A pooled analysis of clinical outcome in driver-gene negative non-small cell lung cancer patients with MET overexpression treated with gumarontinib.

Background: MET overexpression represents the most MET aberration in advanced non-small-cell lung cancer (NSCLC). However, except MET exon 14 (METex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear. Objectives: The purpose of the pooled analysis is to explore the safety and efficiency of gumarontinib, a highly selective oral MET inhibitor, in drive-gene negative NSCLC patients with MET overexpression. Design and methods: NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, METex14 skipping mutation or other known drive gene alternations who received Gumarontinib 300 mg QD from two single arm studies were selected and pooled for the analysis. The efficacy [objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS)] and safety [treatment emergent adverse event (TEAE), treatment related AE (TRAE) and serious AE (SAE) were assessed. Results: A total of 32 patients with MET overexpression were included in the analysis, including 12 treatment naïve patients who refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ⩾1 lines of prior systemic anti-tumour therapies. Overall, the ORR was 37.5% [95% confidence interval (CI): 21.1-56.3%], the DCR was 81.3% (95% CI: 63.6-92.8%), median PFS (mPFS) and median OS (mOS) were 6.9 month (95% CI: 3.6-9.7) and 17.0 month (95% CI: 10.3-not evaluable), respectively. The most common AEs were oedema (59.4%), hypoalbuminaemia (40.6%), alanine aminotransferase increased (31.3%). Conclusion: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT03457532; NCT04270591.

Anterior segment optical coherence tomography for superficial keratectomy.

PURPOSE: To report the use of anterior segment optical coherence tomography (AS-OCT) for superficial keratectomy (SK) in anterior corneal opacity. METHODS: The characteristics of 43 eyes (39 patients) with various lesions responsible for anterior corneal opacity were included in this retrospective non-comparative study. AS-OCT was performed on all eyes before surgery. The thickness of corneal opacity and the underlying healthy stroma were measured. SK was performed on each individual. RESULTS: Four types of anterior corneal opacity were evaluated, including corneal degeneration (26/43), Reis-Bücklers corneal dystrophy (8/43), alkali burn (1/43) and corneal tumors (8/43). Based on AS-OCT images, all eyes showed abnormal hyper-reflective signals in the superficial cornea to less than one-third of the normal corneal thickness in the deepest corneal opacity. All 43 eyes underwent an SK procedure. In addition, 1 eye with alkali burns and 7 eyes with corneal tumors were combined with amniotic membrane transplantation. All eyes restored transparency without significant complications. CONCLUSION: AS-OCT is a valuable method for objective preoperative and noninvasive assessments of anterior corneal opacities and is useful for guiding SK.

Pushing Forward the DNA Walkers in Connection with Tumor-Derived Extracellular Vesicles.

Extracellular vesicles (EVs) are microparticles released from cells in both physiological and pathological conditions and could be used to monitor the progression of various pathological states, including neoplastic diseases. In various EVs, tumor-derived extracellular vesicles (TEVs) are secreted by different tumor cells and are abundant in many molecular components, such as proteins, nucleic acids, lipids, and carbohydrates. TEVs play a crucial role in forming and advancing various cancer processes. Therefore, TEVs are regarded as promising biomarkers for the early detection of cancer in liquid biopsy. However, the currently developed TEV detection methods still face several key scientific problems that need to be solved, such as low sensitivity, poor specificity, and poor accuracy. To overcome these limitations, DNA walkers have emerged as one of the most popular nanodevices that exhibit better signal amplification capability and enable highly sensitive and specific detection of the analytes. Due to their unique properties of high directionality, flexibility, and efficiency, DNA walkers hold great potential for detecting TEVs. This paper provides an introduction to EVs and DNA walker, additionally, it summarizes recent advances in DNA walker-based detection of TEVs (2018-2024). The review highlights the close relationship between TEVs and DNA walkers, aims to offer valuable insights into TEV detection and to inspire the development of reliable, efficient, simple, and innovative methods for detecting TEVs based on DNA walker in the future.

The cellular localization and oncogenic or tumor suppressive effects of angiomiotin-like protein 2 in tumor and normal cells.

