177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Anaplastic Lymphoma Kinase/therapeutic use* ; Crizotinib/therapeutic use* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/pharmacology* ; Gene Frequency

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Objective:To explore the value of monoenergetic imaging on dual-layer spectral detector CT combined with individual injection protocol of contrast medium in brain CT angiography (CTA).Methods:Seventy-six patients who underwent brain CTA on the Philips IQon dual-layer spectral detector CT and individual injection protocol of contrast medium in Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from August to November 2020 were retrospectively analyzed. Objective and subjective evaluation of image quality was performed in conventional energetic images (conventional group) which derived from 120 kVp hybrid iterative reconstruction algorithm and 50 keV virtual monoenergetic images (test group) which derived from spectral reconstruction algorithm. The objective evaluation content included CT values, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of internal carotid artery and middle cerebral artery, CT values and standard deviation (SD) of brain parenchyma. The subjective evaluation was completed by two senior radiologists according to the 5-point scale, and the inter-agreement between two radiologists was evaluated by Kappa test. Paired t test or Wilcoxon rank test was used for analysis between two groups. Results:The SNR and CNR of both internal carotid artery and middle cerebral artery, as well as CT values of internal carotid artery, middle cerebral artery and brain parenchyma, were significantly higher in test group than that in conventional group (all P<0.001). The subjective scores of two radiologists for test group were both 5 (5, 5) points, and the subjective scores for conventional group were both 4 (4, 4) points. The subjective scores of the radiologists were in good agreement, and the Kappa values were 0.74 and 0.84 respectively. The subjective scores of test group were significantly higher than that of conventional group ( Z=-11.15, P<0.001). Conclusion:Monoenergetic imaging on dual-layer spectral detector CT combined with individual injection protocol of contrast medium can improve SNR, CNR and the image quality of brain CTA.

Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) - a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3
Animals ; Hippocampus ; Long-Term Potentiation ; Mice ; Neuronal Plasticity ; Nuclear Receptor Coactivator 3/genetics* ; Synapses

Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) – a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3

Objective:To analyze the molecular epidemiology and virulence characteristics of polymyxin-resistant Klebsiella pneumoniae ( K. pneumoniae). Methods:From 2011 to 2016, 1 376 strains of K. pneumoniae were isolated from various clinical specimens of hospitalized patients in First Affiliated Hospital of Wenzhou Medical University. Agar dilution method was used to screen out the polymyxin-resistant strains.Polymerase chain reaction (PCR) was used to detect the genes related to polymyxin resistance, and real-time fluorescence quantitative PCR was used to detect the relative mRNA expression level of drug resistant genes. Pulsed-field gel electrophoresis, multilocus sequence typing and Galleria mellonella larvae infection model were performed to analyze the molecular epidemiological and virulent characteristics. Results:A total of 14 strains (1.02%) of polymyxin-resistant K. pneumoniae were detected among 1 376 K. pneumoniae isolates. Subsequent sequencing identified mutations leading to amino-acid changes (K2E, F28C) in MgrB of 10 isolates and D150G in PhoQ of nine isolates, and genes such as mcr and crrB were not detected in all drug-resistant strains. Compared with standard strains, the relative expression levels of pmrH and pmrD mRNA of these drug resistant strains were increased. Analysis of the molecular epidemiology indicated that the 14 drug-resistant strains were divided into nine clones. Galleria mellonella larvae infection model revealed polymyxin-resistant K. pneumoniae isolates had higher virulence. Conclusions:Polymyxin-resistant K. pneumoniae has mutations in mgrB and phoQ genes, and mgrB mutation may play a key role in the change of virulence profiles. The homology among the polymyxin-resistant K. pneumoniae stains in this study is low.

Objective:To investigate the application value of third-generation dual-source CT(3-G DSCT) low-dose scan mode combined with iterative reconstruction technology in the screening of COVID-19 and to evaluate the radiation dose.Methods:One hundred and twenty patients suspected of COVID-19 from December 2019 to February 2020 were retrospectively analysed and randomly divided into two groups (test group and conventional group, 60 patients in each). The parameters for test group included 3-G DSCT, Turbo Flash scan mode, CARE kV, with reference 90 kV, pitch 2.0, and ADMIRE algorithm, while those parameters for conventional group included the 128-slice CT, conventional spiral scan mode, 120 kV, pitch 1.2, and FBP algorithm. The CT values of aorta, spinal posterior muscle, and subcutaneous fat, the aortic noise, signal-to-noise ratio (SNR), and contrast noise ratio (CNR) were compared to evaluate the image quality between two groups. Two experienced doctors scored the image quality using a double-blind method, and compared the CT dose index volume (CTDI vol), dose-length product (DLP), and effective dose ( E) of the two groups. Results:The CT value of the aorta and spinal posterior muscle and the aortic SNR in the test group were (45.38±4.77), (53.41±8.44) HU, and 2.82±0.59, and significantly higher than those in the conventional group [(39.68±6.26), (42.66±6.32) HU, 2.58±0.61, t=5.608, 7.897, 2.162, P<0.05]. The aortic noise, CNR and subjective scores between the two groups had no significant difference( P>0.05). The CTDI vol, DLP, and E in the test group were (3.09±1.02) mGy, (107.57±32.81) mGy·cm, (1.51±0.46) mSv, significantly lower than those in the conventional group [(7.00±1.80) mGy, (261.65±73.93) mGy·cm, (3.66±1.03) mSv; t=-14.680, -14.756, -14.756, P<0.05]. Conclusions:In the screening of COVID-19, using low-dose scanning mode of 3-G DSCT combined with iterative reconstruction technology would provide diagnostic quality images and meanwhile effectively reduce the radiation dose and improve the SNR of the image.

