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ObjectiveTo predict whether antiviral therapy is required in patients with chronic hepatitis B virus (HBV) infection and an age of ≤30 years by establishing a noninvasive model, and to investigate the diagnostic value of this model. MethodsA retrospective analysis was performed for the clinical data of 175 patients with chronic HBV infection who were admitted to Shenzhen Third People’s Hospital from January 2017 to January 2023 and met the inclusion criteria, and according to the results of liver biopsy, they were divided into treatment group with 41 patients (with indications for antiviral therapy) and observation group with 134 patients (without indications for antiviral therapy). The two groups were analyzed in terms of the indicators including clinical data, imaging examinations, and serum biochemical parameters. The univariate and multivariate Logistic regression analyses were used to investigate the parameters affecting the indication for antiviral therapy, and different models for predicting the need for antiviral therapy were constructed based on related parameters. The receiver operating characteristic (ROC) curve was used to compare the diagnostic value of different models. The independent-samples t test was used for comparison of normally distributed continuous variables between groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous variables between groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsThere were significant differences between the treatment group and the observation group in alanine aminotransferase, ferritin, total cholesterol (CHOL), triglyceride, platelet count, liver stiffness measured by sound touch elastography (STE), and procollagen III N-terminal propeptide (PIIIP) (all P<0.05). The multivariate Logistic regression analysis showed that CHOL (odds ratio [OR]=0.4, 95% confidence interval [CI]: 0.2 — 1.0), STE (OR=1.5, 95%CI: 1.0 — 2.1), and PIIIP (OR=1.1, 95%CI: 1.0 — 1.1) were independent predictive factors for the indications for antiviral therapy. Model 1 (STE+PIIIP+CHOL), model 2 (STE+PIIIP), model 3 (STE+CHOL), model 4 (PIIIP+CHOL) had an area under the ROC curve of 0.908, 0.848, 0.725, and 0.725, respectively, while STE, PIIIP, and CHOL used alone had an AUC of 0.836, 0.725, and 0.634, respectively, suggesting that model 1 had the largest AUC, with a specificity of 77.34% and a sensitivity of 96.36%, and had a significant difference compared with STE, PIIIP, CHOL, and the models 2, 3, and 4 (Z=0.21, 3.08, 3.06, 3.23, 0.89, and 0.88, all P<0.05). ConclusionThe noninvasive model established based on CHOL, STE, and PIIIP has a good value in predicting the need for antiviral therapy in patients with chronic HBV infection and an age of ≤30 years.
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Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.
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Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.
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ABSTRACT Introduction: Basketball has become popular, and important basketball groups have been created for fun and training. However, many athletes do not acquire a professional education, creating a gap between athletes and sports enthusiasts. Objective: Study the technical characteristics of the jump shot in basketball and explore its training methods. Methods: Intra-group control was selected to train the volunteer enthusiasts. The experiment was conducted twice a week for 6 weeks. Data regarding physical performance were acquired before and after the experiment, subjected to analysis, and discussed confronting the literature. Results: After six weeks of training, the total time of the three phases on the sports enthusiasts was 1.14378s, and the average time of the ball preparation phase was 0.72262s, representing 63.178% of the total time. The average time spent in the take-off phase was 0.2011s, representing 17.582% of the total time; the average time spent in the vacancy phase was 0.22006s, representing 19.240% of the total time. Conclusion: The jump-throw training protocol showed benefits over 6 weeks of training. The technical characteristics of the participants in the sports enthusiast group were improved statistically. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução: O basquetebol tem se tornado popular, e importantes grupos de basquetebol foram criados para diversão e treinamento. No entanto, muitos esportistas não adquirem um ensino profissionalizante, gerando uma lacuna entre os atletas e os entusiastas do esporte. Objetivo: Estudar as características técnicas do salto para arremesso no basquetebol e explorar seus métodos de treinamento. Métodos: O controle intra-grupo foi selecionado para treinar os entusiastas voluntários. O experimento foi realizado duas vezes por semana durante 6 semanas. Os dados referentes ao desempenho físico foram adquiridos antes e após o experimento, submetidos a análise e discutidos confrontando a literatura. Resultados: Após seis semanas de treinamento, o tempo total das três fases sobre os entusiastas do esporte foi de 1.14378s, e o tempo médio da fase de preparação da bola foi de 0,72262s, representando 63,178% do tempo total. O tempo médio gasto na fase de decolagem foi de 0,2011s, representando 17,582% do tempo total; o tempo médio gasto na fase de vacância foi de 0,22006s, representando 19,240% do tempo total. Conclusão: O protocolo de treinamento de salto para arremesso apresentou benefícios ao longo de 6 semanas de treinamento. As características técnicas dos participantes no grupo de entusiastas do esporte foram aprimoradas estatisticamente. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.