Angiomiotin (AMOT) family comprises three members: AMOT, AMOT-like protein 1 (AMOTL1), and AMOT-like protein 2 (AMOTL2). AMOTL2 is widely expressed in endothelial cells, epithelial cells, and various cancer cells. Specifically, AMOTL2 predominantly localizes in the cytoplasm and nucleus in human normal cells, whereas associates with cell-cell junctions and actin cytoskeleton in non-human cells, and locates at cell junctions or within the recycling endosomes in cancer cells. AMOTL2 is implicated in regulation of tube formation, cell polarity, and shape, although the specific impact on tumorigenesis remains to be conclusively determined. It has been shown that AMOTL2 enhances tumor growth and metastasis in pancreatic, breast, and colon cancer, however inhibits cell proliferation and migration in lung, hepatocellular cancer, and glioblastoma. In addition to its role in cell shape and cytoskeletal dynamics through co-localization with F-actin, AMOTL2 modulates the transcription of Yes-associated protein (YAP) by binding to it, thereby affecting its phosphorylation and cellular sequestration. Furthermore, the stability and cellular localization of AMOTL2, influenced by its phosphorylation and ubiquitination mediated by specific proteins, affects its cellular function. Additionally, we observe that AMOTL2 is predominantly downregulated in some tumors, but significantly elevated in colorectal adenocarcinoma (COAD). Moreover, overall analysis, GSEA and ROC curve analysis indicate that AMOTL2 exerts as an oncogenic protein in COAD by modulating Wnt pathway, participating in synthesis of collagen formation, and interacting with extracellular matrix receptor. In addition, AMOTL2 potentially regulates the distribution of immune cells infiltration in COAD. In summary, AMOTL2 probably functions as an oncogene in COAD. Consequently, further in-depth mechanistic research is required to elucidate the precise roles of AMOTL2 in various cancers.

Cystatin SA attenuates gastric cancer cells growth and increases sensitivity to oxaliplatin via PI3K/AKT signaling pathway.

PURPOSE: Cystatin SA (CST2) belongs to the superfamily of cysteine protease inhibitors. Emerging research indicates that CST2 is often dysregulated across various cancers. Its role and molecular mechanisms in gastric cancer remain underexplored. This study aims to explore the expression and function of CST2 in gastric cancer. METHODS: CST2 expression was analyzed and validated through Western blot. CST2 overexpression was induced by lentivirus in GC cells, and the correlation between CST2 expression levels and downstream signaling pathways was assessed. In addition, multiple assays, including cell proliferation, colony formation, wound-healing, and transwell migration/invasion, were considered to ascertain the influence of CST2 overexpression on gastric cancer. The cell cycle and apoptosis were detected by flow cytometry. RESULTS: CST2 expression at the protein level was decreased to be reduced in both gastric cancer tissues and cell lines, and CST2 expression attenuate gastric cancer growth, an effect restricted to gastric cancer cells and absent in gastric epithelial GES-1 cells. Furthermore, CST2 was demonstrated to improve chemosensitivity to Oxaliplatin in gastric cancer cells through the PI3K/AKT signaling pathway. CONCLUSION: These findings indicate that CST2 is downregulated at the protein level in gastric cancer tissues and cell lines. Additionally, CST2 was found to attenuate the growth of gastric cancer cells and to enhance sensitivity to Oxaliplatin through the PI3K/AKT signaling pathway, specific to gastric cancer cell lines. CST2 may serve as a tumor suppressor gene increasing sensitivity to Oxaliplatin in gastric cancer.

Extracellular matrix stiffness and tumor-associated macrophage polarization: new fields affecting immune exclusion.

In the malignant progression of tumors, there is deposition and cross-linking of collagen, as well as an increase in hyaluronic acid content, which can lead to an increase in extracellular matrix stiffness. Recent research evidence have shown that the extracellular matrix plays an important role in angiogenesis, cell proliferation, migration, immunosuppression, apoptosis, metabolism, and resistance to chemotherapeutic by the alterations toward both secretion and degradation. The clinical importance of tumor-associated macrophage is increasingly recognized, and macrophage polarization plays a central role in a series of tumor immune processes through internal signal cascade, thus regulating tumor progression. Immunotherapy has gradually become a reliable potential treatment strategy for conventional chemotherapy resistance and advanced cancer patients, but the presence of immune exclusion has become a major obstacle to treatment effectiveness, and the reasons for their resistance to these approaches remain uncertain. Currently, there is a lack of exact mechanism on the regulation of extracellular matrix stiffness and tumor-associated macrophage polarization on immune exclusion. An in-depth understanding of the relationship between extracellular matrix stiffness, tumor-associated macrophage polarization, and immune exclusion will help reveal new therapeutic targets and guide the development of clinical treatment methods for advanced cancer patients. This review summarized the different pathways and potential molecular mechanisms of extracellular matrix stiffness and tumor-associated macrophage polarization involved in immune exclusion and provided available strategies to address immune exclusion.

