Wireless Sensing System Based on Biodegradable Triboelectric Nanogenerator for Evaluating Sports and Sleep Respiratory.

The rapid growth of the Internet of Things and wearable sensors has led to advancements in monitoring technology in the field of health. One such advancement is the development of wearable respiratory sensors, which offer a new approach to real-time respiratory monitoring compared to traditional methods. However, the energy consumption of these sensors raises concerns about environmental pollution. To address the issue, this study proposes the use of a triboelectric nanogenerator (TENG) as a sustainable energy source. The electrical conductivity of the TENG is improved by incorporating chitosan and carbon nanotubes, with the added benefit of chitosan's biodegradability reducing negative environmental impact. A wireless intelligent respiratory monitoring system (WIRMS) is then introduced, which utilizes a degradable triboelectric nanogenerator for real-time respiratory monitoring, diagnosis, and prevention of obstructive respiratory diseases. WIRMS offers stable and highly accurate respiratory information monitoring, while enabling real-time and nondestructive transmission of information. In addition, machine learning technology is used for sleep respiration state analysis. The potential applications of WIRMS extend to wearables, medical monitoring and sports monitoring, thereby presenting innovative ideas for modern medical and sports monitoring.

Dual-mode optical thermometry design in K3YSi2O7:Eu multi-site phosphor.

In this study, a dual-mode optical thermometer is designed based on radiative transitions from Eu3+ and Eu2+ ions at different K3YSi2O7 lattice sites. In the luminescence-intensity-ratio strategy, a ratiometric signal composed of Eu3+:5D0→7F1 and Eu3+:5D0→7F2 emissions at 593 and 616 nm, respectively, is employed. Meanwhile, the intensity ratio of the 593-nm emission under O2-→Eu3+ charge transfer excitation (λex = 249 nm) to that upon Eu2+:4f7→4f65d1 excitation (λex = 349 nm) is selected as a thermometric parameter in the single-band-ratio approach. The study findings show that combining the two strategies is conducive to the improvements in sensing-sensitive and anti-interference performance.

Robotic versus laparoscopic abdominoperineal resections for low rectal cancer: A single-center randomized controlled trial.

BACKGROUND AND OBJECTIVES: Robotic surgery for rectal cancer is gaining popularity, but persuasive evidence on reducing surgical trauma is still lacking. This study compared robotic and laparoscopic abdominoperineal resections (APRs) for the risk of postoperative complications in low rectal cancer. METHODS: Between December 2013 and 2016, patients with rectal cancer ≤5 cm from anal verge, cT1-T3 N0-1, or ycT1-T3 Nx stage, and no distant metastases were enrolled in a single-center, randomized, controlled trial. Eligible patients were randomly allocated to robotic or laparoscopic APRs at 1:1 ratio. The primary outcome was 30-day postoperative complication rate (Clavien-Dindo grade II or higher) of the intent-to-treat population. The trial registration number is NCT01985698 (http://www. CLINICALTRIALS: gov). RESULTS: Totally 347 eligible patients were enrolled: 174 in robotic and 173 in laparoscopic group. Robotic APRs significantly reduced postoperative complication rate (13.2% vs. 23.7%, p = 0.013), also reduced open conversion rate (0% vs. 2.9%, p = 0.030), intraoperative hemorrhage (median, 100 vs. 130 ml; p < 0.001), 30-day readmission rate (2.3% vs. 6.9%; p = 0.044), postoperative hospital stay (median, 5.0 vs. 7.0 days; p < 0.001), and improved urinary and sexual function. No significant difference was observed in long-term oncological outcomes. CONCLUSIONS: Compared with laparoscopic APRs, robotic APRs significantly reduced surgical trauma and promoted postoperative recovery.

Comparison between robotic natural orifice specimen extraction surgery and traditional laparoscopic low anterior resection for middle and low rectal cancer: A propensity score matching analysis.

