Objective To explore the impacts of compensatory function of the anterior communicating artery(ACoA)on the measurement of blood flow velocity and the degree of stenosis of the non-operative carotid artery in patients with bilateral carotid atherosclerotic stenosis.Methods A total of 161 patients with carotid artery stenosis and the ACoA patency,who underwent unilateral carotid endarterectomy(CEA)from January 2019 to January 2021,were enrolled into this study.Examination was performed using transcranial color-coded Doppler(TCCD)and(or)transcranial Doppler ultrasound(TCD)and confirmed by DSA and(or)CT angiography(CTA).According to whether the ACoA compensation was complete,all patients were divided into complete ACoA group(69 cases)and incomplete ACoA group(92 cases).The peak systolic velocity(PSV)and end-diastolic velocity(EDV)measured by the carotid ultrasound were compared between the complete ACoA group and the incomplete ACoA group before and after CEA.In addition,the results of stenosis degree of non-operative carotid artery evaluated by the ultrasound and DSA or CTA were analysed for the consistency.Results There was no significant difference in age,gender and risk factors for cerebrovascular disease between the two groups(all P＞0.05).Within 1 week after CEA,the PSV([107±35]cm/s,[122±40]cm/s)and EDV([37±12]cm/s,[47±16]cm/s)of the nonoperative carotid artery decreased significantly when compared with those before CEA in both complete and incomplete ACoA patent groups(PSV[177±58]cm/s,[163±54]cm/s and EDV[64±21]cm/s,[76±25]cm/s,all P＜0.01).In the complete ACoA group,the stenosis degrees of non-operative carotid arteries assessed by the CDU were inconsistent with that assessed by the DSA or CTA(Kappa=0.074).Of the 58 patients with mild stenosis assessed by DSA or CTA,55(94.8％)were overestimated as moderate stenosis,and 2(3.4％)were overestimated as severe stenosis.Of the 9 patients with moderate stenosis assessed by DSA or CTA,8 had ultrasound overestimation to severe stenosis.In the incomplete ACoA group,it was highly consistent with that assessed by the DSA or CTA(Kappa=0.920).Of 70 patients with mild stenosis assessed by DSA or CTA,2 cases(2.9％)were overestimated as moderate stenosis by ultrasound.Of the 9 patients with moderate stenosis assessed by DSA or CTA,1 was overestimated by ultrasound to be severe stenosis.Conclusion Non-operative carotid artery PSV and EDV were significantly higher in patients with bilateral carotid artery stenosis with patency and complete compensatory function of ACoA,leading to overestimation the degree of carotid artery stenosis.

Humans ; COVID-19 Vaccines/therapeutic use* ; COVID-19/prevention & control* ; SARS-CoV-2 ; China ; Antibodies, Viral

Ferroptosis is a new form of regulated cell death discovered in recent years, which is iron-dependent cell death characterized by peroxidation of polyunsaturated fatty acid phospholipids. Recent studies have shown that radiotherapy can induce ferroptosis in cancer cells via ionizing radiation. Targeting ferroptosis plays a synergistic role in tumor suppression with radiation, which not only further deepens the connotation of radiobiology, but also provides a new perspective for tumor radiosensitization. This review systematically summarizes the occurrence and defense of ferroptosis, focusing on the key role of ferroptosis in the radiobiological effects of tumor cells and the potential application of ferroptosis in radiosensitization.

In order to further strengthen the training and management of clinical teachers, broaden the career development channels of clinical teachers, and truly stimulate their teaching enthusiasm and initiative, this study further classifies clinical teachers according to the principle of the Snell model, focuses on the training of educational clinicians, and explores the training mechanism of teaching talents in line with the actual development needs of hospitals affiliated to universities from the aspects of selection, training, incentive, and assessment. The results of practice show that related practices have a good effect, and the mean number of teaching achievements was 1.98 for the 56 educational physicians, which was 3.9 times that for non-educational physicians. The per capita teaching achievements of educational physicians tended to increase every year compared with those of non-educational physicians. The training path for educational physicians provides useful experience for the construction of clinical teaching team and the high-quality development of education and teaching, and at the same time, it is necessary to further strengthen the dynamic adjustment of talent echelon, the improvement of operating mechanism, and the introduction of new technology.

