SUMOylation-induced membrane localization of TRPV1 suppresses proliferation and migration in gastric cancer cells.

Gastric cancer (GC) remains a significant health challenge due to its high mortality rate and the limited efficacy of current targeted therapies. A critical barrier in developing more effective treatments is the lack of understanding of specific mechanisms driving GC progression. This study investigates the role of Transient Receptor Potential Vanilloid 1 (TRPV1), a non-selective cation channel known for its high Ca2+ permeability and tumor-suppressive properties in gastrointestinal cancers. Specifically, we explore the impact of SUMOylation-a dynamic and reversible post-translational modification-on TRPV1's function in GC. We demonstrate that SUMOylation of TRPV1 inhibits cell proliferation and migration in MGC-803 and AGS GC cells. By mutating amino acids near TRPV1's existing SUMO motif (slKpE), we created a bidirectional SUMO motif (EψKψE) that enhances TRPV1 SUMOylation, resulting in further suppression of GC cell proliferation and migration. In vivo studies support these findings, showing that TRPV1 SUMOylation prevents spontaneous tumorigenesis in a mouse GC model. Further investigation reveals that TRPV1 SUMOylation increases the protein's membrane expression by inhibiting its interaction with the adaptor-related protein complex 2 mu 1 subunit (AP2M1). This elevated membrane expression leads to increased intracellular Ca2+ influx, activating the AMP-activated protein kinase (AMPK) pathway, which in turn inhibits the proliferation and migration of GC cells.

AB074. Propensity-score matched analysis to evaluate the safety and utility of intraoperative cell-salvaged autologous blood transfusion in metastatic spine tumour surgery.

BACKGROUND: Blood loss is an important consideration in metastatic spine tumour surgery (MSTS). Allogeneic blood transfusion (ABT) is the current standard of blood replenishment for MSTS despite known complications. Salvaged blood transfusion (SBT) through intraoperative cell salvage addresses the majority of complications related to ABT. However, the use of SBT in MSTS still remains controversial. We aim to conduct a prospective propensity-score (PS) matched analysis to evaluate the long-term clinical outcomes of intraoperative cell salvage (IOCS) in MSTS. METHODS: Our study included 98 patients who underwent MSTS from 2014-2017. A PS matched cohort was created using the relevant and available predictors of treatment assignment and outcomes of interest. Clinical outcomes consisting of overall survival (OS), as well tumour progression (TP) that was evaluated using RECIST (v1.1) were compared in the matched cohort. RESULTS: Our study had a total of 98 patients with a mean age of 60 years old. A total of 33 patients received SBT. Overall median blood loss was 600 mL [interquartile range (IQR): 300-1,000 mL] and overall median blood transfusion (BT) was 620 mL (IQR: 110-1,600 mL). Group PS matching included 30 patients who received ABT and 28 patients who received SBT. There was also no significant difference between the OS of patients who underwent ABT or SBT (P=0.19). SBT did not show any significant increase in 4-year tumour progression [PS matched hazard ratio (HR) 3.659; 95% confidence interval (CI): 0.346-38.7; P=0.28]. CONCLUSIONS: SBT has been shown to have similar clinical outcomes to that of ABT in patients undergoing MSTS, with potential benefits of avoiding complications and costs of ABT. This will be the first long-term PS matched analysis to report on the clinical outcomes of SBT and affirms the clinical role of SBT in MSTS today.

AB075. When would minimally invasive spinal surgery not be preferable for metastatic spine disease?-a narrative review.

