assay respectively.The expression levels of IFN-γ,IL-2 and TNF-α were detected by ELISA.CD8+,CD8+/CD4+,PD1+,IFN-γ+,CD28+cells were detected by immunofluorescence and flow cytometry.The protein levels of PD1,CD69 and CD28 were detected by Western blot.RESULTS Yiqi Yangyin Jiedu Recipe has anti-tumor effects,prolonging survival,promo-ting apoptosis of tumor cells and aggravating DNA damage of tumor cells.Drug treatment promoted the expression of IFN-γ,IL-2 and TNF-α,increased the proportion of CD8+T,CD8+/CD4+T,IFN-γ+and CD28+cells,and inhibited the proportion of PD1+cells and protein expression,and the protein levels of CD69 and CD28 were significantly increased.CONCLUSION Yiqi Yangyin Jiedu Reci-pe can inhibit the development of tumor,and its regulation of immune function is the potential mechanism of its anti-tumor effect.
2.Immunoregulation and Antitumor Effect of Yiqi Yangyin Jiedu Recipe on Lewis Lung Cancer Mice
Lianfang LIU ; Zihan LU ; Xia HU ; Qinfeng ZHOU ; Yin QIN ; Yubo MEI
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(1):95-101
OBJECTIVE To explore the anti-tumor effect of Yiqi Yangyin Jiedu Recipe on Lewis lung cancer mice and its influ-ence on immunomodulation.METHODS Lewis lung cancer mouse model was constructed by subcutaneous injection of Lewis lung cancer cells under the armpit and divided into model group,low dose group,medium dose group and high dose group.The tumor vol-ume,tumor inhibition rate and survival rate were calculated.The apoptosis and DNA damage of tumor cells were detected by HE stai-ning,TUNEL assay and comet assay respectively.The expression levels of IFN-γ,IL-2 and TNF-α were detected by ELISA.CD8+,CD8+/CD4+,PD1+,IFN-γ+,CD28+cells were detected by immunofluorescence and flow cytometry.The protein levels of PD1,CD69 and CD28 were detected by Western blot.RESULTS Yiqi Yangyin Jiedu Recipe has anti-tumor effects,prolonging survival,promo-ting apoptosis of tumor cells and aggravating DNA damage of tumor cells.Drug treatment promoted the expression of IFN-γ,IL-2 and TNF-α,increased the proportion of CD8+T,CD8+/CD4+T,IFN-γ+and CD28+cells,and inhibited the proportion of PD1+cells and protein expression,and the protein levels of CD69 and CD28 were significantly increased.CONCLUSION Yiqi Yangyin Jiedu Reci-pe can inhibit the development of tumor,and its regulation of immune function is the potential mechanism of its anti-tumor effect.
3.Measurement of IL-1β,IL-6,IFN-γ levels in peripheral blood of lung cancer patients using multiple microsphere flow immunofluorescence technique and correlation analysis with hs-CRP
Fang WANG ; Lianfang LIU ; Lei WANG ; Guoxin XU ; Li HE ; Qinfeng ZHOU
International Journal of Laboratory Medicine 2024;45(21):2561-2565
Objective To investigate the expression of interleukin(IL)-1β,IL-6 and interferon γ(IFN-γ)cytokines in peripheral blood of patients with lung cancer detected by multiple microsphere flow immunofluo-rescence technique and to analyze the correlation with hypersevsitive C-reactive protein(hs-CRP).Methods A retrospective study was conducted to select 30 patients with lung cancer patients admitted to De-partment of Oncology and Department of Pulmonary Diseases in Zhangjiagang Hospital of Traditional Chinese Medicine(the hospital)as the lung cancer group,select 30 patients with pneumonia admitted in the hospital during the same period as the pneumonia group,and select 30 healthy people who underwent the physical ex-amination in the hospital in the same period as the control group.The serum levels of IL-1β,IL-6 and IFN-γwere detected by multiple microsphere flow immunofluorescence technique.Meanwhile,the level of hs-CRP in peripheral blood was determined by latex enhanced immunoscattering nephelometry.Results Compared with the control group,the levels of IL-1β,IL-6 and hs-CRP in lung cancer group were significantly increased,and the differences were statistically significant(P<0.001),while the difference in the level of IFN-γ was not sta-tistically significant(P>0.05).Compared with the control group,the levels of IL-1β,IL-6,IFN-γ and hs-CRP in the pneumonia group were significantly increased,and the differences were statistically significant(P<0.001).Compared with pneumonia group,the levels of IL-6,IFN-γ and hs-CRP in lung cancer group were sig-nificantly decreased and IL-1β level was increased,and the differences were statistically significant(P<0.05).Pearson correlation analysis was conducted on the levels of IL-6 and hs-CRP in the lung cancer group and pneumonia group,but no significant correlation was observed.Conclusion IL-1β,IL-6 and IFN-γ could be used as auxiliary indexes to effectively evaluate the immune function of patients with lung cancer.The applica-tion of multiple microsphere flow immunofluorescence technique has potential clinical application value for the diagnosis and monitoring of lung cancer.
