OBJECTIVE: To evaluate the application effect of mindfulness-based stress reduction (MBSR) therapy on the patients treated with image fusion-guided transperineal prostate biopsy. METHODS: A total of 160 patients who underwent image fusion-guided transperineal prostate biopsy in the Urology Department from April 2023 to April 2024 were included. Patients were randomly assigned to a control group and an observation group, with 80 cases in each group. The control group received routine care, while the observation group received combined MBSR on the basis of routine care. The surgical indicators, pain levels, psychological states, nursing satisfaction, and postoperative complication rates of both groups were compared. RESULTS: There was no statistically significant difference in general personal information and clinical data between the two groups（P>0.05）. The surgery duration, secondary fusion rate, and postoperative complication rate in the observation group were all lower than those in the control group (［23.54±2.07］min vs ［26.25±1.69］min, P<0.05； 8.75% vs 22.50%, P=0.017； 17% vs 29%, P=0.036), and nursing satisfaction was higher in the observation group than in the control group ( 77% vs 69%, P=0.025). The VAS scores biopsy (5.11±0.93 vs 6.27±1.32, P=0.041), discharge (0.74±0.67 vs 1.85±0.95, P=0.004), and scores of SDS (47.76±2.06 vs 50.46±2.07, P=0.009) and SAS (46.89±2.68 vs 49.75±2.83, P=0.031) in the observation group were all lower than those in the control group. CONCLUSION The application of MBSR in image fusion-guided prostate biopsy can synergistically utilize the advantages of minimally invasive technology, significantly optimize surgical indicators, and improve patients' psychological experiences, which is worthy of clinical application and promotion.
Humans ; Male ; Mindfulness ; Prostate/pathology* ; Image-Guided Biopsy ; Stress, Psychological/therapy* ; Middle Aged ; Prostatic Neoplasms/pathology* ; Aged

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Non-alcoholic fatty liver disease (NAFLD) is a pathological syndrome characterized by the excessive deposition of lipids in hepatocytes but not caused by alcohol and other definite liver damage factors. The pathogenesis of NAFLD is complex. When the liver is damaged, a large amount of lipids deposited in hepatocytes will induce oxidative stress injury, endoplasmic reticulum stress and metabolic disorders in hepatocytes, and immune cells further secrete inflammatory cytokines and release them into the blood, causing systemic inflammation. In the process of NAFLD, the inflammatory response plays an important role. Macrophages are the most abundant non-parenchymal cells in the liver and play an important role in liver inflammatory injury. Hepatic macrophages include liver-native and monocyte-derived macrophages, and their activation and polarization processes are involved in the different development stages of NAFLD. Traditional Chinese medicine (TCM) compound and its active compounds have been found to regulate macrophages to participate in the process of inflammation, injury and recovery of NAFLD. Based on the existing research reports, this paper elaborates the relationship between the source, activation and polarization of macrophages and NAFLD as the breakthrough point, and systematically reviews the mechanism of TCM in the prevention and treatment of NAFLD by regulating the activation, recruitment and polarization of macrophages. This paper aims to provide new ideas for the discovery of novel NAFLD candidate drugs from TCM via targeting macrophages.

Objective:To explore the impact of transcatheter edge-to-edge repair (TEER) devices on mitral valve regurgitant flow convergence post-procedure using computational fluid dynamics(CFD), and to seek solutions for accurately measuring effective regurgitant orifice area(EROA) after TEER.Methods:Multimodal fusion was conducted based on preoperative cardiac CT images and intraoperative three-dimensional transesophageal echocardiography(3DTEE) of 33 patients with mitral valve regurgitation undergoing TEER at Renmin Hospital of Wuhan University from January 2020 to August 2023. Using this data, CFD models of mitral valve regurgitation post-TEER, including with and without the TEER device, were constructed. The distance (D) from the midpoint of the mitral regurgitation orifice to the TEER device was measured. The proximal isovelocity surfice area(PISA) radius with and without the TEER device was measured, and the corresponding EROA1 and EROA2 based on this was calculated. The EROA correction factor CC=EROA2/EROA1 was calculated.Results:A total of 42 sets of CFD models with mild or greater residual mitral regurgitation, both with and without the TEER device, and 50 sets of PISA were obtained. Based on the relative position of PISA to the TEER device, four types of PISA were observed: Type 1: PISA away from the TEER device (D>R, 14 cases), with a CC of 0.93±0.07; Type 2: PISA adjacent to the TEER device (D

