Parathyroid hormone related-protein (PTHrP) in tissues with poor prognosis in prostate cancer patients.

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) is known to have a pivotal role in the progression of various solid tumors, among which prostate cancer stands out. However, the extent of PTHrP expression and its clinical implications in prostate cancer patients remain shrouded in obscurity. The primary objective of this research endeavor was to shed light on the relevance of PTHrP in the context of prostate cancer patients and to uncover the potential underlying mechanisms. METHODS: The expression of PTHrP, E-cadherin, and vimentin in tumor tissues of 88 prostate cancer patients was evaluated by immunohistochemical technique. Subsequently, the associations between PTHrP and clinicopathological parameters and prognosis of patients with prostate cancer were analyzed. RESULTS: Immunohistochemical analysis showed that the expression rates of PTHrP, E-cadherin, and vimentin in prostate cancer tissues were 95.5%, 88.6%, and 84.1%, respectively. Patients with a high level of PTHrP had a decreased expression of E-cadherin (P = .013) and an increased expression of vimentin (P = .010) compared with patients with a low level of PTHrP. Besides, the high expression of PTHrP was significantly correlated with a higher level of initial prostate-specific antigen (P = .026), positive lymph node metastasis (P = .010), osseous metastasis (P = .004), and Gleason score (P = .026). Moreover, patients with a high level of PTHrP had shorter progression-free survival (P = .002) than patients with a low level of PTHrP. CONCLUSION: The present study indicates that PTHrP is associated with risk factors of poor outcomes in prostate cancer, while epithelial-mesenchymal transition may be involved in this process.

Characterization and verification of CAF-relevant prognostic gene signature to aid therapy in bladder cancer.

Cancer-associated fibroblasts (CAFs) are significantly involved in determining the patient's prognosis and response to bladder cancer (BLCA) therapy. CAFs can induce epithelial-mesenchymal transformation (EMT) as well as complex interaction with immune cells. Hence, it is imperative to identify potential markers for enhancing our understanding of CAFs in BLCA progression and immune regulation. A variety of algorithms and analyses were employed in the study, leading to the development of a novel prognostic feature for CAFs-Stromal-EMT (CSE)-prognostic feature. This feature was constructed based on the genes MFAP5, PCOLCE2, and JUN. Furthermore, we revealed that patients with higher CSE risk scores responded to immunotherapy better compared to those with lower. Finally, we verified two CSE-related genes using in vitro experiments. Our results suggested that the CSE-prognostic feature could predict the prognosis and evaluate the response of patients to immune and chemotherapies. This would aid clinicians in designing treatment strategies for patients with BLCA.

Assessing the Relationship Between Gut Microbiota and Posttransplant Diabetes Mellitus.

OBJECTIVES: The incidence of diabetes significantly increases after kidney transplant, and the associated gut microbiota are closely related to diabetes. However, the gut microbiota of recipients with diabetes after kidney transplant remain unexplored. MATERIALS AND METHODS: Feces samples from recipients with diabetes 3 months after kidney transplant were collected and analyzed using high-throughput 16S rRNA gene sequencing. RESULTS: Our study included 45 transplant recipients: 23 posttransplant diabetes mellitus recipients, 11 recipients without diabetes mellitus, and 11 recipients with preexisting diabetes mellitus. No significant differences in intestinal flora richness and α diversity were observed among the 3 groups. However, principal coordinate analysis based on UniFrac distance revealed significant differences in ß diversity. At the phyla level, the abundance of Proteobacteria in posttransplant diabetes mellitus recipients decreased (P = .028), whereas that of Bactericide (P = .004) increased. At the class level, the abundance of Gammaproteobacteria (P = .037) decreased, whereas thatofBacteroidia (P=.004)increased.Attheorderlevel, the abundanceof Enterobacteriales (P = .039)decreased, whereasBacteroidales (P=.004)increased.Atthe family level, the abundance of Enterobacteriaceae (P = .039) and Peptostreptococcaceae (P = .008) decreased, whereas Bacteroidaceae (P = .010) increased. At the genus level,the abundance of Lachnospiraceae incertae sedis (P = .008) decreased, whereas Bacteroides (P = .010) increased. Furthermore, KEGG analysis identified 33 pathways, among which the biosynthesis of unsaturated fatty acids was closely related to gut microbiota and posttransplant diabetes mellitus. CONCLUSIONS: To our knowledge, this is the first comprehensive analysis of the gut microbiota from posttransplant diabetes mellitus recipients. The microbial composition of stool samples of post- transplant diabetes mellitus recipients was significantly different from recipients without diabetes and with preexisting diabetes. The number of bacteria producing short-chain fatty acids decreased, whereas pathogenic bacteria increased.

