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 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.

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 explore the clinical value of adenosine stress myocardial contrast echocardiography in detecting myocardial blood perfusion abnormalities in patients with type 2 diabetes mellitus.Methods:Twenty-six patients with type 2 diabetes mellitus clinically diagnosed from May 2019 to January 2020 in the endocrinology department of Fuwai Central China Cardiovascular Hospital and 28 healthy examinees with gender and age matched during the same period were enrolled. Routine echocardiography, rest and adenosine stress myocardial contrast echocardiography were performed, the plateau signal intensity(A value), curve rising slope(K value) and A×K value of the myocardial perfusion time-intensity curve were obtained by offline analysis. And general data such as age, gender, disease course, body mass index and glycated hemoglobin were collected, and results of the two groups were compared statistically.Results:In the rest state, the A value of the myocardial perfusion parameter in the diabetic group was not significantly different from that of the control group, both in whole and in segments ( P>0.05), while the K value and A×K value of the myocardial perfusion parameters in the diabetic group were significantly lower than those in the control group ( P<0.05). In the stress state, the A value, K value and A×K value of myocardial perfusion parameters in the diabetic group were significantly lower than those in the control group, both in whole and in segments ( P<0.05). The detection rate of myocardial perfusion abnormality in the stress state was significantly higher than that in the rest state, and the difference was statistically significant ( P<0.05). The myocardial blood flow reserve in the diabetic group was negatively correlated with the course of disease and the level of glycated hemoglobin ( r=-0.580, P=0.020; r=-0.481, P=0.013). Conclusions:Adenosine stress myocardial contrast echocardiography can be used for detection of left ventricular myocardial perfusion abnormalities in patients with type 2 diabetes mellitus, which has great clinical application value.

Objective To compare and analyze differences in macular thickness and to discuss the correlation between macular thickness and visual field mean defect (MD) in early and moderate,late pseudoexfoliation glaucoma (PXG) patients and normal control subjects.Methods A series of cases-observation study was adopted.Thirty-three early and moderate PXG patients (33 eyes) and 24 late PXG patients (24 eyes) were collected in the First Hospital of Shijiazhuang from May 2013 to May 2018.Meanwhile,34 age,gender and diopermatched healthy subjects (34 eyes) were included as normal control group.Spectral domain optical coherence tomography (SD-OCT) was used to measure macular thickness and volume in every quadrant.The correlation between the macular thickness and visual field MD were analyzed.This study followed the Helsinki declaration and was approved by the ethics committee of the First Hospital of Shijiazhuang.Written informed consent was obtained from each subject prior to any medical examination.Results The average macular thickness in normal control group,early and moderate PXG group and late PXG group were (305 ± 15),(297 ± 15) and (287 ± 17) μm,respectively;the average macular volume were (0.94 ± 0.05),(0.91 ± 0.05) and (0.89 ± 0.05) μm3,respectively.The macular thickness and volume differences between the 3 groups were statistically significant in nasal inner macula,superior inner macula,temporal inner macula,inferior inner macula,superior outer macula,temporal outer macula,inferior outer macula quadrants (Fthickness =4.226,9.335,12.133,10.115,11.298,8.243,12.142;all at P＜0.05.Fvolume =3.812,9.152,12.774,8.889,11.284,7.937,11.652;all at P＜0.05).The macular thickness of early and moderate PXG group in superior inner macula,temporal inner macula,inferior inner macula,superior outer macula and temporal outer macula quadrants were statistically thinner than those in the normal control group (all at P＜0.05);the macular thickness of late PXG group in inferior inner macula,temporal inner macula,superior outer macula and inferior outer macula quadrants were statistically thinner than those in the early and moderate PXG group (all at P＜0.05);the macular thickness of late PXG group in inner and outer rings were statistically thinner than those in the normal control group (all at P＜0.05).The macular thickness was not correlated with visual field MD in normal control group and the early and moderate PXG group in every quadrants (all at P＞0.05),but it was positively correlated with visual field MD in the late PXG group in nasal inner macula,superior outer macula and temporal inner macula quadrants (r =0.527,0.544,0.417;all at P＜0.05).Conclusions SD-0CT can quantify the macular thickness,and can be used an important reference index for the staging and follow-up of PXG combined with perimetry.

