Lysine Methyltransferase 5A Promotes the Progression of Growth Hormone Pituitary Neuroendocrine Tumors through the Wnt/ß-Catenin Signaling Pathway.

INTRODUCTION: Growth hormone (GH) secreting pituitary adenoma is considered one of the most harmful types of Pituitary Neuroendocrine Tumors (PitNETs). Our previous research has found that high expression of Lysine methyltransferase 5A (KMT5A) is closely related to the proliferation of PitNETs. The aim of this study was to investigate the role and molecular mechanism of KMT5A in the progression of GH PitNETs. METHODS: Immunohistochemistry, qRT-PCR, and Western blot (WB) were used to assess the expression levels of KMT5A in human normal pituitary and GH PitNETs, as well as in rat normal pituitary and GH3 cells. Additionally, we utilized RNA interference technology and treatment with a selective KMT5A inhibitor to decrease the expression of KMT5A in GH3 cells. CCK-8, EdU, flow cytometry (FCM), clone formation, and WB assay were further employed to evaluate the impact of KMT5A on the proliferation of GH3 cells in vitro. A xenograft model was established to evaluate the role of KMT5A in GH PitNETs progression in vivo. RESULTS: KMT5A was highly expressed in GH PitNETs and GH3 cells. Moreover, the reduction of KMT5A expression led to inhibited growth of GH PitNETs and increased apoptosis of tumor cells, as indicated by the findings from CCK-8, EdU, clone formation, and FCM assays. Additionally, WB analysis identified the Wnt/ß-catenin signaling pathway as a potential mechanism through which KMT5A promotes GH PitNETs progression. CONCLUSION: Our research suggests that KMT5A may facilitate the progression of GH PitNETs via the Wnt/ß-catenin signaling pathway. Therefore, KMT5A may serve as a potential therapeutic target and molecular biomarker for GH PitNETs.

Optimizing oil spill emergency logistics: a time-varying multi-resource collaborative scheduling model.

Emergency resource scheduling is at the heart of the response to an oil spill, as it lays the foundation for all other emergency operations. Extant studies address the dynamicity inherent to these operations primarily by modeling a dynamic network flow with static data, which is not applicable to continuously changing conditions resulting from oil film movement. To enhance the responsiveness and cost-efficiency of the response to oil spills, this paper takes a novel approach and formulates a multi-objective location-routing model for multi-resource collaborative scheduling, namely, harnessing time-varying parameters rather than static data to model real-time changes in the demand for emergency resources and the transportation network. Additionally, the model considers various operational factors, including the transportation of multiple resources in the order of operating procedures; the coordination of split delivery with the consumption of emergency resources; and the matching of multiple resources with suitable vehicles. To solve the proposed model, a hybrid heuristic algorithm of PSO-PGSA is developed, which utilizes particle swarm optimization (PSO) to search widely for non-dominated solutions. The algorithm then makes use of the plant growth simulation algorithm (PGSA) to find the more effective vehicle routes based on the obtained solutions. Finally, a numerical analysis is used to illustrate the practical capabilities of the developed model and solution strategies. Most significantly, our work not only validates the methodology proposed here but also underlines the importance of incorporating the features of an oil spill emergency response into emergency logistics in general.

Individual risk and prognostic value prediction by machine learning for distant metastasis in pulmonary sarcomatoid carcinoma: a large cohort study based on the SEER database and the Chinese population.

Background: This study aimed to develop diagnostic and prognostic models for patients with pulmonary sarcomatoid carcinoma (PSC) and distant metastasis (DM). Methods: Patients from the Surveillance, Epidemiology, and End Results (SEER) database were divided into a training set and internal test set at a ratio of 7 to 3, while those from the Chinese hospital were assigned to the external test set, to develop the diagnostic model for DM. Univariate logistic regression was employed in the training set to screen for DM-related risk factors, which were included into six machine learning (ML) models. Furthermore, patients from the SEER database were randomly divided into a training set and validation set at a ratio of 7 to 3 to develop the prognostic model which predicts survival of patients PSC with DM. Univariate and multivariate Cox regression analyses have also been performed in the training set to identify independent factors, and a prognostic nomogram for cancer-specific survival (CSS) for PSC patients with DM. Results: For the diagnostic model for DM, 589 patients with PSC in the training set, 255 patients in the internal and 94 patients in the external test set were eventually enrolled. The extreme gradient boosting (XGB) algorithm performed best on the external test set with an area under the curve (AUC) of 0.821. For the prognostic model, 270 PSC patients with DM in the training and 117 patients in the test set were enrolled. The nomogram displayed precise accuracy with AUC of 0.803 for 3-month CSS and 0.869 for 6-month CSS in the test set. Conclusion: The ML model accurately identified individuals at high risk for DM who needed more careful follow-up, including appropriate preventative therapeutic strategies. The prognostic nomogram accurately predicted CSS in PSC patients with DM.