RESUMEN Introducción: El baloncesto se ha popularizado y se han creado importantes grupos de baloncesto para divertirse y entrenar. Sin embargo, muchos deportistas no adquieren una formación profesionalizante, lo que genera una brecha entre los atletas y los aficionados al deporte. Objetivo: Estudiar las características técnicas del salto para lanzar en baloncesto y explorar sus métodos de entrenamiento. Métodos: Se seleccionó un control intragrupo para entrenar a los voluntarios entusiastas. El experimento se realizó dos veces por semana durante 6 semanas. Los datos relativos al rendimiento físico se adquirieron antes y después del experimento, se sometieron a análisis y se discutieron confrontándolos con la bibliografía. Resultados: Tras seis semanas de entrenamiento, el tiempo total de las tres fases en los entusiastas del deporte fue de 1,14378s, y el tiempo medio de la fase de preparación del balón fue de 0,72262s, lo que representa el 63,178% del tiempo total. El tiempo medio empleado en la fase de despegue fue de 0,2011s, lo que representa el 17,582% del tiempo total; el tiempo medio empleado en la fase de vacante fue de 0,22006s, lo que representa el 19,240% del tiempo total. Conclusión: El protocolo de entrenamiento de salto para lanzamiento presentó beneficios a lo largo de 6 semanas de entrenamiento. Las características técnicas de los participantes del grupo de entusiastas del deporte mejoraron estadísticamente. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.
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EIDD-2801 is an orally bioavailable prodrug, which will be applied for emergency use authorization from the U.S. Food and Drug Administration for the treatment of COVID-19. To investigate the optimal parameters, EIDD-2801 was optimized
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Objective:To investigate the value of combined detection of biomarkers in early diagnosis and prognosis of patients with septic myocardial injury.Methods:The clinical data of 103 patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology from October 2018 to January 2021 were enrolled. According to the cardiac troponin I (cTnI) at admission of ICU, they were divided into septic myocardial injury group (cTnI ≥ 0.15 μg/L) and non-septic myocardial injury group (cTnI < 0.15 μg/L). The serum levels of heart-type fatty acid-binding protein (H-FABP), procalcitonin (PCT), C-reactive protein (CRP), MB isoenzyme of creatine kinase (CK-MB), cTnI and N-terminal pro-brain natriuretic peptide (NT-proBNP) within 6 hours after ICU admission and the worst value of acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score within 24 hours after ICU admission in 103 patients was recorded as well as the 28-day prognosis of patient with septic myocardial injury. Spearman correlation analysis was used to analyze the correlation of each index; receiver operating characteristic curve (ROC curve) was drawn, and the area under ROC curve (AUC) was calculated to analyze the early diagnosis and prognostic value of each index and APACHEⅡ score alone or combined detection in patients with septic myocardial injury.Results:① Among 103 patients with sepsis, 58 patients were complicated with myocardial injury and 45 patients were not complicated with myocardial injury. The serum levels of PCT, CRP, NT-proBNP, CK-MB, cTnI, H-FABP and APACHEⅡ score in patients with septic myocardial injury were significantly higher than those in patients without septic myocardial injury [PCT (μg/L): 3.46±1.35 vs. 1.89±0.43, CRP (mg/L): 81.1±26.8 vs. 65.3±19.1, NT-proBNP (U/L): 8 261.4±2 346.9 vs. 6 120.2±1 809.6, CK-MB (U/L): 15.89±6.25 vs. 12.14±4.24, cTnI (μg/L): 1.50 (0.91, 2.21) vs. 0.18 (0.16, 0.19), H-FABP (μg/L): 26.45±8.24 vs. 12.82±5.73, APACHEⅡ score: 24.0 (18.0, 29.0) vs. 16.0 (14.0, 18.0), all P < 0.01]. Spearman correlation analysis showed that PCT, CRP and APACHEⅡ scores were positively correlated with NT-proBNP, CK-MB, cTnI and H-FABP. ROC curve analysis showed that H-FABP in the diagnosis of septic myocardial injury (AUC = 0.916) was superior to NT-proBNP (AUC = 0.756) and CK-MB (AUC = 0.675); the AUC of NT-proBNP and CK-MB combined with H-FABP was 0.921, the sensitivity was 82.1%, and the specificity was 88.2%.② Twenty-three patients survived in 28 days, and 35 died. The levels of serum PCT, CRP, NT-proBNP, CK-MB, cTnI, H-FABP and APACHEⅡ score in death group were significantly higher than those in survival group [PCT (μg/L): 3.86±1.27 vs. 2.84±1.24, CRP (mg/L): 92.3 (65.0, 101.7) vs. 74.3 (65.7, 79.8), NT-proBNP (ng/L): 9 106.4±2 013.9 vs. 6 975.5±2 266.7, CK-MB (U/L): 17.90±6.49 vs. 12.82±4.46, cTnI (μg/L): 2.11±0.86 vs. 1.12±0.44, H-FABP (μg/L): 30.08±7.90 vs. 20.93±5.14, APACHEⅡ score: 25.0 (20.0, 30.0) vs. 19.0 (17.0, 24.0), all P < 0.01]. ROC curve analysis showed that H-FABP in evaluating 28-day death of patients with septic myocardial injury (AUC = 0.839) was superior to PCT (AUC = 0.707), CRP (AUC = 0.716), NT-proBNP (AUC = 0.761), CK-MB (AUC = 0.733), cTnI (AUC = 0.824) and APACHEⅡ score (AUC = 0.724); the AUC of NT-proBNP and cTnI combined with H-FABP was 0.888, the sensitivity was 91.4%, and the specificity was 82.6%. Conclusions:H-FABP plays an important role in the early diagnosis and prognosis of septic myocardial injury. Early combined detection of NT-proBNP, CK-MB and H-FABP can significantly improve the diagnostic ability of septic myocardial injury, and NT-proBNP and cTnI combined with H-FABP can significantly improve the ability to predict the adverse prognosis of sepsis myocardial injury.
