Association between fibrinogen/albumin ratio and arterial stiffness in patients with type 2 diabetes: A cross-sectional study.

Background: Fibrinogen albumin ratio (FAR) is significantly correlated with the severity and prognosis of cardiovascular disease (CVD). Arterial stiffness is an early lesion of CVD, but no studies have examined the correlation between arterial stiffness and FAR. This study aimed to examine the relationship between FAR and arterial stiffness in patients with type 2 diabetes (T2D), as measured by brachial-ankle pulse wave velocity (baPWV). Methods: In this cross-sectional investigation, patients with T2D were enrolled between January 2021 and April 2022. In each patient, the levels of fibrinogen and albumin in the serum, and baPWV in the serum were measured. A baPWV greater than 1800 cm/s was utilized to diagnose arterial stiffness. Results: The study included 413 T2D patients. The mean age of these participants was 52.56 ± 11.53 years, 60.8% of them were male, and 18.6% of them had arterial stiffness. There were significant differences in baPWV level and proportion of arterial stiffness (p < .001) between the four subgroups categorized by the FAR quartile. The relationships between the FAR and baPWV and arterial stiffness were significantly favorable in the overall population and subgroups of elderly men and non-elderly men (p < .01), while they were insignificant in subgroups of elderly and non-elderly women (p > .05). To investigate the correlation between the FAR and baPWV, the arterial stiffness and the FAR in male T2D patients, respectively, multivariable logistic regression analysis and multiple linear regression analysis were developed. The lnFAR and lnbaPWV had a significant relationship in the multiple linear regression analysis fully adjusted model. After adjusting for potential covariables, multivariable logistic regression analysis revealed that the FAR was independently associated with arterial stiffness [OR (95% CI), 1.075 (1.031-1.120)]. In addition, receiver operating characteristic analysis indicated that the best FAR cutoff value for detecting arterial stiffness in male T2D patients was 76.67 mg/g. Conclusion: The level of FAR had an independent and positive correlation with baPWV and arterial stiffness in male patients with T2D, but not in female patients.

Integrative Analysis of Minichromosome Maintenance Proteins and Their Prognostic Significance in Melanoma.

BACKGROUND: Minichromosome maintenance (MCM) is known for participating in cell cycle progression, as well as DNA replication. While the diverse expression patterns and prognostic values of MCMs in melanoma still remained unclear. METHODS: In the present study, the transcriptional and clinical profiles of MCMs were explored in patients with melanoma from multiple databases, including GEO, TCGA, ONCOMINE, GEPIA, UALCAN, cBioPortal, and TIMER databases. RESULTS: We found that the elevated expressions of MCM2-6 and MCM10 were significantly expressed in melanoma compared to normal skin. High mRNA levels of MCM4, MCM5, and MCM10 were closely related to worse prognosis in patients with melanoma. GSEA showed hallmark pathways were most involved in mTORC1 signaling, G2M checkpoint, E2F targets, and mitotic spindle. Furthermore, we found potential correlations between the MCM expression and the immune cell infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. CONCLUSION: Upregulated MCM gene expression in melanoma probably played a crucial part in the development and progression of melanoma. The upregulated MCM4/5/10 expressions could be used as potential prognostic markers to improve the poor outcome and prognostic accuracy in patients with melanoma. Our study might shed light on the selection of prognostic biomarkers as well as the underlying molecular pathogenesis of melanoma.

SphK1-targeted miR-6784 inhibits functions of skin squamous cell carcinoma cells.