A method for simultaneous determination of 12 kinds of chlorinated disinfection byproducts (DBPs) in drinking water was developed based on liquid-liquid extraction gas chromatography equipped with electron capture detector (GC/ECD).The procedural standard calibration was adopted to eliminate the interference of different matrix.The method detection limits for 12 DBPs were 0.08-0.21 μg/L and the entire analytical procedure was finished in 21.50 min.The recoveries were in the range of 80.9%-115.7% and the relative standard deviations (RSD) were between 0.9% and 9.9% at different concentration levels (5 and 50 μg/L) in tap water and surface water.The correlation coefficients for all 12 kinds of DBPs were greater than 0.99 in the linearity range of 0.5-200 μg/L.The method was applied to determine DBPs in drinking water and source water.This method was rapid and competent for detection of volatile DBPs in drinking water.

Objective: To observe the effects of moxibustion at different times on prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α) and arginine vasopressin (AVP), in the uterine tissues of rats with dysmenorrhea due to cold-dampness retention, and to explore the differences and possible mechanisms of moxibustion at different times in easing pain in dysmenorrhea due to cold-dampness retention. Methods: Forty-three female Wistar rats were randomly divided into a blank control group (n=7), a model group (n=9), a pre-moxibustion group (n=9), an immediate-moxibustion group (n=9) and a pre-moxibustion plus immediate-moxibustion group (n=9). Rat models of primary dysmenorrhea due to cold-dampness retention were established using (0±1) ℃ ice water immersion method combined with injection of estradiol benzoate for 10 d, followed by injection of oxytocin on the 11th day. Rats in the 3 intervention groups received moxibustion to Shenque (CV 8) and Guanyuan (CV 4), 10 min for each acupoint, once a day. Rats in pre-moxibustion group were given mild moxibustion, beginning on the 8th day during modeling, for 3 continuous days; rats in immediate-moxibustion group were given one time mild moxibustion, immediately after injection of oxytocin on the 11th day during modeling; rats in pre-moxibustion plus immediate-moxibustion group were given mild moxibustion, beginning on the 8th day during modeling till immediately after injection of oxytocin on the 11th day during modeling, for 4 continuous days. The level of PGF2α in the rat uterine tissues was measured by enzyme-linked immunosorbent assay (ELISA), and the levels of PGE2 and AVP in rat uterine tissues were measured by radioimmunoassay. Results: Compared with the blank control group, the levels of PGF2α and AVP, the PGF2α/PGE2 ratio in the model group were significantly increased (P<0.01), and the PGE2 level was significantly decreased (P<0.01) in the rat uterine tissues in the model group. Compared with the model group, the writhing latency was significantly prolonged, the writhing number and the total writhing score were all decreased in the pre-moxibustion group, the immediate-moxibustion group and the pre-moxibustion plus immediate-moxibustion group (all P<0.01); the levels of PGF2α and AVP, and the PGF2α/PGE2 ratio were all significantly decreased (P<0.05, P<0.01), and the PGE2 level was significantly increased (P<0.01) in the rat uterine tissues of the 3 treatment groups. Compared with the pre-moxibustion group, the writhing number and the total writhing score were all decreased in the immediate-moxibustion group and the pre-moxibustion plus immediate-moxibustion group (all P<0.01), the writhing latency was significantly prolonged in the pre-moxibustion plus immediate-moxibustion group(P<0.01); the levels of PGF2α and PGF2α/PGE2 ratio were significantly decreased (P<0.05, P<0.01), and the PGE2 level was significantly increased (P<0.01) in rat uterine tissues in the immediate-moxibustion group and the pre-moxibustion plus immediate-moxibustion group. Compared with the immediate-moxibustion group, the writhing latency was significantly prolonged and the writhing number was decreased (all P<0.05), and the total writhing score was decreased (P<0.01) in the pre-moxibustion plus immediate-moxibustion group; the PGF2α level and the PGF2α/PGE2 ratio were significantly decreased (P<0.01), and the PGE2 level was significantly increased (P<0.01) in rat uterine tissues in the pre-moxibustion plus immediate-moxibustion group. Conclusion: Moxibustion at different times all can produce obvious analgesic effects on dysmenorrhea due to cold-dampness retention in rats, and pre-moxibustion plus immediate-moxibustion ranks the top. The mechanism of this analgesic effect may be via the regulation of abnormal PGF2α, PGE2 and AVP levels, to effectively inhibit the spastic contraction of uterine smooth muscle in dysmenorrhea rat, thereby improving the ischemia and hypoxia in uterus.