Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Aim To explore the mechanism of action of Guizhi Jia Gegen decoction(GGD)in treating pneu-monia-enteritis induced by H1N1 influenza virus infec-tion in a mouse model,using network pharmacology and molecular docking techniques,followed by in vivo verification.Methods A pneumonia-enteritis mouse model was established,and the intervention effects of GGD on the model mice were evaluated using indica-tors such as body weight,rectal temperature,lung in-dex,colon length,H1N1 M gene expression,relative mRNA expression levels of inflammatory cytokines,and pathological sections of the lung and intestine.The targets of the blood-absorbed components of GGD were identified using the Swiss Target Prediction platform,and the disease targets were retrieved from the Gene-Cards platform.The intersecting targets were analyzed through PPI network analysis using the STRING data-base to identify core targets.GO analysis and KEGG pathway enrichment analysis were performed using the Metascape database.RT-qPCR was employed to vali-date the core targets and pathways.Molecular docking was conducted using AutoDock Tools software to verify the interactions between blood-absorbed components and key targets.Results GGD demonstrated signifi-cant therapeutic effects on the pneumonia-enteritis mouse model.The results of network pharmacology in-dicated that the therapeutic effects of GGD were strong-ly associated with targets such as TNF,ALB,PTGS2,MMP9,EGFR,ESR1,SRC,HSP90AA1,PPARG and MMP2.RT-qPCR results indicated that GGD could intervene in pneumonia-enteritis by regulating the targets TNF,ALB,EGFR and the related targets of the NF-κB pathway.Molecular docking results re-vealed that blood-absorbed components such as puerar-in and liquiritin could stably bind to TNF,ALB and EGFR.Conclusion Components such as puerarin and liquiritin in GGD may exert therapeutic effects on pneumonia-enteritis induced by H1N1 influenza virus infection by acting on targets such as TNF,ALB and EGFR.

Depression is primarily characterized by persistent low mood,emotional disorders,and loss of interest.Somatization disorder is a type of neurotic disorder,primarily featuring recurrent,varied,and non-organic physical discomfort symptoms.In traditional Chinese medicine,depression with somatization disorder can be classified under the category of"depression"and"hysteria"according to its clinical symptoms.This article focuses on the dynamic evolution of the functions of the kidney,spleen,and liver,and explains the core pathogenesis of depression with somatization disorder based on the theory of"cold water,damp earth,and stagnant wood"proposed by HUANG Yuanyu.It explores the causes and related manifestations.Symptoms mainly characterized by cramps and convulsions can be attributed to the liver;symptoms primarily characterized by heaviness,distension,and dull pain accompanied by weakness can be attributed to the spleen;symptoms primarily characterized by stiffness,reluctance to move or inability to move,and reluctance to extend outward can be attributed to the kidney.Liver depression and spleen dampness,as well as wood depression and earth congestion,are treated by strengthening the spleen and soothing the liver,drying dampness and calming wind,and the modified Xiaoyao Powder combined with Yueju Pill is recommended.Spleen dampness and kidney coldness,earth failure and water overflow,are treated by tonifying the spleen and kidney,warming water and transforming dampness,and the modified Jingui Shenqi Pill combined with Linggui Zhugan Decoction is recommended.Kidney coldness and liver hyperactivity,water not nourishing wood,are treated by warming the kidney and enriching essence,replenishing water and nourishing wood,and the modified Dihuang Yinzi is recommended.This article explores the corresponding etiology,pathogenesis,treatment methods,and prescriptions for depression with somatization disorder,with the aim of providing new insights for clinical diagnosis and treatment.

