Purpose: We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. Materials and Methods: This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. Results: The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. Conclusion EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Objective:To prepare specific molecular probe 18F-AlF-1, 4, 7-triazacylononane-1, 4, 7-triacetic acid-(polyethylene glycol) 4-ZD2 ( 18F-AlF-NOTA-PEG 4-ZD2) for targeting extradomain-B fibronectin (EDB-FN), and evaluate its properties in vitro and in vivo. Methods:18F-AlF-NOTA-PEG 4-ZD2 was prepared by one-step chelation labeling with Al 18F. The radiochemical purity and in vitro stability were determined by high performance liquid chromatography (HPLC). The partition coefficient (logP) of 18F-AlF-NOTA-PEG 4-ZD2 was evaluated, and the cell uptake experiment was carried out (triple-negative breast cancer (MDA-MB-231) cells (1×10 6/tube) were divided into 3 groups ( n=3 per group); positive group, inhibition group, control group). MicroPET imaging was performed on MDA-MB-231 bearing nude mice ( n=3) after 18F-AlF-NOTA-PEG 4-ZD2 injection (30, 60, 90, 120 min) and compared with blocking group ( n=3, NOTA-PEG 4-ZQ 2 was preinjected at 0.5 h before 18F-AIF-NOTA-PEG a-ZD2 injection). Independent-sample t test was used to analyze the data. Results:18F-AlF-NOTA-PEG 4-ZD2 was successfully prepared. The optimized radiochemical yield was (33.8±2.1)% (undecay corrected, n=8) and the radiochemical purity was >96%. After incubating 120 min at 37 ℃, the radiochemical purity of 18F-AlF-NOTA-PEG 4-ZD2 in human serum and PBS was >93%, indicating its good stability in vitro. The specific activity was (11.1±3.2) GBq/μmol, and logP was -1.43±0.05. The uptake value of tumor cells was (1.77±0.28) percentage applied activity (%AR)/10 6 cells at 120 min post-injection in positive group, and the total uptake value of the inhibition group was (0.76±0.07) %AR/10 6 cells ( t=4.30, P=0.032). MicroPET imaging in tumor bearing nude mice showed that 18F-AlF-NOTA-PEG 4-ZD2 was mainly metabolized by the liver and kidneys. The tumor uptake value was (1.94±0.21) percentage activity of injection dose per gram of tissue (%ID/g) at 60 min post-injection and the tumor/muscle ratio was 3.80±0.25 at 90 min post-injection in the experimental group, while the tumor uptake value of tumor bearing nude mice in the blocking group was (0.43±0.09) %ID/g at 60 min post-injection ( t=3.18, P=0.006). Conclusions:18F-AlF-NOTA-PEG 4-ZD2 can be prepared simply with high labeling rate and good stability in vitro, with high tumor uptake and tumor/muscle ratio in microPET imaging, and good specificity and long tumor residence time. The probe has good application prospect in breast cancer with high expression of fibronectin subtype EDB-FN.

To investigate the effect of multiple propofol anesthesia and operative trauma on neuroinflammation and cognitive function in development rats and its mechanism. A total of 104 13-day-old neonatal Sprague-Dawley rats were randomly divided into 4 groups with 26 rats in each group: control group was treated with saline q.d for propofol group was treated with propofol q.d for surgery group received abdominal surgery under local anesthesia and then treated with saline q.d for surgery with propofol group received propofol anesthesia plus abdominal surgery under local anesthesia with ropivacaine at d1, then treated with propofol q.d for At d2 of experiment, 13 rats from each group were sacrificed and brain tissue samples were taken, the concentration of TNF-α in hippocampus was detected with ELISA, the expression of caspase-3 and c-fos in hippocampal tissue was determined with immunohistochemical method, the number of apoptotic neurons in hippocampus was examined with TUNEL assay. Morris water maze test was used to examine the cognitive function of the rest rats at the age of 60 d, and the TNF-α concentration, caspase-3, c-fos expressions and the number of apoptotic neurons in hippocampus were also detected. Compared with control group, TNF-α concentration, caspase-3, c-fos expression and the neuroapoptosis in hippocampus increased significantly in other three groups (all <0.05). Compared with surgery group, propofol group and surgery with propofol group showed increased TNF-α level, caspase-3 and c-fos expressions and apoptotic cell numbers (all <0.05), but there was no significant difference between last two groups (all >0.05). Morris water maze test showed that there were no significant differences in swimming speed, escape latency, target quadrant residence time and crossing times among groups (all >0.05). TNF-α level, expressions of caspase-3 and c-fos and apoptotic cell numbers in hippocampus had no significant differences among the 4 adult rats groups (all >0.05). Abdominal surgery and multiple propofol treatment can induce neuroinflammation and neuroapoptosis in hippocampus of neonatal rats, however, which may not cause adverse effects on neurodevelopment and cognitive function when they grown up.
Anesthesia ; Animals ; Cognition ; Hippocampus ; Propofol/adverse effects* ; Rats ; Rats, Sprague-Dawley

To study the role of the activity in reducing the incidence of water leakage in digestive endoscopy, through the activity of the quality control circle (QCC), the reasons for water leakage and high maintenance cost are analyzed deeply. Then, the author formulated and implemented targeted measures to intervene in the non-standard aspects of daily management of endoscopy. Then targeted measures has been taken to improve the nonstandard daily management.Results demonstrate that the application of the quality control circle can significantly reduce the incidence of water leakage in the digestive endoscope and control the other faults caused by the leakage. This not only reduces the high maintenance cost of endoscopy, improves the utilization rate and turnover rate of endoscopy, but also fully explores personal potential, enhances team cohesion, and improves quality management awareness.