BACKGROUND AND OBJECTIVES: This study aimed to find the advantages of robotic natural orifice specimen extraction surgery (NOSES) for middle and low rectal cancer, compared with traditional laparoscopic low anterior resection (LAR). METHODS: Patients receiving robotic NOSES or traditional laparoscopic LAR were retrospectively enrolled from 2013-10 to 2019-06, with middle and low rectal cancer, maximum diameter ≤ 5 cm, pT1-3 or ypT1-3 stage, no distant metastases. The baseline of the two groups was balanced using the propensity score matching method. Surgical quality, postoperative recovery, and long-term oncological outcomes were compared. RESULTS: Totally 137 eligible patients with robotic NOSES and 137 matched patients with traditional laparoscopic LAR were enrolled. Robotic NOSES had a significantly lower open conversion rate (0 vs. 4.4%, p = .030), less intraoperative hemorrhage (50 ml vs. 80 ml, p < .001) and longer distance from distal resection margin of low rectal cancer (1.5 cm vs. 1.0 cm, p = .030). Robotic NOSES significantly reduced the 30-day postoperative complication rate of Clavien-Dindo grade II or higher (17.5% vs. 31.4%, p = .008), promoted gastrointestinal and urinary function recovery, reduced postoperative pain and hospital stay (6.0 vs. 7.0 d, p = .022). The two groups were similar in long-term survival. CONCLUSIONS: Compared with traditional laparoscopic LAR, robotic NOSES had significant advantages in improving surgical quality and promoting postoperative recovery.

Robotic colorectal cancer surgery in China: a nationwide retrospective observational study.

BACKGROUND: Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series. METHOD: A total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed. RESULTS: A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien-Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384, P < 0.001), traditional low anterior resection (tumor at low rectum) (OR 1.968, P = 0.017) and intersphincteric resection (OR 5.468, P = 0.006) were significant independent risk factors for anastomotic leakage. Female gender (OR 0.557, P = 0.005), age ≥ 60 years (OR 0.684, P = 0.040), and preventive stoma (OR 0.496, P = 0.043) were significant independent protective factors. Body mass index, preoperative chemotherapy/radiotherapy, tumor size, and TNM stage did not independently affect the occurrence of anastomotic leakage. CONCLUSION: Robotic colorectal cancer surgery was safe and reliable and might have advantages in patients at high risk of anastomotic leakage.

Analysis of relapse-associated alternative mRNA splicing and construction of a prognostic signature predicting relapse in I-III colon cancer.

The literature comprehensively analyzed alternative splicing (AS) events in colon cancer is little and corresponding prognostic signature is still a lack. Based on data of TCGA, the relapse-associated ASs were comprehensively analyzed and a signature was further constructed to predict the relapse in I-III colon cancer. In total 1912 ASs of 1384 mRNA were identified as relapse-associated ASs, protein-protein interactions (PPI) and ASs-splicing factors (SF) interactions network were identified. We finally built a robust signature to predict the relapse of I-III colon cancer with a considerable AUC value in both the training group and the test group. The AUC in the entire set at 1, 3 and 5 year was 0.85, 0.83 and 0.836. Our study provided a profile of relapse-associated ASs in I-III colon cancer and built a robust signature to predict the relapse of I-III colon cancer.

A signature predicting relapse based on integrated analysis on relapse-associated alternative mRNA splicing in I-III rectal cancer.

Researches focusing on the effects of alternative splicing (AS) on relapse of rectal cancer is little and signature based on the AS is blank. In this study, bioinformatic analysis was performed to identify and analyze the relapse-associated ASs, a signature was also constructed. In conclusion, 829 relapse-associated ASs of 676 mRNA were identified. 603 proteins with 2119 interactions were involved in the PPI (protein-protein interactions) network. 43 relapse-associated ASs and 64 SFs (splicing factors) with 160 interactions were indicated. Finally, we built a robust signature to predict the relapse of I-III rectal cancer with a high AUC (0.98) of ROC at 1 year. Based on the ASs involved in the signature, 4 molecular subgroups that could distinguish the relapse rate in diverse groups were identified. Our research provided an overview of relapse-associated ASs in I-III rectal cancer.

Posttranscriptional regulation of MMP-9 by HuR contributes to IL-1ß-induced pterygium fibroblast migration and invasion.

