Objective To systematically review the efficacy and safety of repetitive transcranial magnetic stimulation(rTMS)combined with agomelatine in the treatment of depression.Methods PubMed,Embase,Cochrane Library,Web of Science,CNKI,VIP,WanFang Data,SinoMed and Yiigle databases were electronically searched to collect randomized controlled trials(RCTs)of comparison between rTMS combined with agomelatine(combined group)and agomelatine or combined pseudostimulation(control group)in the treatment of depression from inception to May 10,2024.Meta-analysis was performed by using RevMan 5.4 software,GRADE grading system for evaluating the level of evidence for observational indicators,and TSA 0.9.5.lBeta software for trial sequential analysis.Results A total of 15 RCTs involving 1 196 patients were included.Meta-analysis showed that compared with control group,combination group had a higher effective rate(RR=1.24,95％CI 1.15 to 1.34,P＜0.001),lower depression scale score(SMD=-2.95,95％CI-3.71 to-2.19,P＜0.001),anxiety scale score(SMD=-2.21,95％CI-3.29 to-1.14,P＜0.001),PSQI score(MD=-1.69,95％CI-2.79 to-0.59,P=0.003).There was no statistical difference between the two groups in terms of NE level,5-HT level and incidence of adverse reactions(P＞0.05).GRADE quality grading of the evidence showed moderate-quality evidence for the effectiveness rate and incidence of adverse reactions,with the depression scale score and the NE level of the evidence being low-quality,and the level of evidence for the anxiety scale score,the PSQI score,and the 5-HT content was very low.The trial sequential analysis results showed that in terms of effective rate,the analysis results of combination group superior to control group were reliable,and the conclusion could exclude false positives.Conclusion The rTMS combined with agomelatine in the treatment of depression has advantages in improving effective rate,depression scale score,anxiety scale score and PSQI score compared with agomelatine alone or combined pseudostimulation,incidence of adverse reactions were equivalent to those of agomelatine aloneor or combined pseudostimulation.

ObjectiveTo explore the mechanism of Astragali Radix-Aconiti Lateralis Radix Praeparata in the treatment of heart failure and substance basis based on ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometer （UPLC-Q-TOF-MS） and network pharmacology. MethodThe chemical components of Astragali Radix-Aconiti Lateralis Radix Praeparata solution was analyzed by UPLC-Q-TOF-MS， and the active components and targets were screened out by the PubChem database. The targets related to heart failure disease were retrieved from Comparative Toxicogenomics Database（CTD）， Online Mendelian Inheritance in Man （OMIM）， and GeneCard databases， and the common targets were obtained by Venn analysis. The target protein-protein interactions （PPI） were analyzed using the STRING database. Gene ontology （GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis were performed using the Metascape database， and molecular docking verification of key targets and active components was performed using SYBYL-X 2.1.1. Experimental validation of key targets was carried out using the rat model of heart failure. ResultThere were 202 chemical components identified in Astragali Radix-Aconiti Lateralis Radix Praeparata solution， of which 64 active components were predicted to act on 183 targets for the treatment of heart failure. The important active components were caffeic acid， L-arginine， biochanin A， adenine， nicotinic acid， trans-ferulic acid， p-coumaric acid， riboflavin， calycosin， etc. The main targets were interleukin （IL）-6， cysteine aspartic acid specific protease （Caspase）-3， vascular endothelial growth factor A （VEGFA）， protein kinase B1 （Akt1）， tumor necrosis factor （TNF）， IL-1B， matrix metallopeptidase （MMP）-9， etc. The main signaling pathways involved hypoxia-inducible factor （HIF）-1 signaling pathway， TNF signaling pathway， phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway， Toll-like receptor signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， forkhead box O （FoxO） signaling pathway， etc. The molecular docking results showed that the active components in Astragali Radix-Aconiti Lateralis Radix Praeparata solution had a good binding ability with HIF-1α， VEGFA， Akt1， Caspase-3， and IL-6， which were the key proteins in the HIF-1 signaling pathway. Animal experiments showed that Astragali Radix-Aconiti Lateralis Radix Praeparata solution significantly improved the hemodynamic indexes， reduced the serum atrial natriuretic peptide （ANP）， brain natriuretic peptide （BNP）， and IL-6 levels， improved the myocardial histopathological changes， protected the mitochondrial morphology of cardiomyocytes， down-regulated the expression of HIF-1α， VEGFA and phosphorylation（p）-Akt， and reduced the activation of Caspase-3 in the myocardial tissue of rats with heart failure. ConclusionAstragali Radix-Aconiti Lateralis Radix Praeparata treats heart failure in a multi-component， multi-target， and multi-pathway manner. The experimental validation indicates that it treats heart failure by improving myocardial histopathological changes and regulating HIF-1 signaling pathway， which provides references for the subsequent pharmacodynamic substance research.

