[Role of neoadjuvant rectal score in prognosis and adjuvant chemotherapy decision-making in locally advanced rectal cancer following neoadjuvant short-course radiotherapy and consolidation chemotherapy].

Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS). Results: Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% (P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status (HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy (HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not (P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions: The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

[A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors].

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

Apolipoprotein C1 promotes tumor progression in gastric cancer.

Background: Gastric cancer (GC) is a malignancy with the worst prognosis that seriously threatens human health, especially in East Asia. Apolipoprotein C1 (apoc1) belongs to the apolipoprotein family. In addition, apoc1 has been associated with various tumors. However, its role in GC remains unclear. Methods: Firstly, we quantified its expression in GC and adjacent tumor tissues, using The Cancer Genome Atlas (TCGA). Next, we assessed cell invasion and migration abilities. Finally, we revealed the role of apoc1 in the tumor microenvironment (TME), immune cell infiltration and drug sensitivity. Results: Firstly, in TCGA database, it has been shown that elevated expression of apoc1 was identified in various cancers, including GC, then we found that high expression of apoc1 was significantly correlated with poor prognosis in GC. Histologically, apoc1 expression is proportional to grade, cancer stage, and T stage. The experimental results showed that apoc1 promoted cell invasion and migration. Then GO, KEGG, and GSEA pathway analyses indicated that apoc1 may be involved in the WNT pathway and immune regulation. Furthermore, we found out the tumor-infiltrating immune cells related to apoc1 in the tumor microenvironment (TME) using TIMER. Finally, we investigated the correlation between apoc1 expression and drug sensitivity, PD-1 and CTLA-4 therapy. Conclusions: These results suggest that apoc1 participates in the evolution of GC, and may represent a potential target for detection and immunotherapy in GC.

Evaluación de la supervivencia de los pacientes con cáncer de recto metastásico mediante parámetros radiómicos y volumétricos de la PET/TC con [18F]FDG de estadificación / Evaluation of the survival of patients with metastatic rectal cancer by staging [18F]FDG PET/CT radiomic and volumetric parameters

Objetivo El objetivo de este estudio es predecir el pronóstico de pacientes con cáncer de recto metastásico (CRM) mediante la obtención de un modelo con algoritmos de aprendizaje automático (AA) a través de datos volumétricos y radiómicos obtenidos de la PET/TC basal. Métodos Pacientes con CRM que se sometieron a imágenes PET/TC con [18F]FDG para estadificación en nuestro hospital entre enero 2015 y enero de 2021 se evaluaron mediante el software LIFEx. El volumen de interés (VOI) del tumor primario fue generado. Además, se evaluaron los valores del volumen metabólico tumoral total (tMTV) y la glucólisis de lesión total (TLG) de los focos tumorales en todo el cuerpo. Se evaluaron los datos clínicos y radiómicos con algoritmos de AA para crear un modelo que predijera la supervivencia. Se investigaron asociaciones significativas entre estas características y la supervivencia a 1 y 2 años. Resultados El algoritmo de bosque aleatorizado fue el algoritmo más exitoso para predecir la supervivencia a 2 años (AUC: 0,843; PRC: 0,822 y CCM: 0,583). Los valores de tMTV y tTLG tuvieron éxito en la predicción de la supervivencia a un año (p 0,002 y 0,007, respectivamente). Conclusiones Además del importante papel de la PET/TC con [18F]FDG en la estadificación de pacientes con CRM, este estudio muestra que es posible predecir la supervivencia con métodos de AA, con parámetros obtenidos mediante el análisis de textura a partir del tumor primario y parámetros volumétricos de todo el cuerpo (AU)

Objective The aim of this study was to predict the prognosis in patients with metastatic rectal cancer (mRC) by obtaining a model with machine learning (ML) algorithms through volumetric and radiomic data obtained from baseline 18-Fluorine Fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) images. Methods Sixty-two patients with mRC who underwent [18F]FDG PET/CT imaging for staging between January 2015 and January 2021 were evaluated using LIFEx software. The volume of interest (VOI) of the primary tumor was generated and volumetric and textural features were obtained from this VOI. In addition, the total metabolic tumor volume (tMTV) and total lesion glycolysis (TLG) values of tumor foci in the whole body were evaluated. Clinical and radiomic data were evaluated with ML algorithms to create a model that predicts survival. Significant associations between these features and 1- and 2-year survival were investigated. Results The random forest algorithm was the most successful in predicting 2-year survival (AUC: 0.843, precision-recall curve: 0.822 and Matthew's correlation coefficient: 0.583). The model obtained with this algorithm was able to predict 49 patients with 79.03% accuracy. While tMTV and TLG values were successful in predicting 1-year survival (p: 0.002 and 0.007, respectively), texture characteristics of the primary tumor did not show a significant relationship with 1-year survival. Conclusions In addition to the important role of [18F]FDG PET/CT in staging patients with mRC, this study shows that it is possible to predict survival with ML methods, with parameters obtained using texture analysis of the primary tumor and whole body volumetric parameters (AU)