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@#Using ALK5 inhibitor LY-3200882 as a lead compound, ten structurally novel compounds were designed by bioisosterism, conformational restriction and molecular docking technology. All structures were synthesized and confirmed by 1H NMR and HR-MS. The results of in vitro activity screening showed that most compounds had good kinase inhibitory activity. Among them, compound B4 showed significantly better ALK5 inhibitory activity than LY-3200882 (IC50 = 1.4 nmol/L vs 41.1 nmol/L), and had good inhibitory activity against TGFβ-ALK5-SMAD2/3 signaling pathway in NIH3T3 cells (IC50 = 14.2 nmol/L). Besides, compound B4 had good pharmacokinetic properties, such as oral exposure and bioavailability, which is worthy of further development.
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Surgical resection is the best therapeutic option for patients with colorectal cancer liver metastasis. As patients with synchronous liver metastases from colorectal cancer, simultaneous resection of primary and metastatic lesions has been widely used. With the gradual maturation of laparoscopic technology, its minimally invasive, safe and effective characteristics make it better for simultaneous resection of colorectal cancer with liver metastasis. On the basis of grasping the principles of surgical treatment for colorectal cancer with liver metastasis, reasonable and full combination of the advantages of laparoscopy can enable patients get greater benefits with minimal trauma.
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Objective:To investigate the definition and influencing factors of early recurrence after resection for synchronous colorectal cancer liver metastases (sCRLM).Methods:Patients with sCRLM in Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from December 2008 to December 2016 were included. Restricted cubic spline was used to determine the correlations between the time of recurrence and the long-term prognosis. The univariable and multivariable Cox was performed to measure the feasibility of recurrence within 6 months as the early recurrence. Then apply logistic regression, support vector machine, decision tree, random forest, artificial neural network and XGBoost, these machine learning algorithm to comprehensively rank the importance of every clinicopathological variable to early recurrence, and according to the comprehensively ranks, we introduced variables into the multivariable logistic regression model and observed the receiver operating characteristic curve (ROC) of the logistic regression model, based on the ROC area under curve, Akaike information criterion, and Bayesian information criterion, we identified the best performed variable combination and introduced them into the multivariate logistic regression analysis to confirm the independent risk factors for early recurrence. Subsequently, inverse probability weighting (IPTW) was performed on the therapy-associated independent risk factor to evaluate and validate its influence on the early recurrence of sCRLM patients after reducing the standardized mean difference of all covariates.Results:A total of 228 sCRLM patients who received resection were enrolled and followed up from 2.10 to 108.57 months. There were 142 males and 86 females, aged (55.89±0.67) years old. In 170 (74.6%) patients with recurrence, restricted cube analysis determined that the hazard ratio (HR) of disease free survival (DFS) and overall survival (OS) satisfies a linear relationship ( P<0.05), and Cox analysis indicated that 6 months as the time cutoff for defining early recurrence was feasible ( HR=3.405, 95% CI: 2.098-5.526, P<0.05). Early recurrence was occurred in 93 (40.79%) patients. The survival rate of patients in early recurrence group was significantly lower than that in the late recurrence group ( HR=3.405, 95% CI: 2.098-5.526, P<0.05, and the 5-year survival rate was 14.0% vs 52.0%). Comprehensive analysis of 6 machine learning algorithms identified that the total number of lymph node dissection >22 ( OR=0.258, 95% CI: 0.132-0.506, P<0.05) is an independent protective factor for early recurrence, while the number of liver metastases>3 ( OR=4.715, 95% CI: 2.467-9.011, P<0.05) and postoperative complications ( OR=2.334, 95% CI: 1.269-4.291, P<0.05) are independent risk factors. Finally, the IPTW analysis fully reduced the influence of covariate confounding influence via causal inference to prove lymph node dissection associated with early recurrence (IPTW OR=0.29, P<0.05), benefiting the DFS (IPTW HR=0.4887, P<0.05), but without influence on OS (IPTW HR=0.6951, P>0.05). Conclusion:Six months after sCRLM as the definition of early recurrence, it has significant feasibility. The long-term survival of patients with early recurrence is poor. The independent influencing factors of early recurrence after sCRLM are the total number of lymph node dissection, the number of liver metastases and postoperative complications disease.