4.An analysis of breast cancer patients with ultrasound BI-RADS 3 lesions after minimally invasive excision in clinicopathological features and influencing factors of residual tumor
Liang LI ; Zequn FENG ; Lianfang ZHANG ; Ruiqing WANG ; Xiaoxia ZHANG ; Liyuan LIU ; Lixiang YU ; Zhigang YU ; Zhongcheng GAO
Chinese Journal of Surgery 2024;62(2):135-140
Objectives:To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision.Methods:In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People′s Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n=39) and non-tumor residual group ( n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results:The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR=16.852, 95% CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions:BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.
5.Targeted axillary dissection after neoadjuvant chemotherapy for highly selective patients with initial cN1 breast cancer: A single-center prospective trial
Xiuchun CHEN ; Zhenduo LU ; Chengzheng WANG ; Minhao LYU ; Jianghua QIAO ; Xianfu SUN ; Lianfang LI ; Chongjian ZHANG ; Zhenzhen LIU
Chinese Medical Journal 2024;137(12):1421-1430
Background::Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging).Methods::This prospective trial included patients with initial pre-NAC cT1–3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated.Results::A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30).Conclusions::In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%.Registration::chictr.org.cn, ChiCTR2100049093
6.An analysis of breast cancer patients with ultrasound BI-RADS 3 lesions after minimally invasive excision in clinicopathological features and influencing factors of residual tumor
Liang LI ; Zequn FENG ; Lianfang ZHANG ; Ruiqing WANG ; Xiaoxia ZHANG ; Liyuan LIU ; Lixiang YU ; Zhigang YU ; Zhongcheng GAO
Chinese Journal of Surgery 2024;62(2):135-140
Objectives:To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision.Methods:In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People′s Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n=39) and non-tumor residual group ( n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results:The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR=16.852, 95% CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions:BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.
7.Surgical technique of lateral unicompartmental knee arthroplasty and discussion of the maximum correction value in the treatment of knee valgus deformity.
Xin LIU ; Kai ZHENG ; Feng ZHU ; Yijun WANG ; Lianfang ZHANG ; Weicheng ZHANG ; Dechun GENG ; Jun ZHOU ; Yaozeng XU
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(10):1238-1245
OBJECTIVE:
To investigate the surgical technique and the short-term effectivenss of lateral unicompartmental knee arthroplasty (LUKA) through lateral approach in the treatment of valgus knee and to calculate the maximum value of the theoretical correction of knee valgus deformity.
METHODS:
A retrospective analysis was performed on 16 patients (20 knees) who underwent LUKA and met the selection criteria between April 2021 and July 2022. There were 2 males and 14 females, aged 57-85 years (mean, 71.5 years). The disease duration ranged from 1 to 18 years, with an average of 11.9 years. Knee valgus was staged according to Ranawat classification, there were 6 knees of type Ⅰ, 13 knees of type Ⅱ, and 1 knee of type Ⅲ. All patients were assigned the expected correction value of genu valgus deformity by preoperative planning, including the correction value of lateral approach, intra-articular correction value, and residual knee valgus deformity value. The actual postoperative corrected values of the above indicators were recorded and the theoretical maximum correctable knee valgus deformity values were extrapolated. The operation time, intraoperative blood loss, incision length, hospital stay, hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibia angle (mMPTA), joint line convergence angle (JLCA), posterior tibial slope (PTS), range of motion (ROM), Hospital for Special Surgery (HSS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were also recorded for effectiveness evaluation.