Inflammation is considered to be critical in the pterygium progression and recurrence. However, the underlying molecular mechanism is not well understood. Herein, we investigated the potential role of RNA binding protein human antigen R (HuR) responsible for the impact of inflammation on pterygium development. The expression of HuR and matrix metallopeptidase-9 (MMP-9) in pterygium and normal conjunctiva was detected with immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The influence of interleukin-1ß (IL-1ß) on HuR expression and cellular distribution was determined with western blot and immunofluorescence. The pterygium fibroblast (PTF) migration was determined with scratch wound healing assay and Transwell migration assay. MMP-9 production was determined with qRT-PCR and gelatin zymography. The interaction between HuR and MMP-9 was investigated with RNP immunoprecipitation (IP) followed by RT-PCR and messenger RNA (mRNA) stability analysis. HuR and MMP-9 expression are elevated in pterygium, especially progressive pterygium compared with normal conjunctiva. IL-1ß could increase the expression and nucleus-cytoplasm shuttle of HuR in cultured PTFs. HuR mediated the stimulatory effect of IL-1ß on PTF migration and MMP-9 production. HuR bound to MMP-9 mRNA and in turn increased it stability. Our results suggest that posttranscriptional regulation of MMP-9 via stabilizing mRNA by HuR might contribute to the stimulatory effect of inflammatory factor IL-1ß on pterygium progression. These findings shed light on the pathogenesis of pterygium and provide a promising target for adjuvant treatment of pterygium.

Cytokine fibroblast growth factor 10 (FGF10) polymorphisms are associated with risk of myopia in young children.

Myopia has become a major public health issue worldwide. Identification of genetic loci related to myopia in young children may advance our knowledge of the pathogenesis of myopia. Fibroblast growth factor 10 (FGF10) plays essential roles for the development of myopia through modulating extracellular matrix-associated genes. Studies revealed that genetic variants of FGF10 were associated with extreme myopia in adults. However, their associations with susceptibility of myopia in young children, which are less affected by confounding factors and more suitable for studying genetic factors of myopia, have not been explored. In the current study, we evaluated 13 tagSNPs that captured 100% of genetic variation in the FGF10 gene region for their associations with myopia in a large Chinese case-control study with 900 myopia children and 900 nonmyopia children. We found rs2973644 was significantly associated with increased risk of myopia (odds ratio [OR]: 1.26; 95% confidence intervals [CI]: 1.06-1.49; P = 0.009). furthermore, rs339501 (OR: 1.73; 95% CI: 1.18-2.53; P = 0.005), rs2973644 (OR: 1.57; 95% CI: 1.13-2.19; P = 0.007), and rs79002828 (OR: 1.83; 95% CI: 1.20-2.77; P = 0.005) were significantly associated with increased risk of high myopia in young children. Functional assessment of rs2973644 by luciferase assays revealed the risk G allele causes a higher expression level of FGF10 than the protective A allele. Our results do support that genetic variants of cytokine FGF10 are associated with susceptibility of myopia (as well as high myopia) in young children and further exploration are needed for myopia in children.

Low tumor infiltrating mast cell density confers prognostic benefit and reflects immunoactivation in colorectal cancer.

The role of mast cells (MCs) in colorectal cancer (CRC) progression was controversial. Thus, our study was designed to evaluate the prognostic value of MCs as well as their correlation with immune microenvironment. A retrospective cohort of CRC patients of stages I-IV was enrolled in our study. Consecutive patients (854) were divided into training set (427 patients) and validation set (427 patients) randomly. The findings were further validated in a GEO cohort, GSE39582 (556 patients). The mast cell density (MCD) was measured by immunohistochemical staining of tryptase or by CIBERSORT algorithm. Low MCD predicted prolonged overall survival (OS) in training and validation set. Moreover, MCD was identified as an independent prognostic indicator in both sets. Better stratification for CRC prognosis can be achieved by building a MCD based nomogram. The prognostic role of MCD was further validated in GSE39582. In addition, MCD predicted improved survival in stages II and III CRC patients receiving adjuvant chemotherapy (ACT). Multiple immune pathways were enriched in low MCD group while cytokines/chemokines promoting anti-tumor immunity were highly expressed in such group. Furthermore, MCD was negatively correlated with CD8+ T cells infiltration. In conclusion, MCD was identified as an independent prognostic factor, as well as a potential biomarker for ACT benefit in stages II and III CRC. Better stratification of CRC prognosis could be achieved by building a MCD based nomogram. Moreover, immunoactivation in low MCD tumors may contributed to improved prognosis.