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Objective:To investigate the application value of machine learning algorithms and COX nomogram in the survival prediction of hepatocellular carcinoma (HCC) after resection.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 375 patients with HCC who underwent radical resection in the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College from January 2012 to January 2017 were collected. There were 304 males and 71 females, aged from 21 to 79 years, with a median age of 57 years. According to the random numbers showed in the computer, 375 patients were divided into training dataset consisting of 300 patients and validation dataset consisting of 75 patients, with a ratio of 8∶2. Machine learning algorithms including logistic regression (LR), supporting vector machine (SVM), decision tree (DT), random forest (RF), and artificial neural network (ANN) were used to construct survival prediction models for HCC after resection, so as to identify the optimal machine learning algorithm prediction model. A COX nomogram prediction model for predicting postoperative survival in patients with HCC was also constructed. Comparison of performance for predicting postoperative survival of HCC patients was conducted between the optimal machine learning algorithm prediction model and the COX nomogram prediction model. Observation indicators: (1) analysis of clinicopathological data of patients in the training dataset and validation dataset; (2) follow-up and survival of patients in the training dataset and validation dataset; (3) construction and evaluation of machine learning algorithm prediction models; (4) construction and evaluation of COX nomogram prediction model; (5) evaluation of prediction performance between RF machine learning algorithm prediction model and COX nomogram prediction model. Follow-up was performed using outpatient examination or telephone interview to detect survival of patients up to December 2019 or death. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was analyzed by the paired t test. Measurement data with skewed distribution were expressed as M ( P25, P75) or M (range), and comparison between groups was analyzed by the Mann-Whitney U test. Count data were represented as absolute numbers. Comparison between groups was performed using the chi-square test when Tmin ≥5 and N ≥40, using the calibration chi-square test when 1≤ Tmin ≤5 and N ≥40, and using Fisher exact probability when Tmin <1 or N <40. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. The COX proportional hazard model was used for univariate analysis, and variables with P<0.2 were included for the Lasso regression analysis. According to the lambda value, variables affecting prognosis were screened for COX proportional hazard model to perform multivariate analysis. Results:(1) Analysis of clinicopathological data of patients in the training dataset and validation dataset: cases without microvascular invasion or with microvascular invasion, cases without liver cirrhosis or with liver cirrhosis of the training dataset were 292, 8, 105, 195, respectively, versus 69, 6, 37, 38 of the validation dataset, showing significant differences between the two groups ( χ2=4.749, 5.239, P<0.05). (2) Follow-up and survival of patients in the training dataset and validation dataset: all the 375 patients received follow-up. The 300 patients in the training dataset were followed up for 1.1-85.5 months, with a median follow-up time of 50.3 months. Seventy-five patients in the validation dataset were followed up for 1.0-85.7 months, with a median follow-up time of 46.7 months. The postoperative 1-, 3-year overall survival rates of the 375 patients were 91.7%, 79.5%. The postoperative 1-, 3-year overall survival rates of the training dataset were 92.0%, 79.7%, versus 90.7%, 81.9% of the validation dataset, showing no significant difference in postoperative survival between the two groups ( χ2=0.113, P>0.05). (3) Construction and evaluation of machine learning algorithm prediction models. ① Selection of the optimal machine learning algorithm prediction model: according to information divergence of variables for prediction of 3 years postoperative survival of HCC, five machine learning algorithms were used to comprehensively rank the variables of clinicopathological factors of HCC, including LR, SVM, DT, RF, and ANN. The main predictive factors were screened out, as hepatitis B e antigen (HBeAg), surgical procedure, maximum tumor diameter, perioperative blood transfusion, liver capsule invasion, and liver segment Ⅳ invasion. The rank sequence 3, 6, 9, 12, 15, 18, 21, 24, 27, 29 variables of predictive factors were introduced into 5 machine learning algorithms in turn. The results showed that the area under curve (AUC) of the receiver operating charateristic curve of LR, SVM, DT, and RF machine learning algorithm prediction models tended to be stable when 9 variables are introduced. When more than 12 variables were introduced, the AUC of ANN machine learning algorithm prediction model fluctuated significantly, the stability of AUC of LR and SVM machine learning algorithm prediction models continued to improve, and the AUC of RF machine learning algorithm prediction model was nearly 0.990, suggesting RF machine learning algorithm prediction model as the optimal machine learning algorithm prediction model. ② Optimization and evaluation of RF machine learning algorithm prediction model: 29 variables of predictive factors were sequentially introduced into the RF machine learning algorithm to construct the optimal RF machine learning algorithm prediction model in the training dataset. The results showed that when 10 variables were introduced, results of grid