The research and development of innovative drug have progressed remarkably, but the long development circle and high failure rate have become the bottleneck. Drug repurposing, discovering new indications of approved drugs, is a strategy to overcome these obstacles. By exploring new indications for approved drugs, rapid progress has been made in basic research and clinical translation in recent years. Rich resources of drugs, proven security, efficient development workflow and reduced cost are core advantages of this strategy, making the strategy a crucial direction of optimizing the pipeline of drug research and development. This review systematically summarizes drug repurposing cases that have received clinical approval over the past five years, and proposes core strategies for drug repurposing, including approaches based on targets, pathways, drug similarity, post-treatment phenotypes, and clinical side effects, aiming to provide some strategic guidance for drug repurposing efforts.

This paper explores the research progress of acupuncture for the prevention and treatment of Alzheimer's disease (AD) based on the "kidney-governor vessel-brain" axis. According to the fundamental pathogenesis of AD in traditional Chinese medicine (TCM), which attributes to kidney deficiency, marrow depletion, and impaired mental faculties, as well as the governor vessel's connection between the kidney and brain, the concept of the "kidney-governor vessel-brain" axis is proposed. The theoretical basis of the "kidney-governor vessel-brain" axis is analyzed based on the meridian pathway and physiological functions of the governor vessel, as well as the interdependent and mutually reinforcing relationships among the kidney, governor vessel, and brain. The relationship between AD and the "kidney-governor vessel-brain" axis is elucidated from both traditional medical theories and modern biological perspectives. Integrating clinical and mechanistic research on AD prevention and treatment based on this axis, it is suggested that the "kidney-governor vessel-brain" axis provides valuable insights and references for future research on AD prevention and treatment.
Humans ; Alzheimer Disease/physiopathology* ; Acupuncture Therapy ; Kidney/blood supply* ; Brain/blood supply* ; Meridians ; Blood Vessels/physiopathology*

The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Male ; Depression/genetics* ; Humans ; Hippocampus/drug effects* ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

The important studies in the field of extracorporeal life support (ECLS) in 2024 focused on the application of cardiac support technologies in acute myocardial infarction (AMI) with cardiogenic shock (CS): veno-arterial extracorporeal membrane oxygenation (V-A ECMO) has not shown advantages in either short- or long-term outcomes and may increase the risk of bleeding and vascular complications; in contrast, micro-axial flow pumps demonstrate potential in improving mortality. The effects of veno-venous extracorporeal membrane oxygenation (V-V ECMO) combined with prone positioning on severe acute respiratory distress syndrome (ARDS) remain uncertain. The survival benefit of extracorporeal cardiopulmonary resuscitation (ECPR) in out-of-hospital cardiac arrest (OHCA) patients has been further validated. The potential benefits of extracorporeal carbon dioxide removal (ECCO2R) require further investigation. Additionally, new guidelines released in 2024 focus on Neurological monitoring and management during ECMO, as well as the Definition and management of right ventricular injury during veno-venous ECMO. ECMO management requires more refined strategies, including optimized oxygenation targets, anticoagulation, blood transfusion, and weaning strategies to improve patient outcomes.
Humans ; Extracorporeal Membrane Oxygenation/methods* ; Shock, Cardiogenic/therapy* ; Cardiopulmonary Resuscitation ; Myocardial Infarction/therapy*

