Objective:To evaluate the changes of right atrial volume and function in patients with atrial septal defect（ASD）by four-dimensional ultrasound automatic quantitative technology，and to explore the predictive value and clinical significance for ASD with pulmonary arterial hypertension（PAH）.Methods:Sixty-one patients with ASD and 32 healthy volunteers（control group）who attended Central China Fuwai Hospital of Zhengzhou University，Fuwai Central China Cardiovascular Hospital from March 2023 to April 2024 were prospectively collected，and classified ASD patients into ASD without PAH group（non-PAH group， n=30）and ASD with PAH group（PAH group， n=31）according to whether or not they had PAH，and obtained right atrial reserve，ductal，systolic longitudinal and circumferential strains（RASr，RAScd，RASct，RASr-c，RAScd-c，RASct-c），right atrial minimal，maximal，and presystolic volumes（RAVmin，RAVmax，and RAVpreA），and calculated right atrial total，passive，and active ejection fraction（RAEF，RAPEF，RAAEF）. The ultrasound parameters and clinical data were compared between groups. Pearson's linear correlation was applied to analyse the correlation between the parameters（RASr，RAA，PASP，NT-proBNP）and mean pulmonary artery pressure（mPAP）. ROC curves were plotted and the area under the curve（AUC）was calculated to analyse the value of the four-dimensional strain parameters of the right atrium in independently and jointly predicting the combination of ASD with PAH. Results:①Compared with the control group，RAVmin，RAVmax，and RAVpreA were elevated in the non-PAH and PAH groups，and the absolute values of RAPEF and RAScd were decreased，whereas the absolute values of RAEF，RAAEF，RASr，RASct，RASr-c，and RASct-c were elevated in the non-PAH group，and decreased in the PAH group（all P<0.05）；compared with the non-PAH group，only RAVmin，RAVmax，and RAVpreA were elevated in the PAH group，and the rest of the above parameters were reduced，with statistically significant differences（all P<0.05）. ②The right atrial four-dimensional strain parameter RASr had the highest predictive value for ASD combined with PAH，with an AUC of 0.876，a specificity of 83.3%，and a sensitivity of 77.4%，respectively. ③RASr was negatively correlated with mPAP（ r=-0.591， P<0.001）and RAA，PASP and NT-proBNP were positively correlated with mPAP（ r=0.539，0.697，0.616；all P<0.001）. ④The predictive value of RASr combined with RAA，PASP，and NT-proBNP was superior for ASD combined with PAH（AUC=0.933）. Conclusions:Four-dimensional ultrasound automatic quantitative technology can effectively evaluate the changes of right atrial volume and function in patients with ASD. ASD patients without PAH have increased right atrial reserve and pump function，and decreased right atrial pipeline function. The right atrial function of ASD patients with PAH is significantly reduced，and the impairment is more severe. Among the right atrial four-dimensional strain parameters，RASr has the highest efficacy in predicting ASD combined with PAH. Moreover，the combination of RASr with RAA，PASP，and NT-proBNP has the best predictive efficacy for ASD combined with PAH，which holds significant clinical value.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To evaluate the changes of right atrial volume and function in patients with atrial septal defect（ASD）by four-dimensional ultrasound automatic quantitative technology，and to explore the predictive value and clinical significance for ASD with pulmonary arterial hypertension（PAH）.Methods:Sixty-one patients with ASD and 32 healthy volunteers（control group）who attended Central China Fuwai Hospital of Zhengzhou University，Fuwai Central China Cardiovascular Hospital from March 2023 to April 2024 were prospectively collected，and classified ASD patients into ASD without PAH group（non-PAH group， n=30）and ASD with PAH group（PAH group， n=31）according to whether or not they had PAH，and obtained right atrial reserve，ductal，systolic longitudinal and circumferential strains（RASr，RAScd，RASct，RASr-c，RAScd-c，RASct-c），right atrial minimal，maximal，and presystolic volumes（RAVmin，RAVmax，and RAVpreA），and calculated