LncRNA UCA1 promotes vasculogenic mimicry by targeting miR-1-3p in gastric cancer.

Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been implicated in several tumors. UCA1 promotes cell proliferation, migration and invasion of GC cells, but the molecular mechanism has not been fully elucidated. This study revealed the oncogenic effects of UCA1 on cell growth and invasion. Furthermore, UCA1 expression was significantly correlated with the overall survival of GC patients, and the clinicopathological indicators, including tumor size, depth of invasion, lymph node metastasis, and TNM stage. Additionally, miR-1-3p was identified as a downstream target of UCA1, which was negatively regulated by UCA1. MiR-1-3p inhibited cell proliferation and vasculogenic mimicry (VM), and induced cell apoptosis by upregulating BAX, BAD, and tumor suppressor TP53 expression levels. Moreover, miR-1-3p almost completely reversed the oncogenic effect caused by UCA1, including cell growth, migration and VM formation. This study also confirmed UCA1 promoted tumor growth in vivo. In this study, we also revealed the correlation between UCA1 and VM formation, which is potentially crucial for tumor metastasis. Meanwhile, its downstream target miR-1-3p inhibited VM formation in GC cells. In summary, these findings indicate that UCA1/miR-1-3p axis is potential target for GC treatment.

Review of Personalized Medicine and Pharmacogenomics of Anti-Cancer Compounds and Natural Products.

In recent years, the FDA has approved numerous anti-cancer drugs that are mutation-based for clinical use. These drugs have improved the precision of treatment and reduced adverse effects and side effects. Personalized therapy is a prominent and hot topic of current medicine and also represents the future direction of development. With the continuous advancements in gene sequencing and high-throughput screening, research and development strategies for personalized clinical drugs have developed rapidly. This review elaborates the recent personalized treatment strategies, which include artificial intelligence, multi-omics analysis, chemical proteomics, and computation-aided drug design. These technologies rely on the molecular classification of diseases, the global signaling network within organisms, and new models for all targets, which significantly support the development of personalized medicine. Meanwhile, we summarize chemical drugs, such as lorlatinib, osimertinib, and other natural products, that deliver personalized therapeutic effects based on genetic mutations. This review also highlights potential challenges in interpreting genetic mutations and combining drugs, while providing new ideas for the development of personalized medicine and pharmacogenomics in cancer study.

Construction and external validation of a scoring prediction model for mortality risk within 30 days of community-acquired pneumonia in children admitted to the pediatric intensive care unit: A multicenter retrospective case-control study.

In this study, we constructed and validated a scoring prediction model to identify children admitted to the pediatric intensive care unit (PICU) with community-acquired pneumonia (CAP) at risk for early death. Children with CAP who were admitted to the PICU were included in the training set and divided into death and survival groups according to whether they died within 30 days of admission. For univariate and multifactorial analyses, demographic characteristics, vital signs at admission, and laboratory test results were collected separately from the 2 groups, and independent risk factors were derived to construct a scoring prediction model. The ability of the scoring model to predict CAP-related death was validated by including children with CAP hospitalized at 3 other centers during the same period in the external validation set. Overall, the training and validation sets included 296 and 170 children, respectively. Univariate and multifactorial analyses revealed that procalcitonin (PCT), lactate dehydrogenase (LDH), activated partial thromboplastin time (APTT), and fibrinogen (Fib) were independent risk factors. The constructed scoring prediction model scored 2 points each for PCT ≥ 0.375 ng/mL, LDH ≥ 490 U/L, and APTT ≥ 31.8 s and 1 point for Fib ≤ 1.78 g/L, with a total model score of 0-7 points. When the score was ≥ 5 points, the sensitivity and specificity of mortality diagnosis in children with CAP were 72.7% and 87.5%, respectively. In the external validation set, the sensitivity, specificity, and accuracy of the scoring model for predicting the risk of CAP-related death were 64.0%, 92.4%, and 88.2%, respectively. Constructing a scoring prediction model is worth promoting and can aid pediatricians in simply and rapidly evaluating the risk of death in children with CAP, particularly those with complex conditions.

