OBJECTIVE To discuss the impact of Wenyang lishui formula on ventricular remodeling in rats with pulmonary hypertension-induced right heart failure （RHF） based on the Hippo/Yes-associated protein （YAP） signaling pathway. METHODS Ten rats were randomly selected as the control group. The remaining 63 rats were given a single intraperitoneal injection of monocrotaline to establish the pulmonary hypertension-induced RHF model. The 50 rats that successfully underwent the model establishment were randomly divided into the RHF group， low-dose group of Wenyang lishui formula （4.25 g/kg）， high-dose group of the Wenyang lishui formula （17.00 g/kg）， furosemide group （20 mg/kg）， and high-dose group of Wenyang lishui formula+ Hippo/YAP signaling pathway activator group （17.00 g/kg of Δ Wenyang lishui formula+16 mg/kg of PY-60）， with 10 rats in each group. The rats in each group were given the corresponding drug solution or normal saline by gavage or/andtail vein injection， once a day， for 4 consecutive weeks. During the experiment， the general conditions of the rats in each group were observed； after the last administration， the right ventricular diameter， right atrial diameter， end-diastolic volume， pulmonary artery blood flow acceleration time （PAAT） and its ratio to ejection time （ET） （PAAT/ET）， pulmonary artery pressure and its ratio to pulmonary arterial flow velocity （pulmonary artery pressure/velocity） were measured. The plasma levels of brain natriuretic peptide and angiotensin Ⅱ （Ang Ⅱ） were detected. The pathological changes of the right ventricular tissue were observed， and the collagen volume fraction， the phosphorylation levels of the large tumor suppressor 1/2 （LATS1/2） and YAP， and the protein expression of the transcriptional coactivator of PDZ-binding motif （TAZ） were also detected. RESULTS Compared with the RHF group， the rats in Wenyang lishui formula low-dose and high-dose groups showed improved hair color， movement， diet， and mental state. The atrophy of right ventricular myocardial cells， the increase of inflammatory cells， collagen deposition， and hypertrophy of myocardial fibers were significantly alleviated. The right ventricular internal diameter， right atrial internal diameter， end-diastolic volume， pulmonary artery pressure， pulmonary artery pressure/velocity， the plasma levels of brain natriuretic peptide and AngⅡ ， collagen volume fraction， the phosphorylation level of YAP and protein expression of TAZ were significantly decreased， while the PAAT， PAAT/ET and the phosphorylation level of LATS1/2 were significantly increased （P＜0.05）. PY-60 could significantly reverse the improvement effects of high-dose Wenyang lishui formula on the above quantitative indicators （P＜ 0.05）. CONCLUSIONS Wenyang lishui formula can restore the right heart function of pulmonary hypertension-induced RHF rats， reduce their pulmonary artery pressure， alleviate the pathological changes in their cardiac tissues， and the above effects may be related to the activation of Hippo expression and the inhibition of YAP phosphorylation.

Objective:To investigate the clinical efficacy of moxibustion(Mox)combined with low-dose tadalafil(TAD)in the treatment of diabetes mellitus-induced erectile dysfunction(DMED)with the syndrome of Qi deficiency and blood stasis.Meth-ods:According to the inclusion and exclusion criteria,we selected 90 patients with DMED for this trial and equally randomized them into a Mox,a TAD,and a Mox combined with TAD(Mox+TAD)group to be treated by mild Mox applied to the acupoints Zusanli,Sanyinjiao and Yinlingquan qd alt,oral medication with low-dose TAD at 5 mg per dose qd,and combination of the above two thera-pies,respectively,all for 4 weeks.We obtained from the patients their IIEF-5 scores,traditional Chinese medicine(TCM)symptoms scores,Erectile Hardness Scale(EHS)scores,corpus cavernosal hemodynamic indexes,and the peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)of the corpus cavernosal arteries before and after treatment,and compared them among the three groups.Results:The total effectiveness rate was significantly higher in the Mox+TAD(90.0％)than in the Mox(46.7％)and TAD groups(60.0％)(P＜0.05).Compared with the baseline,the IIEF-5 and EHS scores were increased,while the TCM symptoms scores decreased in all the three groups after treatment,more significantly in the Mox+TAD group than in the other two(P＜0.05).And the PSV and RI were remarkably increased,while the EDV decreased(P＜0.05)in all the three groups(P＜0.05)after treatment,with PSV even higher in the Mox+TAD than in the Mox and TAD groups(P＜0.05).Conclusion:Moxi-bustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED,which can effectively improve the erectile function of the patients by increasing penile blood supply,benefiting qi and activating blood circulation.

