Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To evaluate the efficacy of superselective embolization of the supplying arteries of uterine fibroids under the guidance of 3D angiography in treating uterine fibroids.Methods The clinical data of 14 patients with uterine fibroids,who received interventional embolization therapy at the Third Affiliated Hospital of Zhengzhou University of China,were retrospectively analyzed.Of the 14 patients,5 received microcatheter superselective embolization of the supplying arteries of uterine fibroids after the origin and path of the supplying arteries were clarified by 3D uterine artery angiography(group A),and 9 received embolization of the bilateral uterine arteries up to their main trunks because the fibroids had complex blood supply(group B).The sums of the preoperative and postoperative one-year maximum diameter of uterine fibroids,and the reduction rate of fibroid were statistically analyzed.Results The mean sum of the preoperative and postoperative one-year maximum diameter of uterine fibroids in group A were(85.00±43.35)mm and(35.20±25.96)mm respectively,and the difference was statistically significant(P=0.006),which in group B were(65.00±12.68)mm and(49.44±24.83)mm respectively,and the difference was not statistically significant(P=0.052).There was no statistically significant differences in the mean sum of the preoperative maximum diameter of uterine fibroids and in the postoperative one-year maximum diameter of uterine fibroids between the two groups(P=0.366 and P=0.331).The median reduction rate of uterine fibroids in group A and group B was 62％and 25％respectively,and the difference was statistically significant(P=0.031).Conclusion For the treatment of uterine fibroids,3D angiography-guided superselective embolization of the supplying arteries of uterine fibroids is superior to the embolization of the bilateral uterine arteries in clinical curative efficacy.(J Intervent Radiol,2024,33:533-536)

Objective:To investigate the medication rules of Xin'an medicine for the treatment of melancholia and further analyze the medication ideas of Xin'an physicians in the treatment of melancholia.Methods:The documents of Xin'an physicians treating melancholia in the fifth edition of the Chinese Medical Code and the online database of ancient Chinese medicine were retrieved. Excel was used to extract the prescription information to establish the database. R language was used to analyze the data regarding the medication frequency, nature and taste, association rules, and clustering of the traditional Chinese medicine used in the prescription. Results:A total of 127 effective prescriptions were sorted out, and 177 kinds of Chinese medicines were used with a total medication frequency of 1 031 times. The top three Chinese medicines with the highest frequency of use were Poria cocos (57 times), Licorice (46 times), and Paeonia Lactiflora (40 times). The main nature of herbs was plain and warm nature. The warm herbs were the most frequently used (298 times). The first five flavors of the herbs which were the most used were pungent taste (475 times, 28.70%), bitter taste (459 times, 27.73%), and sweet taste (453 times, 27.37%). The commonly used herbs with confidence coefficient > 0.800 were Licorice + Angelica sinensis, Licorice + Angelica sinensis and Paeonia Lactiflora, Licorice + Bupleurum, Licorice + Atractylodes macrocephala, Cyperus root + Ligusticum Chuanxiong, Angelica sinensis + Atractylodes macrocephala and Licorice, Paeonia Lactiflora + Angelica sinensis and Poria cocos, Licorice + Angelica sinensis and Poria cocos, Licorice + Atractylodes macrocephala and Angelica sinensis, Licorice + Bupleurum and Paeonia Lactiflora, Licorice + Atractylodes macrocephala and Ginseng, Licorice + Ginseng and Angelica sinensis, Cyperus root + Medicated leaven, Ginseng + Astragalus mongholicus, Licorice + Astragalus mongholicus.Conclusion:Xin'an medicine for the treatment of melancholia mainly uses pungent, bitter, sweet, and warm herbs. It can adjust the chill and fever, Yin and Yang of the human body, diminishes the urgency, and regulates the flow of Qi.

