Objective To investigate the effect and mechanism of long chain non-coding RNA(ln-cRNA)SNHG16 regulating PAR1 on the proliferation,migration and invasion of lung cancer.Methods From March 2020 to August 2021,lung cancer tissues and adjacent tissues of 35 patients with lung cancer were col-lected,and lung cancer cell lines(HCC827,A549,SK-LU-1,A427)and normal lung cell lines(MRC5)were simultaneously cultured.The overexpression model of PAR1(pcDNA-PAR1)was constructed by using the expression vector pcDNA3.1.A549 cells were divided into four groups after transfection:si-SNHG16,si-PAR1,si-SNHG16+pcDNA-PAR1 and control(transfection with si-NC).The expression levels of lncRNA SNHG16 and PAR1 in lung cancer cell lines(HCC827,A549,SK-LU-1,A427),lung cancer tissues and adja-cent tissues were detected by real-time fluorescence quantitative reverse transcription-polymerase chain reac-tion(qRT-PCR),and the transfection efficiency of each group was verified.MTT assay and clonal formation were used to determine the proliferation of cells in each group,flow cytometry was used to detect the apopto-sis of cells in each group,cell scratch and Transwell test were used to detect the migration and invasion ability of cells in each group,and Western blot was used to detect the protein expression of PAR1.Results The ex-pression level of lncRNA SNHG16 in lung cancer tissue was higher than that in adjacent tissues(P＜0.05).The expression level of lncRNA SNHG16 in lung cancer cell lines(HCC827,A549,SK-LU-1,A427)was higher than that in normal lung cell lines(MRC5),with statistical significance(P＜0.05).The results of qRT-PCR showed that the expression level of lncRNA SNHG16 gene was(21.02±0.04)％of the control af-ter transfection of si-SNHG16,the expression level of PAR1 gene was(19.06±0.02)％of the control after transfection of si-PAR1,and the expression level of PAR1 gene was 2.70±0.00 folds of the control after transfection of pcDNA-PAR 1,the difference was statistically significant(P＜0.05).The results of Western blot showed that the expression level of transfected in each PAR1 protein was different from that of the con-trol(P＜0.05).Compared with the control,the activity of cells transfected with si-SNHG16 was lower,the a-bility of clone formation,cell migration and invasion was obviously inhibited,and the apoptosis rate was higher(P＜0.05),while pcDNA-PAR1 could weaken the influence of transfected si-SNHG16 on cell proliferation,apoptosis,migration and invasion(P＜0.05).lncRNA SNHG16 was positively correlated with the expression level of PAR1(r=0.61).Conclusion lncRNA SNHG16 can regulate the occurrence and development of lung cancer by targeting PAR1.

ObjectiveTo observe the apoptosis induced by paeoniflorin （PF） in non-small cell lung cancer （NSCLC） cells and explore its mechanism. MethodCell counting kit-8 （CCK-8） was used to detect the inhibition rates of H1299， H292 and A549 cells with different concentrations of PF （2.5， 5， 10， 20， 25 µmol·L^-1）， and to screen suitable concentrations of PF and experimental cells. The inhibitory effect of PF on lung cancer cells was detected by clone formation assay. The effect of PF on cell apoptosis was detected by flow cytometry with annexin V-FITC/propidium iodide （PI） double staining. With the right concentration of drugs， levels of apoptosis-associated protein B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved Caspase-3 and Caspase-3 were detected by Western blot. At the same time， the molecular expressions of hypoxia inducible factor -1α （HIF-1α） and Hippo signaling pathway were determined. ResultCompared with the blank group， PF significantly inhibited the growth of H1299， H292 and A549 cells of human lung cancer （P<0.01）. PF significantly induced apoptosis in A549 cells （P<0.01）， decreased the Bcl-2/Bax ratio （P<0.01）， and significantly increased the cleaved Caspase-3 expression （P<0.01）. Compared with those in the blank group， the expression levels of HIF-1α， transcriptional coactivator with PDZ-binding motif （TAZ）， large tumor suppressor 1 （LATS1）， Mps one binding 1 （MOB1） and Yes-associated protein （YAP） in A549 cells of the PF treatment group were significantly decreased （P<0.01）， while the expressions of p-LATS1， p-MOB1 and p-YAP were significantly increased （P<0.01）. At the same time， there was no significant effect on the expression levels of phosphorylated mammalian Ste20-like kinase 1 （p-MST1） and MST1， which did not reach a statistical difference. ConclusionAll data demonstrated that PF showed an anti-tumor effect by improving hypoxic conditions and inhibiting the abnormally activated Hippo signaling pathway， thereby inducing and promoting apoptosis in non-small cell lung cancer.