right atrial total，passive，and active ejection fraction（RAEF，RAPEF，RAAEF）. The ultrasound parameters and clinical data were compared between groups. Pearson's linear correlation was applied to analyse the correlation between the parameters（RASr，RAA，PASP，NT-proBNP）and mean pulmonary artery pressure（mPAP）. ROC curves were plotted and the area under the curve（AUC）was calculated to analyse the value of the four-dimensional strain parameters of the right atrium in independently and jointly predicting the combination of ASD with PAH. Results:①Compared with the control group，RAVmin，RAVmax，and RAVpreA were elevated in the non-PAH and PAH groups，and the absolute values of RAPEF and RAScd were decreased，whereas the absolute values of RAEF，RAAEF，RASr，RASct，RASr-c，and RASct-c were elevated in the non-PAH group，and decreased in the PAH group（all P<0.05）；compared with the non-PAH group，only RAVmin，RAVmax，and RAVpreA were elevated in the PAH group，and the rest of the above parameters were reduced，with statistically significant differences（all P<0.05）. ②The right atrial four-dimensional strain parameter RASr had the highest predictive value for ASD combined with PAH，with an AUC of 0.876，a specificity of 83.3%，and a sensitivity of 77.4%，respectively. ③RASr was negatively correlated with mPAP（ r=-0.591， P<0.001）and RAA，PASP and NT-proBNP were positively correlated with mPAP（ r=0.539，0.697，0.616；all P<0.001）. ④The predictive value of RASr combined with RAA，PASP，and NT-proBNP was superior for ASD combined with PAH（AUC=0.933）. Conclusions:Four-dimensional ultrasound automatic quantitative technology can effectively evaluate the changes of right atrial volume and function in patients with ASD. ASD patients without PAH have increased right atrial reserve and pump function，and decreased right atrial pipeline function. The right atrial function of ASD patients with PAH is significantly reduced，and the impairment is more severe. Among the right atrial four-dimensional strain parameters，RASr has the highest efficacy in predicting ASD combined with PAH. Moreover，the combination of RASr with RAA，PASP，and NT-proBNP has the best predictive efficacy for ASD combined with PAH，which holds significant clinical value.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

AIM:To investigate the molecular mechanism of a novel bromobenzene substituted trifluoromethylbenzo Cyclopentanone WW02 inhib-iting the viability and proliferation of human lung cancer A549 and H1299 cells.METHODS:The ef-fect of different concentrations of WW02(6.25,12.5,25,50 μg/mL)on cell viability and prolifera-tion of A549 and H1299 were measured using CCK-8 and EdU methods.After 24 hours of stimulation of A549 and H1299 cells with different concentra-tions of WW02,the changes in Akt and mTOR phos-phorylation levels under different concentrations of WW02 were detected through Western blot as-say.Macromolecular docking was carried out be-tween WW02,AKT and mTOR through MOE Dock.RESULTS:After treating A549 and H1299 cells with WW02 using different concentrations(6.25,12.5,25,50 μg/mL),the activity of A549 and H1299 cells decreased in a concentration dependent manner compared with the DMSO control group(P<0.05).The proliferation of cells showed a concentration dependent decrease compared to the DMSO con-trol group(P<0.05).Compared with the DMSO con-trol group,after 24 hours of WW02 stimulation,the phosphorylation levels of Akt and mTOR in A549 cells decreased under the concentration of WW02(12.5,25,50 μg/mL,P<0.05).Compared with the DMSO control group,the phosphorylation levels of Akt and mTOR in H1299 cells decreased af-ter 24 hours of WW02 stimulation(25,50 μg/mL,P<0.05).Based on pattern analysis,it was found that WW02 had a strong binding with Akt and mTOR,with the highest score of-8.3 kcal/mol for WW02 and mTOR,while the highest score for WW02 and Akt was-7.3 kcal/mol.CONCLUSION:WW02 inhib-its the activity and proliferation of lung cancer A549 and H1299 cells,and its mechanism of action may be achieved by directly binding to Akt and mTOR proteins to inhibit Akt and mTOR phosphory-lation.