OBJECTIVE: To identify the risk factors for acute respiratory distress syndrome (ARDS) in geriatric patients following gastrointestinal perforation surgery, and constructed a model to validate its predictive value. METHODS: A retrospective analysis was conducted. The clinical data of geriatric patients (aged ≥ 60 years) after gastrointestinal perforation surgery admitted to the intensive care unit (ICU) of Hebei General Hospital from October 2017 to October 2024 were enrolled. Two groups were divided according to whether ARDS occurred postoperatively, and the differences in each index between the groups were compared. Lasso regression and multifactorial Logistic regression analyses were used to identify independent risk factors for the development of ARDS, and a prediction model was constructed based on these, which was presented using a nomogram. The receiver operator characteristic curve (ROC curve), calibration curve, and decision curve analysis (DCA) were plotted to evaluate the discrimination, accuracy, and clinical practicability of the model. RESULTS: A total of 155 geriatric patients following gastrointestinal perforation surgery were ultimately included in the analysis, among whom 43 developed ARDS, with an incidence rate of 27.7%. There were significantly differences in age, body mass index (BMI), acute kidney injury comorbidity, heart rate, onset time, the duration of surgery, the site of perforation, seroperitoneum, amount of bleeding, shock comorbidity, central venous pressure (CVP), C-reactive protein, and albumin between ARDS and non-ARDS groups. Lasso regression identified nine significant predictors: age, BMI, acute kidney injury comorbidity, onset time, seroperitoneum, shock comorbidity, CVP, hemoglobin, and albumin. Multivariate Logistic regression analysis identified BMI [odds ratio (OR) = 1.310, P < 0.001], hemoglobin (OR = 1.019, P = 0.045), seroperitoneum (OR = 1.001, P = 0.017), and albumin (OR = 0.871, P < 0.001) as independent risk factors for the occurrence of ARDS. A prediction model was constructed based on the above four independent risk factors, and the ROC curve showed that the area under the curve (AUC) of the model for predicting the occurrence of ARDS was 0.885 [95% confidence interval (95%CI) was 0.824-0.946], and internal validation was performed using bootstrap resampling (Bootstrap 500 times), which showed that the AUC value of the model was 0.886 (95%CI was 0.883-0.889). Calibration curves revealed excellent concordance between observed outcomes and model predictions. DCA indicated a high net benefit value for the model, which has good clinical utility. CONCLUSIONS BMI, hemoglobin, seroperitoneum, and albumin were identified as independent risk factors for ARDS in geriatric patients following gastrointestinal perforation surgery. The prediction model constructed using these four indicators facilitates early identification of high-risk individuals by clinicians.
Humans ; Respiratory Distress Syndrome/etiology* ; Retrospective Studies ; Aged ; Risk Factors ; Logistic Models ; Postoperative Complications ; Intestinal Perforation/surgery* ; Male ; ROC Curve ; Female ; Middle Aged ; Intensive Care Units ; Nomograms

Objective To apply a random forest model combined with logistic regression in the understudied area of pneumoconiosis complications,and to investigate the incidence and risk factors of pneumoconiosis complicated by bacterial pneumonia,and the effect of concomitant bacterial pneumonia on the survival and prognosis of patients with pneumoconiosis.Methods Pneumoconiosis patients admitted to the West China Fourth Hospital,Sichuan University,between January 2018 and April 2022 were enrolled and divided into a group of those with only pneumoconiosis and another group of those with pneumoconiosis complicated by bacterial pneumonia.Univariate analyses,including chi-squared test,t-test,or rank sum test,were conducted to examine the differences between the groups.A random forest model was used to screen the variables,and the risk factors of pneumoconiosis complicated by bacterial pneumonia were identified by stepwise forward logistic regression method.Cox regression was applied to the survival data to assess the effect of concomitant bacterial pneumonia on the survival and prognosis of pneumoconiosis patients.Results Among the 742 pneumoconiosis patients,536 cases(72.24%)had concomitant bacterial pneumonia.Among the 55 deaths,36 cases(65.45%)had concomitant bacterial pneumonia.Univariate analysis showed statistically significant differences in age,duration of disease,lung function,duration of exposure,lung lavage,pulmonary tuberculosis,and emphysema between the two groups(P<0.05).The variables were screened using the random forest model,and the risk factors were ranked in a descending order of their importance—the types of dust,duration of exposure,lung function,lung lavage,and pulmonary tuberculosis.After screening,multivariate logistic regression analysis showed that the types of dust(compared with silica dust,silicate dust:odd ratio[OR]=8.100,95%CI,1.386-47.331;carbon dust:OR=1.728,95%CI,1.034-2.887;artificial inorganic dust:OR=2.138,95%CI,1.146-3.988),impaired lung function(compared with undamaged lung function group,the group of patients with mild,moderate,and moderately severe damage:OR=2.292,95%CI,1.482-3.544),and pulmonary tuberculosis(OR=1.559,95%CI,1.071-2.271)were risk factors for pneumoconiosis complicated by bacterial pneumonia.The median follow-up was 30.0 months,ranging from 1.0 month to 64.0 months.Cox regression analysis showed that the mortality risk for pneumoconiosis patients with concomitant bacterial pneumonia was 2.369 times higher than that for patients without bacterial pneumonia(95%CI,1.286-4.367).Conclusion Pneumoconiosis patients are susceptible to bacterial pneumonia and are influenced by multiple risk factors.Concomitant bacterial pneumonia markedly affects the patient prognosis.

