Endoscopic injection of lauromacrogol foam sclerotherapy for rectal cavernous hemangioma: A case report.

RATIONALE: Rectal cavernous hemangioma is a rare, benign vascular disease that seldom causes lower gastrointestinal bleeding, characterized by a high rate of misdiagnosis and missed diagnoses. Surgical treatment is considered to be relatively effective; however, it is accompanied by certain employed in the treatment of superficial hemangioma, boasting the advantages of minimally invasive surgery, including safety, effectiveness, reduced trauma, and rapid recovery. However, there is a lack of literature regarding the application of foam sclerosing agents for gastrointestinal hemangiomas. CASE CONCERNS: We present a case of a 60-year-old male who was admitted to our hospital with a history of recurrent hematochezia for >1 year and worsening symptoms for 1 week. The patient's medical history was unremarkable. DIAGNOSES: Following colonoscopy, nuclear magnetic resonance imaging, computed tomography, and other examinations, the final diagnosis was rectal cavernous hemangioma. INTERVENTIONS: Due to the patient's refusal of surgery, endoscopic foam sclerotherapy using a lauromacrogol injection was performed after obtaining informed consent from the patient and their relatives. OUTCOMES: Post-sclerotherapy, hematochezia symptoms ceased, and no adverse reactions were observed. Two months later, colonoscopy and nuclear magnetic resonance imaging showed that the hemangioma had almost completely disappeared, with only a small amount of tumor remnants, yielding a satisfactory curative effect. CONCLUSION: Our findings indicate that endoscopic injection of a lauromacrogol foam sclerosing agent is a safe, effective, and minimally invasive treatment option for gastrointestinal cavernous hemangiomas.

Cup-like nuclei in adult B-cell acute lymphoblastic leukemia with the translocation (4;11)(q21;q23).

Cuplike Nuclei(CLN) cells, particularly rare in Acute Lymphoblastic Leukemia(ALL), have been documented in only few cases to date. A recent study has revealed a correlation between CLN and IKZF1 deletions in pediatric B-ALL. This study introduces a case of CLN in adult B-ALL with a translocation (4;11)(q21;q23), while discussing the current relevant literature on the subject. Through this examination, several unique characteristics of CLN cells in both ALL and Acute Myeloid Leukemia are highlighted. It is essential to accumulate further data to confirm these distinctive traits, and investigate the potential association between CLN and cytogenetic/molecular abnormalities.

A preliminary study on the reference intervals of serum tumor marker in apparently healthy elderly population in southwestern China using real-world data.

BACKGROUND: The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method. METHODS: Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method. RESULTS: In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0-6.75 ng/ml, carcinoembryonic antigen (CEA) 0-4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0-22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0-28.10 U/ml, carbohydrate antigen125 (CA125) 0-20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0-4.66 U/ml, neuron-specific enolase (NSE) 0-19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0-5.26 ng/ml and 0-1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes. CONCLUSION: This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.

ALKBH5 promotes the development of lung adenocarcinoma by regulating the polarization of M2 macrophages through CDCA4.

OBJECTIVE: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, with high morbidity and mortality. N6-methyladenosine (m6A) is an important regulator of LUAD progression. Here, we investigated the potential biological functions of ALKBH5 (a m6A demethylated enzyme) and cell division cycle associated protein 4 (CDCA4) in the progression of LUAD. METHODS: The expressions of CDCA4, METTL3, ALKBH5, FTO, YTHDC2 and YTHDC1 mRNA and proteins in LUAD and adjacent tissues, as well as NCI-H1299 and NCI-H157 cells were detected by RT-qPCR and western blot. Meanwhile, the role of ALKBH5 and CDCA4 in macrophage polarization was explored through tumor formation in Lewis lung carcinoma (LLC) mice and the co-culture system of NCI-H1299 and NCI-H157/THP-1 cells. Cell characterization was further analyzed. The expression of Ki-67 in tumor tissue was tested by immunohistochemistry. The scale of M1 and M2 macrophages was determined by flow cytometry. RESULTS: CDCA4 was significantly overexpressed in NCI-H1299 and NCI-H157 cell lines compared with BEAS-2B cells. The fold enrichment of CDCA4 m6A level in the overexpression (oe)-METTL3 or short hairpin (sh)-ALKBH5 cells was enhanced. Overexpression of CDCA4 promoted the cell viability, proliferation and migration, and inhibited apoptosis, which was reversed by sh-ALKBH5 intervention. Overexpression of YTHDC2 (not YTHDC1) inhibited the effect of CDCA4 on sh-ALKBH5 cells. sh-CDCA4 inhibited tumor growth and weight of LLC cells in mice, and promoted M1/M2 ratio in LLC mice and NCI-H1299/THP-1 and NCI-H157/THP-1 co-culture systems. Oe-CDCA4 promoted the volume and weight of tumor and inhibited the M1/M2 ratio of tumor tissue in LLC mice, but was reversed by sh-ALKBH5 intervention. CONCLUSION: m6A demethylase ALKBH5 promotes the development of LUAD through CDCA4 regulation of malignant characterization and M1/M2 macrophage polarization.

