[Clinical and chest CT features of immune checkpoint inhibitor-related pneumonitis].

Objective: To explore the clinical and chest computed tomography (CT) features and the outcome of immune checkpoint inhibitor-related pneumonitis (CIP). Methods: Clinical and chest CT data of 38 CIP patients with malignant tumors from the Cancer Hospital, Chinese Academy of Medical Sciences between August 2017 and April 2021 were retrospectively reviewed, and the outcomes of pneumonitis were followed up. Results: The median time from the administration of immune checkpoint inhibitors (ICIs) to the onset of CIP was 72.5 days in 38 patients with CIP, and 22 patients developed CIP within 3 months after the administration of ICIs. The median occurrence time of CIP in 24 lung cancer patients was 54.5 days, earlier than 119.0 days of non-lung cancer patients (P=0.138), with no significant statistical difference. 34 patients (89.5%) were accompanied by symptoms when CIP occurred. The common clinical symptoms were cough (29 cases) and dyspnea (27 cases). The distribution of CIP on chest CT was asymmetric in 31 cases and symmetrical in 7 cases. Among the 24 lung cancer patients, inflammation was mainly distributed ipsilateral to the primary lung cancer site in 16 cases and diffusely distributed throughout the lung in 8 cases. Ground glass opacities (37 cases) and consolidation (30 cases) were the common imaging manifestations, and organizing pneumonia (OP) pattern (15 cases) was the most common pattern. In 30 CIP patients who were followed up for longer than one month, 17 cases had complete absorption (complete absorption group), and 13 cases had partial absorption or kept stable (incomplete absorption group). The median occurrence time of CIP in the complete absorption group was 55 days, shorter than 128 days of the incomplete absorption group (P=0.022). Compared with the incomplete absorption group, there were less consolidation(P=0.010) and CIP were all classified as hypersensitivity pneumonitis (HP) pattern (P=0.004) in the complete absorption group. Conclusions: CIP often occurs within 3 months after ICIs treatment, and the clinical and CT findings are lack of specificity. Radiologic features may have a profound value in predicting the outcome of CIP.

[Diagnostic values of conventional tumor markers and their combination with chest CT for patients with stageâ A lung cancer].

Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage ⅠA lung cancer. Methods: A total of 1 155 patients with stage ⅠA lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of ⅠA1 to ⅠA3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageⅠA1, ⅠA2 and ⅠA3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage ⅠA lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage ⅠA lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage ⅠA lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.

[The performance of digital chest radiographs in the detection and diagnosis of pulmonary nodules and the consistency among readers].

Objective: To investigate the detection and diagnostic efficacy of chest radiographs for ≤30 mm pulmonary nodules and the factors affecting them, and to compare the level of consistency among readers. Methods: A total of 43 patients with asymptomatic pulmonary nodules who consulted in Cancer Hospital, Chinese Academy of Medical Sciences from 2012 to 2014 and had chest CT and X-ray chest radiographs during the same period were retrospectively selected, and one nodule ≤30 mm was visible on chest CT images in the whole group (total 43 nodules in the whole group). One senior radiologist with more than 20 years of experience in imaging diagnosis reviewed CT images and recording the size, morphology, location, and density of nodules was selected retrospectively. Six radiologists with different levels of experience (2 residents, 2 attending physicians and 2 associate chief physicians independently reviewed the chest images and recorded the time of review, nodule detection, and diagnostic opinion. The CT imaging characteristics of detected and undetected nodules on X images were compared, and the factors affecting the detection of nodules on X-ray images were analyzed. Detection sensitivity and diagnosis accuracy rate of 6 radiologists were calculated, and the level of consistency among them was compared to analyze the influence of radiologists' seniority and reading time on the diagnosis results. Results: The number of nodules detected by all 6 radiologists was 17, with a sensitivity of detection of 39.5%(17/43). The number of nodules detected by ≥5, ≥4, ≥3, ≥2, and ≥1 physicians was 20, 21, 23, 25, and 28 nodules, respectively, with detection sensitivities of 46.5%, 48.8%, 53.5%, 58.1%, and 65.1%, respectively. Reasons for false-negative result of detection on X-ray images included the size, location, density, and morphology of the nodule. The sensitivity of detecting ≤30 mm, ≤20 mm, ≤15 mm, and ≤10 mm nodules was 46.5%-58.1%, 45.9%-54.1%, 36.0%-44.0%, and 36.4% for the 6 radiologists, respectively; the diagnosis accuracy rate was 19.0%-85.0%, 16.7%-6.5%, 18.2%-80.0%, and 0%-75.0%, respectively. The consistency of nodule detection among 6 doctors was good (Kappa value: 0.629-0.907) and the consistency of diagnostic results among them was moderate or poor (Kappa value: 0.350-0.653). The higher the radiologist's seniority, the shorter the time required to read the images. The reading time and the seniority of the radiologists had no significant influence on the detection and diagnosis results (P>0.05). Conclusions: The ability of radiographs to detect lung nodules ≤30 mm is limited, and the ability to determine the nature of the nodules is not sufficient, and the increase in reading time and seniority of the radiologists will not improve the diagnostic accuracy. X-ray film exam alone is not suitable for lung cancer diagnosis.