Middle Aged ; Humans ; Siblings ; Mutation ; TATA-Binding Protein Associated Factors/genetics*

【Objective】 To investigate the improvement of signal uniformity in cardiac magnetic resonance image by adjusting the transmit gain (TG). 【Methods】 For this study we recruited 11 volunteers for cardiac MR scans between July and September 2018. The scanner of US GE Discovery 750 3.0T superconducting MRI was used. We divided the volunteers into normal group and overweight group according to their individual BMI index. The imaging sequences consisted of the black blood double inversion recovery sequence (T1 weighted image and T2 weighted image) and breath-holding black blood three-inversion recovery sequence (FST1 weighted image and FST2 weighted image). All sequences were performed across different TG values, including 150, 160, 170, 180, and 190. The images’ quality was scored by two experienced radiologists using a four-point system based on the blinding principle. The paired variance analysis was made to compare the image quality of different TG groups. 【Results】 We observed consistent results in both normal and overweight groups. The optimal TG value was 160 for black blood triple inversion recovery sequence and 170 for black blood double inversion recovery sequence. 【Conclusion】 Adjusting the TG value can improve the signal uniformity of the myocardium, thereby improving the quality of images.

【Objective】 To develop a prognosis model based on CT images using radiomics method for patients with osteonecrosis of the femoral head (ONFH) and to investigate the additional prediction value of the imaging features of the contralateral normal femoral head regions for the prognosis prediction. 【Methods】 A total of 51 patients were included in this retrospective study. All the patients had preoperative CT images. For each patient, two regions of interest (ROIs) were involved, including the osteonecrosis region and the contralateral normal femoral head region. A total of 968 radiomics features were extracted for each patient. We made both the univariate and multivariable analyses. Three models were developed based on the features of osteonecrosis region, contralateral normal femoral head region, and both regions. The 10 times of repeated random experiments were used for model construction and validation. The average performance of the 10 times of experiments was reported as the results. 【Results】 For the features of osteonecrosis region, 37 features showed significant predictive value, with the mean AUC value of 0.708 2±0.029 9. The AUC of the constructed prediction model was 0.911 0±0.029 4 and 0.688 6±0.089 3 for the training set and validation set, respectively. For the features of contralateral normal femoral head region, 14 features showed significant predictive value, with the mean AUC value of 0.703 6±0.006 9. The AUC value of the constructed model for the training set and validation set was 0.867 2±0.039 5 and 0.669 0±0.072 6, respectively. For the models developed based on combined features, the AUC value was higher than that of the models developed based on osteonecrosis region features (training set: 0.935 8±0.016 6 vs. validation set: 0.737 9±0.090 8). 【Conclusion】 We developed a novel CT images-based radiomics method to predict postoperative prognosis in patients with ONFH. Furthermore, the features of contralateral normal femoral head region has additional prediction value. Combining the imaging features of osteonecrosis region and contralateral normal femoral head region can obtain more accurate prediction of prognosis in patients with ONFH.

OBJECTIVE: To explore the genetic etiology of a patient with glycogen storage diseases. METHODS: Clinical data of child and his parents were collected. The genes associated with glycogen storage diseases were subjected to high-throughput sequencing to screen the variants. Candidate variant was validated by Sanger sequencing. Pathogenicity of the variant was predicted by bioinformatic analysis. RESULTS: High-throughput sequencing results showed that the boy has carried a hemizygous c.749C>T (p.S250L) variant of the PHKA2 gene. Sanger sequencing verified the results and confirmed that it was inherited from his mother. This variant was unreported previously and predicted to be pathogenic by bioinformatic analysis. CONCLUSION The patient was diagnosed with glycogen storage disease type IXa due to a novel c.749C>T (p.S250L) hemizygous variant of the PHKA2 gene. High-throughput sequencing can facilitate timely and accurate differential diagnosis of glycogen storage disease type IXa.
Child ; Family ; Genetic Testing ; Glycogen Storage Disease/pathology* ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Male ; Mutation ; Phosphorylase Kinase/genetics*

