Background and aims:Early and accurate diagnosis of the coexistence of Wilson's disease(WD)and chronic hepatitis B(CHB)presents a significant challenge for clinicians.The objective of this study was to retrospectively analyse the characteristics of such patients to improve clinical practice and provide a reference for clinical management.Methods:From January 2011 to December 2022,35 patients with concurrent CHB and WD(CHB+WD group)were identified.A total of 127 patients with CHB(CHB group)and 168 patients with WD(WD group)were included in the control group between January 2016 and December 2021.Propensity score matching(PSM)was performed to balance the baseline values between groups.The Kaplan-Meier(K-M)survival analysis and log-rank test were performed to compare the prognoses.Results:In the cohort of 35 patients with concurrent CHB and WD,74.3％of patients(26 patients)faced a substantial delay of up to 10 years(range:0-40 years)in WD diagnosis following their CHB diagnosis.Twenty-three(65.7％)patients had cirrhosis at the time of WD diagnosis,and 26(74.3％)patients experienced liver failure.The levels of serum copper and uric acid were lower in patients in the CHB+WD group than in those in the CHB group.Patients in the CHB+WD group presented higher alanine transaminase and total bile acid levels compared to those in the WD group.K-M survival analysis indicated that patients with CHB and WD had poorer outcomes than those with CHB alone;however,the outcomes were similar to those of individuals with WD alone.The optimal cut-point of serum ceruloplasmin(CP)in identifying WD in CHB patients was 0.10 g/L before PSM and after PSM.Conclusions:The present study emphasizes the importance of clinicians being vigilant for concurrent CHB and WD diagnoses,as delays in WD diagnosis may adversely affect patient outcomes.CHB patients with serum CP below 0.10 g/L are highly recommended to screen for WD.

Objective To explore the separation and purification efficiency of domestic and imported agarose gel filtration chromatography media for the inactivated SARS-CoV-2 Omicron vaccine, in order to provide data support for promoting the domestic substitution of chromatography media.Methods Three batches of concentrated SARS-CoV-2 Omicron strain inactivated virus were used in the experiments, and the purification was conducted using domestic and imported agarose gel filtration chromatography media under identical experimental conditions respectively. The virus peaks were collected, and relevant quality parameters, including antigen content, protein content, residual DNA of Vero cells, residual host proteins of Vero cells, and residual bovine serum albumin content in the collected components, were measured. The specific activity and antigen recovery rates were calculated.Results After loading and purification using a 10% column volume and a linear flow rate of 30 cm/h for both media, the average antigen recovery rates for the collected components were 55. 29% and 53. 31%,respectively, with no significant difference(t = 1. 44, P > 0. 05). Moreover, there was no significant difference in specific activity, residual DNA of Vero cells and residual host proteins of Vero cells(t =-0. 25, 1. 31 and 0. 66, respectively, each P >0. 05). Only the residual bovine serum albumin content exhibited a significant difference(t =-2. 73, P < 0. 05).Conclusion The domestic and imported agarose gel filtration chromatography media were used to purify the concentrated solution of SARS-CoV-2 Omicron strain inactivated virus, and the quality parameters of the collected components had no significant difference except for the residual bovine serum albumin content. Therefore, in the purification of the inactivated SARS-CoV-2 Omicron vaccine, the domestic chromatography media could be considered as a viable alternative to imported media

BACKGROUND: Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population. METHODS: Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately. RESULTS: In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model. CONCLUSIONS In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.
Male ; Humans ; Female ; Coronary Artery Disease/genetics* ; Biological Specimen Banks ; East Asian People ; Risk Assessment/methods* ; Genetic Predisposition to Disease/genetics* ; Risk Factors ; Genome-Wide Association Study

