Association between albumin-corrected anion gap level and the risk of acute kidney injury in intensive care unit.

PURPOSE: This study was to investigate the association between albumin-corrected anion gap (AG) (ACAG) levels and the risk of acute kidney injury (AKI) in intensive care unit (ICU) patients. METHODS: The ICU patients of this retrospective cohort study were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database between 2008 and 2019. ACAG = AG + {4.4 - [albumin (g/dl)]} × 2.5. The incidence of AKI was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) definition. The logistic regression model was used to evaluate the association between ACAG levels and the risk of AKI. Subgroup analyses were applied based on age, gender, mechanical ventilation, vasopressors, the Charlson comorbidity index (CCI), and the Simplified Acute Physiology Score II (SAPS II). RESULTS: Totally, 5586 patients were enrolled, of which 1929 patients (34.53%) occurred AKI. The higher levels of ACAG were associated with the risk of AKI in ICU patients, with the odds ratio (OR) value being 1.23 [95% confidence interval (CI): 1.22-1.24, P = 0.005] in ACAG level between 16.5 and 19.5, and OR value being 1.20 (95% CI 1.16-1.24, P = 0.016) in ACAG level > 19.5. A higher ACAG level was associated with a higher risk of AKI in ICU patients aged < 65 years, in ICU patients of female gender, in ICU patients who used mechanical ventilation, in ICU patients who did not use vasopressors, in patients without cardiogenic shock, and in ICU patients with CCI ≥ 2, and SAPS II > 31 (all P < 0.05). CONCLUSION: There is an association between ACAG level and the risk of AKI in ICU patients. A higher ACAG value in ICU patients should therefore receive more attention.

Diagnostic value of the combination of DAPK methylation in urinary sediment and B ultrasound for recurrent urinary bladder cancer.

BACKGROUND: Urinary bladder cancer (UBC) is the most common malignancy affecting the urinary system. This study aimed to investigate the diagnostic value of combining DAPK methylation in urinary sediment and B ultrasound in the detection of recurrent UBC. METHODS: A total of 1021 cases with primary UBC who underwent electrocision of bladder tumor through urethra were included in this study and followed up. Various parameters including B ultrasound, DAPK methylation in urinary sediment, examination of exfoliated cells in the urine, and cystoscopy were performed. The data collected was analyzed using the Kappa test, and receiver operating characteristic (ROC) curve was constructed to assess the diagnostic role in recurrent UBC. RESULTS: Among the 1021 patients, 115 patients experienced recurrence confirmed by cystoscopy and biopsy within two years and were excluded from the study, resulting in an effective sample size of 906 primary UBC cases. The results of cystoscopy showed agreement with B ultrasound (Kappa = 0.785, P < 0.05), as well as with DAPK methylation in urinary sediment, and the combination of B ultrasound and DAPK methylation (Kappa = 0.517, P < 0.05, Kappa = 0.593, P < 0.05). The combination of B ultrasound with DAPK methylation yielded an area under the curve of 0.922, with a sensitivity of 92.86%, specificity of 91.63%, and a negative predictive value of 99.4%, suggesting that a negative result indicates a low risk of recurrence. CONCLUSION: The combination of DAPK methylation in urinary sediment with B ultrasound demonstrates high diagnostic performance for recurrent UBC.

SKA3 is a prognostic biomarker and associated with immune infiltration in bladder cancer.

BACKGROUND: Spindle and kinetochore­associated complex subunit 3 (SKA3) has recently been considered a key regulator of carcinogenesis. However, the connection between SKA3 and immune cell infiltration remains unknown. METHODS: The current study investigated the expression mode, prognostic effect, and functional role of SKA3 in different tumors, particularly bladder cancer using numerous databases, comprising TIMER, GEPIA, HPA, UALCAN, PrognoScan, and Kaplan-Meier Plotter. Differentially expressed gene and enrichment analyses were implemented on SKA3 using R packages "edgR" and "clusterProfiler". Immunohistochemistry was further used to validate the expression of SKA3 gene in bladder cancer. Following that, the relevance of SKA3 expression to immune infiltration level in bladder cancer was evaluated using TIMER. RESULTS: Overall, the level of SKA3 expression in tumor tissue significantly increased than in normal tissue. In bladder cancer and other tumors, patients with high SKA3 expression levels had worse overall survival (OS) (p = 0.016), disease-specific survival (DSS) (p = 0.00004), and disease-free survival (DFS) (p = 0.032). Additionally, the major molecular functions for SKA3 included nuclear division, mitotic nuclear division, mitotic sister chromatid segregation, humoral immune response, and cell chemotaxis. Additionally, SKA3 expression was found to be positively associated with enhanced M2 macrophage and T helper (Th) 2 cell infiltration in bladder cancer. CONCLUSIONS: Our study implies that SKA3 contributes to M2 macrophage and Th2 cell polarization by acting as an oncogene in bladder cancer. SKA3 might be a novel biomarker for evaluating prognosis and immune infiltration in bladder cancer.