Objective:To investigate the value of 18F-FDG PET/CT imaging signs and metabolic parameters in predicting tumor spread through air spaces (STAS) of stage Ⅰ lung adenocarcinoma. Methods:From January 2019 to December 2021, clinical, imaging and metabolic parameters of 381 patients (126 males, 255 females, age (61.2±9.2) years) with stage Ⅰ lung adenocarcinoma were retrospectively analyzed in the Affiliated Hospital of Qingdao University. According to the postoperative pathological results, patients were divided into STAS positive group and STAS negative group. According to the operation time, patients were divided into training set ( n=254) and verification set ( n=127). χ2 test or Mann-Whitney U test was used to compare the differences of different parameters between patients with STAS positive and negative, and binary logistic regression analysis was used to select the predictors of STAS status. The prediction model was established, and ROC curve was used to evaluate the predictive efficacy. Results:There were 49(19.3%, 49/254) patients with STAS positive and 205(80.7%, 205/254) patients with STAS negative in the training set, while those were 35(27.6%, 35/127) and 92(72.4%, 92/127) in the verification set. In the training set, the differences of age ( z=-2.30, P=0.021), type of lesions ( χ2=6.81, P=0.009), spiculation ( χ2=12.64, P<0.001), bronchus truncation ( χ2=6.98, P=0.008), ground glass ribbon sign ( χ2=26.93, P<0.001) and SUV max ( z=-4.62, P<0.001) between the two groups were statistically significant. Multivariate logistic regression analysis showed that age (odds ratio ( OR)=1.048, 95% CI: 1.004-1.094, P=0.032), ground glass ribbon sign ( OR=3.857, 95% CI: 1.693-8.788, P=0.001) and SUV max ( OR=1.133, 95% CI: 1.001-1.282, P=0.049) were independent predictors of STAS status in stage Ⅰ lung adenocarcinoma patients. The logistic regression model was P=1/(1+ e - x), x=-5.292+ 0.480×age (year)+ 1.493×ground glass ribbon sign+ 0.170×SUV max. The AUCs of the model in the training set and verification set were 0.770 and 0.801, with the sensitivity of 81.6%(40/49) and 82.9%(29/35), and the specificity of 69.8%(143/205) and 65.2%(60/92), respectively. Conclusion:Age, ground glass ribbon sign and SUV max have good predictive effects on the occurrence of STAS in stage Ⅰ lung adenocarcinoma.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Objective:To compare the performance of four commercial kits for anti-HIV confirmatory assay and to provide a reference for clinical application.Methods:Two western blot (WB) kits and two recombinant immunoblot assay/line immune assay kits were used to detect 185 samples in parallel, McNermar test was used to analyze the consistency between the testing results and HIV infection status. Compared to the testing result of the most used MP company’s WB kit, the odds ratio ( OR) was calculated. Results:The consistency of the testing results with the status of HIV infection by the four kits was 83.24%-92.43%, and the Kappa value was 0.558-0.831.The OR value of IMT company’s WB kit obtained from 57 HIV-uninfected samples was 0.932(95% CI: 0.446-1.946, P=0.851), and the OR values of WT company’s recombinant immunoblot assay (RIBA) and MK company’s line immune assay (LIA) were 2.348(95% CI: 1.069-5.158, P=0.034) and 23.064 (95% CI: 5.125-103.789, P<0.001), respectively. The OR value of LIA obtained from 128 HIV-infected samples was 0.153 (95% CI: 0.034-0.700, P=0.016). LIA showed fewest reactions by testing 95 HIV positive screening samples, which was significantly different from any other kit ( P< 0.05). There was no significant difference among the other three kits. In the case of non-specific reactions, the numbers of bands were all ≤4, and the proportion of light-colored bands accounted for 52.1% (37/71). The main bands were gp160(81.3%), p24(71.9%), and p17(28.1%). Conclusions:There was no significant difference between the two WB kits. The RIBA/LIA detection kits could reduce the generation of indeterminate result, but the LIA kit has the risk of false negative for weakly reactive samples.

