1. Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology
Xiao-Dan ZHANG ; Yu-Liang XIE ; Meng-Dan GAO ; Ao-Xue YUAN ; Han-Fei LI ; Tian-Tian ZHU ; Xiao-Dan ZHANG ; Yu-Liang XIE ; Meng-Dan GAO ; Ao-Xue YUAN ; Han-Fei LI ; Tian-Tian ZHU ; Xiao-Dan ZHANG ; Yu-Liang XIE ; Meng-Dan GAO ; Ao-Xue YUAN ; Han-Fei LI ; Tian-Tian ZHU
Chinese Pharmacological Bulletin 2024;40(3):565-573
Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.
2.Relationship between executive function and social adjustment in children with developmental dyslexia
YIN Feifei, XIAO Xinyu, ZHANG Han, ZUO Pengxiang,LI Dan
Chinese Journal of School Health 2024;45(6):835-839
Objective:
To explore the characteristics of executive function of developmental dyslexic children and the relationship with social adaptability, in order to provide a scientific basis for promoting healthy development of developmental dyslexic children.
Methods:
From June to September 2023, 85 students in the developmental dyslexia group, 85 students in the biological agematched group and 85 students in the reading levelmatched group were selected from the third to sixth grades of two elementary school in a region of Xinjiang by cluster random sampling method. Their executive function was assessed by the Stroop procedure, the 2-back procedure and the numerical conversion procedure, respectively, and their social adaptive ability was assessed by the Social Adaptation Scale for Children and Adolescents. An analysis of variance (ANOVA) was used to compare the differences in executive function and social adjustment among the three groups, and Pearsons correlation was used to analyze the relationship between executive function and social adjustment in developmental dyslexic children.
Results:
Children in the developmental dyslexia group had lower correctness on the Stroop colorword task (0.72±0.21), the 2-back task (0.32±0.13), the digitswitching task (0.54±0.16) and the total score of social adjustment (165.39±31.36) than children in the biological agematched (0.80±0.19,0.38±0.11,0.61±0.15,181.71±31.85) and reading levelmatched group (0.79±0.17,0.35±0.07,0.58±0.15,175.71±27.48) (F=4.54,5.05,4.97,6.31,P<0.01). The inhibition (Stroop colorword task correct rate) and conversion subcomponent (digitswitching task correct rate) of the executive function of children in the developmental dyslexia group were both positively correlated with their social adaptive ability (r=0.34,0.43), and the refreshing subcomponent of the executive function (2-back task correct rate) was negatively correlated with their social adaptive ability (r=-0.27) (P<0.05).
Conclusions
Children with developmental dyslexia have executive function deficits and social maladjustment, and their executive function is related to social adjustment. Measures should be taken to improve the executive function of developmental dyslexic children and to improve their social adaptation.
3.Clinical value of joint detection of cerebrospinal fluid and blood routine indicators in differentiating between multiple gliomas and primary central nervous system lymphoma
Hua JIANG ; Limin ZHANG ; Dan WANG ; Ping HAN ; Yuehong SUN ; Yuwen LI ; Chenxi ZHANG ; Wencan JIANG ; Xiao LI ; Hui ZHAO
The Journal of Practical Medicine 2024;40(13):1864-1868,1873
Objective To investigate the clinical significance of combined cerebrospinal fluid(CSF)and routine blood parameter analysis in differentiating between multiple cerebral glioma(MCG)and primary central nervous system lymphoma(PCNSL).Methods We Rretrospectively analyzed the clinical data,CSF and routine blood indicators levels of 62 MCG patients and 56 PCNSL patients admitted to Beijing Tiantan Hospital,Capital Medical University from November 2017 to March 2023.Additionally,we assessed the diagnostic value of individual meaningful indicators as well as their combinations in distinguishing between MCG and PCNSL.Results The levels of CSF total cell count,CSF white cell count,CSF:pro,lactate,routine bloodperipheral neutrophil count,and neu-trophil percentage were significantly higher in the MCG group than in the PCNSL group(P<0.05);while the levels of CSF:Glu,CSF:cl,routine blood lymphocyte count,eosinophil,lymphocyte percentage,and eosinophil percent-age were significantly higher in the PCNSL group than in the MCG group(P<0.05).The AUCs of CSF cell count,CSF white cell count,CSF:pro,lactate,routine blood neutrophil count,neutrophil percentage for differentiating MCG from PCNSL were 0.900,0.899,0.797,0.867,0.828 and 0.772 respectively;sensitivities were 72.4%,77.6%,63.8%,67.2%,72.4%,82.8%,77.6%and 81%,with sensitivities of 97.1%,100%,88.2%,91.2%,88.2%,64.7%,100%and 94.1%,respectively.In addition,the combined detection of CSF total cell count,CSF white cell count,CSF:pro,routine blood neutrophil count and neutrophil percentage in CSF had an AUC of 0.919 for differentiating MCG from PCNSL,with a sensitivity and specificity of 77.6%and 100%,respectively.Conclusions Combined detection of CSF indicators including CSF total cell count,CSF white cell count,CSF:pro,along with routine blood markers such as neutrophil count and neutrophil percentage,holds significant clinical utility for differ-entiating between MCG and PCNSL.