The role of GTPase-activating protein ARHGAP26 in human cancers.

Rho GTPases are molecular switches that play an important role in regulating the behavior of a variety of tumor cells. RhoA GTPase-activating protein 26 (ARHGAP26) is a GTPase-activating protein and inhibits the activity of Rho GTPases by promoting the hydrolytic ability of Rho GTPases. It also affects tumorigenesis and progression of various tumors through several methods, including formation of abnormal fusion genes and circular RNA. This review summarizes the biological functions and molecular mechanisms of ARHGAP26 in different tumors, proposes the potential clinical value of ARHGAP26 in cancer treatment, and discusses current issues that need to be addressed.

Efficacy of a Novel Exoskeletal Robot for Locomotor Rehabilitation in Stroke Patients: A Multi-center, Non-inferiority, Randomized Controlled Trial.

Objective: To investigate the efficacy and safety of a novel lower-limb exoskeletal robot, BEAR-H1 (Shenzhen Milebot Robot Technology), in the locomotor function of subacute stroke patients. Methods: The present study was approved by the ethical committee of the First Affiliated Hospital of Nanjing Medical University (No. 2019-MD-43), and registration was recorded on the Chinese Clinical Trial Registry with a unique identifier: ChiCTR2100044475. A total of 130 patients within 6 months of stroke were randomly divided into two groups: the robot group and the control group. The control group received routine training for walking, while in the robot group, BEAR-H1 lower-limb exoskeletal robot was used for locomotor training. Both groups received two sessions daily, 5 days a week for 4 weeks consecutively. Each session lasted 30 min. Before treatment, after treatment for 2 weeks, and 4 weeks, the patients were assessed based on the 6-minute walking test (6MWT), functional ambulation scale (FAC), Fugl-Meyer assessment lower-limb subscale (FMA-LE), and Vicon gait analysis. Results: After a 4-week intervention, the results of 6MWT, FMA-LE, FAC, cadence, and gait cycle in the two groups significantly improved (P < 0.05), but there was no significant difference between the two groups (P > 0.05). The ratio of stance phase to that of swing phase, swing phase symmetry ratio (SPSR), and step length symmetry ratio (SLSR) was not significantly improved after 4 weeks of training in both the groups. Further analyses revealed that the robot group exhibited potential benefits, as the point estimates of 6MWT and Δ6MWT (post-pre) at 4 weeks were higher than those in the control group. Additionally, within-group comparison showed that patients in the robot group had a significant improvement in 6MWT earlier than their counterparts in the control group. Conclusions: The rehabilitation robot in this study could improve the locomotor function of stroke patients; however, its effect was no better than conventional locomotor training.

Pharmacokinetics of Bismuth following Oral Administration of Wei Bi Mei in Healthy Chinese Volunteers.

BACKGROUND: Bismuth-containing quadruple therapy achieves higher eradication rate of Helicobacter pylori. High level of bismuth in blood may result in damage of many organs. Wei Bi Mei is a new bismuth-containing drug combining chemicals and Chinese medicine portions. The present research is to study the pharmacokinetics of bismuth to evaluate the safety and rational use of Wei Bi Mei granules. Material and Methods. Seven healthy Chinese adult subjects were enrolled in this research, which included a single-dose study and a multiple-dose study. Wei Bi Mei granules were administered orally to the subjects at corresponding time. Blood and urine were collected. All samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: For single-dose Wei Bi Mei granules administration, the mean time to peak concentration (t max) of bismuth was 2.29 ± 0.76 h, and the mean peak concentration (C max) of bismuth was 0.85 ± 0.55 ng/mL. For multiple-dose Wei Bi Mei granules administration, the C max was 2.25 ± 1.18 ng/mL at day two, and the volume of distribution (V d ) was (22.97 ± 9.82) × 103 L. The urinary excretion of bismuth was the fastest during the first two days, with a mean excretion rate of 3.84 ± 1.23 ng/h. The bismuth concentration in urine was significantly reduced at day 16. CONCLUSION: Bismuth has a washout period of approximately two months. The concentration of bismuth in blood was far less than the "safe level." Thus, Wei Bi Mei is a highly safe therapeutic medicine, with a good clinical application value. Wei Bi Mei should be recommended more widely for use in bismuth-containing quadruple therapy for the treatment of Helicobacter pylori infection.

