Objective:To compare the short-term efficacy and perioperative safety of neoadjuvant chemoradiotherapy (nCRT) with total neoadjuvant treatment (TNT) in patients with locally advanced rectal cancer (LARC).Methods:A retrospective cohort analysis was carried out. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology with a distance from tumor inferior border to anal verge within 12 cm; (2) clinical stage cT3-4N0 or cT1-4N1-2 diagnosed by magnetic resonance imaging (MRI) or endorectal ultrasonography; (3) a single rectal tumor confirmed by colonoscopy; (4) patients suitable for chemoradiotherapy; (5) no previous history of other tumors. Exclusion criteria: (1)patients with previous rectal cancer surgery and local recurrence; (2) those who did not complete nCRT course; (3) those with distant metastases; (4) those with defective clinicopathological data. According to the above criteria, a total of 134 LARC patients at the Department of General Surgery of Beijing Chaoyang Hospital from January 2016 to January 2019 were enrolled, including 82 males and 52 females, with a male-female ratio of 1.58∶1.00 and mean age of (59.6±11.2) (26-81) years. Based on neoadjuvant regimen, patients were divided into nCRT group ( n=55) and TNT group ( n=79). There were no statistically significant differences in baseline data, such as age, sex, distance from tumor to anal verge, Eastern Cooperative Oncology Group (ECOG) performance status and clinical TNM stage, between the two groups (all P>0.05). All the patients received pelvic intensity-modulated radiotherapy (IMRT) with a total dose of 50.4 Gy in 28 fractions. Patients in nCRT group received oral capecitabine chemotherapy during radiotherapy and underwent surgery 6-8 weeks after chemoradiation. Patients in TNT group received one cycle of induction CapeOX (oxaliplatin and capecitabine) and concurrent chemoradiotherapy, then underwent a radical surgery two weeks after completion of consolidation chemotherapy. The efficacy of neoadjuvant therapy, adverse events of chemoradiotherapy and perioperative safety were compared between the two groups. Results:Patients of two groups completed the course of neoadjuvant therapy. There were no statistically significant differences between nCRT group and TNT group in the incidence of adverse events in neutropenia [7.3% (4/55) vs. 10.1% (8/79)], anemia [3.6% (2/55) vs. 3.8% (3/79)], thrombocytopenia [5.5% (3/55) vs. 7.6% (6/79)], gastrointestinal dysfunction [3.6% (2/55) vs. 6.3% (5/79)] and radiation enteritis [9.1% (5/55) vs. 8.9% (7/79)] (all P>0.05). One hundred and thirty patients completed TME surgery, including 54 patients in nCRT group and 76 patients in the TNT group. Compared with the nCRT group, the proportion of abdominoperineal resection (APR) was higher in the TNT group [31.6% (25/76) vs. 13.0% (7/54), χ 2=9.382, P=0.009]. No statistically significant differences in morbidity of postoperative complication, operation time, intraoperative blood loss and postoperative hospital stay between the two groups were found (all P>0.05). The distal and circumferential margins were negative in all the patients. Seventeen patients in the TNT group 22.4% (17/76) got pathologic complete response (pCR), which was significantly higher than 7.4% (4/54) in nCRT group (χ 2=5.217, P=0.022). There were no statistically significant differences in ypTNM classification, perineural invasion and venous invasion between the two groups (all P>0.05). Conclusion:The pCR of TNT is higher than that of nCRT without increasing the incidence of toxicity and complications of radiotherapy and chemotherapy for patients with locally advanced rectal cancer.

