Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α _v β ₃ because of the multivalent interactions between larger active nanoparticles and integrin α _v β ₃. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.

Objective:The purpose of this study was to investigate the evaluating value of modified critical care ultrasonic examination(M-CCUE) scheme for the etiological diagnosis of shock in ICU patients.Methods:The prospective study collected relevant clinical data of various shock patients admitted to the Department of Intensive Care Medicine, Henan Provincial People's Hospital from May 2020 to July 2021, including hemodynamic、blood indicators、organ/tissue perfusion and prognostic evaluation indicators.All selected patients completed the initial M-CCUE assessment within 30 minutes, were scored according to the M-CCUE score system and related data results were analyzed.Results:Ninety-three patients were included in this study,Two of them were not completed the M-CCUE assessment due to emergency treatment immediately after entering our department, and five were excluded due to inconsistent ultrasound judgments by the two physicians. In the end, a total of 86 patients were enrolled in the group. In patients applied with M-CCUE scheme,time to preliminary diagnosis and final diagnosis were (13.02±3.15)min and (67.70±20.20)min respectively, the accuracy of diagnosis was 83.7%. Among them, distributed shock accounted for 60.4%, hypovolemic shock accounted for 25.6%, cardiogenic shock and obstructive shock accounted for 3.5%, and mixed shock accounted for 7%; MCS is (13.27±4.91), M-CCUE scheme had the high sensitivity and specificity for the diagnosis of distributed shock (sensitivity 91.2%, specificity 93.9%), hypovolemic shock (sensitivity 96.0%, specificity 96.7%), cardiogenic shock (sensitivity 85.7%, specificity 98.7%) and obstructive shock (sensitivity 60.0%, specificity 100%); MCS has a good positive correlation with APACHEⅡ score ( r=0.861, P<0.001), and has no correlation with ICU cost ( r=0.012, P=0.915). There is no significant difference in MCS between the 28d death group and the recovery group ( P=0.391). Conclusions:For shock patients admitted to ICU with unknown etiology, the initial diagnosis of the cause of the M-CCUE program takes less time, has a higher correct diagnosis rate, sensitivity and specificity, and its quantitative evaluation results can predict the patient's criticality.

Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; COVID-19 Vaccines ; Humans ; Immunization Schedule ; SARS-CoV-2 ; Vaccines, Inactivated

Objective:To investigate the effect of triptolide on radiosensitivity of lung cancer cells and its mechanism.Methods:The lung cancer cells H1299, A549, H157 and H838 were cultured. The strongest radio resistance cell line, H1299 was selected by cell clone formation experiment and for the subsequent experiments. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) was used to detect the effect of different concentrations of triptolide on the proliferation of H1299 cells. The optimal concentration of triptolide was 50nmol/L, and the optimal treatment time was 48 hours. The H1299 cells were divided into the control group, triptolide group (50 nmol/L), 4 Gy group and triptolide+ 4 Gy group. Flow cytometry was used to detect the apoptosis rate of H1299 cell. Western Blot was used to detect the proteins expression levels of p-Chk2, p-ATM, p-p53, Bcl-2, Bax and cleaved-Caspase 3.Results:The apoptotic rate and protein levels of Bax, cleaved-Caspase 3, p-Chk2, p-ATM and p-p53 in the 4 Gy group were (12.38±1.34)%, 0.42±0.04, 0.38±0.04, 0.98±0.11, 0.73±0.08, 0.95±0.09, respectively, higher than (3.26±2.43)%, 0.22±0.02, 0.23±0.03, 0.32±0.03, 0.21±0.02, 0.25±0.03 in the control group ( P<0.05). However, the protein level of Bcl-2 was (0.52±0.05), lower than (0.93±0.09) of the control group ( P<0.05). The survival fraction (0.462) and protein level of Bcl-2 (0.44±0.04) in the triptolide group were lower than those of the control group (0.702 and 0.93±0.09, P<0.05). The apoptotic rate and the protein levels of Bax and cleaved-Caspase 3 in the triptolide group were (9.27±1.08)%, 0.45±0.05, 0.41±0.04, respectively, higher than (3.26±2.43)%, 0.22±0.02, 0.23±0.03 in the control group ( P<0.05), and the sensitization ratio in the triptolide group was 1.579. The apoptosis rate, Bax and cleaved Caspase 3 protein expression levels in triptolide + 4 Gy group were (26.53±2.19)%, 0.91±0.09 and 0.79±0.08, respectively, higher than (12.38±1.34)%, 0.42±0.04 and 0.38±0.04 in 4 Gy group ( P<0.05). The expression level of Bcl-2 protein was (0.21±0.02), lower than (0.52±0.05) in 4 Gy group ( P<0.05). Conclusion:Triptolide increases the radiosensitivity of radiation-induced lung cancer cells by inhibiting DNA repair and inducing apoptosis.

