Factors Affecting the Diagnostic Discordance Between Frozen and Permanent Sections in Mucinous Ovarian Tumors.

Purpose: To investigate the accuracy of intraoperative frozen section (FS) diagnosis for predicting the permanent section (PS) diagnosis of mucinous ovarian tumors and evaluate the factors affecting the diagnostic discordance. Patients and Methods: This retrospective cohort study was performed in Tianjin Medical University General Hospital. All women who underwent ovarian surgery with FS between January 2011 and December 2022 were identified, and those with a diagnosis of mucinous ovarian tumor (MOT) by FS or PS were reviewed. Clinical and pathologic data were extracted. Results: A total of 180 women were included, of which 141 (78.33%) had diagnostic concordance between FS and PS, yielding a sensitivity of 83.43% and a positive predictive value (PPV) of 92.76%. Under- and over-diagnosis occurred in 28 cases (15.56%) and 11 cases (6.11%). Tumor size > 13cm (OR 3.79, 95% CI 1.12-12.73) was an independent risk factor for under-diagnosis, and tumor size ≤ 13cm (OR 16.78, 95% CI 0.01-0.49), laparoscopic surgery (OR 0.14, 95% CI 0.02-0.92), the combination of other tumor components (including serous, Brenner tumor, and chocolate cyst; OR 7.00, 95% CI 1.19-41.12) were independently associated with over-diagnosis. The Kaplan-Meier survival curves and the Log rank test showed no significant difference between misdiagnosed and accurately diagnosed patients (all P > 0.05). Conclusion: Intraoperative frozen pathology of MOT is problematic for under- and over-diagnosis. The incorrect diagnosis of FS was related to determining the extent of surgery but had no impact on the patients' long-term recurrence and survival outcomes. In future clinical practice, surgeons need to obtain material accurately and enhance communication with pathologists during the operation to improve the accuracy of FS diagnosis.

A novel reverse perilesional home phototherapy can promote the repigmentation of vitiligo patches with complete leukotrichia: A 12-week, open-label, double-arm, multicenter, randomized clinical trial.

BACKGROUND/PURPOSE: Existing phototherapies are ineffective for treating patients with vitiligo with complete leukotrichia. We compared the efficacy of reverse perilesional irradiation, during which only the lesional areas are covered, with conventional narrowband ultraviolet B (NB-UVB) home phototherapy for repigmentation of non-segmental vitiligo in patients with complete leukotrichia. METHODS: This was a 12-week, open-label, double-arm, multicenter clinical trial, with a total of 121 patients with non-segmental vitiligo who were randomly divided into two groups (both received topical tacrolimus): the conventional NB-UVB irradiation (CI) and reverse perilesional NB-UVB irradiation (RI) groups. RESULTS: A statistically significant difference in improvement from baseline was observed in the RI group compared with the findings in the CI group (-30.8% ± 11.8% vs. -25.5% ± 11.05%, respectively [p = .010]; pair-wise comparison p = .900 at week 4, p = .104 at week 8, and p = .010 at week 12). At week 12, the average percentage change from baseline of leukotrichia in the irradiation area significantly decreased from 100% to 82.2% ± 13.65% in the RI group, and from 100% to 88.7% ± 9.64% in the CI group (p = .027). Adverse events were minor, including desquamation, dryness, erythema, and blisters. No severe or lasting side effects were observed during the study. CONCLUSION: RI mediated better repigmentation of vitiligo with complete leukotrichia than CI.

Long-term efficacy of Waveflex semi-rigid-dynamic-internal-fixation system in delaying intervertebral disc degeneration at adjacent segments and improving spinal sagittal imbalance.

