Astaxanthin alleviates chronic prostatitis/chronic pelvic pain syndrome by increasing colonization of Akkermansia muciniphila in the intestine.

BACKGROUND: Astaxanthin (AST) is a natural compound with anti-inflammatory/immunomodulatory properties that has been found to have probiotic properties. However, the role and mechanism of AST in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still not fully understood. PURPOSE: The aim of this study was to evaluate the effect of AST on CP/CPPS and elucidate the mediating role of the gut microbiota. MATERIALS AND METHODS: An experimental autoimmune prostatitis (EAP) mouse model was utilized to test the potential role of AST on CP/CPPS. Antibiotic cocktail (ABX) treatment and fecal microbiota transplantation (FMT) were used to elucidate the gut microbiota-mediated effects on AST. In addition, 16S rRNA gene sequencing and qRT-PCR analyses were used to analyze changes in the gut microbiota of EAP mice and CP/CPPS patients. Finally, the mechanism by which AST exerts a protective effect on CP/CPPS was explored by untargeted metabolomics and gut barrier function assays. RESULTS: Oral administration of AST reduced prostate inflammation scores, alleviated tactile sensitization of the pelvic region in EAP mice, reduced CD4+ T cell and CD68+ macrophage infiltration in the prostatic interstitium, and inhibited the up-regulation of systemic and localized pain/pro-inflammatory mediators in the prostate. After ABX, the protective effect of AST against CP/CPPS was attenuated, whereas colonization with fecal bacteria from AST-treated EAP mice alleviated CP/CPPS. 16S rRNA gene sequencing and qRT-PCR analyses showed that Akkermansia muciniphila in the feces of EAP mice and CP/CPPS patients showed a trend toward a decrease, which was associated with poor progression of CP/CPPS. In contrast, oral administration of AST increased the relative abundance of A. muciniphila, and oral supplementation with A. muciniphila also alleviated inflammation and pain in EAP mice. Finally, we demonstrated that both AST and A. muciniphila interventions increased serum levels of SCFAs acetate, up-regulated expression of colonic tight junction markers, and decreased serum lipopolysaccharide levels in EAP mice. CONCLUSION: Our results showed that AST improved CP/CPPS by up-regulating A. muciniphila, which provides new potentially effective strategies and ideas for CP/CPPS management.

Risk factors for postoperative myocardial injury-related cardiogenic shock in patients undergoing cardiac surgery.

BACKGROUND: Myocardial injury-related cardiogenic shock (MICS) is significantly associated with poor outcomes in patients after cardiac surgery. Herein, we aimed to investigate the risk factor for postoperative MICS. METHODS: We performed a case-control study on 792 patients undergoing cardiac surgery from 2016 to 2019, including 172 patients with postoperative MICS and 620 age- and sex-matched controls. MICS was defined as composite criteria: a cardiac index of < 2.2 L/m2/min, arterial lactate levels of > 5 mmol/L at the end of the surgery, a vasoactive-inotropic score of > 40 at the end of the surgery, and a cardiac troponin T (cTnT) level of > 0.8 µg/L on postoperative day 1 (POD1) with an increase of > 10% on POD 2. RESULTS: A total of 4671 patients who underwent cardiac surgery in our hospital between 2016 and 2019 were included; of these, 172 (3.68%) had MICS and the remaining 4499 did not. For investigating the risk factors, we selected 620 age- and sex-matched controls. In the univariate analysis, MICS was significantly associated with death (P < 0.05), extracorporeal membrane oxygenation (P < 0.05), continuous renal replacement therapy (P < 0.01), and ventricular arrhythmias (P < 0.05). Multivariable logistic regression analysis revealed that diabetes mellitus (OR:8.11, 95% CI: 3.52-18.66, P < 0.05) and a cardiopulmonary bypass (CPB) time of > 2 h (OR: 3.16, 95% CI: 1.94-5.15, P < 0.05) were associated with postoperative MICS. Moreover, long-time administration of preoperative calcium channel blocker (CCB) was associated with a less incidence of MICS (OR: 0.11, 95% CI: 0.05-0.27, P < 0.05). CONCLUSIONS: Postoperative MICS is significantly associated with poor outcomes. Diabetes mellitus and long CPB time are associated with MICS. Preoperative CCB administration is associated with less incidence of MICS.