search method showed 4 as the optimal number of nodes in DT, and 1 000 as the optimal number of DT. When the number of introduced variables were not less than 10, the AUC of RF machine learning algorithm prediction model was about 0.990. When 10 variables were introduced, the RF machine learning algorithm prediction model had an AUC of 0.992 for postoperative overall survival of 3 years, a sensitivity of 0.629, a specificity of 0.996 in the training dataset, an AUC of 0.723 for postoperative overall survival of 3 years, a sensitivity of 0.177, a specificity of 0.948 in the validation dataset. (4) Construction and evaluation of COX nomogram prediction model. ① Analysis of postoperative survival factors of HCC patients in the training dataset. Results of univariate analysis showed that HBeAg, alpha fetoprotein (AFP), preoperative blood transfusion, maximum tumor diameter, liver capsule invasion, and degree of tumor differentiation were related factors for postoperative survival of HCC patients [ hazard ratio ( HR)=1.958, 1.878, 2.170, 1.188, 2.052, 0.222, 95% confidence interval ( CI): 1.185-3.235, 1.147-3.076, 1.389-3.393, 1.092-1.291, 1.240-3.395, 0.070-0.703, P<0.05]. Clinico-pathological data with P<0.2 were included for Lasso regression analysis, and the results showed that age, HBeAg, AFP, surgical procedure, perioperative blood transfusion, maximum tumor diameter, tumor located at liver segment Ⅴ or Ⅷ, liver capsule invasion, and degree of tumor differentiation as high differentiation, moderate-high differentiation, moderate differentiation, moderate-low differentiation were related factors for postoperative survival of HCC patients. The above factors were included for further multivariate COX analysis, and the results showed that HBeAg, surgical procedure, maximum tumor diameter were independent factors affecting postoperative survival of HCC patients ( HR=1.770, 8.799, 1.142, 95% CI: 1.049- 2.987, 1.203-64.342, 1.051-1.242, P<0.05). ② Construction and evaluation of COX nomogram prediction model: the clinicopathological factors of P≤0.1 in the COX multivariate analysis were induced to Rstudio software and rms software package to construct COX nomogram prediction model in the training dataset. The COX nomogram prediction model for predicting postoperative overall survival had an consistency index of 0.723 (se=0.028), an AUC of 0.760 for postoperative overall survival of 3 years in the training dataset, an AUC of 0.795 for postoperative overall survival of 3 years in the validation dataset. The verification of the calibration plot in the training dataset showed that the COX nomogram prediction model had a good prediction performance for postoperative survival. COX nomogram score=0.627 06×HBeAg (normal=0, abnormal=1)+ 0.134 34×maximum tumor diameter (cm)+ 2.107 58×surgical procedure (laparoscopy=0, laparotomy=1)+ 0.545 58×perioperative blood transfusion (without blood transfusion=0, with blood transfusion=1)-1.421 33×high differentiation (non-high differentiation=0, high differentiation=1). The COX nomogram risk scores of all patients were calculated. Xtile software was used to find the optimal threshold of COX nomogram risk scores. Patients with risk scores ≥2.9 were assigned into high risk group, and patients with risk scores <2.9 were assigned into low risk group. Results of Kaplan-Meier overall survival curve showed a significant difference in the postoperative overall survival between low risk group and high risk group of the training dataset ( χ2=33.065, P<0.05). There was a significant difference in the postoperative overall survival between low risk group and high risk group of the validation dataset ( χ2=6.585, P<0.05). Results of further analysis by the decision-making curve showed that COX nomogram prediction model based on the combination of HBeAg, surgical procedure, perioperative blood transfusion, maximum tumor diameter, and degree of tumor differentiation was superior to any of the above individual factors in prediction performance. (5) Evaluation of prediction performance between RF machine learning algorithm prediction model and COX nomogram prediction model: prediction difference between two models was investigated by analyzing maximun tumor diameter (the important variable shared in both models), and by comparing the predictive error curve of both models. The results showed that the postoperative 3-year survival rates predicted by RF machine learning algorithm prediction model and COX nomogram prediction model were 77.17% and 74.77% respectively for tumor with maximum diameter of 2.2 cm ( χ2=0.182, P>0.05), 57.51% and 61.65% for tumor with maximum diameter of 6.3 cm ( χ2=0.394, P>0.05), 51.03% and 27.52% for tumor with maximum diameter of 14.2 cm ( χ2=12.762, P<0.05). With the increase of the maximum tumor diameter, the difference in survival rates predicted between the two models turned larger. In the validation dataset, the AUC for postoperative overall survival of 3 years of RF machine learning algorithm prediction model and COX nomogram prediction model was 0.723 and 0.795, showing a significant difference between the two models ( t=3.353, P<0.05). Resluts of Bootstrap cross-validation for prediction error showed that the integrated Brier scores of RF machine learning algorithm prediction model and COX nomogram prediction model for predicting 3-year survival were 0.139 and 0.134, respectively. The prediction error of COX nomogram prediction model was lower than that of RF machine learning algorithm prediction model. Conclusion:Compared with machine learning algorithm prediction models, the COX nomogram prediction model performs better in predicting 3 years postoperative survival of HCC, with fewer variables, which is easy for clinical use.