Objective:To invest the risk factors associated with delayed hemorrhage after pancreaticoduodenectomy occurred.Methods:A retrospective analysis was performed from January 2012 to June 2015 Shengjing hospital 511 cases of patients who accepted pancreaticoduodenectomy.Results:The incidence of PD postoperative delayed hemorrhage was 8.81％ (45/511).Univariate analysis shows:Preoperative bilirubin levels,pancreatic fistula,biliary fistula,postoperative abdominal infection are all the meaningful related factors(P＜0.05).With the application of multivariate logistic regression analysis,pancreatic fistula (OR=2.158) and abdominal infection (OR=3.051) were independent risk factors for postoperative delayed hemorrhages (P＜0.05).Conclusion:Dealing with the postoperative complications of PD like pancreatic fistula,abdominal infection and others,early detection and rapid diagnosis and correct treatment can effectively reduce the incidence of delayed hemorrhage.

Objective To investigate the correlation between serum level of insulin growth factor 1 (IGF-1) and the degree of liver fibrosis in patients with chronic hepatitis C (CHC) complicated to type 2 diabetes mellitus (T2DM). Methods The cases were divided into CHC with T2DM (39 cases), CHC (96 cases), T2DM (60 cases), and healthy control (60 cases) groups. Their human data were collected and the fasting blood glucose, insulin and insulin-like growth factor-1 levels were detected, and the insulin resistance index ( HOMA-IR) wwer calculated. The serum levels of alanine transaminase ( ALT) , aspartate transaminase ( AST) , hepatitis C virus ( HCV) RNA load and HCV genotypes were detected simultaneously in patients with hepatitis C, and liver stiffness were measured ( LSM) by transient elastography ( TE) and aspartate aminotransferase-to-platelet ratio index ( APRI) score was performed. Results ⑴ There was no significant difference between CHC with T2DM group and CHC group in diabetes family history(P>0. 05), but two groups were significantly lower than that of T2DM group (P<0. 05). ⑵The levels of fasting insu-lin (FI) and HOMA-IR in CHC with T2DM group and T2DM group were significantly higher than those in the other two groups (P<0. 05), while the levels of IGF-1 in two groups were significantly lower than those in the CHC group, and were more lower than the control group (P<0. 05). ⑶Compared the serum ALT, AST and HCV RNA load between CHC with T2DM group and CHC group, there had no significant differ-ence (P>0. 05);however, the proportion of 1b genotype, LSM and APRI score of CHC with T2DM group were significantly higher than those in CHC group(P<0. 05). ⑷ The level of serum IGF-1 was negatively correlated with HOMA-IR, LSM and APRI in CHC with T2DM group (r= -0. 71, -0. 75, -0. 69, P<0. 01). Conclusions The degree of hepatic fibrosis and the damage of IGF-1 synthesis in CHC patients with T2DM were significantly higher than those in non T2DM patients, which might be related to the insulin resistance caused by 1b genotype HCV infection.

OBJECTIVETo explore the anesthetic effects of repeated administration of propofol combined with vitamin C in mice.

METHODSForty mice were subjected to daily intraperitoneal injections of 80 mg/kg propofol (P80 group), 70 mg/kg propofol and 50 mg/kg vitamin C (P70+Vc50 group), 55 mg/kg propofol and 100 mg/kg vitamin C (P55+Vc100 group), or 50 mg/kg propofol and 200 mg/kg vitamin C (P50+Vc200 group) for 6 consecutive days, and the anesthesia induction time and anesthesia duration were recorded.

RESULTSCompared with the P80 group, the mice in P55 + Vc100 group and P50 + Vc200 group showed significantly shorter anesthesia duration on the first 3 days (P<0.05). In all the groups, anesthesia duration was significantly shortened in the following days compared with that on day 1 (P<0.01); anesthesia duration was shorter on day 3 than on day 2 in P50 + Vc200 group (P<0.01), and was shorter on days 4, 5, and 6 than on day 2 in all the groups (P<0.01). In all the groups, the rate of loss of righting reflex (LORR) decreased gradually with time in a similar pattern.

CONCLUSIONVitamin C can reduce the dose of propofol without obviously affecting the anesthetic effect to reduce the incidence of drug tolerance and potential dose-related side effects of propofol.