Objective To observe the effects of grain-sized moxibustion on Th1 cell/Th2 cell(Th1/Th2)balance and transcription factors T-box transcription factor(T-bet)and GATA binding protein 3(GATA3)in immunosuppressive mice induced by chemotherapy.Methods According to the random number table method,32 SPF male CD-1(ICR)mice were randomly divided into the normal group,model group,levamisole hydrochloride group,and grain-sized moxibustion group,with eight mice per group.Except for the normal group,the immunosuppressive model was established by intraperitoneal injection of cyclophosphamide(80 mg/kg,once daily for three consecutive days).Mice in the levamisole hydrochloride group were given levamisole hydrochloride solution(10 mg/kg)by gavage.Mice in the grain-sized moxibustion group was given grain-sized moxibustion at"Guanyuan"(CV4),bilateral"Zusanli"(ST36),and bilateral"Sanyinjiao"(SP6),with three Zhuang at each acupoint for approximately 30 s each.The intervention was administered once daily for seven consecutive days.The general condition of mice was observed.The spleen mass and spleen index were detected.The pathological changes of spleen tissue were observed by HE staining.The protein and mRNA expressions of T-bet,GATA3,interferon-γ(IFN-γ),and interleukin(IL)-4 in spleen tissue of mice were detected by Western blotting and real-time PCR.The contents of IFN-γ,IL-2,and IL-4 in serum of mice were detected by enzyme-linked immunosorbent assay.Results Compared with the normal group,the mice in the model group were slow in response,unstable in gait;the spleen weight and spleen index were increased(P<0.05);the structure of spleen tissue was disordered,the mRNA and protein expressions of T-bet and IFN-γ in spleen tissue were decreased,and the mRNA and protein expressions of GATA3 and IL-4 were increased(P<0.05);the contents of IFN-γ and IL-2 in serum were decreased,and the content of IL-4 was increased(P<0.05).Compared with the model group,the general condition of mice in the levamisole hydrochloride group and the grain-sized moxibustion group was improved,the structure of spleen tissue was improved,the mRNA and protein expressions of T-bet and IFN-γ in spleen tissue were decreased,and the mRNA and protein expressions of GATA3 and IL-4 were increased(P<0.05);the contents of IFN-γ and IL-2 in serum were decreased,and the content of IL-4 was increased(P<0.05).Conclusion Grain-sized moxibustion can significantly improve the immunosuppressive symptoms induced by chemotherapy.The mechanism may be through regulating the expressions of transcription factors T-bet and GATA3,regulating Th1/Th2 balance,and thus restoring the immune balance.

Objective To investigate the changes of macrophage polarization during acute rejection (AR) after intestinal transplantation. Methods Six Brown Norway (BN) rats and 24 Lewis rats were divided into the sham operation group (6 Lewis rats), syngeneic transplantation group (Lewis→Lewis, 6 donors and 6 recipients) and allogeneic transplantation group (BN→Lewis, 6 donors and 6 recipients). At postoperative 7 d, the intestinal graft tissues in all groups were collected for hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Pathological manifestations and cell apoptosis were observed. The expression levels of serum cytokines related to M1 and M2 macrophage polarization were determined by enzyme-linked immunosorbent assay (ELISA). Surface markers of M1 and M2 macrophages of intestinal graft tissues in each group were co-localized and counted by immunofluorescence staining. Results HE staining and TUNEL assay showed that the intestinal epithelial morphology and structure were normal and no evident apoptotic bodies were found in the sham operation and syngeneic transplantation groups. At 7 d after transplantation, the epithelial villi structure of intestinal graft tissues was severely damaged, the number of crypts was decreased, the number of apoptotic bodies was increased, and inflammatory cells infiltrated into the whole intestinal wall, manifested with moderate to severe AR in the allogeneic transplantation group. ELISA revealed that the expression levels of serum cytokines related to M1 macrophage polarization, such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-12, of the recipient rats in the allogeneic transplantation group were higher than those in the sham operation and syngeneic transplantation groups. The expression levels of serum cytokines related to M2 macrophage polarization, such as IL-10 and transforming growth factor (TGF)-β, in the syngeneic transplantation group were higher compared with those in the sham operation and allogeneic transplantation group, and the differences were statistically significant (all P<0.05). Immunofluorescence staining showed that the number of M1 macrophages in the allogeneic transplantation group was higher than those in the sham operation and syngeneic transplantation groups, and the number of M2 macrophages in the syngeneic transplantation group was higher than those in the sham operation and allogeneic transplantation groups, and the differences were statistically significant (all P<0.05). Conclusions Among the allografts with AR after intestinal transplantation, a large number of macrophages, mainly M1 macrophages secreting a large number of pro-inflammatory cytokines, infiltrate into the whole intestinal wall. Regulating the direction of macrophage polarization is a potential treatment for AR after intestinal transplantation.