BACKGROUND: Metastatic spine tumour surgery (MSTS) is an important treatment modality of metastatic spinal disease (MSD). Open spine surgery (OSS) was previously the gold standard of treatment. However, advancements in MSTS in recent years has resulted in a current paradigm shift towards today's gold standard of minimally invasive spinal surgery (MISS) and early adjuvant RT in treating MSD patients. Nonetheless, there are still certain situations whereby MISS is not desirable or even suitable. There has also yet to be any literature describing the considerations for not using MISS in MSD in today's clinical context. We aim to bridge the gap where OSS should be considered with caution and highlight situations where MISS is preferable using the available literature and personal experience. METHODS: This narrative review was conducted using PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), The Cochrane Library and Scopus databases through August 31, 2023. Inclusion criteria for the review were studies with discussion on the type of surgery in MSTS. RESULTS: A total of 52 studies were included in this review. We discussed various advantages and situations appropriate for MISS for MSD in today's clinical context. Nonetheless, there are still various unique circumstances in which MISS may be less suitable. MISS is less feasible in patients of paediatric profile, having short stature or having had previous surgery at the level of operation. Occipitocervical and cervicothoracic location of vertebrae metastasis also makes MISS less feasible due to access and imaging difficulty. MISS for tumours which are hypersclerotic and hypervascular can also result in more difficulty for cannulation of MISS probes as well as control of bleeding respectively, and hence will be less encouraged in the above settings. CONCLUSIONS: Our review will be the first to discuss circumstances in which MISS is less applicable, despite the advantages it may confer over traditional OSS. MSTS should be individualized to the patient, depending on the experience of the surgeon. OSS is still a time-tested approach that holds weight in MSTS and should be readily utilized depending on the clinical situation.

AB078. Patterns of treatment delay in patients with symptomatic metastatic epidural spinal cord compression.

BACKGROUND: Delayed treatment in symptomatic metastatic epidural spinal cord compression (MESCC) is significantly associated with poorer functional outcomes. In this study, we aim to identify the patterns of treatment delay in patients and factors predictive of postoperative ambulatory function. METHODS: Retrospective review of patients with symptomatic MESCC treated surgically between January 2015 and January 2022. MESCC symptoms were categorized into symptoms suggesting cord compression requiring immediate referral and symptoms suggestive of spinal metastases. Multivariate analysis was performed to identify factors predictive of postoperative ambulatory function. Delays in treatment were identified and categorized into patient delay (onset of symptoms till initial medical consultation), diagnostic delay (medical consultation till radiological diagnosis of MESCC), referral delay (from diagnosis till spine surgeon review) and surgical delay (from spine surgeon review till surgery) and compared between patients. RESULTS: One hundred and seventy-eight patients were identified. In this cohort 92 (52.0%) patients were able to ambulate independently, and 86 (48.3%) patients were non independent. One hundred and thirty-nine (78.1%) of patients had symptoms of cord compression and 93 (52.3%) had neurological deficits on presentation. On multivariate analysis, pre-operative neurological deficits (P=0.01) and symptoms of cord compression (P=0.01) were significantly associated with post-operative ambulatory function. Mean total delay was 66 days, patient delay was 41 days, diagnostic delay was 16 days, referral delay was 3 days and surgical delay was 6 days. In patients with neurological deficits, there was a significant decrease in all forms of treatment delay (P<0.05). There was no significant decrease in patient delay, diagnostic delay and referral delay in patients with symptoms of cord compression. CONCLUSIONS: Both patients and physicians understand the need for urgent surgical treatment of MESCC with neurological deficits, however there is still a need for increased education and recognition of the symptoms of MESCC.

AB077. An evaluation of prognostic scoring systems for survival in a surgically treated cohort of 318 metastatic spine tumour surgery patients.

