Value of endoscopic grading of gastroesophageal flap valve in gastroesophageal reflux disease.

OBJECTIVE: To investigate the significance of endoscopic grading (Hill's classification) of gastroesophageal flap valve (GEFV) in the examination of patients with gastroesophageal reflux disease (GERD). METHODS: One hundred and sixty-two patients undergoing gastroscopy in the Department of Gastroenterology, Xingyi People's Hospital between Apr. 2022 and Sept. 2022 were selected by convenient sampling, and data such as GEFV grade, and findings of esophageal high-resolution manometry (HRM) and esophageal 24-h pH/impedance reflux monitoring, and Los Angeles (LA) classification of reflux esophagitis (RE) were collected and compared. RESULTS: Statistically significant differences in age (F = 9.711, P < 0.001) and hiatal hernia (χ = 35.729, P < 0.001) were observed in patients with different GEFV grades. The resting LES pressures were 12.12 ± 2.79, 10.73 ± 2.68, 9.70 ± 2.29, and 8.20 ± 2.77 mmHg (F = 4.571, P < 0.001) and LES lengths were 3.30 ± 0.70, 3.16 ± 0.68, 2.35 ± 0.83, and 2.45 ± 0.62 (F = 3.789, P = 0.011), respectively, in patients with GEFV grades I-IV. DeMeester score (Z = 5.452, P < 0.001), AET4 (Z = 5.614, P < 0.001), acid reflux score (upright) (Z = 7.452, P < 0.001), weak acid reflux score (upright) (Z = 3.121, P = 0.038), liquid reflux score (upright) (Z = 3.321, P = 0.031), acid reflux score (supine) (Z = 6.462, P < 0.001), mixed reflux score (supine) (Z = 3.324, P = 0.031), gas reflux score (supine) (Z = 3.521, P = 0.024) were different in patients with different GEFV grades, with statistically significant differences. Pearson correlation analysis revealed a positive correlation between RE grade and LA classification of GERD (r = 0.662, P < 0.001), and the severity of RE increased gradually with the increase of the Hill grades of GEFV. CONCLUSION: The Hill grade of GEFV is related to age, hiatal hernia, LES pressure, and the consequent development and severity of acid reflux and RE. Evaluation of esophageal motility and reflux based on the Hill grade of GEFV is of significance for the diagnosis and treatment of GERD.

Sublethal effects of niclosamide on the aquatic snail Pomacea canaliculata.

Pomacea canaliculata is a malignant invasive aquatic snail found worldwide, and niclosamide (NS) is one of the primary agents used for its control. NS applied to water will exist in non-lethal concentrations for some time due to degradation or water exchange, thus resulting in sublethal effects on environmental organisms. To identify sublethal effects of NS on Pomacea canaliculata, we studied the aspects of histopathology, oxygen-nitrogen ratio (RO∶N), enzyme activity determination, and gene expression. After LC30 NS treatment (0.310 g/L), many muscle fibers of the feet degenerated and some acinar vesicles of the hepatopancreas collapsed and dissolved. The oxygen-nitrogen ratio (RO∶N) decreased significantly from 15.0494 to 11.5183, indicating that NS had changed the metabolic mode of Pomacea canaliculata and shifted it primarily to protein catabolism. Transcriptome analysis identified the sublethal effects of LC30 NS on the snails at the transcriptional level. 386, 322, and 583 differentially expressed genes (DEGs) were identified in the hepatopancreas, gills, and feet, respectively. GO (Gene Ontology) functional analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotations showed that DEGs in the hepatopancreas were mainly enriched for sugar metabolism, protein biosynthesis, immune response, and amino acid metabolism functional categories; DEGs in the gills were mainly enriched for ion transport and amino acid metabolism; DEGs in the feet were mainly enriched for transmembrane transport and inositol biosynthesis. In the future, we will perform functional validation of key genes to further explain the molecular mechanism of sublethal effects.

Early Diagnosis and Prediction of Death Risk in Patients with Sepsis by Combined Detection of Serum PCT, BNP, Lactic Acid, and Apache II Score.

