Enhanced Runge-Kutta-driven feature selection model for early detection of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) profoundly compromises the quality of life, with prolonged untreated cases posing a heightened risk of severe complications such as esophageal injury and esophageal carcinoma. The imperative for early diagnosis is paramount in averting progressive pathological developments. This study introduces a wrapper-based feature selection model based on the enhanced Runge Kutta algorithm (SCCRUN) and fuzzy k-nearest neighbors (FKNN) for GERD prediction, named bSCCRUN-FKNN-FS. Runge Kutta algorithm (RUN) is a metaheuristic algorithm designed based on the Runge-Kutta method. However, RUN's effectiveness in local search capabilities is insufficient, and it exhibits insufficient convergence accuracy. To enhance the convergence accuracy of RUN, spiraling communication and collaboration (SCC) is introduced. By facilitating information exchange among population individuals, SCC expands the solution search space, thereby improving convergence accuracy. The optimization capabilities of SCCRUN are experimentally validated through comparisons with classical and state-of-the-art algorithms on the IEEE CEC 2017 benchmark. Subsequently, based on SCCRUN, the bSCCRUN-FKNN-FS model is proposed. During the period from 2019 to 2023, a dataset comprising 179 cases of GERD, including 110 GERD patients and 69 healthy individuals, was collected from Zhejiang Provincial People's Hospital. This dataset was utilized to compare our proposed model against similar algorithms in order to evaluate its performance. Concurrently, it was determined that features such as the internal diameter of the esophageal hiatus during distention, esophagogastric junction diameter during distention, and external diameter of the esophageal hiatus during non-distention play crucial roles in influencing GERD prediction. Experimental findings demonstrate the outstanding performance of the proposed model, with a predictive accuracy reaching as high as 93.824 %. These results underscore the significant advantage of the proposed model in both identifying and predicting GERD patients.

Identification of hub genes within the CCL18 signaling pathway in hepatocellular carcinoma through bioinformatics analysis.

Introduction: Hepatocellular carcinoma (HCC) is an aggressive malignancy, and CCL18, a marker of M2 macrophage activation, is often associated with tumor immune suppression. However, the role of CCL18 and its signaling pathway in HCC is still limited. Our study focuses on investigating the prognostic impact of CCL18 and its signaling pathway in HCC patients and biological functions in vitro. Methods: HCC-related RNA-seq data were obtained from TCGA, ICGC, and GEO. The 6 hub genes with the highest correlation to prognosis were identified using univariate Cox and LASSO regression analysis. Multivariate Cox regression analysis was performed to assess their independent prognostic potential and a nomogram was constructed. In vitro experiments, including CCK8, EdU, RT-qPCR, western blot, and transwell assays, were conducted to investigate the biological effects of exogenous CCL18 and 6 hub genes. A core network of highly expressed proteins in the high-risk group of tumors was constructed. Immune cell infiltration was evaluated using the ESTIMATE and CIBERSORT packages. Finally, potential treatments were explored using the OncoPredict package and CAMP database. Results: We identified 6 survival-related genes (BMI1, CCR3, CDC25C, CFL1, LDHA, RAC1) within the CCL18 signaling pathway in HCC patients. A nomogram was constructed using the TCGA_LIHC cohort to predict patient survival probability. Exogenous CCL18, as well as overexpression of BMI1, CCR3, CDC25C, CFL1, LDHA, and RAC1, can promote proliferation, migration, invasion, stemness, and increased expression of PD-L1 protein in LM3 and MHCC-97H cell lines. In the high-risk group of patients from the TCGA_LIHC cohort, immune suppression was observed, with a strong correlation to 21 immune-related genes and suppressive immune cells. Conclusion: Exogenous CCL18 promotes LM3 and MHCC-97H cells proliferation, migration, invasion, stemness, and immune evasion. The high expression of BMI1, CCR3, CDC25C, CFL1, LDHA, and RAC1 can serve as a biomarkers for immune evasion in HCC.

Heat-shock protein 90α protects NME1 against degradation and suppresses metastasis of breast cancer.

BACKGROUND: NME1 has been exploited as a potential translational target for decades. Substantial efforts have been made to upregulate the expression of NME1 and restore its anti-metastasis function in metastatic cancer. METHODS: Cycloheximide (CHX) chase assay was used to measure the steady-state protein stability of NME1 and HSP90α. The NME1-associating proteins were identified by immunoprecipitation combined with mass spectrometric analysis. Gene knockdown and overexpression were employed to examine the impact of HSP90AA1 on intracellular NME1 degradation. The motility and invasiveness of breast cancer cells were examined in vitro using wound healing and transwell invasion assays. The orthotopic spontaneous metastasis and intra-venous experimental metastasis assays were used to test the formation of metastasis in vivo, respectively. RESULTS: HSP90α interacts with NME1 and increases NME1 lifetime by impeding its ubiquitin-proteasome-mediated degradation. HSP90α overexpression significantly inhibits the metastatic potential of breast cancer cells in vitro and in vivo. A novel cell-permeable peptide, OPT22 successfully mimics the HSP90α function and prolongs the life span of endogenous NME1, resulting in reduced metastasis of breast cancer. CONCLUSION: These results not only reveal a new mechanism of NME1 degradation but also pave the way for the development of new and effective approaches to metastatic cancer therapy.

