Lone-Star retractor perineal exposure method for laparoscopic abdominal perineal resection of rectal cancer.

BACKGROUND: The abdominal perineal resection (APR), historically referred to as Mile's procedure, stands as a time-honored surgical intervention for rectal cancer management. Advancements in surgical techniques and the advent of neoadjuvant therapies have significantly improved the rate of sphincter preservation among patients afflicted with rectal cancer, including those with ultralow rectal cancer. Despite these improvements, APR maintains its irreplaceable role in the clinical landscape, particularly for cases involving low rectal cancer with encroachment on the external anal sphincter or levator ani muscles. Optimal perineal exposure stands as a pivotal phase in APR, given that the precision of this maneuver is directly correlated with both the safety of the surgery and the patient's subsequent long-term prognosis. AIM: To evaluate the value of Lone-Star retractor (LSR) perineal exposure method in the treatment for laparoscopic APR of rectal cancer. METHODS: We reviewed the records of 38 patients with rectal cancer at Anqing Municipal Hospital from January 2020 to December 2023, including 20 patients who underwent the APR procedure with a LSR perineal exposure method (LSR group) and 18 patients who underwent the APR procedure with a conventional perineal exposure method (control group). In the LSR group, following incision of the skin and subcutaneous tissue, the LSR was placed and dynamically adjusted according to the surgical plane to fully expose the perineal operative field. RESULTS: A total of 38 patients underwent laparoscopic APR, none of whom were found to have distant metastasis upon intraoperative exploration. Perineal blood loss, the postoperative hospital stays and the wound pain scores in the LSR group were significantly lower than those in the control group. A single surgeon completed the perineal operation significantly more often in the LSR group than in the control group (P < 0.05). The incidence of infection via the perineal incision in the LSR group was significantly lower than that in the control group (P < 0.05). No cases of distant metastasis or local recurrence were found among the patients at the postoperative follow-up. CONCLUSION: The application of the LSR technique might be helpful for performing perineal exposure during APR for rectal cancer and could reduce the incidence of perineal complications, shorten the postoperative hospital stay, improve postoperative pain, and allow one surgeon to perform the perineal operation.

Catalytic Upcycling of Polyolefins.

The large production volumes of commodity polyolefins (specifically, polyethylene, polypropylene, polystyrene, and poly(vinyl chloride)), in conjunction with their low unit values and multitude of short-term uses, have resulted in a significant and pressing waste management challenge. Only a small fraction of these polyolefins is currently mechanically recycled, with the rest being incinerated, accumulating in landfills, or leaking into the natural environment. Since polyolefins are energy-rich materials, there is considerable interest in recouping some of their chemical value while simultaneously motivating more responsible end-of-life management. An emerging strategy is catalytic depolymerization, in which a portion of the C-C bonds in the polyolefin backbone is broken with the assistance of a catalyst and, in some cases, additional small molecule reagents. When the products are small molecules or materials with higher value in their own right, or as chemical feedstocks, the process is called upcycling. This review summarizes recent progress for four major catalytic upcycling strategies: hydrogenolysis, (hydro)cracking, tandem processes involving metathesis, and selective oxidation. Key considerations include macromolecular reaction mechanisms relative to small molecule mechanisms, catalyst design for macromolecular transformations, and the effect of process conditions on product selectivity. Metrics for describing polyolefin upcycling are critically evaluated, and an outlook for future advances is described.

Case report: Near-fatal hypermagnesemia resulting from the use of Epsom salts in a patient with normal renal function.

