A novel perineal exposure method in laparoscopic abdominal perineal resection of rectal cancer: a case series study.

BACKGROUND: Abdominal perineal resection (APR) of rectal cancer, also known as Mile's procedure, is a classic procedure for the treatment of rectal cancer. Through the improvement of surgical skills and neoadjuvant therapy, the sphincter-preserving rate in rectal cancer patients has improved, even in patients with ultralow rectal cancer who underwent APR in the past. However, APR cannot be completely replaced by low anterior resection (LAR) in reality. APR still has its indications, when the tumor affects the external sphincter, etc. Good perineal exposure in APR is difficult and can seriously affect surgical safety and the long-term prognosis. METHODS: We reviewed the records of 16 consecutive patients with rectal cancer who underwent APR at Anqing Municipal Hospital from January 2022 to April 2023, including 11 males and 5 females, with an average age of 64.8 ± 10.3 years. The perineal operation was completed with the Lone-Star® retractor-assisted (LSRA) exposure method. After incising the skin and subcutaneous tissue, a Lone-Star® retractor was placed, and the incision was retracted in surrounding directions with 8 small retractors, which facilitated the freeing of deep tissues. We dynamically adjusted the retractor according to the plane to fully expose the surgical field. RESULTS: All 16 patients underwent laparoscopic-assisted APR successfully. Thirteen procedures were performed independently by a single person, and the others were completed by two persons due to intraoperative arterial hemostasis. All specimens were free of perforation and had a negative circumferential resection margin (CRM). Postoperative complications occurred in 4 patients, including urinary retention in 1 patient, pulmonary infection in 1 patient, intestinal adhesion in 1 patient and peristomal dermatitis in 1 patient, and were graded as ClavienDindo grade 3 or lower and cured. No distant metastasis or local recurrence was found for any of the patients in the postoperative follow-up. CONCLUSIONS: The application of the LSRA exposure method might be helpful for perineal exposure during APR for rectal cancer, which could improve intraoperative safety and surgical efficiency, achieve one-person operation, and increase the comfort of operators.

Magnetic Graphene Oxide Nanocomposites Boosts Craniomaxillofacial Bone Regeneration by Modulating circAars/miR-128-3p/SMAD5 Signaling Axis.

Background: The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism. Methods: The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites. Results: We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites. Conclusion: We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.

Optimization of BBR Congestion Control Algorithm Based on Pacing Gain Model.

In 2016, Google proposed a congestion control algorithm based on bottleneck bandwidth and round-trip propagation time (BBR). The BBR congestion control algorithm measures the network bottleneck bandwidth and minimum delay in real-time to calculate the bandwidth delay product (BDP) and then adjusts the transmission rate to maximize throughput and minimize latency. However, relevant research reveals that BBR still has issues such as RTT unfairness, high packet loss rate, and deep buffer performance degradation. This article focuses on its most prominent RTT fairness issue as a starting point for optimization research. Using fluid models to describe the data transmission process in BBR congestion control, a fairness optimization strategy based on pacing gain is proposed. Triangular functions, inverse proportional functions, and gamma correction functions are analyzed and selected to construct the pacing gain model, forming three different adjustment functions for adaptive adjustment of the transmission rate. Simulation and real experiments show that the three optimization algorithms significantly improve the fairness and network transmission performance of the original BBR algorithm. In particular, the optimization algorithm that employs the gamma correction function as the gain model exhibits the best stability.

Graphdiyne Oxide-Mediated Photodynamic Therapy Boosts Enhancive T-Cell Immune Responses by Increasing Cellular Stiffness.

Purpose: Nanomaterial-based photodynamic therapy (PDT) has been commonly used for the treatment of cancerous tumors. Despite significant achievements made in this field, the intrinsic impact of nanomaterials-based PDT on the mechanical properties of oral squamous cell carcinoma (OSCC) cells is not entirely understood. Here, we used atomic force microscopy (AFM) to measure the stiffness of OSCC cells subjected to PDT in co-culture systems to evaluate the T cell-mediated cancer cell-killing effects. Methods: In this study, AFM was used to assess the stiffness of PDT-subjected cells. The phototoxicity of graphdiyne oxide (GDYO) was assessed using confocal laser scanning microscopy (CLSM), measurements of membrane cholesterol levels, and assessments of the F-actin cytoskeleton. A co-culture system was used to evaluate the effects of CD8+ T cells (cytotoxic T lymphocytes), demonstrating how PDT modulates the mechanical properties of cancer cells and activates T cell responses. The antitumor immunotherapeutic effect of GDYO was further evaluated in a murine xenograft model. Results: GDYO increased the mechanical stiffness of tumor cells and augmented T-cell cytotoxicity and inflammatory cytokine secretion (IFN-γ and TNF-α) under laser in vitro. Furthermore, GDYO-based PDT exerted inhibitory effects on OSCC models and elicited antitumor immune responses via specific cytotoxic T cells. Conclusion: These results highlight that GDYO is a promising candidate for OSCC therapy, shifting the mechanical forces of OSCC cells and breaking through the barriers of the immunosuppressive tumor microenvironment. Our study provides a novel perspective on nanomaterial-based antitumor therapies.