Sphingosine kinase 1 (SphK1) is overexpressed in skin squamous cell carcinoma (SCC). It has emerged as a novel therapeutic oncotarget. The current study identified a novel SphK1-targeting microRNA, microRNA-6784 (miR-6784). Here, we show that miR-6784 is located at the cytoplasm of A431 skin SCC cells. It directly binds to SphK1 mRNA. Ectopic overexpression of miR-6784 inhibited SphK1 3'-untranslated region (UTR) luciferase activity and downregulated its expression. Moreover, miR-6784 overexpression caused ceramide accumulation in skin SCC cells. Functional studies in established (A431 and SCC9) and primary skin SCC cells revealed that miR-6784 overexpression inhibited cell viability, proliferation, migration, and invasion. It also simultaneously provoked apoptosis activation. Conversely, miR-6784 silencing by antagomiR-6784 induced SphK1 elevation and augmented A431 cell proliferation, migration, and invasion. miR-6784 overexpression-induced anti-A431 cell activity was inhibited by the expression of an UTR-null SphK1 construct. CRISPR/Cas9-induced SphK1 knockout inhibited A431 cell growth. Importantly, miR-6784 was completely ineffective when treating SphK1-knockout A431 cells. Collectively, miR-6784 silences SphK1 and inhibits skin SCC cell progression.

virB11 gene potentially involves in ATP metabolism to provide energy in H. pylori infection.

Helicobater pylori (H. pylori) is the most important bacteria known to be associated with various gastroduodenal diseases. virB11 gene is a structural gene of tfs3a genes cluster in the plasticity region of H. pylori. In this study, the structure and biology of virB11 gene were analyzed and elucidated with bioinformatics analysis. After cloning, expression and purification, VirB11 protein was generated for the cytotoxicity to GES-1 cells and the anti-VirB11 protein antibody production for localization and interaction proteins analysis. The results showed that VirB11 protein is a hydrophilic protein, mainly locates in cell membrane. IL-8 productions from GES-1 cells co-culture with VirB11 protein were increased gradually with time (p < 0.001). The interaction proteins of VirB11 protein were F0F1 ATP synthase subunit alpha, ATP synthase subunit beta and isocitrate dehydrogenase. We demonstrate that VirB11 protein possesses cytotoxicity and potentially plays important roles in ATP metabolism to provide energy in the course of H. pylori infection.

miRNA-221 promotes cutaneous squamous cell carcinoma progression by targeting PTEN.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is a common type of skin malignancy. MicroRNA-221 (miRNA-221) is a critical non-coding RNA in tumor initiation and progression. However, the molecular mechanisms of miRNA-221 in the development of CSCC remain unknown. This study investigated the expression of miRNA-221 in CSCC and its potential tumor biological functions. METHODS: MTT assay, colony assay, PCR, and Western blot were adopted. RESULTS: In this study, miRNA-221 expression was significantly higher in CSCC tissues and cell lines than in normal tissues and cells (P < 0.05). Further functional experiments indicated that miRNA-221 knockdown inhibited the proliferation and cell cycle, while upregulation of miRNA-221 presented the opposite role. The dual reporter gene assays indicated that PTEN is a direct target gene of miRNA-221. PTEN protein or mRNA levels were decreased after the cells were transfected with miR-221 mimics. CONCLUSIONS: Taken together, the obtained results indicated that miR-221 plays an oncogenic function in CSCC by targeting PTEN and further suggest that miR-221 may be a potential target for CSCC diagnosis and treatment.

Reduced glutathione and glutathione disulfide in the blood of glucose-6-phosphate dehydrogenase-deficient newborns.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency. METHODS: The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard. RESULTS: G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 µmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 µmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P < 0.001 for DBS samples plus sodium citrate that were examined the first day after preparation, there were no significant differences in the mean GSH concentration and GSH/GSSG ratio between the G6PD deficiency-positive and negative groups when examined three days after sample preparation. CONCLUSION: The concentration of GSH and the ratio of GSH/GSSG in blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.

Association of plasminogen activator inhibitor-1 and vitamin D receptor expression with the risk of keloid disease in a Chinese population.