Objective:To investigate the relationship between HIV-infected men who have sex with men and their sexual partners in Zhejiang province.Methods:A cross-sectional survey was conducted to recruit newly confirmed HIV/AIDS among MSM from 2015 to 2017, including sexual partner identification and molecular epidemiological study. Plasma was collected to extract RNA, and the pol gene of HIV-1 was amplified by RT-PCR/nested PCR. Phylogenetic tree and molecular transmission cluster were analyzed to identify the transmission relationship between sexual partners. Results:A total of 937 HIV/AIDS among MSM were recruited to promote HIV testing for their sexual partners, and 173 positive sexual partners were identified. 50.8% (61/120) of the gene sequences were clustered among the positive sex partners. Seven pairs of clustered sex partners combined with the results of recent infection preliminarily determined the transmission direction. In the clusters, there were statistical differences between the partners who were diagnosed in the same year ( OR=12.190, 95% CI: 1.563-95.054) or with current residence in the different districts ( OR=17.054, 95% CI: 1.742-166.982). Conclusions:Combined with a molecular transmission network, HIV test for the sexual partners of HIV/AIDS among MSM can improve the accurate tracking of cases and preliminarily determine the direction of transmission, according to the results of recent infection. It is suggested that after HIV is confirmed for HIV/AIDS among MSM, HIV tests should be carried out as soon as possible for their sexual partners, including a cross-regional sexual partner tracking test, which is helpful to improve the tracing procedure.

Objective:To construct a computed tomography (CT)-based radiomics model for predicting tumor recurrence of early-stage hepatocellular carcinoma (HCC) after resection, and explore its application value.Methods:The retrospective cohort study was conducted. The clinicopathological data of 243 patients with early-stage HCC who underwent hepatectomy in 2 medical centers between January 2009 and December 2016 were collected, including 165 in the First Affiliated Hospital of Nanjing Medical University and 78 in the Wuxi People′s Hospital. There were 182 males and 61 females, aged from 30 to 86 years, with a median age of 57 years. According to the random numbers showed in the computer, 243 patients were randomly assigned into training dataset consisting of 162 patients and test dataset consisting of 81 patients, with a ratio of 2∶1. Using radiomics technique, a total of 3 384 radiomics features were extracted from the tumor and its periphery at arterial-phase and portal-phase images of CT scan. In the training dataset, a radiomics signature was constructed and predicted its performance after dimension reduction of stable features by using aggregated feature selection algorithms [feature ranking via maximal relevance and minimal redundancy (MRMR) combined with random survival forest (RSF) + LASSO-COX regression analysis]. Risk factors for tumor recurrence were selected using the univariate COX regression analysis, and two radiomics models including radiomics 1 (preoperative) and radiomics 2 (postoperative) were constructed and predicted their performance using backward stepwise multivariate COX regression analysis. The two models were validated in the training and test dataset. Observation indicators: (1) follow-up; (2) construction of HCC recurrence-related radiomics signature for early-stage HCC after resection; (3) prediction performance of HCC recurrence-related radiomics signature for early-stage HCC after resection; (4) construction of HCC recurrence-related radiomics prediction model for early-stage HCC after resection; (5) validation of HCC recurrence-related radiomics prediction model for early-stage HCC after resection; (6) comparison of the prediction performance of radiomics model with that of other clinical statistical models and current HCC staging systems; (7) stratification analysis of postoperative recurrence risk based on radiomics models for early-stage HCC after resection. Patients were followed up using outpatient examination or telephone interview once every 3 months within the first 2 years and once every 6 months after 2 years. The follow-up included collection of medical history, laboratory examination, and abdominal ultrasound examination. Contrast-enhanced CT or magnetic resonance imaging (MRI) examination was performed once every 6 months, and they were performed in advance on patients who had suspected recurrence based on laboratory examination or abdominal ultrasound for further diagnosis. Follow-up was up to January 2019. The endpoint was time to recurrence, which was from the date of surgery to the date of first detected disease recurrence or metastasis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed by the Mann-Whitney U test. Count data were described