Immune checkpoint inhibitor-based therapy for advanced clear cell renal cell carcinoma: A narrative review.

The prognosis for advanced clear cell renal cell carcinoma (ccRCC) is not satisfactory, even though its treatment has evolved rapidly over the past 20 years. Systemic ccRCC treatment options mainly involve antiangiogenic therapy, immune checkpoint blockade, or a combination of these therapies, and as more clinical evidence becomes available, immune checkpoint inhibitors (ICIs) are increasingly dominant. Conventional ICIs lead to the restoration of T-cell activation and a reduction in T-cell depletion by specifically blocking programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen 4 (CTLA-4), ultimately enhancing the antitumor immune response. There is no doubt that these therapies have achieved some clinical efficacy in the overall ccRCC population, but response rates and durability remain a great challenge. Therefore, novel immune checkpoints or new combination therapeutic strategies based on ICIs continue to be sought and developed. This review will provide a comprehensive overview of ICI-based therapeutic strategies in advanced ccRCC, including their mechanisms of action and the latest clinical evidence.

Integrated Analysis of Microarray Studies to Identify Novel Diagnostic Markers in Bladder Pain Syndrome/Interstitial Cystitis with Hunner Lesion.

Background: The aim of this study was to identify novel genetic features of Hunner's lesion interstitial cystitis (HIC) via comprehensive analysis of the Gene Expression Omnibus (GEO) database. Methods: The GSE11783 and GSE28242 datasets were downloaded from GEO for further analysis. Differentially expressed genes (DEGs) were identified and analyzed for functional annotation. The diagnostic markers for HIC were screened and validated using the least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms. Finally, the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm was adopted to investigate the correlation between immune cell infiltration and diagnostic markers in HIC. Results: A total of 7837 DEGs were identified in GSE11783 and 1583 DEGs in GSE28242. Venn diagrams were used to obtain 16 overlapping upregulated and 67 overlapping downregulated DEGs separately. The LASSO logistic model and SVM-RFE algorithm were used to identify 6 genes including KRT20, SLFN11, CD86, ITGA4, PLAC8, and BTN3A3 from DEGs as diagnostic markers for HIC. Their diagnostic potential in HIC and bladder pain syndrome/interstitial cystitis (BPS/IC) were acceptable. PLAC8 exhibited the best diagnostic performance in BPS/IC with an area under the curve of 0.916. The results of immune infiltration involving GSE11783 revealed that the plasma cell ratio (p = 0.017), activated memory CD4+ T cells (p = 0.009), activated dendritic cells (p = 0.01), eosinophils (p = 0.004), and neutrophils (p = 0.03) were significantly higher in HIC than in normal samples, in contrast to resting mast cells (p = 0.022). A positive correlation existed between diagnostic markers and infiltrating immune cells. Conclusion: KRT20, SLFN11, CD86, ITGA4, PLAC8, and BTN3A3 represent novel and potent diagnostic markers for HIC. They also exhibit certain diagnostic potential in BPS/IC. Immune cell infiltration might play a key role in the pathogenesis and progression of BPS/IC.

Robot-assisted retroperitoneal laparoscopic excision of perirenal vascular tumor: A case report.

BACKGROUND: A vascular tumor is a benign tumor with unique clinical and pathological features. Perirenal vascular tumor is extremely rare and has not yet been reported. Clinically, it manifests as soreness and swelling. Color ultrasound and renal angiography illustrated the perirenal mass, which was closely connected with the kidney and the surrounding tissues and organs. Histology showed extensive embedded perirenal fat, and thin-walled vascular tissue displayed a pink stain due to red blood cells. CASE SUMMARY: Herein, a case of robot-assisted retroperitoneal laparoscopic excision of a perirenal vascular tumor is reported. Analysis of the clinical, biological, and histological features of the perirenal vascular tumor can provide an in-depth understanding of the disease, which provides a theoretical and practical basis for better diagnosis and treatment. CONCLUSION: This study contributes to a practical basis for the diagnosis and treatment of perirenal hemangiom.

[Mechanisms Involved in the Inhibition of Melanin Synthesis by Bushen Quban Granule].