Size-optimized nuclear-targeting phototherapy enhances the type I interferon response for "cold" tumor immunotherapy.

There is growing interest in the effect of innate immune silencing in "cold" tumors, which always fail in the immune checkpoint blockade monotherapy using PD-L1 monoclonal antibodies (aPD-L1). Combination of aPD-L1 with photodynamic therapy, i.e., photoimmunotherapy, is a promising strategy to improve the mono immunotherapy. Nuclear-targeting nanoparticles could elicit a type I interferon (IFN)-mediated innate immune response and reverse the immunosuppressive microenvironment for long-term immunotherapy of "cold" tumors. Photosensitizers such as zinc phthalocyanine (ZnPc) have limited ability to target the nucleus and activate innate sensing pathways to minimize tumor recurrence. Additionally, the relationship between nanoparticle size and nuclear entry capacity remains unclear. Herein, graphene quantum dots (GQDs) were employed as aPD-L1 and ZnPc carriers. Three particle sizes (200 nm, 32 nm and 5 nm) of aPD-L1/ZnPc/GQD-PEG (PZGE) were synthesized and tested. The 5 nm nanoparticles achieved the best nuclear enrichment capacity contributing to their ultrasmall size. Notably, 5 nm PZGE-based photodynamic therapy enabled an amplification of the type I IFN-mediated innate immune response and could convert "immune-cold" tumors into "immune-hot" ones. Utilizing their size advantage to target the nucleus, 5 nm nanoparticles induced DNA damage and activated the type I IFN-mediated innate immune response, subsequently promoting cytotoxic T-lymphocyte infiltration and reversing negative PD-L1 expression. Furthermore, the nanoplatform we designed is promising for the effective suppression of distant oral squamous cell carcinoma. Thus, for the first time, this study presents a size design strategy for nuclear-targeted photo-controlled immune adjuvants and the nuclear-targeted phototherapy-mediated immunomodulatory functions of type I IFN innate immune signalling for "immune-cold" tumors. STATEMENT OF SIGNIFICANCE: The potential of commonly used photosensitizers to activate innate sensing pathways for producing type I IFNs is limited due to the lack of nuclear targeting. Facilitating the nuclear-targeting of photosensitizers to enhance innate immune response and execute long-term tumor killing effect would be a promising strategy for "cold" tumor photoimmunotherapy. Herein, we report an optimal size of PZGE nanoparticles that enable the nuclear-targeting of ZnPc, which reinforces the type I IFN-mediated innate immune response, synergistically reversing "cold tumors" to "hot tumors" for effective primary and distant tumor photoimmunotherapy. This work highlights the marked efficacy of ultrasmall nuclear-located nanocarriers and offers new insight into "immune-cold tumors" via prominent innate immune activation mediated by nuclear-targeting photoimmunotherapy.

Transcriptome-wide m6A methylome analysis uncovered the changes of m6A modification in oral pre-malignant cells compared with normal oral epithelial cells.

As the most common post-transcriptional RNA modification, m6A methylation extensively regulates the structure and function of RNA. The dynamic and reversible modification of m6A is coordinated by m6A writers and erasers. m6A reader proteins recognize m6A modification on RNA, mediating different downstream biological functions. mRNA m6A modification and its corresponding regulators play an important role in cancers, but its characteristics in the precancerous stage are still unclear. In this study, we used oral precancerous DOK cells as a model to explore the characteristics of transcriptome-wide m6A modification and major m6A regulator expression in the precancerous stage compared with normal oral epithelial cell HOEC and oral cancer cell SCC-9 through MeRIP-seq and RT-PCR. Compared with HOEC cells, we found 1180 hyper-methylated and 1606 hypo-methylated m6A peaks and 354 differentially expressed mRNAs with differential m6A peaks in DOK cells. Although the change of m6A modification in DOK cells was less than that in SCC-9 cells, mRNAs with differential m6A in both cell lines were enriched into many identical GO terms and KEGG pathways. Among the 20 known m6A regulatory genes, FTO, ALKBH5, METTL3 and VIRMA were upregulated or downregulated in DOK cells, and the expression levels of 10 genes such as METTL14/16, FTO and IGF2BP2/3 were significantly changed in SCC-9 cells. Our data suggest that precancerous cells showed, to some extent, changes of m6A modification. Identifying some key m6A targets and corresponding regulators in precancerous stage may provide potential intervention targets for the prevention of cancer development through epigenetic modification in the future.

Fire Source Localization Based on Distributed Temperature Sensing by a Dual-Line Optical Fiber System.

We propose a method for localizing a fire source using an optical fiber distributed temperature sensor system. A section of two parallel optical fibers employed as the sensing element is installed near the ceiling of a closed room in which the fire source is located. By measuring the temperature of hot air flows, the problem of three-dimensional fire source localization is transformed to two dimensions. The method of the source location is verified with experiments using burning alcohol as fire source, and it is demonstrated that the method represents a robust and reliable technique for localizing a fire source also for long sensing ranges.