Immature Colon Carcinoma Transcript-1 (ICT1) Expression Correlates with Unfavorable Prognosis and Survival in Patients with Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the third leading cause of death from cancer worldwide. Immature colon carcinoma transcript-1 (ICT1) has been reported to be correlated with lung cancer; however, whether ICT1 is a functional gene in CRC, as well as the molecular mechanism underlying ICT1 mediation of colorectal-tumor formation, remains unknown. METHODS: The expression of ICT1 was firstly determined by using immunohistochemistry in 861 CRC specimens. The correlation of ICT1 expression with clinicopathological parameters and the survival rate was analyzed. Furthermore, we investigated the effect of ICT1 silencing on CRC cell proliferation and migration by MTT, colony formation, flow cytometry, and transwell in vitro. RESULTS: ICT1 is highly expressed in a cohort of human CRCs, and that higher ICT1 expression may lead to reduced overall survival rate of CRC. Likewise, ICT1 silencing lowered the cell viability through cell-cycle arrest, inhibited cell migration, and induced apoptosis in CRC. We further revealed a novel mechanism in which ICT1 promoted CRC growth via the intracellular AMPK, SAPK/JNK, and PARP signaling pathways. CONCLUSIONS: Our data showed that ICT1 could be an important target for CRC diagnosis and treatment.

Self-expandable metallic stent as a bridge to elective surgery versus emergency surgery for acute malignant colorectal obstruction.

BACKGROUD: The efficacy and safety of self-expandable metallic stents (SEMSs) as a bridge for patients with acute malignant colorectal obstructions (AMCOs) are still controversial. We conducted this study to evaluate the outcomes of patients with AMCOs treated by different strategies. METHODS: From January 2010 to March 2014, a total of 171 patients with AMCOs from Zhongshan Hospital were retrospectively enrolled in this study. One hundred twenty patients successfully received stent placement followed by one-stage laparoscopic or open resection in the stent group, and 51 patients received emergency operations in the emergency group. RESULTS: The operation duration and postoperative hospital stay were significantly shorter in the stent group (114.51 ± 28.65 vs. 160.39 ± 58.94 min, P < 0.001; 8.00 ± 3.97 vs. 12.59 ± 9.07 days, P = 0.001). The stent group also had significantly reduced intraoperative blood loss and the incidence of postoperative complications compared with the emergency group (61.00 ± 43.70 vs. 121.18 ± 85.90 ml, P < 0.001; 16.7 vs. 37.3%, P = 0.003). Kaplan-Meier survival curves showed that the median survival time in the stent group was significantly longer than that in the emergency group (53 vs. 41 months, P = 0.034). In subgroup analysis of stent group, the stent laparoscopy group had significantly decreased postoperative complications (P = 0.025), and similar long-term survival (P = 0.81). CONCLUSIONS: Stent placement as a bridge to surgery is a safe and feasible procedure and provides significant advantages in terms of short-term outcomes and favorable prognoses for patients with AMCOs. Laparoscopic surgery could be considered as an optimal treatment after stent placement.

Aberrant expression of sphingosine-1-phosphate receptor 1 correlates with metachronous liver metastasis and poor prognosis in colorectal cancer.

There are currently no accurate predictive markers of metachronous liver metastasis from colorectal cancer. Recent studies demonstrated that the expression patterns of sphingosine-1-phosphate receptor 1 (S1PR1) are altered in several tumors, but in colorectal cancer, the patterns remain unknown. Our study was designed to evaluate the expression and prognostic significance of S1PR1 protein in patients with colorectal cancer. The expression of S1PR1 was detected using the tissue microarray technique and immunohistochemical method and compared with clinicopathological parameters in 153 colorectal cancer patients. The prognostic value of S1PR1 expression was evaluated by Kaplan-Meier and Cox regression analysis. A molecular prognostic stratification scheme incorporating S1PR1 expression was determined by using receiver operating characteristic (ROC) analysis. S1PR1 was significantly highly expressed in 70.6 % (108/153) of the colorectal cancer lesions compared to their high expressions in only 5.9 % (9/153) of the adjacent non-cancerous tissues. Upregulated expression of S1PR1 was significantly associated with depth invasion and metachronous liver metastasis. Increased S1PR1 expression in colorectal cancer was positively correlated with poor overall survival. Multivariate survival analysis suggested that S1PR1 expression was an independent prognostic indicator for the disease. Applying the prognostic value of S1PR1 density to TNM stage system showed a better prognostic value in patients with colorectal cancer. Aberrant S1PR1 expression in colorectal cancer was associated with metachronous liver metastasis and worse survival outcome, and also, it was an independent prognostic factor. According to our analysis, combined TNM stage and intratumoral expression of S1PR1 demonstrated a better prognostic value than any of these two parameters alone. Conclusively, we suggest that detection and analysis of S1PR1 expression in colorectal cancer tissue might be used for predicting prognosis of colorectal cancer.