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.
Humans ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; NF-kappa B ; Interleukin-6 ; Lipopolysaccharides ; Molecular Docking Simulation ; Respiratory Distress Syndrome ; Tumor Necrosis Factor-alpha ; Sepsis/genetics* ; NLR Proteins

Objective: To study the clinical pathological characteristics, immunophenotype, molecular changes and prognosis of the papillary renal neoplasm with reverse polarity (PRNRP). Methods: Nine cases of PRNRP, diagnosed from 2013 to 2019, were retrieved from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histomorphology, immunophenotype and molecular genetics were analyzed with review of the literatures. Results: There were five male and four female patients, aged from 49 to 70 years, with an average age of 60.1 years. During a mean follow-up of 29 months, one patient died for other cause, and the others survived without disease. Microscopically, the tumor cells arranged in papillary structure with a fibrovascular core, the surface of which was covered with a single layer of cuboidal or columnar cells. The most prominent feature was that the tumor nuclei located at the top of the cytoplasm far from the basement membrane, and they were monotonous in size and arranged neatly with no or few nucleoli. Immunohistochemically, all nine cases of PRNRP showed diffuse positive expression of CK7 and E-cadherin, various degrees of P504s expression, and no expression of CD10 and CD117, with a Ki-67 index of 1%-3%. Unlike other papillary renal cell carcinoma, the nine cases of PRNRP all showed characteristic positive expression of GATA3. The fluorescence in situ hybridization assay showed that the majority of PRNRPs (8/9) did not have triploids on chromosomes 7 and 17. The sequencing of the KRAS gene confirmed the presence of a nonsense KRAS mutation in 8 of the 9 cases. Conclusions: PRNRP is a subtype of papillary renal cell carcinoma with characteristic morphological, immunophenotypic and molecular features, and indolent behaviors. More data are needed to define PRNRP as "carcinoma", and a definitive diagnosis of PRNRP is of great significance for proper treatment choice and accurate prognostication.
Biomarkers, Tumor ; Carcinoma, Renal Cell/genetics* ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Kidney ; Kidney Neoplasms/genetics* ; Male ; Middle Aged ; Prognosis