Objective To identify risk factors associated with lymphatic leakage after laparoscopic radical prostatectomy(LRP)and to develop a machine learning-based nomogram for predicting such outcomes to support clinical prevention strategies.Methods We retrospectively analyzed perioperative data from 248 patients who underwent radical prostatectomy for prostate cancer between January 2020 and January 2024.Independent risk factors were identified through univariate and multivariate logistic regression analyses.A predictive model was developed,and its diagnostic performance was assessed by the area under the receiver operating characteristic curve(AUC).Five-fold cross-validation was performed to evaluate the model's generalizability.A nomogram was subsequently constructed to facilitate individualized risk quantification.Results Among the 248 patients,89(35.9%)developed lymphatic leakage,while 159(64.1%)did not.Independent risk factors for lymphatic leakage included intraopera-tive lymph node dissection(OR=5.415,95%CI:2.167～13.532,P<0.001),intraoperative plasma transfusion(OR=2.952,95%CI:1.524～5.718,P=0.001),and postoperative fasting duration of≥2 days(OR=1.412,95%CI:1.089～1.829,P=0.009).The predictive model showed good discrimination and calibration(AUC=0.711,95%CI:0.647～0.776,P<0.001;sensitivity:0.764;specificity:0.597).Model robustness was confirmed through five-fold cross-validation(training set AUC=0.822;test set AUC=0.829).The nomogram provided a clinically useful tool for quantifying individual risk of lymphatic leakage.Conclusions Intraoperative lymph node dissection,plasma transfusion,and postoperative fasting lasting≥2 days are independent risk factors for lymphatic leakage following radical prostatectomy.The validated predictive model demonstrates favorable clinical utility.

Objective To identify risk factors associated with lymphatic leakage after laparoscopic radical prostatectomy(LRP)and to develop a machine learning-based nomogram for predicting such outcomes to support clinical prevention strategies.Methods We retrospectively analyzed perioperative data from 248 patients who underwent radical prostatectomy for prostate cancer between January 2020 and January 2024.Independent risk factors were identified through univariate and multivariate logistic regression analyses.A predictive model was developed,and its diagnostic performance was assessed by the area under the receiver operating characteristic curve(AUC).Five-fold cross-validation was performed to evaluate the model's generalizability.A nomogram was subsequently constructed to facilitate individualized risk quantification.Results Among the 248 patients,89(35.9%)developed lymphatic leakage,while 159(64.1%)did not.Independent risk factors for lymphatic leakage included intraopera-tive lymph node dissection(OR=5.415,95%CI:2.167～13.532,P<0.001),intraoperative plasma transfusion(OR=2.952,95%CI:1.524～5.718,P=0.001),and postoperative fasting duration of≥2 days(OR=1.412,95%CI:1.089～1.829,P=0.009).The predictive model showed good discrimination and calibration(AUC=0.711,95%CI:0.647～0.776,P<0.001;sensitivity:0.764;specificity:0.597).Model robustness was confirmed through five-fold cross-validation(training set AUC=0.822;test set AUC=0.829).The nomogram provided a clinically useful tool for quantifying individual risk of lymphatic leakage.Conclusions Intraoperative lymph node dissection,plasma transfusion,and postoperative fasting lasting≥2 days are independent risk factors for lymphatic leakage following radical prostatectomy.The validated predictive model demonstrates favorable clinical utility.