VIC Regimen (Vemurafenib/Irinotecan/Cetuximab) Versus Bevacizumab Plus Chemotherapy as First-Line Treatment for BRAF V600E-Mutated Unresectable or Metastatic Colorectal Cancer in Asian Patients: A Prospective Cohort Study.

BACKGROUND: Colorectal cancers (CRC) with BRAF V600E mutation exhibit limited chemotherapy response and a poor prognosis. Safety and efficacy of the VIC (Vemurafenib/Irinotecan/Cetuximab) regimen in the first-line setting for patients with BRAF V600E-mutated CRC remain undetermined. METHODS: In the prospective cohort study, the untreated, BRAF V600E-mutated, unresectable or metastatic CRC patients were enrolled. The VIC regimen and bevacizumab plus chemotherapy were compared in the first-line setting. The objective response rate (ORR), disease control rate (DCR), conversion resection rate, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: In the intent-to-treat analysis, 38 patients received VIC regimen and 40 received bevacizumab plus chemotherapy. The ORR and DCR in the VIC group were significantly higher than in the bevacizumab-therapy group (ORR: 63.2% vs. 37.5%, P = .025; DCR: 94.7% vs. 75.0%, P = .019). The VIC regimen significantly outperformed bevacizumab plus chemotherapy in both PFS (11.9 vs. 7.7 months; hazard ratio [HR] = 0.51, 95% CI, 0.30-0.87; P = .010) and OS (25.3 vs. 14.6 months; HR = 0.43, 95% CI, 0.22-0.82; P = .011). In the VIC group, the conversion resection rate for liver metastases was 34.8% (8 of 23 patients), and for unresectable local CRC it was 54.5% (6 of 11 patients). The adverse events rates of Grade 3 to 4 were 34.2% and 32.5% for the VIC regimen and bevacizumab plus chemotherapy respectively. CONCLUSIONS: Among Asian patients with BRAF V600E-mutated CRC, the VIC regimen showed favorable outcomes compared to bevacizumab plus chemotherapy in terms of tumor response and oncological survival, with a tolerable and manageable toxicity profile in the first-line setting.

Self-Powered, Flexible, Wireless and Intelligent Human Health Management System Based on Natural Recyclable Materials.

Combining wearable sensors with modern technologies such as internet of things and big data to monitor or intervene in obesity-induced chronic diseases, such as obstructive sleep apnea, type II diabetes, cardiovascular diseases, and Alzheimer's disease, is of great significance to the self-health management of human beings. This study designed a loofah-conducting graphite four friction layer enhanced triboelectric nanogenerator (LG-TENG) and developed a health management system for human motion recognition and early warning of sleep breathing abnormalities. By uniformly spraying and depositing conductive graphite on the surface of the loofah and the elastic film cross-interlocking bending structure design, the signal strength of the LG-TENG has been improved by 390%. The stable output signal is still maintained after 1500 s of continuous operation at a frequency of 2 Hz. LG-TENG can realize accurate motion analysis by muscle contraction state. Combining different deep learning models resulted in 98.1% accuracy in recognizing seven categories of displacement speeds for an individual and 96.46% accuracy in recognizing seven categories of displacement speeds for three individuals. In addition, the sleep breathing monitoring early warning system was developed by integrating Bluetooth wireless transmission and upper computer analysis technology. This system aims to analyze and provide real-time warnings for sleep-breathing abnormalities. This research promotes an innovation of TENG technology based on the advantages of natural materials, recyclability and low cost. It offers new ideas for self-health management and scientific exercise for obese people, showing a broad application prospect.

High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer.

