[Relationship between short-chain fatty acids in the gingival crevicular fluid and periodontitis of stage â ¢ or â £].

OBJECTIVE: To analyze the concentration of formic acid, propionic acid and butyric acid in gingival crevicular fluid (GCF) of patients with stages Ⅲ and Ⅳ periodontitis, and their relationship with periodontitis. METHODS: The study enrolled 37 systemically healthy patients with periodontitis and 19 healthy controls who visited Department of Periodontology, Peking University School and Hospital of Stomatology from February 2008 to May 2011. Their GCFs were collected from the mesial-buccal site of one molar or incisor in each quadrant. Periodontal clinical parameters, including plaque index(PLI), probing depth(PD), bleeding index(BI), and attachment loss(AL). Concentrations of formic acid, propionic acid and butyric acid in the supernatant of the GCFs were analyzed by high-performance capillary electrophoresis (HPCE). The prediction ability of formic acid, propionic acid and butyric acid with the risk of periodontitis and the differences between grade B and grade C periodontitis were analyzed. RESULTS: In this study, 32 patients with stage Ⅲ and 5 patients with stage Ⅳ were enrolled, including 9 patients with grade B and 28 patients with grade C. Clinical periodontal variables in the patients with periodontitis were significantly higher than those in the control group (P<0.001). Formic acid was significantly lower in periodontitis than that in the control group [5.37 (3.39, 8.49) mmol/L vs. 12.29 (8.35, 16.57) mmol/L, P<0.001]. Propionic acid and butyric acid in periodontitis were significantly higher than those in the control group: Propionic acid, 10.23 (4.28, 14.90) mmol/L vs. 2.71 (0.00, 4.25) mmol/L, P < 0.001; butyric acid, 2.63 (0.47, 3.81) mmol/L vs. 0.00 (0.00, 0.24) mmol/L, P<0.001. There was no significant difference in formic acid, propionic acid and butyric acid concentrations between grade B and grade C periodontitis (P>0.05). Propionic acid and butyric acid in the deep pocket were significantly higher than in the shallow pocket, while the concentration of formic acid decreased with the increase of PD. Propionic acid (OR=1.51, 95%CI: 1.29-1.75) and butyric acid (OR=3.72, 95%CI: 1.93-7.17) were risk factors for periodontitis, while formic acid (OR=0.87, 95%CI: 0.81-0.93) might be a protective factor for periodontitis. Propionic acid (AUC=0.852, 95%CI: 0.805－0.900), butyric acid (AUC=0.889, 95%CI: 0.841－0.937), f (formic acid, AUC=0.844, 95%CI: 0.793－0.895) demonstrated a good predictive capacity for the risk of periodontitis. CONCLUSION: The concentration of formic acid decrease in the GCF of periodontitis patients, which is a protective factor for periodontitis, its reciprocal have good predictive capacity. However, propionic acid and butyric acid increase, which are risk factors for periodontitis and have good predictive capacity. The concentration of formic acid, propionic acid, and butyric acid vary with probing depth, but there is no significant difference between grade B and grade C periodontitis.

Effect of Preoperative Lifestyle Management and Prehabilitation on Postoperative Capability of Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The surgical intervention serves as the paramount and prevalent remedy for individuals afflicted with colorectal malignancies, with the significance of perioperative stewardship and convalescence being indisputable. Prehabilitation coupled with preoperative lifestyle modulation has demonstrated efficacy in patients subjected to certain classifications of abdominal procedures. However, the evidence pertaining to its impact on those battling colorectal cancer remains equivocal. METHODS: A meta-analysis, grounded in pairwise contrast, of randomized controlled trials (RCTs) was orchestrated, coupled with a systematic review, to probe the efficacy of preoperative lifestyle modulation and prehabilitation on patients' postoperative functionality and recuperation. An exhaustive exploration of 8 electronic databases and trial registries was undertaken to encompass all pertinent RCTs disseminated in English or Chinese from January 2012 through December 2022. Employing a random-effects model, we evaluated parameters such as the 6-minute walk test (6 MWT), complications, quality of life (QoL), aggregate and postoperative duration of hospitalization (tLHS and postLHS), and healthcare expenditure (HExp) for postoperative patients. RESULTS: A total of 28 RCTs were incorporated into the systematic review and meta-analysis. Relative to conventional preoperative care, rehabilitation or preoperative lifestyle management was found to enhance postoperative 6MWT (SMD 1.30, 95% CI 0.30 to 2.29) and diminish the complication rate (OR 0.53, 95% CI 0.40 to 0.69). Nonetheless, no significant discrepancies were observed in QoL (SMD 1.81, 95% CI -0.26 to 3.87), tLHS (SMD -0.26, 95% CI -0.68 to 0.15), and postLHS (SMD -1.46, 95% CI -3.12 to 0.20) between the groups. HExp could not be evaluated due to a lack of sufficient data for synthesis. Most pooled outcomes exhibited significant heterogeneity, urging a cautious interpretation. Subgroup analysis revealed that nutritional interventions could mitigate the incidence of complications, and preoperative exercise could improve tLHS and postLHS. A combined approach of physical, nutritional, and psychological intervention or prehabilitation proved superior to any single intervention in enhancing postoperative capabilities. CONCLUSION: This meta-analysis delineated the efficacy of preoperative interventions on postoperative capabilities in patients with colorectal cancer, thereby offering evidence for clinical practice. It was concluded that preoperative interventions are unequivocally beneficial for postoperative functional recovery and the reduction of complication rates in patients with colorectal cancer. Nonetheless, the acquisition of more high-level evidence is still necessitated to further ascertain the effectiveness of this strategy for other patient groups and to establish its best practices. The heterogeneity in the pooled outcomes underlines the need for future studies to be more uniform in their design and reporting, which would facilitate more robust and reliable meta-analyses.