The Waveflex semi-rigid-dynamic-internal-fixation system shows good short-term effects in the treatment of lumbar degenerative diseases, but there are few long-term follow-up studies, especially for recovery of sagittal balance. Fifty patients with lumbar degenerative diseases treated from January 2016 to October 2017 were retrospectively analysed: 25 patients treated with Waveflex semi-rigid-dynamic-internal-fixation system (Waveflex group) and 25 patients treated with double-segment PLIF (PLIF group). Clinical efficacy was evaluated by Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI). Imaging data before surgery and at 3 months, 1 year, and 5 years postoperatively was used for imaging indicator assessment. Local disc degeneration of the cephalic adjacent segment (including disc height index (DHI), intervertebral foramen height (IFH), and range of motion (ROM)) and overall spinal motor function (including lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), and |PI-LL|) were analysed. Regarding clinical efficacy, comparison of VAS and ODI scores between the Waveflex and PLIF groups showed no significant preoperative or postoperative differences. The comparison of the objective imaging indicators showed no significant differences in the DHI, IFH, LL, |PI-LL|, and SS values between the Waveflex and PLIF groups preoperatively and 3 months postoperatively (P > 0.05). These values were significantly different at 1 and 5 years postoperatively (P < 0.05), and the Waveflex group showed better ROM values than those of the PLIF group (P < 0.05). PI values were not significantly different between the groups, but PT showed a significant improvement in the Waveflex group 5 years postoperatively (P < 0.05). The Waveflex semi-rigid dynamic fixation system can effectively reduce the probability of intervertebral disc degeneration in upper adjacent segments. Simultaneously, patients in the Waveflex group showed postoperative improvements in LL, spinal sagittal imbalance, and quality of life.

Comparing Sonazoid contrast-enhanced ultrasound to contrast-enhanced CT and MRI for differentially diagnosing renal lesions: a prospective multicenter study.

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.

Comparative long-term outcomes of natural orifice specimen extraction surgery and conventional laparoscopic colectomy for left-sided colorectal cancer: a propensity score-matched analysis.

BACKGROUND: Natural orifice specimen extraction surgery (NOSES) is currently widely used in left-sided colorectal cancer. Some clinical comparative studies have been conducted, providing evidence of its safety and oncological benefits. However, these studies are typically characterized by small sample sizes and short postoperative follow-up periods. Consequently, in this research, the authors adopt the propensity score matching method to undertake a large-scale retrospective comparative study on NOSES colectomy for left-sided colorectal cancer, with the goal of further augmenting the body of evidence-based medical support for NOSES. METHODS: This retrospective study involved patients who underwent NOSES colectomy and conventional laparoscopic (CL) colectomy for left-sided colorectal cancer between January 2014 and April 2021. In the NOSES group, specimens were extracted through the anus with the help of a Cai tube (homemade invention: ZL201410168748.2). The patients were matched at a ratio of 1:1 according to age, sex, BMI, tumor diameter, tumor location (descending and splenic flexure colon/ sigmoid colon/ middle and upper rectum), tumor height from anal verge, ASA grade, previous abdominal surgery, clinical pathologic stage, preoperative CEA. After matching, 132 patients in the NOSES group and 132 patients in the CL group were eligible for analysis. RESULTS: Compared with CL group, NOSES group was associated with decreased postoperative maximum pain score (2.6±0.7 vs. 4.7±1.7, P=0.000), less additional analgesia required (6.8 vs. 34.8%, P=0.000), faster time to passage of flatus (2.3±0.6 days vs. 3.3±0.7 days, P=0.000), less wound infection (0.0 vs. 6.1%, P=0.007), and longer operative time (212.5±45.8 min vs. 178.0±43.4 min, P=0.000). No significant differences were observed in estimated blood loss, time to resume regular diet, postoperative hospital stay, conversion to open surgery or conventional minilaparotomy, total morbidity, readmission, mortality, pathologic outcomes, and Wexner incontinence score between groups. After a median follow-up of 63.0 months, the 5-year overall survival rates were 88.3 versus 85.0% (P=0.487), disease-free survival rates were 82.9 versus 83.6% (P=0.824), and the local recurrence rates were 4.4 versus 4.0% (P=0.667) in the NOSES and CL groups, respectively. CONCLUSIONS: This study suggests that NOSES colectomy using a Cai tube for left-sided colorectal cancer is a safe and feasible option with better cosmetic results, less pain, faster recovery of gastrointestinal function, and comparable long-term clinical and oncologic outcomes to CL colectomy.

Vulvar Hidradenoma Papilliferum.

