Intravenous leiomyomatosis in the inferior vena cava and right atrium with pulmonary benign metastasizing leiomyoma secondary to a pelvic arteriovenous fistula: A case report and literature review.

BACKGROUND: To report the diagnosis and treatment of a rare disease of intravenous leiomyomatosis (IVL) originating from the uterus, growing in the inferior vena cava (IVC) and extending into the right atrium (RA) associated with a pelvic arteriovenous fistula (AVF). This is the first reported case of IVL in the IVC and RA with pulmonary benign metastasizing leiomyoma (PBML) secondary to a pelvic AVF despite the use of GnRH agonists in a nonmenopausal woman. CASE PRESENTATION: The patient was a 50-year-old premenopausal woman with a history of surgical resection for and antiestrogen conservative drug for pulmonary benign metastasizing leiomyoma (PBML) 5 years. The patient nevertheless developed IVL in the IVC, internal iliac vein and RA accompanied by AVF. Vaginal ultrasound combined with echocardiography and computerized tomographic venography imaging assists in the diagnosis of IVL combined with AVF, with histopathology and immunohistochemistry ultimately confirming the diagnosis. The patient ultimately was performed with a combination of hysterectomy, bilateral adnexectomy, and resection of tumors in the IVC and RA without cardiopulmonary bypass and sternotomy. CONCLUSION: BML may be difficult to control with incomplete removal of the uterus and ovaries even with the use of antiestrogenic medications, and medically induced AVF resulting from fibroid surgery may accelerate this process and the development of IVL.

The Effect of Preoperative Anemia on the Odds of Allogeneic Blood Transfusion and Patient Outcomes in Colorectal Neoplasm Patients.

BACKGROUND: The optimal preoperative hemoglobin (Hb) value of colorectal neoplasm patients is still being debated. This study aimed at determining the effect of preoperative anemia on patient outcomes and allogeneic blood transfusion (ABT). METHODS: This retrospective cohort study enrolled colorectal neoplasm patients, that underwent surgery, from January 1, 2012, to December 31, 2021. The primary outcomes were the association between anemia and average length of stay (ALOS) and the odds of ABT. The secondary outcomes were the risk factors of the primary outcomes. Univariate and multivariate logistic regression analyses were applied to identify the association and risk factors. RESULTS: A total of 14,352 inpatients were included in the study, of whom 3,035 experienced (21.15%) mild anemia, 1,500 (10.45%) moderate anemia, and 104 (0.72%) severe anemia. Overall, 1,418 (9.88%) patients received ABT during the hospitalization, and 546 (3.80%) patients received perioperative ABT. In the multivariate logistic regression analysis, compared with the no anemic group, the odds ratio [OR] of ABT during the hospitalization for patients with mild/moderate/severe anemia were 5.915, 95% confidence interval [CI]: 4.717 - 7.418; 104.777, 95% CI: 84.345 - 130.160; and 13,361.442, 95% CI: 816.004 - 218,783.511, respectively, and the OR of periopera¬tive ABT were 4.332, 95% CI: 3.245 - 5.785; 27.492, 95% CI: 20.974 - 36.037; and 20.912, 95% CI: 11.832 - 36.959, respectively. Besides, the ALOS was longer, ß were 0.619, 95% CI: 0.346 - 0.892; 1.188, 95% CI: 0.821 - 1.554; and 1.395, 95% CI: 0.107 - 2.684, respectively. CONCLUSIONS: Anemia is a common phenomenon in colorectal neoplasm surgical patients, and even mild anemia could be a deleterious predictor on the outcomes of colorectal neoplasm patients that underwent surgery.

Mechanically stimulated osteocytes maintain tumor dormancy in bone metastasis of non-small cell lung cancer by releasing small extracellular vesicles.

