Objective To investigate the evaluation value of oxygenation index at different times of mechanical ventilation (MV) on the prognosis of patients with acute respiratory distress syndrome (ARDS).Methods A retrospectively analysis was conducted. A total of 228 patients with ARDS admitted to Department of Emergency of China Medical University Affiliated First Hospital from February 2014 to June 2016 were enrolled. All patients underwent MV treatment, and recruitment maneuver (RM) was performed by pressure-controlled ventilation (PCV) 30 minutes after the implementation of the protective ventilation strategy. Arterial blood gas analysis was performed at MV immediately, after RM and at 6, 12, 24 hours of MV, and oxygenation index was calculated. Vital signs, laboratory data, ultrasonic echocardiography, sequential organ failure assessment (SOFA) score, duration of MV, and ventilator related parameters of patients were collected. The patients were divided into survivors and non-survivors according to the prognosis of 28 days. The survivors were subdivided into high and low oxygenation group (oxygenation index was ≥ 150 mmHg and < 150 mmHg, respectively, 1 mmHg = 0.133 kPa). Differences in clinical indicators between survivors and non-survivors were compared. The correlation between the oxygenation index after RM and the oxygenation index at each time after MV was analyzed by bivariate correlation analysis. Receiver operating characteristic (ROC) curve was plotted to analyze predictive value of oxygenation index measured at different times for the 28-day outcome of patients with ARDS.Results Among 228 patients, 99 patients died within 28 days, and 129 survived, with mortality rate of 43.4%. ① The oxygenation index after RM and at 6, 12, 24 hours after MV in survivors and non-survivors showed a continuously increased tendency, which was significantly lower in non-survivors than that in survivors (allP < 0.05). There was no significant difference in the duration of MV between high oxygenation group and low oxygenation group at MV immediately and after RM, but the duration of MV in high oxygenation group was significantly shorter than that of the low oxygenation group at 6, 12, 24 hour of MV (allP < 0.01). ② After ventilation for 24 hours, serum creatinine (SCr), brain natriuretic peptide (BNP), lactate (Lac), right ventricular internal diameter, and SOFA score in non-survivors were significantly higher than those of survivors, and arterial partial pressure of oxygen (PaO2), platelet (PLT) and right ventricular ejection fraction (RVEF) were significantly lower than those of survivors (allP < 0.05). ③ After 24 hours ventilation, positive end-expiratory pressure (PEEP), tidal volume (VT), and minute ventilation (VE) in non-survivors were significantly higher than those of survivors, and static compliance of thorax (Cdyn) was significantly lower than that of survivors (allP < 0.01). ④ It was shown by correlation analysis that the oxygenation index after RM was positively correlated with those at 6, 12, 24 hours of MV (r values were 0.856, 0.765, and 0.758, respectively, allP < 0.001). ⑤ It was shown by ROC curve that the area under the ROC curve (AUC) of the oxygenation index after RM for predicting 28-day prognosis was 0.688. When the cut-off value was 80.75 mmHg, the sensitivity was 97.7%, and the specificity was 42.4%, which could only be used for preliminary judgment of prognosis. The AUC of oxygenation index at 6, 12,24 hours of MV for 28-day survival of ARDS patients were 0.719, 0.727, 0.754, respectively. When the cut-off values were 171.50, 192.14, and 161.75 mmHg, the sensitivity was 69.8%, 67.4%, 86.0%, and the specificity was 78.8%, 78.8%, and 63.6%, respectively. It indicated that the predictive value was higher, and no significant difference was found among the oxygenation index at different time points.Conclusions The oxygenation index after the early stage of RM can preliminarily determine the prognosis of patients. The predictive value of oxygenation index after MV for 28-day survival of ARDS patients was higher, so the oxygenation index measured at 6 hours of MV may be considered to evaluate the prognosis of patients with ARDS.