Objective:To investigate the preventive effect of Xiyanping injection on radioactive esophagitis in patients with radical radiotherapy and chemotherapy for esophageal cancer.Methods:A total of 70 patients with esophageal cancer undergoing radical radiotherapy and chemotherapy were selected from the Department of Radiation Oncology of Jiangsu Provincial People′s Hospital from January to September 2020. They were divided into experimental group ( n=35) and control group ( n=35) according to random number table method. The control group received standard concurrent radiotherapy and chemotherapy, and the experimental group received concurrent radiotherapy and chemotherapy combined with Xiyanping. The white blood cell count, neutrophil count, procalcitonin (PCT) and interleukin-6 (IL-6) levels before and after treatment were compared between the two groups, as well as the occurrences of radioactive esophagitis and radioactive pneumonia during radiotherapy. Results:Before treatment, there were no significant differences in white blood cell count [4.57 (2.52)×10 9/L vs. 5.59 (2.23)×10 9/L] and neutrophil count [2.95 (1.66)×10 9/L vs. 3.69 (1.56)×10 9/L] between the control group and experimental group ( Z=1.44, P=0.151; Z=1.52, P=0.130). After treatment, there were no statistically significant differences in white blood cell count [4.28 (2.50)×10 9/L vs. 4.25 (1.88)×10 9/L] and neutrophil count [2.99 (2.50)×10 9/L vs. 2.94 (1.61)×10 9/L] between the two groups ( Z=0.67, P=0.503; Z=0.69, P=0.489). There were no statistically significant differences in white blood cell count and neutrophil count between the patients after treatment and before treatment in the two groups ( Z=0.77, P=0.443; Z=1.08, P=0.279; Z =1.06, P=0.289; Z=0.68, P=0.495). Before treatment, there were no statistically significant differences in serum inflammation indexes PCT [0.02 (0.03) μg/L vs. 0.02 (0.05) μg/L] and IL-6 [0.04 (0.21) μg/L vs. 0.04 (0.12) μg/L] between the two groups ( Z=0.70, P=0.482; Z=0.77, P=0.439). After treatment, there were statistically significant differences in serum inflammation indexes PCT [0.06 (0.17) μg/L vs. 0.03 (0.08) μg/L] and IL-6 [0.10 (0.25) μg/L vs. 0.01 (0.08) μg/L] between the two groups ( Z=2.08, P=0.038; Z=2.92, P=0.003). There were no statistically significant differences in serum inflammation indexes PCT and IL-6 in the experimental groups after treatment compared with before treatment ( Z=1.20, P=0.230; Z=1.19, P=0.235). In the control group, the serum inflammation index PCT level increased after treatment compared with before treatment, with a statistically significant difference ( Z=2.82, P=0.005), and the serum inflammation index IL-6 level increased compared with before treatment, but with no statistically significant difference ( Z=1.41, P=0.158). During the treatment, the incidence of radioactive esophagitis in the two groups was mainly grade Ⅰ-Ⅱ, with 24 cases in the control group and 28 cases in the experimental group. There were 8 patients with grade Ⅲ-Ⅳ radioactive esophagitis in the control group and 1 in the experimental group. There was a statistically significant difference in the occurrence of radioactive esophagitis between the two groups ( χ2=10.34, P=0.035). During the treatment period, most patients with radioactive pneumonia were rated as grade 0. There were 10 cases of mild radioactive pneumonia (grade Ⅰ-Ⅱ) in the control group had and 6 cases in the experimental group. There were 2 cases of grade Ⅲ radioactive pneumonia in the control group and experimental group respectively. There was no grade Ⅳ radioactive pneumonia in either group. There was no significant difference in radioactive pneumonia between the two groups ( χ2=1.34, P=0.720). Conclusion:Xiyanping injection can prevent the rise of serum inflammatory index PCT and reduce the severity of radioactive esophagitis in patients with esophageal cancer after treatment.