BACKGROUND: Survival prognostication plays a key role in the decision-making process for the surgical treatment of patients with spinal metastases. In the past traditional scoring systems such as the modified Tokuhashi and Tomita scoring systems have been used extensively, however in recent years their accuracy has been called into question. This has led to the development of machine learning algorithms to predict survival. In this study, we aim to compare the accuracy of prognostic scoring systems in a surgically treated cohort of patients. METHODS: This is a retrospective review of 318 surgically treated spinal metastases patients between 2009 and 2021. The primary outcome measured was survival from the time of diagnosis. Predicted survival at 3 months, 6 months and 1 year based on the prognostic scoring system was compared to actual survival. Predictive values of each scoring system were measured via area under receiver operating characteristic curves (AUROC). The following scoring systems were compared, Modified Tokuhashi (MT), Tomita (T), Modified Bauer (MB), Van Den Linden (VDL), Oswestry (O), New England Spinal Metastases score (NESMS), Global Spine Study Tumor Group (GSTSG) and Skeletal Oncology Research Group (SORG) scoring systems. RESULTS: For predicting 3 months survival, the GSTSG 0.980 (0.949-1.0) and NESM 0.980 (0.949-1.0) had outstanding predictive value, while the SORG 0.837 (0.751-0.923) and O 0.837 (0.775-0.900) had excellent predictive value. While for 6 months survival, only the O 0.819 (0.758-0.880) had excellent predictive value and the GSTSG 0.791(0.725-0.857) had acceptable predictive value. For 1 year survival, the NESM 0.871 (0.822-0.919) had excellent predictive value and the O 0.722 (0.657-0.786) had acceptable predictive value. The MT, T and MB scores had an area under the curve (AUC) of <0.5 for 3-month, 6-month and 1-year survival. CONCLUSIONS: Increasingly, traditional scoring systems such as the MT, T and MB scoring systems have become less predictive. While newer scoring systems such as the GSTSG, NESM and SORG have outstanding to excellent predictive value, there is no one survival scoring system that is able to accurately prognosticate survival at all 3 time points. A multidisciplinary, personalised approach to survival prognostication is needed.

Assembling Retinal Organoids with Microglia.

Due to the limited accessibility of the human retina, retinal organoids (ROs) are the best model for studying human retinal disease, which could reveal the mechanism of retinal development and the occurrence of retinal disease. Microglia (MG) are unique resident macrophages in the retina and central nervous system (CNS), serving crucial immunity functions. However, retinal organoids lack microglia since their differentiation origin is the yolk sac. The specific pathogenesis of microglia in these retinal diseases remains unclear; therefore, the establishment of a microglia-incorporated retinal organoid model turns out to be necessary. Here, we successfully constructed a co-cultured model of retinal organoids with microglia derived from human stem cells. In this article, we differentiated microglia and then co-cultured to retinal organoids in the early stage. As the incorporation of immune cells, this model provides an optimized platform for retinal disease modeling and drug screening to facilitate in-depth research on the pathogenesis and treatment of retinal and CNS-related diseases.

A novel nanoplatform-based circCSNK1G3 affects CBX7 protein and promotes glioma cell growth.

Bioenvironmental and biological factors have the potential to contribute to the development of glioma, a type of brain tumor. Recent studies have suggested that a unique circular RNA called circCSNK1G3 could play a role in promoting the growth of glioma cells. It does this by stabilizing a specific microRNA called miR-181 and reducing the expression of a tumor-suppressor gene known as chromobox protein homolog 7 (CBX7). To further investigate circCSNK1G3 and its effects on glioma, we utilized a nanoplatform called adeno-associated virus (AAV)-RNAi.To explore the functional implications of circCSNK1G3, we employed siRNA to silence its expression. Along with these effects, the silencing of circCSNK1G3 led to a depletion of miR-181d and an upregulation of CBX7. When we introduced miR-181d mimics, which artificially increase the levels of miR-181d, the anti-glioma cell activity induced by circCSNK1G3 siRNA was almost completely reversed. Conversely, inhibiting miR-181d mimicked the effects of circCSNK1G3 silencing. Moreover, when we overexpressed circCSNK1G3 in glioma cells, we observed an elevation of miR-181d and a depletion of CBX7. We found that the growth of A172 xenografts (tumors) carrying circCSNK1G3 shRNA was significantly inhibited. In these xenograft tissues, we detected a depletion of circCSNK1G3 and miR-181d, as well as an upregulation of CBX7.