Objective:To compare the short-term efficacy and perioperative safety of neoadjuvant chemoradiotherapy (nCRT) with total neoadjuvant treatment (TNT) in patients with locally advanced rectal cancer (LARC).Methods:A retrospective cohort analysis was carried out. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology with a distance from tumor inferior border to anal verge within 12 cm; (2) clinical stage cT3-4N0 or cT1-4N1-2 diagnosed by magnetic resonance imaging (MRI) or endorectal ultrasonography; (3) a single rectal tumor confirmed by colonoscopy; (4) patients suitable for chemoradiotherapy; (5) no previous history of other tumors. Exclusion criteria: (1)patients with previous rectal cancer surgery and local recurrence; (2) those who did not complete nCRT course; (3) those with distant metastases; (4) those with defective clinicopathological data. According to the above criteria, a total of 134 LARC patients at the Department of General Surgery of Beijing Chaoyang Hospital from January 2016 to January 2019 were enrolled, including 82 males and 52 females, with a male-female ratio of 1.58∶1.00 and mean age of (59.6±11.2) (26-81) years. Based on neoadjuvant regimen, patients were divided into nCRT group ( n=55) and TNT group ( n=79). There were no statistically significant differences in baseline data, such as age, sex, distance from tumor to anal verge, Eastern Cooperative Oncology Group (ECOG) performance status and clinical TNM stage, between the two groups (all P>0.05). All the patients received pelvic intensity-modulated radiotherapy (IMRT) with a total dose of 50.4 Gy in 28 fractions. Patients in nCRT group received oral capecitabine chemotherapy during radiotherapy and underwent surgery 6-8 weeks after chemoradiation. Patients in TNT group received one cycle of induction CapeOX (oxaliplatin and capecitabine) and concurrent chemoradiotherapy, then underwent a radical surgery two weeks after completion of consolidation chemotherapy. The efficacy of neoadjuvant therapy, adverse events of chemoradiotherapy and perioperative safety were compared between the two groups. Results:Patients of two groups completed the course of neoadjuvant therapy. There were no statistically significant differences between nCRT group and TNT group in the incidence of adverse events in neutropenia [7.3% (4/55) vs. 10.1% (8/79)], anemia [3.6% (2/55) vs. 3.8% (3/79)], thrombocytopenia [5.5% (3/55) vs. 7.6% (6/79)], gastrointestinal dysfunction [3.6% (2/55) vs. 6.3% (5/79)] and radiation enteritis [9.1% (5/55) vs. 8.9% (7/79)] (all P>0.05). One hundred and thirty patients completed TME surgery, including 54 patients in nCRT group and 76 patients in the TNT group. Compared with the nCRT group, the proportion of abdominoperineal resection (APR) was higher in the TNT group [31.6% (25/76) vs. 13.0% (7/54), χ 2=9.382, P=0.009]. No statistically significant differences in morbidity of postoperative complication, operation time, intraoperative blood loss and postoperative hospital stay between the two groups were found (all P>0.05). The distal and circumferential margins were negative in all the patients. Seventeen patients in the TNT group 22.4% (17/76) got pathologic complete response (pCR), which was significantly higher than 7.4% (4/54) in nCRT group (χ 2=5.217, P=0.022). There were no statistically significant differences in ypTNM classification, perineural invasion and venous invasion between the two groups (all P>0.05). Conclusion:The pCR of TNT is higher than that of nCRT without increasing the incidence of toxicity and complications of radiotherapy and chemotherapy for patients with locally advanced rectal cancer.

Objective:To explore the effect of peripheral blood T lymphocyte subsets on locally advanced rectal cancer after neoadjuvant chemoradiotherapy.Methods:108 patients were included at the Department of General Surgery of Beijing Chaoyang Hospital from Jun 2016 to Jun 2017. Peripheral blood was collected within one week before neoadjuvant therapy and one week before rectal surgery. Flow cytometry was applied to detect the CD3 + 、CD4 + 、CD8 + 、CD45RA + 、CD45RO + expression. Receiver operating characteristic (ROC) curve analysis was performed to determine the best cut-off value of the ratio of lymphocytes. A logistic regression model was obtained in multivariate analysis. Results:The values of CD3 + , CD4 + and CD8 + T lymphocytes in peripheral blood of the patients decreased compared with that before neoadjuvant treatment (all P<0.05). There was no significant decrease in the proportion of CD4 + , CD8 + , CD45RA + T and CD45RO + lymphocytes in patients′ peripheral blood (all P>0.05). The CD45RO in peripheral blood decreases during neoadjuvant therapy for locally advanced rectal cancer, and it is associated with better tumor regression( P<0.05). The best cut-off value for the ratio changes of CD45RO was 1.07. The ratio changes of CD45RO were the only significant factor for tumor regression in multivariate analysis ( P=0.005, OR=26.867, 95% CI: 1.530-471.635). Conclusion:The percentage of peripheral blood CD45RO may predict the sensitivity of neoadjuvant therapy in rectal cancer patients.

Objective To investigate the correlation between serum miR-320b and carotid atherosclerosis in patients with acute ischemic stroke.Methods From January 2017 to December 2017,patients with acute ischemic stroke visited the Department of Neurology,the Affiliated Hospital of Yangzhou University were enrolled.According to the findings of carotid artery ultrasonography,they were divided into plaque group and plaque-free group.The baseline clinical data such as demographic data,vascular risk factors,and blood biochemical indicators were collected.Reverse transcription quantitative polymerase chain reaction was used to detect the expression level of serum miR-320b.Multivariatelogistic regression analysis was used to determine the independent risk factors for carotid atherosclerosis.Results A total of 135 patients with acute ischemic stroke were enrolled in this study,including 58 females and 77 males,aged 58.4 ± 10.6 years.There were 85 patients in the plaque group and 50 in the plaque-free group.The total cholesterol (t =5.523,P =0.023) and low-density lipoprotein cholesterol (t =4.415,P =0.044) in the plaque group were significantly higher than those in the plaque-free group,while high-density lipoprotein cholesterol (t =5.849,P=0.017) and serum miR-320b (t =4.331,P=0.039) were significantly lower than those in the plaque-free group.Multivariate logistic regression analysis showed that referring to the highest quartile group,the low serum miR-320b level might be an independent risk factor for carotid atherosclerosis (the first quartile group:odds ratio 2.701,95％ confidence interval 1.154-6.321,P =0.022;the second quartile group:odds ratio 2.521,95％ confidence interval 1.249-5.091,P =0.010;and the third quartile group:odds ratio 1.849,95％ confidence interval 1.041-3.283,P=0.036).Conclusion The low serum miR-320b level might be an independent risk factor for carotid atherosclerosis in patients with acute ischemic stroke.