Objective:To investigate the effect of triptolide on radiosensitivity of lung cancer cells and its mechanism.Methods:The lung cancer cells H1299, A549, H157 and H838 were cultured. The strongest radio resistance cell line, H1299 was selected by cell clone formation experiment and for the subsequent experiments. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) was used to detect the effect of different concentrations of triptolide on the proliferation of H1299 cells. The optimal concentration of triptolide was 50nmol/L, and the optimal treatment time was 48 hours. The H1299 cells were divided into the control group, triptolide group (50 nmol/L), 4 Gy group and triptolide+ 4 Gy group. Flow cytometry was used to detect the apoptosis rate of H1299 cell. Western Blot was used to detect the proteins expression levels of p-Chk2, p-ATM, p-p53, Bcl-2, Bax and cleaved-Caspase 3.Results:The apoptotic rate and protein levels of Bax, cleaved-Caspase 3, p-Chk2, p-ATM and p-p53 in the 4 Gy group were (12.38±1.34)%, 0.42±0.04, 0.38±0.04, 0.98±0.11, 0.73±0.08, 0.95±0.09, respectively, higher than (3.26±2.43)%, 0.22±0.02, 0.23±0.03, 0.32±0.03, 0.21±0.02, 0.25±0.03 in the control group ( P<0.05). However, the protein level of Bcl-2 was (0.52±0.05), lower than (0.93±0.09) of the control group ( P<0.05). The survival fraction (0.462) and protein level of Bcl-2 (0.44±0.04) in the triptolide group were lower than those of the control group (0.702 and 0.93±0.09, P<0.05). The apoptotic rate and the protein levels of Bax and cleaved-Caspase 3 in the triptolide group were (9.27±1.08)%, 0.45±0.05, 0.41±0.04, respectively, higher than (3.26±2.43)%, 0.22±0.02, 0.23±0.03 in the control group ( P<0.05), and the sensitization ratio in the triptolide group was 1.579. The apoptosis rate, Bax and cleaved Caspase 3 protein expression levels in triptolide + 4 Gy group were (26.53±2.19)%, 0.91±0.09 and 0.79±0.08, respectively, higher than (12.38±1.34)%, 0.42±0.04 and 0.38±0.04 in 4 Gy group ( P<0.05). The expression level of Bcl-2 protein was (0.21±0.02), lower than (0.52±0.05) in 4 Gy group ( P<0.05). Conclusion:Triptolide increases the radiosensitivity of radiation-induced lung cancer cells by inhibiting DNA repair and inducing apoptosis.

Objective To investigate the effectiveness and safety of thermal ablation of patients with 3－5 cm hepatocellular carcinoma ( HCC ) under the assistance of ultrasound fusion imaging . Methods From December 2010 to December 2017 ,76 HCC patients with 78 medium‐size ( 3 －5 cm ) lesions who underwent radiofrequency ablation ( RFA ) or microwave ablation ( M WA ) were included in the study . Ultrasound fusion imaging was used to assist the ablation procedures and assess the technical success immediately ,then guided supplementary ablation . Contrast‐enhanced CT/M R was performed one month after ablation to assess the technique efficacy rate . T he complication ,local tumor progression ( L T P ) rate were followed up . Results According to the ultrasound fusion imaging evaluation ,24 lesions ( 30 .8% , 24/78) received supplementary ablation immediately during the ablation procedure . Seventy‐one of 78 liver tumors were evaluated to achieve 5 mm ablative margin while the other 7 liver tumors were not achieved . T here were no ablation‐related deaths ,and the major complication rate was 6 .6% ( 5/76 ) .T he technique efficacy rate was 100% ( 78/78) according to the contrast‐enhanced CT/M R one‐month later . Patients were followed up from 6 to 79 months with a median time of 22 months . L T P occurred in 4 lesions and the LT P rate was 5 .1% ( 4/78) . Conclusions With the assistance of ultrasound fusion imaging ,thermal ablation of medium‐sized HCC is effective and safe w hich could achieve a higher technique efficacy rate and a lower L T P rate .

