Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.

Objective To investigate the effect and mechanism of astragaloside Ⅳ(AS-Ⅳ) activating ROCK/JNK to regulate autophagy in improving isoproterenol (ISO) induced myocardial fibrosis (MF) in mice. Methods The mice were randomly divided into control operation group (Control group), ISO induced myocardial fibrosis group (MF group), AS-Ⅳ treatment group (AS-Ⅳ group) and combination group of astragaloside IV and Y-33075 (ROCK inhibitor) (astragaloside IV+Y-33075 group). After repeated administration for 30 days. The serum levels of LDH, BNP, CTGF in each group were detected. The cardiac function was detected by ultrasound. Myocardial structure and tissue fibrosis degree in each group were detected by Sirius Red and Masson staining. Oxidative stress (ROS) levels in myocardial tissue of each group were detected by DHE staining and the expression of ROCK, JNK, Atg5, Beclin 1, and LC3 Ⅰ/Ⅱ in myocardial tissue were detected by Western blotting. Results Compared with AS-Ⅳ group, the EF value of AS-Ⅳ+Y-33075 group decreased and the degree of myocardial fibrosis increased (P<0.05). The serum level of LDH, BNP, CTGF increased and the level of ROS in myocardial tissue increased while the expression of ROCK, JNK, Atg5, Beclin 1, LC3 Ⅰ/Ⅱ decreased (P<0.05). Y-33075 could block the protective effect of AS-Ⅳ on myocardial injury induced by MF and inhibit the regulation of AS-Ⅳ on ROCK and JNK. Conclusion AS-Ⅳ could attenuate myocardial fibrosis in mice by activating ROCK/JNK signal and promoting autophagy.

Objective To retrospectively evaluate the clinical efficacy and safety of brentuximab vedotin(BV) combined with chemotherapy in the treatment of malignant lymphoma. Methods We collected the data of 32 lymphoma patients with CD30-positive status, including 14 cases of Hodgkin's lymphomas, 2 cases of diffuse large B-cell lymphomas, and 16 cases of mature T/NK cell lymphomas. Chemotherapy combined with BV was administered to all patients for a minimum of two cycles. The efficacy of the treatment was evaluated according to Lugano criteria every two cycles. Results Complete response rate and overall response rate after four cycles of treatment were 22% and 50%, respectively. Sixteen cases (50.0%) had grades 1 and 2 toxicity, and 16 cases (50.0%) had grade 3 toxicity or higher. The most common adverse events were neutropenia (50.0%), pneumonia (46.9%), and anemia (43.8%). The most common grade 3 or higher adverse events were pneumonia (18.8%) and febrile neutropenia (12.5%). Four patients discontinued brentuximab vedotin because of severe adverse events. Conclusion BV is effective in treating relapsed and refractory CD30- positive Hodgkin's lymphoma and peripheral T-cell lymphoma, and its overall safety is acceptable.