Objective:To compare the preliminary clinical effect of mitral valve replacement and mitral valvuloplasty on hypertrophic obstructive cardiomyopathy with mitral regurgitation.Methods:From January 2010 to December 2013, the patients undergoing cardiac surgery at Bakulev Cardiovascular Surgery Research Center in Russia were randomly divided into two groups: Forty-one patients received left ventricular outflow tract hypertrophy myocardial resection (Morrow operation) combined with mitral valve replacement (MVR) as MVR group; Forty-seven patients received Morrow surgery combined with mitral valve repair (MVr) as MVr group.The primary end point: death, secondary end point: thrombosis complications (cerebral infarction, peripheral arterial embolism), recurrence of mitral regurgitation and left ventricular outflow tract pressure difference were compared between the two groups.Results:In the MVr group, 6 cases were converted to MVR and were excluded from the study.The survival rates of MVR group and MVR group were 78.9% and 96.6%, respectively , and the thromboembolic free survival rates of MVR group and MVr group were 83.2% and 100%, respectively. The differences were statistically significant( P=0.034, 0.026, respectively). There was no significant difference in mitral regurgitation and left ventricular outflow tract pressure difference between MVR group and MVR group 24 months after operation( P=1.000, 0.934, respectively). Conclusion:Operation combined with MVR or MVr is an effective method to relieve left ventricular outflow tract obstruction and mitral regurgitation. Morrow operation combined with MVr can improve survival rate and reduce thrombosis complications.

OBJECTIVE: To observe the cell death pattern induced by gefitinib in non-small cell lung cancer A549 and H1975 cells and explore the possible mechanism in light of glycolysis. METHODS: The inhibitory effects of gefitinib at 20, 30, or 40 μmol/L in A549 cells and at 20, 40, or 80 μmol/L in H1975 cells were examined using MTT assay. The changes of lactic acid level in the cells were determined with a lactic acid kit, and the expression levels of glycolysis-related proteins (PKM2 and HK2) and the proteins in PI3K-Akt-mTOR signaling pathway were detected using Western blotting. 2-NBDG was used for detecting glucose uptake capacity of the cells, and ATP kit was used to detect the intracellular ATP level. The mitochondrial membrane potential of the cells was examined with the JC-1 kit, and cell apoptosis was analyzed with Annexin V-FITC/PI double staining. The relative expression levels of the apoptotic proteins Bax and Bcl-2 and the autophagy marker protein LC3B were detected with Western blotting. RESULTS: MTT assay showed that gefitinib inhibited the proliferation of A549 and H1975 cells in a time- and dose-dependent manner ( < 0.05). The IC of gefitinib at 24, 48 and 72 h was 48.6, 28.6 and 19.7 μmol/L in A549 cells and was 321.6, 49.1 and 14.6 μmol/L in H1975 cells, respectively. Gefitinib significantly lowered intracellular lactic acid level of the cells ( < 0.05) and down-regulated the expressions of PKM2 and HK2 proteins ( < 0.05) and PI3K-Akt-mTOR signaling pathway-associated proteins ( < 0.05). Gefitinib obviously inhibited glucose uptake and ATP levels in both A549 and H1975 cells ( < 0.05). Treatment with gefitinib induced obviously enhanced apoptosis in the cells, resulting in apoptosis rates of (10.77± 1.0)%, (14.5±0.4)%, (17.4±0.2)% and (32.1±0.6)% at 0, 20, 30 and 40 μmol/L in A549 cells ( < 0.05) and of (10.5±0.6)%, (13.2± 0.92)%, (18.9±0.98)% and (35.1±1.4)% at 0, 20, 40 and 80 μmol/L in H1975 cells, respectively ( < 0.05). The protein expression of Bax increased and that of Bcl-2 decreased following gefitinib treatment in the cells ( < 0.05). Gefitinib significantly increased autophagy in A549 and H1975 cells as shown by increased LC3B expressions following the treatment ( < 0.05). CONCLUSIONS Gefitinib can inhibit the proliferation, induce apoptosis and increase autophagy in A549 and H1975 cells. Gefitinib induces apoptosis of the cells possibly by affecting glycolysis and PI3K-Akt-mTOR signaling pathway.
Apoptosis ; Carcinoma, Non-Small-Cell Lung ; Cell Line, Tumor ; Cell Proliferation ; Gefitinib ; Glycolysis ; Humans ; Lung Neoplasms ; Phosphatidylinositol 3-Kinases

