AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95％ethanol cold soaked ultrasonic extract(EC),95％ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2％formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.

AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95％ethanol cold soaked ultrasonic extract(EC),95％ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2％formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

[Abstract] Objective: To explore the expression patterns of melanoma lineage antigens and nuclear antigen Ki-67 and their correlations with survival in melanoma patients. Methods: A retrospective analysis was conducted to analyze the pathological data of melanoma patients treated at the Department of Melanoma, Peking University Cancer Hospital from February 2008 to August 2020, mainly including the expression patterns of melanoma lineage antigens (S-100, HMB-45, Melan-A) and Ki-67, demographics, clinical features and survival. The correlation between expression patterns of melanoma lineage antigens, Ki-67 and melanoma-specific survival (MSS) was analyzed. Results: In total, 603 patients were included in this study. The median follow-up time was 47.4 months. The positive rates of S-100, HMB, and Melan-A were 92.8%, 92.1% and 90.0%, respectively. The percentages of patients with melanoma lineage antigen scores (S-100, HMB-45 and Melan-A was scored each, as 1 when positive and 0 when negative) of 0, 1, 2, and 3 were 0.5%, 5.0%, 15.6%, and 78.8%, respectively. The percentages of patients with Ki-67 scores of 0, 1, 2, and 3 were 43.0%, 36.3%, 16.3%, and 4.5%, respectively. Ki-67 was highly expressed in mucosal and progressive melanomas. In a multivariate analysis, Ki-67 expression was an independent prognostic factor for poorer MSS (HR=1.506, 95%CI: 1.248-1.818, P<0.001) as the incidence of MSS event increased by 50% per 25% increase in Ki-67 expression, whereas there was no statistical correlation between melanoma lineage antigen expression and MSS (HR=0.991, 95%CI: 0.759-1.293, P=0.94). Conclusion: High expressions melanoma lineage antigens are ubiquitous in melanoma tissues, and Ki-67 is an independent prognostic factor for MSS.

BACKGROUND: Functional dyspepsia (FD) has rarely been investigated in areas with a high prevalence of esophageal squamous cell carcinoma (ESCC). This study aims to reveal the epidemiological and clinical features of FD and organic dyspepsia (OD) in such a population. METHODS: A middle-aged and elderly population-based study was conducted in a region with a high incidence of ESCC. All participants completed the Gastroesophageal Reflux Disease Questionnaire and Functional Gastrointestinal Disease Rome III Diagnostic Questionnaire, and they underwent gastroscopy. After exclusion of gastroesophageal reflux disease, uninvestigated dyspepsia (UID) was divided into OD and FD for further analyses. RESULTS: A total of 2916 participants were enrolled from July 2013 to March 2014 in China. We detected 166 UID cases with questionnaires, in which 17 patients with OD and 149 with FD were diagnosed via gastroscopy. OD cases presented as reflux esophagitis (RE), ESCC, and duodenal ulcer. Heartburn (52.94%) and reflux (29.41%) were common in OD, but no symptomatic differences were found between FD and OD. Male sex, low education level, and liquid food were the risk factors for OD, while frequent fresh vegetable consumption was a protective factor. FD included 56 (37.58%) cases of postprandial distress syndrome (PDS), 52 (34.89%) of epigastric pain syndrome (EPS), nine (6.04%) of PDS + EPS, and 32 (21.48%) of FD + functional esophageal disorders. The Helicobacter pylori infection rate in FD patients was not higher than that in the control group (34.23% vs. 42.26%, P = 0.240). Frequent spicy food consumption was associated with PDS (odds ratio [OR]: 2.088, 95% confidence interval [CI]: 1.028-4.243), while consumption of deep well water was protective for PDS (OR: 0.431, 95% CI: 0.251-0.741). CONCLUSIONS: The prevalence of FD was 5.11% in the studied population. Gastroscopy should be prescribed for dyspepsia patients in case that ESCC and RE would be missed in UID cases diagnosed solely by the Rome III questionnaire. TRIAL REGISTRATION ClinicalTrials.gov, NCT01688908; https://clinicaltrials.gov/ct2/show/record/NCT01688908.
Aged ; China/epidemiology* ; Dyspepsia/epidemiology* ; Esophageal Neoplasms/epidemiology* ; Esophageal Squamous Cell Carcinoma ; Helicobacter Infections ; Helicobacter pylori ; Humans ; Incidence ; Male ; Middle Aged