Objective:To investigate the effect of enhancing the strength of the hamstring on the stability of the knee joint.Methods:Thirty patients with anterior cruciate ligament (ACL) tears were randomly divided into a training group ( n=15) and a control group ( n=15). After the injury′s edema stage, all of the subjects received the standard 6-stage rehabilitation training for ACL injury, including isokinetic exercise, isometric tension and contraction exercise, single or bipedal jumping, proprioception exercises and cardiovascular exercise. On the basis of that standard training, additional hamstring strengthening training was given to the training group. It involved three sessions of weight-bearing flexion of the knee joint six to eight times, at least five times a week for three months. All of the subjects underwent the passive relaxation test (PRT), knee function scoring (Lysholm scores) and weight-bearing MRI before and within 1 month after the training. Anterior shift of the tibia (TAS) was measured using weight-bearing magnetic resonance imaging (MRI). Results:Before the training there were no significant differences between the groups in terms of average PRT or Lysholm scores. After the training, the average PRT score in neither group had improved significantly. The average Lysholm scores of the training and control groups were not significantly different either, though both groups′ averages had improved significantly compared with before the training. The average tibial shifts were also significantly smaller than before the training, with the training group′s average significantly smaller than that of the control group.Conclusion:Increasing hamstring muscle strength can reduce tibial anteversion in the weight-bearing upright position and improve the stability of the knee joint after ACL injury.

Objective To investigate the relationship between low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LHR) and asymptomatic carotid plaques and their stability in high-risk stroke population.Methods Between December 2012 and April 2015,a total of 39 944 permanent resident population ≥40 years were used as subjects of the survey from 11 rural communities in Haitou Town,Banzhuang Town and Tashan Town,Ganyu District,and 9 urban communities in Xinpu District and Haizhou District,Lianyungang City using epidemiological survey method of cluster sampling.Excluding those who took lipid-lowering drugs within 3 months and had a history of stroke or transient ischemic attack,6 592 people at high risk of stroke were finally screened out.Ultrasound was used to detect carotid plaques.The subjects were divided into plaque-free group and plaque group.The latter was further divided into stable plaque group and unstable plaque group.Multivariate logistic regression analysis was used to evaluate the independent risk factor for carotid plaques and their stability.The odds ratio (OR) and 95％ confidence interval (CI) were calculated.Receiver Operating Characteristic (ROC) curve was used to evaluate the prediction efficiency of LHR on carotid plaques.Results Multivariate logistic regression analysis showed that low-density lipoprotein cholesterol (LDL-C) was an independent risk factor for carotid plaques,while high-density lipoprotein cholesterol (HDL-C) was an independent protection factor of carotid plaques.Using the lowest quintile (Q1) of LHR as a reference,carotid plaque risk increased significantly with the increasing LHR (Q2:OR 1.448,95％ CI 1.082-1.937,P =0.013;Q3:OR 2.414,95％ CI 1.754-3.322,P＜0.001;Q4:OR 2.939,95％ CI 1.945-4.441,P＜0.001;Q5:OR 4.884,95％ CI 3.143-7.115,P＜0.001).ROC curve analysis showed that the area under the curve (AUC) of LHR predicting carotid plaques was 0.795 (95％ CI 0.792-0.807;P＜ 0.001),and the optimal cut-off value was 3.00 (sensitivity 68.37％,specificity 75.65％).LHR ≥3.92 (LHR in the Q4 and Q5 subgroups) was an independent risk factor for unstable carotid plaques (OR 2.915,95％ CI 2.104-4.040;P＜0.001).The AUC of the LHR predicting unstable carotid plaques was 0.658 (95％ CI 0.633-0.684;P＜0.001).Conclusions LHR was an independent predictor of carotid plaques in high-risk stroke patients.It had higher predictive value for carotid plaques,and its conversion threshold for promoting plaque formation was 3.00.When LHR was ≥3.92,there was a significant increase in the risk of unstable carotid plaques.