[Risk factor assessment and adverse outcome prediction of placenta accreta in pregnant women after cesarean section complicated with placenta previa: a national multicenter retrospective study].

Objective: To study the risk factors of adverse pregnancy outcomes for the diagnosis and treatment of pregnancy after cesarean section complicated with placenta previa. Methods: A national multicenter retrospective study was conducted to select a total of 747 pregnant women with the third trimester singleton pregnancy after cesarean section complicated with placenta previa from 12 tertiary hospitals in January 1st to December 31st, 2018. The risk factors of severe adverse outcomes [hysterectomy, intraoperative blood loss ≥1 000 ml, intraoperative diagnosis of placenta accreta spectrum disorders (PAS)] in pregnant women with second pregnancy complicated with placenta previa after cesarean section were investigated by logistic regression analysis. The roles of prenatal ultrasonography and magnetic resonance imaging (MRI) in the prediction of PAS and severe adverse outcomes were observed. According to whether vascular intervention was performed (uterine artery embolization or abdominal aortic balloon occlusion), the pregnant women were divided into the blocked group and the unblocked group, and the maternal and infant perinatal outcomes between the two groups were compared. Results: (1) General information: the hysterectomy rate of 747 pregnant women with second pregnancy complicated with placenta previa after cesarean section was 10.4% (78/747), the intraoperative blood loss ≥1 000 ml in 55.8% (417/747), and PAS was confirmed in 47.5% (355/747). The incidence of uterine rupture was 0.8% (6/747). (2) Analysis of risk factors for severe adverse outcomes: based on binary unconditioned logistic regression univariate and multivariate analysis, the risk factors for hysterectomy were the mode of vascular embolization and intraoperative blood loss. The probability of hysterectomy with uterine artery embolization was 5.319 times higher than that with abdominal aortic balloon occlusion (95%CI: 1.346-21.018). The risk factors of intraoperative blood loss ≥1 000 ml were the number of cesarean section delivery, ultrasonography indicated PAS and suspected PAS, intraoperative PAS and complete placenta previa. The risk factors for intraoperative PAS were uterine scar thickness, ultrasonography indicated PAS and suspected PAS, MRI indicated PAS and suspected PAS, and complete placenta previa. (3) The roles of ultrasonography and MRI in predicting PAS: the sensitivity and specificity of ultrasonography in predicting PAS were 47.5% and 88.4%; the kappa value was 0.279 (P<0.001), with fair agreement. The sensitivity and specificity of MRI to predict PAS were 79.2% and 97.8%, respectively. The kappa value was 0.702 (P<0.001), indicating a good agreement. The intraoperative blood loss and hysterectomy rate of pregnant women with PAS indicated by ultrasonography and MRI were significantly higher than those with PAS only by ultrasonography or MRI. (4) Influence of vascular occlusion on pregnancy outcome: there were no significant differences in intraoperative blood loss and incidence of intraoperative bleeding ≥1 000 ml between the blocked group and the unblocked group (all P>0.05). There was no significant difference in intraoperative blood loss between the pregnant women with abdominal aortic balloon occlusion, uterine artery embolization and those without occlusion (P=0.409). The hysterectomy rate of pregnant women with uterine artery embolization was significantly higher than those with abdominal aortic balloon occlusion [39.3% (22/56) vs 10.0% (5/50), P=0.001]. Conclusions: In the third trimester of pregnancy with placenta previa after cesarean section, MRI examination has better consistency in predicting PAS than ultrasonography examination. Ultrasonography examination combined with MRI examination could effectively predict the hysterectomy rate and intraoperative blood loss. Vascular occlusion could not reduce the amount of intraoperative blood loss. The hysterectomy rate of pregnant women with uterine artery embolization is higher than those with abdominal aortic balloon occlusion.