OBJECTIVE: Appraisal of treatment outcomes in integrative medicine is a challenge due to a gap between the concepts of Western medicine (WM) disease and traditional Chinese medicine (TCM) syndrome. This study presents an approach for the appraisal of integrative medicine that is based on targeted metabolomics. We use non-alcoholic fatty liver disease with spleen deficiency syndrome as a test case. METHODS: A patient-reported outcome (PRO) scale was developed based on literature review, Delphi consensus survey, and reliability and validity test, to quantitatively evaluate spleen deficiency syndrome. Then, a metabonomic foundation for the treatment of non-alcoholic fatty liver disease with spleen deficiency syndrome was identified via a longitudinal interventional trial and targeted metabolomics. Finally, an integrated appraisal model was established by identifying metabolites that responded in the treatment of WM disease and TCM syndrome as positive outcomes and using other aspects of the metabonomic foundation as independent variables. RESULTS: Ten symptoms and signs were included in the spleen deficiency PRO scale. The internal reliability, content validity, discriminative validity and structural validity of the scale were all qualified. Based on treatment responses to treatments for WM disease (homeostasis model assessment of insulin resistance) or TCM syndrome (spleen deficiency PRO scale score) from a previous randomized controlled trial, two cohorts comprised of 30 participants each were established for targeted metabolomics detection. Twenty-five metabolites were found to be involved in successful treatment outcomes to both WM and TCM, following quantitative comparison and multivariate analysis. Finally, the model of the integrated appraisal system was exploratively established using binary logistic regression; it included 9 core metabolites and had the prediction probability of 83.3%. CONCLUSION This study presented a new and comprehensive research route for integrative appraisal of treatment outcomes for WM disease and TCM syndrome. Critical research techniques used in this research included the development of a TCM syndrome assessment tool, a longitudinal interventional trial with verified TCM treatment, identification of homogeneous metabolites, and statistical modeling.
Humans ; Drugs, Chinese Herbal ; Integrative Medicine ; Medicine, Chinese Traditional/methods* ; Non-alcoholic Fatty Liver Disease/therapy* ; Reproducibility of Results ; Spleen ; Syndrome ; Treatment Outcome ; Clinical Trials as Topic

Objective:To establish a prediction model using the random forest (RF) and support vector machine (SVM) algorithms to achieve the numerical and classification predictions of the gamma passing rate (GPR) for volumetric arc intensity modulation (VMAT) validation.Methods:A total of 258 patients who received VMAT radiotherapy in the 1 st Affiliated Hospital of Wenzhou Medical University from April 2019 to August 2020 were retrospectively selected for patient-specific QA measurements, including 38 patients who received VMAT radiotherapy for head and neck, and 220 patients who received VMAT radiotherapy for chest and abdomen. Thirteen complexity parameters were extracted from the patient′s VMAT plans and the GPRs for VMAT validation under the analysis criteria of 3%/3 mm and 2%/2 mm were collected. The patients were randomly divided into a training cohort (70%) and a validation cohort (30%) , and the complexity parameters for the numerical and classification predictions were screened using the RF and minimum redundancy maximum correlation (mRMR) method, respectively. Complexity models and mixed models were established using PTV volume, subfield width, and smoothness factors based on the RF and SVM algorithms individually. The prediction performance of the established models was analyzed and compared. Results:For the validation cohort, the GPR numerical prediction errors of the complexity models based on RF and SVM under the two analysis criteria are as follows. The root-mean-square errors (RMSEs) under the analysis criterion of 3%/3 mm were 1.788% and 1.753%, respectively; the RMSEs under the analysis criterion of 2%/2 mm were 5.895% and 5.444%, respectively; the mean absolute errors (MAEs) under the analysis criterion of 3%/3 mm were 1.415% and 1.334%, respectively, and the MAEs under the analysis criteria of 2%/2 mm were 4.644% and 4.255%, respectively. For the validation cohort, the GPR numerical prediction errors of the mixed models based on RF and SVM under the two analysis criteria were as follows. The RMSEs under the analysis criterion of 3%/3 mm were 1.760% and 1.815%, respectively; the RMSEs under the analysis criterion of 2%/2 mm were 5.693% and 5.590%, respectively; the MAEs under the analysis criterion of 3%/3 mm were 1.386% and 1.319%, respectively, and the MAEs under the analysis criteria of 2%/2 mm were 4.523% and 4.310, respectively. For the validation cohort, the AUC result of the GPR classification prediction of the complexity models based on RF and SVM were 0.790 and 0.793, respectively under the analysis criterion of 3%/3 mm and were 0.763 and 0.754, respectively under the analysis criterion of 2%/2 mm. For the validation cohort, the AUC result of the GPR classification prediction of the mixed models based on RF and SVM were 0.806 and 0.859, respectively under the analysis criterion of 3%/3 mm and were 0.796 and 0.796, respectively under the analysis criterion of 2%/2 mm cohort.Conclusions:Complexity models and mixed models were developed based on the RF and SVM method. Both types of models allow for the numerical and classification predictions of the GPRs of VMAT radiotherapy plans under analysis criteria of 3%/3 mm and 2%/2 mm. The mixed models have higher prediction accuracy than the complexity models.