Aim: This study examines the clinical and pathological characteristics, immune profile, histological occurrence, diagnosis, and differential diagnosis of vulvar hidradenoma papilliferum. Methods: An analysis was conducted on clinical data, histological patterns, and immunohistochemical findings from 45 cases of vulvar hidradenoma papilliferum, and relevant published articles were reviewed. Simultaneously, high-risk HPV typing was performed on these 45 cases. Results: The 45 cases of vulvar hidradenoma papilliferum displayed tumor sizes ranging from 0.3 to 2.0 cm and were observed to be pink or red in appearance. Vacuolated cytoplasm, large abnormal nuclei, distinct nucleoli, and scattered eosinophilic luminal secretions were observed in the glands. Positive staining for CK7 and progesterone receptor (PR) with focal mammaglobin and GCDFP-15 expression was found through immunohistochemistry. CK20 staining was noted as negative. Conclusion: Hidradenoma papilliferum is a rare benign tumor that originates in secretory glands. The diagnosis of this condition is aided by gross and immunohistochemical results, and differentiation from other conditions is necessary.

Toxicity and oxidative stress of HepG2 and HL-7702 cells induced by PAH4 using oil as a carrier.

Polycyclic aromatic hydrocarbons (PAHs), a widespread class of food pollutants, are commonly exposed to humans along with edible oil. The dietary exposure pattern of PAH4 was simulated to study the toxicity and oxidative stress of oil-based PAH4 on hepatocytes. The findings demonstrated that oil-based PAH4 induced cell viability and mitochondrial membrane potential decreased and promoted apoptosis and oxidative stress in a concentration-dependent manner. Benzo[a]pyrene had the strongest toxicity and HL-7702 cells were more sensitive to toxicity than HepG2 cells, due to differences in induced CYP1A enzyme activity. Oil-based PAH4 had greater cytotoxicity than PAH4, attributed to the synergistic effect of oil and PAH4. Furthermore, oil-based PAH4 induced oxidative stress in HepG2 and HL-7702 cells through the same AHR-Nrf2-KEAP1 pathway, which was elucidated by detecting genes and proteins expression. This study lays the foundation for elucidating the harm of dietary exposure to PAHs and reminds us that food composition may increase the harm of PAHs.

Targeting NEAT1 Affects the Sensitivity to PARPi in Serous Ovarian Cancer by Regulating the Homologous Recombination Repair Pathway.

Objective: Patients initially sensitive to PARPi (PARP inhibitor) regain resistance because of homologous recombination (HR) restoration, although PARPi has a synthetic lethality effect on serous ovarian cancer cells with BRCA1/2 mutations. This study aimed to investigate the role of NEAT1 in HR function and whether targeting NEAT1 in serous ovarian cancer cells could increase PARPi sensitivity. Methods: Ovarian cancer patients' clinical information and the expression of NEAT1 were collected from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Ovarian cancer (OC) cells HeyA8 and SKOV3 were silenced by transfecting NEAT1 ASO. QRT-PCR confirmed the mRNA expression of RAD51, FOXM1, NEAT1_1 and NEAT1_2. We assessed the expression of RAD51, FOXM1, and γ-H2AX by Western blotting and Immunofluorescence. Comet Assays were used to detect DNA double-strand damage levels. In OC cells transfected with NEAT1 ASO or co-transfected overexpression RAD51/empty vector and si-NEAT1/si-ctrl, the sensitivity to Olaparib was determined using CCK8 assay. The Kaplan-Meier survival curves assessed the prognostic and predictive roles of NEAT1 in OC. Results: NEAT1 was an independent prognostic marker of ovarian cancer. NEAT1 knockdown reduced the expression of NEAT1_1, NEAT1_2, RAD51, and FOXM1 and increased the expression of γ-H2AX. In addition, Olaparib increased the expression of RAD51, representing HR repair efficiency, which was inhibited by NEAT1 knockdown. Moreover, the knockdown of NEAT1 increased the DNA damage caused by Olaparib, demonstrated by increased nuclear γ-H2AX foci, DNA in the tail, and expression of γ-H2AX. NEAT1 knockdown sensitized ovarian cancer cells to Olaparib by targeting RAD51-HR. NEAT1 expression could predict response to chemotherapy for ovarian cancer. Conclusions: NEAT1 knockdown inhibited HR capacity and increased DNA damage caused by Olaparib in serous ovarian cancer cells, making them more sensitive to Olaparib and providing a crucial therapeutic advantage of increasing sensitivity to Olaparib.