Retrospective clinical study analysis of skin adverse reactions related to epidermal growth factor receptor inhibitors.

Background: Epidermal growth factor receptor inhibitors (EGFRIs) represent a cornerstone in the targeted therapy of malignant tumors. While effective, dermatological adverse events (dAEs) associated with EGFRIs pose a significant challenge, often necessitating treatment discontinuation due to their severity and potential to impede the continuity of cancer therapy. Despite extensive research, the specific mechanisms and predictors of these adverse events remain poorly understood, particularly in diverse populations. This gap in knowledge underscores the need for targeted studies to better predict and manage these events, enhancing patient outcomes and adherence to life-saving therapies. Methods: This observational study was conducted at The First Affiliated Hospital of Guangxi Medical University, covering cancer patients treated with EGFRIs from 2020 to 2022. We analyzed clinical data including patient demographics, treatment specifics, and the development and timing of dAEs. The study employed SPSS 26.0 software for data analysis, focusing on the incidence of dAEs and factors influencing their occurrence. We used Kaplan-Meier and Cox regression methods to establish a predictive model for dAEs, tracking their onset and impact on treatment continuity. Results: In our study of 120 patients treated with EGFR inhibitors at The First Affiliated Hospital of Guangxi Medical University, we found a high prevalence of dAEs, with 84.2% of patients experiencing such effects. The most common manifestations were papulopustular rashes, observed as pustules in 52.5% and papules in 57.4% of cases, followed by nail lesions in 62.4% of patients, oral or other mucosal ulcers in 34.7%, and hair changes in 26.7%. The median incubation time (MIT) for dAEs was 5 weeks. We identified drug type, ethnicity, and occupation as statistically significant risk factors (P<0.05 for all) that influenced the MIT, which the Cox regression model further identified as protective factors. Nomograms were developed to assess the risk of dAEs, although it is important to note that these models have only been internally validated, lacking external validation data at this stage. Conclusions: The study highlights the high incidence of EGFRIs-associated dAEs, with specific dermatological manifestations posing significant challenges in cancer therapy. The identification of drug type, ethnicity, and occupation as influential factors on the MIT for dAEs informs clinical decisions. Our prediction model serves as a practical tool for evaluating the risk of developing dAEs over time, aiming to optimize patient management and mitigate treatment interruptions.

Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.

Numerous studies have revealed that the ATP-gated ion channel purinergic 2X7 receptor (P2X7R) plays an important role in tumor progression and the pathogenesis of cancer pain. P2X7R requires activation by extracellular ATP to perform its regulatory role functions. During tumor development or cancer-induced pain, ATP is released from tumor cells or other cells in the tumor microenvironment (such as tumor-associated immune cells), which activates P2X7R, opens ion channels on the cell membrane, affects intracellular molecular metabolism, and regulates the activity of tumor cells. Furthermore, peripheral organs and receptors can be damaged during tumor progression, and P2X7R expression in nerve cells (such as microglia) is significantly upregulated, enhancing sensory afferent information, sensitizing the central nervous system, and inducing or exacerbating pain. These findings reveal that the ATP-P2X7R signaling axis plays a key regulatory role in the pathogenesis of tumors and cancer pain and also has a therapeutic role. Accordingly, in this study, we explored the role of P2X7R in tumors and cancer pain, discussed the pharmacological properties of inhibiting P2X7R activity (such as the use of antagonists) or blocking its expression in the treatment of tumor and cancer pain, and provided an important evidence for the treatment of both in the future.

IRF7 overexpression alleviates CFA-induced inflammatory pain by inhibiting nuclear factor-κB activation and pro-inflammatory cytokines expression in rats.