Objective:To explore the prognostic value of PD-L1 expression level in patients with metastatic renal cell carcinoma (mRCC).Methods:The clinicopathological and survival data of patients with mRCC in our hospital from Jan 2014 to Apr 2016 were retrospectively analyzed including 46 males and 15 females. The median age of these patients was 56 years(range: 29-75 years), with 41 patients ≤60 years and 20 patients >60 years. The baseline data before the systemic therapy showed 36 patients(59.0%)had 1 metastatic organ and 25 patients (41.0%) had equal or more than 2 organs to be metastasized. Among them, 17 patients(27.9%)had lung metastasis and 54 patients(88.5%)had liver metastasis. Abnormal baseline LDH occurred in 4 patients and 52 patients had normal LDH. Favorite and intermediate risk patients categorized by MSKCC risk stratification accounted for 59.6%(34 patients)and 40.4%(23 patients), respectively. Six patients(9.8%)experienced distant metastasis at initial diagnosis, with 4 of them undergoing primary site resection, and the other 55 patients undergoing radical nephrectomy. PD-L1 expression was detected by the immunohistochemical staining method. PD-L1 staining rate ≥1% detected on the tumor cell membrane was defined as positive expression. The correlation between PD-L1 expression and clinicopathological characteristics were compared. Kaplan-Meier method and log-rank test were used to compare the differences about DFS and OS under different factors. Cox proportional hazards regression model is used for multivariable analysis of survival data.Results:The detailed pathological types of the 61 patients with renal cell carcinoma were classified as 53 clear cell carcinomas, 3 papillary carcinomas, 1 collecting duct carcinoma, 2 translocation renal cell carcinomas and 2 being unclassified. There were 4, 20, 19 and 9 patients categorized as WHO/ISUP nuclear grade 1, 2, 3 and 4, and 26, 12, 20 and 2 patients were categorized as T 1, T 2, T 3 and T 4 stage, respectively. Five patients had regional lymph node metastasis(N+), and the other 56 patients had no regional lymph node metastasis(N-). The numbers of patients categorized as stage Ⅰ, Ⅱ, Ⅲ and Ⅳ diseases according to TNM staging system were 20, 11, 21 and 8, respectively. The total PD-L1 positive rate was 24.6%(15/61). The corresponding PD-L1 expression rate of patients with WHO/ISUP nuclear grade 1-4 were 0(0 patient), 5.0%(1 patient), 31.6%(6 patients)and 44.4%(4 patients), respectively; With the increasing WHO/ISUP nuclear grade, the positive rate of PD-L1 gradually escalated with a linear correlation ( P=0.006). The PD-L1 expression of the normal and abnormal LDH group were 19.2%(10 patients)and 75.0%(3 patients), respectively, with significant difference( P=0.035). Univariate analysis of disease-free survival time(DFS)showed that the prognostic factors include PD-L1( P=0.045), age group( P=0.014), WHO/ISUP nuclear grade( P<0.001), T stage( P=0.015), N stage( P=0.026)and TNM stage( P=0.005). However multivariate analysis only suggested WHO/ISUP nuclear grade as the independent prognostic factors for DFS( HR=1.8, 95% CI 1.1-2.9, P=0.018). Either in univariate or multivariate analysis, PD-L1 was not a prognostic factor for overall survival (OS)of mRCC patients(univariate analysis: P=0.154; multivariate analysis: P=0.902). The independent prognostic factors of OS include WHO/ISUP nuclear grade( HR=3.0, 95% CI 1.1-8.0, P=0.033)and MSKCC risk stratification( HR=5.9, 95% CI 1.2-29.7, P=0.03). Conclusions:This study showed that the higher the WHO/ISUP nuclear grade of patients with mRCC, the higher the positive rate of PD-L1. PD-L1 expression was not the independent prognostic factor for DFS or OS of mRCC.