Objective To discuss the value of contrast-enhanced ultrasound (CEUS) in evaluating gallbladder injury during the thermal ablation of liver tumors adjacent to the gallbladder. Methods From January 2016 to March 2017, 40 patients with 42 hepatic tumors adjacent to the gallbladder who underwent ultrasonography-guided percutaneous microwave ablation or radiofrequency ablation in the Third Affiliated Hospital of Sun Yat-sen University were included in the study. Ultrasonography (US) was used to assess the change of gallbladder wall thickness before and after procedure. CEUS was used to assess the perfusion of gallbladder wall and determine the gallbladder injury immediately after ablation. Patients with bad perfusion of gallbladder wall accept combined treatment with cholecystectomy. The safety and therapeutic efficacy of the procedures were assessed in follow-up examinations. The change of gallbladder wallthickness were compared by signed ranks sum test. Results Assessed by US immediately after the ablations, gallbladder wall thickening adjacent to the ablated zone was noted in 8 of 40 patients. According the results of CEUS immediately after ablations, 38 patients was evaluated with good perfusion of gallbladder wall and 2 patients was evaluated with bad perfusion, who were treated with cholecystectomy. Perforation of the gallbladder was found in one of them. However, the necrosis of serosal tissue in gallbladder wall was confirmed by postoperative pathology. Another 4 patients with multiple gallbladder stones were also treated with cholecystectomy. Gallbladder wall thickening developed in six patients (17.6%) within 3 days after the ablation. Wall thickening showed complete disappearance on subsequent follow up US in 4 patients, and showed existence in 2 patients. However, complications related to the ablation such as acute cholecystitis and gallbladder perforation were not noted in 34 patients without cholecystectomy. There was significant difference in gallbladder wall thickness between preoperative and intraoperative assessment [5.00 mm (4.00-6.25 mm) vs 3.50 mm (3.00-5.00 mm), Z=-3.741, P < 0.001], as well as between preoperative and postoperative assessment[5.0 mm(3.0-8.0 mm)vs 3.5 mm(3.0-5.0 mm),Z=-3.735,P < 0.001].The complete ablation rate was 97.6% (41/42) based on one-month follow-up CT or MR imaging. Local tumor progression was not found in these completely ablated tumors during the follow-up period. Conclusion Immediate post-procedural CEUS can be used to demonstrate the perfusion of gallbladder wall in US-guided ablation of hepatic tumors adjacent to the gallbladder, which is helpful to determine thermal injury of the gallbladder.

Objective To explore the feasibility and convenience of automatic registration ultrasound-CT/MR fusion imaging based on hepatic vessel trees. Methods The PercuNav fusion imaging system of Philips Epiq 7 was used to perform ultrasound-CT/MR fusion imaging on 22 patients with focal liver lesions detected by contrast-enhanced CT or MR.Both automatic registration ultrasound-CT/MR fusion imaging based on hepatic vessel trees and the conventional ultrasound-CT/MR fusion imaging based on internal anatomic landmarks were employed for alignment in these patients.The results including the success rate of registration,duration time of initial registration,error of initial registration,number of times of fine-tuning, duration time of fine-tuning and the overall duration time of registration were compared between these two methods.Results The success rates of registration,duration time of initial registration,errors of initial registration,numbers of times of fine-tuning,duration time of fine-tuning and the overall duration time of registration for automatic registration ultrasound-CT/MR fusion imaging based on hepatic vessel trees and the conventional ultrasound-CT/MR fusion imaging based on internal anatomic landmarks were 72.73% and 95.45%,16.5 s (10~30 s) and 13 s (8~24 s),3 mm (1~14 mm) and 14 mm (2~43 mm),0 time (0 to 2 times) and 1 time (0~3 times),0 s(0~46 s) and 30 s (0~88 s),and 20 s (12~61 s) and 42 s (9~102 s),successively and respectively. There was no statistically significant difference in the success rates between these two methods ( P >0.05).The duration time of initial registration of conventional method was less than that of automatic registration method( P <0.05).The error of initial registration,number of times of fine-tuning,duration time of fine-tuning and the overall duration time of registration of automatic registration method were superior to those of conventional method ( P < 0.05).Conclusions Automatic registration ultrasound-CT/MR fusion imaging based on hepatic vessel trees is feasible. It is also more convenient than conventional ultrasound-CT/MR fusion imaging based on internal anatomic landmarks.