BACKGROUND: It is known that nerve signals arising from sites of inflammation lead to persistent changes in the spinal cord and contribute to the amplification and persistence of pain. Nevertheless, the underlying mechanisms have not yet been completely elucidated. We identified differentially expressed genes in the lumbar (L4-L6) segment of the spinal cord from complete Freund's adjuvant (CFA) rats compared to control animals via high throughput sequencing. Based on differential gene expression analysis, we selected interferon regulatory factor 7 (IRF7) for follow-up experiments to explore its antinociceptive potential. METHODS: An animal model of inflammatory pain was induced by intraplantar injection of CFA. We evaluated the effects of adeno-associated viral (AAV)-mediated overexpression of IRF7 in the spinal cord on pain-related behavior after CFA injection. Moreover, the activation of the nuclear factor-κB (NF-κB) and the expression of inflammatory cytokines were investigated to understand the underlying mechanisms related to the contribution of IRF7 to inflammatory pain. RESULTS: CFA intraplantar injection caused a significant decrease in the level of spinal IRF7, which is mainly expressed in the dorsal horn neurons and astrocytes. Moreover, IRF7 overexpression significantly attenuated pain-related behaviors, as well as the activity of NF-κB/p65 and the production of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the spinal cord of CFA rats. CONCLUSIONS: Our data indicated that spinal IRF7 plays an important role in the regulation of inflammatory pain. Thus, IRF7 overexpression at the spinal cord level might represent a potential target for the treatment of inflammatory pain.

Effects of fluorescent protein tdTomato on mouse retina.

Fluorescent proteins (FPs) have been widely used to investigate cellular and molecular interactions and trace biological events in many applications. Some of the FPs have been demonstrated to cause undesirable cellular damage by light-induced ROS production in vivo or in vitro. However, it remains unknown if one of the most popular FPs, tdTomato, has similar effects in neuronal cells. In this study, we discovered that tdTomato expression led to unexpected retinal dysfunction and ultrastructural defects in the transgenic mouse retina. The retinal dysfunction mainly manifested in the reduced photopic electroretinogram (ERG) responses and decreased contrast sensitivity in visual acuity, caused by mitochondrial damages characterized with cellular redistribution, morphological modifications and molecular profiling alterations. Taken together, our findings for the first time demonstrated the retinal dysfunction and ultrastructural defects in the retinas of tdTomato-transgenic mice, calling for a more careful design and interpretation of experiments involved in FPs.

The Role of m6A-Mediated DNA Damage Repair in Tumor Development and Chemoradiotherapy Resistance.

Among the post-transcriptional modifications, m6A RNA methylation has gained significant research interest due to its critical role in regulating transcriptional expression. This modification affects RNA metabolism in several ways, including processing, nuclear export, translation, and decay, making it one of the most abundant transcriptional modifications and a crucial regulator of gene expression. The dysregulation of m6A RNA methylation-related proteins in many tumors has been shown to lead to the upregulation of oncoprotein expression, tumor initiation, proliferation, cancer cell progression, and metastasis.Although the impact of m6A RNA methylation on cancer cell growth and proliferation has been extensively studied, its role in DNA repair processes, which are crucial to the pathogenesis of various diseases, including cancer, remains unclear. However, recent studies have shown accumulating evidence that m6A RNA methylation significantly affects DNA repair processes and may play a role in cancer drug resistance. Therefore, a comprehensive literature review is necessary to explore the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.In conclusion, m6A RNA methylation is a crucial regulator of gene expression and a potential player in cancer development and drug resistance. Its dysregulation in many tumors leads to the upregulation of oncoprotein expression and tumor progression. Furthermore, the impact of m6A RNA methylation on DNA repair processes, although unclear, may play a crucial role in cancer drug resistance. Therefore, further studies are warranted to better understand the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.

Multidirectional instability of the shoulder: a systematic review with a novel classification.