BACKGROUND: The contact lenses were easily contaminated by adsorbing components from the tear film, particularly protein after wearing for a period of time. Lysozyme adsorption dynamics of fluorosilicone acrylate contact lenses has been studied in order to further improve data of protein adsorption, reduce adsorbing amount of surface protein, and prevent surface contamination of contact lenses.OBJECTIVE: To investigate the adsorption dynamics of fluorosilicone acrylate contact lenses to lysozyme in vitro. METHODS: A stock solution of lysozyme was prepared in Hanks balanced salt solution (2.0 g/L, solution Ⅰ) and different trifluoroacetic acid (TFA) concentrations were prepared. Recovery experiment, the contact lenses were placed in shaking incubator at 37 ℃ for varying time intervals. After incubation there was a single rinsing in Hanks balanced salt solution. Contact lenses in control group were placed in diluted water, and contact lenses in the other group were placed in different concentrations of TFA. For deposition, FSA contact lenses in experimental group were placed in shaking incubator at 37 ℃ for varying time intervals. After incubation there was a single rinsing in Hanks balanced salt solution. Then FSA contact lenses were immersed in 0.2% TFA solution. The amount of lysozyme was assayed with BCA method.RESULTS AND CONCLUSION: Lysozyme which attached to fluorosilicone acrylate contact lenses could be resolved by TFA, and the recovery was influenced by the immersed time and the concentration of TFA. The optimal time was 1 hour, and the optimum concentration was 0.2%. The adsorption dynamics of lysozyme on FSA contact lenses was a second-phased process, i.e., lysozyme adsorption increased rapidly during 10 minutes-1 hour, reached a plateau at 1 hour, stably adsorbed during 1-24 hours, and reached a saturation of 0.349 mg/cm~2. The recovery of lysozyme was lower at 10 and 30 minutes, but reached 90%-100% while the time of incubation was between 40 minutes and 24 hours.

Objective To find out the clinical indicators related to prognosis in patients with acute mushroom poisoning, and approach its correlation with prognosis. Methods Clinical data of patients with mushroom poisoning admitted to the First Hospital of China Medical University, the Ninth People's Hospital of Shenyang, Xiuyan Central People's Hospital, and Fushun Central Hospital from August 2015 to August 2017 were retrospectively analyzed. The biochemical indicators within 24 hours after admission, sequential organ failure assessment (SOFA) score, model for end-stage liver disease (MELD) score, whether plasmapheresis (PE) was carried out or not and 28-day prognosis of patients were collected. According to prognosis, the patients were divided into death group and survival group, and the differences in above parameters between the two groups were compared. Spearman or Pearson correlation method was used to analyze the relationship between MELD score and prognosis. Receiver operating characteristic (ROC) curve was used to analyze the prognostic value of MELD score for prognosis. Further analysis of the patients receiving PE treatment was conducted. Results A total of four Liaoning hospitals with 89 patients with mushroom poisoning were enrolled, with 6 died within 28 days, and 83 survived. There were 17 patients with severely impaired liver and coagulant functions accepted PE treatment, with 6 patients died within 28 days, and 11 survived. ① In 89 patients, compared with survival group, MELD score, prothrombin time (PT), activated partial thromboplastin time (APTT), total bilirubin (TBil), international normalized ratio (INR), blood glucose (Glu), alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) in death group were significantly increased [MELD score: 32.34 (28.31, 41.06) vs. 8.76 (3.77, 21.19), PT (s): 53.5 (52.4, 113.2) vs. 14.5 (13.8, 19.5), APTT (s): 58.6 (48.9, 70.8) vs. 36.9 (34.4, 43.2), TBil (μmol/L): 134.8 (31.3, 155.6) vs. 21.5 (15.1, 41.4), INR: 6.0 (5.6, 14.7) vs. 1.2 (1.1, 1.5), Glu (mmol/L): 9.2 (9.0, 11.0) vs. 6.6 (5.7, 7.8), ALT (U/L):5 923.0 (1 105.0, 6 000.0) vs. 35.0 (18.0, 1 767.0), GGT (U/L): 49.0 (32.0, 57.0) vs. 25.0 (16.0, 41.0), all P < 0.05], but the prothrombin activity (PTA), albumin (ALB), serum Na+, Cl- were significantly decreased [PTA: 13.0% (6.0%, 14.0%) vs. 80.0% (61.0%, 87.0%), ALB (g/L): 31.1 (29.8, 39.0) vs. 42.4 (37.9, 