Exosomes as Powerful Biomarkers in Cancer: Recent Advances in Isolation and Detection Techniques.

Exosomes, small extracellular vesicles derived from cells, are known to carry important bioactive molecules such as proteins, nucleic acids, and lipids. These bioactive components play crucial roles in cell signaling, immune response, and tumor metastasis, making exosomes potential diagnostic biomarkers for various diseases. However, current methods for detecting tumor exosomes face scientific challenges including low sensitivity, poor specificity, complicated procedures, and high costs. It is essential to surmount these obstacles to enhance the precision and dependability of diagnostics that rely on exosomes. Merging DNA signal amplification techniques with the signal boosting capabilities of nanomaterials presents an encouraging strategy to overcome these constraints and improve exosome detection. This article highlights the use of DNA signal amplification technology and nanomaterials' signal enhancement effect to improve the detection of exosomes. This review seeks to offer valuable perspectives for the enhancement of amplification methods applied in practical cancer diagnosis and prognosis by providing an overview of how these novel technologies are utilized in exosome-based diagnostic procedures.

Transmembrane protein 176B regulates amino acid metabolism through the PI3K-Akt-mTOR signaling pathway and promotes gastric cancer progression.

BACKGROUND: The present study aimed to investigate the expression level, biological function, and underlying mechanism of transmembrane protein 176B (TMEM176B) in gastric cancer (GC). METHODS: TMEM176B expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). The function of TMEM176B was determined by various in vitro assays including colony formation, 5-ethynyl-2'-deoxyuridine (EdU), Transwell, and flow cytometry. Bioinformatics techniques were then used to elucidate the signaling pathways associated with TMEM176B activity. Tumor formation experiments were conducted on nude mice for in vivo validation of the preceding findings. TMEM176B expression was cross-referenced to clinicopathological parameters and survival outcomes. RESULTS: It was observed that TMEM176B was overexpressed in GC cells and tissues. Targeted TMEM176B abrogation inhibited colony formation, proliferation, migration, and invasion but promoted apoptosis in GC cell lines while TMEM176B overexpression had the opposite effects. Subsequent experimental validation disclosed an association between TMEM176B and the phosphatidylinositol 3-carboxykinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling axis. Moreover, TMEM176B affects GC cancer progression by regulating asparagine synthetase (ASNS). The in vivo assays confirmed that TMEM176B is oncogenic and the clinical data revealed a connection between TMEM176B expression and the clinicopathological determinants of GC. CONCLUSION: The foregoing results suggest that TMEM176B significantly promotes the development of gastric cancer and is an independent prognostic factor of it.

Effects of Heated Infiltration Solutions and Forced-Air Heating Blankets on Intraoperative Hypothermia During Liposuction: A Factorial Randomized Controlled Trial.

BACKGROUND: This study was conducted to compare the effects of heat preservation by two recommended methods, heated infiltration solutions and forced-air heating blankets, in patients undergoing liposuction under general anesthesia. METHODS: Forty patients were divided into four groups based on whether heated infiltration solutions or forced-air heating blankets were used. Group A received general anesthesia liposuction plastic surgery routine temperature care. Based on the care measures of group A, heated infiltration solutions were used in group B; forced-air heating blanket was used in group C; and heated infiltration solutions and forced-air heating blankets were both used in group D. The primary end point was intraoperative and perioperative temperature measured with an infrared tympanic membrane thermometer. Secondary end points included surgical outcomes, subjective experience, and adverse events. RESULTS: Compared with group A, the intraoperative body temperatures of groups B, C, and D were significantly higher, indicating that the two intervention methods were helpful on increasing the core body temperature. Pairwise comparisons of these three groups showed that there was no significant difference between group C and group D. However, using forced-air heating blankets had a marked effect compared with using heated infiltration solutions alone at three time points. The same trend could be seen in other surgical outcomes. CONCLUSIONS: Heated infiltration solutions and forced-air heating blankets could reduce the incidence of intraoperative hypothermia and improve patients' prognosis after liposuction under general anesthesia. Compared with the heated infiltration fluid, the forced-air heating blanket may have a better thermal insulation effect. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Self-assembled nanovesicles based on chiral bis-H8-BINOL for Fe3+ recognition and secondary recognition of l-cysteine by 1 + 1 complex.