Keloid disease (KD) is a benign fibroproliferative scarring condition of unknown etiopathogenesis. Plasminogen activator inhibitor-1 (PAI-1) and vitamin D receptor (VDR) have been shown to play important roles in the progression of tissue fibrosis; therefore, both these genes are potential susceptibility genes for KD. We aimed to determine whether the gene expression levels of PAI-1 and VDR are altered in Chinese KD patients. We measured the expression of PAI and VDR in human peripheral blood lymphocytes in 236 patients with keloid and 219 age- and sex-matched healthy controls by quantitative real-time polymerase chain reaction. We found that PAI-1 expression in peripheral blood lymphocytes was significantly higher in patients with KD than in control individuals (p < 0.0001), while VDR expression was significantly lower in KD patients than in control individuals (p < 0.0001). High levels of PAI-1 and low levels of VDR expression were significantly associated with an increased risk for KD. PAI-1 and VDR might play important roles in keloid development. Gene expression levels of PAI-1 and VDR may, therefore, be used as potential markers for the prediction of keloid development after scarring.

Cloning of mating-type gene MAT1-1 from the caterpillar medicinal mushroom, Cordyceps militaris (Ascomycetes) using TAIL-PCR technology.

Cordyceps militaris and Ophiocordyceps sinensis (syn. Cordyceps sinensis), 2 well-known traditional Chinese medicines, contain the same bioactive components and share a similar developmental process. In this study, one C. militaris strain preserved in our laboratory was proven to be a MAT1 mating-type strain using a polymerase chain reaction-based mating-type assay. A 5000-bp nucleotide sequence of the mating-type MAT1-1 from C. militaris was amplified by thermal asymmetric interlaced polymerase chain reaction, but genes within the mating-type MAT1-2 remain undetectable. Sequence analysis shows that the mating-type gene MAT1-1 idiomorph contains 2 genes, MAT1-1-1 and MAT1-1-2. The MAT1-1-1 gene consists of 1480-bp nucleotides that encode 456 amino acids and contain the conserved a-box domain interrupted by 2 introns; the MAT1-1-2 gene consists of 1066 nucleotides that encode 377 amino acids interrupted by one intron. The intervening distance between MAT1-1-1 and MAT1-1-2 is 778 bp. The C. militaris MAT1-1 idiomorph organization is the same as that of Cordyceps takaomontana. The MAT1-1 mating-type idiomorph of both Cordyceps species lacks the MAT1-1-3 gene, which is typically present in Pyrenomycetes. These studies provide some insights for further study of the morphological development of C. militaris and will eventually benefit the domestication of O. sinensis.

[Blood spot carnitine and acylcarnitine in newborn to adolescence: measured by tandem mass spectrometry].

