1.Feasibility of interim multipoint core needle biopsy pathological evaluation to predict effect of neoadjuvant therapy for breast cancer (with video)
Shikai HONG ; Shuhan WANG ; Zhengzhi ZHU ; Jianjun LIU ; Kuojun REN ; Shengying WANG
Chinese Journal of Endocrine Surgery 2023;17(5):524-529
Objective:To investigate the feasibility of multipoint core needle biopsy (CNB) at mid-stage to predict the treatment effect of neoadjuvant systemic therapy for breast cancer.Methods:A total of 67 breast cancer cases with indications of neoadjuvant systemic therapy were selected from Mar. 2021 to Nov. 2022.In the fourth cycle of neoadjuvant systemic therapy, core needle biopsy was performed at 3, 6, 9, 12 points of tumor bed and residual tumor foci of breast respectively.The results of CNB were compared with the results of routine pathology of surgery after the completion of neoadjuvant therapy. Matched biopsy and surgical specimens were compared to assess pCR. The accuracy and false negative rate (FNR) of interim pathological assessment were analyzed. The coincidence probability of interim biopsy pathology and pathology of standard surgical excision was verified.Results:The median age of enrolled patients was 49.2 years (21-69 years) .Median maximum tumor diameter before neoadjuvant systemic therapy and residual tumor diameter after neoadjuvant therapy were 40.4 mm (range 21-93mm) and 19.6 mm (range 0-41mm) respectively. A total of 28 patients achieved pCR, and the PCR rates of hormone receptor-positive and HER2-nagative,triple-negative,hormone receptor negative and HER2-positive and hormone receptor-positive and HER2-positive disease were 4/24 (16.7%) ,6/14 (42.9%) ,11/18 (61.1%) ,7/11 (63.6%), respectively. Two cases had no preoperative imaging abnormalities. The results of core needle biopsy pathology of residual tumor lesions in 55 patients were consistent with those of routine post-operation pathology.The results of core needle biopsy pathology of tumor bed of 56 patients was consistent with the routine pathology of surgery. The false negative rate of interim multipoint biopsy pathology of residual tumor foci was 17.9% (12/67). The false negative rate of tumor bed with core needle biopsy was 5.9% (4/67) .Conclusions:CNB guided under ultrasound is feasible in predicting tumor retreat situation in the tumor bed area and residual tumor foci at mid-stage of neoadjuvant therapy. Increasing the number of core needles and improving biopsy techniques may improve the accuracy of pathological evaluation of interim multipoint biopsy.
2.Chemical Constituents of Ethyl Acetate Extracts from Stirps of Semiliquidambar cathayensis
Yu XU ; Haozhen ZHANG ; Muhammad ISHAQ ; Jiajia WU ; Wenpei WANG ; Shasha LI ; Xue XIAO ; Shikai YAN ; Huizi JIN
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(11):3497-3505
Objective To study the chemical constituents from ethyl acetate extracts of the strips of Semiliquidambar cathayensis.Methods The strips of S.cathayensis were extracted by 80%ethanol and the extracts were evaporated.Fourteen compounds in ethyl acetate extracts were isolated and purified by various chromatographic techniques,such as silica gel,Sephadex LH-20 column and pre-HPLC,etc.Their structures were identified on the basis of physicochemical properties and spectroscopic analysis.Antioxidant activity test was used to evaluate total extraction,each extraction part and the isolates.Results Fourteen compounds were isolated from the strips of S.cathayensis and identified by NMR as tetradecanoic acid(1),stearic acid(2),sesamin(3),9-octadecenoic acid(4),linoleic acid(5),dibutylphthalate(6),stigmasterol(7),β-sitosterol(8),lupeol(9),oleanolic acid(10),lup-20(29)-ene-3-[3-keto-hexadecanoate](11),peujaponisin(12),C-veratroylglycol(13),and 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(14).Conclusion Compounds 1,3,4,5,6,7,9,11,12,13 and 14 were isolated from this plant for the first time.The EA part,compounds 13(C-veratroylglycol)and 14(2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone)showed significant antioxidative effects.
3.Two new phenolic amides from Allium chinense.
Xiaoqing LI ; Shikai YAN ; Jihong LU ; Rui WANG ; Xianpeng MA ; Xue XIAO ; Yan ZHANG ; Huizi JIN
Chinese Herbal Medicines 2023;15(4):603-606
OBJECTIVE:
To isolate the phenolic amides from the dried bulbs of Allium chinense and investigate their myocardium protective activities.
METHODS:
The chemical constituents were isolated and purified by combining with silica gel column, Sephadex LH-20 column, HPLC and other chromatography techniques. Their structures were elucidated by NMR techniques and mass spectrometry. The isolated compounds were evaluated to determine their protective effect for myocardium cells in vitro.