A novel fluorescent "off" sensor, R-ß-d-1, was obtained in high yield (91.2%) by using octahydronaphthol as a backbone, introducing an alkyne group at the 2-position, and linking azido-glucose via a click reaction. The sensor was analyzed by scanning electron microscopy and transmission electron microscopy and was found to be a self-assembled vesicle. AFM results showed that the fluorescence burst was extinguished by the addition of Fe3+, and the fluorescence was restored by the addition of cysteine. This is due to charge transfer within the molecular structure, resulting in the ICT effect and phototransfer of electrons (PET), as well as redshifting (from 331 nm to 351 nm) and quenching of the fluorescence. The self-assembled vesicles of the fluorescent sensor R-ß-d-1 encapsulated Fe3+, but upon addition of cysteine, the vesicles of R-ß-d-1-Fe3+ were also complexed with it, forming the R-ß-d-1-Fe3+-l-Cys complex, at which point fluorescence gradually returned. Therefore, the fluorescence test of this probe showed that the lowest detection limit of iron ions was 1.67 × 10-7 mol L-1, and its complexation mode was in the form of 1 + 1. The novel probe formed by R-ß-d-1-Fe3+ can be used for the fluorescence detection of cysteine.

Tousled-like kinase 1 promotes gastric cancer progression by regulating the tumor growth factor-beta signaling pathway.

BACKGROUND: The role of Tousled-like kinase 1 (TLK1) in in gastric cancer (GC) remains unclear. AIM: To investigate the expression, biological function, and underlying mechanisms of TLK1 in GC. METHODS: We measured TLK1 protein expression levels and localized TLK1 in GC cells and tissues by western blot and immunofluorescence, respectively. We transfected various GC cells with lentiviruses to create TLK1 overexpression and knockdown lines and established the functional roles of TLK1 through in vitro colony formation, 5-ethynyl-2`-deoxyuridine, and Transwell assays as well as flow cytometry. We applied bioinformatics to elucidate the signaling pathways associated with TLK1. We performed in vivo validation of TLK1 functions by inducing subcutaneous xenograft tumors in nude mice. RESULTS: TLK1 was significantly upregulated in GC cells and tissues compared to their normal counterparts and was localized mainly to the nucleus. TLK1 knockdown significantly decreased colony formation, proliferation, invasion, and migration but increased apoptosis in GC cells. TLK1 overexpression had the opposite effects. Bioinformatics revealed, and subsequent experiments verified, that the tumor growth factor-beta signaling pathway was implicated in TLK1-mediated GC progression. The in vivo assays confirmed that TLK1 promotes tumorigenesis in GC. CONCLUSION: The findings of the present study indicated that TLK1 plays a crucial role in GC progression and is, therefore, promising as a therapeutic target against this disease.

Application and evaluation of surgical tool and tool tip recognition based on Convolutional Neural Network in multiple endoscopic surgical scenarios.

BACKGROUND: In recent years, computer-assisted intervention and robot-assisted surgery are receiving increasing attention. The need for real-time identification and tracking of surgical tools and tool tips is constantly demanding. A series of researches focusing on surgical tool tracking and identification have been performed. However, the size of dataset, the sensitivity/precision, and the response time of these studies were limited. In this work, we developed and utilized an automated method based on Convolutional Neural Network (CNN) and You Only Look Once (YOLO) v3 algorithm to locate and identify surgical tools and tool tips covering five different surgical scenarios. MATERIALS AND METHODS: An algorithm of object detection was applied to identify and locate the surgical tools and tool tips. DarkNet-19 was used as Backbone Network and YOLOv3 was modified and applied for the detection. We included a series of 181 endoscopy videos covering 5 different surgical scenarios: pancreatic surgery, thyroid surgery, colon surgery, gastric surgery, and external scenes. A total amount of 25,333 images containing 94,463 targets were collected. Training and test sets were divided in a proportion of 2.5:1. The data sets were openly stored at the Kaggle database. RESULTS: Under an Intersection over Union threshold of 0.5, the overall sensitivity and precision rate of the model were 93.02% and 89.61% for tool recognition and 87.05% and 83.57% for tool tip recognition, respectively. The model demonstrated the highest tool and tool tip recognition sensitivity and precision rate under external scenes. Among the four different internal surgical scenes, the network had better performances in pancreatic and colon surgeries and poorer performances in gastric and thyroid surgeries. CONCLUSION: We developed a surgical tool and tool tip recognition model based on CNN and YOLOv3. Validation of our model demonstrated satisfactory precision, accuracy, and robustness across different surgical scenes.