Objective To construct a database for molecular mass spectra of toxins and drugs in order to facilitate the management and retrieval of mass spectra for nerve agents,metabolites and other small molecules.Methods Requirement analysis and functional design were performed using software engineering methods.The Spec2Vec algorithm was used for vector representation of mass spectra,while SMILES molecular structures were vectorized using the extended connectivity fingerprint(ECFP).A data storage model integrating structured information and vector representations was established using the Milvus database.Similarity search of mass spectra and molecular structures was conducted via vector similarity comparison and the FlashEntropySearch algorithm.Results The constructed database of mass spectra encompassed over 400,000 entries from such sources as OCAD,NIST,MASSBANK,metabolic products,and natural products of TCM,which was capable of searching for similarities in mass spectra and molecular structures.On a standard server,similarity search of mass spectra took no more than 5 seconds,while that of molecular structures took no more than 1 second.Conclusion The system enables efficient management of complex mass spectra and provides rapid retrieval and comparison of mass spectra-related information through advanced vector indexing technology,offering robust data support and research tools for toxicology and pharmacology.

BACKGROUND:Transcranial magneto-acoustical electrical stimulation(TMAES)is a non-invasive,high-precision neurofocused stimulation method based on magneto-acoustic coupling electrical effect,which can regulate the rhythmic oscillation of nerve activity,thereby affecting the brain's movement,cognition and other functions. OBJECTIVE:To explore the effect of TMAES on beta oscillations in the neural circuits of healthy rats and Parkinson's rats. METHODS:(1)Animal experiments:Twenty-four Wistar rats were randomly divided into four groups(n=6 per group).The rats in the normal control group received no intervention,while those in the normal stimulation group received TMAES(the average spatial peak pulse intensity:13.33 W/cm2,fundamental frequency:0.4 MHz,the number of fundamental wave cycles:1000,and pulse frequency:200 Hz).The model control group and model stimulation group were established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.After successful modeling,the rats in the model control group received sham TMAES stimulation in the prefrontal cortex,and those in the model stimulation group received TMAES in the prefrontal cortex,and the duration of stimulation was 2.0 minutes per day.After an interval of 8-10 minutes,the local field potential signals of rats were collected during the execution of T-maze test and the correct rate of behavior was recorded at the same time to compare and analyze the time-frequency distribution of local field potential signals and behavioral differences among the groups.The stimulation experiment and T-maze test were stopped when the correct rate of rats was higher than 80%for 3 consecutive days.(2)Modeling and simulation experiments:The cortical-basal ganglion circuit model under TMAES was established,and the ultrasonic emission period(5,10,20 ms),ultrasonic emission duty cycle(30%,50%,90%)and induced current density(20,50,100 μA/cm2)were changed respectively to compare the power spectral density values of beta oscillations in healthy rats and Parkinson's rats under different stimulation parameters. RESULTS AND CONCLUSION:(1)Animal experiments:The spatial learning ability of the rats in the normal control group was stronger than that of the model control group(P＜0.001),the spatial learning ability of the rats in the normal stimulation group was stronger than that of the normal control group(P＜0.05),and the spatial learning ability of the rats in the model stimulation group was stronger than that of the model control group(P＜0.01).The distribution of beta oscillation energy in the normal control group was more concentrated,and the beta oscillation signal energy was reduced in the normal stimulation group compared with the normal control group.The beta oscillation energy was widely distributed and the energy value was significantly higher in the model control group and the model stimulation group than the normal control and normal stimulation groups.Moreover,the beta oscillation signal energy in the model stimulation group was significantly lower than that in the model control group.(2)Modeling and simulation experiments:the peak power spectral density of the beta band of healthy rats without stimulation(30 dB)was significantly lower than that of Parkinson's rats(55 dB).The power spectral density value generally decreased after stimulation.The peak power spectral density in the beta band was positively correlated with the ultrasonic emission period and negatively correlated with the induced current density.In addition,the peak power spectral density value was the lowest when the duty cycle of ultrasonic emission was 50%.These findings indicate that TMAES suppresses beta oscillations in healthy and Parkinson's disease rats,thereby improving motor function and decision-making cognitive function in rats.