Assessment of laparoscopic intracorporeal intestinal anastomosis training using simulation-based 3D printed models: exploring surgical performance and learning curves.

BACKGROUND AND AIMS: Intestinal anastomosis is a clinical procedure widely used to reconstruct the digestive tract, but authentic laparoscopic intracorporeal intestinal anastomosis (LIIA) models are lacking. However, three-dimensional (3D) printing can enable authentic and reusable models. In this paper, a novel cost-effective 3D-printing training model of LIIA is designed and the authenticity and validity of the model are tested. METHODS: A fused deposition modeling 3D printing and an assembled lab model were built to test LIIA. Fifteen surgeons were required to perform LIIA, and their operation score and time were recorded and analyzed. Five experts were invited to assess the face and content validity of the models. A study was also performed to further evaluate and validate the learning curve of surgeons. RESULTS: The difference in modified anastomosis objective structured assessment of technical skills (MAOSATS) scores between the expert, intermediate, and novice groups were significant (64.1±1.8: 48.5±1.7: 29.5±3.1, P <0.001). In addition, the operation time of the procedure was statistically different for all three groups (21.5±1.9: 30.6±2.8:70.7±4.0, P<0.001 ). The five experts rated the face and content validity of the model very highly, with the median being four out of five. Surgeons who underwent repeated training programs showed improved surgical performance. After eight training sessions, the novices' performance was similar to that of the average level of untrained intermediates, while the operation scores of the intermediates were close to that of the average level of experts. CONCLUSIONS: In this study, it is found that the LIIA model exhibits excellent face, content, and construct validity. Repeated simulation training of the LIIA training program improved the surgeon's operative performance, so the model is considered one of the most effective methods for LIIA training and assessment of surgical quality in the future and for reducing healthcare costs.

Multifunctional high-simulation 3D-printed hydrogel model manufacturing engineering for surgical training.

Advanced bionic organ models with vivid biological structures and wetness and softness are essential for medical-surgical training. Still, there are many challenges in the preparation process, such as matching mechanical properties, good feedback on surgical instruments, reproducibility of specific surgical scenarios, and distinguishability between structural levels. In this paper, we achieved tissuemimicking dual-network (DN) hydrogels with customizable stiffness by adjusting the composition of the hydrogel matrix and the immersion time of the ionic solution to match different biological soft tissues precisely. Combined with advanced threedimensional (3D) printing fabrication techniques, various performance-tunable bionic hydrogel organ models with structural complexity and fidelity, including kidney, liver, pancreas, and vascular tissues, were perfectly fabricated. The simulation and applicability of the model were also simulated for the forced change of the suture needle in the puncture and suture of a single tissue and between different tissues, the cutting of substantive organs by ultrasonic scalpel, the coagulation and hemostasis of blood vessels, the visualization of the internal structure under ultrasound, and the microwave ablation of liver tumors. By constructing advanced biomimetic organ models based on hydrogel with specific and tunable properties, the development of surgical training, medical device testing, and medical education reform will be significantly promoted.

Sources of information on surgical options for patients undergoing antireflux surgery: a single-center questionnaire-based survey.

BACKGROUND: To explore the sources of information on antireflux surgery for patients undergoing this surgery in China. METHODS: Patients who underwent antireflux surgery in the Gastroesophageal Reflux Center of the Zhejiang Provincial People's Hospital from January 2016 to June 2021 were selected as survey subjects, and a questionnaire survey was conducted by telephone. RESULTS: A total of 358 questionnaires were distributed, and 320 valid questionnaires were recovered, yielding a 89.4% completion rate. Among patients' sources of information about antireflux surgery, the media was the primary source (33.8%) followed by recommendations from relatives or friends (27.8%), referrals from physicians (23.4%) and other sources (15.0%). Patients of different ages and educational levels have different sources for obtaining information about the procedure. Most of the information on surgery for patients aged 20 to 49 years was derived from recommendations from friends or relatives, whereas most of the information on surgery for patients aged 50 to 80 years was obtained from the media. Most of the information on surgery for patients with a primary school education or less was derived from physicians' recommendations, whereas most of the information for patients with a junior secondary school education or higher was obtained from the media. The recommendation of patients for surgery varied among the different departments (X2 = 36.011, p < 0.001), and a two-to-two comparison found that the recommended rates for cardiology and gastroenterology differed from the rates of other groups (p < 0.001, Table 2). CONCLUSIONS: The results of this investigation show that a large number of patients who underwent antireflux surgery learned about the operation through the media and recommendations from relatives or friends rather than physicians at the hospital. Notably, physicians specializing in GERD need to increase their knowledge of the disease and surgical treatment options to provide correct medical information to patients and to conduct media campaigns.