[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

Effects of dietary carnitine supplementation on semen output and quality of boars.

Carnitine is an amino acid derivative that performs the functions of increasing energy production as well as acting as an antioxidant for sperm cells. This study was conducted to investigate the effects of the inclusion of carnitine in boar diets on semen output and quality. Sixty-four purebred and hybrid boars at a commercial boar stud were blocked by age and semen quality and randomly allotted to receive a daily 30 g top-dress of either soybean meal (CON) or soybean meal and 625 mg of L-Carnitine (CARN). Supplementation lasted for 12 weeks from May to July 2021 during which weekly semen collection was performed. Semen was evaluated in the stud for concentration and motility parameters using computer-assisted semen analysis (CASA). Samples were shipped to Purdue University for detailed morphology, viability, and CASA analysis performed in samples stored at 17 °C for 5 days. PROC Mixed (SAS v 9.4) was used to analyze data, with boar nested within treatment used in repeated measures analysis. Semen quality estimates from the week before supplementation were used as covariates in the statistical model. Tukey-Kramer adjustment was used for means separation. Carnitine supplementation had no effects on total sperm produced (P = 0.35). Percentage of motile sperm cells (P = 0.63), morphologically normal sperm (P = 0.42), viable sperm (P = 0.43), or sperm with normal acrosomes (P = 0.61) in the ejaculates were not different among treatments. Sperm kinematics in CARN ejaculates tended to have greater straight-line velocity and distance (P = 0.06 and P = 0.07, respectively). There were several interactions of treatment and day of storage for the kinematic parameters. However, these interactions do not show observable trends for CARN to improve or depress sperm function. Overall, the inclusion of 625 mg/d of carnitine in the diet of boars for 12 weeks had no effects on sperm output or quality with minor changes to sperm cell kinematics.

¿Existe asociación del tiempo entre el urocultivo y la cirugía intrarrenal retrógrada y la tasa de síndrome de respuesta inflamatoria sistémica? / Does time elapsed between urine culture and retrograde intrarenal surgery affect the rate of systemic inflammatory response syndrome?

Objetivo: Identificar los factores preoperatorios e intraoperatorios que podrían causar el síndrome de respuesta inflamatoria sistémica (SRIS) tras la cirugía intrarrenal retrógrada (CRIR) y estudiar el efecto del tiempo de espera entre la fecha del urocultivo vesical preoperatorio (UCVP) y la fecha de la cirugía en el SRIS postoperatorio.Materiales y métodos: La población objetivo la constituyeron 467 pacientes intervenidos mediante CRIR entre enero de 2013 y junio de 2020. Se obtuvieron UCVP de todos los pacientes antes de la cirugía. En el postoperatorio, los pacientes recibieron seguimiento estrecho en busca de fiebre y otros signos de SRIS. Se realizaron análisis de regresión logística univariante y multivariante para revelar los factores predictivos de SRIS después de CRIR.Resultados: La cohorte completa del estudio estaba formada por 467 pacientes. La tasa de SRIS fue del 5,6%. En el análisis univariante, la tasa de diabetes mellitus, los antecedentes de infección urinaria recurrente, el tiempo quirúrgico y la carga litiásica fueron factores predictivos significativos de SRIS. Según el análisis multivariante, la tasa de antecedentes de infección urinaria recurrente, el tiempo quirúrgico y la carga litiásica eran factores predictivos estadísticamente significativos. El tiempo transcurrido entre la fecha de realización del UCVP y la fecha de la cirugía fue el mismo en el grupo con SRIS y en el grupo normal.Conclusión: El intervalo de tiempo entre la fecha de realización del UCVP y la fecha de la cirugía no es un factor influyente para el SRIS. Aclarar esta cuestión mediante estudios prospectivos puede ayudar a resolver este problema con el que los endourólogos se enfrentan con frecuencia en la práctica diaria. (AU)