Objective To observe the molecular mechanism of Bushen Quban Granule (BQG) for inhibiting the synthesis of intracellular melanin. Methods Twenty SPF grade female SD rats were di- vided into four groups by completely randomized method, i.e., the control group (fed with normal saline) , high, middle, and low dose BQG groups (administered with BQG at 4. 8, 2. 4, 1. 2 g/kg by gastrogavage, equivalent to 24, 12, and 6 times clinical doses, respectively, twice per day for 3 days in total) , 5 in each group. Drug containing serum was collected. Expressions of melanocortin 1 receptor (MC1 R) , mi- crophthalmia-associated transcription factor ( MITF) , tyrosinase ( TYP) , tyrosinase-related protein I (TYRP1) , and tyrosinase-related protein 2 (TYRP2) at the mRNA level were detected by RT-PCR. Ex- pressions of phosphorylated-extracellular regulated MAP kinasel/2 (p-ERK) , TYP, TYRP1 and TYRP2 at the protein level were detected by Western blot. Intracellular melanin contents were determined by NaOH dissolving method. Activities of tyrosinase were determined by Dopa pigment method, and the cell viability was detected by MTT. Results Compared with the control group, expressions of MC1R, MITF, TYP, TYRP1 and TYRP2 at the mRNA level were down-regulated (P <0. 05), and those of TYP, TYRP1 and TYRP2 at the protein level were also down-regulated (P <0. 05), intracellular contents of melanin and the activity of tyrosinase decreased (P <0. 05) , but the level of p-ERK and the proliferation of cells increased in each medicated group (P <0. 05). When ERK was inhibited by its inhibitor PD98059, there was no sta- tistical difference in expressions of MC1 R or MITF at the mRNA level among all medicated groups (P > 0. 05). Compared with the control group, mRNA expressions of TYP, TYRP1 and TYRP2 decreased in the high dose BQG group (P <0. 05), but with no significant difference in protein expressions of p-ERK, TYP, TYRP1 and TYRP2 (P >0. 05). There was no statistical difference in the content of melanin, the activity of TYP, or the proliferation of cells between the control group and the high dose BQG group (P >0. 05). Con- clusion BQG could inhibit the synthesis of intracellular melanin through up-regulating p-ERK to inhibit the expression of tyrosinase and its related proteins.

Graft pathology at the time of harvest: impact on long-term survival / Patologia do enxerto no momento da coleta: impacto na sobrevida a longo prazo

Objective: This study aims to present the graft pathology at the time of harvest and its impact on long-term survival. Methods: The remnants of the bypass grafts from 66 consecutive patients with coronary artery disease receiving a coronary artery bypass grafting were investigated pathologically, and pertinent predictive risk factors and survival were analyzed. Results: Medial degenerative changes with or without intimal proliferation were present in 36.8%, 37.8% and 35.6% of left internal mammary artery (IMA), radial artery and saphenous vein grafts. There were 2 (3.0%) hospital deaths and 9 (14.1%) late deaths. Multinomial logistic regression revealed left IMA pathological changes, dyslipidemia, history of percutaneous transluminal coronary angioplasty/stent deployment and Y-graft were significant predictive risk factors negatively influencing the patients’ long-term survival. Kaplan-Meier survival analysis revealed that the long-term survival of patients with left IMA pathological changes were significantly reduced compared with those without (74.1% vs. 91.4%, P=0.002); whereas no differences were noted in long-term survivals between patients with and without pathological changes of the radial arterial or saphenous vein grafts. Conclusion: Pathological changes may be seen in the bypass graft at the time of harvest. The subtle ultrastructural modifications and the expressions of vascular tone regulators might be responsible for late graft patency. The pathological changes of the left IMA at the time of harvest rather than those of the radial artery or saphenous vein graft affect significantly longterm survival. Non-traumatic maneuver of left IMA harvest, well-controlled dyslipidemia and avoidance of using composite grafts can be helpful in maintaining the architecture of the grafts. .