Objective:To observe the effects of preventative moxibustion on analgesia,substance P(SP),prostaglandin(PG)F2α and PGE2 in rats with dysmenorrhea due to cold-dampness stagnation,and to explore the analgesic mechanism. Methods:Sixty-four female Wistar non-pregnant rats were randomly divided into a blank group,a model group,a Western medicine group,and a preventative moxibustion group,with 16 rats in each group.Eight qualified diestrus rats were selected from each group.Except for the blank group,the other three groups established models of dysmenorrhea due to cold-dampness stagnation using an ice water bath combined with estradiol benzoate and oxytocin.On the 8th day after modeling,the preventative moxibustion group was treated with gentle moxibustion at Shenque(CV8)and Guanyuan(CV4),and the Western medicine group was given ibuprofen solution for 4 consecutive days.On the 11th day,the intervention groups(i.e.the Western medicine group and the preventative moxibustion group)were treated once again after being injected with oxytocin.The writhing score and the pain threshold of rats were determined;the serum levels of brain-derived neurotrophic factor(BDNF),SP,PGF2α,and PGE2 were measured;the mRNA and protein expression levels of BDNF and its receptor tropomyosin receptor kinase B(TrkB)in the spinal dorsal horn and hypothalamus were detected. Results:Compared with the blank group,the writhing score increased(P<0.01),the pain threshold decreased(P<0.01),the serum levels of BDNF,SP,and PGF2α increased(P<0.01),while the PGE2 decreased(P<0.01);the protein and mRNA expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus increased(P<0.01)in the model group.Compared with the model group,the writhing score decreased,the pain threshold increased,the serum BDNF,SP,and PGF2α levels decreased significantly,the serum PGE2 level increased,and the protein and mRNA expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus decreased significantly in the preventative moxibustion group and the Western medicine group,while the inter-group differences were significant(P<0.01).Compared with the Western medicine group,the writhing score decreased,the pain threshold increased,the serum BDNF,SP,and PGF2α,levels decreased,the serum PGE2 level increased,and the protein and mRNA expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus in the preventative moxibustion group decreased significantly,while the inter-group differences were significant(P<0.05 or P<0.01). Conclusion:Preventative moxibustion at Shenque(CV8)and Guanyuan(CV4)can improve the pain sensitization state of rats with dysmenorrhea due to cold-dampness stagnation,down-regulate the mRNA and protein expression levels of BDNF and TrkB in the spinal dorsal horn and hypothalamus;regulation of the serum SP,PGF2α,and PGE2 levels may be part of the mechanism.

Objective:To detect the abnormal changes of myocardial blood perfusion in patients with hypertrophic cardiomyopathy(HCM) by myocardial contrast echocardiography (MCE) combined with adenosine stress test.Methods:Fifteen adult patients with HCM who were treated in Fuwai Central China Cardiovascular Hospital from May 2021 to March 2022 were prospectively selected as the HCM group, and eighteen healthy volunteers matched by gender, age and body surface area during the same period were chosen as the control group. All subjects underwent routine echocardiography, rest and adenosine stress MCE. The MCE images were analyzed by QLab software to obtain the myocardial perfusion parameters: peak signal intensity (A value), rising slope of the curve (β value) and A×β value, and the differences of above parameters between the two groups were compared.According to whether the end-diastolic wall thickness ≥12 mm, the myocardial segments in the HCM group were divided into hypertrophic segments and non-hypertrophic segments. The differences in myocardial perfusion parameters were compared among control group segments, hypertrophic segments and non-hypertrophic segments of the HCM group. The correlations of stress myocardial blood flow with maximal left ventricular wall thickness (MLVWT), left ventricular mass index (LVMI) and left atrial volume index (LAVI) in the HCM group were analyzed.Results:Compared with the control group, the A value, β value and A×β value of whole myocardium, hypertrophic segments and non-hypertrophic segments in the HCM group were significantly decreased in the rest and adenosine stress state, and the differences were statistically significant (all P<0.05). In the stress state, the A value, β value and A×β value of the hypertrophic segments were significantly lower than those in the non-hypertrophic segments in the HCM group, and the detection rate of abnormal perfusion segments in the HCM group was significantly higher than that in the rest state(all P<0.05). Compared with the control group, the myocardial blood flow reserve of whole myocardium, hypertrophic segments and non-hypertrophic segments in the HCM group were significantly decreased, and the differences were statistically significant(all P<0.05). The stress myocardial blood flow in the HCM group was negatively correlated with MLVWT, LVMI and LAVI ( r=-0.815, -0.805, -0.742; all P<0.05). Conclusions:Myocardial blood perfusion abnormalities can occur in both hypertrophic and non-hypertrophic myocardial segments in patients with HCM, and adenosine stress MCE can significantly improve the sensitivity of detecting myocardial perfusion abnormalities. The stress myocardial blood flow in patients with HCM is negatively correlated with MLVWT, LVMI and LAVI.

