Purpose: Irreversible electroporation (IRE) is a promising alternative treatment for low-intermediate-risk localized prostate cancer. In this systematic review we aim to evaluate the safety profile and functional and oncological outcomes of this new technique. Materials and Methods: A systematic review of the literature was performed on PubMed, EMBASE, and Scopus up to 24 August 2023. Nineteen studies were analyzed, including 12 prospective studies and 7 retrospective studies. A total of 1,452 patients underwent IRE as the sole primary treatment modality. Results: The in-field clinically significant prostate cancer rate was reported between 0%–15.6% in the repeat biopsy. The retreatment rate was reported from 8% to 36.6%. The 3 years failure-free survival was presented between 90%–96.8%. The post-operative pad-free rate ranged between 96.7%–100%. Greater heterogeneity exists considering the change in erectile function. The most common reported complications were urinary tract infection and hematuria. Major complications were rare. Conclusions These results underline that IRE achieves favorable oncological control with an excellent safety profile, in the meantime preserving patients’ urinary and erectile function

Purpose: Irreversible electroporation (IRE) is a promising alternative treatment for low-intermediate-risk localized prostate cancer. In this systematic review we aim to evaluate the safety profile and functional and oncological outcomes of this new technique. Materials and Methods: A systematic review of the literature was performed on PubMed, EMBASE, and Scopus up to 24 August 2023. Nineteen studies were analyzed, including 12 prospective studies and 7 retrospective studies. A total of 1,452 patients underwent IRE as the sole primary treatment modality. Results: The in-field clinically significant prostate cancer rate was reported between 0%–15.6% in the repeat biopsy. The retreatment rate was reported from 8% to 36.6%. The 3 years failure-free survival was presented between 90%–96.8%. The post-operative pad-free rate ranged between 96.7%–100%. Greater heterogeneity exists considering the change in erectile function. The most common reported complications were urinary tract infection and hematuria. Major complications were rare. Conclusions These results underline that IRE achieves favorable oncological control with an excellent safety profile, in the meantime preserving patients’ urinary and erectile function

Purpose: Irreversible electroporation (IRE) is a promising alternative treatment for low-intermediate-risk localized prostate cancer. In this systematic review we aim to evaluate the safety profile and functional and oncological outcomes of this new technique. Materials and Methods: A systematic review of the literature was performed on PubMed, EMBASE, and Scopus up to 24 August 2023. Nineteen studies were analyzed, including 12 prospective studies and 7 retrospective studies. A total of 1,452 patients underwent IRE as the sole primary treatment modality. Results: The in-field clinically significant prostate cancer rate was reported between 0%–15.6% in the repeat biopsy. The retreatment rate was reported from 8% to 36.6%. The 3 years failure-free survival was presented between 90%–96.8%. The post-operative pad-free rate ranged between 96.7%–100%. Greater heterogeneity exists considering the change in erectile function. The most common reported complications were urinary tract infection and hematuria. Major complications were rare. Conclusions These results underline that IRE achieves favorable oncological control with an excellent safety profile, in the meantime preserving patients’ urinary and erectile function

Purpose: Irreversible electroporation (IRE) is a promising alternative treatment for low-intermediate-risk localized prostate cancer. In this systematic review we aim to evaluate the safety profile and functional and oncological outcomes of this new technique. Materials and Methods: A systematic review of the literature was performed on PubMed, EMBASE, and Scopus up to 24 August 2023. Nineteen studies were analyzed, including 12 prospective studies and 7 retrospective studies. A total of 1,452 patients underwent IRE as the sole primary treatment modality. Results: The in-field clinically significant prostate cancer rate was reported between 0%–15.6% in the repeat biopsy. The retreatment rate was reported from 8% to 36.6%. The 3 years failure-free survival was presented between 90%–96.8%. The post-operative pad-free rate ranged between 96.7%–100%. Greater heterogeneity exists considering the change in erectile function. The most common reported complications were urinary tract infection and hematuria. Major complications were rare. Conclusions These results underline that IRE achieves favorable oncological control with an excellent safety profile, in the meantime preserving patients’ urinary and erectile function

Purpose: Irreversible electroporation (IRE) is a promising alternative treatment for low-intermediate-risk localized prostate cancer. In this systematic review we aim to evaluate the safety profile and functional and oncological outcomes of this new technique. Materials and Methods: A systematic review of the literature was performed on PubMed, EMBASE, and Scopus up to 24 August 2023. Nineteen studies were analyzed, including 12 prospective studies and 7 retrospective studies. A total of 1,452 patients underwent IRE as the sole primary treatment modality. Results: The in-field clinically significant prostate cancer rate was reported between 0%–15.6% in the repeat biopsy. The retreatment rate was reported from 8% to 36.6%. The 3 years failure-free survival was presented between 90%–96.8%. The post-operative pad-free rate ranged between 96.7%–100%. Greater heterogeneity exists considering the change in erectile function. The most common reported complications were urinary tract infection and hematuria. Major complications were rare. Conclusions These results underline that IRE achieves favorable oncological control with an excellent safety profile, in the meantime preserving patients’ urinary and erectile function