44.3), Na+(mmol/L): 126.5 (122.4, 131.0) vs. 137.0 (134.9, 141.0), Cl- (mmol/L): 93.5 (87.6, 95.0) vs. 104.0 (101.3, 106.0), all P < 0.05]. Spearson correlation analysis showed that MELD score of patients with mushroom poisoning was positively correlated with the 28-day mortality (r = 0.423, P = 0.001). ROC curve analysis showed that the area under ROC curve (AUC) of MELD score for prognosis of patients with mushroom poisoning was 0.926; when the cut-off value was 27.30, the sensitivity was 100%, and the specificity was 84.3%. ② In 17 patients who accepted PE treatment, compared with survival group, the MELD score, TBil, Glu, and ALT in the death group were significantly increased [MELD score: 36.81±5.18 vs. 29.01±5.23, TBil (μmol/L): 145.2±13.9 vs. 93.2±44.0, Glu (mmol/L): 9.1±1.9 vs. 6.0±2.7, ALT (U/L): 5 961.5±44.5 vs. 3 932.9±1 625.7, all P < 0.05], and Cl- was significantly lowered (mmol/L: 94.3±1.2 vs. 100.5±5.7, P < 0.05), but SOFA score showed no significant difference (5.83±2.71 vs. 5.91±1.58, P > 0.05). Correlation analysis showed that the MELD score in patients with mushroom poisoning who accepted PE treatment was positively correlated with 28-day mortality (r = 0.355, P = 0.001), but no correlation with SOFA score was found (r = 0.427, P = 0.087). ROC curve analysis showed that the AUC of MELD score in the prediction of mushroom poisoning patients undergoing PE treatment was 0.545; when the cut-off value was 32.19, the sensitivity was 33.3%, and the specificity was 100%. Conclusions In mushroom poisoning patients, especially those undergoing PE treatment, the higher the MELD score, the higher the mortality is. MELD score could assess the prognosis of patients with acute mushroom poisoning.

Objective To explore the related factors of lymph node metastasis in early gastric cancer and to analyze the clinical efficacy between laparoscopic D2 radical resection and endoscopic submucosal dissection(ESD).Methods A retrospective cohort study was conducted on 404 patients with early gastric cancer undergoing surgical treatment in our hospital from June 2018 to June 2022 were recruited in this study.According to their surgical treatment,they were divided into laparoscopy group(n=271)and ESD group(n=133).The lymph node metastases were compared in the patients with different clinical features,and the factors affecting lymph node metastasis were analyzed with multivariate logistic regression analysis.The lymph node metastasis rate of patients with absolute and expanded indications of ESD was calculated.Kaplan-Meier survival analysis was used to compare the long-term efficacy of ESD and laparoscopic D2 radical resection in these patients.Stratified regression analysis was applied to explore the relationship between surgical methods and long-term outcome in them.Results In the 404 patients with early gastric cancer,the rate of lymph node metastasis was 12.38％(50/404).Univariate analysis showed that 7 clinical features,such as ulcer,tumor pathological features and pathological differentiation,were related to lymph node metastasis.Multivariate logistic regression analysis revealed that low differentiation and tumor infiltration depth of submucous membrane(SM)were related factors affecting lymph node metastasis in early gastric cancer.The overall survival rate was 96.29％(389/404)in the 404 patients,96.31％in the laparoscopic group and 96.24％in the ESD group,and no statistical difference was seen between the 2 groups(P＞0.05).There was no obvious difference in 5-year survival rate between the patients who met the absolute indications for ESD and underwent laparoscopic D2 radical surgery and those receiving ESD treatment(96.00％vs 96.55％),and between those who were in accordance with the expanded indications for ESD and underwent laparoscopic D2 radical surgery and those receiving ESD treatment(94.74％vs 91.67％).After adjusting the clinical features such as lesion size,pathological differentiation and depth of tumor invasion by stratified regression analysis,the mode of operation for early gastric cancer was still correlated with the long-term efficacy(β=1.173,P=0.003).Conclusion The depth of tumor infiltration and differentiation are closely related to lymph node metastasis in early gastric cancer patients.The efficacy of laparoscopic D2 radical surgery on the patients with absolute and expanded indications for ESD is comparable to that of ESD treatment.