Combined toxicity of oil-based PAH4 mixtures on HL-7702 cells.

Polycyclic aromatic hydrocarbons (PAHs) as a group of prevalent persistent organic pollutants in the environment are always found as mixtures. The combined toxicity of oil-based PAH4 seems seldom to be mentioned. To evaluate the combined toxicity of oil-based PAH4 mixtures on HL-7702 cells, the effects of single, binary, ternary, and quaternary mixtures on cell viability were examined, and the concentration addition model and combination index (CI)-isobologram model were selected to predict the toxicological interactions of the mixtures. The results showed that the PAH4 mixtures had a concentration-dependent effect on cell viability. The CI model was more suitable for elucidating the toxicity interactions of mixtures. In addition, the combined toxicity of BaA + BaP and BaA + Chr + BbF + BaP was antagonistic, BaA + Chr, BaA + BbF, Chr + BbF, and BaA + Chr + BbF was synergistic, and the remaining mixtures shifted from antagonistic to synergistic. Antagonistic effects were observed in all mixtures containing BaP, indicating that oil-based PAH4 mixtures containing BaP had a mitigating effect on cytotoxicity. Furthermore, BbF was identified as playing a key role in the synergistic effects in binary and ternary mixtures. This study provided a new acknowledgment to assess the interactions of PAH4 mixtures which is helpful for further study of the toxicity risks in the environment.

Long-term efficacy of transanal local excision versus total mesorectal excision after neoadjuvant treatment for rectal cancer: A meta-analysis.

AIM: The purpose of this meta-analysis is to compare the long-term efficacy of transanal local excision (TLE) versus total mesorectal excision (TME) following neoadjuvant therapy for rectal cancer. METHOD: The Web of Science, Pubmed, Medline, Embase, and the Cochrane Library were systematically searched for correlational research. The Newcastle-Ottawa Scale and the Cochrane risk of bias tool were used to assess the quality of cohort studies (CSs) and randomized controlled trials (RCTs), respectively. Statistically analyzed using RevMan5.4. RESULT: A total of 13 studies, including 3 randomized controlled trials (RCTs) and 10 cohort studies (CSs), involving 1402 patients, were included in the analysis. Of these, 570 patients (40.66%) underwent TLE, while 832 patients (59.34%) underwent TME. In the meta-analysis of CSs, no significant difference was observed between the TLE group and TME group regarding 5-year overall survival (OS) and 5-year disease-free survival (DFS) (P > 0.05). However, the TLE group had a higher rates of local recurrence (LR) [risk ratio (RR) = 1.93, 95%CI (1.18, 3.14), P = 0.008] and a lower rates of 5-years local recurrence-free survival (LRFS) [hazard ratio (HR) = 2.79, 95%CI (1.04, 7.50), P = 0.04] compared to the TME group. In the meta-analysis of RCTs, there was no significant difference observed between the TLE group and TME group in terms of LR, 5-year OS, 5-year DFS, and 5-year disease-specific survival (P > 0.05). CONCLUSION: After undergoing neoadjuvant therapy, TLE may provide comparable 5-year OS and DFS to TME for rectal cancer. However, neoadjuvant therapy followed by TLE may has a higher LR and lower 5-year LRFS compared to neoadjuvant therapy followed by TME, so patients should be carefully selected. Neoadjuvant therapy followed by TLE may be a suitable option for patients who prioritize postoperative quality of life. However, the effectiveness of this approach requires further research to draw a definitive conclusion.

The mechanism of copper transporters in ovarian cancer cells and the prospect of cuproptosis.

Copper transporters can not only carry copper (Cu) to maintain the homeostasis of Cu in cells but also transport platinum-based chemotherapy drugs. The effect of copper transporters on chemosensitivity has been demonstrated in a variety of malignancies. In addition, recent studies have reported that copper transporters can act as vectors to induce cuproptosis. Therefore, copper transporters can act on cells through different mechanisms to achieve different purposes. This review mainly describes the current research progress of the intracellular transport mechanism of copper transporters and cuproptosis, and prospects for the application of them in the treatment of ovarian cancer (OC).

The Roles of Exosomes in Ovarian Cancer Chemo-resistance.