4.Adolescents and Children Age Estimation Using Machine Learning Based on Pulp and Tooth Volumes on CBCT Images
Jia-Xuan HAN ; Shi-Hui SHEN ; Yi-Wen WU ; Xiao-Dan SUN ; Tian-Nan CHEN ; Jiang TAO
Journal of Forensic Medicine 2024;40(2):143-148
Objective To estimate adolescents and children age using stepwise regression and machine learning methods based on the pulp and tooth volumes of the left maxillary central incisor and cuspid on cone beam computed tomography(CBCT)images,and to compare and analyze the estimation re-sults.Methods A total of 498 Shanghai Han adolescents and children CBCT images of the oral and maxillofacial regions were collected.The pulp and tooth volumes of the left maxillary central incisor and cuspid were measured and calculated.Three machine learning algorithms(K-nearest neighbor,ridge regression,and decision tree)and stepwise regression were used to establish four age estimation models.The coefficient of determination,mean error,root mean square error,mean square error and mean ab-solute error were computed and compared.A correlation heatmap was drawn to visualize and the monotonic relationship between parameters was visually analyzed.Results The K-nearest neighbor model(R2=0.779)and the ridge regression model(R2=0.729)outperformed stepwise regression(R2=0.617),while the decision tree model(R2=0.494)showed poor fitting.The correlation heatmap demon-strated a monotonically negative correlation between age and the parameters including pulp volume,the ratio of pulp volume to hard tissue volume,and the ratio of pulp volume to tooth volume.Con-clusion Pulp volume and pulp volume proportion are closely related to age.The application of CBCT-based machine learning methods can provide more accurate age estimation results,which lays a founda-tion for further CBCT-based deep learning dental age estimation research.
5.Mechanism and clinical study of cardiac contractility modulation for heart failure
Qun LU ; Xiao LIANG ; Ling BAI ; Dan-Jun ZHU ; Xiao-Lin XUE ; Ke HAN
Chinese Journal of Interventional Cardiology 2024;32(8):457-462
Cardiac contractility modulation(CCM),as a new implantable electronic therapy device for treating chronic heart failure with reduced ejection fraction(HFrEF),has rapidly become a hot topic in the cardiovascular field due to its ability to enhance ventricular myocardial contractility,improve patients'symptoms and signs,cardiac function indexes and even long-term prognosis.This article reviews the mechanism and clinical studies of CCM in treating HFrEF,and based on its mechanism and signal transduction algorithm,further analyzes and prospects its efficacy in patients with heart failure with preserved ejection fraction,cardiac resynchronization therapy non-response,and HFrEF with concomitant atrial fibrillation,aiming to promote CCM to meet the needs of more diverse clinical situations in heart failure patients.
6.Research progress on neurobiological mechanisms underlying antidepressant effect of ketamine
Dong-Yu ZHOU ; Wen-Xin ZHANG ; Xiao-Jing ZHAI ; Dan-Dan CHEN ; Yi HAN ; Ran JI ; Xiao-Yuan PAN ; Jun-Li CAO ; Hong-Xing ZHANG
Chinese Pharmacological Bulletin 2024;40(9):1622-1627
Major depressive disorder(MDD)is a prevalent con-dition associated with substantial impairment and low remission rates.Traditional antidepressants demonstrate delayed effects,low cure rate,and inadequate therapeutic effectiveness for man-aging treatment-resistant depression(TRD).Several studies have shown that ketamine,a non-selective N-methyl-D-aspartate receptor(NMDAR)antagonist,can produce rapid and sustained antidepressant effects.Ketamine has demonstrated efficacy for reducing suicidality in TRD patients.However,the pharmaco-logical mechanism for ketamine's antidepressant effects remains incompletely understood.Previous research suggests that the an-tidepressant effects of ketamine may involve the monoaminergic,glutamatergic and dopaminergic systems.This paper provides an overview of the pharmacological mechanism for ketamine's anti-depressant effects and discuss the potential directions for future research.