Aim To perform high-throughput screen-ing of immunomodulatory traditional Chinese medicine(TCMs)based on an in vitro B cell differentiation-antibody secretion model,identifying active herbal candidates with immune-enhancing properties to pro-vide novel therapeutic options and theoretical support for influenza virus treatment in immunocompromised in-dividuals.Methods B cells were stimulated with dif-ferent concentrations of cytosine-phosphate-guanine oli-godeoxynucleotide 2006(CpG)and nterleukin-2(IL-2)to promote proliferation,differentiation,and anti-body secretion,and the effects of varying concentra-tions of the solvent DMSO were also evaluated.The op-timal conditions for the B cell differentiation-anti-body secretion model were determined based on the se-cretion levels of three antibody isotypes.The feasibility of the model was further validated using rapamycin,a known B cell function inhibitor.On this basis,a high-throughput screening platform for immunomodulatory a-gents was optimized and established.Subsequently,the immune-enhancing activity of 465 polarity extract from TCMs was evaluated.Results The optimal con-ditions for the model were determined as 2 mg·L-1 CpG,1.67 × 106 nkat·L-1 IL-2,and DMSO with a volume fraction of 0.1％.Rapamycin effectively inhib-ited B cell differentiation into plasmablast and signifi-cantly reduced antibody production,indicating the reli-ability of the model.Multiple rounds of screening re-vealed that the dichloromethane extract of licorice,the dichloromethane extract of Vinegar-processed Curcumae Rhizoma,the cyclohexane extract of Honey-prepared Radix Asteris,and the aqueous extract of Siphonostegia chinensis Benth were identified to significantly promote both B cell proliferation and differentiation and anti-body secretion at a concentration of 600 μg·L-1.Conclusion This study successfully optimizes an in vitro B cell differentiation-antibody secretion model and identifies several TCM extracts,including licorice,with potential immune-enhancing activity.

Depression is primarily characterized by persistent low mood,emotional disorders,and loss of interest.Somatization disorder is a type of neurotic disorder,primarily featuring recurrent,varied,and non-organic physical discomfort symptoms.In traditional Chinese medicine,depression with somatization disorder can be classified under the category of"depression"and"hysteria"according to its clinical symptoms.This article focuses on the dynamic evolution of the functions of the kidney,spleen,and liver,and explains the core pathogenesis of depression with somatization disorder based on the theory of"cold water,damp earth,and stagnant wood"proposed by HUANG Yuanyu.It explores the causes and related manifestations.Symptoms mainly characterized by cramps and convulsions can be attributed to the liver;symptoms primarily characterized by heaviness,distension,and dull pain accompanied by weakness can be attributed to the spleen;symptoms primarily characterized by stiffness,reluctance to move or inability to move,and reluctance to extend outward can be attributed to the kidney.Liver depression and spleen dampness,as well as wood depression and earth congestion,are treated by strengthening the spleen and soothing the liver,drying dampness and calming wind,and the modified Xiaoyao Powder combined with Yueju Pill is recommended.Spleen dampness and kidney coldness,earth failure and water overflow,are treated by tonifying the spleen and kidney,warming water and transforming dampness,and the modified Jingui Shenqi Pill combined with Linggui Zhugan Decoction is recommended.Kidney coldness and liver hyperactivity,water not nourishing wood,are treated by warming the kidney and enriching essence,replenishing water and nourishing wood,and the modified Dihuang Yinzi is recommended.This article explores the corresponding etiology,pathogenesis,treatment methods,and prescriptions for depression with somatization disorder,with the aim of providing new insights for clinical diagnosis and treatment.