[Prevalence and risk factors of coronary artery calcification on lung cancer screening with low-dose CT].

Objective: To investigate the prevalence and risk factors of coronary artery calcification (CAC) on lung cancer screening with low-dose computed tomography (LDCT). Methods: A total of 4 989 asymptomatic subjects (2 542 males and 2 447 females) who underwent LDCT lung cancer screening were recruited at Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2017. The visual scoring method was used to assess coronary artery calcification score. χ(2) test or independent t-test was used to compare the difference of CAC positive rate among different groups. Multivariate logistic regression was used to analyze risk factors associated with CAC in the study. Results: Of the 4 989 asymptomatic subjects, CAC occurred in 1 018 cases. The positive rate was 20.4%, of which mild, moderate and severe calcification accounted for 86.3%, 11.4% and 2.3%, respectively. Gender, age, BMI, education level, occupation, smoking history, diabetes, hypertension and hyperlipidemia had statistically significant differences in CAC positive rates among groups. Multivariate logistic regression analysis showed that gender, age, diabetes, hypertension, hyperlipidemia and smoking history were risk factors for CAC. Age, diabetes, hypertension and smoking history were statistically significant risk factors between the mild and moderate CAC group. A total of 1 730 coronary arteries in 1 018 CAC positive cases had calcification, CAC positive rate of left anterior descending was the highest(51.3%); 568 cases (55.8%) were single vessel calcification, 450 cases (44.2%) were multiple vessel calcification. Conclusions: LDCT can be used for the 'one-stop' early detection of lung cancer and coronary atherosclerosis. Gender, age, diabetes, hypertension, hyperlipidemia and smoking are related risk factors for coronary atherosclerosis.

[Evaluation of the diagnosis and treatment of cesarean scar pregnancy induced in the second trimester: a national multicenter retrospective study].

Objective: To study the risk factors of adverse pregnancy outcomes for induced abortion of cesarean scar pregnancy in midtrimester. Methods: A national multicenter retrospective study was conducted. A total of 154 singletons pregnant women with cesarean scar pregnancy during the second trimester induced abortion by various reasons in 12 tertiary A hospitals were selected, their pregnant outcomes were observed and the risk factors of serious adverse outcomes were analyzed with univariate and multivariate logstic regression; the role of ultrasound and MRI in predicting placenta accreta and severe adverse outcomes was evaluated, the effectiveness of uterine artery embolization (UAE) in preventing hemorrhage in pregnant women with and without placenta accreta was compared. Results: Among 154 subjects, the rate of placenta accreta was 42.2% (65/154), the rate of postpartum hemorrhage≥1 000 ml was 39.0% (60/154), the rate of hysterectomy was 14.9% (23/154), the rate of uterine rupture was 0.6% (1/154). The risk factor of postpartum hemorrhage≥1 000 ml and hysterectomy was placenta accreta (P<0.01). For each increase in the number of parity, the risk of placenta accreta increased 2.385 times (95%CI: 1.046-5.439; P=0.039); and the risk of placenta accreta decreased with increasing ultrasound measurement of scar myometrium thickness (OR=0.033, 95%CI: 0.001-0.762; P=0.033). The amount of postpartum hemorrhage and hysterectomy rate in the group with placenta accreta diagnosed by ultrasound combined with MRI were not significantly different from those in the group with placenta accreta diagnosed by ultrasound only or MRI only (all P>0.05). For pregnant women with placenta accreta, there were no significant difference in the amount of bleeding and hysterectomy rate between the UAE group [median: 1 300 ml; 34% (16/47)] and the non-embolization group (all P>0.05); in pregnant women without placenta accreta, the amount of bleeding in the UAE group was lower than that in the non-embolization group (median: 100 vs 600 ml; P<0.01), but there was no significant difference in hysterectomy rate [2% (1/56) vs 9% (3/33); P>0.05]. Conclusions: (1) Placenta accreta is the only risk factor of postpartum hemorrhage≥1 000 ml with hysterectomy for induced abortion of cesarean scar pregnancy in midtrimester; multi-parity and ultrasound measurement of scar myometrium thickness are risk factors for placenta accreta. (2) The technique of using ultrasound and MRI in predicting placenta accreta of cesarean scar pregnancy needs to be improved. (3) It is necessary to discuss of UAE in preventing postpartum hemorrhage for induced abortion of cesarean scar pregnancy in midtrimester.