Hypermagnesemia commonly occurs in patients with renal dysfunction. Diagnosing hypermagnesemia represents a challenge due to its rarity and the absence of routine monitoring of magnesium levels. Furthermore, the lack of awareness among clinicians regarding this uncommon condition frequently leads to delayed diagnoses. Few patients survive with a serum magnesium level exceeding 7 mmol/L. This article presents a case study of near-fatal hypermagnesemia resulting from the oral administration of Epsom salts in a patient with normal renal function. A 60-year-old female presented to the gastroenterology department on Oct. 6, 2023, with a 3-day history of black stools. She underwent subtotal gastrectomy in 2005 and has a stable history of nephrotic syndrome. To investigate the cause of her bleeding, electronic gastroscopy and colonoscopy were scheduled for Oct. 11, 2023. She experienced a sudden loss of consciousness 30 min after the ingestion of Epsom salts. The attending physician suspected a severe magnesium poisoning. She was promptly administered calcium gluconate, underwent tracheal intubation with ambu bag ventilation, and received early continuous renal replacement therapy (CRRT). Swift diagnosis and CRRT contributed to a reduction in her serum magnesium levels from an initial 8.71 mmol/L to 1.35 mmol/L, leading to a remarkable improvement in the toxic symptoms associated with hypermagnesemia. Subsequently, she was managed in the gastroenterology department, with gastroscopy revealing bleeding from the gastrointestinal anastomotic ulcer. Following conservative treatments including acid suppression, stomach protection, and hemostasis, her symptoms improved, and she was successfully discharged. This study aims to alert clinicians to the possibility of hypermagnesemia in individuals with normal renal function. Physicians should exercise caution when prescribing Epsom salts to patients with underlying gastrointestinal conditions. If necessary, alternative drug therapies may be considered to mitigate the risk of hypermagnesemia. Timely intervention is pivotal in averting life-threatening complications linked to hypermagnesemia.

[Shenfu Injection regulates macrophage polarization via TLR4/NF-κB pathway to reduce inflammation in chronic heart failure].

This study aimed to investigate the therapeutic effect of Shenfu Injection on mice with chronic heart failure(CHF) and its effect on macrophage polarization. C57BL/6J mice were randomly assigned to the normal and model groups. The CHF model was established by intraperitoneal injection of isoproterenol(ISO, 7.5 mg·kg~(-1), 28 d). The successful modeling was determined by asses-sing the cardiac function and N-terminal pro-brain natriuretic peptide(NT-proBNP). The modeled mice were randomly divided into the model group, Shenfu Injection group, and TAK-242 group, and were injected intraperitoneally with the corresponding drugs for 15 days. Cardiac function was evaluated using echocardiography. Hematoxylin-eosin(HE) staining was used to detect the pathomorphology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the values of serum NT-proBNP, interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), IL-10, and arginase 1(Arg-1). Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. Quantitative polymerase chain reaction(qPCR) and Western blot were used to detect the changes in the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) pathway-related mRNA and protein expressions. Compared with the normal group, mice in the model group had lower values of left ventricular ejection fraction(LVEF) and left ventricular fractional shorte-ning(LVFS), higher values of left ventricular internal diastolic end-diastolic(LVIDd), left ventricular internal diastolic end-systolic(LVIDs), NT-proBNP, TNF-α, and IL-6(P<0.01); the number of macrophages increased in cardiac tissues(P<0.05), and the values of M1-F4/80~+CD86~+ were increased(P<0.01), while the values of M2-F4/80~+CD163~+ decreased(P<0.05); the mRNA and protein expressions of TLR4, myeloid differentiation factor 88(MyD88), IκB kinase α(IKKα), and NF-κB p65 in myocardial tissues were significantly elevated(P<0.05, P<0.01). Compared with the model group, mice in the Shenfu Injection and TAK-242 groups showed elevated LVEF, LVFS, IL-10, and Arg-1 levels, and decreased LVIDd, LVIDs, NT-proBNP, TNF-α, and IL-6 levels(P<0.05, P<0.01); the cardiac F4/80~+CD11b~+(macrophage) and M1-F4/80~+ CD86~+ values were significantly down-regulated, while M2-F4/80~+CD163~+ values were increased(P<0.05, P<0.01); and the mRNA and protein expressions of TLR4, MyD88, IKKα, and NF-κB p65 in myocardial tissues were notably decreased(P<0.05, P<0.01). CHF mice have an imbalance of M1/M2 macrophage polarization, with M1-type macrophages predominating. Shenfu Injection promotes macrophage polarization towards M2, inhibits M1-type macrophage activation, and attenuates inflammatory responses in heart failure by regulating the TLR4/NF-κB signaling pathway.