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Objective To determine the clinicopathological risk factors and reliable biochemical predictors of the development of hypoparathyroidism after total thyroidectomy plus central compartment node dissection in papillary thyroid carcinoma (PTC).Methods A study was performed on 93 patients who underwent a total thyroidectomy with central compartment node dissection due to PTC.The rate of hypoparathyroidism was calculated.We evaluated the correlations between hypoparathyroidism and clinicopathological factors by chi-square test and logistic regression model for multivariate analysis.The prediction value of PTH and serum calcium level was assessed by a 2×2 contingency table and ROC curve analysis.Results Postoperative hypoparathyroidism was found in 46 patients (49.5%) and 2 with permanent hypoparathyroidism.Univariate analysis showed that tumor size (P=0.034),perithyroidal extension (P=0.003),bilateral cancer(P=0.045)and bilateral central neck dissection (P=0.028)were risk factors for postoperative hypoparathyroidism in patients with PTC.Multivariate analysis showed that perithyroidal extension (P=0.003) and bilateral central neck dissection(P=0.044)were independent risk factors for postoperative hypoparathyroidism in patients with PTC.ROC curve analysis showed that PTH level in the first after operation played significant roles in predicting hypoparathyroidism(AUC 0.875).Conclusions Hypoparathyroidism is the most common complication after total/near-total thyroidectomy.Perithyroidal extension and bilateral central neck dissection are the important risk factors of hypoparathyroidism.The level of PTH is a reliable and early predictive indicator of postoperative hypoparathyroidism.
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The treatment of breast cancer is becoming more individualized and minimally invasive,which makes sentinel lymph node biopsy becoming the standard treatment for axillary in patients with early-stage breast cancer who are negative in clinical axillary lymph nodes.Tracers image sentinel lymph nodes or lymphatic vessels for the successful detection of sentinel lymph node biopsy.Tracers selection is also more diverse,such as nano carbon mixed suspension,methylene blue,radioisotope,indocyanine green,etc.Different tracers and combined applications have their advantages and limitations.As for the selection of tracing methods,many factors need to be weighed.
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Ductal carcinoma in situ (DCIS) is a precursor of invasive ductal breast cancer,and up to 40% of these lesions will progress to invasive disease if untreated.The micro-environment,genetic aberrations,signal pathways and epigenetics play important roles during the infiltration and transformation of DCIS.Further studies of the infiltration and transformation of DCIS will promote the accurate assessment and prognosis prediction of the patients with DCIS,for finding a comprehensive evaluation standard and the balance between the over and low treatment.
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Objective To investigate the clinical features,diagnosis and treatment strategies for primary retroperitoneal neurofibromas.Methods The clinical data of 7 patients with primary retroperitoneal neurofibromas admitted to Cancer Institute & Hospital,Chinese Academy of Medical Sciences,from Jan 2000 to Jul 2017,were retrospectively analyzed.Results The average age was (42 ± 11) years and six were female.6 cases were with solitary tumor and 1 case was with multiple tumors.Clinical symptoms and imaging were of no help in determining tumor type.All patients underwent surgical resection.Postoperative pathology confirmed retroperitoneal neurofibroma in all seven patients,including 1 case with neurofibromatosis type Ⅰ and retroperitoneal malignant peripheral nerve sheath tumor.On immunohistochemistry all of the tumors were S-100 protein positive.At the end of the follow-up period ranging from 14 months to 166 months,sevent patients were alive and two patients experienced tumor recurrence.The longest disease-free survival time was 166 months.Conclusion Primary retroperitoneal neurofibromas are a rare type of primary retroperitoneal tumors that require diagnosis at pathology.Clinical symptoms and imaging of primary retroperitoneal neurofibromas patients were found to be ineffective at determining tumor type.Patients had a good prognosis after tumor resection.