RESULTS:
The patients' incision length averaged 13.83 cm, operation time averaged 85.8 minutes, intraoperative blood loss averaged 74.9 mL, and hospital stay averaged 6.7 days. None of the patients suffered any significant intraoperative neurological or vascular injuries. All patients were followed up 10-27 months, with a mean of 17.9 months. One patient with bilateral knee valgus deformities had intra-articular infection in the left knee at 1 month after operation and the remaining patients had no complication such as prosthesis loosening, dislocation, and infection. The ROM, HSS score, and WOMAC score of knee joint significantly improved at each time point after operation when compared to those before operation, and the indicators further improved with time after operation, the differences were all significant ( P<0.05). Imaging measurement showed that HKA, mLDFA, JLCA, and PTS significantly improved at 3 days after operation ( P<0.05) except for mMPTA ( P>0.05). Postoperative evaluation of the knee valgus deformity correction values showed that the actual intra-articular correction values ranged from 0.54° to 10.97°, with a mean of 3.84°. The postoperative residual knee valgus deformity values ranged from 0.42° to 5.30°, with a mean of 3.59°. The actual correction values of lateral approach ranged from 0.21° to 12.73°, with a mean of 4.26°.
CONCLUSION
LUKA through lateral approach for knee valgus deformity can achieve good early effectiveness. Preoperative planning can help surgeons rationally allocate the correction value of knee valgus deformity, provide corresponding treatment strategies, and the maximum theoretical correction value of knee valgus deformity can reach 25°.
Male
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Female
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Humans
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Arthroplasty, Replacement, Knee/methods*
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Retrospective Studies
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Blood Loss, Surgical
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Osteoarthritis, Knee/surgery*
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Knee Joint/surgery*
8.Study of the malignant potential of histopathological category B3 and B5a lesions from percutaneous core needle biopsy process under the guidance of ultrasonography
Hui LI ; Chao JIA ; Jing WANG ; Penglin ZOU ; Long LIU ; Gang LI ; Xin LI ; Rong WU ; Lianfang DU ; Qiusheng SHI
Chinese Journal of Ultrasonography 2023;32(12):1076-1082
Objective:To investigate the malignant potential of histopathological class B3 and B5a lesions by ultrasound-guided core needle biopsy (CNB).Methods:Retrospective analysis of the histopathological results of 712 breast lesions that successively underwent CNB process and surgical resection in the Shanghai General Hospital from January 2018 to December 2022, of which 47 lesions were reported as class B3 and 70 lesions as class B5a.Results:CNB identified 47 category B3 lesions, comprising 19 cases of atypical ductal hyperplasia, 17 papillary lesions, 8 phyllodes tumors, and 3 complex sclerosing lesions. Of these cases, surgical pathology was in full agreement with CNB pathology in 27 instances, indicating a concordance rate of 57.4% (27/47) and an inconsistency rate of 42.6% (20/47). Out of the 20 inconsistent cases, 70.0% (14/20) were upgraded based on the findings from the surgical pathology.Specifically, 4 cases of atypical ductal hyperplasia and 2 cases of intraductal papilloma were upgraded to invasive breast cancer (B5b) after surgery. Among the 4 cases with puncture pathology indicating atypical ductal hyperplasia and one complex sclerosing lesion, these five lesions were upgraded to ductal carcinoma in situ (B5a) after surgery. Two puncture pathologies were diagnosed as atypical ductal hyperplasia, and these were upgraded to ductal carcinoma in situ with microinvasion (B5b) after surgery. One puncture pathology indicated a borderline phyllodes tumor, and this was upgraded to malignant phyllodes tumor (B5b) after surgery. And 30.0% (6/20) resulted in downgrade after surgery, specifically 4 cases of atypical ductal hyperplasia, which were downgraded to breast adenopathy (B2). Of these, 1 puncture pathology was identified as atypical ductal hyperplasia and one as a borderline phyllodes tumor, which were both downgraded to fibroadenoma (B2). Seventy lesions were diagnosed as B5a lesions by CNB pathology, with 28 of them showing complete concurrence with the surgical pathology, a concordance rate of 40.0% (28/70), and an inconsistency rate of 60.0% (42/70). Of the 42 cases with discrepancies, all 42 were upgraded, yielding an upgrading rate of 100% (42/42). Of these, 21 were upgraded to ductal carcinoma in situ with microinvasion (B5b) and 21 to invasive breast cancer (B5b).Conclusions:Lesions with CNB pathology in categories B3 and B5a have a high rate of postoperative escalation. B3 and B5a lesions should be treated with considerable care, especially atypical ductal hyperplasia, which should be surgically resected, and CNB examination should be performed twice if necessary.