Background::Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or enhance viral infection by various mechanisms, there is lack of information on the role of DUBs in virus regulation, which needs to be further investigated.Methods::Immunoblotting, real-time polymerase chain reaction, in vivo/ in vitro deubiquitination, protein immunoprecipitation, immunofluorescence, and co-localization biological techniques were employed to examine the effect of ubiquitin-specific protease 3 (USP3) on APOBEC3G (A3G) stability and human immunodeficiency virus (HIV) replication. To analyse the relationship between USP3 and HIV disease progression, we recruited 20 HIV-infected patients to detect the levels of USP3 and A3G in peripheral blood and analysed their correlation with CD4 + T-cell counts. Correlation was estimated by Pearson correlation coefficients (for parametric data). Results::The results demonstrated that USP3 specifically inhibits HIV-1 replication in an A3G-dependent manner. Further investigation found that USP3 stabilized 90% to 95% of A3G expression by deubiquitinating Vif-mediated polyubiquitination and blocking its degradation in an enzyme-dependent manner. It also enhances the A3G messenger RNA (mRNA) level by binding to A3G mRNA and stabilizing it in an enzyme-independent manner. Moreover, USP3 expression was positively correlated with A3G expression ( r= 0.5110) and CD4 + T-cell counts ( r= 0.5083) in HIV-1-infected patients. Conclusions::USP3 restricts HIV-1 viral infections by increasing the expression of the antiviral factor A3G. Therefore, USP3 may be an important target for drug development and serve as a novel therapeutic strategy against viral infections.

Objective:To investigate reference intervals for anemia-related routine blood test indicators in Hainan oldest-old and Hainan centenarians.Methods:A cross-sectional data set of China Hainan Centenarians Cohort Study (CHCCS) was used. Household interview, physical examinations, and blood sample analysis were conducted in accordance with standardized procedures. The hemoglobin level, red blood cell count, and hematocrit were analyzed with automatic biochemical analyzer and the reference intervals were determined following CLSI C28-A3 guidelines using a non-parametric method.Results:A total of 715 centenarians, including 137 males (19.2%), and 767 long-lived individuals aged ≥80 years, including 312 males (40.7%), were surveyed. The reference interval of hemoglobin level was 89.1-173.5 g/L in males and 94.4-146.0 g/L in females, respectively, in long-lived individual group. The reference interval of hemoglobin level was 68.4-145.6 g/L in males and 81.0-140.0 g/L in females, respectively, in centenarian group.Conclusion:The reference intervals of hemoglobin level, red blood cell count, and hematocrit were set for the first time for the oldest-old and centenarians in Hainan, which was lower than that currently used in adults.

Objective:To explore the blood pressure levels and the influencing factors of hypertension among Hainan centenarians, and provide basic data for the further blood pressure related studies of the centenarian population.Methods:The baseline data were from China Hainan Centenarian Cohort Study (CHCCS). This cross-sectional data, based on the community population, was a complete sample study of centenarians, including questionnaire survey, physical examination and physiological index detection. A total of 1 002 centenarians were recruited to describe the blood pressure level. According to the guidelines for the prevention and treatment of hypertension in Chinese adults in 2018, the prevalence of hypertension was analyzed.Results:The median levels of systolic blood pressure, diastolic pressure and pulse pressure were 152.0, 76.0 and 76.5 mmHg, respectively. Blood pressure level was higher in females than in males. The prevalence of hypertension was 71.9%, mainly in isolated systolic hypertension with the prevalence of 60.1%. The results of multivariate analysis showed that the risk of hypertension in women was higher than that in men ( OR=1.624, 95% CI: 1.155-2.283), and the risk of hypertension in the northern ( OR=0.625, 95% CI: 0.434-0.901) and central areas ( OR=0.586, 95% CI: 0.346-0.993) was lower than that of the Eastern. Conclusion:The prevalence of hypertension, mainly in isolated systolic hypertension, showing gender and regional distribution differences.