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Objective@#To investigate the correlation between postoperative peripheral blood neutrophil to lymphocyte ratio (NLR) and recurrence and prognosis of patients with hepatocellular carcinoma (HCC).@*Methods@#The clinicopathological and follow-up data of 344 patients with HCC who underwent radical liver resection from May 2010 to April 2014 were analyzed retrospectively.@*Results@#Of the 344 patients, 104 had early recurrence and 84 had late recurrence. Receiver operating characteristic (ROC) curve analysis showed that the NLR predicted area under the curve (AUC) of early recurrence was 0.622 (P<0.001), the optimal cut-off value was 2.41. The AUC of late recurrence was 0.634 (P=0.001), the optimal cut-off value was 2.15. Cox multivariate analysis showed the serum concentration of hepatitis B surface antigen (HR=2.508, 95% CI: 1.311-4.798), microvascular invasion (HR=2.422, 95% CI: 1.239-4.734), Milan criteria (HR=2.373, 95% CI: 1.427-3.948) and postoperative NLR (HR=2.285, 95% CI: 1.379-3.788) were independent risk factors of early recurrence after HCC resection. Postoperative NLR (HR=2.927, 95% CI: 1.630-5.255), liver cirrhosis (HR=2.531, 95% CI: 1.291-4.962) and serum concentration of albumin (HR=2.257, 95% CI: 1.251-4.073) were independent risk factors of late recurrence after HCC resection. The median recurrence-free survival (RFS) of the 344 patients was 45.0 months, and the median overall survival (OS) was 63.2 months. ROC curve analysis showed that the postoperative NLR predicted 5-year survival AUC was 0.689 (P<0.05), with an optimal cutoff of 2.29. Cox multivariate analysis showed microvascular invasion (HR=2.247, 95% CI: 1.534-3.291), postoperative NLR (HR=2.217, 95% CI: 1.653-2.974), and liver cirrhosis (HR=1.685, 95% CI: 1.168-2.431), Milan criteria (HR=1.679, 95% CI: 1.238-2.277), serum concentration of hepatitis B surface antigen (HR=1.623, 95% CI: 1.102-2.392), serum concentration of albumin (HR=1.43, 95% CI: 1.066-1.918) were independent factors of RFS after HCC resection, while microvascular invasion (HR=3.862, 95% CI: 2.407-6.197), Barcelona staging (HR=2.864, 95% CI: 1.600-5.125), postoperative NLR (HR=2.688, 95% CI: 1.782-4.055), liver cirrhosis (HR=2.039, 95% CI: 1.184-3.514), serum concentration of albumin (HR=1.81, 95% CI: 1.204-2.720) were independent factors of OS.@*Conclusions@#For HCC patients who receive radical liver resection, postoperative NLR ≥2.29 implicates poor prognosis. Moreover, postoperative NLR ≥2.41 suggests early recurrence, while NLR ≥2.15 suggests late recurrence.
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Objective@#To investigate the clinical value of intraoperative radiofrequency ablation (RFA) in the treatment of colorectal liver metastasis (CLM).@*Methods@#A retrospectively analysis of 187 patients with CLM who underwent liver resection with or without RFA from January 2009 to August 2016 in Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences was performed. According to whether RFA was used intraoperatively, patients were divided into resection only group and combined treatment group. The clinical and pathological characteristics of the two groups were compared to explore factors influencing survival and recurrence. Imbalance of background characteristics between the two groups was further overcome by propensity score matching method (PSM).@*Results@#The number of liver metastases (267), simultaneous liver metastases (100%), bilobar involvement (73.3%) and preoperative chemotherapy (93.3%) rates were significantly higher in the combined treatment group than those in the resection only group(471, 74.7%, 42.0% and 63.1%)(all P<0.05). In the combined treatment group, median overall survival (OS) was 25.7 months; and 3-year and 5-year OS were 47.9% and 28.8%, respectively. In the resection only group, the median survival time was 46.9 months; and 3-year and 5-year OS rate was 59.1% and 42.4%, respectively (χ2=4.579, P=0.034). Median disease-free survival (DFS) was 5.4 months in the combined treatment group, and 10.1 months in the resection only group (χ2=5.399, P=0.023). In multivariate analysis, intraoperative RFA was not an independent prognostic factor for OS and DFS (HR=0.98, 95%CI: 0.47-2.08, P=0.965; HR=1.21, 95%CI: 0.71-2.07, P=0.465). After PSM, the median OS of the resection only and the combined treatment groups were 30.2 and 25.7 months (χ2=0.876, P=0.350). The median DFS in the two groups was 5.3 and 4.2 months, respectively (χ2=0.199, P=0.650).@*Conclusion@#In patients with similar tumor burden, liver resection combined with intraoperative RFA for unresectable CLM can achieve long-term outcomes similar to hepatectomy alone for resectable CLM.