As common gynecological oncology, ovarian cancer has a high fatality rate and poor overall survival, mainly because of nonspecific symptoms in the early stages and chemotherapy resistance. Exosomes, nano-sized vesicles secreted by almost all types of cells, carry valuable commodities such as proteins, lipids, enzymes, mRNAs, and miRNAs between cells. They take part in remodeling the tumor microenvironment, promoting tumor angiogenesis and metastasis, and regulating immune metastasis and chemotherapy resistance in ovarian cancer. Previous studies have reported that exosomes could transfer chemotherapy resistance from drug-resistant tumor cells to sensitive ones by delivering proteins and miRNAs. Also, exosomes are involved in chemotherapy resistance by transferring multidrug-resistance-related transporters, decreasing apoptosis, promoting epithelial-to-mesenchymal transition, and changing signal transduction pathways. Furthermore, they play a significant role in early detection, chemotherapy efficacy evaluation, and treatment of ovarian cancer. Exosomes are applied as chemotherapeutic delivery vehicles and therapeutic targets to inhibit anti-tumor immune responses. In addition, exosomes can be developed for cancer immunotherapy because of their immunomodulatory potential. Therefore, the article reviews the latest research progress of exosomes in ovarian cancer to elaborate on the mechanisms of exosome-mediated chemotherapy resistance in ovarian cancer patients and provide a forecast on their clinical therapeutic potential in improving chemotherapy sensitivity.

Walnut Protein: A Rising Source of High-Quality Protein and Its Updated Comprehensive Review.

Recently, plant protein as a necessary nutrient source for human beings, a common ingredient of traditional processed food, and an important element of new functional food has gained prominence due to the increasing demand for healthy food. Walnut protein (WP) is obtained from walnut kernels and walnut oil-pressing waste and has better nutritional, functional, and essential amino acids in comparison with other vegetable and grain proteins. WP can be conveniently obtained by various extraction techniques, including alkali-soluble acid precipitation, salting-out, and ultrasonic-assisted extraction, among others. The functional properties of WP can be modified for desired purposes by using some novel methods, including free radical oxidation, enzymatic modification, high hydrostatic pressure, etc. Moreover, walnut peptides play an important biological role both in vitro and in vivo. The main activities of the walnut peptides are antihypertensive, antioxidant, learning improvement, and anticancer, among others. Furthermore, WP could be applied in the development of functional foods or dietary supplements, such as delivery systems and food additives, among others. This review summarizes recent knowledge on the nutritional, functional, and bioactive peptide aspects of WP and possible future products, providing a theoretical reference for the utilization and development of oil crop waste.

Abnormal expression of long non-coding RNA FGD5-AS1 affects the development of ovarian cancer through regulating miR-107/RBBP6 axis.

Long non-coding RNAs (lncRNAs) are important players in cancer development. LncRNA FGD5-AS1 has been reported as a potential oncogene in ovarian cancer (OC). The present paper focused on the action mechanism of FGD5-AS1 in OC. Clinical OC samples were collected for expression analyses of FGD5-AS1, RBBP6, and miR-107. The expression of FGD5-AS1, RBBP6, and miR-107 in OC cells was altered by transfection. OC cell proliferation was assessed by MTT and colony formation assays, and angiogenesis of human umbilical vein endothelial cells (HUVECs) cultured with OC cell supernatants by matrigel angiogenesis assay. The interactions among FGD5-AS1, miR-107, and RBBP6 were detected by luciferase reporter assay. FGD5-AS1 and RBBP6 were strongly expressed and miR-107 was poorly expressed in clinical OC samples and OC cell lines. FGD5-AS1 or RBBP6 overexpression in Hey and SKOV3 cells could potentiate OC cell proliferation and HUVEC angiogenesis, while FGD5-AS1 or RBBP6 knockdown in OC cells inhibited the above cellular processes. FGD5-AS1 targeted miR-107 to positively regulate RBBP6 expression. Additionally, miR-107 overexpression or RBBP6 knockdown in SKOV3 cells partially reversed the FGD5-AS1-dependent stimulation of OC cell proliferation and HUVEC angiogenesis. FGD5-AS1 may act as a promoter of OC via miR-107/RBBP6 axis.

Formation, migration, derivation, and generation mechanism of polycyclic aromatic hydrocarbons during frying.