Objective:To evaluate the right atrial volume and function abnormalities in patients with pulmonary hypertension (PH) by four-dimensional automatic quantitation technique, and to explore the application value of this technique in evaluating the risk stratification and World Health Organization functional class(WHO-FC) of PH patients.Methods:Eighty-four adult patients with PH diagnosed by right heart catheterization from April to October 2022 in Fuwai Central China Cardiovascular Hospital were consecutively enrolled as the PH group. All cases were divided into 3 groups according to the mean pulmonary arterial pressure (mPAP): mild PH group ( n=28), moderate PH group ( n=28), severe PH group ( n=28). Twenty-eight healthy volunteers matched by gender and age were included in the same period as the control group. The volume and strain parameters of the right atrium were obtained by analyzing the four-dimensional image of the right atrium using four-dimensional automatic quantitation technique, including right atrial minimum volume index (RAVImin), right atrial maximum volume index (RAVImax), right atrial presystolic volume index (RAVIpreA), right atrial ejection fraction (RAEF), right atrial passive ejection fraction (RAPEF), right atrial active ejection fraction, RAAEF, longitudinal strains of right atrial reserve, conduit and systolic period (RASr, RAScd, RASct), circumferential strains of right atrial reserve, conduit and systolic period (RASr-c, RAScd-c, RASct-c). The differences in right atrial parameters among four groups were compared.ROC curve was used to analyze the diagnostic efficiency of right atrial four-dimensional strain parameters for PH patients with WHO-FC≥Ⅲ. Pearson linear correlation analysis was used to investigate the relationships between RASr and right atrial area (RAA), NT-proBNP and tricuspid annular plane systolic excursion to pulmonary arterial systolic pressure ratio (TAPSE/sPAP). Results:①Compared with the control group, RAEF, RAPEF, RASr, RAScd, RASr-c, RAScd-c were significantly decreased in mild, moderate and severe PH groups; while RAAEF, RASct, RASct-c were significantly increased in mild PH group and significantly decreased in moderate and severe PH groups, and the differences were statistically significant (all P<0.05). RAVImin, RAVImax, RAVIpreA gradually increased among the control, mild PH, moderate PH and severe PH groups, and the differences were statistically significant (all P<0.05). RAEF, RAPEF, RAAEF, RASr, RAScd, RASct, RASr-c, RAScd-c, RASct-c were decreased successively among mild, moderate and severe PH groups, and the differences were statistically significant (all P<0.05). ②ROC curve showed that RASr had the highest diagnostic efficiency in PH patients with WHO-FC ≥Ⅲ, and the cut-off value was 20.5% (AUC=0.914, P<0.001). ③Correlation analysis showed that RASr was correlated with RAA, NT-proBNP and TAPSE/sPAP ( r=-0.803, -0.621, 0.739; all P<0.001). Conclusions:The degree of right atrial function impairment increased in patients with mild, moderate and severe PH in turn. RASr is the best predictor of WHO-FC ≥Ⅲ in patients with pulmonary hypertension and is a potential parameter for risk stratification in patients with PH.