Aim To perform high-throughput screen-ing of immunomodulatory traditional Chinese medicine(TCMs)based on an in vitro B cell differentiation-antibody secretion model,identifying active herbal candidates with immune-enhancing properties to pro-vide novel therapeutic options and theoretical support for influenza virus treatment in immunocompromised in-dividuals.Methods B cells were stimulated with dif-ferent concentrations of cytosine-phosphate-guanine oli-godeoxynucleotide 2006(CpG)and nterleukin-2(IL-2)to promote proliferation,differentiation,and anti-body secretion,and the effects of varying concentra-tions of the solvent DMSO were also evaluated.The op-timal conditions for the B cell differentiation-anti-body secretion model were determined based on the se-cretion levels of three antibody isotypes.The feasibility of the model was further validated using rapamycin,a known B cell function inhibitor.On this basis,a high-throughput screening platform for immunomodulatory a-gents was optimized and established.Subsequently,the immune-enhancing activity of 465 polarity extract from TCMs was evaluated.Results The optimal con-ditions for the model were determined as 2 mg·L-1 CpG,1.67 × 106 nkat·L-1 IL-2,and DMSO with a volume fraction of 0.1％.Rapamycin effectively inhib-ited B cell differentiation into plasmablast and signifi-cantly reduced antibody production,indicating the reli-ability of the model.Multiple rounds of screening re-vealed that the dichloromethane extract of licorice,the dichloromethane extract of Vinegar-processed Curcumae Rhizoma,the cyclohexane extract of Honey-prepared Radix Asteris,and the aqueous extract of Siphonostegia chinensis Benth were identified to significantly promote both B cell proliferation and differentiation and anti-body secretion at a concentration of 600 μg·L-1.Conclusion This study successfully optimizes an in vitro B cell differentiation-antibody secretion model and identifies several TCM extracts,including licorice,with potential immune-enhancing activity.

Objective:To construct an integrated management model for early screening and diagnosis of PCa based on the In-novative Care for Chronic Conditions Framework(ICCC)and the 1+1 contract-based tiered diagnosis and treatment system(TDTS)in China.Methods:Based on the 1+1 contract-based TDTS platform,we conducted PCa screening for the male residents aged 60 years and above during health check-ups in Pujin Community Health Center from January 1,2023 to December 31,2023.For those with abnormal total prostate-specific antigen(tPSA)≥4 μg/L,we promptly referred them to higher-level hospitals for further diagno-sis and treatment via the two-way referral green channel platform and information sharing service using the 1+1 contract model.We further analyzed the relevant data on screening and diagnosis.Results:A total of 4 080 males aged 71.39±5.059 years received PCa screening from January to December 2023.PSA screening was performed in 43.96％of the male residents,revealing 654 cases of PSA abnormality,with a PSA positivity rate of 16.03％,which was higher than that found in the previous large-scale PCa screenings in other regions of China.Among the males with PSA abnormality,292(44.65％)expressed their willingness for medical referral,while the others did not seek further medical attention for reasons of being asymptomatic,low awareness of the disease,no accompany for medical visits,and concerns about further costs of diagnosis and treatment.Prostate biopsy was recommended to 154 cases after further examinations,which was accepted by 92(59.74％).Fifty-eight cases were diagnosed with Pa,and thedetection rate reached 63.04％.Conclusion:The integrated management model for PSA examination-based early screening and diagnosis of PCa using the 1+1 contract-based TDTS platform is plays a significant role in enhancing peoples awareness and knowledge of PCa and improving the early detection rate of the malignancy.

Objective:To retrieve, evaluate and summarize the best evidence for the management of oral intake in stroke patients with dysphagia.Methods:A systematic search was conducted in Chinese and English databases and subject-specific professional websites for clinical decisions, best practices, guidelines, systematic reviews, expert consensuses and evidence summaries on the management of oral intake in stroke patients with dysphagia. The retrieval time limit was from the establishment of the database to March 31, 2024. The included literatures were screened, quality-evaluated, and evidence was extracted and summarized.Results:A total of 16 articles were included, including three clinical decisions, four guidelines, four expert consensuses, four evidence summaries and one systematic review. A total of 28 pieces of evidence were summarized from eight aspects, namely, swallowing function screening, nutritional risk screening, feeding management, oral medication management, water drinking management, oral care, aspiration management, and training and education.Conclusions:This study systematically summarizes the best evidence for the management of oral intake in stroke patients with dysphagia, providing scientific guidance and strategic support for the improvement of patients' long-term quality of life.