Endovascular Treatment of Transplant Renal Artery Stenosis: A Single-Center Retrospective Cohort Study.

OBJECTIVES: Endovascular therapy is the most common treatment for transplant renal artery stenosis; however, its long-term outcomes remain controversial, with no uniform standard for percutaneous transluminal angioplasty versus percutaneous transluminal stenting. MATERIALS AND METHODS: We retrospectively analyzed 26 patients with transplant renal artery stenosis who underwent endovascular therapy. We evaluated long-term efficacy of endovascular therapy and the reasonable choice of treatment. RESULTS: Serum creatinine increased significantly at onset of transplant renal artery stenosis (113.88 ± 37.573 before vs 279.31 ± 94.98 µmol/L during stenosis; P1 < .001), and endovascular therapy had a good short-term effect (279.31 ± 94.98 during stenosis vs 139.54 ± 124.40 µmol/L at 2 weeks posttreatment; P2 = .002). Long-term efficacy of endovascular therapy was stable (139.54 ± 124.40 at 2 weeks posttreatment vs 150.69 ± 180.72 at 6 months vs 161.58 ± 174.49 µmol/L at last follow-up; P3 > .05). Blood pressure increased significantly at onset of transplant renal artery stenosis (126.65 ± 16.11 before vs 159.62 ± 25.84 mm Hg during stenosis; P1 < .001). Moreover, the short-term effect of endovascular therapy was good (159.62 ± 25.84 during stenosis vs 128.73 ± 14.22 mm Hg at 2 weeks posttreatment; P2 < .001). Long-term effects remained stable (128.73 ± 14.22 at 2 weeks posttreatment vs 131.15 ± 14.55 at 6 months vs 138.50 ± 16.82 mm Hg at last follow-up; P3 > .05). Peak systolic velocity decreased significantly after endovascular therapy (176.6 ± 67.93 during stenosis vs 114.24 ± 67.93 cm/s at 2 weeks posttreatment; P < .001). CONCLUSIONS: Endovascular therapy is effective in transplant renal artery stenosis treatment and has a low incidence of complications. Percutaneous transluminal angioplasty should be performed routinely during endovascular therapy. After dilation, if stenosis remains >25% or retracted, then percutaneous transluminal stenting is recommended. Otherwise, percutaneous transluminal angioplasty is preferred.

Study on the effect of additives on microbial diversity, predicted functional profiles, and fermentation quality of Broussonetia papyrifera and Pennisetum sinese mixed ensilage in the karst region.

In this research, we evaluated the effect of exogenous lactic acid bacteria and Amomum villosum essential oil (AVEO) on the chemical composition, microbial community composition, microbial functional diversity, and fermentation quality of Broussonetia papyrifera (BP) and Pennisetum sinese (PS) mixed silages. The BP:PS mixing ratios were 100:0, 70:30, 50:50, 30:70, and 0:100. After 3 and 30 days of ensiling at 22°C-25°C, microbial diversity and function, and fermentation quality, were assessed. Increasing PS content resulted in decreased ammoniacal nitrogen and pH, increased water-soluble carbohydrate content, increased relative abundance of Lactococcus and Acinetobacter, and reduced relative abundance of Caproiciproducens and Pseudomonas. A 50:50 BP:PS ratio effectively improved the fermentation quality compared to anaerobic fermentation with BP or PS alone, while AVEO treatment further improved fermentation quality by increasing Lactococcus relative abundance. Moreover, as fermentation proceeded, ensiling enhanced the 'Human diseases', 'Environmental information processing', and 'Cellular processes' functions at the first level, as well as the 'Two-component system' and 'ABC transporters' functions at the third level. Different additives affected the fermentation of BP and PS mixed silage by regulating microbial community succession and metabolic pathways during ensiling.

Fermentation quality, bacterial community, and predicted functional profiles in silage prepared with alfalfa, perennial ryegrass and their mixture in the karst region.