OBJECTIVE: To determine the levels of blood spot carnitine and acylcarnitine in children aged 0-15 years by tandem mass spectrometry, offer basic data for evaluating carnitine nutritional status and diagnosing metabolic diseases of organic acid and fatty acid. METHODS: The concentration of carnitine and acylcarnitines were measured in blood spot by tandem mass spectrometry using underivatized samples. The samples included those from 1376 perinatal neonates, 49 neonates above 1 week of life, 64 children aged up to 1 year and 401 children aged 1 year to 15 years. A few premature infants and low birth weight infants were involved in perinatal neonates without selection. Other samples were taken from mainly outdoor patients for little surgical preoperative examination. Patients suffering from fever, diarrhea, liver disease, severe fat-metabolic diseases were excluded from this study. RESULTS: The concentrations of carnitine (C(0)); short-chain acylcarnitines (SC-AC), including acetyl (C(2)), propionyl (C(3)), malonyl (C(3)DC), butyryl (C(4)), methylmalonyl (C(4)DC), isovaleryl (C(5)), glutaryl (C(5)DC); middle-chain acylcarnitines (MC-AC), including hexanoyl (C(6)), hexanediol (C(6)DC), octylenoyl (C(8:1)), octanoyl (C(8)), decadienoyl (C(10:2)), decanoyl (C(10:1)), decanoyl (C(10)); total carnitine and acylcarnitines (TCAC)were lower in neonate, highest in 1-3 months of age, higher in 6-12 months of age, and kept at the same level between 2 and 15 years of age. The concentrations of total long-chain acylcarnitines (LC-AC), including lauren (C(12:1)), lauroyl (C(12)), tetradecanoyl (C(14:1)), tetradecanoyl (C(14)), 3-hydroxy-tetradecanoyl (C(14)OH), hexadecenoyl (C(16:1)), hexadecanoyl (C(16)), 3-hydroxy-hexadecanoyl (C(16)OH), 3-hydroxy-hexadecanoyl (C(16:1)OH), octadecadienoyl (C(18:2)), octadecenoyl (C(18:1)), octadecanoyl (C(18)), 3-hydroxy-octadecenoyl (C(18:1)OH), and 3-hydroxy-octadecanoyl (C(18)OH) were the highest in neonate, decreased gradually, and kept the same level between 2 and 15 years of age. The concentrations of C(0) (23.387 ± 7.702) µmol/L, (30.064 ± 8.252) µmol/L, (25.021 ± 6.630) µmol/L, of LC-AC (4.998 ± 1.557) µmol/L, (2.854 ± 0.821) µmol/L, (2.459 ± 0.553) µmol/L, of TCAC (43.497 ± 12.632) µmol/L, (49.013 ± 12.497) µmol/L, (39.656 ± 9.257) µmol/L were significantly different among the groups of neonate, up to 1 year and above 1 year (P < 0.01). The concentrations of C(0) (24.115 ± 7.715) µmol/L and TCAC (43.65 ± 5.252) µmol/L in perinatal male neonates were higher than that (22.696 ± 7.246) µmol/L, TCAC (41.90 ± 5.038) µmol/L in female neonates. The C(0)/TCAC ratio of neonatal group (54.0% ± 7.1%) was significantly lower than that in the children group (62.1% ± 6.1%, P < 0.05), LC-AC/TCAC (33.5% ± 6.0%), MC-AC/TCAC (1.3% ± 0.3%), SC-AC/TCAC (11.6% ± 2.5%)ratios of neonatal group were higher than that of children group respectively (30.1% ± 4.9%; 0.9% ± 0.6%; 6.5% ± 2.3%, P < 0.05). CONCLUSIONS: Concentrations and profiles of carnitine and acylcarnitines change significantly during the first year of life, the age should be considered as a factor when evaluating carnitine nutritional status and diagnosing metabolic diseases of organic acid and fatty acid. Concentrations of carnitine and acylcarnitines were a little higher in male neonates than in female.

[Value of ultrasonography in the diagnosis and differential diagnosis of testicular tumor].

OBJECTIVE: To evaluate ultrasonography in the diagnosis and differential diagnosis of testicular tumor. METHODS: Ultrasound findings and post-operation pathological results were retrospectively studied in 172 men with testicular mass 1998 to 2005. RESULTS: Of the total number, 50 cases were testicular hematoma, 13 testicular cyst, 26 testicular inflammatory node, 25 testicular tuberculosis and 58 testicular tumor. Among 59 testicular tumor cases, 50 were germ cell tumor (including 41 cases of seminoma and 9 cases of nonseminoma germ cell tumor), 6 were non-germ cell tumor and 3 were secondary tumor. The sonographic features of typical seminoma, teratomas, epidemic cyst, interstitial cell tumor and malignant lymphoma were obvious. CONCLUSION: Ultrasonography, contributive to the preliminary diagnosis and differential diagnosis of testicular tumor and capable of evidence for further treatment, can be the first choice in medical imaging for the diagnosis of testicular tumors.

[Omission factors in detecting early stage prostate cancer by TRUS needle biopsy].

OBJECTIVE: To analyze and reduce the omission factors in detecting early stage prostate cancer by TRUS needle biopsy, and to improve the diagnosis of the disease. METHODS: A total of 80 benign prostatic hyperplasia patients suspected of prostatic carcinoma underwent TRUS sextant biopsies. The pathological results being negative, the patients received transurethral resection of the prostate (TURP). RESULTS: After TURP, 25 cases were pathologically diagnosed as prostate cancer, with an omission rate of 31.25% (25/80). Of the diagnosed cancer patients, 10 were treated by radical perineum prostatectomy, 8 by surgical castration, and 7 by medical castration. CONCLUSION: Some tumors may fail to be detected by TRUS needle biopsy. Serial or multi-core needle biopsies can decrease the omission rate in the diagnosis of organ confined cancer.