BACKGROUND: Patatin like phospholipase domain containing 8 (PNPLA8) has been shown to play a significant role in various cancer entities. Previous studies have focused on its roles as an antioxidant and in lipid peroxidation. However, the role of PNPLA8 in colorectal cancer (CRC) progression is unclear. AIM: To explore the prognostic effects of PNPLA8 expression in CRC. METHODS: A retrospective cohort containing 751 consecutive CRC patients was enrolled. PNPLA8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive scores. CRC patients were divided into high and low PNPLA8 expression groups based on the cut-off values, which were calculated by X-tile software. The prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression analysis. The overall survival (OS) rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank test. RESULTS: PNPLA8 expression was significantly associated with distant metastases in our cohort (P = 0.048). CRC patients with high PNPLA8 expression indicated poor OS (median OS = 35.3, P = 0.005). CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter OS. For patients with left-sided colon and rectal cancer, the survival curves of two PNPLA8-expression groups showed statistically significant differences. Multivariate analysis also confirmed that high PNPLA8 expression was an independent prognostic factor for overall survival (hazard ratio HR = 1.328, 95%CI: 1.016-1.734, P = 0.038). CONCLUSION: PNPLA8 is a novel independent prognostic factor for CRC. These findings suggest that PNPLA8 is a potential target in clinical CRC management.

Siglec9 + tumor-associated macrophages predict prognosis and therapeutic vulnerability in patients with colon cancer.

BACKGROUND: Siglec9 has been identified as an immune checkpoint molecule on tumor-associated macrophages (TAMs). Nevertheless, the expression profile and clinical significance of Siglec9 + TAMs in colon cancer (CC) are still not fully understood. METHODS: Two clinical cohorts from distinct medical centers were retrospectively enrolled. Immunohistochemistry and immunofluorescence were conducted to evaluate the infiltration of immune cells. Single-cell RNA sequencing and flow cytometry were utilized to identify the impact of Siglec9 + TAMs on the tumor immune environment, which was subsequently validated through bioinformatics analysis of the TCGA database. Prognosis and the benefit of adjuvant chemotherapy (ACT) were also evaluated using Cox regression analysis and the Kaplan-Meier method. RESULTS: High infiltration of Siglec9 + TAMs was associated with worse prognosis and better benefit from 6-month ACT. Siglec9 + TAMs contributed to immunoevasion by promoting the infiltration of immunosuppressive cells and the dysfunction process of CD8 + T cells. Additionally, high infiltration of Siglec9 + TAMs was associated with the mesenchymal-featured subtype and overexpression of the VEGF signaling pathway, which was validated by the strongest communication between Siglec9 + TAMs and vascular endothelial cells. CONCLUSIONS: Siglec9 + TAMs may serve as a biomarker for prognosis and response to ACT in CC. Furthermore, the immunoevasive contexture and angiogenesis stimulated by Siglec9 + TAMs suggest potential treatment combinations for CC patients.

Apolipoprotein L3 enhances CD8+ T cell antitumor immunity of colorectal cancer by promoting LDHA-mediated ferroptosis.

Aim: Colorectal cancer (CRC) is the leading cause of cancer associated death worldwide and immune checkpoint blockade therapy only benefit a small set of CRC patients. Tumor ferroptosis of CRC reflected immune-activation in our previous findings. Understanding the mechanisms underlying how to bolster CD8+ T cells function through ferroptosis in CRC tumor microenvironment (TME) will greatly benefit cancer immunotherapy. Methods: Genes between ferroptosis and CD8+ T cell function in CRC were screened through Cox, WGCNA and differential expression analysis. Immunohistochemistry and Immunofluorescence analysis were performed. Co-immunoprecipitation were performed to determine protein-protein interaction, mRNA level was determined by qRT-PCR. RSL3 was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring Transmission Electron Microscope analysis, MDA, Fe2+level and cell viability. Results: We screened APOL3 as the significant modulator for ferroptosis-related CD8+ infiltration in CRC. Next, by in vitro and in vivo, we found that increased APOL3 expression was positively correlated with sensitivity to ferroptosis and antitumor ability of CD8+ T cells. Next, we demonstrated that APOL3 can binds LDHA and promote its ubiquitylation-related degradation. Then, based on in vivo analysis and tumor specimen, we discovered the APOL3-LDHA axis can facilitate the tumor ferroptosis and cytotoxic ability of CD8+ T cells through increased IFNγ and decreased lactic acid concentration. Conclusion: The present study demonstrated that APOL3 promotes ferroptosis and immunotherapy in colorectal cancer cells. The present work provides us with a novel target to overcome drug resistance to ferroptosis and immunotherapy.