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Objective@#To establish a new scoring system based on the clinicopathological features of hepatocellular carcinoma (HCC) to predict prognosis of patients who received hepatectomy.@*Methods@#A total of 845 HCC patients who underwent hepatectomy from 1999 to 2010 at Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. 21 common clinical factors were selected in this analysis. Among these factors, the cut-off values of alpha-fetoprotein (AFP), alkaline phosphatase (ALP) and intraoperative blood loss were evaluated by using a receiver operating characteristic (ROC) curve analysis.The Kaplan-Meier method and Cox regression model were used to evaluate the independent risk factors associated with the prognosis of HCC patients after hepatectomy. HCC postoperatively prognostic scoring system was established according to the minimum weighted method of these independent risk factors, and divided the patients into 3 risk groups, including low-risk, intermediate-risk and high-risk group. The relapse-free survival (RFS) and overall survival (OS) were compared among these groups.@*Results@#The univariate analysis showed that clinical symptoms, preoperative α-fetoprotein (AFP) level, serum alkaline phosphatase (ALP) level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with median RFS of these HCC patients (P<0.05). Alternatively, clinical symptoms, preoperative AFP level, serum ALP level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological lymphocyte invasion, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with the median OS of these HCC patients (P<0.05). The multivariate analysis showed that AFP ≥20 ng/ml, clinical symptoms, tumor diameter ≥5 cm, multiple tumors, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, moderate and severe liver cirrhosis, non- anatomic resection were the independent risk factors of RFS and OS (P<0.05). The independent risk factor of RFS was intraoperative bleeding loss ≥325 ml (P<0.05); The independent risk factors of OS were abdominal lymph node metastasis and pathological tumors thrombus (P<0.05). The respective weight of 11 independent factors was used to establish the scoring system (scores range from 0 to 26). In the score system, 0 to 5 points were defined as the low-risk group (286 cases), 6 to 12 points were determined as the intermediate-risk group (503 cases), more than 13 points were classified as the high-risk group (56 cases). The median RFS of the low-risk, intermediate-risk and high-risk group were 80, 27 and 6 months, respectively. The differences were statistically significant (P<0.001). The median OS of the three groups were 134, 51 and 15 months, respectively, and the differences were statistically significant (P<0.001).@*Conclusion@#This new score system provides effective prediction of postoperative prognosis for HCC patients.
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The cyclin-dependent protein kinase 9 (CDK9) is a member of the family of cyclin-dependent protein kinases.Different from other CDKs,CDK9 mainly works on the transcription regulation and has no affects on the cell cycle progress.There are many kinds of CDK9 inhibitors in the clinical research.The detailed structure and action mechanism of CDK9,its difference of protein structure from other CDKs,several selective or nonselective CDK9 inhibitors,as well as their structure-activity relationship (SAR) are discussed in this paper.
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Objective To investigate the effect of nano carbon tracer for protecting parathyroid function in the surgery of thyroid cancer.Methods A total of 178 patients with thyroid cancer admitted in our hospital from Jun.2014 to Mar.2016 were collected and divided into the control group and the observation group according to the random number table method,89 cases in each group.The control group received routine surgery,while the observation group received nanocarbon suspension during surgery.The levels of serum parathyroid hormone and serum calcium in the 2 groups were measured at 3 days after surgery,and the patients with low parathyroid hormone,normal parathyroid hormone and low calcium were counted.Results The rate of ormal serum calcium in the observation group was 91.01%(81/89),significantly higher than 67.42%(60/89) in the control group (P< 0.05).The rate of normal parathyroid hormone in observation group was 94.38% (84/89),significantly higher than 64.04% (57/89) in the control group (P<0.05).Conclusion The nano carbon tracer is helpful for protection of parathyroid function in the surgery of thyroid cancer.
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@#To strengthen the quality control of palbociclib, three related substances were separated from the bulk drug. These substances were identified as 8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido [2, 3-d] pyrimidin-7(8H)-one(A), 8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridine-2-yl)amino)-6-vinylpyrido [2, 3-d] pyrimidin-7(8H)-one(B), tert-butyl4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7, 8-dihydropyrido [2, 3-d] pyrimidin-2-yl)amino)pyridin-3-yl)piperazi-ne-1-carboxylate(C). Based on the structures of the impurities, the possible routes to them were discussed, and their structures were elucidated by 1H NMR and MS.