Patients with novel coronavirus infection still have many functional disorders during the recovery period. The timely intervention of rehabilitation treatment has important clinical significance in improving the patients’ functions and their ability of daily living. Based on the current evidence of evidence-based medicine and clinical practice, this paper summarizes the rehabilitation treatment and precautions of patients with simple novel coronavirus infection and different groups with previous dysfunction and novel coronavirus infection (such as neurological dysfunction, chronic pain, and bone and joint diseases) with a view to providing clinical reference for the rehabilitation treatment of patients with novel coronavirus infection during the recovery period.

Bipolar androgen therapy (BAT), as a new therapy, can effectively reduce the serum prostate specific antigen (PSA) level of a part of patients with castration resistant prostate cancer (CRPC), delay tumor progression, improve their quality of life and restore the sensitivity to drug therapy. This paper will review the background, possible mechanism, clinical research progress and development prospect of BAT.

Objective:To explore the feasibility of predicting axillary lymph node metastasis of breast cancer using radiomics analysis based on dynamic contrast-enhanced (DCE) MRI.Methods:The retrospective study enrolled 163 patients (163 lesions) with breast cancer diagnosed by core needle biopsy from January 2013 to December 2013 in Peking University First Hospital. The status of axillary lymph nodes in all patients was pathologically confirmed, and they had complete preoperative breast MRI images. Among the 163 patients, 94 patients were confirmed with axillary lymph node metastasis, and 69 patients without axillary lymph node metastasis. They were randomly divided into the training dataset ( n=115) and testing dataset ( n=48) in a 7∶3 ratio. The radiomics analysis was performed in the training dataset, including image preprocessing and labeling, radiomics feature extraction, radiomics model establishment and model predictive performance inspection. Model performance was tested in the testing dataset. Receiver operating characteristic curve and area under curve (AUC) was used to analyze the model prediction performance. Results:Of the 1 075 features extracted from the training dataset, principal component analyses (PCA) features 8, 41 and 67 were selected by random forest classifier. The radiomics model including 3 PCA features reached an AUC of 0.956 (95%CI 0.907-0.988), with sensitivity of 91.2%, specificity of 100% and accuracy of 94.8%. In the testing dataset, the radiomics model including 3 PCA features reached an AUC of 0.767 (95%CI 0.652-0.890), with sensitivity of 80.8%, specificity of 72.7% and accuracy of 77.1%.Conclusion:It is feasible to predict axillary lymph node metastasis using radiomics features based on DCE-MRI of breast cancer.

Objective:To compare the dosimetric difference between 3D-printed multi-channel applicator and conventional vaginal single-channel applicator for brachytherapy, aiming to provide guidance for patients receiving brachytherapy after cervical cancer surgery.Methods:From January 2019 to November 2020, 25 cervical cancer patients complicated with VAIN Ⅲ receiving 192Ir high-dose-rate brachytherapy after cervical cancer surgery were selected. Each patient was located by CT scanning with 3D-printed multi-channel applicator and conventional vaginal single-channel applicator, and corresponding plan and evaluation were carried out. The dose volume histogram (DVH) was obtained by inverse dose optimization algorithm. The dosimetric differences of high-risk clinical target volume (HRCTV), bladder and rectum during brachytherapy were compared with those of source applicators. The optimal treatment plan was selected. Results:D 90%, D 100%, V 100% and V 150% of the plans designed by 3D-printed individual multi-channel applicator had no significant differences compared with those designed by conventional single-channel applicator (all P>0.05). The bladder and rectal D 2cm 3 designed by 3D-printed multi-channel applicator were significantly lower than those using conventional single-channel applicator, and the differences were statistically significant (both P<0.05). Conclusion:The multi-channel individual applicator target made by 3D-printing technology has good conformal property, properly protects the bladder and rectum and possesses treatment advantages over conventional single-channel applicator.