Objective To explore the value of probe-based confocal laser endomicroscopy(pCLE)in the differential diagnosis of fundic gland polyps.Methods A total of 63 patients who underwent conventional white light image(WLI)and suggested with gastric polyps in our gastroenterology endoscopy center during June and December 2023 were enrolled,and their clinical data,WLI,narrow band images(NBI),pCLE images and postoperative histopathological findings were collected.The characteristics of fundic gland polyps under pCLE were statistically verified,and the sensitivity,specificity,accuracy and consistency of different endoscopic diagnoses were calculated respectively.Results Under pCLE,fundic gland polyps were mainly manifested as elongated gastric pit opening,"hand-in-hand"gastric pit opening,well-arranged blood vessels around the pit opening,and no luciferin oozing.The sensitivity,specificity,accuracy of WLI were 72.73％,75.00％,73.13％and 0.343 for fundic gland polyps,and 81.82％,71.43％,71.64％and 0.354 for hyperplastic polyps,respectively.While,the above values of NBI were 87.27％,83.33％,86.57％and 0.673 for fundic gland polyps,and 81.82％,85.71％,85.07％and 0.554 for hyperplastic polyps;and those of pCLE were 92.73％,91.67％,92.53％and 0.769 for fundic gland polyps,and 90.91％,94.64％,94.03％and 0.797 for hyperplastic polyps pCLE had better sensitivity,specificity and accuracy than WLI and NBI,and had the results consistent with histopathological findings.Conclusion pCLE can be used in the differential diagnosis of fundic gland polyps.

Objective To evaluate the diagnostic value of endoscopic ultrasonography(EUS)in the preoperative staging and ductal dilatation of duodenal papillary carcinoma and analyze the factors influencing its diagnostic accuracy.Methods A cross-sectional trial was conducted on the patients with pathologically-diagnosed duodenal papillary carcinoma and undergoing EUS in the First Affiliated Hospital of Army Medical University from January 2018 to August 2023.The diagnostic value of EUS for the preoperative staging of duodenal papillary carcinoma was evaluated using sensitivity,specificity,positive predictive value,negative predictive value,and accuracy.Univariate and multivariate analyses were performed to determine the factors affecting the diagnostic accuracy of EUS.Results A total of 102 patients with duodenal papillary carcinoma were included,including 59 males and 43 females,at a mean age of 62 years,and all of them underwent EUS before diagnosis.The accuracy of EUS for tumor T-staging was 86.27％,the sensitivity and specificity for T1,T2,T3,and T4 lesions were 84.21％,92.31％,85.00％,60.00％,and 95.31％,88.89％,96.34％,and 98.97％,respectively.The positive predictive value for T-staging of T1,T2,T3,and T4 lesions was 91.43％,83.72％,85.00％,and 75.00％,and the negative predictive values were 91.04％,94.92％,96.34％,and 97.96％,respectively.There were 14 patients whose T-staging was incorrectly staged by EUS.The accuracy of EUS in assessing intraductal dilatation was 75.49％,and the sensitivity,specificity,positive predictive value,and negative predictive value for ductal dilatation were 96.97％,66.67％,98.97％,and 40.00％,respectively.In addition,the independent predictors of diagnostic accuracy of EUS for pancreatic duct dilatation were nerve infiltration,tumor size,and T stage;whereas the independent risk factors for diagnostic accuracy of bile duct dilatation were nerve infiltration and alkaline phosphatase.Conclusion EUS has quite higher diagnostic value for preoperative staging of duodenal papillary carcinoma,and nerve infiltration,tumor size,T stage,T stage and alkaline phosphatase may be the influencing factors for its diagnostic accuracy.