9.Impact of molecular subtypes on prognosis of postoperative patients with invasive breast cancer
Dechuang JIAO ; Jiujun ZHU ; Xuhui GUO ; Yue YANG ; Hao DAI ; Yajie ZHAO ; Lianfang LI ; Chengzheng WANG ; Zhenduo LU ; Xiuchun CHEN ; Zhenzhen LIU
Chinese Journal of General Surgery 2022;37(8):573-578
Objective:To investigate the prognostic value of molecular subtypes in patients with resected invasive breast cancer.Methods:Between 2015 and 2018 7 869 patients with invasive breast cancer after undergoing surgery were included in this analysis. Breast cancer was classified into four subtypes according to the status of hormone receptor (HR) and HER2: HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. Kaplan-Meier curves and COX regression were used to compare disease-free survival (DFS) and overall survival (OS) among different subtypes.Results:The 5-year DFS and OS were 86.30% and 94.29%, respectively. Proportions of HR+/HER2-、HR+/HER2+、HR-/HER2+ and HR-/HER2- were 52.9%、17.5%、14.1%和15.5%, respectively. The 5-year DFS of HR+/HER2- subtype (88.12%) was higher than HR+/HER2+ (84.67%, P=0.026), HR-/HER2+ (84.19%, P<0.001) and HR-/HER2- (83.70%, P<0.001). The 5-year OS of HR+/HER2- (95.38%) was not different from HR+/HER2+ (95.17%, P=0.187), while it was higher than that of HR-/HER2+ (92.26%, P<0.001) and HR-/HER2- (91.69%, P<0.001). Subtype was still a significant factor regarding DFS and OS in multivariable analyses adjusting for age, sex, stage, Ki67, types and time of surgery. The DFS ( P=0.257) and OS ( P=0.511) was not different between HR-/HER2+与HR+/HER2- subtypes, while HR-/HER2+ and HR-/HER2- patients had worse DFS ( P<0.05) and OS ( P<0.05) than that with HR+/HER2-. Conclusions:Molecular subtype is a significant independent prognostic factor for DFS and OS in operable invasive breast cancer. HR+ subtypes have better prognosis compared with HR- subtypes. The DFS and OS were not different between HR+/HER2- and HR+/HER2+, or between HR-/HER2+ and HR-/HER2-.
10.Study on the efficacy and influencing factors of Dabigatran in elderly patients
Lianfang NI ; Meilin LIU ; Qing LIN ; Dan SUN ; Zeng ZENG
Chinese Journal of Geriatrics 2020;39(2):133-136
Objective:To observe the efficacy of Dabigatran etexilate anticoagulation therapy and analyze its influencing factors in elderly patients.Methods:The clinical data of the elderly patients using Dabigatran etexilate anticoagulation for prevention or treatment of thrombosis in the Department of Geriatrics, Peking University First Hospital were collected.Changes of coagulation indexes and its influencing factors were analyzed when taking Dabigatran in different doses.Results:A total of 142 patients receiving Dabigatran therapy were collected, with an average age of(79.0±7.5)years.Among them, 128 patients had atrial fibrillation and 14 had deep venous thrombosis and/or pulmonary embolism.After taking Dabigatran, the trough values of activated partial thromboplastin time(APTT)and thrombin time(TT)were increased significantly in all patients compared with that before administration( P<0.001). In patients taking Dabigatran 110 mg once a day, APTT was(32.4±3.0)s before administration, with a trough value of(41.4±5.4)s and a peak value of(53.9±9.8)s.In patients taking Dabigatran 110 mg twice a day, APTT was(31.0±3.1)s before administration, with a trough value of(42.4±5.5)s and a peak value of(48.7±7.3)s.Compared with patients taking Dabigatran 220 mg/d, those who took Dabigatran 110 mg/d were older( P<0.0001), often women( P<0.0001), had lower body weight( P=0.001), body mass index( P=0.018)and creatinine clearance rate( P<0.001), and higher basal( P=0.008)and peak values( P=0.002)of APTT, but with similar trough values.Multivariate analysis showed that the APTT trough values were significantly related with APTT basal value( β=0.885, P<0.001), creatinine clearance rate( β=-0.121, P<0.001), dosage of Dabigatran( β=0.037, P<0.001)and combined amiodarone( β=3.784, P=0.022). Conclusions:There are individual differences in the anticoagulant effect of Dabigatran etexilate.The APTT trough value is higher in patients with high APTT basal value, high Dabigatran dose, low creatinine clearance rate and combined use of amiodarone.Dabigatran 110 mg/d was often used in women, elderly patients, and those with low body weight, and decreased renal function, and with a similar trough value and a high peak value of APTT compared with patients on Dabigatran 220 mg/d.

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