There is little information regarding the dynamics of fermentation products and the bacterial community in silage prepared with alfalfa (MS), perennial ryegrass (LP), and their mixture in the karst region. In this study, we explored the effects of combining MS with LP in different ratios (100% MS, 70% MS + 30% LP, 50% MS + 50% LP, 30% MS + 70% LP and 100% LP; fresh matter basis) on silage chemical composition, fermentation quality, bacterial communities and predicted functions during the ensiling process. Each treatment was prepared in triplicate and stored at room temperature (22-25°C) for 7, 15, and 45 days. The dry matter (DM) and water-soluble carbohydrate content of the silages increased as the LP proportion in the mixed silage increased; at 45 days, the 70% MS + 30% LP, 50% MS + 50% LP and 30% MS + 70% LP silages contained higher (p < 0.05) CP content than the 100% MS and 100% LP silages. The 30% MS + 70% LP and 100% LP silages exhibited lower (p < 0.05) pH and higher (p < 0.05) LA content than the other silages; at 45 days, none of the silages contained PA or BA. As fermentation proceeded, the abundance of harmful (Enterobacteriaceae and Sphingomonas) and beneficial (Lentilactobacillus, Lactiplantibacillus, Secundilactobacillus, and Levilactobacillus) microorganisms decreased and increased, respectively, as the LP proportion in the mixed silage increased. The predicted functional distribution of microbial communities and metabolic pathways revealed that the 30% MS + 70% LP and 100% LP silages had a stronger capacity for fermentation and a weaker capacity for nitrate reduction than the other silages. Moreover, as the fermentation proceeded, the 30% MS + 70% LP and 100% LP treatments enhanced the functions of "Metabolism," "Genetic information processing" and "Organismal systems" at level 1, the functions of "Amino acid metabolism" and "Nucleotide metabolism" at level 2, and the functions of "Metabolic pathways," "Biosynthesis of secondary metabolites," "Biosynthesis of antibiotics" and "Purine metabolism" at level 3. Thus, adding LP could improve the fermentation quality of MS silage by changing the composition and metabolic function of microbes; furthermore, ensiling 30% alfalfa with 70% ryegrass can produce high-quality silage in the karst region.

Effect of Amomum villosum essential oil as an additive on the chemical composition, fermentation quality, and bacterial community of paper mulberry silage.

Paper mulberry (Broussonetia papyrifera L., PM) is being used as a new type of animal protein feed to address the feed crisis. To investigate the effect of additives on the chemical composition, fermentation quality, and bacterial community of PM silage (at room temperature, 25°), paper mulberry was fermented with formic acid (FA), Amomum villosum essential oil (AVEO) and lactic acid bacteria (LAB) inoculant treatments. The results showed that fresh PM had a low water-soluble carbohydrate (WSC) content and large amounts of unclassified bacteria. Compared with the CK and LAB treatments, the FA and AVEO treatments significantly (P < 0.05) decreased the pH and increased the lactic acid content of PM silage after 60 days of ensiling. In the AVEO-treated silages the abundance of Lactococcus in the early stage of ensiling increased by 14.09%, the abundances of Levilactobacillus and Lentilactobacillus in the late stage of ensiling increased by 58.34 and 91.12%, respectively, and the abundance of Stenotrophomonas decreased by 94.71%, resulting in improved PM silage quality. These results confirmed that AVEO could potentially be developed as a new additive for improving the fermentation quality of silage.

Analysis of Targeted Post-operative Nursing Outcome in 1246 Patients with Percutaneous Transhepatic Biliary Drainage.

Jaundice is a detection index in many disease conditions commonly characterized by yellowish staining of the skin and mucous membranes. This work studies the postoperative care outcome in 1,246 patients (669 males and 577 females) with obstructive jaundice who underwent percutaneous transhepatic biliary drainage (PTBD). These patients were admitted to the interventional vascular surgery department of our hospital from February 2017 to February 2022. From the results, frequent wound re-dressing and maintenance of the drainage tube had significant positive influence on wound healing and patient recovery. The data also showed strict adherence by patients to the doctor's recommendation advising them to visit the interventional specialist care clinic in time for wound dressing change and drainage tube maintenance. As a result, there was no significant difference in wound allergy, exudation, redness and loosening among patients. A cross-sectional analysis of the effect of age on recovery revealed variations in the healing pattern (wound loosening and the redness) between patients of different ages although the relationship is not very clear due to the limited sample size. Efficient drainage tube maintenance promoted recovery and prevented the occurrence of related complications such as PTBD tube blockage and biliary tract infection. The establishment of the interventional specialist care clinic used in this study additionally ensures patients' safety, and the incidence of complications have been reduced drastically. These achievements are attributable to the implementation of regular dressing change, drainage tube maintenance and health education for patients with PTBD tube. These practices have also improved on the level of specialty in nursing practice, increased the professional value of nurses and better recognition by the society.

