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.

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.

Objective:To explore the patterns of failure after postoperative intensity-modulated radiotherapy for gastric cancer.Methods:Clinical data of patients diagnosed with gastric cancer or gastroesophageal junction carcinoma with pathological stages T 3-4N 0 or T xN 1-3 admitted to Cancer Hospital of Chinese Academy of Medical Sciences from May 2009 to December 2018 were retrospectively analyzed. All patients received postoperative radiotherapy. During the follow-up, tumor recurrence was confirmed by imaging or endoscopic or pathological data, etc. According to the location of tumor recurrence, recurrence patterns were divided into local, regional and distant recurrence. Differences in recurrence patterns among different groups were compared using t-test and Chi-square test. Patient survival was assessed through Kaplan-Meier method. Results:A total of 76 patients were enrolled, with a median age of 49 years old (27-67 years old), 34 cases (45%) were classified as T 3 stage, 40 cases (53%) of T 4 stage, and 75 cases (99%) of N 1-3 stage, respectively. Seventy-three patients (92%) were classified as stage Ⅲ, and 38 patients (50%) underwent D2 dissection. The median follow-up time was 32.8 months (7.1-138.5 months). The median time of recurrence was 17.6 months (2.9-113.6 months). The median survival time after recurrence was 8.19 months (0.6-91.9 months). There were 13 cases (17%) of local recurrence, 6 cases (8%) of regional recurrence, and 72 cases (95%) of distant metastasis in patients. Peritoneal metastasis (33 cases, 43%) and distant lymph node metastasis (12 cases, 16%) were the main patterns of distant recurrence. Conclusions:By intensity-modulated radiotherapy technology, adjuvant radiotherapy yields favorable local and regional control for gastric cancer. Distant metastasis is still the main pattern of recurrence.

Objective:To evaluate the predictive value of hematological inflammatory markers such as preoperative monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and several tumor-related factors in differentiating malignant and benign primary retroperitoneal tumors (PRTs) .Methods:This study retrospectively collected the data of 159 pathologic confirmed PRTs patients who underwent surgery in the First Affiliated Hospital of Wenzhou Medical University and Taizhou Municipal Hospital between Dec. 2009 and Aug. 2020. Univariate analysis of clinic data was performed to identify the differences between the benign and malignant PRTs. Logistic regression analysis was used to determine the independent predictive parameters for malignant PRTs.Results:Among the 159 patients with PRTs, 80 were malignant, 68 were benign, and 11 were borderline. Contrast with benign and borderline tumor, univariate analysis demonstrated that tumor size, preoperative neutrophil count, platelet count, albumin level, MLR, NLR and PLR exhibited significant differences in malignant tumor (all P<0.05). PLR (HR=1.025, P=0.020) and tumor size (HR=1.085, P=0.006) were independent risk factors for predicting malignant PRTs in the multivariate logistic analyses. According to the ROC curve, the optimal cutoff value of tumor size and PLR for predicting malignant PRTs were 194.85 (sensitivity 38.7%, specificity 93.5%), 8.75 cm (sensitivity 69.3%, specificity 72.7%), respectively. Conclusions:Preoperative PLR is useful in differentiating malignant and benign PRTs and it is an independent risk parameter for malignant PRTs. Preoperative PLR could be considered as a new significant predictor for malignant PRTs.

Objective:To evaluate the predictive value of hematological inflammatory markers such as preoperative monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and several tumor-related factors in differentiating malignant and benign primary retroperitoneal tumors (PRTs) .Methods:This study retrospectively collected the data of 159 pathologic confirmed PRTs patients who underwent surgery in the First Affiliated Hospital of Wenzhou Medical University and Taizhou Municipal Hospital between Dec. 2009 and Aug. 2020. Univariate analysis of clinic data was performed to identify the differences between the benign and malignant PRTs. Logistic regression analysis was used to determine the independent predictive parameters for malignant PRTs.Results:Among the 159 patients with PRTs, 80 were malignant, 68 were benign, and 11 were borderline. Contrast with benign and borderline tumor, univariate analysis demonstrated that tumor size, preoperative neutrophil count, platelet count, albumin level, MLR, NLR and PLR exhibited significant differences in malignant tumor (all P<0.05). PLR (HR=1.025, P=0.020) and tumor size (HR=1.085, P=0.006) were independent risk factors for predicting malignant PRTs in the multivariate logistic analyses. According to the ROC curve, the optimal cutoff value of tumor size and PLR for predicting malignant PRTs were 194.85 (sensitivity 38.7%, specificity 93.5%), 8.75 cm (sensitivity 69.3%, specificity 72.7%), respectively. Conclusions:Preoperative PLR is useful in differentiating malignant and benign PRTs and it is an independent risk parameter for malignant PRTs. Preoperative PLR could be considered as a new significant predictor for malignant PRTs.