Objective:To introduce a surgical technique of " short distances and multi-segment" buried-guiding suture method and its effects in the surgery of early descent of prosthesis after augmentation mammaplasty.Methods:From August 2019 to January 2022, 15 cases of early descent of prosthesis after augmentation mammaplasty due to axillary approach breast augmentation for micromastia were admitted to the Plastic Surgery Department of Sichuan Provincial People′s Hospital, aged 23-35 years (27.3±3.6) and duration of dislocation from 16 to 35 days (23.8±5.8). There were 12 patients showed unilateral prosthesis drops and 3 patients showed bilateral prosthesis drops. " Short distances and multi-segment" buried-guiding suture method was used to solve the problem, i. e., 2-0 non-absorbable sutures were used to eliminate the lower pole of prosthetic cavity with " short distances and multi-segment" sutures. The distance from the nipple to the midline of the sternum, the distance from the sternotomy to the nipple, the distance from the nipple to the inframammary fold and the distance from the midclavicular point to the inframammary fold were measured bilaterally before and after surgery, and statistical analysis was performed to evaluate the efficacy of the " short distances and multi-segment" buried-guiding suture method for early descent of prosthesis after breast augmentation.Results:All incisions healed by first intention without complications such as hematoma, infection, or scar hyperplasia. 15 patients were followed up for 6-12 months (8.0±1.9). 14 patients were satisfied with the results after surgery, and 1 patient received satisfactory results after secondary surgery. The distance from nipple to inframammary fold was shortened by 0.8-1.4 cm after surgery (1.2±0.2), and the distance from mid-clavicle to inframammary fold was shortened by 1.0-1.6 cm (1.3±0.4), and the differences were statistically significant as compared with the values before surgery ( t=31.17, P<0.05; t=33.78, P<0.05). After surgery, the change in the distance from nipple to sternal was 0.1-0.3 cm (0.16±0.10), and the change in the distance from sternal notch to nipple was 0-0.2 cm (0.12±0.10), and the differences were not statistically significant ( P>0.05). Conclusions:With the advantages of simple operation, little trauma and no additional incision, the " short distance and multi-stage" buried-guiding suture method in the surgery of early descent of prosthesis after augmentation mammaplasty is worthy of clinical application.

Objective To investigate the value of polar residual network(PResNet)model for assisting evaluation on rat myocardial infarction(MI)segment in myocardial contrast echocardiography(MCE).Methods Twenty-five male SD rats were randomly divided into MI group(n=15)and sham operation group(n=10).MI models were established in MI group through ligation of the left anterior descending coronary artery using atraumatic suture,while no intervention was given to those in sham operation group after thoracotomy.MCE images of both basal and papillary muscle levels on the short axis section of left ventricles were acquired after 1 week,which were assessed independently by 2 junior and 2 senior ultrasound physicians.The evaluating efficacy of MI segment,the mean interpretation time and the consistency were compared whether under the assistance of PResNet model or not.Results No significant difference of efficacy of evaluation on MI segment was found for senior physicians with or without assistance of PResNet model(both P＞0.05).Under the assistance of PResNet model,the efficacy of junior physicians for diagnosing MI segment was significantly improved compared with that without the assistance of PResNet model(both P＜0.01),and was comparable to that of senior physicians.Under the assistance of PResNet model,the mean interpretation time of each physician was significantly shorter than that without assistance(all P＜0.001),and the consistency between junior physicians and among junior and senior physicians were both moderate(Kappa=0.692,0.542),which became better under the assistance(Kappa=0.763,0.749).Conclusion PResNet could improve the efficacy of junior physicians for evaluation on rat MI segment in MCE images,shorten interpretation time with different aptitudes,also improve the consistency to some extent.