Objective: To identify the preoperative and intraoperative factors that might cause systemic inflammatory response syndrome (SIRS) after retrograde intrarenal surgery (RIRS), and to investigate the effect of time elapsed between the date of performing preoperative bladder urine culture (PBUC) and surgery date on postoperative SIRS.Materials and methods: Four hundred sixty-seven patients who had RIRS between January 2013 and June 2020 constituted the target population of this study. PBUC were obtained from all patients before undergoing surgery. Postoperatively, patients were closely monitored for fever and other signs of SIRS. Univariate and multivariate logistic regression analysis were performed to reveal the predictive factors for SIRS after RIRS.Results: The entire study cohort consisted of 467 patients. The rate of SIRS was 5.6%. In univariate analysis, the rate of diabetes mellitus, recurrent urinary tract infection history, surgical time, and stone burden were significant predictive factors for SIRS. In multivariate analysis, the rate of recurrent urinary tract infection history, surgical time and stone burden were observed to be statistically significant predictive factors. Time elapsed between the date of performing PBUC and surgery date was not different between the SIRS group and the normal group.Conclusion: We conclude that the time between the date of performing PBUC and surgery date is not an influential factor for SIRS. Clarifying this issue with prospective studies may be useful, as endourologists frequently encounter this situation in daily practice. (AU)

[Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase â ¡ trial].

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

Proton pump inhibitor therapy and risk of knee replacement surgery: a general population-based cohort study.

OBJECTIVE: Proton pump inhibitors (PPIs) are among the most commonly used medications for patients with osteoarthritis (OA). Various types of PPIs have different impacts on lowering serum magnesium level that may affect knee OA progression. We aimed to compare the risk of clinically relevant endpoint of knee replacement (KR) among initiators of five different PPIs with that among histamine-2 receptor antagonist (H2RA) initiators. DESIGN: Among patients with knee OA (≥50 years) in The Health Improvement Network database in the UK we conducted five sequential propensity-score matched cohort studies to compare the risk of KR over 5-year among patients who initiated omeprazole (n = 2,672), pantoprazole (n = 664), lansoprazole (n = 3,747), rabeprazole (n = 751), or esomeprazole (n = 827) with those who initiated H2RA. RESULTS: The prevalence of PPI prescriptions among participants with knee OA increased from 12.7% in 2000-44.0% in 2017. Two-hundred-and-seventy-four KRs (30.8/1,000 person-years) occurred in omeprazole initiators and 230 KRs (25.4/1,000 person-years) in H2RA initiators. Compared with H2RA initiators, the risk of KR was 21% higher in omeprazole initiators (hazard ratio [HR] = 1.21,95% confidence interval [CI]:1.01-1.44). Similar results were observed when pantoprazole use was compared with H2RA use (HR = 1.38,95%CI:1.00-1.90). No such an increased risk of KR was observed among lansoprazole (HR = 1.06,95%CI:0.92-1.23), rabeprazole (HR = 0.97,95%CI:0.73-1.30), or esomeprazole (HR = 0.83,95%CI:0.60-1.15) initiators compared with that among H2RA initiators. CONCLUSIONS: In this population-based cohort study, initiation of omeprazole or pantoprazole use was associated with a higher risk of KR than initiation of H2RA use. This study raises concern regarding an unexpected risk of omeprazole and pantoprazole on accelerating OA progression.

[Treatment and prognostic analysis of isolated chest wall recurrence of breast cancer after mastectomy].

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.

[Comparison of preoperative chemotherapy with concurrent chemoradiotherapy combined with TME for 305 patients with locally advanced rectal cancer].