Objective:To observe any effect of intermittent theta burst stimulation (iTBS) on the spatially-delayed responses of working memory using cynomolgus macaques.Methods:The working memory of six male cynomolgus macaques (8-9 years old) was trained using a spatially-delayed response task. They were then randomly divided into an iTBS group and a control group, each of 3. The iTBS group was given iTBS at an intensity of 35% of the maximum output, with 2 seconds of stimulation followed by 8 seconds of rest with trains of 50Hz bursts repeated at a frequency of 5Hz over a period of 192 seconds once daily for 5 days, while the control group was given sham iTBS. Before and after the 5 days, the body weight and working memory of each animal were evaluated. The total number of effective feeding episodes, and of effective feeding episodes with short and long delay periods were recorded.Results:There was no significant change in the average body weight of either group before and after the modeling and iTBS intervention. After the intervention the number of total effective feeding cases and those with a short delay period were both significantly higher in the iTBS group than in the control group. However, no significant inter-group differences in the effective feeding cases with a long delay period were observed.Conclusions:iTBS is effective in improving the spatially-delayed responses of working memory, at least in cynomolgus macaques.

Objective:To understand the current situation and influencing factors of psychological stress reaction in patients with multi-drug resistance tuberculosis (MDR-TB) and to analyze the moderating effect of social support level between medical coping style and psychological stress reaction.Methods:This study was a cross-sectional study. Using the convenient sampling method, a total of 273 patients with MDR-TB who were hospitalized in the Tuberculosis Department of West China Hospital, Sichuan University from July 2019 to December 2020 were selected as the research objects. The Impact of Event Scale-Revised (IES-R) , Social Support Rating Scale (SSRS) and Medical Coping Modes Questionnaire (MCMQ) were used to investigate them. The χ 2 test and t test were used for univariate analysis, binomial logistic regression analysis was used for multivariate analysis and PROCESS V 3.3 software was used for moderating effect analysis. Results:A total of 37.36% (102/273) of MDR-TB patients had severe psychological stress reaction. Logistic regression analysis showed that age ( OR=1.039, 95% CI: 1.003-1.076) , marital status ( OR=0.136, 95% CI: 0.024-0.773) , occupation ( OR=0.057, 95% CI: 0.011-0.312) , daily alcohol consumption ( OR=28.968, 95% CI: 2.387-351.609) , social support level ( OR=0.927, 95% CI: 0.866-0.993) and patients' yielding psychology in the face of disease ( OR=2.216, 95% CI: 1.761-2.788) were independent factors affecting the psychological stress response of MDR-TB patients. The level of social support had significant moderating effects on avoidance (β=-0.132, P=0.002) , confrontation (β=-0.068, P=0.038) and psychological stress in MDR-TB patients. The more the patients with high social support level adopted the coping style of facing or avoiding, the lower the score of the event impact scale, that was, the weaker the psychological stress reaction. Conclusions:Medical staff should pay attention to the psychological stress reaction of MDR-TB patients and conduct targeted psychological counseling to enhance social support level of patients and improve treatment compliance, thereby reducing the recurrence rate of tuberculosis.

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.

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.

Objective:To classify the symptom characteristics of young and middle-aged peritoneal dialysis patients and to explore the differences of demographic functional status and social function of patients with different symptom categories.Methods:A total of 179 peritoneal dialysis patients from 3 peritoneal dialysis centers in Shanghai were investigated from December 2019 to August 2020 by General Information Questionnaire, Peritoneal Dialysis Symptom Distress Scale. Latent class analysis was used to classify young and middle-aged peritoneal dialysis patients according to symptom characteristics. Multiple Logistic regression was used to explore the differences of demographic and disease characteristics of different categories of patients.Results:Peritoneal dialysis patients could be divided into three potential categories according to symptom characteristics ( P<0.05). According to the conditional probability of each category, they were named "low symptom group" (111 cases,62.0%), "high psychological-moderate physical symptom group" (22 cases, 12.3%), "high symptom group" (46 cases,25.7%). There were differences in working status ( OR=0.029, P<0.01), education level ( OR=152.799, P<0.01), duration ( OR=81.307, P<0.05), diabetic nephropathy ( OR=80.619, P<0.01) and CCI score ( OR=91.188, P<0.01) distribution among different potential categories of young and middle-aged peritoneal dialysis patients. Conclusions:There are three types of potential symptoms in young and middle-aged patients undergoing peritoneal dialysis. In clinical practice, medical staff should focus on the psychological status of young and middle-aged patients with low educational background and early stage of dialysis, and encourage them to return to work; at the same time, they should regularly evaluate the symptom burden of patients with diabetic nephropathy and high complication index peritoneal dialysis patients, in order to provide targeted intervention measures to prevent the progression of the disease.