7.Establishment and efficiency test of a clinical prediction model of bronchopulmonary dysplasia associated pulmonary hypertension in very premature infants
Jingke CAO ; Haoqin FAN ; Yunbin XIAO ; Dan WANG ; Changgen LIU ; Xiaoming PENG ; Xirong GAO ; Shanghong TANG ; Tao HAN ; Yabo MEI ; Huayu LIANG ; Shumei WANG ; Feng WANG ; Qiuping LI
Chinese Journal of Pediatrics 2024;62(2):129-137
Objective:To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants.Methods:This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1 st, 2015 to December 31 st, 2021 of the Seventh Medical Center of the People′s Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children′s Hospital from January 1 st, 2020 to December 31 st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks′ corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model′s discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results:A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95% CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions:A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.
8.Comparative efficacy of double Z-shaped suture and modified Kessler suture in repair of acute closed Achilles tendon rupture
Han XUE ; Dan LIU ; Fengxu XIAO ; Chen ZHANG ; Miao LI
Chinese Journal of Trauma 2024;40(9):817-825
Objective:To compare the efficacy of double Z-shaped suture and modified Kessler suture in the repair of acute closed Achilles tendon rupture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 27 patients with acute closed Achilles tendon rupture admitted to the Second Affiliated Hospital of Xi′an Jiaotong University from July 2018 to July 2022, including 24 males and 3 females, aged 14-53 years [(35.7±8.2)years]. All the patients underwent primary open surgical repair of the Achilles tendon, among whom 16 patients were treated with the double Z-shaped suture technique (double Z-shaped suture group) and 11 with the modified Kessler suture technique (modified Kessler suture group). Visual analogue scale (VAS) scores preoperatively and at 2, 4, and 6 weeks postoperatively as well as at the last follow-up were compared between the two groups. American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores, Achilles tendon total rupture scores (ATRS), ankle range of motion (dorsiflexion and plantarflexion angles), and shear wave elastography (SWE) [with its results recorded as shear wave velocity (SWV)] were applied to evaluate the recovery of tendon function and quality. High-frequency ultrasonography was also used to evaluate the recovery of morphological structure of the Achilles tendon and soft tissue adhesion. Tolerance to early rehabilitation at 2 weeks postoperatively and the incidence of postoperative complications were compared between the two groups.Results:All the patients were followed up for 6-12 months [(9.6±1.3)months]. There was no statistically significant difference in preoperative VAS scores between the two groups ( P>0.05). At 2, 4, and 6 weeks postoperatively, the VAS scores in the double Z-shaped suture group were 4.6(4.0, 5.0)points, 1.6(1.0, 2.0)points, and 0.5(0.0, 1.0)points respectively, significantly lower than those in the modified Kessler suture group [6.9(6.0, 8.0)points, 2.5(2.0, 3.0)points, and 1.4(1.0, 2.0)points] ( P<0.05 or 0.01). At the last follow-up, the VAS decreased to 0.0(0.0, 0.0)points in both groups. VAS score in the double Z-shaped suture group significantly decreased at 2 weeks postoperatively compared to that preoperatively, with a consistent downward trend observed at all the postoperative time points ( P<0.05). In the modified Kessler suture group, there was no significant difference in VAS scores preoperatively and at 2 weeks postoperatively ( P>0.05), but a downward trend was noted at 4 and 6 weeks postoperatively and at the last follow-up ( P<0.05). There were no significant differences in AOFAS ankle-hindfoot scores, ATRS or SWV at 2, 4, and 6 weeks postoperatively and at the last follow-up ( P>0.05). At 2, 4, and 6 weeks postoperatively, dorsiflexion angles in the double Z-shaped suture group were (-18.2±3.9)°, (-13.7±2.8)°, and (-6.6±2.4)° respectively, significantly better than those in the modified Kessler suture group [(-24.1±2.7)°, (-18.3±3.0)°, and (-12.0±2.8)°] ( P<0.01). No significant difference in dorsiflexion angles was observed between the groups at the last follow-up ( P>0.05). No significant differences in plantarflexion angles were noted at 2 weeks postoperatively and at the last follow-up ( P>0.05). At 4 and 6 weeks postoperatively, plantarflexion angles in the double Z-shaped suture group were (37.5±3.8)° and (42.1±3.3)°respectively, significantly better than those in the modified Kessler suture group [(34.6±2.0)° and (38.0±1.4)°] ( P<0.05 or 0.01). Both groups showed increasing trends in AOFAS ankle-hindfoot scores, dorsiflexion and plantarflexion angles, and SWV at 4 and 6 weeks postoperatively, as well as at the last follow-up ( P<0.05 or 0.01). No significant differences were noted in ATRS at 2 and 4 weeks postoperatively in the double Z-shaped suture group ( P>0.05), but significant improvements were observed at 6 weeks postoperatively and at the last follow-up ( P<0.05 or 0.01). In the modified Kessler suture group, no significant changes in ATRS scores were observed at 2, 4 and 6 weeks postoperatively ( P>0.05), except a significant increase at the last follow-up ( P<0.05). High-frequency ultrasonography at 2, 4, and 6 weeks postoperatively as well as at the last follow-up indicated good morphological recovery of the Achilles tendon in both groups, while soft tissue adhesion was significantly less in the double Z-shaped suture group compared with that of the modified Kessler suture group. Thirteen patients (81.3%) in the double Z-shaped suture group and 3 patients (27.3%) in the modified Kessler suture group were observed to tolerate the early rehabilitation at 2 weeks postoperatively as scheduled in the rehabilitation plan ( P<0.05). There was no statistically significant difference in the incidence of postoperative complications between the groups ( P>0.05). Conclusion:Compared with the modified Kessler suture technique, the double Z-shaped suture technique can reduce postoperative pain at an early stage, enhance the restoration of ankle joint mobility, lower the risk of postoperative soft tissue adhesion, and improve tolerance to rehabilitation in the repair of acute closed Achilles tendon rupture.