as absolute numbesr or percentages, and comparison between groups was analyzed using the chi-square test. The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method, and the survival analysis was performed using the Log-rank test. Serum alpha-fetoprotein level was analyzed after the natural logarithm transformation. X-tile software was used to select the optimal cut-point for continuous markers. Results:(1) Follow-up: all the 243 HCC patients received follow-up. Patients in the training dataset were followed up for 4.2-109.2 months, with a median follow-up time of 51.6 months. Patients in the test dataset were followed up for 12.7-107.6 months, with a median follow-up time of 73.2 months. The 2-, 5-year disease-free survival rates were 77.8% and 53.1% of the training dataset respectively, versus 86.4% and 61.7% of the test dataset. There was no significant difference in terms of disease-free survival between two datasets ( χ2=1.773, P>0.05). (2) Construction of HCC recurrence-related radiomics signature for early-stage HCC after resection: of the 3 384 radiomics features, 2 426 radiomics features with high stability were selected for analysis. There were 37 radiomics features identified after combining the top 20 radiomics features ranked by MRMR and RSF algorithms. LASSO-COX regression algorithm further reduced their dimensionality to retain 7 radiomics features and construct a radiomics signature. The indicators including region, scanning phase, and weighting coefficient of above mentioned seven features were Feature 1 (peritumoral, arterial phase, 0.041), Feature 2 (peritumoral, arterial phase, -0.103), Feature 3 (peritumoral, arterial phase, -0.259), Feature 4 (intratumoral, arterial phase, 0.211), Feature 5 (peritumoral, portal venous phase, -0.170), Feature 6 (intratumoral, portal venous phase, 0.130), and Feature 7 (intratumoral, portal venous phase, 0.090), respectively. Radiomics signature score=0.041×Feature 1-0.103×Feature 2-0.259×Feature 3+ 0.211×Feature 4-0.170×Feature 5+ 0.130×Feature 6+ 0.090×Feature 7. (3) Prediction performance of HCC recurrence-related radiomics signature for early-stage HCC after resection: the radiomics signature showed favorable prediction performance in both training and test datasets, with respective C-index of 0.648 [95% confidence interval ( CI): 0.583-0.713] and 0.669 (95% CI: 0.587-0.750). (4) Construction of HCC recurrence-related radiomics prediction model for early-stage HCC after resection: results of univariate analysis showed that ln(serum alpha-fetoprotein), liver cirrhosis, tumor margin status, arterial peritumoral enhancement, intratumoral necrosis, radiomics signature, satellite nodules, and microvascular invasion were related factors for tumor recurrence after resection of early-stage HCC ( hazard ratio=1.202, 1.776, 1.889, 2.957, 1.713, 4.237, 4.364, 4.258, 95% CI: 1.083-1.333, 1.068-2.953, 1.181-3.024, 1.462-5.981, 1.076-2.728, 2.593-6.923, 2.468-7.717, 2.427-7.468, P<0.05 ). Results of multivariate analysis showed that the radiomics model 1 (preoperative) consisted of ln(serum alpha-fetoprotein), tumor margin status, and radiomics signature ( hazard ratio=1.145, 1.838, 3.525, 95% CI: 1.029-1.273, 1.143-2.955, 2.172-5.720, P<0.05); the radiomics model 2 (postoperative) consisted of ln(serum alpha-fetoprotein), radiomics signature, microvascular invasion, and satellite nodules ( hazard ratio=1.123, 2.386, 3.456, 3.481, 95% CI: 1.005-1.254, 1.501-3.795, 1.863-6.410, 1.891-6.408, P<0.05). Risk prediction formulas: radiomics model 1 = 0.135×ln(serum alpha-fetoprotein)+ 0.608×tumor margin status (0: smooth; 1: non-smooth)+ 1.260×radiomics signature; radiomics model 2 = 0.116×ln(serum alpha-fetoprotein)+ 0.870×radiomics signature + 1.240×microvascular invasion (0: absent; 1: present)+ 1.247×satellite nodules (0: absent; 1: present). (5) Validation of HCC recurrence-related radiomics prediction model for early-stage HCC after resection: in both training and test datasets, radiomics model 1 provided good prediction performance, with respective C-index of 0.716 (95% CI: 0.662-0.770) and 0.724 (95% CI: 0.642-0.806), while radiomics model 2 provided better prediction performance, with respective C-index of 0.765 (95% CI: 0.712-0.818) and 0.741 (95% CI: 0.662-0.820). Calibration curves demonstrated good agreement between model-predicted probabilities and observed outcomes. (6) Comparison of the prediction performance of radiomics model with that of other clinical statistical models and current HCC staging systems: in the training dataset, the prediction performance of radiomics model 1 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (preoperative), Barcelona clinic liver cancer (BCLC) staging, Hong Kong liver cancer (HKLC) staging, and cancer of the liver Italian program (CLIP) classification (C-index=0.562, 0.484, 0.520, 0.622, 95% CI: 0.490-0.634, 0.311-0.658, 0.301-0.740, 