Objective To investigate the precision of full six-degree target shift corrections using the ArcCHECK system.Metbods Fourteen patients receiving intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) in Fujian Medical University Cancer Hospital from May to September,2015 were selected.The first treatment setup errors were obtained using cone-beam computed tomography.The setup errors were simulated in ArcCHECK,and the full six-degree target shift corrections was used to correct the errors.The plans without and with setup errors and the plan with corrected setup errors were taken.The paired t-test was used to compare dose to agreement (DTA) and Gamma passing rates between the plan without setup errors and the plan with setup errors and plan with corrected setup errors.Results The DTA and Gamma passing rates were (96.76± 1.57)％ and (98.35±0.92)％ for the plan without setup errors,(59± 21.42) ％ and (62.86± 21.63) ％ for the plan with setup errors,and (91.41± 4.82) ％ and (94.11±4.33)％ for the plan with corrected setup errors.There were significant differences between the plan without setup errors and the plan with setup errors and plan with corrected setup errors in DTA passing rate (t=6.64 and 5.13,both P＜0.05) and Gamma passing rate (t=6.15 and 4.19,both P＜0.05).Conclusions The full six-degree target shift corrections can be used in IMRT for NPC,with good results in correcting setup errors and improving the precision for IMRT dose distribution.

Objective To evaluate the clinical application value of intra-biliary contrast-enhanced ultrasound (IB-CEUS) in the evaluation of degree of biliary obstruction.Methods Clinical data of 105 patients with biliary obstructive disease who were diagnosed and treated in the Third Affiliated Hospital of Sun Yat-sen University from January 2008 to December 2012 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. There were74 males and 31 females with the age ranging from 30 to 88 years old and the median age of 55 years old. Conventional ultrasound (CUS) and IB-CEUS were used to detect the biliary obstructive lesions in 105 patients. X-ray or CT cholangiography was used as the gold standard for diagnosis. The diagnostic efficacy of two methods was compared. The differences between these two methods and the gold standard in diagnosing the degree of biliary obstruction were evaluated by McNemar test. The consistency of the Results was assessed by Kappa consistency.Results The diagnostic sensitivity and negative predictive value of two methods were 100％ in diagnosing the complete obstruction of primary and second grade intrahepatic bile ducts. The specificity, positive predictive value and accuracy of IB-CEUS in diagnosing the complete obstruction of primary grade intrahepatic bile ducts was respectively 95.8％, 91.9％ and 97.1％, higher than 57.7％, 53.1％ and 71.4％ of CUS. The specificity, positive predictive value and accuracy of IB-CEUS in diagnosing the complete obstruction of second grade intrahepatic bile ducts was respectively 97.3％, 83.3％ and 97.6％, higher than 58.6％, 24.6％ and 63.5％ of CUS. Significant difference was observed in the diagnosis between CUS and gold standard (χ2=28.033, 46.000; P<0.05). CUS was fair or poor for the consistency of Results in diagnosing the complete biliary obstruction of primary and second grade intrahepatic bile ducts (k=0.470, 0.252), while no significant difference was observed between IB-CEUS and gold standard (P=0.250) and the consistency of Results was good (k=0.936, 0.896).Conclusions IB-CEUS can accurately evaluate the degree of intrahepatic biliary obstruction. The efficacy of IB-CEUS is better than that of CUS, and it has a good diagnostic consistency with the gold standard.