Development and evaluation of a portable and soft 3D-printed cast for laparoscopic choledochojejunostomy model in surgical training.

BACKGROUND: Laparoscopic choledochojejunostomy (LCJ) is an essential basic skill for biliary surgeons. Therefore, we established a convenient and effective LCJ 3D printing model to evaluate whether the model could simulate the actual operation situation and determine its effectiveness and validity in surgical training. METHODS: A 3D printing dry laboratory model was established to simulate LCJ. The face and content validity of the model were evaluated by six experienced biliary surgeons based on 5-point Likert scale questionnaires. A total of 15 surgeons with different levels of experience performed LCJ on the model and evaluated the structural validity of the model using the objective structured assessment of technical skills (OSATS). Simultaneously, the operation time of each surgery was also recorded. A study was also performed to further evaluate the learning curve of residents. RESULTS: The operating space score of the model was 4.83 ± 0.41 points. The impression score of bile duct and intestinal canal was 4.33 ± 0.52 and 4.17 ± 0.41 points, respectively. The tactile sensation score of bile duct suture and intestinal canal suture was 4.00 ± 0.63 and 3.83 ± 0.41points, respectively. The OSATS score for model operation in the attending group was 29.20 ± 0.45 points, which was significantly higher than that in the fellow group (26.80 ± 1.10, P = 0.007) and the resident group (19.80 ± 1.30, P < 0.001). In addition, there was a statistical difference in operation time among surgeons of different experience levels (P < 0.05). Residents could significantly improve the surgical score and shorten the time of LCJ through repeated training. CONCLUSIONS: The 3D printing LCJ model can simulate the real operation scenes and distinguish surgeons with different levels of experience. The model is expected to be one of the training methods for biliary tract surgery in the future.

Oncoprotein SET dynamically regulates cellular stress response through nucleocytoplasmic transport in breast cancer.

SETß is the predominant isoform of oncoprotein SE translocation (SET) in various breast cancer cell lines. Interactome-transcriptome analysis has shown that SETß is intimately associated with cellular stress response. Among various exogenous stimuli, formaldehyde (FA) causes distinct biological effects in a dose-dependent manner. In response to FA at different concentrations, SET dynamically shuttles between the nucleus and cytoplasm, performing diverse biofunctions to restore homeostasis. At a low concentration, FA acts as an epidermal growth factor (EGF) and activates the HER2 receptor and downstream signaling pathways in HER2+ breast cancer cells, resulting in enhanced cell proliferation. Nucleocytoplasmic transport of SETß is controlled by the PI3K/PKCα/CK2α axis and depletion or blockade of the transport of SETß suppresses EGF-induced activation of AKT and ERK. SETß also inhibits not only stress-induced activation of p38 MAPK signaling pathway, but also assembly of stress granules by hindering formation of the G3BP1-RNA complex. Our findings suggest that SET functions as an important regulator which modulates cellular stress signaling pathways dynamically.

SET/PP2A signaling regulates macrophage positioning in hypoxic tumor regions by amplifying chemotactic responses.

Tumor-associated macrophages (TAMs) are one of the main cellular components in the tumor microenvironment (TME). In many types of solid tumors, TAMs tend to accumulate in hypoxic areas and are intimately related to poor patient prognosis. However, the underlying mechanisms by which TAMs infiltrate hypoxic tumor regions remain unclear. In this study, we report that genetic deletion of SE translocation (SET) in myeloid cells inhibited the entry of TAMs into the hypoxic tumor region and abated their proangiogenic and immunosuppressive functions, ultimately inhibiting tumor growth. Mechanistically, in response to hypoxic tumor supernatant stimulation, SET in macrophages shuttled between the nucleus and cytoplasm via the PKC-CK2α signaling axis. Cytoplasmic retention of SET increased ERK and P38 signaling by inhibiting PP2A, which promoted TAM migration into the hypoxic area and polarization toward the M2 phenotype. Therefore, we conclude that SET modulates tumor immunity by acting as a key regulator of macrophage positioning and function in the tumor.

Validity of a Soft and Flexible 3D-Printed Nissen Fundoplication Model in Surgical Training.

Rapid development of three-dimensional (3D) printing technique has enabled the production of many new materials for medical applications but the dry laboratory surgical training model made of soft and flexible materials is still insufficient. We established a new 3D-printed Nissen fundoplication training model of which materials simulate the real mechanical properties. In this study, 16 participants were divided into two groups: Experimental group and control group. The validity of model was tested using Likert scale by the experts and the experimental group. To evaluate the efficacy, performances of the experimental group were scored at the first, fourth, and eighth training by OSATS system and the duration of procedure was compared through the use of recorded video. Meanwhile, an ex vivo model was used to compare the performance of the experiment group and control group after the training in the same way. Our results showed that the 3D-printed model can support the future surgical applications, help improve surgical skills, and shorten procedure time after training.