Unlocking Clinical Insights: Lymphocyte-Specific Protein Tyrosine Kinase Candidates as Promising Therapeutic Targets for Pancreatic Cancer Risk Stratification.

Background: Uncover the pivotal link between lymphocyte-specific protein tyrosine kinase (Lck)-related genes and clinical risk stratification in pancreatic cancer. Methods: This study identifies shared genes between differentially expressed genes (DEGs) and Lck-related genes in pancreatic cancer using a methodological framework rooted in The Cancer Genome Atlas database. Feature gene selection is accomplished and a signature model is constructed. Statistical significant clinical endpoints such as overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were defined. Results: After performing random survival forest, Lasso regression, and multivariate Cox regression model, 7 trait genes out of 272 Lck-associated DEGs are selected to create a signature model that is independent of other clinical factors and can predict OS and DSS. It appears that high-risk patients have activated the TP53 signaling pathway and the cell cycle signaling pathway. LAMA3 turned out to be the hub gene of the signature with high expression in pancreatic cancer. Patients with increased expression of LAMA3 had a short OS, DSS, and PFI in comparison. The candidate competing endogenous RNA network of LAMA3 turned out to be OPI5-AS1/hsa-miR-186-5p/LAMA3 axis. Conclusions: A characteristic signature of seven Lck-related genes, especially LAMA3, has been shown to be a key factor in clinical risk stratification for pancreatic cancer.

IGSF8 is an innate immune checkpoint and cancer immunotherapy target.

Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors. An antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells in vitro and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T cell signaling in vivo. In syngeneic tumor models, anti-IGSF8 alone, or in combination with anti-PD1, inhibits tumor growth. Our results indicate that IGSF8 is an innate immune checkpoint that could be exploited as a therapeutic target.

Progress of lymphocyte activation gene 3 and programmed cell death protein 1 antibodies for cancer treatment: A review.

The application of immune checkpoint inhibitors has proven to be an effective treatment for cancer. Immune checkpoints such as programmed cell death protein 1/programmed cell death protein 1 ligand 1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T-cell immunoglobulin-3 (TIM-3), T-cell immunoglobulin and ITIM domain (TIGIT), and lymphocyte activation gene-3 (LAG-3) have received extensive attention, and the efficacy of antibodies or inhibitors against these checkpoints (either alone or in combination) has been evaluated in many tumors. This paper provides a brief overview of the PD-1 and LAG-3 checkpoints, and then shifts focus to the combined use of PD-1 and LAG-3 antibodies in both in vivo and in vitro experiments. In the in vitro experiments, we examined the correlation between the expression and activation of these inhibitors on T cells, and also assessed toxicity in animals in preparation for in vivo experiments. The effects of the combined use of PD-1 and LAG-3 antibodies were then summarized in animal models of melanoma, MC38 carcinoma, and other tumors. In clinical studies, the combined application of these antibodies was assessed in patients with melanoma, colorectal, breast, and renal cell cancers, as well as other solid tumors. In general, the combination of PD-1 and LAG-3 antibodies has shown promising results in both in vivo and in vitro studies.

Endothelial extracellular vesicles induce acute lung injury via follistatin-like protein 1.