0.509-0.736, P<0.05); the prediction performance of radiomics model 2 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (postoperative), Korean model, and the eighth edition TNM staging (C-index=0.601, 0.523, 0.513, 95% CI: 0.524-0.677, 0.449-0.596, 0.273-0.753, P<0.05). In the test dataset, the prediction performance of radiomics model 1 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (preoperative), BCLC staging, HKLC staging, CLIP classification (C-index=0.540, 0.473, 0.504, 0.545, 95% CI: 0.442-0.638, 0.252-0.693, 0.252-0.757, 0.361-0.730, P<0.05); the prediction performance of radiomics model 2 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (postoperative), Korean model, and the eighth edition TNM staging (C-index=0.562, 0.513, 0.521, 95% CI: 0.451-0.672, 0.399-0.626, 0.251-0.791, P<0.05). (7) Stratification analysis of postoperative recurrence risk based on radiomics models for tumor recurrence after resection of early-stage HCC: according to the analysis of X-tile, the score of radiomics model 1 < 1.4 (corresponding to total points < 62.0 in nomogram) was classified into low-risk group while the score of radiomics model 1 ≥ 1.4 (corresponding to total points ≥ 62.0 in nomogram) was classified into high-risk group. The score of radiomics model 2 < 1.7 (corresponding to total points < 88.0 in nomogram) was classified into low-risk group while the score of radiomics model 2 ≥ 1.7 (corresponding to total points ≥ 88.0 in nomogram) was classified into high-risk group. In the training dataset, the 2- and 5-year recurrence rates were 14.1%, 35.3% for low-risk patients and 63.0%, 100.0% for high-risk patients, which were predicted by radiomics model 1. There were significant differences between the two groups ( χ2= 70.381, P<0.05). The 2- and 5-year recurrence rates were 12.9%, 38.2% for low-risk patients and 81.8%, 100.0% for high-risk patients, which were predicted by radiomics model 2. There were significant differences between the two groups ( χ2= 98.613, P<0.05). In the test dataset, the 2- and 5-year recurrence rates were 5.6%, 29.3% for low-risk patients and 70.0%, 100.0% for high-risk patients, which were predicted by radiomics model 1. There were significant differences between the two groups ( χ2= 64.453, P<0.05). Ther 2- and 5-year recurrence rates were 5.7%, 28.1% for low-risk patients and 63.6%, 100.0% for high-risk patients, which were predicted by radiomics model 2. There were significant differences between the two groups ( χ2= 58.032, P<0.05). Conclusions:The 7-feature-based radiomics signature is built by selection of CT radiomics features in this study, and then HCC recurrence-related radiomics prediction model for early-stage HCC after resection is constructed. The proposed radiomics models can complement the existing clinical-radiological-pathological prognostic sources, accurately and individually predict tumor recurrence risk preoperatively and postoperatively, which facilitate clinical decision-support for patients with early-stage HCC.

Objective:To evaluate the applicability of limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA, LAg for short) in determining the new HIV-1 infection status of MSM population with seroconversion and make correlation analysis of other biological indicators.Methods:The 15 cases with HIV seroconversion were found in a MSM observation cohort for calculating the HIV prevalence in Zhejiang.The subjects were conducted epidemiological investigation and sampled.The interval of infection time was estimated according to the exposure history and the time of HIV-positive confirmation.LAg, immunoblotting, CD4 cell counting and viral load test were applied in the testing of the related blood samples. McNermar test was conducted for consistency of the two methods.Results:Of 15 cases, the average age was (31.5±8.0) years old, ranging from 24 to 57 years old. The interval of infection time ranged from 40 days to 366 days, and the median was 134 days, with inter-quartile range from 89 to 180 days. A total of 7 cases were classified as new HIV-1 infection by LAg, and 8 cases were classified as chronic infection.The consistent rate was high to 86.67%, and kappa value was 0.73.The samples lacking at least two bands in p31, p51, p66 and gp120 by immunoblotting were determined as recent infection, of which the new infection proportion was significantly higher than that of other samples ( P=0.029).There was no statistical difference in the distribution of CD4 counts ( P=0.533) and viral loads ( P=0.467) between the new infection and chronic infection groups that divided by LAg. Conclusion:By combining with exposure history, the limiting antigen avidity enzyme immunoassay can be used to estimate the new HIV-1 infection.The other biological indicators such as immunoblotting bands, CD4 cell counts and viral loads, can be used as accessory indicators in evaluating the status of new HIV-1 infection.