Although preclinical and clinical studies have shown that exercise can inhibit bone metastasis progression, the mechanism remains poorly understood. Here, we found that non-small cell lung cancer (NSCLC) cells adjacent to bone tissue had a much lower proliferative capacity than the surrounding tumor cells in patients and mice. Subsequently, it was demonstrated that osteocytes, sensing mechanical stimulation generated by exercise, inhibit NSCLC cell proliferation and sustain the dormancy thereof by releasing small extracellular vesicles with tumor suppressor micro-RNAs, such as miR-99b-3p. Furthermore, we evaluated the effects of mechanical loading and treadmill exercise on the bone metastasis progression of NSCLC in mice. As expected, mechanical loading of the tibia inhibited the bone metastasis progression of NSCLC. Notably, bone metastasis progression of NSCLC was inhibited by moderate exercise, and combinations with zoledronic acid had additive effects. Moreover, exercise preconditioning effectively suppressed bone metastasis progression. This study significantly advances the understanding of the mechanism underlying exercise-afforded protection against bone metastasis progression.

Decision-Making Error in Platelet Transfusion Caused by EDTA-Dependent Pseudothrombocytopenia: a Case Report and Literature Review.

BACKGROUND: Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP) is a rare phenomenon characterized by pseudo low platelet counts when using EDTA as anticoagulant and can result in false decision making of platelet transfusion. METHODS: An application for platelet transfusion from a patient who planned to undergo spinal surgery was received by the Department of Transfusion service. The preoperative laboratory test results showed thrombocytopenia (platelet counts: 27 x 109/L). The surgeon planned to transfuse platelets before the operation to avoid bleeding in operation due to thrombocytopenia. However, the lab technologist found that there was aggregation of platelets under the microscope. Samples used with sodium citrate and heparin as anticoagulants were rechecked. RESULTS: The platelet count of the patient was normal in sodium citrate and heparin anticoagulant tubes. The patient had no history and clinical symptoms of thrombocytopenia. Therefore, the doctor canceled the platelet order. We also reviewed the relevant literature of EDTA-PTCP. CONCLUSIONS: EDTA-PTCP is rare and may result of a wrong decision of platelet transfusion. Correct understanding and treatment of this situation can avoid unnecessary platelet transfusion.

Molecular cloning of estrogen receptor and its function on vitellogenesis in pompano (Trachinotus ovatus).

Estrogen receptors (ERs) play a critical role in vitellogenesis (Vtgs). However, the contribution of each ER for the regulation of vtgs expression was not analyzed clearly in teleosts. In the present study, three ers isoforms (erα, erß1, and erß2) were cloned in pompano (Trachinotus ovatus). Real-time PCR and enzyme-linked immunosorbent assay (ELISA) was used to detect the effects of 17ß-estradiol (E2) on ERs and Vtgs in the liver of pompano. In vivo injection experiments showed that E2 significantly increased the expressions of ers and vtgs. ER broad spectrum antagonist Fulvestrant significantly attenuated the E2- induced up-regulation of ers and vtgs in a dose-dependent manner. ERα antagonist Methyl-piperidino pyrazole (MPP) significantly attenuated the up-regulation of erα, erß2, vtg-B and vtg-C, and promoted the expressions of erß1 and vtg-A. ERß antagonist Cyclofenil significantly inhibited the expressions of erß1, erß2, vtg-A and vtg-C, and promoted the expressions of erα and vtg-B. In addition, E2 significantly increased the protein level of Vtg, while Fulvestrant, MPP and Cyclofenil significantly inhibited the protein level of Vtg in a dose-dependent manner. Our results indicate that E2 may regulate the expression of each vtg with different subtypes of ERs, and shows a distinct compensatory expression effect on the regulation for ers and vtgs, which provides a theoretical basis for reproductive endocrinology study in pompano.

Generation of a human induced pluripotent stem cell line (SMUSHi002-A) from an ALS patient carrying a heterozygous mutation c.1562G > A in the FUS gene.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Affected patients experience gradual loss of their spinal cord and cortical motor neurons with consequent muscle weakness and emaciation, and eventual respiratory failure. The pathogenesis of ALS remains largely unknown although the FUS (sarcoma fusion gene) gene is known to be one of the major pathogenic genes. We have generated an induced pluripotent stem cell line SMUSHi002-A from an ALS patient who carries a heterozygous mutation c.1562G > A in FUS. This cell line will serve as a useful model to investigate disease pathogenesis and develop potential therapeutic approaches for ALS.

Overexpression of Glutathione S-Transferases in Human Diseases: Drug Targets and Therapeutic Implications.