Objetivo: Este estudo tem como objetivo apresentar a patologia do enxerto no momento da coleta e do impacto na sobrevida a longo prazo. Métodos: Os remanescentes de pontes de safena de 66 pacientes consecutivos com doença arterial coronária que receberam uma cirurgia de revascularização coronariana foram investigados patologicamente, e os fatores de risco preditivos e a sobrevivência foram analisados. Resultados: Alterações degenerativas da artéria medial, com ou sem proliferação da íntima estavam presentes em 36,8%, 37,8% e 35,6% de pontes da artéria torácica interna esquerda (ATIE), artéria radial e veia safena. Houve dois (3,0%) óbitos hospitalares e nove (14,1%) óbitos tardios. A regressão logística multinomial revelou que alterações patológicas na ATIE, dislipidemia, história de angioplastia/stent implantação coronariana transluminal percutânea e Y-enxerto foram significativos fatores de risco preditivos que influenciam negativamente a sobrevivência a longo prazo dos pacientes. Análise de sobrevida de Kaplan- Meier revelou que a sobrevivência a longo prazo de pacientes com alterações patológicas da ATIE foi significativamente reduzida em comparação com aqueles sem (74,1% vs. 91,4%, P=0,002), considerando que não foram observadas diferenças na sobrevivência de longo prazo entre pacientes com e sem alterações patológicas dos enxertos da artéria radial ou de veia safena. Conclusão: As alterações patológicas podem se desenvolver na revascularização no momento da coleta. As modificações ultraestruturais sutis e as expressões de reguladores do tônus vascular podem ser responsáveis pela patência tardia do enxerto. As alterações patológicas da ATIE no momento da coleta, em vez do enxerto da artéria radial ou da veia safena, podem afetar significativamente a sobrevida de longo prazo. Manobra não traumática da ATIE na coleta, bom controle da dislipidemia e para evitar uso de enxertos compostos pode ser útil na manutenção da arquitetura dos enxertos. .

Graft pathology at the time of harvest: impact on long-term survival.

OBJECTIVE: This study aims to present the graft pathology at the time of harvest and its impact on long-term survival. METHODS: The remnants of the bypass grafts from 66 consecutive patients with coronary artery disease receiving a coronary artery bypass grafting were investigated pathologically, and pertinent predictive risk factors and survival were analyzed. RESULTS: Medial degenerative changes with or without intimal proliferation were present in 36.8%, 37.8% and 35.6% of left internal mammary artery (IMA), radial artery and saphenous vein grafts. There were 2 (3.0%) hospital deaths and 9 (14.1%) late deaths. Multinomial logistic regression revealed left IMA pathological changes, dyslipidemia, history of percutaneous transluminal coronary angioplasty/stent deployment and Y-graft were significant predictive risk factors negatively influencing the patients' long-term survival. Kaplan-Meier survival analysis revealed that the long-term survival of patients with left IMA pathological changes were significantly reduced compared with those without (74.1% vs. 91.4%, P=0.002); whereas no differences were noted in long-term survivals between patients with and without pathological changes of the radial arterial or saphenous vein grafts. CONCLUSION: Pathological changes may be seen in the bypass graft at the time of harvest. The subtle ultrastructural modifications and the expressions of vascular tone regulators might be responsible for late graft patency. The pathological changes of the left IMA at the time of harvest rather than those of the radial artery or saphenous vein graft affect significantly longterm survival. Non-traumatic maneuver of left IMA harvest, well-controlled dyslipidemia and avoidance of using composite grafts can be helpful in maintaining the architecture of the grafts.

The mitogenome of Liobagrus nigricauda (Teleostei, Siluriformes: Amblycipitidae).

Liobagrus nigricauda is endemic to the Yangtze River system (Ding 1994, The fishes of Sichuan province. pp. 470-78) and listed as an endangered species (IUCN 2012, Red list of threatened species. http://www.iucnredlist.org ). In this study, the complete mitochondrial genome sequence of L. nigricauda has been obtained with polymerase chain reaction (PCR), which contains 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a noncoding control region with the total length of 16,512 bp. The gene arrangement and composition are similar to that of other vertebrates. Most of the genes are encoded on heavy strand, except for eight tRNA and ND6 genes. Just like most other vertebrates, the bias against G has a universality in different statistics results. The mitogenome sequence of L. nigricauda would contribute to better understand population genetics and to protect its genetic diversity.