Objective:To explore the impacts of comprehensive geriatric assessment (CGA) on setup errors during the radiotherapy of elderly patients with rectal cancer.Methods:A total of 45 patients over 70 years of age and receiving radiotherapy were enrolled in the study. A comprehensive geriatric assessment was conducted before the radiotherapy. The enrolled patients had a median age of 77 years, including 28 male and 17 female cases. Meanwhile, 31 patients were determined to be in a good CGA status and 14 were determined to be in a poor CGA status, and 35 patients received radiotherapy in the prone position and 10 in the supine position. Cone beam CT (CBCT) was used for setup correction during radiotherapy. CBCT was performed daily in the first week and once a week from the second week. By fusing and aligning the CBCT images with simulation CT images according to the lumbar vertebra, setup errors in the left-right ( x axis), cranio-caudal ( y axis), and anterior-posterior ( z axis) directions were obtained. A total of 338 CBCT images were obtained. A generalized linear model was used to evaluate the effects of multiple factors on the setup errors. Results:During the radiotherapy, setup errors of all patients were (0.24±0.19) cm in the left-right direction, (0.33±0.25) cm in the cranio-caudal direction, and (0.19±0.15) cm in the anterior-posterior direction. The setup error in the cranio-caudal direction was more than that in the left-right direction and that in the anterior-posterior direction ( Z=-4.86, -7.72, P< 0.001). The setup error in the left-right direction was greater than that in the anterior-posterior direction ( Z=-2.79, P=0.005). The mean setup errors of the good and poor status groups in the left-right direction were (0.21 ± 0.17) and (0.30 ± 0.22) cm, respectively ( Z=2.16, P=0.031). There was no statistically significant difference in the setup errors between cranio-caudal direction and anterior-posterior direction ( P>0.05). The setup errors in the anterior-posterior direction were (0.17 ± 0.13) and (0.27 ± 0.19) cm, respectively for the prone and supine positions during the radiotherapy ( Z=2.85, P=0.004). There was no statistically significant difference in the setup errors between the left-right direction and the cranio-caudal direction ( P>0.05). Conclusion:The status of CGA elderly patients with rectal cancer affects the setup error in the left-right direction. It may be necessary to clinically adjust the PTV margin.

Objective:To compare the outcomes of watch&wait (W&W) strategy in patients with locally advanced rectal cancer who achieved complete clinical response (cCR) after neoadjuvant therapy, with those who obtained pathological complete response (pCR) after total mesorectal excision (TME).Methods:This is a retrospective cohort analysis study. Patients histologically proven with locally advanced rectal adenocarcinoma (stage Ⅱ-Ⅲ) who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing neoadjuvant therapy and follow-up ≥1 year (W&W group), and patients who did not have cCR but pCR after TME (pCR group). The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (NR-DFS), and organ preservation rate. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM).Results:A total of 118 patients were enrolled, 49 of whom had cCR and managed by W&W, 69 had pCR, with a median follow-up period of 49.5 months (12.1-79.9 months). No difference was observed in the 3-year OS (97.1% vs. 96.7%) and 5-year OS (93.8% vs. 90.9%, P=0.696) between the W&W and pCR groups. Patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs. 43.5%, P<0.001), better 3-year DFS (83.6% vs. 97.0%) and 5-year DFS (83.6% vs. 91.2%, P=0.047) compared with those achieving pCR. The 3-year NR-DFS (95.9% vs. 97.0%) and 5-year NR-DFS (92.8% vs. 97.0%, P=0.407) did not significantly differ between the W&W and pCR groups. Local regeneration occurred in six cases, and 87.7% of patients had successful rectum preservation in the W&W group. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs. 26.5%, P<0.001) was noted in the W&W group. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19.0 vs. 9.8 weeks, P<0.001). Conclusions:The oncological outcomes of W&W strategy in patients with locally advanced rectal cancer are safe and effective, significantly improving the quality of life. Longer interval for cCR evaluation may improve rectal organ preservation rate.