Cardiopulmonary bypass has been speculated to elicit systemic inflammation to initiate acute lung injury (ALI), including acute respiratory distress syndrome (ARDS), in patients after cardiac surgery. We previously found that post-operative patients showed an increase in endothelial cell-derived extracellular vesicles (eEVs) with components of coagulation and acute inflammatory responses. However, the mechanism underlying the onset of ALI owing to the release of eEVs after cardiopulmonary bypass, remains unclear. Plasma plasminogen-activated inhibitor-1 (PAI-1) and eEV levels were measured in patients with cardiopulmonary bypass. Endothelial cells and mice (C57BL/6, Toll-like receptor 4 knockout (TLR4-/-) and inducible nitric oxide synthase knockout (iNOS-/-)) were challenged with eEVs isolated from PAI-1-stimulated endothelial cells. Plasma PAI-1 and eEVs were remarkably enhanced after cardiopulmonary bypass. Plasma PAI-1 elevation was positively correlated with the increase in eEVs. The increase in plasma PAI-1 and eEV levels was associated with post-operative ARDS. The eEVs derived from PAI-1-stimulated endothelial cells could recognize TLR4 to stimulate a downstream signaling cascade identified as the Janus kinase 2/3 (JAK2/3)-signal transducer and activator of transcription 3 (STAT3)-interferon regulatory factor 1 (IRF-1) pathway, along with iNOS induction, and cytokine/chemokine production in vascular endothelial cells and C57BL/6 mice, ultimately contributing to ALI. ALI could be attenuated by JAK2/3 or STAT3 inhibitors (AG490 or S3I-201, respectively), and was relieved in TLR4-/- and iNOS-/- mice. eEVs activate the TLR4/JAK3/STAT3/IRF-1 signaling pathway to induce ALI/ARDS by delivering follistatin-like protein 1 (FSTL1), and FSTL1 knockdown in eEVs alleviates eEV-induced ALI/ARDS. Our data thus demonstrate that cardiopulmonary bypass may increase plasma PAI-1 levels to induce FSTL1-enriched eEVs, which target the TLR4-mediated JAK2/3/STAT3/IRF-1 signaling cascade and form a positive feedback loop, leading to ALI/ARDS after cardiac surgery. Our findings provide new insight into the molecular mechanisms and therapeutic targets for ALI/ARDS after cardiac surgery.

EpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors.

The efficacy of CAR-T cells for solid tumors is unsatisfactory. EpCAM is a biomarker of epithelial tumors, but the clinical feasibility of CAR-T therapy targeting EpCAM is lacking. Here, we report pre- and clinical investigations of EpCAM-CAR-T cells for solid tumors. We demonstrated that EpCAM-CAR-T cells costimulated by Dectin-1 exhibited robust antitumor activity without adverse effects in xenograft mouse models and EpCAM-humanized mice. Notably, in clinical trials for epithelial tumors (NCT02915445), 6 (50%) of the 12 enrolled patients experienced self-remitted grade 1/2 toxicities, 1 patient (8.3%) experienced reversible grade 3 leukopenia, and no higher-grade toxicity reported. Efficacy analysis determined two patients as partial response. Three patients showed >23 months of progression-free survival, among whom one patient experienced 2-year progress-free survival with detectable CAR-T cells 200 days after infusion. These data demonstrate the feasibility and tolerability of EpCAM-CAR-T therapy.

Chimeric Antigen Receptor-T Cell Therapy Decreases Distant Metastasis and Inhibits Local Recurrence Post-surgery in Mice.

Distant metastasis and primary tumor relapse are the two main hurdles to the success of surgical treatment for cancer patients. Circulating tumor cells (CTCs) and incomplete surgical resection are the primary cause of distant metastasis and local recurrence of tumors, respectively. Chimeric antigen receptor (CAR)-modified T cells target residual carcinomas and CTCs hold the potential to inhibit primary recurrence and reduce tumor metastasis, but the experimental evidence is lacking. Here, we developed a surgery-induced tumor metastasis model in immunocompetent mice to investigate the efficacy of CAR-T cells therapy in preventing metastasis and local recurrence. We observed that subcutaneous tumor resection has induced a large number of CTCs intravasated into circulation. EpCAM-specific CAR-T was effective in clearing CTCs following surgical removal of the tumor. This resulted in less pulmonary metastasis and longer survival in mice when compared to mice treated with surgery followed by Mock-T cells infusion. In addition, the local relapse was obviously inhibited at the surgical site followed by EpCAM-CAR-T cell treatment. This study demonstrated that CAR-T cell therapy can be an adjuvant treatment following surgery to prevent tumor metastasis and inhibit primary tumor relapse for cancer patients.