BACKGROUND: Coronary atherosclerotic plaque could go through rapid progression and induce adverse cardiac events. This study aimed to evaluate the impacts of smoking status on clinical outcomes of coronary non-target lesions. METHODS: Consecutive patients with coronary heart disease who underwent two serial coronary angiographies were included. All coronary non-target lesions were recorded at first coronary angiography and analyzed using quantitative coronary angiography at both procedures. Patients were grouped into non-smokers, quitters, and smokers according to their smoking status. Clinical outcomes including rapid lesion progression, lesion re-vascularization, and myocardial infarction were recorded at second coronary angiography. Multivariable Cox regression analysis was used to investigate the association between smoking status and clinical outcomes. RESULTS: A total of 1255 patients and 1670 lesions were included. Smokers were younger and more likely to be male compared with non-smokers. Increase in percent diameter stenosis was significantly lower (2.7 [0.6, 7.1] % vs. 3.5 [0.9, 8.9]%) and 3.4 [1.1, 7.7]%, P = 0.020) in quitters than those in smokers and non-smokers. Quitters tended to have a decreased incidence of rapid lesions progression (15.8% [76/482] vs. 21.6% [74/342] and 20.6% [89/431], P = 0.062), lesion re-vascularization (13.1% [63/482] vs. 15.5% [53/432] and 15.5% [67/431], P = 0.448), lesion-related myocardial infarction (0.8% [4/482] vs. 2.6% [9/342] and 1.4% [6/431], P = 0.110) and all-cause myocardial infarction (1.9% [9/482] vs. 4.1% [14/342] and 2.3% [10/431], P = 0.128) compared with smokers and non-smokers. In multivariable analysis, smoking status was not an independent predictor for rapid lesion progression, lesion re-vascularization, and lesion-related myocardial infarction except that a higher risk of all-cause myocardial infarction was observed in smokers than non-smokers (hazards ratio: 3.00, 95% confidence interval: 1.04-8.62, P = 0.042). CONCLUSION Smoking cessation mitigates the increase in percent diameter stenosis of coronary non-target lesions, meanwhile, smokers are associated with increased risk for all-cause myocardial infarction compared with non-smokers.

Objective: To investigate the impact of type 2 diabetes mellitus on progression and revascularization of coronary non-target lesions in patients with coronary heart disease. Methods: From January 2010 to September 2014, we retrospectively analyzed the clinical data of patients with coronary heart disease who underwent two consecutive coronary angiographies at Fuwai Hospital. At least one coronary non-target lesion was recorded at the first procedure in these patients. Patients were grouped according to the diagnose of type 2 diabetes mellitus. Demographic features, risk factors of coronary heart disease, laboratory results as well as characteristics of coronary non-target lesions were collected at baseline (first coronary angiography) and follow-up (second coronary angiography). Lesion progression was defined by quantitative coronary angiography analysis. Lesions revascularization was recorded. Multivariable Cox regression analysis was used to define the impacts of diabetes mellitus on progression and revascularization of non-target lesions. Subgroup analysis in diabetic and non-diabetic groups were further performed. Receiver operating characteristics curve was used to identify the predictive value of HbA1c. Results: A total of 1 255 patients were included, and 1 003(79.9%) were male, age was(58.0±9.7) years old. And 486 patients were diagnosed with type 2 diabetes mellitus. Follow-up time was (14.8±4.5) months. Compared with non-diabetic group, diabetic group were older with less male and had higher BMI index as well as higher prevalence of hypertension, dyslipidemia, prior myocardial infarction and prior percutaneous coronary intervention(all P<0.05). Diabetic patients also had higher level of white blood cells, erythrocyte sedimentation rate, C-reactive protein, endothelin and HbA1c at both baseline and follow-up compared with non-diabetic patients (all P<0.01). There was no significant difference on progression of non-target lesions (20.0%(97/486) vs. 18.5%(142/769), P=0.512), revascularization of non-target lesions (13.2%(64/486) vs. 15.9%(122/769), P=0.190) and non-target lesion related myocardial infarction(1.9%(9/486) vs. 1.3%(10/769), P=0.436) between diabetic and non-diabetic patients. Multivariable Cox regression analysis revealed that diabetes mellitus was not an independent predictor for progression and revascularization of non-target lesions (Both P>0.05). Subgroup analysis in diabetic patients showed that baseline HbA1c level(HR=1.160, 95%CI 1.009-1.333, P=0.037) was an independent predictor for non-target lesion progression. Cut-off value of HbA1c was 6.5% (Area Under Curve(AUC) 0.57, specificity 88.7%; sensitivity 24.2%, P=0.046) by receiver operating characteristics curve. Patients with HbA1c level above 6.5% had 2.8 times higher risk of lesion progression compared with patients with HbA1c level below 6.5% (HR=2.838, 95%CI 1.505-5.349, P=0.001). Compared with non-diabetic patients, diabetic patients with HbA1c below 6.5% also had lower risk of lesion progression (HR=0.469, 95%CI 0.252-0.872, P=0.012). ST-segment elevated myocardial infarction was an independent predictor for revascularization of non-target lesions in diabetic patients. Conclusion: Type 2 diabetes mellitus is not an independent predictor for progression and revascularization of coronary non-target lesions in patients with coronary heart disease. However, elevated HbA1c level is a risk factor for progression of non-target lesion in patients with type 2 diabetes mellitus.
Aged ; Coronary Angiography ; Coronary Artery Disease/complications* ; Diabetes Mellitus, Type 2/complications* ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Retrospective Studies ; Risk Factors ; Treatment Outcome