Objective:To investigate the effect and mechanism of the gastric cancer cells-derived exosome miR-382-5p in-duced by Helicobacter pylori(H.pylori)on the autophagy and polarization of macrophages,providing new clues for further elucidating the carcinogenic mechanism of H.pylori.Methods:Ultracentrifugation and exosome extraction kit were used to extract the exosomes re-leased by the H.pylori stimulated group and the blank control group AGS cells cells,then transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA)and Western blot were employed to identify exosomes.qRT-PCR was used to detect the expres-sion of miR-382-5p in H.pylori induced AGS-derived exosomes.miR-382-5p mimic was transfected into THP-1 macrophages,then the expressions of autophagy markers(LC3Ⅱ,p62,and Beclin-1)were evaluated by Western blot,the number of autophagosomes was detected by immunofluorescence.The expression levels of PTEN protein,downstream proteins PI3K,AKT,mTOR and its phosphory-lated proteins p-PI3K,p-AKT,p-mTOR were detected by Western blot.Flow cytometry was used to detect the expression levels of macrophage phenotypic molecules CD206 and HLA-DR.ELISA was used to detect the secretion of cytokines TNF-α,IL-6,IL-10 and Arginase1 in macrophage supernatants.Results:The extracted exosomes were consistent with exosome morphology and highly ex-pressed the surface marker proteins CD9,CD63 and TSG101.Compared with the blank control group,the expression level of exosom-al miR-382-5p in H.pylori-infected group was significantly increased.miR-382-5p mimic transfection resulted in decreased expression of LC3 Ⅱ and Beclin-1 in macrophages,increased expression of P62 and decreased number of autophagosomes.Moreover,the protein expression level of PTEN was significantly decreased in the miR-382-5p mimic transfection group,while the expression levels of p-PI3K,p-AKT and p-mTOR were significantly increased.miR-382-5p mimic transfection also resulted in increased expression of mac-rophage M2 type marker protein CD206 and decreased expression of M1 type marker protein HLA-DR,as well as increased expres-sions of IL-10 and Arginine1,whereas decreased expression of IL-6 and TNF-α.Pretreatment with the pathway inhibitor BEZ235 par-tially reverses the effects of miR-382-5p on macrophage autophagy and polarization.Conclusion:H.pylori-induced gastric cancer cells-derived exosomal miR-382-5p suppresses macrophage autophagy and induces M2 polarization through down-regulation of PTEN ex-pression and activation of the PI3K/AKT/mTOR signaling pathway.

Objective:To evaluate the value of whole-brain radiotherapy (WBRT) combined with simultaneous integrated boost (SIB) and WBRT plus sequential stereotactic radiosurgery (SRS) in the treatment of small-cell lung cancer (SCLC) patients with brain metastases (BM).Methods:A retrospective analysis was performed among 135 SCLC patients with BM who were admitted to Tianjin Medical University Cancer Institute and Hospital from 2007 to 2023. They all received cisplatin- or carboplatin-based first-line chemotherapy and WBRT with 94 patients receiving thoracic radiotherapy after chemotherapy. All patients were divided into the WBRT+SIB ( n=66) and WBRT+SRS groups ( n=69) according to the treatment methods. After propensity score matching (PSM), 63 patients were assigned into each group. The primary endpoints were overall survival (OS) and brain metastasis-related local control (BMRLC) rates. Categorical data, such as gender and age, were compared by Chi-square test. OS and BMRLC were calculated by Kaplan-Meier method. The survival curves between two groups were compared by log-rank test. The risk factors of OS and BMRLC were assessed by multivariate Cox regression models. Results:In all the patients, the median follow-up time was 24.9 (range 6.30-109.57) months. The 2-year OS and BMRLC rates were 49.0% and 85.0%, respectively. Cerebral necrosis occurred in 2 patients. Multivariate analysis revealed that shorter time interval of BM after diagnosis (≤10 months) ( P=0.041), control of extracranial progression ( P=0.029), and lower diagnosis-specific graded prognostic assessment (DS-GPA) (≥2) ( P=0.006) significantly improved OS. After PSM, the 2-year OS rate in the WBRT+SIB group was significantly higher than that in the WBRT+SRS group ( P=0.041), while the 2-year BMRLC rate was not significantly improved ( P=0.203). In the DS-GPA<2 subgroup, the OS in the WBRT+SIB group was significantly higher than that in the WBRT+SRS group ( P=0.016), whereas no significant difference was observed in BMRLC between two groups ( P=0.205). In the DS-GPA≥2 subgroup, no significant difference was found in OS between two groups ( P=0.266), while BMRLC in the WBRT+SIB group was significantly lower compared with that in the WBRT+SRS group ( P=0.027). Conclusions:WBRT+SIB is more suitable for SCLC patients with BM than WBRT+SRS. However, WBRT+SRS yields higher local control for DS-GPA≥2 patients.