Erratum: [Corrigendum] MicroRNA­23a inhibits endometrial cancer cell development by targeting SIX1.

[This corrects the article DOI: 10.3892/ol.2019.10694.].

Surgical Treatment of Osteosarcoma Induced Distant Pre-Metastatic Niche in Lung to Facilitate the Colonization of Circulating Tumor Cells.

Recently, the major challenge in treating osteosarcoma patients is the metastatic disease, most commonly in the lungs. However, the underlying mechanism of recurrence and metastasis of osteosarcoma after surgical resection of primary tumor remains unclear. This study aims to investigate whether the pulmonary metastases characteristic of osteosarcoma is associated with surgical treatment and whether surgery contributes to the formation of pre-metastatic niche in the distant lung tissue. In the current study, the authors observe the presence of circulating tumor cells in patients undergoing surgical resection of osteosarcoma which is correlated to tumor recurrence. The pulmonary infiltrations of neutrophils and Gr-1+ myeloid cells are characterized to form a pre-metastatic niche upon the exposure of circulating tumor cells after surgical resection. It is found that mitochondrial damage-associated molecular patterns released from surgical resection contribute to the formation of pre-metastatic niche in lung through IL-1ß secretion. This study reveals that surgical management for osteosarcoma, irrespective of the primary tumor, might promote the formation of postoperative pre-metastatic niche in lung which is with important implications for developing rational therapies during peri-operative period.

Deep learning enabled miniature mass spectrometer for rapid qualitative and quantitative analysis of pesticides on vegetable surfaces.

Excessive pesticide use poses a significant threat to food safety. Rapid on-site detection of multi-target pesticide residues in vegetables is crucial due to their widespread distribution and limited shelf life. In this study, a rapid on-site screening method for pesticide residues on vegetable surfaces was developed by employing a miniature mass spectrometer. A direct pretreatment method involves placing vegetables and elution solution into a customized flexible ziplock bag, allowing thorough mixing, washing, and filtration. This process effectively removes pesticide residues from vegetable surfaces with minimal organic solvent usage and can be completed within 2 min. Moreover, this study introduced a deep learning algorithm based on a one-dimensional convolutional neural network, coupled with a feature database, to autonomously discriminate detection outcomes. By combining full scan MS and tandem MS analysis methods, the proposed method achieved a qualitative recognition accuracy of 99.62%. Following the qualitative discrimination stage, the target pesticide residue and internal standard can be simultaneously isolated and fragmented in the ion trap, thus enabling on-site quantitative analysis and warning. This method achieved a quantitative detection limit of 10 µg/kg for carbendazim in cowpea. These results demonstrate the feasibility of the proposed analytical system and strategy in food safety applications.

Effect evaluation and influencing factor analysis of vaginal carbon dioxide laser in the treatment of stress urinary incontinence.

To evaluate the clinical efficacy of carbon dioxide laser in the treatment of female stress urinary incontinence and analyze the influencing factors. A total of 46 patients with stress urinary incontinence treated in the Affiliated Hospital of Nantong University from March 2021 to August 2022 were included through strict inclusion criteria and exclusion criteria. All patients were treated with transvaginal carbon dioxide laser therapy, and Patient Global Impression of Change (PGI-C) was used to evaluate patients' subjective satisfaction after treatment. The efficacy was evaluated by patient's subjective assessment of leakage, IngelmanSundberg scale, 1-h urine pad test, and international consultation on incontinence questionnaire short form (ICI-Q-SF) before and after treatment, and the adverse reactions after treatment were recorded. The treatment effect was divided into "significant effect group" and "no significant effect group" by subjective satisfaction and post-treatment-related scale evaluation. After laser treatment, patients' subjective symptom improved, the volume of 1-h urine pad test was reduced, and the ICI-Q-SF score was decreased, and the differences were statistically significant (P < 0.05). There was no significant difference in IngelmanSundberg scale before and after treatment (P = 1.00). Multivariate logistic regression analysis showed that pad test volume was significantly correlated with treatment effect (P = 0.007). Transvaginal carbon dioxide laser is a safe and effective method for the treatment of mild to moderate stress urinary incontinence in females. The less severe the urinary leakage, the better the treatment effect.