[Association between healthy lifestyle and risk of rehospitalization in male or female patients with chronic heart failure].

Objective: To explore the association between healthy lifestyle and risk of rehospitalization in male or female patients with chronic heart failure (CHF). Methods: Discharged patients with CHF of Henan Provincial People's Hospital Collaboration Hospital were recruited in our study from January 1,2017 to December 31, 2018. The basic information of patients were collected through the electronic medical record system,the questionnaires were used to collect the related influencing factors. Healthy lifestyle includes 4 items, namely non-smoking, moderate exercise, healthy body mass index (BMI) and reasonable diet.Multivariate logistic regression was used to analyze the association between healthy lifestyle and the risk of rehospitalization of CHF patients of different genders. Results: A total of 2 697 patients with CHF were enrolled in this study, including 1 308 male patients(621 rehospitalizations,687 controls)and 1 389 female patients(684 rehospitalizations,705 controls).Among male patients, there was no significant difference in age, residence, marital status, education level, average monthly income, and medical insurance between the rehospitalization group and the control group (all P>0.05). Among female patients, there was no significant difference in age, residence, marital status, education level, average monthly income, and medical insurance between the rehospitalization group and the control group (all P>0.05). Whether in male or female patients with CHF, we found that patients with 4 healthy lifestyles were associated with reduced risk of rehospitalization: male patients OR=0.34, 95%CI 0.11-0.99, P=0.002,female patients OR=0.27, 95%CI 0.13-0.79, P=0.012. A combination of non-smoking and any other 2 healthy lifestyles was associated with reduced risk of rehospitalization: male patients with no smoking, moderate exercise, healthy BMI, OR=0.32, 95%CI 0.11-0.99, P=0.043; female patients OR=0.28, 95%CI 0.12-0.93, P=0.032;male patients with no smoking, moderate exercise, reasonable diet OR=0.42, 95%CI 0.24-0.98, P=0.044,female patients OR=0.40, 95%CI 0.12-0.94, P=0.031;male patients with no smoking, healthy BMI, reasonable diet OR=0.31, 95%CI 0.21-0.92, P=0.039,female patients OR=0.27,95%CI 0.11-0.87, P=0.014. In female patients with CHF, the combination of non-smoking and moderate sports was associated with reduced risk of hospitalization (OR=0.23, 95%CI 0.19-0.97, P=0.038), while no similar results were seen in male patients (OR=0.65, 95%CI 0.33-1.84, P=0.315). Conclusion: Healthy lifestyle is associated with reduced risk of rehospitalization in patients with CHF, and the related healthy lifestyle and its combination may differ between male and female patients.

[Risk factors for lung cancer based on low-dose computed tomography screening].

Objective: To analyze the risk factors related to lung cancer in participants with low-dose computed tomography (LDCT) screening, to provide data support for identifying high-risk groups of lung cancer and to improve the effectiveness of LDCT lung cancer screening. Methods: A total of 5 366 asymptomatic subjects (2 762 males and 2 604 females) who underwent LDCT lung cancer screening were recruited at Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2017. The result of LDCT and the risk factors of participants were analyzed. The LDCT positive results were defined as solid or part-solid nodules≥5 mm and non-solid nodule≥8 mm. A total of 12 factors were included and multivariate logistic regression was used to analyze the risk factors associated with lung cancer in the study. Results: Of the 5 366 asymptomatic subjects, 389 were positive and 4 977 were negative for LDCT screening. Among them, 26 of 389 positive cases were confirmed as lung cancers pathologically, and the detection rate of stage I lung cancer was 92.3% (24/26). Multivariate logistic regression showed that age, smoking, low level of education were the relevant risk factors for lung cancer and positive nodules. A stratified analysis of age showed that no risk factors were detected in the 40-49 years old group, while age, smoking, low level of education (primary school and below) were recognized as risk factors in the ≥50 years old group. No statistically significant risk factor was detected between the lung cancer group and the positive nodules group. Conclusions: Age, smoking, and low level of education (primary school and below) are related risk factors for lung cancer and positive nodules. People aged 50 years or older, smoking, and low level of education may be a high risk group for lung cancer. LDCT can effectively detect early lung cancer.