Objective:To investigate the role and mechanism of mitochondrial DNA N6-methyladenine (6mA) in the hippocampal neurons in vascular cognitive impairment.Methods:(1) In vivo experiments: SPF male rats were randomly divided into sham-operated group and chronic cerebral hypoperfusion (CCH) group ( n=12). CCH models in the CCH group were established by ligating bilateral carotid arteries, while rats in the sham-operated group were only bilaterally dissected without ligation. Exploratory ability was detected by open field test 50 d after modeling, cognitive function was evaluated by novel object recognition test 51-53 d after modeling, and learning and memory abilities were tested by Morris water maze 54-59 d after modeling. And then, rats were sacrificed; ATP concentration and reactive oxygen species (ROS) level in the hippocampal tissues were detected, and neuron apoptosis in the hippocampal CA1 area was detected by TUNEL. (2) In vitro experiments: HT-22 cells were divided into normal control (NC) group, oxygen-glucose deprivation (OGD) group, OGD+siControl group, and OGD+siMETTL4 group. Cells in the NC group were cultured routinely, cells in the OGD group were subjected to low sugar and low oxygen for 12 h, and cells in the OGD+siControl group and OGD+siMETTL4 group were, respectively, transfected with NC-siRNA or METTL4-siRNA after being subjected to low sugar and low oxygen for 12 h. Mitochondria morphology was observed by transmission electron microscopy, ROS was detected by flow cytometry, mitochondria membrane potential was detected by JC-1 fluorescent staining, and mitochondrial complex I and III activity was detected by kit. (3) In vivo and in vitro experiments: METTL4 and DNA 6mA expressions in neuronal mitochondria of rat hippocampal tissues and mitochondria of HT-22 cells were detected by immunofluorescent staining and Western blotting. Results:(1) CCH rats had cognitive impairment: compared with the sham-operated group, CCH group had significantly increased frequency of entering the central area and reduced time in exploring new objects in open field experiment,and significantly decreased frequency of crossing the platform and prolonged escape latency in water maze experiment ( P<0.05). Compared with rats in the sham-operated group, rats in the CCH group had significantly decreased hippocampal ATP content ([18.820±1.177] nmol/L vs. [10.190±0.519] nmol/L) and increased ROS content ([4 488.00±255.70] AU vs. [11 644.00±530.20] AU, P<0.05). TUNEL results showed that the number of apoptotic neurons in the hippocampal CA1 area of CCH group was obviously increased than that in sham-operated group. Immunofluorescent staining results showed that 6mA and METTL4 mainly distributed in the mitochondria of hippocampal neurons in CCH group, and the 6mA and METTL4 expressions were obviously increased compared with those in the sham-operated group. Western blotting results showed that METTL4 expression in the hippocampal mitochondria of CCH group was significantly higher than that in the sham-operated group (1.729±0.168 vs. 1.000±0.000). (2) In vitro experiment: under transmission electron microscope, compared with the NC group, HT-22 cells in the OGD group showed obvious mitochondrial ridge disappearance, membrane rupture and vacuolation. Compared with the OGD group, the OGD+siMETTL4 group had significantly increased ATP production, decreased mtROS production, increased mitochondrial membrane potential, and increased mitochondrial complex I and III activities ( P<0.05). Immunofluorescent staining results showed that the mtDNA 6mA and METTL4 expressions in the OGD group were obviously higher than those in the NC group, and both mainly expressed in the mitochondria; mtDNA 6mA expression in the OGD+siMETTL4 group was obviously lower than that in OGD group. Western blotting results showed that METTL4 expression in the OGD+siMETTL4 group was significantly higher than that in the OGD group (1.578±0.261 vs. 2.970±0.280). Conclusion:Specific high expression of methylase METTL4 in hippocampal neurons of rats with cognitive impairment after CCH promotes the increased mtDNA 6mA expression and leads to mitochondrial energy metabolism disorders and increased ROS, which is speculated to be one of the mechanisms causing vascular cognitive impairment.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.