Objective: To retrospectively analyze the long-term efficacy and prognostic factors of preoperative chemotherapy (PCT) or chemoradiotherapy (PCRT) combined with total mesorectal excision in locally advanced rectal cancer. Methods: Clinical pathology data of 305 patients with localized advanced rectal cancer admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from 2006 to 2018 were collected, of whom 246 patients received PCRT (PCRT group), 59 patients received PCT (PCT group). Kaplan-Meier and Log rank test were used for the survival analysis, Cox regression model was used for multivariate analysis, and the prognosis of two groups of patients were compared by the propensity score matching (PSM). Results: In the whole group of 305 patients, 20 cases of tumors located in the upper part of the rectum and at the junction of rectum and colon, 96 cases in the middle of the rectum and 189 cases in the lower part of the rectum. PCRT group included 38 cases of cT2-3 phase, 11 cases of cT4a stage, 10 cases of cT4b stage, while the cases in PCT group were 184, 0 and 62 cases, respectively, the difference is statistically significant (P<0.05). The R0 excision rates of PCRT group and PCT group were 100% (246/246) and 96.6% (57/59), respectively, and the total pathological remission rates were 13.4% and 3.3%, respectively (P<0.05). After PSM, the 3-year survival rates of PCRT group and the PCT group were 86.6% and 89.9% (P>0.05), respectively, and the progression-free survival rates were 74.6% and 77.2% (P>0.05), local recurring free survival rates were 100% and 92.3% (P>0.05), distant metastasis free survival rate were 75.6% and 77.3% (P>0.05). Pre-treatment N-positive, N-degeneration and MRF-positive were all associated with total survival (P<0.05). Conclusion: In the PCRT group, with a higher proportion of patients with stage T4b and lower rectal cancer, the long-term efficacy of PCRT was similar to that of PCT, and higher R0 excision rate and pathological complete response rate could be obtained.

[Long-term efficacy and safety of simultaneous integrated boost radiotherapy in non-operative esophageal squamous cell carcinoma: a multicenter retrospective data analysis (3JECROG R-05)].

Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

The function of floral traits and phenotypic selection in Aconitum gymnandrum (Ranunculaceae).

Floral evolution in angiosperms is thought to be driven by pollinator-mediated selection. Understanding flower integration and adaptation requires resolving the additive and nonadditive contributions of floral pollinator attraction and pollination efficiency traits to fitness components. In this study, a flower manipulation experiment with a factorial design was used to study the adaptive significance of galea height (a putative attraction trait) and entrance width (a putative efficiency trait) in Aconitum gymnandrum Maxim. flowers. Simultaneously, phenotypic selection analysis was conducted to examine selection by pollinators on galea height, entrance width, nectar production and plant height. Increased galea height increased the pollinator visitation rate, which confirmed its attractiveness function. Increasing floral entrance width by spreading the lower sepals increased the seed number per fruit without affecting pollinator visitation. This suggests a pollination efficiency role for the entrance width. The phenotypic selection analysis, however, did not provide evidence of pollinator-mediated selection for either of these traist, but it did for plant height. According to the manipulation treatment and correlational selection results, the combined variation in galea height and entrance width of A. gymnandrum flowers did not have nonadditive effects on female reproductive success. This study demonstrated the adaptive value of A. gymnandrum flowers through manipulation of an attractiveness trait and an efficiency trait. However, neither trait was associated with pollinator-mediated selection. A combination of manipulating traits and determining current phenotypic selection could help to elucidate the mechanism of selection on floral traits involved in different functions and flower integration.

A survey of values and related factors among 200 guardians of children with epilepsy.

OBJECTIVES: Epilepsy is a common disease in the pediatric neurology department; as it a chronic disease, many years are spent seeing doctors and taking drugs. The objective of the study is to understand the values of parents to help doctors to more effectively communicate and to improve patient compliance. STUDY DESIGN: The study was designed to investigate guardians' values of children with epilepsy and analyze the relevant factors that may affect these values and the correlation of the guardians' values and medical decision making. METHODS: Two hundred guardians (93 men and 107 women) of children with epilepsy from three hospitals in Wuhan, China, were selected at random and investigated by means of interview survey. Statistical analysis by ratio was conducted on the general data, whereas statistical analyses by Pearson and Spearman rank correlation were conducted for the relative factors. RESULTS: A high educational level among male guardians indicated a strong tendency to read up on epilepsy, which influenced their care given. A high educational level among female guardians indicated better capability to take care of child patients and follow directions for antiepileptic drug administration. Female guardians were more likely to see the same doctors during a long disease period than male guardians. CONCLUSION: The guardians' values were influenced by many factors, such as gender, education, and duration of disease. Guardians' values need to be considered as they are helpful for doctors in decision-making.

Does smoking cessation increase risk of knee replacement? a general population-based cohort study.