This study aimed to investigate the effect of saltwater stir-fried Plantaginis Semen(SPS) on renal fibrosis in rats and decipher the underlying mechanism. Thirty-six Sprague-Dawley rats were randomly assigned into control, model, losartan potassium, and low-, medium-, and high-dose(15, 30, and 60 g·kg~(-1), respectively) SPS groups. Rats in other groups except the control group were subjected to unilateral ureteral obstruction(UUO) to induce renal fibrosis, and the modeling and gavage lasted for 14 days. After 14 consecutive days of treatment, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in rats of each group were determined by an automatic biochemical analyzer. Hematoxylin-eosin(HE) and Masson staining were used to evaluate pathological changes in the renal tissue. Western blot and immunofluorescence assay were conducted to determine the protein levels of fibronectin(FN), collagen Ⅰ, vimentin, and α-smooth muscle actin(α-SMA) in the renal tissue. The mRNA levels of epithelial-mesenchymal transition(EMT)-associated transcription factors including twist family bHLH transcription factor 1(TWIST1), snail family transcriptional repressor 1(SNAI1), and zinc finger E-box binding homeobox 1(ZEB1), as well as inflammatory cytokines such as interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), were determined by RT-qPCR. Human renal proximal tubular epithelial(HK2) cells exposed to transforming growth factor-β(TGF-β) for the modeling of renal fibrosis were used to investigate the inhibitory effect of SPS on EMT. Network pharmacology and Western blot were employed to explore the molecular mechanism of SPS in alleviating renal fibrosis. The results showed that SPS significantly reduced Scr and BUN levels and alleviated renal injury and collagen deposition in UUO rats. Moreover, SPS notably down-regulated the protein levels of FN, collagen Ⅰ, vimentin, and α-SMA as well as the mRNA levels of SNAI1, ZEB1, TWIST1, IL-1β, IL-6, and TNF-α in the kidneys of UUO rats and TGF-β-treated HK-2 cells. In addition, compared with Plantaginis Semen without stir-frying with saltwater, SPS showed increased content of specific compounds, which were mainly enriched in the mitogen-activated protein kinase(MAPK) signaling pathway. SPS significantly inhibited the phosphorylation of extracellular signal-regulated kinase(ERK) and p38 MAPK in the kidneys of UUO rats and TGF-β-treated HK2 cells. In conclusion, SPS can alleviate renal fibrosis by attenuating EMT through inhibition of the MAPK signaling pathway.
Animals ; Epithelial-Mesenchymal Transition/drug effects* ; Rats, Sprague-Dawley ; Male ; Rats ; Fibrosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Kidney Diseases/pathology* ; Kidney Tubules/pathology* ; Humans

OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Interleukin-35(IL-35)is an important immunosuppressive cytokine that has been shown to play a role in the immune response of various diseases.In this study,we cloned the coding sequence of human IL-35 gene,constructed single subunit expression vectors pXC17.4-p35 and pcDNA3.1(+)-EBI3,and co-transfected CHO-K1 cells to express IL-35 in vitro.No binding was found between subunits of p35 and EBI3.Knobs-into-Holes(KIH)can solve the problem of heavy chain mismatch of heterolo-gous antibodies.Therefore,expression vectors pXC17.4-p35-Fch and pcDNA3.1(+)-EBI3-Fck were constructed by fusing KIH structures on the basis of the original sequences to express the recombinant fu-sion protein of KIH-IL-35.The expression vectors of two subunits were exchanged at the same time to verify the influence of different vectors on the expression level of KIH-IL-35.The analysis of various pro-tein detection methods showed that the correct expression rate of KIH-IL-35 structure was significantly im-proved.Affinity purification of KIH-IL-35 was performed after large amount of expression,and the bind-ing activity of KIH-IL-35 to glycoprotein 130(gp130)was detected by ELISA.The results showed that the binding of KIH-IL-35 to gp130 was concentration dependent.The indirect activity of KIH-IL-35 and M1 cells was detected by cell activity assay.Further results showed that the inhibition rate of M1 cells in-creased in a dose-dependent manner with the concentration of KIH-IL-35.In addition,a method for de-termining IL-35 activity by activated human peripheral blood mononuclear cells was successfully estab-lished.Activated PBMCs increased in a dose-dependent manner with KIH-IL-35 concentration.In sum-mary,this study utilized the KIH-IL-35 model to enhance the expression of recombinant human IL-35 and validated its high activity in vitro,providing new ideas for the study of IL-35 and the recombinant expres-sion of similar heterodimeric cytokines.