Pan-Cancer Analysis of Microfibrillar-Associated Protein 2 (MFAP2) Based on Bioinformatics and qPCR Verification.

MFAP2 has been reported to play an oncogenic role in several types of human cancers. However, the expression profile of MFAP2 in various cancers and its impact on prognosis and immune infiltration remain unclear. In this study, the mRNA expression and protein expression of MFAP2 in normal tissues, tumor cell lines, and 33 malignant tumor tissues were analyzed comprehensively using Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), and The Cancer Genome Atlas (TCGA), Oncomine and UALCAN databases, and the expression of MFAP2 in different grades and stages of cancers was assessed using Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Tumor and Immune System Interaction Database (TISIDB). In general, MFAP2 showed distinct expression in most tumor and normal tissues, closely associated with higher tumor grade, higher tumor stage, and poor survival in multiple cancers. A search of the UALCAN database and the cBioPortal database revealed that this difference in mRNA level expression could be partly attributed to abnormal DNA methylation and mutations at the genomic level. In addition, MFAP2 expression was also associated with tumor mutation burden, microsatellite instability, and neoantigens in different cancer types. More importantly, the TIMER and TISIDB databases also showed that MFAP2 levels were significantly correlated with immune infiltration abundance and immune-related gene markers, as well as ESTIMATE scores. By qPCR, MFAP2 expression was validated in four kinds of tumor tissue samples. The present study combined several databases and performed a pan-cancer analysis of the expression profile, methylation, and mutation for MFAP2 and its implications for prognosis and immune infiltration, suggesting that MFAP2 could contribute to malignant properties of many tumors. MFAP2 may be an important biomarker with prognostic value and has the potential to be a target for tumor immunotherapy.

Acetone Sensing Properties and Mechanism of Rh-Loaded WO3 Nanosheets.

WO3 nanosheets was prepared by an acidification method and the Rh catalyst was dispersed on the surface of the nanosheets with a wet impregnation method. The morphology of pristine WO3 and Rh modified WO3 nanosheets and their responses to acetone gas were studied. According to oxygen adsorption combined with TPR results, the sensing and sensitization mechanism of acetone were discussed. It was found that no visible changes in nanostructures or morphologies were observed in WO3 nanosheets with Rh, however, the sensor resistance and sensor response were greatly promoted. The basic sensitization mechanism could be caused by the electronic interaction between oxidized Rh and WO3 surface.

The inhibitory effects of soybean isoflavones on testicular cell apoptosis in mice with type 2 diabetes.

The aim of the study was to investigate the inhibitory effects of soybean isoflavones (SI) on testicular cell apoptosis in mice with type-2 diabetes, as well as any possible mechanisms of action. Thirty male C57BL/6J mice were randomly divided into the control, diabetic (model), and treatment (SI) groups (n=10 each). After treatment for 20 weeks, testicular cell apoptosis was detected and evaluated using DAPI staining. The expression and distribution of caspase-3 protein in testicular tissues was detected via immunohistochemistry, while caspase-3 mRNA expression was detected using RT-PCR. Bax and Bcl-2 protein expression was detected by western blot analysis. At week 20, DAPI staining showed that SI treatment significantly decreased testicular tissue cell apoptosis in diabetic mice. Immunohistochemical staining revealed that caspase-3 expression in the SI group was significantly reduced relative to the model group. RT-PCR showed that SI treatment significantly decreased caspase-3 mRNA expression relative to the model group. Western blot analysis revealed that SI treatment significantly decreased Bax protein expression and increased Bcl-2 protein expression (P<0.01). SI exhibited an inhibitory effect on testicular tissue cell apoptosis in mice with type 2 diabetes, with this effect possibly mediated by a decreased expression of caspase-3 and Bax and increased Bcl-2 protein expression.

Clinical evaluation of embolization of the superior vesical prostatic artery for treatment of benign prostatic hyperplasia: a single-center retrospective study.