RESULTS:
Two new phenolic amides, namely, alichinemide I ( 1) and alichinemide II ( 2), and six konwn amides were isolated from the dried bulbs of A. chinense. The structures of compounds 3- 8 were identified as 3-indolcarbaldehyde ( 3), 1-(2-aminophenyl)urea ( 4), 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid ( 5), N-trans-feruloyltyramine ( 6), N-trans-p-coumaroyltyramine ( 7), and N-(3,4-dimethoxyphenethyl) acetamide ( 8). Compound 3 (50 μmol/L) showed significant inhibitory effect on the damage of H9c2 myocardial cells induced by H2O2in vitro.
CONCLUSION
Compounds 1 and 2 were new phenolic amides. Compound 3 could be one of the potential myocardium protective constituents of A. chinense.
4.Modulating effects of RAMPs on signaling profiles of the glucagon receptor family.
Lijun SHAO ; Yan CHEN ; Shikai ZHANG ; Zhihui ZHANG ; Yongbing CAO ; Dehua YANG ; Ming-Wei WANG
Acta Pharmaceutica Sinica B 2022;12(2):637-650
Receptor activity-modulating proteins (RAMPs) are accessory molecules that form complexes with specific G protein-coupled receptors (GPCRs) and modulate their functions. It is established that RAMP interacts with the glucagon receptor family of GPCRs but the underlying mechanism is poorly understood. In this study, we used a bioluminescence resonance energy transfer (BRET) approach to comprehensively investigate such interactions. In conjunction with cAMP accumulation, Gα q activation and β-arrestin1/2 recruitment assays, we not only verified the GPCR-RAMP pairs previously reported, but also identified new patterns of GPCR-RAMP interaction. While RAMP1 was able to modify the three signaling events elicited by both glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), and RAMP2 mainly affected β-arrestin1/2 recruitment by GCGR, GLP-1R and glucagon-like peptide-2 receptor, RAMP3 showed a widespread negative impact on all the family members except for growth hormone-releasing hormone receptor covering the three pathways. Our results suggest that RAMP modulates both G protein dependent and independent signal transduction among the glucagon receptor family members in a receptor-specific manner. Mapping such interactions provides new insights into the role of RAMP in ligand recognition and receptor activation.
5.Infections in newly diagnosed systemic lupus erythematosus patients with high disease activity: a retrospective cohort study
Yuhong ZHOU ; Haiting WANG ; Liqin YU ; Wanlong WU ; Shikai GENG ; Fangfang SUN ; Danting ZHANG ; Yi CHEN ; Shuang YE
Chinese Journal of Rheumatology 2021;25(10):654-658
Objective:To determine the characteristics of hospitalized newly diagnosed systemic lupus erythematosus (SLE) patients with high disease activity, and identify the risk factors.Methods:Data from 194 newly diagnosed SLE patients at Shanghai Renji Hospital between May 2013 and December 2018 were collected retrospectively. All patients were followed up for 1 year or until death. Patients' demographic, clinical, and laboratory characteristics on admission and medication history were retrospectively collected as baseline data. Patients were divided into two groups, lupus patients with infection (51 cases) and lupus patients without infection (143 cases). The method of univariate analysis of data depended on the data distribution type. Variables that suggested association in the univariate analysis ( P<0.05) were entered into Cox regression model. Results:Among 194 patients with newly diagnosed SLE, 21 cases (11%) died and 51 cases (26%) were infected during 1-year follow-up. Regarding the infection site, 34 cases (67%) had lung infection, 9 cases (18%) had central nervous system infection and 9 cases (18%) had blood stream infection. Common bacteria were identified in 19 cases (45%), followed by fungal infection in 18 cases (43%) and mycobacterium infection in 7 cases (17%). Among the 51 patients with infection, 38 patients (75%) had infection within the first 3 months after diagnosis, and mortality in this group was significantly higher than that in the uninfected group (39%, 15/38 vs 2%, 3/143 , P<0.01). Comparing baseline parameters between patients with 3-month infection and without, significant differences ( P<0.05) were detected in age (≥40 years), systemic lupus erythematosus disease activity index (SLEDAI) score (>10 points), Systemic Lupus International Collaborating Clinic (SLICC)/American College of Rheumatology(ACR) systemic lupus erythematosus damage index (SDI) (≥1 point), pericardial effusion, nephritis, gastrointestinal vasculitis, diabetes, lymphocyte count <0.8×10 9/L platelet count <100×10 9/L, serum creatinine >104 mmol/L and serum globulin level <20 g/L. Finally, clinically meaningful candidate predictors were included in the Cox regression model and it showed that lymphocyte count <0.8×10 9/L, nephritis and gastrointestinal vasculitis were independently predictive for 3-month infection in new-onset lupus patients. Conclusion:Understanding disease spectrums and risk factors of infection in newly diagnosed SLE patients will help clinicians to manage those patients with infection effectively to achieve favorable prognosis.