The relationship between physical activity, self-efficacy and quality of life in colorectal cancer survivors: a multicenter cross-sectional study.

PURPOSE: This study aimed to investigate the current situation and factors influencing physical activity, self-efficacy, and quality of life in Chinese colorectal cancer survivors. Additionally, this study explored the associations between physical activity, self-efficacy, and quality of life. METHODS: A multicenter, cross-sectional study was conducted, involving 173 colorectal cancer survivors with a mean age of 59 years. Self-reported data on basic demographic characteristics, physical activity, self-efficacy, and quality of life were collected. RESULTS: Among 173 colorectal cancer survivors, 90 (52.0%) were engaged in manual work. The self-efficacy score was found to be 25.99 ± 7.10, while the global health status score was 54.96 ± 21.56. Global health status was associated with sex, residence, chemoradiotherapy, and monthly income (p < 0.01). The self-efficacy score exhibited a significant positive correlation with quality of life, while demonstrating a negative correlation with symptom scores (p < 0.01). Recreational PA scores were positively associated with global health status (P < 0.05). Self-efficacy, recreational physical activity during winter, and whether the participants underwent chemoradiotherapy explained 29.3% of the variance in quality of life among colorectal cancer survivors. CONCLUSIONS: Colorectal cancer survivors exhibited low levels of physical activity, self-efficacy, and quality of life. Their health is influenced by self-efficacy, recreational physical activity, and chemoradiotherapy. When developing intervention plans for colorectal cancer survivorship, it is crucial to consider survivors' self-efficacy and the type of physical activity in which they engage.

Hydrogel-based molecular tension fluorescence microscopy for investigating receptor-mediated rigidity sensing.

Extracellular matrix (ECM) rigidity serves as a crucial mechanical cue impacting diverse biological processes. However, understanding the molecular mechanisms of rigidity sensing has been limited by the spatial resolution and force sensitivity of current cellular force measurement techniques. Here we developed a method to functionalize DNA tension probes on soft hydrogel surfaces in a controllable and reliable manner, enabling molecular tension fluorescence microscopy for rigidity sensing studies. Our findings showed that fibroblasts respond to substrate rigidity by recruiting more force-bearing integrins and modulating integrin sampling frequency of the ECM, rather than simply overloading the existing integrin-ligand bonds, to promote focal adhesion maturation. We also demonstrated that ECM rigidity positively regulates the pN force of T cell receptor-ligand bond and T cell receptor mechanical sampling frequency, promoting T cell activation. Thus, hydrogel-based molecular tension fluorescence microscopy implemented on a standard confocal microscope provides a simple and effective means to explore detailed molecular force information for rigidity-dependent biological processes.

Exploring Mechanical Responses of Cells to Geometric Information Using Micropatterned DNA-Based Molecular Tension Probes.