[HRCT features differentiate synchronous multiple primary lung adenocarcinomas from intrapulmonary metastases].

Objective: To investigate the high resolution CT (HRCT) features of lung adenocarcinoma for differentiating synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. Methods: The clinical and imaging features of 131 lesions from 62 patients of synchronous multiple primary lung adenocarcinoma (primary group) and 67 lesions from 31 patients of lung adenocarcinoma with intrapulmonary metastases (metastasis group) were retrospectively analyzed. According to the types of lesion, including pure ground glass nodule (pGGN), mixed ground glass nodule (mGGN) and solid nodule (SN), the image feature matching types of patients were divided into 7 types. The differences of image feature matching types between the primary group and the metastasis group were compared. Multiple lesions in the lung of patients were classified into the main lesion and the concomitant lesions according to their size. The differences including the size of the main lesion and the concomitant lesion (long diameter of nodule, long diameter of solid component in nodule), whether it contains ground glass components in nodule, shape, lobulation, margin, spiculation, bubble-like lucency, pleural retraction and pleural attachment were recorded and analyzed. The differences of image features of main lesion and the concomitant lesion in the primary group and the metastasis group were compared. Results: The image feature matching types of pGGN + mGGN and mGGN + mGGN were more common in the primary group, and the ground glass component contained pGGN or mGGN was accounted for 62.9%(39/62). At least one lesion containing the ground glass component was accounted for 96.8% (60/62). There were two types in metastatic groups, mGGN+ SN and SN+ SN accounting for 6.5% (2/31) and 93.5% (29/31), respectively. There were significant differences in image feature matching types between the primary group and metastatic group (P<0.01). Univariate analysis of the main lesions between the two groups showed that the gender, smoking history, long diameter of the main lesion, long diameter of the solid component, the ground glass component and pleural attachment were statistically different (P<0.05). Further analysis by multivariate logistic regression showed that the male (OR=5.742, P=0.010), SN (OR=41.291, P<0.01) and pleural attachment (OR=9.288, P=0.001) were the three significant risk factors associated with the main lesions in metastasis group.The most common concomitant lesions in primary group were pGGN, containing the ground glass component. However, all of the concomitant lesions in the metastatic group were SN (P<0.01), showing round lesions with well-defined margin, attaching the pleura (P<0.05). Conclusions: The HRCT features of lung adenocarcinoma can differentiate synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. At least one lesion contains ground glass components (pGGN or mGGN) in synchronous multiple primary lung adenocarcinoma, while SN is more common in lung adenocarcinoma with lung metastasis. Lung cancer with intrapulmonary metastasis can be considered when the main lesion is SN with pleural attachment and the intrapulmonary accompanying lesion is also solid nodules without lobular, speculation and bubble-like lucency.

[The volume and mass growth of persisted pulmonary nodules detected in low-dose CT screening and its influence factors].