Purpose: A variety of instabilities are grouped under multidirectional instability (MDI) of the shoulder. This makes understanding its diagnostic process, presentation and treatment difficult due to lack of evidence-based consensus. This review aims to propose a novel classification for subtypes of MDI. Methods: A systematic search was performed on PubMed Medline and Embase. A combination of the following 'MeSH' and 'non-MesH' search terms were used: (1) Glenohumeral joint[tiab] OR Glenohumeral[tiab] OR Shoulder[tiab] OR Shoulder joint[tiab] OR Shoulder[MeSH] OR Shoulder joint[MeSH], (2) Multidirectional[tiab], (3) Instability[tiab] OR Joint instability[MeSH]. Sixty-eight publications which met our criteria were included. Results: There was a high degree of heterogeneity in the definition of MDI. Thirty-one studies (46%) included a trauma etiology in the definition, while 23 studies (34%) did not. Twenty-five studies (37%) excluded patients with labral or bony injuries. Only 15 (22%) studies defined MDI as a global instability (instability in all directions), while 28 (41%) studies considered MDI to be instability in two directions, of which one had to include the inferior direction. Six (9%) studies included the presence of global ligamentous laxity as part of the definition. To improve scientific accuracy, the authors propose a novel AB classification which considers traumatic etiology and the presence of hyperlaxity when subdividing MDI. Conclusion: MDI is defined as symptomatic instability of the shoulder joint in two or more directions. A comprehensive classification system that considers predisposing trauma and the presence of hyperlaxity can provide a more precise assessment of the various existing subtypes of MDI. Level of Evidence: III.

Does Patient Blood Management Affect Outcomes in Metastatic Spine Tumour Surgery? A Review of Current Concepts.

STUDY DESIGN: Narrative review. OBJECTIVE: The spine is the most common site of metastases, associated with decreased quality of life. Increase in metastatic spine tumour surgery (MSTS) has caused us to focus on the management of blood, as blood loss is a significant morbidity in these patients. However, blood transfusion is also not without its own risks, and hence this led to blood conservation strategies and implementation of a concept of patient blood management (PBM) in clinical practise focusing on these patients. METHODS: A narrative review was conducted and all studies that were related to blood management in metastatic spine disease as well as PBM surrounding this condition were included. RESULTS: A total of 64 studies were included in this review. We discussed a new concept of patient blood management in patients undergoing MSTS, with stratification to pre-operative and intra-operative factors, as well as anaesthesia and surgical considerations. The studies show that PBM and reduction in blood transfusion allows for reduced readmission rates, lower risks associated with blood transfusion, and lower morbidity for patients undergoing MSTS. CONCLUSION: Through this review, we highlight various pre-operative and intra-operative methods in the surgical and anaesthesia domains that can help with PBM. It is an important concept with the significant amount of blood loss expected from MSTS. LEVEL OF EVIDENCE: Not applicable.

A novel parallel ant colony optimization algorithm for mobile robot path planning.

With the continuous development of mobile robot technology, its application fields are becoming increasingly widespread, and path planning is one of the most important topics in the field of mobile robot research. This paper focused on the study of the path planning problem for mobile robots in a complex environment based on the ant colony optimization (ACO) algorithm. In order to solve the problems of local optimum, susceptibility to deadlocks, and low search efficiency in the traditional ACO algorithm, a novel parallel ACO (PACO) algorithm was proposed. The algorithm constructed a rank-based pheromone updating method to balance exploration space and convergence speed and introduced a hybrid strategy of continuing to work and killing directly to address the problem of deadlocks. Furthermore, in order to efficiently realize the path planning in complex environments, the algorithm first found a better location for decomposing the original problem into two subproblems and then solved them using a parallel programming method-single program multiple data (SPMD)-in MATLAB. In different grid map environments, simulation experiments were carried out. The experimental results showed that on grid maps with scales of 20 $ \times $ 20, 30 $ \times $ 30, and 40 $ \times $ 40 compared to nonparallel ACO algorithms, the proposed PACO algorithm had less loss of solution accuracy but reduced the average total time by 50.71, 46.83 and 46.03%, respectively, demonstrating good solution performance.