OBJECTIVES: Pelvic lymph node metastasis (PLNM) is an important factor that affects the stage and prognosis of prostate cancer. Invasive extended pelvic lymph node dissection (ePLND) is the most effective method for clinically diagnosing PLNM. Accurate preoperative prediction of PLNM can reduce unnecessary ePLND. This study aims to investigate the clinical value of radiomics nomogram in predicting PLNM of prostate cancer based on T₂-weighted imaging (T₂WI). METHODS: Magnetic resonance (MR) data of 71 patients with prostate cancer who underwent ePLND from January 2017 to June 2021 in Peking University First Hospital were collected retrospectively. All patients were assigned into a training set (January 2017 to December 2020, n=56, containing 186 lymph nodes) and a test set (January 2021 to June 2021, n=15, containing 45 lymph nodes) according to the examination time of multiparametric magnetic resonance imaging (mpMRI). Two radiologists matched the dissected lymph nodes on MRI images, and manually annotated the region of interest (ROI). Based on the outlined ROI, 3 metastatic lymph node prediction models were established: Model 1 (only image features of T₂WI), Model 2 (radiomics features based on random forest), and Model 3 (combination of the image and radiomics features). A nomogram was also established. The clinicopathologic characteristics of the patients were obtained from the medical records, including age, the Gleason score, the level of prostate-specific antigen (PSA), and clinical and pathological T stage. The preoperative radiological features of the pelvic lymph nodes (LNs) include size of LNs (the short and long diameters) and volume of LNs. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of the 3 models and decision curve analysis (DCA) was used to evaluate the clinical benefits of the models. RESULTS: No significant differences were found between the training set and test set regarding age, Gleason scores, PSA level, and clinical and pathological T stage (all P>0.05). The differences in volume, short diameter and long diameter between metastatic and non-metastatic LNs were statistically significant in both training set and test set (all P<0.05). In multivariate regression analysis, the short diameter and marginal status of LNs were included in Model 1. Eighteen omics features were selected to construct Model 2. The signal distribution of LNs and Rad score were the significant risk factors for predicting metastasis of pelvic LNs in Model 3. The C-index of nomogram based on Model 3 reached 0.964, and the calibration curve showed that the model had high calibration degree. In the test set, the area under the curves of Model 1, 2, and 3 were 0.78, 0.93, and 0.96 respectively, Model 2 and Model 3 showed significantly higher diagnostic efficiency than Model 1 (Model 1 vs Model 2, P=0.019; Model 1 vs Model 3, P=0.020). There was no significant difference in the area under the curve between Model 2 and Model 3 (P=0.649). The DCA results of the 3 models showed that all models obtained higher net benefits than the PLNM-all or PLNM-none protocol in different ranges of threshold probabilities and Model 3 had the highest clinical benefit. CONCLUSIONS The radiomics nomogram based on T₂WI shows a good predictive efficacy for preoperative PLNM in patients with prostate cancer, which could be served as an imaging biomarker to optimize decision-making and adjust adjuvant treatments.
Humans ; Lymph Nodes/pathology* ; Lymphatic Metastasis ; Male ; Prostate-Specific Antigen ; Prostatic Neoplasms/pathology* ; Retrospective Studies

Objective : To investigate the influence and molecular mechanism of hypoxia-inducing factor-1 α( HIF- 1 α) gene silencing combined with methyl selenenic acid (MSA) on cervical cancer cell proliferation，apoptosis and cell migration． Methods : HeLa cells were transfected with HIF-1 interference RNA and negative control RNA．Af- ter transfection for 48 h，cells were stimulated with MSA for 24 h，and cell proliferation was determined by CCK-8 assay and colony formation．Apoptosis was determined by flow cytometry combined with Annexin V-FITC / PI．The expression levels of HIF-1α , Bcl-2 ，and E-cadherin were detected by Western blot assay． Cell migration ability was determined by Transwell assay. RNA-seq analysis was used to investigate the differentially expressed genes and differential signaling pathways. Results : Compared with the control group，interfering with HIF-1α combined with MSA significantly inhibited cell proliferation (P ＜0．01) ．Flow cytometry results showed that the combined drug group significantly induced apoptosis．Transwell results showed that interfering with HIF-1α combined with MSA inhibited HeLa cell migration．Compared with the control group，interfering with HIF-1α combined with MSA down- regulated the expression of Bcl-2 and up-regulated the expression of E-cadherin. RNA-sequencing combined with signal pathway enrichment results showed that the expression of apoptotic signal pathway and downstream genes was inhibited． Conclusion HIF-1α gene silencing combined with MSA can synergically inhibit the proliferation and induce apoptosis of cervical cancer cells，and its regulatory mechanism may be related to the expression of Bcl-2 family proteins and the inhibition of p53 signaling pathway.

Objective:To explore the feasibility of classification between carcinoma in situ and invasive carcinoma of breast using intratumoral and peritumoral radiomics based on breast dynamic contrast-enhanced (DCE) MRI.Methods:The retrospective study included consecutive invasive breast carcinoma pathological diagnosed by core needle biopsy or surgery from January 2013 to December 2013 and carcinoma in situ of breast diagnosed by surgery from January 2013 to December 2015 in Peking University First Hospital. All patients had pretreatment breast MRI images. A total of 251 cases (251 lesions) were included, with 208 invasive breast carcinoma and 43 carcinoma in situ of breast. They were all females and median age was 53 (23-82) years old. Patients were randomly divided into the training ( n=176) and testing dataset ( n=75) in a 7∶3 ratio. In the training dataset, combined with DCE mask and early enhancement images, intratumoral and peritumoral area were semi-automatic segmentation, and radiomics features were extracted and dimension reduction, finally a prediction model was established. Model performance was tested in the testing dataset. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to analyze the model prediction performance. Results:The prediction models established by intratumoral, peritumoral and intratumoral combined with peritumoral radiomics had good performance. The AUC of intratumoral, peritumoral and intratumoral combined with peritumoral radiomics prediction models in differentiating breast carcinoma in situ and invasive carcinoma were 0.865, 0.896 and 0.922 in the testing dataset, there was no significant difference in pairwise comparisons ( P>0.05). The sensitivity of intratumoral, peritumoral and intratumoral combined with peritumoral radiomics prediction models were 77.4%, 87.1%, 83.9%, the specificity were 92.3%, 84.6%, 100%, and the accuracy were 80.0%, 85.3%, 86.7%. Conclusion:It is potential feasible for classification between carcinoma in situ and invasive carcinoma of breast using intratumoral and peritumoral radiomics based on breast DCE MRI.