In order to investigate the expression levels of procalcitonin (PCT), B-type brain natriuretic peptide (BNP), and lactic acid (Lac) in serum of patients with sepsis, a retrospective analysis is conducted. 80 sepsis patients admitted to the ICU of our hospital from January 2019 to June 2020 are selected, and the application value of these factors combined with Apache II score in early diagnosis and prediction of death risk is analyzed. All patients are classified into survival group (n = 57) and death group (n = 23), and examined by blood routine. Lac, PCT, and BNP, and the serum PCT, BNP, and Lac levels were compared between the nonsepsis group and the control group. Furthermore, Acute Physiology and Chronic Health Status scoring System II (Apache II) is applied to evaluate the score difference between the sepsis group and the control group. The ROC curve demonstrates that PCT, BNP, and Lac combined with Apache II score can obtain high value for early diagnosis of sepsis. Compared with nonsepsis patients, the scores of serum Lac, PCT, and BNP and Apache II are significantly higher in sepsis patients. It is clearly evident that the combined detection of those indicators is valuable for early diagnosis and prediction of death, and will be suitable for widespread clinical application.

The relationship between BSP mRNA expression and 25(OH)D/OPG in peripheral blood of newly diagnosed T2DM patients with different bone mass.

INTRODUCTION: The objective of the study was to detect the levels of osteoprotegerin (OPG) and 25-hydroxyvitamin D [25(OH)D], as well as the expression of bone sialoprotein (BSP) mRNA, in the peripheral blood of patients with newly diagnosed type 2 diabetes mellitus (T2DM) under different bone mass conditions, and to explore its role and significance in the development process of T2DM combined with osteoporosis (OP). MATERIAL AND METHODS: A total of 225 patients hospitalised in the Endocrinology Department and General Department from May 2017 to May 2018 were enrolled and categorised into five groups: the pure T2DM group (group A, 45 patients), the bone mass reduction group (group B, 45 patients), the T2DM + bone mass reduction group (group C, 45 patients), the OP group (group D, 45 patients), and the T2DM + OP group (group E, 45 patients); meanwhile, age-matched healthy subjects undergoing physical examination in our hospital were collected as the normal control group (group NC, 45 cases). Logistic regression analysis was used to analyse the influencing factors of bone mass in patients with T2DM. RESULTS: Compared with group B, the expression levels of glycated haemoglobin (HbA1c), 25(OH)D, N-terminal propeptide of type I procollagen (PINP), fasting plasma glucose (FPG), fasting plasma insulin (FINS), high-density lipoprotein cholesterol (HDL-C), and BSP mRNA were significantly increased while OPG and b-collagen degradation products (b-CTX) were significantly decreased in group A. CONCLUSION: The expression of BSP mRNA and the decrease of 25(OH)D and OPG in peripheral blood may participate in the development of diabetes and osteoporosis.

Purinostat Mesylate Is a Uniquely Potent and Selective Inhibitor of HDACs for the Treatment of BCR-ABL-Induced B-Cell Acute Lymphoblastic Leukemia.

PURPOSE: This study was to perform preclinical evaluation of a novel class I and IIb HDAC-selective inhibitor, purinostat mesylate, for the treatment of Ph+ B-cell acute lymphoblastic leukemia (B-ALL). EXPERIMENTAL DESIGN: Biochemical assays were used to test enzymatic activity inhibition of purinostat mesylate. Ph+ leukemic cell lines and patient cells were used to evaluate purinostat mesylate activity in vitro. BL-2 secondary transplantation Ph+ B-ALL mouse model was used to validate its efficacy, mechanism, and pharmacokinetics properties in vivo. BCR-ABL(T315I)-induced primary B-ALL mouse model and PDX mouse model derived from relapsed Ph+ B-ALL patient post TKI treatment were used to determine the antitumor effect of purinostat mesylate for refractory or relapsed Ph+ B-ALL. Long-term toxicity and hERG blockade assays were used to safety evaluation of purinostat mesylate. RESULTS: Purinostat mesylate, a class I and IIb HDAC highly selective inhibitor, exhibited robust antitumor activity in hematologic cancers. Purinostat mesylate at low nanomolar concentration induced apoptosis, and downregulated BCR-ABL and c-MYC expression in Ph+ leukemia cell lines and primary Ph+ B-ALL cells from relapsed patients. Purinostat mesylate efficiently attenuated Ph+ B-ALL progression and significantly prolonged the survival both in BL-2 secondary transplantation model with clinical patient symptoms of Ph+ B-ALL, BCR-ABL(T315I)-induced primary B-ALL mouse model, and PDX model derived from patients with relapsed Ph+ B-ALL post TKI treatment. In addition, purinostat mesylate possesses favorable pharmacokinetics and low toxicity properties. CONCLUSIONS: Purinostat mesylate provides a new therapeutic strategy for patients with Ph+ B-ALL, including those who relapse after TKI treatment.

Down-regulation of C12orf59 is associated with a poor prognosis and VHL mutations in renal cell carcinoma.