INTRODUCTION: Non-surgical minimally invasive treatments are greatly needed for patients with symptomatic benign prostatic hyperplasia (BPH), for whom medical treatment has failed and surgery is contraindicated. This study retrospectively evaluated the efficacy and safety of super-selective prostatic artery embolization (PAE) for BPH, relative to transurethral resection of the prostate (TURP). AIM: To clinically evaluate the efficacy and safety of super-selective PAE for BPH, relative to TURP. MATERIAL AND METHODS: From February 2012 to March 2015, patients with BPH underwent selective PAE (n = 17) or TURP (control group; n = 40). Prostate volume, maximum urinary flow rate (Qmax), International Prostate Symptoms Score (IPSS), and quality of life (QoL) score were evaluated at baseline and postoperative 3, 6, and 12 months. Complications were also recorded. RESULTS: All the procedures were technically successfully. At postoperative 1 year, patients given PAE had significantly greater prostate volume (64.6 ±10.2 ml), IPSS (23.9 ±4.9), and QoL (4.1 ±0.7) compared with the control patients (42.0 ±7.5 ml, 13.1 ±3.5, and 2.1 ±0.7, respectively). The Qmax of the PAE group (9.5 ±3.7 ml/s) was significantly lower than that of the control (21.8 ±4.2 ml/s). The changes in parameters of the TURP patients relative to the preoperative baseline were significantly greater than those of the PAE group. No severe complications occurred. CONCLUSIONS: Prostatic artery embolization was demonstrated as safe and effective and may be considered an alternative treatment for BPH patients, especially for those who are not candidates for or refuse surgery.

[Risk factors of prostate cancer in urban Qingdao: a case-control study].

OBJECTIVE: To investigate the risk factors of prostate cancer in urban Qingdao and provide some theoretical evidence for the scientific prevention and treatment of the disease. METHODS: We performed a hospital-based matched case-control study in Qingdao Municipal Hospital. The cases and controls were matched in age, gender, nationality and the place of residence. All the subjects were interviewed face to face in the hospital using a questionnaire, and the data analyzed by the conditional logistic regression method. RESULTS: According to the 258 valid questionnaires collected, the prostate cancer risk was significantly higher in the cases with a family history of cancer than in those without (OR = 2.58), and so was it in the men with the first spermatorrhea at the age of < or = 15 years than in those at the age of > or = 18 years (OR = 2.27). A decreased risk of prostate cancer was found among the men with the first experience of sexual intercourse between 25 to 30 years of age (OR = 0.76). An increased risk was shown in those with sexual intercourses > or = 4 times per week before 35 years old (OR = 2.57), masturbations > or = 3 times per week (OR = 2.30) and a drinking history (alcohol > or = 150 g/d) of > or = 10 years (OR = 2.83). CONCLUSION: Positive family history of cancer, earlier age of the first spermatorrhea, sexual intercourses > or = 4 times per week before 35 years old, frequent masturbations, and heavy drinking for more than 10 years are risk factors for prostate cancer.

Inhibitors of HIV-1 attachment. Part 9: an assessment of oral prodrug approaches to improve the plasma exposure of a tetrazole-containing derivative.

7-(2H-Tetrazol-5-yl)-1H-indole 3 was found to be a potent inhibitor of HIV-1 attachment but the compound lacked oral bioavailability in rats. The cause of the low exposure was believed to be poor absorption attributed to the acidic nature of the tetrazole moiety and, in an effort to address this liability, three more lipohilic tetrazole analogs, N-acetoxymethyl 4, N-pivaloyloxymethyl 5, and N-methyl 6, were evaluated as potential oral prodrugs in rats. Prodrug 5 was ineffective in improving the plasma concentration of 3 in vivo but compound 4 provided a 15-fold enhancement of the plasma concentration of 3. Most interestingly, oral dosing of analog 6 afforded a substantial increase in the plasma concentration of the parent in rats when compared to dosing of parent. This represents a novel example of a methyl tetrazole that acts as a prodrug for a free NH tetrazole-containing compound.

Inhibitors of HIV-1 attachment. Part 8: the effect of C7-heteroaryl substitution on the potency, and in vitro and in vivo profiles of indole-based inhibitors.

As part of the SAR profiling of the indole-oxoacetic piperazinyl benzamide class of HIV-1 attachment inhibitors, substitution at the C7 position of the lead 4-fluoroindole 2 with various 5- and 6-membered heteroaryl moieties was explored. Highly potent (picomolar) inhibitors of pseudotyped HIV-1 in a primary, cell-based assay were identified and select examples were shown to possess nanomolar inhibitory activity against M- and T-tropic viruses in cell culture. These C7-heteroaryl-indole analogs maintained the ligand efficiency (LE) of 2 and were also lipophilic efficient as measured by LLE and LELP. Pharmacokinetic studies of this class of inhibitor in rats showed that several possessed substantially improved IV clearance and half-lives compared to 2. Oral exposure in the rat correlated with membrane permeability as measured in a Caco-2 assay where the highly permeable 1,2,4-oxadiazole analog 13 exhibited the highest exposure.