Objective:To investigate the factors influencing the prognosis of anaplastic thyroid cancer (ATC) and to evaluate the application value of established random survival forest (RSF) model in the prognosis prediction of ATC.Methods:A total of 707 ATC patients diagnosed by histopathology in the Surveillance, Epidemiology and End Results (SEER) database of the National Cancer Institute from 2004 to 2015 were selected and randomly divided into the training set (495 cases) and the validation set (212 cases). Univariate Cox regression risk model was used to analyze the related factors affecting overall survival (OS) of patients in the training set. The multivariate Cox proportional risk model based on the minimum Akaike information criterion (AIC) was used to analyze the above variables and then the variables were screened out. The traditional Cox model for predicting OS was constructed based on the screened variables. The RSF algorithm was used to analyze the variables with P < 0.05 in the univariate Cox regression analysis, and 5 important features were selected. Multivariate Cox proportional risk model was selected based on the minimum AIC. Then the RSF-Cox model for predicting OS was constructed by using screened variables. The time-dependent receiver operating characteristic (tROC) curve and the area under the curve (AUC), calibration curve, decision curve and integrated Brier score (IBS) in the training set and the validation set were used to evaluate the prediction performance of the models. Results:Univariate Cox regression analysis showed that age, chemotherapy, lymph node metastasis, radiotherapy, surgical method, tumor infiltration degree, tumor number, tumor diameter and diagnosis time were factors affecting the prognosis of ATC (all P < 0.05). Multivariate Cox regression analysis based on minimal AIC (4 855.8) showed that younger age (61-70 years vs. > 80 years: HR = 0.732, 95% CI 0.56-0.957, P = 0.023; ≤ 50 years vs. > 80 years: HR = 0.561, 95% CI 0.362-0.87, P = 0.010), receiving chemotherapy (receiving or not: HR = 0.623, 95% CI 0.502-0.773, P < 0.001), receiving radiotherapy (receiving or not: HR = 0.695, 95% CI 0.559-0.866, P = 0.001), receiving surgery (lobectomy, no surgery or unknown: HR = 0.712, 95% CI 0.541-0.939, P = 0.016; total resection or subtotal resection vs. no surgery or unknown: HR = 0.535, 95% CI 0.436-0.701, P < 0.001), and tumor diameter (≤ 2 cm vs. > 6 cm: HR = 0.495, 95% CI 0.262-0.938, P = 0.031; > 2 cm and ≤ 4 cm vs. > 6 cm: HR = 0.714, 95% CI 0.520-0.980, P = 0.037; > 4 cm and ≤ 6 cm vs. > 6 cm: HR = 0.699, 95 % CI 0.545-0.897, P = 0.005) were independent protective factors for OS of ATC patients. Lymph node metastasis (N 1 unknown vs. N 0: HR = 1.664, 95% CI 1.158-2.390, P = 0.006; N 1b: HR = 1.312, 95% CI 1.029-1.673, P = 0.028), more aggressive tumor infiltration degree (group 3 vs. group 1: HR = 1.492, 95% CI 1.062-2.096, P = 0.021; group 4 vs. group 1: HR = 1.636, 95% CI 1.194 - 2.241, P = 0.002) were independent risk factors for OS of ATC patients. Although diagnosis time was not statistically significant (2010-2015 vs.2004-2009: HR = 1.166, 95% CI 0.962-1.413, P = 0.118), the inclusion of it could improve the efficacy of the traditional Cox model. RFS algorithm was used to select out 5 important variables: surgical method, tumor diameter, age group, chemotherapy, and tumor number. Multivariate Cox regression analysis based on minimum AIC (4 884.6) showed that chemotherapy (receiving or not: HR = 0.574, 95% CI 0.476-0.693, P < 0.001), surgical method (lobectomy, no surgery or unknown: HR = 0.730, 95% CI 0.567-0.940, P = 0.015; total resection or subtotal resection vs. no surgery or unknown: HR = 0.527, 95% CI 0.423-0.658, P < 0.001), tumor diameter (≤ 2 cm vs. > 6 cm: HR = 0.428, 95% CI 0.231-0.793, P = 0.007; > 2 cm and ≤ 4 cm vs. > 6 cm: HR = 0.701, 95% CI 0.513-0.958, P = 0.026; > 4 cm and ≤ 6 cm vs. > 6 cm: HR = 0.681, 95% CI 0.536-0.866, P = 0.002) were independent factors for OS of ATC patients. RSF-Cox model was constructed based on 3 variables. The tAUC curve analysis showed that RSF-Cox model for predicting the 6-month, 12-month, and 18-month OS rates were 93.56, 92.62, and 90.80, respectively in the training set, and 93.05, 92.47, and 90.20, respectively in the validation set; in the traditional Cox model, the corresponding OS rates were 89.00, 87.76, 85.24, respectively in the training set, and 86.22, 83.68, 82.86, respectively in the validation set. When predicting OS rate at 6-month, 12-month and 18-month, the calibration curve of RSF-Cox model was closer to 45° compared with that of traditional Cox model, and the clinical net benefit of decision curve in RSF-Cox model was higher than that in traditional Cox model. The IBS of RSF-Cox model (0.089) was lower than that of traditional Cox model (0.111). Conclusions:The RSF model based on chemotherapy, surgical method and tumor diameter can effectively predict the OS of ATC patients.

Objective:To investigate the value of qualitative characteristics of contrast-enhanced ultrasound (CEUS) and VueBox quantitative parameters in the evaluation of pathological molecular typing of breast cancer.Methods:A retrospective analysis was performed on 133 patients with pathologically confirmed breast cancer who underwent CEUS examination in the People′s Hospital of Guangxi Zhuang Autonomous Region from January 2020 to July 2022. The patients were divided into Luminal A type, Luminal B type, human epidermal growth factor receptor-2(HER-2) type and triple negative type according to the results of immunohistochemistry. The differences of qualitative characteristics and quantitative parameters of CEUS in different molecular subtypes of breast cancer were analyzed. The ROC curve was used to evaluate the diagnostic efficacy of CEUS in the differentiation of molecular subtypes of breast cancer.Results:There were significant differences in enhancement intensity, post-enhancement boundary, filling defect and peripheral radial convergence among different molecular subtypes of breast cancer(all P<0.05), while there was no significant difference in enhancement uniformity ( P>0.05). Peak enhancement (PE), wash-in and wash-out areas under the curve (WiWoAUC), and wash-in ratio (WiR) of HER-2 type and triple-negative type breast cancer were higher than Luminal A type and Luminal B type (all P<0.05). ROC curve analysis showed that PE and radial convergence had reasonable diagnostic efficiency in Luminal A type, and the areas under the curve were 0.849 and 0.780, sensitivity was 0.711 and 0.889, specificity was 0.909 and 0.671, accuracy was 0.842 and 0.744, respectively. The areas under the curve of PE in diagnosing Luminal B type was 0.852, the sensitivity, specificity, and accuracy were 0.825, 0.763 and 0.782, respectively. The area under the curve of WiWoAUC and filling defect in diagnosing HER-2 type were 0.912 and 0.898, the sensitivity was 0.903 and 0.903, the specificity was 0.853 and 0.892, and the accuracy was 0.865 and 0.895, respectively. The area under the curve of clear boundary after enhancement in diagnosing triple negative type was 0.919, and the sensitivity, specificity and accuracy were 0.941, 0.897 and 0.902, respectively. Conclusions:There are differences in the qualitative characteristics and quantitative parameters of contrast-enhanced ultrasound in different molecular types of breast cancer. CEUS is suggested as a noninvasive modality for preoperative prediction of molecular subtypes of breast cancer.