The geometric shape of a cell is strongly influenced by the cytoskeleton, which, in turn, is regulated by integrin-mediated cell-extracellular matrix (ECM) interactions. To investigate the mechanical role of integrin in the geometrical interplay between cells and the ECM, we proposed a single-cell micropatterning technique combined with molecular tension fluorescence microscopy (MTFM), which allows us to characterize the mechanical properties of cells with prescribed geometries. Our results show that the curvature is a key geometric cue for cells to differentiate shapes in a membrane-tension- and actomyosin-dependent manner. Specifically, curvatures affect the size of focal adhesions (FAs) and induce a curvature-dependent density and spatial distribution of strong integrins. In addition, we found that the integrin subunit ß1 plays a critical role in the detection of geometric information. Overall, the integration of MTFM and single-cell micropatterning offers a robust approach for investigating the nexus between mechanical cues and cellular responses, holding potential for advancing our understanding of mechanobiology.

Molecular Force Imaging Reveals That Integrin-Dependent Mechanical Checkpoint Regulates Fcγ-Receptor-Mediated Phagocytosis in Macrophages.

Macrophages are a type of immune cell that helps eliminate pathogens and diseased cells. Recent research has shown that macrophages can sense mechanical cues from potential targets to perform effective phagocytosis, but the mechanisms behind it remain unclear. In this study, we used DNA-based tension probes to study the role of integrin-mediated forces in FcγR-mediated phagocytosis. The results showed that when the phagocytic receptor FcγR is activated, the force-bearing integrins create a "mechanical barrier" that physically excludes the phosphatase CD45 and facilitates phagocytosis. However, if the integrin-mediated forces are physically restricted at lower levels or if the macrophage is on a soft matrix, CD45 exclusion is significantly reduced. Moreover, CD47-SIRPα "don't eat me" signaling can reduce CD45 segregation by inhibiting the mechanical stability of the integrin barrier. These findings demonstrate how macrophages use molecular forces to identify physical properties and combine them with biochemical signals from phagocytic receptors to guide phagocytosis.

Albumin-Modified Gold Nanoparticles as Novel Radiosensitizers for Enhancing Lung Cancer Radiotherapy.

Background: Considering the strong attenuation of photons and the potential to increase the deposition of radiation, high-atomic number nanomaterials are often used as radiosensitizers in cancer radiotherapy, of which gold nanoparticles (GNPs) are widely used. Materials and Methods: We prepared albumin-modified GNPs (Alb-GNPs) and observed their radiosensitizing effects and biotoxicity in human non-small-cell lung carcinoma tumor-bearing mice models. Results: The prepared nanoparticles (Alb-GNPs) demonstrated excellent colloidal stability and biocompatibility at the mean size of 205.06 ± 1.03 nm. Furthermore, clone formation experiments revealed that Alb-GNPs exerted excellent radiosensitization, with a sensitization enhancement ratio (SER) of 1.432, which is higher than X-ray alone. Our in vitro and in vivo data suggested that Alb-GNPs enabled favorable accumulation in tumors, and the combination of Alb-GNPs and radiotherapy exhibited a relatively greater radiosensitizing effect and anti-tumor activity. In addition, no toxicity or abnormal irritating response resulted from the application of Alb-GNPs. Conclusion: Alb-GNPs can be used as an effective radiosensitizer to improve the efficacy of radiotherapy with minimal damage to healthy tissues.

Characteristics and outcomes of patients with primary abdominopelvic aggressive angiomyxoma: a retrospective review of 12 consecutive cases from a sarcoma referral center.

BACKGROUND: Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor that mostly arises from the pelvic and perineal soft tissues. Few studies reported its characteristics and outcomes previously due to its rarity and challenges of treatments. This study aimed to investigate the clinical characteristics as well as surgical and short-term survival outcomes of primary abdominopelvic AAM. METHODS: Medical records of patients who were admitted to surgery with pathological confirmation of primary abdominopelvic AAM at Peking University International Hospital from January 2016 through December 2021 were retrospectively retrieved from our retroperitoneal tumor database. Demographics, operative outcomes and pathological findings were collected. Patients received followed-up routinely after the surgery. Survival probabilities were calculated and determined through Kaplan-Meier analysis. RESULTS: A total of 12 consecutive patients (male/female 4:8) were included in this study. The median age was 45 years old. The clinical presentation varied among individuals, consisting of 2 abdominal discomforts, 4 constipations, 1 lumbago, 1 prolonged menstruation, and 1 buttock swelling. R0/R1 resection was achieved in 100% of patients. Postoperatively, 50% of patients developed various complications including 3 fistulas and 3 wound infections. No operative mortality was observed. Histopathology of all patients was suggestive of AAM. Immunohistochemistry was done with a 91.7% positive rate for estrogen and progesterone receptors. The median recurrence-free survival time was 38 months. There were no cases of deceased or presented with distal metastasis during a median of 42 months' follow-up. CONCLUSIONS: The clinical manifestations of abdominopelvic AAM are mostly atypical. Surgical resection with curative intents remains the mainstay treatment of this disease, which was strongly suggested in experienced sarcoma centers due to the high probability of severe postoperative complications. In addition, long-term follow-up is necessary due to the high rate of local recurrences.