Objective:To analyze the gene variation and evolutionary characteristics of human parainfluenza virus 3 (HPIV3) circulating in China based on hemagglutinin-neuraminidase (HN) gene.Methods:Multiple qPCR was used to screen nucleic acid of common pathogens in throat swabs from acute respiratory tract infection cases in five provinces (Beijing, Zhejiang, Anhui, Henan, Hunan) from 2007 to 2020. Subsequently, the HN gene sequence of HPIV3 positive samples was determined and compared with the HN gene sequence of HPIV3 strains from 10 provinces in China and abroad in the GenBank database. The molecular evolution analysis was carried out using a variety of bioinformatics method.Results:A total of 49 strains of HPIV3 HN gene sequences were obtained from 5 provinces, with nucleotide homology ranging from 96.6% to 100%. Among them, 48 strains were subtype C3 and 1 strain was subtype C5. Phylogenetic analysis showed that there were co-epidemics of C1, C3 and C5 strains in 12 provinces of China during 2003—2020, and the nucleotide and amino acid homology among the strains were 95.4%-99.8% and 97.9%-100%, respectively. Among them, C3 is the dominant subtype in China, which is divided into five evolutionary branches of C3a, C3b, C3c, C3e and C3f, and the C3f has the widest range and time of spread. The evolutionary analysis of the C3 subtype showed that the estimated time to the most recent common ancestor (tMRCA) of it dated back to 1990, and its effective population size tended to be stable after expansion from 2002 to 2010. The HN gene evolution rate of the evolutionary branches of C3 HPIV3 varied from 3.69×10 -4 to 5.82×10 -4 substitutions/sites/year; the HN protein of C3 subtype strains shared four potential N-glycosylation sites N308, N351, N485 and N523, and the selection pressure was mainly negative. Conclusions:The C3 is an endemic dominant genotype, which has been widely spread and continuously circulating in China, and has formed different evolutionary clades during epidemic.

Objective:To investigate the efficiency and pharmacoeconomics of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for mobilization of peripheral blood stem cells (PBSCM) in patients with multiple myeloma (MM).Methods:The data of 91 patients with newly treated MM who were hospitalized in the First Hospital of Jilin University and Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 2015 to October 2017 were retrospectively analyzed. According to the patient's wishes, a high-dose chemotherapy combined with subcutaneous injection of PEG-rhG-CSF or recombinant human granulocyte colony-stimulating factor (rhG-CSF) was used for stem cell mobilization in 42 and 49 patients, respectively. The number of mononuclear cells (MNC) and CD34 + cells collected after mobilization, the maximum absolute neutrophil count (mANC), the cost of mobilization, and the engraftment time of white blood cells and platelets after transplantation were compared between the two groups. Results:The median number of MNC collected after mobilization in the PEG-rhG-CSF group and rhG-CSF group were 5.86×10 8/kg [(1.08-24.54)×10 8/kg] and 6.61×10 8/kg [(0.83-33.80)×10 8/kg], and the difference was not statistically significant ( U = 883.00, P = 0.245); while the median number of CD34 + cells collected after mobilization in the PEG-rhG-CSF group was higher than that in the rhG-CSF group [5.56×10 6/kg (0.94-19.90)×10 6/kg and 4.82×10 6/kg (1.12-14.61)×10 6/kg], and the difference was statistically significant ( U = 732.00, P = 0.038). The median number of mANC during mobilization in the PEG-rhG-CSF group was lower than that in the rhG-CSF group [20.50×10 9/L (7.26-61.30)×10 9/L and 32.08×10 9/L (6.92-69.99)×10 9/L], and the difference was statistically significant ( U = 490.00, P = 0.001). After autologous stem cell transplantation (ASCT), the time-to-recovery of white blood cell count (WBC) to 1.0×10 9/L in the PEG-rhG-CSF group was shorter than that in the rhG-CSF group [(11.59±1.98) d vs. (12.93±2.83) d], and the difference was statistically significant ( t = -2.395, P = 0.019), and the time-to-recovery of platelet count (Plt) to 20.0×10 9/L in the PEG-rhG-CSF group was also shorter than that in the rhG-CSF group [(12.86±2.62) d vs. (14.80±5.47) d], but the difference was not statistically significant ( t = -1.749, P = 0.085). The total mobilization cost of the PEG-rhG-CSF group was not statistically different from that of the rhG-CSF group [(21 405.47±7 365.98) yuan vs. (22 976.83±10 264.34) yuan, t = -0.721, P = 0.474]. Conclusions:PEG-rhG-CSF combined with high-dose chemotherapy is an effective option for PBSCM in MM patients, and its mobilization cost is equivalent to rhG-CSF. Therefore, PEG-rhG-CSF may be a better choice for PBSCM in MM patients.

Antibodies, Neutralizing ; Antibodies, Viral/isolation & purification* ; B-Lymphocytes/virology* ; COVID-19/virology* ; Humans ; Immunity/genetics* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Single-Cell Analysis