6.Radiotherapy for and prognosis of breast cancer patients with isolated chest wall recurrence after mastectomy
Liang XUAN ; Xuran ZHAO ; Huiru SUN ; Jun YIN ; Yu TANG ; Hao JING ; Hui FANG ; Yongwen SONG ; Jing JIN ; Yueping LIU ; Hua REN ; Bo CHEN ; Shunan QI ; Ning LI ; Yuan TANG ; Ningning LU ; Yong YANG ; Shikai WU ; Yexiong LI ; Shulian WANG ; Bing SUN
Chinese Journal of Radiation Oncology 2021;30(9):898-902
Objective:To investigate the radiation field and dose selection of patients with isolated chest wall recurrence (ICWR) after modified radical mastectomy, and analyze the prognostic factors related to subsequent chest wall recurrence.Methods:Clinical data of 201 patients with ICWR after mastectomy admitted to the Fifth Medical Center, Chinese PLA General Hospital from 1998 to 2018 were retrospectively analyzed. None of the patients received postoperative adjuvant radiotherapy. After ICWR, 48 patients (73.6%) underwent surgery and 155 patients (77.1%) received radiotherapy. Kaplan-Meier method was used to calculate the post-recurrence progression-free survival (PFS) rates and the difference was compared by log-rank test. Multivariate analysis was performed using Cox regression model. Competing risk model was adopted to estimate the subsequent local recurrence (sLR) rates after ICWR and the difference was compared with Gray test. Multivariate analysis was conducted using F&G analysis. Results:With a median follow up of 92.8 months after ICWR, the 5-year PFS rate was 23.2%, and the 5-year sLR rate was 35.7%. Multivariate analysis showed that patients with surgery plus radiotherapy and recurrence interval o F>12 months had a lower sLR rate. Patients with recurrence interval o F>48 months, local plus systemic treatment and surgery plus radiotherapy had a higher PFS rate. Among the 155 patients who received chest wall radiotherapy after ICWR, total chest wall irradiation plus local boost could improve the 5-year PFS rate compared with total chest wall irradiation alone (34.0% vs. 15.4%, P=0.004). Chest wall radiation dose (≤60 Gy vs.>60 Gy) exerted no significant effect upon the sLR and PFS rates (both P>0.05). In the 53 patients without surgery, the 5-year PFS rates were 9.1% and 20.5%( P=0.061) with tumor bed dose ≤60 Gy and>60 Gy, respectively. Conclusions:Local radiotherapy is recommended for patients with ICWR after modified radical mastectomy of breast cancer, including total chest wall radiation plus local boost. The radiation dose for recurrence should be increased to 60 Gy, and it should be above 60 Gy for those who have not undergone surgical resection. In addition, patients with ICWR still have a high risk of sLR, and more effective treatments need to be explored.
7.Radiotherapy and prognostic analysis of breast cancer patients with isolated regional recurrence after mastectomy
Xuran ZHAO ; Liang XUAN ; Jun YIN ; Yu TANG ; Huiru SUN ; Shikai WU ; Hao JING ; Hui FANG ; Yongwen SONG ; Jing JIN ; Yueping LIU ; Hua REN ; Bo CHEN ; Shunan QI ; Ning LI ; Yuan TANG ; Ningning LU ; Yong YANG ; Yexiong LI ; Bing SUN ; Shulian WANG
Chinese Journal of Radiation Oncology 2021;30(10):1030-1035
Objective:To analyze the prognosis of patients with isolated regional recurrence (RR) after mastectomy, and evaluate the efficacy of radiotherapy and identify the optimal radiation target volumes.Methods:Clinical data of 144 patients with first isolated RR after mastectomy between 2001 and 2018 were retrospectively analyzed. All patients had not received post-mastectomy radiotherapy. The primary endpoints consisted of the subsequent locoregional recurrence (sLRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS).Results:With a median follow-up of 82.5 months after RR, the 5-year sLRR, DM, PFS and OS rates for the entire group were 42.1%, 71.9%, 22.9% and 62.6%, respectively. Local plus systemic therapy was an independent favorable prognostic factor for sLRR ( P<0.001) and PFS ( P=0.013). The sLRR rate in the surgery plus radiotherapy group was the lowest ( P<0.001). Surgery plus radiotherapy significantly reduced the 5-year risk of recurrence within the initially involved nodal regions ( P<0.001). Patients with chest wall irradiation obtained the 5-year subsequent chest wall recurrence rate of 12.1% compared to 14.8%( P=0.873) for those without chest wall irradiation. The subsequent supraclavicular recurrence rate was lower in patients with prophylactic supraclavicular irradiation than that without prophylactic supraclavicular irradiation (9.9% vs. 23.8%, P=0.206). The incidence rates of initially uninvolved axillary and internal mammary nodal recurrence were below 10% regardless of prophylactic irradiation or not. Conclusions:Patients with RR alone have an optimistic 5-year OS in the contemporary era. Comprehensive locoregional treatment including surgery and radiotherapy combined with systemic therapy is recommended. The chest wall, axillary and internal mammary nodal prophylactic irradiation should not be routinely performed for all patients with RR. The value of supraclavicular prophylactic irradiation remains to be evaluated.