Effect of triple therapy with low-dose total body irradiation and hypo-fractionated radiation plus anti-programmed cell death protein 1 blockade on abscopal antitumor immune responses in breast cancer.

Immunostimulatory effects of radiotherapy can be synergistically augmented with immune checkpoint blockade to act both on irradiated tumor lesions and distant, non-irradiated tumor sites. Our hypothesis was that low-dose total body irradiation (L-TBI) combined with hypo-fractionated radiotherapy (H-RT) and anti-programmed cell death protein 1 (aPD-1) checkpoint blockade would enhance the systemic immune response. We tested the efficacy of this triple therapy (L-TBI + H-RT + aPD-1) in BALB/c mice with bilateral breast cancer xenografts. The L-TBI dose was 0.1 Gy. The primary tumor was treated with H-RT (8 Gy × 3). The PD-1 monoclonal antibody was injected intraperitoneally, and the secondary tumors not receiving H-RT were monitored for response. The triple therapy significantly delayed both primary and secondary tumor growths, improved survival rates, and reduced the number of lung metastasis lesions. It increased the activated dendritic and CD8+ T cell populations and reduced the infiltration of myeloid-derived suppressor cells in the secondary tumor microenvironment relative to other groups. Thus, L-TBI could be a potential therapeutic modality, and when combined with H-RT and aPD-1, the therapeutic effect could be enhanced significantly.

Intralesional Bacillus Calmette-Guérin injections and hypo-fractionated radiation synergistically induce systemic antitumor immune responses.

Radiotherapy, an important treatment for multiple malignancies, produces systemic anti-tumor effects in combination with immunotherapies, especially immune checkpoint inhibitors (ICBs). However, for some patients who do not respond to ICB treatment or show ICB-induced autoimmune symptoms, new alternatives need to be explored. Innovative immunomodulatory strategies, including the administration of immunostimulants, could be used to improve the immunogenicity induced by radiotherapy. In this study, we explored the synergistic effect of Bacillus Calmette-Guérin (BCG) combined with hypo-fractionated radiotherapy (H-RT) in inducing anti-tumor immune responses. We observed the systemic and abscopal effects of this combination in mice with 4 T1 breast cancer. H-RT combined with BCG could remodel the immune microenvironment and alleviate leukocyte-like responses by increasing the infiltration of CD8 + T cells, promoting the maturation of dendritic cells (DCs), decreasing the infiltration of immunosuppressive cells, and downregulating the expression of immunosuppressive cytokines. Therefore, this combination could enhance the systemic anti-tumor response, leading to the regression of untreated synchronous tumors and a decrease in the systemic metastatic burden. These results highlight the potential of BCG in assisting antitumor therapy and the therapeutic potential of this combination treatment.

The Transient Receptor Potential Vanilloid 2 (TRPV2) Channel Facilitates Virus Infection Through the Ca2+ -LRMDA Axis in Myeloid Cells.

The transient receptor potential vanilloid 2 (TRPV2) channel is a nonselective cation channel that has been implicated in multiple sensory processes in the nervous system. Here, it is shown that TRPV2 in myeloid cells facilitates virus penetration by promoting the tension and mobility of cell membrane through the Ca2+ -LRMDA axis. Knockout of TRPV2 in myeloid cells or inhibition of TRPV2 channel activity suppresses viral infection and protects mice from herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) infection. Reconstitution of TRPV2 but not the Ca2+ -impermeable mutant TRPV2E572Q into LyZ2-Cre;Trpv2fl/fl bone marrow-derived dendritic cells (BMDCs) restores viral infection. Mechanistically, knockout of TRPV2 in myeloid cells inhibits the tension and mobility of cell membrane and the penetration of viruses, which is restored by reconstitution of TRPV2 but not TRPV2E572Q . In addition, knockout of TRPV2 leads to downregulation of Lrmda in BMDCs and BMDMs, and knockdown of Lrmda significantly downregulates the mobility and tension of cell membrane and inhibits viral infections in Trpv2fl/fl but not LyZ2-Cre;Trpv2fl/fl BMDCs. Consistently, complement of LRMDA into LyZ2-Cre;Trpv2fl/fl BMDCs partially restores the tension and mobility of cell membrane and promotes viral penetration and infection. These findings characterize a previously unknown function of myeloid TRPV2 in facilitating viral infection though the Ca2+ -LRMDA axis.