Objective: To evaluate the changes of volume and mass of pulmonary nodules which were detected in low-dose computed tomography (LDCT) screening, and to analyze the influencing factors. Methods: This retrospective study analyzed the CT images of the participants who underwent at least two chest LDCT scanning from March 2009 to December 2015 in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The inclusion criteria was the nodule diameter ≥6 mm; the volume growth was defined as ≥20%. Fifty-one pulmonary nodules (PNs) were selected among 51 enrolled participants (26 men and 25 women). According to characteristic of nodule and risk stratification of participant, the nodules were classified into different groups (10 non-solid nodules, 17 part-solid nodules and 24 solid nodules; 14 PNs in high-risk group, 12 PNs in moderate-risk group and 25 PNs in low-risk group). The Lung-VCAR software was used to measure the diameter and volume of the PNs, and all nodules were calculated for the volume doubling time (VDT) and mass doubling time (MDT). Results: Among the 51 PNs, the diameter of 33 nodules increased more than 1.5 mm while 18 nodules increased less than 1.5 mm. The median VDT of part-solid nodules was 364 days, which was shorter than that of non-solid nodules and solid nodules (761 and 819 days, respectively), the differences were statistically significant (both P<0.05). The median MDT of part-solid nodules was 351 days, which was lower than that of non-solid nodules and solid nodules (772 days and 840 days, respectively). The difference was statistically significant (P<0.05). The median VDT and MDT of the pulmonary nodules in the high-risk group were 181 days and 256 days, respectively, which were lower than those in the low risk group (1 037 days and 1 035 days, respectively). VDT has good correlation with MDT (r=0.909, P<0.001). Conclusions: Both the characteristic of PNs and the risk status of the participants could affect the growth of nodules in LDCT screening. The part-solid nodules and high-risk group nodules grew relatively faster, which should be closely focused on. Compared with the two-dimensional diameter, the three-dimensional quantitative indicators (VDT and MDT) were more sensitive for nodule growth. The mass changes of part-solid nodules were earlier than that of volume.

First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study.

BACKGROUND: Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. PATIENTS AND METHODS: Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety. RESULTS: Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group. CONCLUSIONS: First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.

Effect of vitrification on the mRNA transcriptome of bovine oocytes.

Vitrification has been shown to decrease the developmental capacity of mammalian oocytes, and this is closely associated with the abnormal mRNA expressions of vitrified oocytes. However, the effect of vitrification on transcriptional machinery of oocytes examined by RNA sequencing (RNA-seq) has yet to be defined. In the present study, the mRNA transcriptomes of fresh and vitrified bovine oocytes were analysed by Smart-seq2 with the differently expressed genes determined by DEseq2 (an adjusted p-value of .05 and a minimum fold change of 2). The differentially expressed mRNAs were then searched against the Gene Ontology (GO) and Genomes (KEGG) database. Finally, the mRNA expressions of 10 candidate genes were validated using quantitative real-time PCR (qRT-PCR). Approximately 12,000 genes were detected in each sample of fresh or vitrified oocytes. Of these, the expression levels of 102 genes differed significantly in vitrified groups: 12 genes mainly involved in cell cycle, fertilization and glucose metabolism were upregulated, and 90 genes mainly involved in mitochondria, ribosomal protein, cytoskeleton, transmembrane protein, cell cycle and calcium ions were downregulated. GO analysis showed that these genes were mainly enriched in terms of membrane-bounded organelles, macromolecular complex, and intracellular part. The mRNA expression levels of 10 candidate genes selected randomly were in agreement with the results of the RNA-seq. In conclusion, our results showed that vitrification affected the mRNA transcriptome of bovine oocytes by downregulating genes, which contributed to the decreased developmental capacity of vitrified oocytes. Our findings will be useful in determining approaches to improve the efficiency of vitrified oocytes.

Comparison of lumbar pedicular dynamic stabilisation systems versus fusion for the treatment of lumbar degenerative disc disease: A meta-analysis.

This study aimed to systematically compare the safety, effectiveness and radiological changes after lumbar pedicular dynamic stabilisation systems and fusion to treat lumbar degenerative disc disease . All studies that were performed to compare various lumbar pedicular dynamic stabilisation systems with any lumbar fusion to treat lumbar degenerative disc disease and were published until April 30, 2015 were acquired through a comprehensive search in various databases. A meta-analysis was performed after the methodological qualities of trials were assessed and after data were extracted. Sixteen trials with 881 patients with a short-term follow-up (within 2 years) and a middle-term follow-up (2 to 4 years) were identified. Patients treated with lumbar pedicular dynamic stabilisation systems experienced more significant advantages in terms of operation time, intra-operative blood loss, complications and adjacent segment degeneration/disease development than those treated with lumbar fusion. The two groups did not significantly differ in terms of improvement in Oswestry Disability Index, visual analogue scale scores, satisfaction rate of operation and range of motion of adjacent segments. Lumbar pedicular dynamic stabilisation systems is superior to lumbar fusion to some extent, although some of its advantages have yet to be verified and compared with those of lumbar fusion. However, the two interventions were not significantly different in terms of relief in symptoms, functional recovery and motion preservation. Thus, lumbar pedicular dynamic stabilisation systems is recommended for its safety. A prudent attitude is necessary to choose between these interventions on the basis of effectiveness and changes in adjacent segments before a large-scale and long-term follow-up study can be performed.