Objective:To develop an automated landmark location system applicable to the case of landmark missing.Methods:Four and eighty-one lateral cephalograms, which contained 240 males and 241 females, with an average age of (24.5±5.6) years, taken from January 2015 to January 2021 in the Department of Orthodontics, Capital Medical University School of Stomatology, and met the inclusion criteria were collected. Five postgraduate orthodontic students were the annotators to manually locate 61 possible landmarks in 481 lateral cephalograms. Two assistant professors in the department as reviewers performed calibration. Two professors as arbitrators, made final decision. Data sets were established (341 were used as training set, 40 as validation set, and 100 as test set). In this paper, an automatic landmarks identification and location model based on convolutional neural networks (CNN), CephaNET, was developed. The model was trained by feeding the original image into the feature extraction module and convolutional pose machine (CPM) module to locate landmarks with high accuracy using deep supervision. Training set was enhanced to 1 684 images by histogram equalization, cropping, and adjustment of brightness. The model was trained to compare the Gaussian heat maps output from the network with the set threshold to identify landmark missing cases. Test set of 100 lateral cephalograms was used to test the accuracy of the model. The evaluation criteria used were success detection rate of missing landmark, mean radial error (MRE) and success detection rate (SDR) in the range of 2.0, 2.5, 3.0, 3.5 and 4.0 mm.Results:The model identified and located 61 commonly used landmarks in 0.13 seconds on average. It had an average accuracy of 93.5% in identifying missing landmarks. The MRE of our testing set was (1.19±0.91) mm. SDR of 2.0, 2.5, 3.0, 3.5 and 4.0 mm were 85.4%, 90.2%, 93.5%, 95.4%, 97.0% respectively.Conclusions:The model proposed in this paper could adapt to the absence of landmark in lateral cephalograms and locate 61 commonly used landmarks with high accuracy to meet the requirements of different cephalometric analysis methods.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective:To evaluate the value of VueBox ? contrast-enhanced ultrasound (CEUS) quantitative analysis combined with ACR TI-RADS classification in the diagnosis of benign and malignant solid thyroid nodules. Methods:A total of 201 patients with thyroid solid nodules (201 nodules) who underwent surgery or puncture biopsy in the People′s Hospital of Guangxi Zhuang Autonomous Region were enrolled from October 2020 to February 2022. The preoperative conventional ultrasound and contrast-enhanced ultrasound images were retrospectively analyzed. According to the pathological results, they were divided into the malignant group and benign group. The differences of the quantitative parameters of CEUS between the two groups were analyzed, including peak enhancement (PE), wash-in and wash-out area under the curve (WiWoAUC), wash-in perfusion index (WiPI). ΔPE, ΔWiWoAUC, ΔWiPI were obtained by calculating the parameter difference between the surrounding normal glands and nodules. ROC curve was used to analyze the value of different quantitative parameters in the differential diagnosis of benign and malignant solid thyroid nodules. The CEUS quantitative parameters with best diagnostic performance was selected and combined with ACR TI-RADS classification system to evaluate the diagnostic efficiency of the single diagnostic approaches and the combined approach.Results:The quantitative parameters of PE, WiWoAUC, WiPI, ΔPE, ΔWiWoAUC, ΔWiPI were significantly different between benign group and malignant group (all P<0.001). ΔPE had the highest diagnostic value among all the quantitative parameters (the area under the ROC curve was 0.802), and the cut-off value was 0.21.ΔPE combined with ACR TI-RADS classification showed the best efficiency in diagnosis of benign and malignant thyroid nodules, with an area under the curve of 0.898, and the sensitivity, specificity, positive predictive value and negative predictive value of 73.39%, 93.48%, 93.02% and 74.78%, respectively. Conclusions:Quantitative parameters of CEUS by using VueBox ? software is valuable for the differential diagnosis of benign and malignant solid thyroid nodules, and its combination with ACR TI-RADS classification can improve the diagnosis accuracy.