Objective:To explore the relationship between parenting styles of toddlers aged 30 months and attention deficit hyperactivity disorder (ADHD) symptom trajectories in preschool children.Methods:The subjects were 2 111 children and their parents in Ma'anshan Birth Cohort. Parenting styles were assessed at 30 months of age using the Brief Toddler Parenting Style Questionnaire, which defines parenting styles on four dimensions: warmth and interaction, attention and acceptance, outdoor and social activities, and neglect and restrictions. The Chinese version of the Conners Abbreviated Symptom Questionnaire was used to examine preschooler's ADHD symptoms aged 3, 5, and 6 years. ADHD symptom trajectories were fitted using group-based trajectory modeling. The multinomial logistic regression model was used to evaluate the relationship between parenting styles at 30 months of age and ADHD symptom trajectories in children. The additive and multiplicative models were applied to analyze the interaction effect of negative parenting styles in children's ADHD symptom trajectories.Results:ADHD symptom trajectories in children included the low-score (48.3%), moderate-score (47.7%), and high-score groups (4.0%). After adjusting for the confounding factors, the results of the multinomial logistic regression analysis showed that negative parenting styles of the father/mother were associated with ADHD symptom trajectories in children ( P<0.05). The father/mother's low warmth and interaction (father: OR=2.07,95% CI:1.68-2.54; mother: OR=2.02,95% CI:1.64-2.48), low attention and acceptance (father: OR=1.94,95% CI:1.57-2.39; mother: OR=1.47,95% CI:1.20-1.81), low outdoor and social (father: OR=1.74,95% CI:1.43-2.13; mother: OR=1.60,95% CI:1.32-1.94), and high neglect and restriction (father: OR=2.09,95% CI:1.67-2.62; mother: OR=2.06,95% CI:1.65-2.56) were associated with ADHD symptom moderate-score trajectories compared to the low-score trajectory group, mother's low warmth and interaction, low outdoor and social, and high neglect and restrictions. Statistically significant association was seen in negative parenting styles of fathers with the high-score group. There was a multiplicative interaction for hostile parenting ( P<0.05). The additive interaction results showed that there was a synergistic effect of hostile parenting, which increased the risk of the high-score trajectories of ADHD symptoms in children. Conclusions:Both parents' parenting styles influenced ADHD symptom change the trajectories in preschoolers. Negative parenting styles of the father/mother increase the risk of the moderate-score and high-score trajectories of ADHD symptoms in children. Hostile parenting by both parents has a synergistic impact on the risk of ADHD symptom trajectories in children, and the simultaneous presence of both increases the risk of the high-score trajectory of ADHD symptoms.

Objective:To investigate the clinical efficacy of moxibustion(Mox)combined with low-dose tadalafil(TAD)in the treatment of diabetes mellitus-induced erectile dysfunction(DMED)with the syndrome of Qi deficiency and blood stasis.Meth-ods:According to the inclusion and exclusion criteria,we selected 90 patients with DMED for this trial and equally randomized them into a Mox,a TAD,and a Mox combined with TAD(Mox+TAD)group to be treated by mild Mox applied to the acupoints Zusanli,Sanyinjiao and Yinlingquan qd alt,oral medication with low-dose TAD at 5 mg per dose qd,and combination of the above two thera-pies,respectively,all for 4 weeks.We obtained from the patients their IIEF-5 scores,traditional Chinese medicine(TCM)symptoms scores,Erectile Hardness Scale(EHS)scores,corpus cavernosal hemodynamic indexes,and the peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)of the corpus cavernosal arteries before and after treatment,and compared them among the three groups.Results:The total effectiveness rate was significantly higher in the Mox+TAD(90.0％)than in the Mox(46.7％)and TAD groups(60.0％)(P＜0.05).Compared with the baseline,the IIEF-5 and EHS scores were increased,while the TCM symptoms scores decreased in all the three groups after treatment,more significantly in the Mox+TAD group than in the other two(P＜0.05).And the PSV and RI were remarkably increased,while the EDV decreased(P＜0.05)in all the three groups(P＜0.05)after treatment,with PSV even higher in the Mox+TAD than in the Mox and TAD groups(P＜0.05).Conclusion:Moxi-bustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED,which can effectively improve the erectile function of the patients by increasing penile blood supply,benefiting qi and activating blood circulation.