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic and lipophilic, which can be found in frying system. This review summarized the formation, migration and derivation for PAHs, hypothesized the possible mechanism for PAHs generation during frying and presented the research prospects. Some factors like high oil consumption, high temperature, long time and oil rich in unsaturated fatty acids promoted the formation of PAHs and the presence of antioxidants inhibited the PAHs formation. The effect of proteins and carbohydrates in foods on the formation of PAHs is inconclusive. The formed PAHs were migrated into food and air. Moreover, some PAHs transformed into more toxic PAHs-derivatives during frying. The generation of PAHs may be related to low-barrier free radical-mediated reaction and the unsaturated hydrocarbons may be precursors of PAHs during frying. In future, the isotope tracer technology and on-line detection may be applied to discover intermediates and provide clues for studying PAHs generation mechanisms.

Acute inflammatory reaction during anti-angiogenesis therapy combined with immunotherapy as a possible indicator of the therapeutic effect: Three case reports and literature review.

The posterior line treatment of unresectable advanced or metastatic gastrointestinal (GI) tumors has always been a challenging point. In particular, for patients with microsatellite stable (MSS)/mismatch repair proficient (pMMR) 0GI tumors, the difficulty of treatment is exacerbated due to their insensitivity to immune drugs. Accordingly, finding a new comprehensive therapy to improve the treatment effect is urgent. In this study, we report the treatment histories of three patients with MSS/pMMR GI tumors who achieved satisfactory effects by using a comprehensive treatment regimen of apatinib combined with camrelizumab and TAS-102 after the failure of first- or second-line regimens. The specific contents of the treatment plan were as follows: apatinib (500 mg/d) was administered orally for 10 days, followed by camrelizumab (200 mg, ivgtt, day 1, 14 days/cycle) and TAS-102 (20 mg, oral, days 1-21, 28 days/cycle). Apatinib (500 mg/d) was maintained during treatment. Subsequently, we discuss the possible mechanism of this combination and review the relevant literature, and introduce clinical trials on anti-angiogenesis therapy combined with immunotherapy.

Establishment of a prognostic model for ovarian cancer based on mitochondrial metabolism-related genes.

Background: Mitochondrial metabolism and mitochondrial structure were found to be altered in high-grade serous ovarian cancer (HGSOC). The intent of this exploration was to systematically depict the relevance between mitochondrial metabolism-related genes (MMRGs) and the prognosis of HGSOC patients by bioinformatics analysis and establish a prognostic model for HGSOC. Methods: First of all, screened differentially expressed genes (DEGs) between TCGA-HGSOC and GTEx-normal by limma, with RNA-seq related HGSOC sourced from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. Subsequently, expressed MMRGs (DE-MMRGs) were acquired by overlapping DEGs with MMRGs, and an enrichment analysis of DE-MMRGs was performed. Kaplan-Meier (K-M) survival analysis and Cox regression analysis were conducted to validate the genes' prognostic value, Gene Set Enrichment Analysis (GSEA) to elucidate the molecular mechanisms of the risk score, and CIBERSORT algorithm to explore the immuno landscape of HGSOC patients. Finally, a drug sensitivity analysis was made via the Drug Sensitivity in Cancer (GDSC) database. Results: 436 HGSOC-related DE-MMRGs (222 up-regulated and 214 down-regulated) were observed to participate in multiple metabolic pathways. The study structured a MMRGs-related prognostic signature on the basis of IDO1, TNFAIP8L3, GPAT4, SLC27A1, ACSM3, ECI2, PPT2, and PMVK. Risk score was the independent prognostic element for HGSOC. Highly dangerous population was characterized by significant association with mitochondria-related biological processes, lower immune cell abundance, lower expression of immune checkpoint and antigenic molecules. Besides, 54 drugs associated with eight prognostic genes were obtained. Furthermore, copy number variation was bound up with the 8 prognostic genes in expression levels. Conclusion: We have preliminarily determined the prognostic value of MMRGs in HGSOC as well as relationship between MMRGs and the tumor immune microenvironment.

Monocytes reprogrammed by tumor microparticle vaccine inhibit tumorigenesis and tumor development.