Objective:To understand the surveillance status of iodine deficiency disorders (IDD) among children aged 8 - 10 years and pregnant women in Yantai City, Shandong Province.Methods:In 2019, Yantai City was divided into four areas: east, west, south and north according to administrative regions. In each area, 125 children aged 8 - 10 years (age balanced, half males and half females) and 75 pregnant women were selected as the survey subjects. The household edible salt samples and morning urine samples of the survey subjects were collected, and the contents of salt iodine and urinary iodine were detected by direct titration and arsenic-cerium catalytic spectrophotometry, respectively. At the same time, a color Doppler ultrasound diagnostic apparatus was used to examine the thyroid volume of children and the goiter rate was calculated.Results:A total of 800 salt samples were tested, and the median salt iodine was 20.9 mg/kg. Among them, 779 were iodized salts, the coverage rate of iodized salt was 97.38% (779/800); 756 were qualified iodized salts, the qualified rate of iodized salt was 97.05% (756/779), and the consumption rate of qualified iodized salt was 94.50% (756/800). A total of 491 urine samples from children aged 8 - 10 years were tested, the median urinary iodine was 169.23 μg/L, which was an appropriate level of iodine. The medians urinary iodine of children aged 8, 9, and 10 years ( n = 150, 209, 132) were 168.28, 164.39, and 171.23 μg/L, respectively, and the difference was not significant ( H = 1.123, P > 0.05). A total of 491 children's thyroid glands were examined, of which 11 were enlarged, with a goiter rate of 2.24%. The goiter rates of children aged 8, 9, and 10 years were 2.00% (3/150), 2.39% (5/209), 2.27% (3/132), respectively, and the difference was not significant (χ 2 = 0.112, P > 0.05). A total of 300 urine samples from pregnant women were tested, and the median urinary iodine was 208.98 μg/L, which was an appropriate level of iodine. Conclusions:In 2019, children aged 8 - 10 years and pregnant women in Yantai City are at an appropriate level of iodine. The consumption rate of qualified iodized salt ( > 90%) and the goiter rate of children ( < 5%) meet the national standards for eliminating IDD.

Objective To investigate the relationship between vWF levels and ADAMTS13 levels of DVT (venous thrombosis) in patients with cervical cancer,and then to evaluate the predictive value of vWF levels and ADAMTS13 levels of cervical cancer patients with DVT. Methods A total of sixty-six patients diagnosed as cervical cancer and treated from June 2015 to June 2016 in Weinan Maternal and Child Health Hospital were enrolled,and their baseline data,pathological type,tumor classification,TNM staging,vWF, ADAMTS13 levels and Autar score were recorded. All patients were followed up for 1 year and the patients with adverse outcomes were defined as poor prognosis group during the follow-up period while the patients whose disease progression free were defined as good prognosis group. Univariate analysis showed that the incidence of venous thrombosis in patients with cervical cancer was affected; Cox proportional hazard model further assessed the impact of all statistically significant factors on the occurrence of venous thrombosis in patients; t test showed the distribution of influential factors between the two groups; ROC curve was used to analyze the sensitivity and specificity of vWF and ADAMTS13 levels in predicting the occurrence of venous thrombosis in cervical cancer patients. Results At the end of the follow-up,among the 66 patients,Six were not followed and 40 had good prognosis without venous thrombosis,which was a good prognosis group; Twenty had poor prognosis,i. e. venous thrombosis,which was a poor prognosis group,including 5 deaths. The poor prognosis rate was 30. 30%. Univariate Cox proportional hazard model results showed that vWF (P＝0. 023, (95%CI: 1. 743－1. 215)) and ADAMTS13 (P＝0. 037,(95%CI: 1. 158－1. 566)) had a significant effect on the patients with venous thrombosis. The levels of vWF (( 0. 535 ± 0. 075) μg/L) and ADAMTS13 ((69. 453±10. 284)%) in good prognosis group were significantly lower than those in poor prognosis group ((0. 592 ± 0. 082 ) μg/L, ( 79. 245 ± 11. 477 )%), and the differences between the two groups were statistically significant (t＝2. 690,3. 345,P＜0. 05). Under ROC curve,the AUC of vWF level was 0. 841,the sensitivity and specificity were 55% and 97. 5% respectively,and that of ADAMTS13 level was 0. 906,the sensitivity and specificity were 85% and 80%,respectively. Conclusion The levels of vWF and ADAMTS13 have a good predictive effect on the occurrence of venous thrombosis in patients with cervical cancer. It is expected to be used as a routine evaluation index to predict the occurrence of venous thrombosis in patients with cervical cancer after treatment.