C12orf59 is newly identified gene in kidney. However, the relation of C12orf59 expression and clinic features is unknown. Here, our study showed that C12orf59 was broadly expressed in normal human tissues with high expression levels in kidney while its expression is beyond detectable in a panel of cancer cell lines. C12orf59 expression in RCC was significantly decreased compared with corresponding adjacent noncancerous tissues (P < 0.01). The decreased C12orf59 expression was correlated with lymph node status (P < 0.05), distant metastases (P < 0.05), poor survival (P < 0.001) (HR 3.00; 95% CI, 1.29-7.53), VHL non-sense mutations or frame-shift mutations (P < 0.01), and UMPP gene non-sense mutations or frame-shift mutations (P = 0.01). Thus, we propose that the decreased C12orf59 expression status is a prognostic biomarker of ccRCC and cooperates with the loss of VHL all the while promoting renal carcinogenesis.

Downregulated ECRG4 is associated with poor prognosis in renal cell cancer and is regulated by promoter DNA methylation.

Esophageal cancer-related gene 4 (ECRG4) has been proposed as a putative tumor suppressor gene in several tumors. However, the role and regulation of ECRG4 in the pathogenesis of human renal cancer remain largely unknown. Our current study revealed that expression of ECRG4 is downregulated in renal cell lines and renal cancer tissues. ECRG4 expression was significantly associated with histological grade of tumors (p < 0.001), primary tumor stage (p = 0.017), and distant metastasis (p = 0.017). Low expression of ECRG4 was an independent prognostic indicator for survival of renal cancer patients. Silencing of ECRG4 expression in renal cell lines was associated with its promoter methylation. Moreover, ectopic expression of ECRG4 markedly inhibited cell proliferation and invasion in renal cancer cell lines. These results indicated that ECRG4 is frequently silenced by the methylation of promoter in renal cell cancers. ECRG4 may be a tumor suppressor in renal cancer and serve as a prognostic marker.

miR-362-3p targets nemo-like kinase and functions as a tumor suppressor in renal cancer cells.

MicroRNAs (miRNAs) have been demonstrated to exhibit abnormal expression patterns in various types of human cancer. The aim of the present study was to identify a novel tumor suppressor microRNA (miR) and investigate its physiological function and mechanism in renal cell carcinoma (RCC). The expression levels of miRNA (miR)­362­3p expres were measured in 47 pairs of RCC and adjacent normal tissue samples, using reverse transcription-quantitative polymerase chain reaction analysis. In addition, miR­362­3p was transfected into renal cancer cells to investigate its role in the regulation of cell proliferation, migration, invasion, apoptosis and cell cycle. Identification of the target gene of miR­362­3p was performed using luciferase reporter assays and western blot analyses. The results demonstrated that the expression levels of miR­362­3p were downregulated in the RCC tissue samples, compared with the adjacent normal tissue samples. The upregulation of miR­362­3p using a synthesized mimic suppressed the proliferation, migration and invasion of the renal cancer cells, and induced cell apoptosis and G1 phase arrest. Further experiments demonstrated that the overexpression of miR­362­3p resulted in decrease expression levels of nemo-like kinase. These results suggested that miR-362-3p functions as a tumor suppressor in RCC, and may serve as a potential molecular target in the treatment of RCC.

Testis expressed 19 is a novel cancer-testis antigen expressed in bladder cancer.

Bladder cancer exhibits high mortality as a result of limited therapeutic options and a high recurrence rate. Accordingly, novel treatments such as immunotherapy have emerged as promising therapeutic modalities to prolong overall patient survival and effect a disease cure, which has renewed enthusiasm for the identification of tumor-specific target antigens. Cancer-testis (CT) antigens are recognized as ideal targets for immunotherapy because of their expression features and high immunogenicity profiles. Here, we investigate the expression pattern of a novel CT antigen, testis-expressed 19 (TEX19), in patients with bladder carcinoma and among multiple human tissues. Six bladder cancer cell lines (T24, UM-UC-3, J82, 5637, SW780, and RT4) were also analyzed for TEX19 expression. Our results reveal that TEX19 expression in normal tissue is restricted to human testis. In addition, TEX19 mRNA expression was detected in 60 % (24/40) bladder cancer samples, whereas 58.20 % (110/189) were positive for TEXT19 protein expression. Compared to low-grade tumors, TEX19 exhibited increased expression in high-grade tumors, from 53.69 to 77.14 %, respectively (P = 0.011). TEX19 was also expressed in all six bladder cancer cell lines. Together, our findings suggest that TEX19 represents a novel CT gene and might play a role in the progression of bladder cancer and that this gene therefore provides a potential target for immunotherapy treatment strategies against bladder cancer.