CDCA4 as a novel molecular biomarker of poor prognosis in patients with lung adenocarcinoma.

Background: Because of the high incidence and poor prognoses of lung adenocarcinoma (LUAD), it is essential to identify cost-effective treatment options and accurate and reliable prognostic biomarkers. CDCA4 upregulation has been identified in many cancers. However, the prognostic importance of CDCA4 and its role in LUAD remain unknown. Methods: CDCA4 expression was assessed through IHC, Western blotting (WB) and RT-PCR. The Cancer Genome Atlas (TCGA) provided data from 513 patients to study the expression and prognostic relevance of CDCA4 in LUAD. This study used gene set enrichment analyses (GSEA), gene ontology and KEGG pathway analyses for elucidating potential mechanisms underpinning the function of CDCA4 in LUAD. We also investigated correlations between immune infiltration and CDCA4 expression with single specimen GSEA (ssGSEA). Results: According to database analysis and identification of patient tissue samples, CDCA4 expression in tumour tissues surpassed that in normal tissues (P< 0.001). Increased CDCA4 expression was positively correlated with a higher T, N, pathologic stage and poor primary therapy outcome. In addition, the Kaplan-Meier plotter exhibited that an elevated CDCA4 expression was related to worse disease-specific survival(DSS) and overall survival (OS) (DSS HR= 5.145, 95% CI=3.413-7.758, P<0.001; OS HR=3.570, 95% CI=2.472-5.155, P<0.001). Then multivariate COX regression analyses indicated that the CDCA4 gene was an independent risk consideration for prognoses. GO and KEGG results showed that CDCA4 and its neighbouring genes were enriched in the cell cycle and DNA replication. As determined by GSEA, CDCA4 was related to various immune-related signalling pathways (SPs), Homologous recombination, DNA replication and the cell cycle. SsGSEA analysis showed a significant association between CDCA4 expression and Th2 cells, mast cells, eosinophils and Th17 cells. Conclusions: CDCA4 expression is increased in LUAD and is a potential predictive biomarker and therapeutic target.

Targeted delivery strategy: A beneficial partner for emerging senotherapy.

Numerous cutting-edge studies have confirmed that the slow accumulation of cell cycle arrested and secretory cells, called senescent cells (SCs), in tissues is an important negative factor, or even the culprit, in age- associated diseases such as non-alcoholic fatty liver, Alzheimer's disease, type 2 diabetes, atherosclerosis, and malignant tumors. With further understanding of cellular senescence, SCs are important effective targets for the treatment of senescence-related diseases, called the Senotherapy. However, existing therapies, including Senolytics (which lyse SCs) and Senostatic (which regulate senescence-associated secretory phenotype), do not have the properties to target SCs, and side effects due to non-specific distribution are one of the hindrances to clinical use of Senotherapy. In the past few decades, targeted delivery has attracted much attention and been developed as a recognized diagnostic and therapeutic novel tool, due to the advantages of visualization of targets, more accurate drug/gene delivery, and ultimately "reduced toxicity and enhanced efficacy". Despite considerable advances in achieving targeted delivery, it has not yet been widely used in Senotherapy. In this review, we clarify the challenge for Senotherapy, then discuss how different targeted strategies contribute to imaging or therapy for SCs in terms of different biomarkers of SCs. Finally, the emerging nano-Senotherapy is prospected.

Mogroside V Improves Follicular Development and Ovulation in Young-Adult PCOS Rats Induced by Letrozole and High-Fat Diet Through Promoting Glycolysis.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. In this study, we induced a young-adult PCOS rat model by oral administration of letrozole combined with a high-fat diet and then treated with mogroside V (MV) to evaluate the protective effects of MV on endocrine and follicle development in young-adult PCOS rats. MV (600 mg/kg/day) administration not only significantly reduced the body weight and ovary weight, but also attenuated the disrupted estrous cycle and decreased the level of testosterone. MV restored the follicular development, especially by increasing the number of corpus luteum and the thickness of the granular layer in young-adult POCS rats. Moreover, metabolomics showed that MV markedly increased the levels of D-Glucose 6-phosphate, lactate and GTP, while decreased the level of pyruvate. Bioinformatic analysis revealed that MV recovered multiple metabolism-related processes including gluconeogenesis, glycolysis and glucose metabolic process. Further real-time quantitative PCR analysis showed that MV upregulated the expression of lactate dehydrogenase A (Ldha), hexokinase 2 (Hk2) and pyruvate kinase M2 (Pkm2). Western blotting and immunohistochemistry analysis showed that MV restored the expression of lactate dehydrogenase A (Ldha), hexokinase 2 (Hk2) and pyruvate kinase M2 (Pkm2). Collectively, these findings indicated that MV could effectively improve the ovarian microenvironment by upregulating the expression of LDHA, HK2 and PKM2 in granulosa cells and enhancing lactate and energy production, which may contribute to follicle development and ovulation of young-adult PCOS rats.