Immune reconstitution inflammatory syndrome drives emergence of HIV drug resistance from multiple anatomic compartments in a person living with HIV.

Reservoirs of HIV maintained in anatomic compartments during antiretroviral therapy prevent HIV eradication. However, mechanisms driving their persistence and interventions to control them remain elusive. Here we report the presence of an inducible HIV reservoir within antigen-specific CD4+T cells in the central nervous system of a 59-year-old male with progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome (PML-IRIS). HIV production during PML-IRIS was suppressed by modulating inflammation with corticosteroids; selection of HIV drug resistance caused subsequent breakthrough viremia. Therefore, inflammation can influence the composition, distribution and induction of HIV reservoirs, warranting it as a key consideration for developing effective HIV remission strategies.

Clinical outcomes of an olive wire and external fixator versus a metallic screw in the treatment of inferior tibiofibular syndesmosis injuries in ankle fractures.

BACKGROUND: Metal screws are the most widely used in treating syndesmotic injuries, but failure and the rigidity of the screws can threaten the success of the treatment and increase the cost of care. We have provided an alternative with an olive wire and external fixator(OWEF) used for syndesmotic fixation. METHODS: A retrospective longitudinal follow-up study was conducted. From February 2011 to January 2018, 58 of 72 patients with ankle fractures and associated syndesmotic disruption were treated with either screw or OWEF fixation. The costs, complications, and clinical outcomes using Olerud-Molander score and Visual Analog score in screw and OWEF fixation group were compared. RESULTS: We found the severity of the injury, BMI of the patients and the different fixation methods were determinants of the complications and clinical outcomes. But if no malreduction of the syndesmosis was present, no difference in clinical result was detected. CONCLUSION: The OWEF method appeared to be at least equally functional and effective to screw fixation while maintaining possible lower complication rate. LEVELS OF CLINICAL EVIDENCE: Level 3.

Implementing reactive secondary electrospray ionization based on gas-droplet reactions for VOC analysis.

Gas-droplet reactions occur at the microdroplet interface and tend to be greatly accelerated, which has great potential value in chemical analysis. To exploit such value, we combined online derivatization with secondary electrospray ionization (SESI) to implement a special ionization technique, termed reactive SESI, for rapid analysis of gas samples. Specifically, a suitable reagent was added to the spray solvent of SESI to initiate rapid derivatization of gas analytes in the microdroplets. The product ions are subsequently detected using a mass spectrometer. Compared to offline derivatization in bulk solution, reactive SESI can provide a higher yield and a faster reaction rate, and it allows the detection of intermediate ions. It is found that the signal changes of the analyte, intermediate, and product ions are highly consistent, indicating that a two-phase derivatization process may occur at the droplet interface. For reactive SESI-MS analysis, the use of a sub-ambient pressure SESI source can significantly improve the detection efficiency, making this technique truly useful for analytical applications, including the quantification of formaldehyde at tens of ppb levels in air, as well as the detection of various trace VOCs in exhaled breath from mice.

NLRP3 inflammasome up-regulates major histocompatibility complex class I expression and promotes inflammatory infiltration in polymyositis.