Anesthesia ; Anesthesia Recovery Period ; Anesthetics, Intravenous ; administration & dosage ; pharmacology ; Animals ; Ascorbic Acid ; administration & dosage ; pharmacology ; Drug Tolerance ; Mice ; Propofol ; administration & dosage ; pharmacology

Background and purpose:Positron emission tomography-computed tomography (PET/CT) is playing an increasingly important role in the diagnosis, therapy and follow-up of lymphoma patients. This study aimed to explore clinical and pathological features and bone marrow infiltration status in lymphoma patients with diffused high bone marrow glucose uptake on18F-FDG PET/CT.Methods:It was a retrospective study. Bone marrow infiltration status, pathological and clinical data from 62 cases of pathologically diagnosed lymphoma and diffused high bone marrow glucose uptake were analyzed.Results:Distribution of histopathological subtype in those cases was in accordance with that in previously reported Chinese lymphoma patients. Significant difference was demonstrated in standard uptake value (SUV) between pa-tients with aggressive and indolent histopathological subtypes (8.43vs 5.38,P=0.048), patients with and without B symp-toms (8.30vs 5.72,P=0.033), and patients with and without bone marrow infiltration (8.78vs 6.96,P=0.020). 32 patients were diagnosed as “bone marrow infiltration” by bone marrow biopsy. There was significant difference in histopathologi-cal subtype distribution between patients with and without bone marrow infiltration (P=0.001). In patients with bone marrow infiltration, there were higher proportions of mantle cell lymphoma, nodal marginal zone B cell lymphoma, Burkitt’s lym-phoma and anaplastic large cell lymphoma. In contrast, patients without bone marrow infiltration suffered more from diffuse large B-cell lymphoma, peripheral T cell lymphoma, enteropathic T cell lymphoma and extranodal NK/T-cell lymphoma (nasal type). False positive results in bone marrow glucose uptake may be caused by fever or anemia.Conclusion:Diffused high bone marrow glucose uptake on18F-FDG PET/CT should be evaluated in combination with the uptake values, clinical features and histological subtypes, to minimize the misdiagnosis and to better guide staging and therapy of lymphoma.

Objective To investigate the difficulty, safety and clinical efficacy of the pterional approach from the side of open A2 plane vs the approach from the side of closed A2 plane for anterosuperior-pointing anterior communicat?ing artery aneurysms (ACoAA). Methods Forty-two patients with anterosuperior-pointing ACoAA treated by microsurgi?cal clipping were divided into two groups of the approach from the side of open A2 plane (n=22) and the approach from the side of closed A2 plane (n=20). Primary objective endpoints were rates of gyrus rectus aspiration, displacement of the ipsilateral A2 and surgical-related complications, clipping results, incidence of cognitive function impairment and Glasgow Outcome Scale (GOS) at 6 months after treatment. Results The incidence of gyrus rectus aspiration and dis?placement of the ipsilateral A2, cognitive impairment at 6 months after treatment and the surgical-related complications was also significant lower in the approach from the side of open A2 plane than in the approach from the side of closed A2 plane [4(18.2%) cases vs. 11(55.0%) cases, χ2=6.185, P<0.05;4(18.2%) cases vs. 10(50.0%) cases, χ2=4.773, P<0.05;1 (4.5%) case vs. 7(35.0%) cases, χ2=4.481 P<0.05]. There were no significant differences in postoperative clipping results and GOS at 6 months after treatment between two approaches (P>0.05). Conclusions The pterional approach from the side of open A2 plane in patients with anterosuperior-pointing ACoAA allows the aneurysmal necks to be secured safely, decreases operation difficulty and prevents surgical-related complications.

Objective To explore the anesthetic effects of repeated administration of propofol combined with vitamin C in mice. Methods Forty mice were subjected to daily intraperitoneal injections of 80 mg/kg propofol (P80 group), 70 mg/kg propofol and 50 mg/kg vitamin C (P70+Vc50 group), 55 mg/kg propofol and 100 mg/kg vitamin C (P55+Vc100 group), or 50 mg/kg propofol and 200 mg/kg vitamin C (P50+Vc200 group) for 6 consecutive days, and the anesthesia induction time and anesthesia duration were recorded. Results Compared with the P80 group, the mice in P55 + Vc100 group and P50 + Vc200 group showed significantly shorter anesthesia duration on the first 3 days (P<0.05). In all the groups, anesthesia duration was significantly shortened in the following days compared with that on day 1 (P<0.01);anesthesia duration was shorter on day 3 than on day 2 in P50+Vc200 group (P<0.01), and was shorter on days 4, 5, and 6 than on day 2 in all the groups (P<0.01). In all the groups, the rate of loss of righting reflex (LORR) decreased gradually with time in a similar pattern. Conclusions Vitamin C can reduce the dose of propofol without obviously affecting the anesthetic effect to reduce the incidence of drug tolerance and potential dose-related side effects of propofol.