A novel 4-1BB/HER2 bispecific antibody shows potent antitumor activities by increasing and activating tumor-infiltrating T cells.

Resistance to HER2-targeted therapy narrows the efficacy of cancer immunotherapy. Although 4-1BB/CD137 is a promising drug target as a costimulatory molecule of immune cells, no therapeutic drug has been approved in the clinic because of systemic toxicity or limited efficacy. Previously, we developed a humanized anti-HER2 monoclonal antibody (mAb) HuA21 and anti-4-1BB mAb HuB6 with distinct antigen epitopes for cancer therapy. Here, we generated an Fc-muted IgG4 HER2/4-1BB bispecific antibody (BsAb) HK006 by the fusion of HuB6 scFv and HuA21 Fab. HK006 exhibited synergistic antitumor activity by blocking HER2 signal transduction and stimulating the 4-1BB signaling pathway simultaneously and strictly dependent on HER2 expression in vitro and in vivo. Strikingly, HK006 treatment enhanced antitumor immunity by increasing and activating tumor-infiltrating T cells. Moreover, HK006 did not induce nonspecific production of proinflammatory cytokines and had no obvious toxicity in mice. Overall, these data demonstrated that HK006 should be a promising candidate for HER2-positive cancer immunotherapy.

Targeting TLK2 inhibits the progression of gastric cancer by reprogramming amino acid metabolism through the mTOR/ASNS axis.

Several recent studies have suggested that TLKs are related to tumor progression. However, the function and mechanism of action of TLK2 in gastric cancer (GC) remain elusive. In this study, TLK2 was found to be significantly upregulated in patients with GC and was identified as an independent prognostic factor for GC. Consistently, TLK2 knockdown markedly reduced the aggressiveness of GC, whereas its overexpression had the opposite effect. IP-MS revealed that the effects of TLK2 on GC were mainly associated with metabolism reprogramming. TLK2 knockdown suppressed amino acid synthesis by downregulating the mTORC1 pathway and ASNS expression in GC cells. Mechanistically, mTORC1 directly interacts with the ASNS protein and inhibits its degradation. Further experiments validated that the ASNS protein was degraded via ubiquitination instead of autophagy. Inhibiting and activating the mTORC1 pathway can upregulate and downregulate ASNS ubiquitination, respectively, and the mTORC1 pathway can reverse the regulatory effects of TLK2 on ASNS. Furthermore, TLK2 was found to regulate the mRNA expression of ASNS. TLK2 directly interacted with ATF4, a transcription factor of ASNS, and promoted its expression. The kinase inhibitor fostamatinib significantly inhibited the proliferative, invasive, and migratory capabilities of GC cells by inhibiting TLK2 activity. Altogether, this study reveals a novel functional relationship between TLK2 and the mTORC1/ASNS axis in GC. Therefore, TLK2 may serve as a potential therapeutic target for GC.

Dibenzocyclooctadiene lignans from the family Schisandraceae: A review of phytochemistry, structure-activity relationship, and hepatoprotective effects.