OBJECTIVE: Smoking represents a major issue for global public health. Owing to methodologic challenges, findings of an association between smoking and risk of knee osteoarthritis (OA) are inconsistent. We sought to assess the relation of onset of smoking cessation to the risk of OA sequelae, i.e., knee replacement, and to perform sub-cohort analysis according to weight change after smoking cessation. DESIGN: Using The Health Improvement Network, we conducted a cohort study to examine the association between smoking cessation and risk of knee replacement among patients with knee OA. Participants who stopped smoking were further grouped into three sub-cohorts: weight gain (body mass index [BMI] increased>1.14 kg/m2), no substantial weight change (absolute value of BMI change<1.14 kg/m2), and weight loss (BMI loss>1.14 kg/m2) after smoking cessation. RESULTS: We identified 108 cases of knee replacement among 1,054 recent quitters (26.7/1,000 person-years) and 1,108 cases among 15,765 current smokers (17.4/1,000 person-years). The rate difference of knee replacement in recent quitter cohort vs current smoker cohort was 10.4 (95% confidence interval [CI]:5.3-15.6)/1,000 person-years and the adjusted hazard ratio (HR) was 1.30 (95%CI:1.05-1.59). Compared with current smokers, risk of knee replacement was higher among quitters with weight gain (HR = 1.42,95%CI:1.01-1.98), but not among those with no substantial weight change (HR = 1.29,95%CI:0.90-1.83) or those with weight loss (HR = 1.11,95%CI:0.71-1.75). CONCLUSIONS: Our large population-based cohort study provides the first evidence that smoking cessation was associated with a higher risk of knee replacement among individuals with knee OA, and such an association was due to weight gain after smoking cessation.

Automation and control of laser wakefield accelerators using Bayesian optimization.

Laser wakefield accelerators promise to revolutionize many areas of accelerator science. However, one of the greatest challenges to their widespread adoption is the difficulty in control and optimization of the accelerator outputs due to coupling between input parameters and the dynamic evolution of the accelerating structure. Here, we use machine learning techniques to automate a 100 MeV-scale accelerator, which optimized its outputs by simultaneously varying up to six parameters including the spectral and spatial phase of the laser and the plasma density and length. Most notably, the model built by the algorithm enabled optimization of the laser evolution that might otherwise have been missed in single-variable scans. Subtle tuning of the laser pulse shape caused an 80% increase in electron beam charge, despite the pulse length changing by just 1%.

[Epidemic situation of malaria in Yunnan Province from 2014 to 2019].

OBJECTIVE: To investigate the epidemiological characteristics of malaria and implementation of the "1-3-7" approach in malaria elimination in Yunnan Province, so as to provide the data support for the development of post-elimination surveillance interventions. METHODS: All data pertaining to malaria cases in Yunnan Province from 2014 to 2019 were captured from the Notifiable Disease Reporting System of Chinese Center for Disease Control and Prevention, and the changes in the epidemic situation of malaria were analyzed during the 5-year period. In addition, the core indexes regarding the "1-3-7" approach in malaria elimination of Yunnan Province from 2014 to 2019 were retrieved from the Malaria Control System in the Parasitic Disease Information Reporting System, and all changes in the indexes were descriptively analyzed. RESULTS: During the period from 2014 to 2019, a total of 2 283 malaria cases were reported in Yunnan Province, including 1 927 cases with vivax malaria, 326 cases with plasmodium malaria, 29 cases with other species of malaria, and one case with unidentified species. There were 64 local cases, 2 219 overseas imported cases. Among the 2 283 malaria cases, the male/female ratio was 4.58∶1, and 80.25% of the cases were aged from 15 to 50 years. Farmer (70.00%) was the predominant occupation, and 76.70% (1 751/2 283) of the cases were identified in 25 border counties (districts). Malaria cases were reported in each month during the 5-year period, and the number of malaria cases increased from April, peaked on May to July, and started to decline on August. From 2014 to 2019, the reporting rate of malaria cases within 24 hours upon diagnosis was 100%, and the detection of malaria cases was 99.69% (2 276/ 2 283) in the laboratory, with a 99.65% (2 275/2 283) rate of definite diagnosis. In addition, the percentage of individual epidemiological investigations within 3 days was 100.00% (2 283/2 283), and the number of epidemic foci survey and treatment within 7 days was 576 during the 3-year period from 2017 to 2019. The goal of malaria elimination was achieved in Yunnan Province on June, 2020. CONCLUSIONS: Malaria has been eliminated in Yunnan Province, and management of overseas imported malaria is the primary challenge to consolidate the malaria elimination achievements in the future. However, the approach in malaria elimination remains to be maintained, and the role of the Yunnan Provincial Malaria Diagnostic Reference Laboratory requires to be strengthened.