Tumor microparticles (T-MPs) are considered as a tumor vaccine candidate. Although some studies have analyzed the mechanism of T-MPs as tumor vaccine, we still lack understanding of how T-MPs stimulate a strong anti-tumor immune response. Here, we show that T-MPs induce macrophages to release a key chemotactic factor CCL2, which attracts monocytes to the vaccine injection site and enhances endocytosis of antigen. Monocytes subsequently enter the draining lymph node, and differentiate into monocyte-derived DCs (moDCs), which present tumor antigens to T lymphocytes and deliver a potent anti-tumor immune response. Mechanically, T-MPs activate the cGAS-STING signaling through DNA fragments, and then induce monocytes to upregulate the expression of IRF4, which is a key factor for monocyte differentiation into moDCs. More importantly, monocytes that have endocytosed T-MPs acquire the ability to treat tumors. Collectively, this work might provide novel vaccination strategy for the development of tumor vaccines and facilitate the application of T-MPs for clinic oncotherapy. Supplementary Information: The online version contains supplementary material available at 10.1186/s12645-023-00190-x.

Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation.

The P2RY1 receptor is known to cause cancer by activating the ERK signal pathway, and its DNA methylation status and corresponding regulatory mechanism remain unknown. This study used the DNA methylation chip to profile the genome-wide DNA methylation level in gastric cancer tissues. The proliferation and apoptosis of the SGC7901 gastric cancer cell line were determined after treatment with a selective P2RY1 receptor agonist, MRS2365. The promoter region of P2RY1 was found to be highly methylated with four hypermethylated sites (|Δß value| > 0.2) in diffuse gastric cancer and was validated by bioinformatics analysis in the TCGA database. Also, immunohistochemical staining data obtained from the HPA database demonstrated the downregulated expression of proteins encoded by P2RY1 in stomach cancer tissue. The analysis of MRS2365-treated cells by annexin V/propidium iodide staining and caspase-3 activity assays indicated the induction of apoptosis in SGC7901 cells. The P2RY1 receptor activation in human SGC7901 gastric cancer cells via the MRS2365 agonist induced apoptosis and reduced cell growth. High DNA methylation in the promoter region of P2RY1 might have contributed to the reduced expression of P2RY1's mRNA, which was likely responsible for the "aggressive" nature of the diffuse gastric cancer.

A Clinicopathological Review of 203 Cases of Atypical Polypoid Adenomyoma of the Uterus.

OBJECTIVE: To provide a reference for the diagnosis and treatment of atypical polypoid adenomyoma (APA). METHODS: This was a retrospective study of 203 APA patients from 2011 to 2021. The clinicopathological characteristics, treatments, and prognosis were analyzed. RESULTS: The average age at diagnosis of APA patients was 39.30 ± 11.01 years, and premenopausal women accounted for 81.3%. Abnormal uterine bleeding or menorrhagia were the most common clinical manifestations of APA. The uterine fundus (78.3%), followed by the lower segment of the uterus (11.8%), was the most common location of the APA lesions. Abnormal blood vessels were seen on the surface of 28 APA tumors. APA can coexist with atypical endometrial hyperplasia (18.2%) and endometrial cancer (10.8%). Immunohistochemical analysis was performed on 99 samples. In the glandular component, ER (94.8%), PR (94.8%), Ki-67 (51.5%), p53 (45.6%), PTEN (18.8%), and mismatch repair proteins (96.4%) were positively expressed. Stromal immunophenotype expression was exhibited as follows: CD10-(89.5%), p16+(86.9%), h-caldesmon-(66.7%), Desmin+(75%), and Vimentin+(88.9%). Fifty-five APA patients received TCR, and 33 of them received adjuvant therapy after the operation. The postoperative recurrence rate (9.1% vs. 36.4%, p < 0.05) and malignant transformation rate (3.0% vs. 18.2%, p < 0.05) of the treated group were significantly lower than the untreated group. CONCLUSIONS: APA usually occurs in women of childbearing age, and the diagnosis is based on pathological morphology. APA has a low malignant potential, and those who have fertility requirements can undergo conservative TCR treatment, supplemented by progesterone treatment after surgery and close follow-up. Total hysterectomy is the treatment of choice for APA patients with atypical endometrial hyperplasia around the lesion.