Enhanced innate responses in microglia derived from retinoblastoma patient-specific iPSCs.

RB1 deficiency leads to retinoblastoma (Rb), the most prevalent intraocular malignancy. Tumor-associated macrophages (TAMs) are related to local inflammation disorder, particularly by increasing cytokines and immune escape. Microglia, the unique resident macrophages for retinal homeostasis, are the most important immune cells of Rb. However, whether RB1 deficiency affects microglial function remain unknown. In this study, microglia were successfully differentiated from Rb patient- derived human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs), and then we investigated the function of RB1 in microglia by live imaging phagocytosis assay, immunofluorescence, RNA-seq, qRT-PCR, ELISA and retina organoids/microglia co-culturing. RB1 was abundantly expressed in microglia and predominantly located in the nucleus. We then examined the phagocytosis ability and secretion function of iMGs in vitro. We found that RB1 deficiency did not affect the expression of microglia-specific markers or the phagocytic abilities of these cells by live-imaging. Upon LPS stimulation, RB1-deficient microglia displayed enhanced innate immune responses, as evidenced by activated MAPK signaling pathway and elevated expression of IL-6 and TNF-α at both mRNA and protein levels, compared to wildtype microglia. Furthermore, retinal structure disruption was observed when retinal organoids were co-cultured with RB1-deficient microglia, highlighting the potential contribution of microglia to Rb development and potential therapeutic strategies for retinoblastoma.

Implant and construct decision-making in metastatic spine tumour surgery: a review of current concepts with a decision-making algorithm.

STUDY DESIGN: Narrative Review. OBJECTIVE: Metastatic spine tumour surgery (MSTS) is an important treatment modality of metastatic spinal disease (MSD). Increase in MSTS has been due to improvements in our oncological treatment, as patients have increased longevity and even those with poorer comorbidities are now being considered for surgery. However, there is currently no guideline on how MSTS surgeons should select the appropriate levels to instrument, and which type of implants should be utilised. METHODS: The current literature on MSTS was reviewed to study implant and construct decision making factors, with a view to write this narrative review. All studies that were related to instrumentation in MSTS were included. RESULTS: A total of 58 studies were included in this review. We discuss novel decision-making models that should be taken into account when planning for surgery in patients undergoing MSTS. These factors include the quality of bone for instrumentation, the extent of the construct required for MSTS patients, the use of cement augmentation and the choice of implant. Various studies have advocated for the use of these modalities and demonstrated better outcomes in MSTS patients when used appropriately. CONCLUSION: We have established a new instrumentation algorithm that should be taken into consideration for patients undergoing MSTS. It serves as an important guide for surgeons treating MSTS, with the continuous evolvement of our treatment capacity in MSD.

P2 purinergic receptors regulate the progression of colorectal cancer.

More and more studies have revealed that P2 purinergic receptors play a key role in the progression of colorectal cancer (CRC). P2X and P2Y purinergic receptors can be used as promoters and regulators of CRC and play a dual role in the progression of CRC. CRC microenvironment is rich in ATP and its cleavage products (ADP, AMP, Ado), which act as activators of P2X and P2Y purinergic receptors. The activation of P2X and P2Y purinergic receptors regulates the progression of CRC mainly by regulating the function of immune cells and mediating different signal pathways. In this paper, we focus on the specific mechanisms and functional roles of P2X7, P2Y12, and P2Y2 receptors in the growth and progression of CRC. The antagonistic effects of these selective antagonists of P2X purinergic receptors on the growth, invasion, and metastasis of CRC were further discussed. Moreover, different studies have reported that P2X7 receptor can be used as an effective predictor of patients with CRC. All these indicate that P2 purinergic receptors are a key regulator of CRC. Therefore, antagonizing P2 purinergic receptors may be an innovative treatment for CRC.

Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis-Related Th17 Response by Host-Microbe Retinoic Acid Biosynthesis.

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.