[Patients of Escherichia coli bloodstream infection: analysis of antibiotic resistance and predictors of mortality].

Objective: To analyze the drug resistance of Escherichia coli (E.coli) from bloodstream infection (BSI) and the predictors of mortality in E. coli bloodstream infection (BSI). Methods: The clinical data of 139 E. coli BSI cases diagnosed from January 2012 to December 2015 in The Second Affiliated Hospital of Zhejiang University School of Medicine, Lanxi Branch (Lanxi People's Hospital), Zhejiang Province, were retrospectively analyzed. The antimicrobial susceptibility testing was performed using Vitek 2 system. Extended-spectrum beta-lactamases (ESBLs) were detected by disk diffusion confirmatory testing. The factors associated with ESBLs-producing strains were identified by univariate analysis. Multivariate analysis was used to identify independent predictors of infection mortality by applying Logistic regression. Results: 42.4% of E. coli isolates were ESBLs-producing. The resistant rate of imipenem was 0.7%. The percent of ESBLs in hospital-acquired infection was higher than that in community-acquired infection but without statistical significance (48.7% versus 40.0%, P=0.350). Univariate analysis suggested that the percent of ESBLs-producing strains in BSI happened on ≥15 d after admission and in BSI of biliary tract infection source was 76.9% and 68.0%, which were much higher than those in BSI happened on <15 d after admission and in BSI of non-biliary tract infection source (34.6% and 36.8%, P=0.013 and 0.004). The overall mortality of E. coli BSI was 13.7%. Multivariate Logistic regression analysis indicated that Sequential Organ Failure Assessment (SOFA ) score (OR=1.393, P<0.001), ceftazidime non-susceptibility (OR=4.444, P=0.018) and liver cirrhosis (OR=13.513, P=0.001) were independent risk factors of mortality. Conclusions: The frequency of ESBLs-producing E. coli was high in primary hospital of Zhejiang Province. SOFA score, ceftazidime non-susceptibility and cirrhosis were predictors of poor outcome in E. coli BSI.

Transcriptome analyses of inner cell mass and trophectoderm cells isolated by magnetic-activated cell sorting from bovine blastocysts using single cell RNA-seq.

Research on bovine embryonic stem cells (bESCs) has been hampered because bESCs are cultured in conditions that are based on information obtained from culturing mouse and human inner cell mass (ICM) cells. The aim of this study was to compare gene expression in ICM and trophectoderm (TE) cell lineages of bovine embryos and to discuss the findings relative to information available for mice and humans. We separated a high-purity (>90%) ICM and TE from bovine blastocysts by magnetic-activated cell sorting and analysed their transcriptomes by single cell RNA-seq. Differentially expressed genes (DEGs) were assessed using Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases. Finally, qRT-PCR was performed to validate the RNA-seq results. From 207 DEGs identified (adjusted p ≤ .05; fold change ≥2), 159 and 48 had greater expression in the ICM and TE cells respectively. We validated 27 genes using qRT-PCR and found their expression patterns were mostly similar to those of RNA-seq, including 12 novel ICM-dominant (HNF4A, CCL24, FGFR4, IFITM3, PTCHD2, GJB5, FN1, KLK7, PRDM14, GRP, FGF19 and GCM1) and two novel TE-dominant (SLC10A1 and WNT4) genes. Bioinformatics analysis showed that these DEGs are involved in many important pathways, such as MAPK and cancer cell pathways, and these pathways have been shown to play essential roles in mouse and human ESCs in the self-renewal and pluripotent maintenance. As a conclusion, there were sufficient differences to allow us to conclude that the control of pluripotency in bovine ICM cells is species-specific.