Female chronic posterior urethritis is underestimated in patients with lower urinary tract symptoms.

BACKGROUND: As one of the causes of urethral symptoms, female chronic posterior urethritis is a common and distressing disease; however, it is often neglected and misdiagnosed as overactive bladder (OAB) or interstitial cystitis/bladder pain syndrome (IC/BPS). Currently, little is known about the urothelium and lamina propria of the bladder neck and proximal urethra. Thus, identifying urethral lesions is necessary for the diagnosis and treatment of female chronic posterior urethritis. Transurethral electroresection is an effective and safe approach for treating female chronic posterior urethritis. This study sought to determine if urethral lesions are necessary for the diagnosis and treatment of female chronic posterior urethritis, and evaluate the efficacy and safety of the transurethral electroresection of mucosa and submucosa in treating female chronic posterior urethritis. METHODS: A single-center, retrospective, observational study was conducted at a teaching and referral hospital. A total of 147 female patients who had been diagnosed with chronic papillary urethritis underwent transurethral electroresection between 2015 and 2018. Each patient underwent a follow-up examination. A chart review was also performed. RESULTS: Patients had a mean age of 54 years (range, 23-82 years), and the average follow-up period was 54.8 months (range, 6-600 months). Urinary frequency and urgency (51.7%) were the most common clinical manifestations of chronic posterior urethritis. Forty-two-point two percent of patients had positive urine culture results, most commonly with Mycoplasma genitalium. The cystoscopic findings revealed that chronic posterior urethritis has tuft-like, pseudopodia-like, finger-like, and follicular-like polyps and villi, and a pebble-like appearance with mucosal hyperemia. The success rate of the transurethral electroresection was 88.6%, and patients showed no apparent or serious complications. CONCLUSIONS: This study showed that female chronic posterior urethritis is a cause that contributes to LUT symptoms. Its characteristic cystoscopic appearance and biopsy play a vital role in its diagnosis. The transurethral electroresection of urethral lesions is simple, effective, and minimally invasive without any apparent complications.

Macelignan protects against renal ischemia-reperfusion injury via inhibition of inflammation and apoptosis of renal epithelial cells.

Ischemia-reperfusion injury (IRI) refers to tissue damage that occurs when blood supply returns to tissue after a period of ischemia, anoxia or hypoxia. It occurs frequently during shock, organ transplantation and heart failure. It can cause impairment or even renal failure. Macelignan is a lignin isolated from the seeds of Myristica fragrans. It has been reported to inhibit neuroinflammation and oxidative toxicity. The preventive or therapeutic effects of macelignan on renal IRI has not been reported. The present study investigated the effects of macelignan on renal IRI in rats, and the underlying mechanism(s). Healthy adult male Sprague Dawley rats (n = 50) aged 7 - 9 weeks (mean weight = 220 ± 20 g) were used in this study. The rats were randomly assigned to five groups of 10 rats each: sham   treated group, IRI group and 40 mg macelignan/kg body weight (bwt) group, 80 mg macelignan/kg bwt group, and 160 mg macelignan/kg bwt group. Ischemia-reperfusion injury was induced in the rats using standard procedure. The results showed that serum levels of creatinine, blood urea nitrogen (BUN), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and gamma interferon (IFN-γ) were significantly higher in IRI group than in sham treated group, but were significantly and dose-dependently reduced after treatment with macelignan (p < 0.05). The activities of catalase and superoxide dismutase (SOD), and reduced glutathione (GSH) level were significantly reduced in IRI group, when compared with sham treated group, but were significantly and dose-dependently increased after treatment with macelignan (p < 0.05). However, the level of malondialdehyde (MDA) was significantly higher in IRI group than in sham treated group, but treatment with macelignan reduced it significantly and dose-dependently (p < 0.05). Macelignan also significantly and dose-dependently inhibited IRI-induced apoptosis in epithelial cells of renal tubules (p < 0.05). The results of Western blotting showed that IRI significantly upregulated the expressions of bax and caspase-3, and down-regulated the expression of bcl-2 in epithelial cells of renal tubules (p < 0.05). However, treatment with macelignan significantly and dose-dependently down-regulated the expressions of bax and caspase-3 in these cells, but significantly and dose-dependently upregulated the expression of bcl-2. These results show that macelignan confers protection on renal IRI via mechanisms involving inhibition of inflammation and apoptosis, and stimulation of natural antioxidant defense system.