Intraocular pressure effect of intravitreal conbercept injection for retinopathy of prematurity.

Purpose: Intravitreal injection of conbercept (IVC) is a novel anti-vascular endothelial growth factor (anti-VEGF) treatment for retinopathy of prematurity (ROP). This study aimed to assess the intraocular pressure (IOP) effect of IVC. Methods: All IVC surgeries were performed in the Department of Ophthalmology, Guangdong Women and Children Hospital, from January 2021 to May 2021. In this study, 30 eyes of 15 infants who received intravitreal injections of conbercept at a dose of 0.25 mg/0.025 mL were included. The IOP of all participants was measured prior to administering the injection and subsequently at 2 min, 1 h, 1 day, and 1 week thereafter. Results: We included 30 eyes (10 boys and 5 girls) with ROP. For the male group, the mean birth weight, mean gestational age at birth, and the mean time of postmenstrual age (PMA) at IVC treatment were 1,174.0 ± 446.0 g, 28.4 ± 3.0 weeks, and 37.1 ± 1.6 weeks, respectively; for the female group, they were 1,108 ± 285.5 g, 28.2 ± 2.5 weeks, and 36.8 ± 2.1 weeks, respectively. For the male group, the IOP at baseline, 2 min, 1 h, 1 day, and 1 week after IVC were 12.4 ± 1.5 mmHg, 49.0 ± 3.1 mmHg, 26.3 ± 2.5 mmHg, 13.4 ± 2.2 mmHg, and 11.6 ± 1.7 mmHg, respectively; for the female group, they were 10.7 ± 2.0 mmHg, 47.3 ± 3.2 mmHg, 26.4 ± 3.2 mmHg, 10.7 ± 1.8 mmHg, and 10.2 ± 1.8 mmHg, respectively. In both groups, the IOP immediately (2 min) after the operation was significantly higher than that at any other time point (p < 0.01). IOP values returned to the preoperative baseline level on the first day after surgery, with no significant difference compared with that before injection (p > 0.05). IOP continued to be maintained at the preoperative baseline level on the first week after surgery, with no significant difference compared with that before surgery (p > 0.05). Conclusion: Infants with ROP who received IVC experienced a sharp increase in the IOP immediately after injection, which decreased to below 30 mmHg after 1 h and maintain that level for 1 week or longer.

Impact of Surgical Management for Relapse After Conversion Hepatectomy for Initially Unresectable Colorectal Liver Metastasis: A Retrospective Cohort Study.

BACKGROUND: For patients with initially unresectable colorectal liver metastasis (IU-CRLM) receiving conversion therapy, disease relapse after conversion hepatectomy is common. However, few studies have focused on the assessment and management of relapse following conversion hepatectomy for IU-CRLM. METHODS: In the retrospective cohort study, 255 patients with IU-CRLM received conversion therapy and underwent subsequent R0 resection. The treatment effects of repeated liver-directed treatment (RLDT) versus non-RLDT for liver relapse were examined. Survival analysis was evaluated with the use of Cox proportional hazards methods. The importance of RLDT was further confirmed in the propensity score matching (PSM) and subgroup analyses. RESULTS: The 5-year overall survival (OS) rate after conversion hepatectomy was 34.9%. Liver relapse was observed in 208 patients. Of these patients, 106 underwent RLDT (65 underwent repeated hepatectomy and the remainder underwent ablation treatment), while 102 received only palliative chemotherapy. The relapse patients who underwent RLDT had a significantly longer OS than those who did not (hazard ratio (HR): 0.382, 95% CI: 0.259-0.563; P<0.001). In a multivariable analysis, RLDT was independently associated to prolonged survival (HR: 0.309, 95%CI: 0.181-0.529; P<0.001). In the PSM and subgroup analyses, RLDT consistently showed evidence of prolonging OS significantly. CONCLUSION: For IU-CRLM patients with liver relapse following conversion hepatectomy, the RLDT is essential for cure and prolonged survival. To avoid missing the opportunity for RLDT, intensive disease surveillance should be proposed.