Resveratrol Improves Follicular Development of PCOS Rats by Regulating the Glycolytic Pathway.

SCOPE: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that can cause infertility; however, the underlying mechanisms remain ill-defined, and there are no available drugs or strategies for the treatment of PCOS. This study examined the therapeutic effect of resveratrol in a rat model of PCOS. METHODS AND RESULTS: PCOS is induced in rats by administration of letrozole and a high fat diet to determine whether resveratrol has a protective effect. Oral administration of resveratrol significantly decreased body weight, as well as the serum levels of testosterone and follicle stimulating hormone. Resveratrol improved the estrous cycle by restoring the thickness and number of granular cells. Resveratrol increased the levels of lactate and ATP, decreased pyruvate levels, and restored the glycolytic process, upregulating LDHA, HK2, and PKM2. Resveratrol also upregulated SIRT2, thereby modulating the expression of rate-limiting enzymes of glycolysis. CONCLUSION: Resveratrol suppressed damage to the ovaries in PCOS rats by restoring glycolytic activity, providing potential targets for the treatment of PCOS.

Retracted Article: Exosome-derived PTENP1 suppresses cisplatin resistance of bladder cancer (BC) by suppressing cell proliferation, migration and inducing apoptosis via the miR-103a/PDCD4 axis.

Bladder cancer (BC) is a lethal cancer that threatens the health of millions of people. Chemotherapy drug resistance, for example, cisplatin (DDP) resistance, is a huge limitation for BC therapy. PTEN pseudogene-1 (PTENP1) has been identified as a significant biomarker of multiple cancers. Therefore, it is essential to illuminate the molecular mechanism of PTENP1 in BC cell DDP resistance and progression. Serum exosomes were isolated using an ExoQuick precipitation kit. Serum exosomes were round-shaped vesicles of 100 ± 60 nm in size. The expression of PTENP1 was down-regulated in serum exosomes isolated from cisplatin non-responsive patients compared with responsive patients. ROC curves certified the diagnostic value of PTENP1. Apparently, PTENP1 transfection inhibited DDP-resistant BC cell proliferation, migration, cisplatin resistance and facilitated apoptosis. Next, we discovered that PTENP1 was a sponge of miR-103a, while PDCD4 was a target of miR-103a. More importantly, PTENP1 regulated DDP-resistant cell viability, migration, apoptosis and cisplatin resistance by interacting with the miR-103a/PDCD4 axis. In addition, PTENP1 hindered tumor growth of cisplatin-resistant mice. Exosome-derived PTENP1 suppressed the DDP resistance of BC by inhibiting cell proliferation, migration and promoting apoptosis through regulating the miR-103a/PDCD4 axis, representing a targeted therapy for DDP-resistant BC patients.

Detection and clinical significance of DNA repair gene ERCC8 tag SNPs in gastric cancer.

BACKGROUND/AIMS: Excision repair cross-complementing group 8 (ERCC8) is one of the members of the nucleotide excision repair pathway. This study aimed to explore the association between ERCC8 tag single nucleotide polymorphisms (SNPs) and gastric cancer. MATERIALS AND METHODS: Totally, 120 patients with gastric cancer treated from March 2010 to March 2011 were selected as the observation group and 120 healthy individuals were selected as the control group during the same period. The Sequenom MassARRAY system was used to identify genotypes in these samples. The genetic locus of ERCC8 tag SNPs and the relevance of gastric cancer risk to the different ERCC8 genotypes alone or in combination with Helicobacter pylori infection were observed and analyzed. The AA, GA, and GG genotypes on rs158572 and rs158916 in the observation and control groups were compared. RESULTS: The results showed that the odds ratio of the different ERCC8 rs158572 and rs158916 genotypes was not significantly increased in the observation group compared with that in the control group. By contrast, in patients with H. pylori infection, the ERCC8 rs158572 GA/GG and rs158916 TT genotypes showed a 7.921-fold and 8.021-fold [95% confidence interval (CI)=4.022-15.921, p=0.029 and 95% CI=3.021-15.092, p=0.021, respectively] increased risk of gastric cancer than the AA and CT/CC genotypes, respectively. CONCLUSION: Helicobacter pylori infection combined with ERCC8 rs158572 and rs158916 can be used as a predictive index of gastric cancer occurrence.

Detection and Clinical Significance of COX-2 Gene SNPs in Gastric Cancer.

Gastric cancer has high morbidity and mortality. Identification of patients with high gastric cancer risk at early stage will improve patient prognosis. In this study, we examined two single nucleotide polymorphism (SNP) sites of COX-2 gene in gastric cancer patients and explored the effect of the SNPs on the morbidity of gastric cancer. We found that the SNPs COX-2-1195G/A and COX-2-8473T/C are correlated with the occurrence of gastric cancer, and the patients with variants A and C of the SNPs are liable to have gastric cancer. Our study provides a potential method for screening of susceptible population of gastric cancer for early-stage intervention in patients.