[Current status of warfarin therapy in Chinese patients with nonvalvular atrial fibrillation: a single center analysis].

Objective: To investigate the current status of warfarin therapy and the related factors in patients with nonvalvular atrial fibrillation(NVAF) based on data from a single center. Methods: We analyzed clinical data including baseline clinical characteristics, complications, concomitant medications and anti-thrombotic treatment in patients who were admitted to our hospital with NVAF from January 2014 to June 2014. The data were analyzed by t test, Chi-square test, fisher exact test and binary logistic regression analysis for the above indexes with warfarin utilization. Results: A total of 600 patients enrolled in this study, 560(93.3%) patients had a CHA2DS2-VASc score≥1, 162(28.9%) patients received warfarin (alone or in combination with antiplatelet agents), 244(43.6%) patients were treated with aspirin, 137(24.5%) patients did not receive anti-thrombotic treatment. Of the 600 patients, 172(28.7%) patients were treated in line with the current guideline recommendation, 266(44.3%) patients were treated improperly, 23(3.8%) patients were over-treated, 139(23.2%) patients received no anti-thrombotic treatment. Factors associated with anti-thrombotic treatment were persistent atrial fibrillation (OR=3.92, 95%CI 1.43-10.78, P=0.008), radiofrequency ablation (OR=26.82, 95%CI 7.03-102.38, P<0.001), the use of statins (OR=3.35, 95%CI 1.30-8.63, P=0.012), anti-arrhythmic therapy (OR=3.42, 95%CI 1.29-9.07, P=0.014), and aspirin (OR=0.02, 95%CI 0-0.07, P<0.001). Conclusions: In this study, 428 (71.3%) NVAF patients were either un-treated, over-treated or inadequately treated. Intensive efforts are necessary to improve anti-thrombotic therapy status in NVAF population in China.

Genetic diversity and classification of Tibetan yak populations based on the mtDNA COIII gene.

To determine the level of genetic diversity and phylogenetic relationships among Tibetan yak populations, the mitochondrial DNA cytochrome c oxidase subunit 3 (COIII) genes of 378 yak individuals from 16 populations were analyzed in this study. The results showed that the length of cytochrome c oxidase subunit 3 gene sequences was 781 bp, with nucleotide frequencies of 29.2, 29.4, 26.1, and 15.2% for T, C, A, and G, respectively. A total of 26 haplotypes were identified, with 69 polymorphic sites, including 11 parsimony-informative sites and 58 single-nucleotide polymorphism sites. No deletions/insertions were found in sequence comparison, indicating that nucleotide mutation types were transitions and transversions. Haplotype and nucleotide diversities were 0.562 and 0.00138, respectively, indicating a high level of genetic diversity in Tibetan yak populations. Phylogenetic relationship analysis indicated that Tibetan yak populations are divided into 2 groups.

Effects of estrogen intervention on the biomechanical characteristics of serum SOD, MDA, and middle cerebral artery in aged female rats.

OBJECTIVE: This study aims to study the biological and biomechanical characteristics of the middle cerebral artery (MCA) in aged and estrogen-intervened aged rats, thereby providing biomechanical basis for clinics. MATERIALS AND METHODS: Thirty 18-month-old Sprague Dawley (SD) rats, 30 18-month-old estrogen-intervened SD rats, and 30 four-month-old SD rats were studied. The estrogen-intervened rats were given estradiol benzoate on the fifth feeding day. Thirty-four days after the feeding, the serum of each rat was obtained. The radioimmunoassay was performed for the content determination of serum E2, ER, malondialdehyde (MDA), and superoxide dismutase (SOD). The tensile test was performed to evaluate the MCA of each rat. RESULTS: Through the estrogen intervention, the serum contents of E2, ER, SOD, and MDA in old rats were restored to normal levels. The maximum stress, maximum strain, and elastic limit of the MCA in the aged estrogen-intervened rat group were greater than those of the non-intervened aged rat group, with a significant difference (p < 0.05). The elastic modulus in the aged estrogen-intervened rat group was less than that of the non-intervened aged rat group, with a significant difference (p < 0.05). CONCLUSION: E2 intervention can improve the flexibility, toughness, and compliance of MCA in aged rats.