Objective:To explore the occurrence and clinical characteristics of hyperprogression of metastatic malignant melanoma caused by toripalimab (JS001).Methods:The medical records of patients with metastatic malignant melanoma treated with JS001 alone or in combination with other antineoplastic agents between February 2018 and September 2019 in Department of Kidney Cancer and Melanoma of Beijng Cancer Hospital were collected. Patients displaying hyperprogression were screened into the case group, who were matched with those without hyperprogression evidence (the control group) in a 1/4 ratio according to baseline age, gender, Eastern Cooperative Oncology Group score, location of the primary lesion, and elevated level of lactate dehydrogenase (LDH). The clinical characteristics and prognosis of patients between the 2 groups were compared and the hyperprogression in the case group was analyzed descriptively.Results:A total of 130 patients with metastatic malignant melanoma who received JS001 alone or in combination with other antineoplastic agents were collected. Hyperprogression occurred in 8 patients (the case group), including 5 males and 3 females, aged (52.5±8.5) years. The incidence of hyperprogression was 6.15%. Thirty-two patients without displaying hyperprogression were matched as the control group according to the baseline characteristics of patients in the case group. Patients with metastatic lesions in more than 2 organs at baseline in the case group were significantly more than those in the control group (6/8 vs. 7/32, P=0.014); the LDH level of patients in the case group significantly increased after treatment than before [(965±710) U/L vs. (264±64) U/L, P=0.025]; the progression-free survival and overall survival in patients were significantly lower than those of patients in the control group [1.7 (95 %CI: 1.4-2.0) months vs. 3.1 (95 %CI: 2.7-3.5) months, P<0.001; 4.8 (95 %CI: 0-11.2) months vs. 10.7 (95 %CI: 10.4-10.9) months, P=0.031]. Conclusions:Patients with melanoma may experience hyperprogression in early stages of JS001 treatment. Patients with metastatic lesions in more than 2 organs before treatment are more likely to develop hyperprogression, and patients displaying hyperprogression have a poor prognosis. Serum LDH level monitoring can help detect tumor hyperprogression as early as possible.

Objective:To explore the occurrence and clinical characteristics of hyperprogression of metastatic malignant melanoma caused by toripalimab (JS001).Methods:The medical records of patients with metastatic malignant melanoma treated with JS001 alone or in combination with other antineoplastic agents between February 2018 and September 2019 in Department of Kidney Cancer and Melanoma of Beijng Cancer Hospital were collected. Patients displaying hyperprogression were screened into the case group, who were matched with those without hyperprogression evidence (the control group) in a 1/4 ratio according to baseline age, gender, Eastern Cooperative Oncology Group score, location of the primary lesion, and elevated level of lactate dehydrogenase (LDH). The clinical characteristics and prognosis of patients between the 2 groups were compared and the hyperprogression in the case group was analyzed descriptively.Results:A total of 130 patients with metastatic malignant melanoma who received JS001 alone or in combination with other antineoplastic agents were collected. Hyperprogression occurred in 8 patients (the case group), including 5 males and 3 females, aged (52.5±8.5) years. The incidence of hyperprogression was 6.15%. Thirty-two patients without displaying hyperprogression were matched as the control group according to the baseline characteristics of patients in the case group. Patients with metastatic lesions in more than 2 organs at baseline in the case group were significantly more than those in the control group (6/8 vs. 7/32, P=0.014); the LDH level of patients in the case group significantly increased after treatment than before [(965±710) U/L vs. (264±64) U/L, P=0.025]; the progression-free survival and overall survival in patients were significantly lower than those of patients in the control group [1.7 (95 %CI: 1.4-2.0) months vs. 3.1 (95 %CI: 2.7-3.5) months, P<0.001; 4.8 (95 %CI: 0-11.2) months vs. 10.7 (95 %CI: 10.4-10.9) months, P=0.031]. Conclusions:Patients with melanoma may experience hyperprogression in early stages of JS001 treatment. Patients with metastatic lesions in more than 2 organs before treatment are more likely to develop hyperprogression, and patients displaying hyperprogression have a poor prognosis. Serum LDH level monitoring can help detect tumor hyperprogression as early as possible.