Objective:To evaluate the effect of definitive radiotherapy with different doses on overall survival (OS) and identify the prognostic factors of patients with non-metastatic esophageal squamous cell carcinoma (ESCC).Methods:Clinical data of 2 344 ESCC patients treated with definitive radiotherapy (RT) alone or chemoradiotherapy from 2002 to 2016 in 10 hospitals were collected and analyzed retrospectively. After the propensity score matching (PSM)(1 to 2 ratio), all patients were divided into the low-dose group (equivalent dose in 2 Gy fractions, EQD 2Gy<60 Gy; n=303) and high-dose group (EQD 2Gy&ge;60 Gy; n=606) based on the dose of radiation. Survival analysis was conducted by Kaplan- Meier method. Multivariate prognostic analysis was performed by Cox′s regression model. Results:The median follow-up time was 59.6 months. After the PSM, the 1-, 3- and 5-year overall survival (OS) rate was 66.5%, 34.7%, 27.2% in the low-dose group, 72.9%, 41.7% and 34.7% in the high-dose group, respectively ( P=0.018). The 1-, 3-and 5-year progression-free survival rate was 52.2%, 27.2%, 23.1% in the low-dose group, 58.3%, 38.1% and 33.9% in the high-dose group, respectively ( P=0.001). The outcomes of univariate analysis indicated that cervical/upper esophagus location, early (stage Ⅱ) AJCC clinical stage, node negative status, tumor length ≤5 cm, receiving intensity-modulated radiation therapy (IMRT), receiving concurrent chemotherapy and EQD 2Gy&ge;60 Gy were closely associated with better OS (all P<0.05). Multivariable analysis demonstrated that tumor location, regional lymph node metastasis, concurrent chemotherapy and EQD 2Gy were the independent prognostic factors for OS (all P<0.05). Conclusion:Three-dimensional conformal or IMRT with EQD 2Gy&ge;60 Gy yields favorable survival outcomes for patients with locally advanced ESCC.

Objective:To compare the expression level of exosomal miR-503 in peritoneal dialysis effluent (PDE) from patients of different peritoneal transport characteristics, predict the target genes of miR-503 and provide bioinformatic data for researches of peritoneal transport characteristics.Methods:Twenty-four stable peritoneal dialysis (PD) patients were selected and divided into high transport group (H group, n=12) and low transport group (L group, n=12) according to the results of peritoneal equilibration tests (PET). The 500 ml PDE that was left on the patient's abdomen overnight was collected and concentrated using ultrafiltration cell. Exosomes in PDE were resuspended in phosphate buffered saline (PBS) after ultracentrifugation and the characteristics of PDE exosomes were identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), Western blotting and fluorescent staining. MicroRNAs were extracted from PDE exosomes. The expression levels of PDE exosomal miR-503 in the two groups were detected by quantitative real-time PCR. Then the relations between the relative quantity of PDE exosomal miR-503 and PET values or 24 h ultrafiltration volume (UF) were analyzed. Targetscan and miRDB databases were used to predict the target genes of miR-503. Gene ontology (GO) functional enrichment and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were relied on DAVID (https://david.ncifcrf.gov/). Results:The exosomes in PDE showed a round and cup-shaped morphology under TEM, and the diameters were approximately 100 nm measured by NTA. The specific biomarkers of exosomes, CD63, CD81 and heat shock protein -70 (HSP-70) were all detected by Western blotting. The internalization and uptake of the exosomes was observed after fluorescent staining. The relative expression level of PDE exosomal miR-503 in H group was found to be significantly higher than that in L group ( P=0.002), and the relative quantity of PDE exosomal miR-503 was significantly positively correlated with PET values ( r=0.547, P=0.006), but not 24 h UF ( r=-0.297, P=0.159). There were 156 target genes of miR-503 in total that could be predicted by two different databases at the same time. GO analysis of these 156 target genes was mainly focused on kinase binding, regulation of protein modification and catabolic process as well as regulation of epithelial cell proliferation. KEGG enriched many tumor associated or classical signaling pathways, including transforming growth factor-β (TGF-β) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway. The prediction showed that vascular endothelial growth factor A (VEGFA) was a direct target gene of miR-503 and it was also related to many proteins involved in fibrosis mechanism. Conclusions:The expression level of PDE exosomal miR-503 is significantly higher in H group, and positively correlates with PET values, which may regulate the angiogenesis of peritoneal vessels by targeting VEGFA.