Glutathione S-transferases (GSTs) are a major class of phase II metabolic enzymes. Besides their essential role in detoxification, GSTs also exert diverse biological activities in the occurrence and development of various diseases. In the past few decades, much research interest has been paid to exploring the mechanisms of GST overexpression in tumor drug resistance. Correspondingly, many GST inhibitors have been developed and applied, solely or in combination with chemotherapeutic drugs, for the treatment of multi-drug resistant tumors. Moreover, novel roles of GSTs in other diseases, such as pulmonary fibrosis and neurodegenerative diseases, have been recognized in recent years, although the exact regulatory mechanisms remain to be elucidated. This review, firstly summarizes the roles of GSTs and their overexpression in the above-mentioned diseases with emphasis on the modulation of cell signaling pathways and protein functions. Secondly, specific GST inhibitors currently in pre-clinical development and in clinical stages are inventoried. Lastly, applications of GST inhibitors in targeting cell signaling pathways and intracellular biological processes are discussed, and the potential for disease treatment is prospected. Taken together, this review is expected to provide new insights into the interconnection between GST overexpression and human diseases, which may assist future drug discovery targeting GSTs.

Transcriptomic analysis of Amaranthus retroflex resistant to PPO-inhibitory herbicides.

Amaranthus retroflexus L. is one of the malignant weeds which can cause a reduction in the soybean yield. We found a population of A. retroflexus (R-Q) resistant to fomesafen through the initial screening of whole-plant dose response bioassay in the research. The resistance index of the population (R-Q) was 183 times of the sensitive population (S-N). The resistant and sensitive populations were used as experimental materials in the paper. Strand-specific RNA-Seq analyses of R‒Q and S‒N populations obtained from herbicide-treated and mock-treated leaf samples after treatment were conducted to generate a full-length transcriptome database. We analyzed differentially expressed genes (DEGs) among the R-Q and S‒N A. retroflexus populations treated with recommended dose and mock-treated on the 1st (24 h) and 3rd (72 h) days to identify genes involved in fomesafen resistance. All 82,287 unigenes were annotated by Blastx search with E-value < 0.00001 from 7 databases. A total of 94,815 DEGs among the three group comparisons were identified. Two nuclear genes encoding PPO (PPX1 and PPX2) and five unigenes belonging to the AP2-EREBP, GRAS, NAC, bHLH and bZIP families exhibited different expression patterns between individuals of S‒N and R-Q populations. The A. retroflexus transcriptome and specific transcription factor families which can respond to fomesafen in resistant and susceptible genotypes were reported in this paper. The PPX1 and PPX2 genes of the target enzyme were identified. The study establishes the foundation for future research and provides opportunities to manage resistant weeds better.

Transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy for bilateral vocal fold paralysis: A retrospective study.

OBJECTIVES: To investigate the effect of transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy for bilateral vocal fold paralysis (BVFP). DESIGN: A retrospective study with medical records from 2017 to 2021 in our hospital. SETTING: A single-centre study. PARTICIPANTS: This retrospective study included 22 patients with BVFP. They underwent transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy in our hospital from 2017 to 2021. MAIN OUTCOME MEASURES: Preoperative and postoperative swallowing and phonation functions were evaluated in all patients. RESULTS: All 22 patients with a tracheostomy were successfully decannulated within 6 months after surgery without subsequent revision operations, and the width of the posterior glottis was more than 3.9 mm in all patients when they inspired. The statistical analysis showed that there was no difference in vocal function and swallowing function in all patients compared to preoperative (p > .05). CONCLUSION: Transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy enlarges the posterior glottis in patients with BVFP, which maintains airway patency without significant worsening in voice and swallowing function.

CircSETDB1 contributes to paclitaxel resistance of ovarian cancer cells by sponging miR-508-3p and regulating ABCC1 expression.