The effect of quality of segmental bowel preparation on adenoma detection rate.

BACKGROUND: The effectiveness in surveillance colonoscopy largely depends on the quality of bowel preparation. We aimed to investigate the quality of bowel preparation segmentally and its effect on Adenoma Detection Rate (ADR) and Advanced Adenoma Detection Rate (AADR) at corresponding bowel segments. METHODS: This is a single-centered and cross-sectional study. A consecutive of 5798 patients who underwent colonoscopy examination were included. Bowel preparation was evaluated based on Bowel Bubble Scale (BBS) in general and Boston Bowel Preparation Scale (BBPS) in each segment (right side, transverse and left side of colon) and total BBPS scores. The quality of bowel preparation was correlated with ADR and AADR. RESULTS: Four thousand nine hundred forty colonoscopies (14,820 bowel segments) were included in the final analysis. In which 30.9% scored 3, 57.5% scored 2, 11.2% scored 1 and 0.4% scored 0 on basis of BBPS. For each score, ADR were 10.8, 7.7, 4.9 and 3.2%, respectively; whereas AADR were 4.5, 2.8,1.8 and 1.6% (P < 0.05). 36.9% of the colonoscopies showed presence of minimal bubbles and 34.3% with no bubble. For bowels without bubbles and with a large amount of bubbles, ADR were 28.3 and 20.0% respectively; and AADR were 13.3 and 7.1% respectively. CONCLUSIONS: Segmental bowels' cleanliness and the amount of bubbles in bowels significantly affect ADR and AADR. The better the bowel preparation at each segment is and the less bubbles in the bowel there are, the higher ADR and AADR we got. We suggest repeating colonoscopy if any segment of the bowel preparation is poor, or if there is more bubbles, even if the total score of BBPS indicates good or fair bowel preparation.

A Simple, Time-Saving Dye Staining of Proteins in Sodium Dodecyl Sulfate-Polyacrylamide Gel Using Coomassie Blue.

Most traditional post-electrophoretic processes need several hours to several days to finish the whole staining process and traditional staining solutions all contain methanol, acetic acid, or phosphoric acid, which not only produce the unpleasant smell but also cause environmental pollution. Here a fixation-free, fast protein staining method in sodium dodecyl sulfate-polyacrylamide gel electrophoresis using Coomassie blue is described. The protocol includes only staining and quick washing steps, can be completed in 0.5 h. It has a sensitivity of 10 ng. In addition, the dye stain does not contain any acid or methanol.

Efficacy and safety of using premedication with simethicone/Pronase during upper gastrointestinal endoscopy examination with sedation: A single center, prospective, single blinded, randomized controlled trial.

BACKGROUND AND AIM: To investigate the efficacy and safety of premedication with simethicone/Pronase during esophagogastroduodenoscopy (EGD) with sedation. METHODS: Six hundred and ten patients were randomly allocated to two groups based on type of premedication given. Premedication used in the control group was 10 mL lidocaine hydrochloride mucilage (LHM, N = 314) and premedication used in the intervention group was 80 mL simethicone/Pronase solution plus 10 mL lidocaine hydrochloride mucilage (SP/LHM, N = 296). EGD was done under sedation. Visibility scores, number of mucosal areas that needed cleansing, water consumption for cleansing, time taken for examination, diminutive lesions, pathological diagnosis, patients' gag reflex and oxygenation (pulse oximetry) were recorded. RESULTS: SP/LHM has significantly lower total visibility score than LHM (7.978 ± 1.526 vs 6.348 ± 1.097, P < 0.01). During the procedure, number of intragastric areas that needed cleansing and amount of water consumed were significantly less in the SP/LHM than in the LHM group (P < 0.01). In SP/LHM (P = 0.01), endoscopy procedure duration was significantly longer. Although there was no significant difference in rate of detection of diminutive lesions between LHM and SP/LHM, the endoscopist carried out more biopsies in SP/LHM. This led to a higher rate of diagnosis of atrophic gastritis (P = 0.014) and intestinal metaplasia (P = 0.024). There was no significant difference in gag reflex (P = 0.604) and oxygenation during the endoscopy procedure for either group of patients. CONCLUSION: Routine use of premedication with simethicone/Pronase should be recommended during EGD with sedation.