Objective: To explore the forces of lower limbs during side slip and forward slip through biomechanical study, and to provide a theoretical basis for the development of lower limb movements. Methods: BTS SMART DX motion capture analysis system, 8 infrared high-speed cameras, Kistler three-dimensional dynamometer, BTS FREEEMG 1000 portable wireless surface electromyography system were used to collect real-time data of side slip and forward slip. SPSS 20.0 univariate analysis of variance (ANOVA) was used to compare the differences of indicators between different groups. Results: In the side sliding movement, there were significant differences in hip motion (P<0.01) between 3-year-old group and 5-year-old group, hip motion(P<0.01) between 4-year-old group and 5-year-old group, knee motion(P<0.05) and ankle motion(P<0.05) between 3-year-old group and 5-year-old group. There was a significant difference in hip motion(P<0.05) between 3-year-old group and 5-year-old group. The Fx force(P<0.01) and vertical Fy force(P<0.01) in the left and right directions of the 3-year-old group and the 5-year-old group were significantly different in the side-slip movement, while the Fx force(P<0.01) in the right and left directions of the 3-year-old group and the 5-year-old group were significantly different in the forward-slip movement, and the vertical Fy force(P<0.05) was significantly different. There were significant differences in the long head of biceps femoris, gastrocnemius and anterior tibial muscle between 3-year-old group and 5-year-old group (P<0.05). There were significant differences in the middle gluteal muscle, gracilis muscle, adductor magnus, pubic muscle, medial femoral muscle and soleus muscle between 3-year-old group and 5-year-old group (P<0.05). There was significant difference in the anterior tibial muscle (P<0.05) between the 3-year-old group and the 5-year-old group in the supporting stage, and significant difference in the gastrocnemius muscle(P<0.05) during the swing stage. There was significant difference in the anterior tibial muscle(P<0.05) between the 3-year-old group and the 5-year-old group in the swing stage. Conclusion The development of side slip and forward slip in children aged 3 to 5 years old showed that the results suggest motor development increases significantly with age among preschoolers. Rhythmic movements of side slip and forward slip should be selected in the critical period of children’s movement development at different ages, laying the foundation for good physical and mental development.

Objective To investigate the value of support vector machine based MRI-radiomics in the differential diagnosis of primary hepatic carcinomas (PHCs). Methods PHCs patients were retrospectively collected from July 2013 to February 2017 in the First Affiliated Hospital of Zhejiang University.All patients underwent unenhanced and enhanced MRI liver scan before surgery,and confirmed by pathology. A total of 294 PHCs patients (305 lesions), including 96 cases (97 lesions) of massive type cholangiocarcinoma (mCC), 107(107 lesions)of hepatocellular carcinoma (HCC), and 91 (101 lesions) of mixed hepatocellular and cholangiocellular carcinomas(HCC-CC).All patients underwent unenhanced and dynamic enhanced MRI liver scan including arterial, portal venous and equilibrium phases. Two hundred and three lesions (65 mCC, 71 HCC, 67 HCC-CC) were assigned into the training set, the remaining 102 lesions(32 mCC,36 HCC,34 HCC-CC)into the validation set,according to a ratio of 2:1.The entire lesions were delineated manually using a region of interest on equilibrium phase of enhanced MRI by using a home-made dedicated software(Analysis Kit,AK,General Electrics,US).Then the least absolute shrinkage and selection operator (LASSO) regression was used to select image features with a method of 10 fold cross-validation, and to reduce the dimensionality. The spearman method was used afterwards to condense the image features by removing redundant.A predictive model of diagnosing the different types of PHCs was established based on support vector machines(SVM),and the accuracy of applying the model in the data sets was used to evaluate the diagnostic efficacy of the model. Results A total of 280 quantitative imaging features were extracted in the training set.Thirty one imaging features were selected after LASSO regression and dimensionality reduction,and 21 features were remained after redundancy removing.The SVM showed the best generalization ability when the first 11 imaging features were used due to the Hughes effect.The 11 imaging features include 4 parameters of histogram,2 of textures,4 of gray-level co-occurrence matrix and 1 of gray-level run length matrix. A predictive model for PHCs was established after the study of the 11 imaging features and a regression analysis using SVM.The accuracy of the predictive model was 80.3% (163/203) in differentiating PHCs in the training set. The accuracy of the model was 75.5% (77/102) after applying it in the validation set. The diagnostic accuracy for HCC-CC, HCC and mCC was 85.3% (29/34), 77.8% (28/36) and 62.5% (20/32), respectively, in the validation set. For HCC-CC, 3 cases were misdiagnosed as mCC and 2 cases as HCC.For HCC,3 cases were misdiagnosed as HCC-CC and 5 cases as mCC.For mCC,9 cases were misdiagnosed as HCC-CC and 3 cases as HCC.The model showed the highest accuracy in predicting HCC-CC.Conclusion Radiomics method based on SVM may have a high accuracy in predicting different pathologic types of PHC,with the highest accuracy for HCC-CC.