Ovarian cancer is a gynecological tumor with a poor prognosis. The chemotherapy failure and recurrence induced by paclitaxel (Ptx) resistance are the main reason for the failure of ovarian cancer treatment. In this study, we aimed to explore the role of circular RNA (circRNA) in the regulation of Ptx resistance in ovarian cancer. Quantitative reverse transcription PCR was performed to detect the expression of circRNA SET domain bifurcated histone lysine methyltransferase 1 (circSETDB1), microRNA (miR)-508-3p and ATP-binding cassette subfamily C member 1 ( ABCC1 ) mRNA. The effects of circSETDB1 on Ptx resistance were explored by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and flow cytometry experiments in vitro . The protein level was assessed by western blot. Dual-luciferase reporter and RNA pull-down assays were carried out to confirm the interactions among circSETDB1, miR-508-3p, and ABCC1 . Xenograft tumor experiment was performed to investigate the effect of circSETDB1 on Ptx resistance in vivo . CircSETDB1 was highly expressed in Ptx-resistant ovarian cancer. CircSETDB1 knockdown inhibited cell proliferation viability, half maximal inhibitory concentration value of Ptx, cell cycle progression, and induced cell apoptosis in Ptx-resistant ovarian cancer cells. miR-508-3p was a target of circSETDB1, and inhibition of miR-508-3p overturned the effects of circSETDB1 knockdown on the Ptx resistance of ovarian cancer cells. miR-508-5p could bind to ABCC1 . Overexpression of ABCC1 reversed the effects of circSETDB1 knockdown on the Ptx resistance of ovarian cancer cells. CircSETDB1 knockdown also enhanced Ptx sensitivity in vivo . In conclusion, circSETDB1 regulated Ptx resistance of ovarian cancer by targeting miR-508-3p/ ABCC1 axis.

Glutathione S-Transferases Mediate In Vitro and In Vivo Inactivation of Genipin: Implications for an Underlying Detoxification Mechanism.

Genipin (GP), the reactive metabolite of geniposide (GE), is responsible for GE-induced hepatotoxicity. As a potential detoxification pathway, the inactivation of GP by glutathione S-transferases (GSTs) has not yet been characterized. In this study, the thiol-GSH conjugates of GP, M532-1 and M532-2 were first identified and the catalytic activities of GSTs were investigated both in vitro and in vivo. GSTA1-1 and GSTA4-4 showed high activity in the formation of both thiol-GSH conjugates, whereas GSTA4-4 specifically catalyzed M532-2 formation in vitro. The active GST isoforms protect against alkylation of N-acetylcysteine (NAC), a classic model nucleophile. GST inhibition attenuated M532-1 formation in rat bile, confirming the in vivo catalytic role of GSTs. In conclusion, this study demonstrated the inactivation of GP by GSTs and implied that interindividual variability of GSTs may be a risk factor for susceptibility to GE-induced hepatotoxicity.

The role of the cd99l2 gene on leukocyte interstitial migration in zebrafish.

Leukocytes play an essential role in ontogeny, tissue regeneration, and innate and adaptive immunity. The migration of leukocytes to the infected or traumatized areas is necessary for their immune response function. As an adhesion molecule, CD99L2 is crucial in the extravasation of leukocytes, however, its role in the interstitial migration of leukocytes remains unclear. In this study, the cd99l2 gene was knock-out by TALEN (transcription activator-like effector nuclease) in zebrafish and discovered that the deletion had no effect on zebrafish development. The number of granulocytes and macrophages recruited to the wounded tissue was significantly reduced in the cd99l2 mutants following caudal fin damage. Further research revealed that the expression of mfap4 was drastically decreased in the cd99l2 mutants, which may be one of the reasons that affect the migration of macrophages to the wound site. Moreover,transgenic lines with labeled vasculature, neutrophils and macrophages demonstrated that neutrophils and macrophages migrate throughout the interstitial space to the wound tissue in both wild-type and mutant zebrafish at 60 hours post-fertilization, indicating that the cd99l2 gene is involved in the interstitial migration of leukocytes. Finally, RNA transcription, protein folding, and the P450 pathway were enriched in cd99l2 mutants by RNA-seq analysis. Previous research had demonstrated that the regulation of transcription and signal transduction could be affected by adhesion molecules, which may suggest that the cd99l2 gene is involved in the cascade signaling pathway of leukocyte migration as an adhesion molecule. In conclusion, this study uncovered a novel function of the cd99l2 gene in the process of leukocyte migration in zebrafish, which is expected to provide a theoretical foundation for inflammatory and immune-related diseases.

Functional characterization of a novel violacein biosynthesis operon from Janthinobacterium sp. B9-8.