Objective:To analyze the potential risk factors for early relapse/progression in patients with multiple myeloma(MM)and develop a risk prediction model based on these factors.Methods:A retrospective analysis was conducted on 187 newly diagnosed multiple myeloma(NDMM)patients who treated at the Affiliated Hospital of North Sichuan Medical College from February 2014 to December 2020.The clinical,laboratory examination,and follow-up data of patients experiencing relapse/progression within 24 months after treatment(ER/EP24)were analyzed using univariate and multivariate analyses,and a nomogram prediction model was established.Results:Among the 187 patients,58(31.0％)experienced ER/EP24,with a median survival time of only 24 months.The results of multivariate logistic regression analysis showed that failure to achieve partial response(PR)or better after 3-4 cycles of chemotherapy and albumin(ALB)levels＜35 g/L were independent risk factors for ER/EP24(P＜0.05).These factors,along with other clinically relevant variables,were further incorporated into the nomogram prediction model.The model demonstrated a concordance index(C-index)of 0.784,indicating strong predictive accuracy.Conclusion:MM patients experiencing ER/EP24 exhibit poor outcome,and the nomogram model developed in this study effectively predicts the risk of ER/EP24 in NDMM patients,providing a valuable tool for clinical risk assessment.

ObjectiveTo explore the process and guidelines for ethical review in decentralized drug clinical trials， promote clinical trial progress， and ensure drug development progress. MethodsThe key points of the ethical review were summarized by studying the relevant laws and regulations on decentralized drug clinical trials， analyzing the advantages and challenges of decentralized drug clinical trials， and combining the experience of the ethics committee of the institution in reviewing decentralized drug clinical trials. ResultsRelevant laws and regulations were the basis for the ethical review， and the ethics committee should adopt appropriate review methods based on regulations and hospital ethical standard operating procedures. The ethics committee should focus on the feasibility， applicability， and rationality， the adequacy of informed consent， the protection of rights and interests and privacy of subjects， as well as the qualification and standard operating procedures of electronic platforms for conducting decentralized drug clinical trials. ConclusionDecentralized drug clinical trials are in their early stages and urgently require guidance from relevant laws and regulations. Ethical review is also constantly being refined through exploration. It is necessary to supervise the implementation of responsibilities by all parties， pay attention to the rights and interests of subjects， and gradually promote the implementation of decentralized drug clinical trials.

Objective:To analyze the potential risk factors for early relapse/progression in patients with multiple myeloma(MM)and develop a risk prediction model based on these factors.Methods:A retrospective analysis was conducted on 187 newly diagnosed multiple myeloma(NDMM)patients who treated at the Affiliated Hospital of North Sichuan Medical College from February 2014 to December 2020.The clinical,laboratory examination,and follow-up data of patients experiencing relapse/progression within 24 months after treatment(ER/EP24)were analyzed using univariate and multivariate analyses,and a nomogram prediction model was established.Results:Among the 187 patients,58(31.0％)experienced ER/EP24,with a median survival time of only 24 months.The results of multivariate logistic regression analysis showed that failure to achieve partial response(PR)or better after 3-4 cycles of chemotherapy and albumin(ALB)levels＜35 g/L were independent risk factors for ER/EP24(P＜0.05).These factors,along with other clinically relevant variables,were further incorporated into the nomogram prediction model.The model demonstrated a concordance index(C-index)of 0.784,indicating strong predictive accuracy.Conclusion:MM patients experiencing ER/EP24 exhibit poor outcome,and the nomogram model developed in this study effectively predicts the risk of ER/EP24 in NDMM patients,providing a valuable tool for clinical risk assessment.