9.A new alkaloid from Huperzia serrata and its biological activity
Xiao-ting QIAO ; Xin-xin CHENG ; Dan WANG ; Mei-han LAI ; Jia-qi WANG ; Xiao-min WANG ; Cai-lian RUAN ; Duo CAO
Acta Pharmaceutica Sinica 2024;59(12):3342-3346
The methanol extract of
10.Expression and Detection Value of 6 Chlamydia Trachomatis Protein Antibodies in Tubal Factor Infertility
Ming-na LIU ; Man-li QI ; Xiao-hong CHEN ; Jin-feng TAN ; Dan ZHANG ; Yu-yan LIU ; Jian-de HAN ; Chun-guang MA
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(1):150-158
ObjectiveTo further study the pathogenic role of different types of Chlamydia trachomatis (CT) proteins in tubal factor infertility, evaluate the clinical detection value of Chlamydia trachomatis protein antibody in predicting tubal factor infertility. MethodsA total of 58 cases of tubal factor infertility (TFI), 41 cases of fertile controls (FC) and 18 cases of infertile controls (IFC) were included. For serum detection, first, CT-IgG ELISA kit was used to detect the expression of CT-IgG in serum of three groups of people; then, 6 kinds of Chlamydia trachomatis proteins were expressed and purified in the early stage to establish the antibody test for these proteins, and ELISA detection method was used to detect the expression of their antibodies in the serum of TFI group, FC group and IFC group, respectively; and finally, the antibody OD value of the 6 kinds of Chlamydia trachomatis proteins in the three groups of subjects were statistically described, and CT-IgG was used as the reference standard to draw the receiver operating characteristic curve (ROC curve) of each CT antibody. The Youden Index determines the cutoff value for each antibody. Taking TFI as the reference class, two disordered multiple classification logistic regression models were established with the FC and IFC groups, respectively; and the reference class was used to explore the value of various antibodies and age in predicting TFI, FC and IFC of Chlamydia trachomatis. The back-off method was used to screen the variables. ResultsThe OD value of CT376 antibody in the TFI group was higher than that in the FC group (0.86 vs. 0.60, P=0.026). The CT376 antibody OD value in the TFI group was higher than that in the IFC group (0.86 vs. 0.64, P=0.026). The CT443 antibody OD value in the IFC group was higher than that in the TFI group (0.59 vs. 0.34, P=0.036) and higher than that in the FC group (0.59 vs. 0.30, P=0.02). The multiple classification logistic regression analysis established between TFI and FC showed that CT-IgG [P<0.001, OR=0.084, 95%CI (0.025, 0.284)], CT376 antibody [P=0.068, OR=0.359, 95%CI (0.120, 1.078)]. CT-IgG is an independent risk factor for tubal infertility, and CT376 antibody cannot be an independent risk factor for tubal infertility. The multiple classification logistic regression analysis established between TFI and IFC showed that among infertile patients, CT-IgG [P<0.05, OR=0.194, 95%CI (0.046, 0.817)], CT376 antibody [P<0.05, OR=0.176, 95%CI (0.038, 0.818)] and CT381 antibody [P<0.05, OR=0.112, 95%CI ( 0.016, 0.796)] were independent risk factors for tubal infertility. ConclusionThe expression of CT376 antibody in tubal infertility patients is higher than that in fertile and infertile controls, suggesting that CT-induced tubal factor infertility may be related to CT376. CT-IgG, and CT376 antibodies are meaningful in predicting CT-induced tubal factor infertility.


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