Liver injury is a common pathological process characterized by massive degeneration and abnormal death of liver cells. With increase in dead cells and necrosis, liver injury eventually leads to nonalcoholic fatty liver disease (NAFLD), hepatic fibrosis, and even hepatocellular carcinoma (HCC). Consequently, it is necessary to treat liver injury and to prevent its progression. The drug Bicylol is widely employed in China to treat chronic hepatitis B virus (HBV) and has therapeutic potential for liver injury. It is the derivative of dibenzocyclooctadiene lignans extracted from Schisandra chinensis (SC). The Schisandraceae family is a rich source of dibenzocyclooctadiene lignans, which possesses potential liver protective activity. This study aimed to comprehensively summarize the phytochemistry, structure-activity relationship and molecular mechanisms underlying the liver protective activities of dibenzocyclooctadiene lignans from the Schisandraceae family. Here, we had discussed the analysis of absorption or permeation properties of 358 compounds based on Lipinski's rule of five. So far, 358 dibenzocyclooctadiene lignans have been reported, with 37 of them exhibited hepatoprotective effects. The molecular mechanism of the active compounds mainly involves antioxidative stress, anti-inflammation and autophagy through Kelch-like ECH-associating protein 1/nuclear factor erythroid 2 related factor 2/antioxidant response element (Keap1/Nrf2/ARE), nuclear factor kappa B (NF-кB), and transforming growth factor ß (TGF-ß)/Smad 2/3 signaling pathways. This review is expected to provide scientific ideas for future research related to developing and utilizing the dibenzocyclooctadiene lignans from Schisandraceae family.

Prognostic model for the prediction of cancer-specific survival in elderly patients with stage I-III gastric cancer.

Elderly patients with gastric cancer (GC) exhibit unique physiological conditions and population characteristics. However, no efficient predictive tools have been developed for this patient subgroup. We extracted data on elderly patients diagnosed with stage I-III GC between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database, and applied Cox regression analysis to examine factors associated with cancer-specific survival (CSS). A prognostic model was developed and validated to predict CSS. We assessed the performance of the prognostic model and stratified patients based on their prognostic scores. Notably, 11 independent prognostic factors, including age, race, grade, the tumor-node-metastasis (TNM) stage, T-stage, N-stage, operation, tumor size, regional nodes, radiation, and chemotherapy, associated with CSS were identified using multivariate Cox regression. A nomogram was constructed based on these predictors. The C-index score of the nomogram was 0.802 (95% (confidence interval) [CI]: 0.7939-0.8114), which is superior to the American Joint Commission on Cancer (AJCC) TNM staging prediction ability in the training cohort (C-index: 0.589; 95% CI: 0.5780-0.6017). Based on the receiver operating characteristic (ROC) and calibration curve, the predicted value of the nomogram demonstrated a satisfactory accuracy with the actual observation value. Additionally, decision curve analysis (DCA) showed that the nomogram had a more ideal clinical net benefit than TNM staging. Survival analysis of the different risk groups confirmed the noteworthy clinical and statistical utility of the nomogram in prognosis stratification. This retrospective study reports the successful creation and validation of a nomogram for predicting CSS at 1-, 3- and 5-years in elderly patients with stage I-III GC. This nomogram critically guides personalized prognostic assessments and may contribute to clinical decision-making and consultation for postoperative survival.

Feasibility, safety and effectiveness of robot-assisted retroperitoneal partial adrenalectomy with a new robotic surgical system: A prospective clinical study.

Objectives: To evaluate the feasibility, safety and efficacy of the newly developed KD-SR-01® robotic system for retroperitoneal partial adrenalectomy. Subjects and Methods: We prospectively enrolled patients with benign adrenal mass undergoing KD-SR-01® robot-assisted partial adrenalectomy in our institution from November 2020 to May 2022. Surgeries were performed via a retroperitoneal approach using the KD-SR-01® robotic system. The baseline, perioperative and short-term follow-up data were prospectively collected. A descriptive statistical analysis was performed. Results: A total of 23 patients were enrolled, including nine (39.1%) patients with hormone-active tumors. All patients received partial adrenalectomy via the retroperitoneal approach without conversions to other procedures. The median operative time was 86.5 min [interquartile range (IQR), 60.0-112.5] and the median estimated blood loss was 50 ml (range, 20-400). Three (13.0%) patients developed Clavien-Dindo grade I-II postoperative complications. The median postoperative stay was 4.0 days (IQR, 3.0-5.0). All surgical margins were negative. The short-term follow-up demonstrated complete or partial clinical and biochemical success as well as absence of imaging recurrence in all patients with hormone-active tumors. Conclusions: Initial results illustrate that the KD-SR-01® robotic system is safe, feasible and effective for the surgical management of benign adrenal tumors.