Exploring Integrin-Mediated Force Transmission during Confined Cell Migration by DNA-Based Tension Probes.

Mechanical forces have profound effects on the morphology and migration of cells in a two-dimensional environment. However, cells in vivo mostly migrate in three-dimensional space while physically constrained, and the mechanism by which cellular dynamic forces drive migration in this confined environment is unclear. Here, we present a method of fabricating microfluidic chips with integrated DNA-based tension probes to measure spatiotemporal variations in integrin-mediated force exerted during confined cell migration. Using this developed device, we measured the spatial locations, magnitudes, and temporal characteristics of integrin-ligand tension signals in motile cells in different microchannels and found that cells exerted less force and underwent increasingly transitory integrin-ligand interactions when migrating in confined spaces. This study demonstrates that the described method provides insights into understanding the migratory machinery of cells in geometrically confined environment that better mimics physiological conditions.

Therapeutic Plasma Exchange: For Cancer Patients.

Therapeutic plasma exchange is used as a trial method for the treatment of cancer patients. Therapeutic plasma exchange uses in vitro technology to remove pathogenic factors in the plasma, returning the replacement and remaining components to the patient to facilitate cure. In the effort to explore new methods of cancer treatment, the introduction of therapeutic plasma exchange brings new hope for cancer treatment; however, the current evidence supporting therapeutic plasma exchange is controversial, and most of the evidence comes from observational studies, lacking large prospective randomized trials. Therefore, this review attempts to focus on the main indications of therapeutic plasma exchange for the treatment of tumors and their complications, including hematological tumors (multiple myeloma cast nephropathy and hyperviscosity syndrome), nervous system tumors (myasthenia gravis associated with thymoma, paraneoplastic neurological syndrome, Lambert-Eaton myasthenia syndrome, and anti-N-methyl-D-aspartate receptor encephalitis), overdose of chemotherapy drugs. In addition, the issues of side-effects and safety in the use of therapeutic plasma exchange are also discussed. However, well-designed prospective trials are needed to better define the role of therapeutic plasma exchange in cancer.

A reversible shearing DNA probe for visualizing mechanically strong receptors in living cells.

In the last decade, DNA-based tension sensors have made significant contributions to the study of the importance of mechanical forces in many biological systems. Albeit successful, one shortcoming of these techniques is their inability to reversibly measure receptor forces in a higher regime (that is, >20 pN), which limits our understanding of the molecular details of mechanochemical transduction in living cells. Here, we developed a reversible shearing DNA-based tension probe (RSDTP) for probing molecular piconewton-scale forces between 4 and 60 pN transmitted by cells. Using these probes, we can easily distinguish the differences in force-bearing integrins without perturbing adhesion biology and reveal that a strong force-bearing integrin cluster can serve as a 'mechanical pivot' to maintain focal adhesion architecture and facilitate its maturation. The benefits of the RSDTP include a high dynamic range, reversibility and single-molecule sensitivity, all of which will facilitate a better understanding of the molecular mechanisms of mechanobiology.

High exposure to statins decrease the risk of new-onset dementia: A nationwide population-based longitudinal cohort study.

Several studies have shown that statin users have a lower risk of new-onset dementia (NOD) compared nonusers. However, other studies have shown opposite results. In this study, we investigated the association between the use of statins and the development of NOD.This was a longitudinal cohort study using data from claim forms submitted to the Taiwanese Bureau of National Health Insurance. The study included patients with NOD and non-NOD subjects from January 2002 to December 2013. We estimated the hazard ratios (HRs) of NOD associated with statin use, whereas nonuser subjects were used as a reference group.A total of 19,522 NOD cases were identified in 100,610 hyperlipidemic patients during the study period. The risk of NOD, after adjusting for sex, age, comorbidities, and concurrent medication, was lower among statin users than nonusers (HR 0.95, 95% CI [confidence interval] 0.94-0.96; P < .001). The adjusted HRs for NOD were 1.53 (95% CI, 1.45-1.62), 0.63 (95% CI, 0.57-0.71), and 0.34 (95% CI, 0.30-0.38) when the cumulative defined daily doses ranged from 28 to 365, 366 to 730, and more than 730 relative to nonusers, respectively.We concluded that statin use is associated with a decreased NOD risk. The protective effect of statins for NOD seemed to be related to high exposure to statins. This study also highlights that high exposure to statins has a dose-response effect on lowering NOD risk.