8.Treatment and prognostic analysis of isolated chest wall recurrence of breast cancer after mastectomy
Xuran ZHAO ; Liang XUAN ; Jun YIN ; Yu TANG ; Huiru SUN ; Shikai WU ; Hao JING ; Hui FANG ; Yongwen SONG ; Jing JIN ; Yueping LIU ; Hua REN ; Bo CHEN ; Shunan QI ; Ning LI ; Yuan TANG ; Ningning LU ; Yong YANG ; Yexiong LI ; Bing SUN ; Shulian WANG
Chinese Journal of Oncology 2021;43(11):1203-1208
Objective:To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment.Methods:A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained.Results:Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval ( HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment ( HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status ( HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval ( HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment ( HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence ( HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status ( HR=1.69, 95% CI: 1.02-2.81), the recurrence interval ( HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence ( HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions:Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.
9.Treatment and prognostic analysis of isolated chest wall recurrence of breast cancer after mastectomy
Xuran ZHAO ; Liang XUAN ; Jun YIN ; Yu TANG ; Huiru SUN ; Shikai WU ; Hao JING ; Hui FANG ; Yongwen SONG ; Jing JIN ; Yueping LIU ; Hua REN ; Bo CHEN ; Shunan QI ; Ning LI ; Yuan TANG ; Ningning LU ; Yong YANG ; Yexiong LI ; Bing SUN ; Shulian WANG
Chinese Journal of Oncology 2021;43(11):1203-1208
Objective:To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment.Methods:A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained.Results:Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval ( HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment ( HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status ( HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval ( HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment ( HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence ( HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status ( HR=1.69, 95% CI: 1.02-2.81), the recurrence interval ( HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence ( HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions:Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.
10.Establishment of a prognostic Nomogram model for predicting the first 72-hour mortality in polytrauma patients
Tian XIE ; Xiangda ZHANG ; Bin CHENG ; Min HUANG ; Shikai WANG ; Sihua OU
Chinese Critical Care Medicine 2020;32(10):1208-1212
Objective:To establish a prognostic Nomogram model for predicting the risk of early death in polytrauma patients.Methods:Data extracted from a polytrauma study on Dryad, an open access database, was selected for secondary analysis. Patients from 18 to 65 years old with polytrauma in the original data were included. All patients with missing variables, such as blood lactic acid (Lac), Glasgow coma score (GCS) and injury severity score (ISS) at admission, were excluded. The differences of gender, age, Lac, ISS and GCS scores between the patients who died within 72 hours and those who survived were analyzed. The risk factors for 72-hour death were analyzed by Logistic regression, and the Nomogram prediction model was established using R software. The receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of the model, and the Bootstrap method was used for internal verification by repeating sample for 1 000 times. Decision curve (DCA) was applied to analyze the clinical practical value of the model.Results:A total of 2 315 polytrauma patients were included. Logistic regression analysis showed that Lac, GCS score and age > 55 years old were the risk factors for early death in polytrauma patients [Lac: odds ratio ( OR) = 1.36, 95% confidence interval (95% CI) was 1.29-1.42, P < 0.001; GCS score: OR = 0.76, 95% CI was 0.73-0.79, P < 0.001; age > 55 years old: OR = 1.92, 95% CI was 1.37-2.66, P < 0.001]. The prediction model was established by using the above risk factors and displayed by Nomogram. ROC curve analysis showed that the area under the ROC curve (AUC) of Nomogram model to predict the risk of death within 72 hours was 0.858, and the predictive ability of Nomogram model was significantly higher than that of Lac (AUC = 0.743), GCS score (AUC = 0.774) and ISS score (AUC = 0.699), all P < 0.05. The model calibration chart showed that the predicting probability was consistent with the actual occurrence probability, and the DCA showed that Nomogram model presented excellent clinical value in predicting the 72-hour death risk for polytrauma patients. Conclusions:The prognostic Nomogram model presents significantly predictive value for the risk of death within 72 hours in polytrauma patients. Prognostic Nomogram model could offer individualized, visualized and graphical prediction pattern, and provide physicians with practical diagnostic tool for triage system and management of polytrauma according to precision medicine.

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