Objective: To observe the effects of ginger-partitioned moxibustion at Shenque (CV8) and Guanyuan (CV4) on the expression levels of endocrine-related molecules and their receptors in rats with primary dysmenorrhea (PD) due to cold-dampness stagnation, thus to explore their analgesic mechanisms. Methods: Thirty-two female Wistar rats were divided into a normal group, a model group, a ginger-partitioned moxibustion group, and a Western medicine group according to the random number table method, with 8 rats in each group. Except for rats in the normal group, all other rats were treated with oxytocin combined with ice-water bath to establish the rat models of PD due to cold-dampness stagnation. After successful modeling, rats in the normal group and the model group did not receive treatment; rats in the ginger-partitioned moxibustion group received treatments with ginger-partitioned moxibustion at Shenque (CV8) and Guanyuan (CV4); rats in the Western medicine group received ibuprofen by intragastric administration. The writhing response of rats was compared among groups, and the serum levels of prostaglandin F2α (PGF2α), estrogen (estradiol, E2), progesterone (P), and the mRNA expression of PGF2α and E2 receptors in the uterine tissues were detected. Results: No writhing behavior was observed in the normal group; compared with the normal group, the serum PGF2α and E2 levels in the model group were increased (P<0.01), while the P level was decreased (P<0.01), and the mRNA expression levels of the uterine PGF2α and E2 receptors were increased (P<0.01, P<0.05). Compared with the model group, the writhing behavior latency was prolonged, and the writhing response score was decreased in the ginger-partitioned moxibustion group and the Western medicine group (P<0.01); the serum PGF2α and E2 levels in the ginger-partitioned moxibustion group and the Western medicine group were decreased, while the P level was increased (P<0.05 or P<0.01); the mRNA expression levels of the uterine PGF2α and E2 receptors in the ginger-partitioned moxibustion group and the Western medicine group were decreased (P<0.05). Compared with the Western medicine group, the ginger-partitioned moxibustion group showed a prolonged writhing behavior latency, reduced writhing response score (P<0.05), and decreased serum E2 level (P<0.05), while no statistical differences in the serum PGF2α and P levels, or the mRNA expression levels of uterine PGF2α and E2 receptors (P>0.05).Conclusion: The analgesic effect of ginger-partitioned moxibustion on PD due to cold-dampness stagnation may be related to regulating the mRNA expression levels of PGF2α and E2 receptors in the uterine tissues.

Objective:To detect the abnormal changes of myocardial blood perfusion in patients with hypertrophic cardiomyopathy (HCM) by myocardial contrast echocardiography(MCE) combined with exercise stress test.Methods:Twenty-seven patients with clinically diagnozed of asymmetric HCM in Fuwai Central China Cardiovascular Hospital from May 2020 to April 2021 were selected as the HCM group, and 29 healthy subjects during the same period were selected as the control group. All patients underwent routine echocardiography, resting and exercise stress MCE. The myocardial perfusion parameters of each segment of interventricular septum in the 2 groups were quantitatively analyzed: the peak plateau intensity (A value), ascending slope of the curve(β value) and value of A×β. According to the end-diastolic myocardial thickness, the interventricular septum of the HCM group was divided into hypertrophic and non-hypertrophic segments, and the myocardial contrast parameters of the interventricular septum of the study group were compared with those of the control group. The myocardial blood flow reserve value of the two groups were calculated, and the correlation of myocardial blood flow reserve value with left ventricular mass index (LVMI) and left ventricular remodeling index (LVRI) were analyzed.Results:No matter at rest or under stress, the A value, β value and A×β value of ventricular septal hypertrophic and non-hypertrophic segments in the hypertrophic cardiomyopathy group were lower than those in the control group, and the differences were statistically significant (all P<0.05). Under stress, the A value, β value and A×β value of interventricular septal hypertrophic segments were lower than those in non-hypertrophic segments in the HCM group, and the differences were statistically significant (all P<0.05). The myocardial blood flow reserve in the HCM group was negatively correlated with LVMI and LVRI( r=-0.899, -0.676; all P<0.001). Conclusions:In patients with HCM under resting and exercise stress, microcirculation disorders were found in both hypertrophic and non-hypertrophic segments of the ventricular wall, and the myocardial blood flow reserve was negatively correlated with LVMI and LVRI.