OBJECTIVE: This study was designed to investigate the role of the nucleotide-binding-domain -and leucine-rich repeat -containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome in the pathogenesis of polymyositis (PM). METHODS: Immunochemistry was performed to analyze the NLRP3, caspase-1 and interleukin-1 beta (IL-1ß) expression in the muscle tissue of PM patients. Rat model of PM and C2C12 cell were used to investigate the potential role of NLRP3 inflammasome in PM. RESULTS: The percentage of CD 68+ macrophages, and the expression levels of NLRP3, caspase-1 and IL-1ß in the muscle tissue were elevated in 27 PM patients. LPS/ATP treatment resulted in activation of NLRP3 inflammasome and secretion of IL-1ß as well as interferons (IFNs) and monocyte chemotactic protein-1 (MCP-1) in the Raw 264.7 macrophages. Meanwhile, LPS/ATP challenged activation of NLRP3 inflammasome induced overexpression of major histocompatibility complex class I (MHC-I), a key molecular of PM in the co-cultured C2C12 cells. The effect was decreased by treatment of NLRP3 inflammasome inhibitor MCC950 or siRNA of NLRP3 inflammasome. These findings suggested certain levels of IL-1ß rather than IFNs up-regulated MHC-I expression in C2C12 cells. IL-1ß blockade using neutralizing IL-1ß monoclonal antibody or siRNA of IL-1ß suppressed MHC-I overexpression. In vivo, NLRP3 inflammasome inhibition by MCC950 reduced the expression of NLRP3, IL-1ß and MHC-I in the muscle tissue of PM modal rats. Also, it attenuated the intensity of muscle inflammation as well as the CRP, CK, and LDH levels in the serum. CONCLUSION: NLRP3/caspase-1/IL-1ß axis may play an important role in the development of PM. Inhibition of NLRP3 activation may hold promise in the treatment of PM.

Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets.

Immunotherapies like the adoptive transfer of gene-engineered T cells and immune checkpoint inhibitors are novel therapeutic modalities for advanced cancers. However, some patients are refractory or resistant to these therapies, and the mechanisms underlying tumor immune resistance have not been fully elucidated. Immunosuppressive cells such as myeloid-derived suppressive cells, tumor-associated macrophages, tumor-associated neutrophils, regulatory T cells (Tregs), and tumor-associated dendritic cells are critical factors correlated with immune resistance. In addition, cytokines and factors secreted by tumor cells or these immunosuppressive cells also mediate the tumor progression and immune escape of cancers. Thus, targeting these immunosuppressive cells and the related signals is the promising therapy to improve the efficacy of immunotherapies and reverse the immune resistance. However, even with certain success in preclinical studies or in some specific types of cancer, large perspectives are unknown for these immunosuppressive cells, and the related therapies have undesirable outcomes for clinical patients. In this review, we comprehensively summarized the phenotype, function, and potential therapeutic targets of these immunosuppressive cells in the tumor microenvironment.

An endorectal ultrasound-based radiomics signature for preoperative prediction of lymphovascular invasion of rectal cancer.

OBJECTIVE: To investigate whether radiomics based on ultrasound images can predict lymphovascular invasion (LVI) of rectal cancer (RC) before surgery. METHODS: A total of 203 patients with RC were enrolled retrospectively, and they were divided into a training set (143 patients) and a validation set (60 patients). We extracted the radiomic features from the largest gray ultrasound image of the RC lesion. The intraclass correlation coefficient (ICC) was applied to test the repeatability of the radiomic features. The least absolute shrinkage and selection operator (LASSO) was used to reduce the data dimension and select significant features. Logistic regression (LR) analysis was applied to establish the radiomics model. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the comprehensive performance of the model. RESULTS: Among the 203 patients, 33 (16.7%) were LVI positive and 170 (83.7%) were LVI negative. A total of 5350 (90.1%) radiomic features with ICC values of ≥ 0.75 were reported, which were subsequently subjected to hypothesis testing and LASSO regression dimension reduction analysis. Finally, 15 selected features were used to construct the radiomics model. The area under the curve (AUC) of the training set was 0.849, and the AUC of the validation set was 0.781. The calibration curve indicated that the radiomics model had good calibration, and DCA demonstrated that the model had clinical benefits. CONCLUSION: The proposed endorectal ultrasound-based radiomics model has the potential to predict LVI preoperatively in RC.