[Oleanolic acid synergizes with cyclosporine A to prolong renal allograft survival in rats].

OBJECTIVE: To investigate the synergistic effect of oleanolic acid (OA) and cyclosporine A (CsA) on the survival of renal allografts in rats. METHODS: Renal allograft transplantation was performed using BN rats as donors and LEW rats as recipients. Forty male LEW rats were randomized into 4 equal groups for interventions with DMSO-PBS (control), OA, CsA, or CsA+OA, starting from 1 day before transplantation. Serum creatinine levels were regularly examined, and the survival of rats were recorded. On day 5 after transplantation, CD4(+) and CD8(+) T-cell infiltration in the renal grafts was analyzed by immunohistochemistry; the concentrations of the proinflammatory cytokines (IL-1ß, IFN-γ, IL-2, IL-4, and IL-17), anti-inflammatory cytokine IL-10 and chemokines (IP-10, MCP-1, MIP, and Mig) were analyzed with Luminex; the T-cell phenotypes (IFN-γ, IL-10, IL-4, and IL-17) were analyzed using ELISpot. RESULTS: In OA+CsA group, renal allograft survival was markedly prolonged and CD4(+) and CD8(+) T cell infiltration in the graft significantly decreased as compared to other groups. A significant decrease in IL-2 was observed in OA group and OA+CsA group, especially the latter. Compared with the control group, all the 3 treated groups showed significantly decreased IL-1ß, IP-10 and MCP-1, increased IL-10 levels, decreased percentages of T cells secreting IFN-γ, IL-4 and IL-17, and increased percentage of T cells secreting IL-10. The increments of serum IL-10 level and T cell percentage were more prominent in OA+CsA group than in the other two intervention groups. CONCLUSIONS: OA and CsA synergistically ameliorate renal graft rejection and inflammation and promote allograft survival and function in rats.

[Growth inhibition and mechanisms of human bladder cancer T24 cells by adenovirus-mediated ING4 gene in vitro].

OBJECTIVE: To explore the inhibitory effect and anti-cancer mechanisms of adenovirus-mediated ING4 gene on the human bladder cancer T24 cells in vitro. METHODS: The methods of reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of ING4 in human bladder urothelial carcinoma T24 line. The influence of Ad-ING4 transfection on cell proliferation was evaluated by MTT assay and cell apoptosis by Hochest33258 staining and flow cytometry. RT-PCR and Western blot were performed to detect the transcriptional level of such apoptosis-related genes as Bcl-2, Bax, p53, HIF-1α and caspase-3. RESULTS: Human ING4 was successfully transcribed in T24 cell. Apoptosis rate of T24 cell in Ad-ING4 group was significant higher than that in control groups (17.2% ± 4.1% vs 4.7% ± 1.2% and 4.8% ± 1.2%, P < 0.05). Ad-ING4 not only up-regulated the expression of p53 and Bax(1.40 ± 0.11 vs 0.27 ± 0.04, 1.50 ± 0.12 vs 0.60 ± 0.05) and down-regulated the expression of Bcl-2 and HIF-1α (0.19 ± 0.02 vs 1.20 ± 0.08, 0.33 ± 0.03 vs 0.98 ± 0.06, all P < 0.05), but also enhanced the caspase-3 activation and eventually led to apoptosis. CONCLUSION: Adenovirus-mediated ING4 gene exhibits anti-tumor capacity in T24 human bladder cancer cell and induces in vitro apoptosis. It may be related to the up-regulation of P53 and Bax/Bcl-2, and the down-regulation of HIF-1α. Thus the caspase-3 activation is enhanced so as to lead to apoptosis.