Violacein is a secondary metabolite mainly produced by Gram-negative bacteria that is formed from tryptophan by five enzymes encoded by a single operon. It is a broad-spectrum antibacterial pigment with various important biological activities such as anti-tumor, antiviral, and antioxidative effects. The newly discovered violacein operon vioABCDE was identified in the genome of the extremophile Janthinobacterium sp. B9-8. The key enzyme-encoding genes were cloned to construct the multigene coexpression plasmids pET-vioAB and pRSF-vioCDE. The violacein biosynthesis pathway was heterologously introduced into engineered Escherichia coli VioABCDE and VioABCDE-SD. The factors affecting violacein production, including temperature, pH, inoculum size, carbon and nitrogen source, precursor, and inducers were investigated. The violacein titer of VioABCDE-SD reached 107 mg/L in a two-stage fermentation process, representing a 454.4% increase over the original strain. The violacein operon from B9-8 provides a new microbial gene source for the analysis of the violacein synthesis mechanism, and the constructed engineering E. coli strains lay a foundation for the efficient and rapid synthesis of other natural products.Key points• The newly discovered violacein operon vioABCDE was identified in the genome of the extremophile Janthinobacterium sp. B9-8.• The violacein synthesis pathway was reconstructed in E. coli using two compatible plasmids.• A two-stage fermentation process was optimized for improved violacein accumulation.

Bioinformatics analysis for identifying micro-RNAs, long noncoding RNAs, transcription factors, and immune genes regulatory networks in diabetic cardiomyopathy using an integrated bioinformatics analysis.

OBJECTIVES: We identified functional genes and studied the underlying molecular mechanisms of diabetic cardiomyopathy (DCM) using bioinformatics tools. METHODS: Original gene expression profiles were obtained from the GSE21610 and GSE112556 data sets. We used GEO2R to screen the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on DEGs. Protein-protein interaction (PPI) networks of DEGs were constructed using STRING and hub genes of signaling pathways were identified using Cytoscape. Aberrant hub gene expression was verified using The Cancer Genome Atlas data set. RESULTS: The DEGs in DCM were mainly enriched in the nuclei and cytoplasm and involved in DCM and chemokine-related signaling pathways. In the PPI network, 32 nodes were chosen as hub nodes and an RNA interaction network was constructed with 517 interactions. The expression of key genes (JPIK3R1, CCR9, XIST, WDFY3.AS2, hsa-miR-144-5p, and hsa-miR-146b-5p) was significantly different between DCM and normal tissues. CONCLUSIONS: The identified hub genes could be associated with DCM pathogenesis and could be used for treating DCM.

Dynamic detection of HER2 of circulating tumor cells in patients with gastric carcinoma and its clinical application.

The aim of the present study was to construct and characterize human epidermal growth factor receptor 2 (HER2) lipid magnetic ball (H­LMB) for separating circulating tumor cells (CTCs) in patients with gastric carcinoma (GC) and to compare the result of separated CTC counts with that of next­generation sequencing (NGS) for single­gene analysis to verify the consistency for evaluating the association between the detection results and the progress of clinical treatment, so as to facilitate early diagnosis and dynamic monitoring of GC. A lipid magnetic ball (LMB), coated with Fe3O4 nanoparticles, was synthesized by microemulsion technique and an anti­HER2 antibody was conjugated to the surface of LMB to form H­LMB, followed by the characterization of the prepared H­LMB. The detection of capture efficiency of LMBs in GC cells was tested by MTT and expression of HER2 mRNA was determined by reverse transcription­quantitative PCR. The positive detection rate of HER2 was verified by HER2­fluorescence in situ hybridization (FISH) test on the separated CTCs from GC. Further verification was performed based on the consistency between the result of separated CTCs and that of single­gene NGS assay of HER2, associated with the determination of clinical consistency. The constructed H­LMB exhibited good stability and specificity. The mutation rate of HER2 by the FISH test was 14% in the blood samples of 50 patients with GC and was 14% by NGS assay. The mutation rate of HER2 was 12% in H­LMB and the positive detection rate was 85.7% compared with the results of the FISH test, indicating consistency with the clinical diagnosis and pathological examination results. In conclusion, the anti­HER2 antibody­modified LMB can separate CTCs with HER2 abnormal expression, which exhibits an application potential in GC diagnosis and treatment and is of great clinical significance for the diagnosis and evaluation of its therapeutic effect on GC.