Inhibitors of HIV-1 attachment. Part 7: indole-7-carboxamides as potent and orally bioavailable antiviral agents.

A series of substituted carboxamides at the indole C7 position of the previously described 4-fluoro-substituted indole HIV-1 attachment inhibitor 1 was synthesized and the SAR delineated. Heteroaryl carboxamide inhibitors that exhibited pM potency in the primary cell-based assay against a pseudotype virus expressing a JRFL envelope were identified. The simple methyl amide analog 4 displayed a promising in vitro profile, with its favorable HLM stability and membrane permeability translating into favorable pharmacokinetic properties in preclinical species.

Inhibitors of HIV-1 attachment. Part 3: A preliminary survey of the effect of structural variation of the benzamide moiety on antiviral activity.

1-(4-Benzoylpiperazin-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione (1a) has been characterized as an inhibitor of HIV-1 attachment that interferes with the interaction of viral gp120 with the host cell receptor CD4. In previous studies, the effect of indole substitution pattern on antiviral activity was probed. In this Letter, the effect of structural variation of the benzamide moiety is described, a study that reveals the potential or the phenyl moiety to be replaced by five-membered heterocyclic rings and a restricted tolerance for the introduction of substituents to the phenyl ring.

Inhibitors of HIV-1 attachment. Part 2: An initial survey of indole substitution patterns.

The effects of introducing simple halogen, alkyl, and alkoxy substituents to the 4, 5, 6 and 7 positions of 1-(4-benzoylpiperazin-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione, an inhibitor of the interaction between HIV gp120 and host cell CD4 receptors, on activity in an HIV entry assay was examined. Small substituents at C-4 generally resulted in increased potency whilst substitution at C-7 was readily tolerated and uniformly produced more potent HIV entry inhibitors. Substituents deployed at C-6 and, particularly, C-5 generally produced a modest to marked weakening of potency compared to the prototype. Small alkyl substituents at N-1 exerted minimal effect on activity whilst increasing the size of the alkyl moiety led to progressively reduced inhibitory properties. These studies establish a basic understanding of the indole element of the HIV attachment inhibitor pharmacophore.

[Retroperitoneal laparoscopy combined with urethral resection for treatment of renal pelvic carcinoma].

OBJECTIVE: The purpose of this study is to explore the operation method and efficacy through retroperitoneal laparoscopy combined with urethral resection for treatment of renal pelvic carcinoma. METHODS: Total nephroureterectomy with excision of bladder cuff by retroperitoneal laparoscopy plus urethral resection was performed in 18 patients with pathologically confirmed pelvic transitional cell carcinoma (II-III, T1N0M0-T2N0M0). The operation was performed using Olympus celioscope (30 degrees or 0 degree) under general anesthesia. First, a 10 mm incision was made at the intersection of midaxillary line and superior border 2 cm from crista iliaca, then a self-made hyponome filled with 250-300 ml water was put through the small incision in order to open the retroperitoneal space, followed by getting the hyponome out and perfusing CO2 into the retroperitoneal space to make a pneumoretroperitoneum. Finally, the celioscope was put into the retroperitoneal space to operate. During the operation, electric coagulation was used to stop bleeding and the bladder was not irrigated. RESULTS: The operation was successfully performed in 18 patients without any complication. The operative time ranged from 150 to 190 min with a mean of 160 min. The hospital stay after operation was 7 to 10 days. There was no tumor recurrence or metastasis or implantation in all these patients after follow-up of 1-19 months. CONCLUSION: Compared with regular operation mode, retroperitoneal laparoscopy plus urethral resection for treatment of renal pelvic carcinoma is a minimally invasive treatment with less bleeding and quick recovery.

Photocycloaddition of four-carbon-tethered pyridones. Intramolecular hydrogen bonding and facilitated amide hydrolysis by a proximal secondary alcohol.

Four-carbon-tethered pyridones undergo photocycloaddition to give exclusively trans-[4 + 4] products. The presence of a tether alcohol engenders a solvent-dependent diastereoselectivity for the cycloaddition by intramolecular hydrogen bonding to the adjacent pyridone. Following cycloaddition, the alcohol can deliver a carbonyl group to the proximal, hindered amide nitrogen, leading to a very facile amide hydrolysis.