Chemical interference with DSIF complex formation lowers synthesis of mutant huntingtin gene products and curtails mutant phenotypes.

Earlier work has shown that siRNA-mediated reduction of the SUPT4H or SUPT5H proteins, which interact to form the DSIF complex and facilitate transcript elongation by RNA polymerase II (RNAPII), can decrease expression of mutant gene alleles containing nucleotide repeat expansions differentially. Using luminescence and fluorescence assays, we identified chemical compounds that interfere with the SUPT4H-SUPT5H interaction and then investigated their effects on synthesis of mRNA and protein encoded by mutant alleles containing repeat expansions in the huntingtin gene (HTT), which causes the inherited neurodegenerative disorder, Huntington's Disease (HD). Here we report that such chemical interference can differentially affect expression of HTT mutant alleles, and that a prototypical chemical, 6-azauridine (6-AZA), that targets the SUPT4H-SUPT5H interaction can modify the biological response to mutant HTT gene expression. Selective and dose-dependent effects of 6-AZA on expression of HTT alleles containing nucleotide repeat expansions were seen in multiple types of cells cultured in vitro, and in a Drosophila melanogaster animal model for HD. Lowering of mutant HD protein and mitigation of the Drosophila "rough eye" phenotype associated with degeneration of photoreceptor neurons in vivo were observed. Our findings indicate that chemical interference with DSIF complex formation can decrease biochemical and phenotypic effects of nucleotide repeat expansions.

The effect of 5-α reductase inhibitor on Th1, Th2, and Th17 cell-related inflammatory response in BPH.

OBJECTIVE: To investigate the effect of 5-α reductase inhibitor on the expression of inflammation-related cytokines in Benign prostatic hyperplasia (BPH) specimens after transurethral prostatic resection (TUR-P). METHODS: We prospectively examined the expression of inflammation-related cytokines with immunohistochemistry in the paraffin blocks of 60 patients who underwent TUR-P. 30 cases in the 5-α-reductase inhibitor group were treated with finasteride, 5 mg qd, for more than 6 months; 30 cases in the control group were not treated with medicine before operation. HE staining was used to analyze the difference of inflammation reaction between the two groups, and immunohistochemical staining was used to analyze the effect of 5-α reductase inhibitor on the expression of B-cell lymphoma-2 (Bcl-2), Interleukin-2 (IL-2), Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-17 (IL-17), Interleukin-21 (IL-21) and Interleukin-23 (IL-23) in prostatic tissue. RESULTS: There was no statistical difference in the location, range and degree of inflammation between the two groups (P > 0.05). When IL-17 expression was low, there was statistical difference between the two groups (P < 0.05). Bcl-2 expression was positively correlated with IL-2, IL-4, IL-6 and IFN-γ (P < 0.05). There was no statistical difference in the expression of IL-21, IL-23 and high expression of IL-17 between the two groups (P > 0.05). CONCLUSIONS: 5-α Reductase inhibitor can inhibit the expression of Bcl-2 in prostatic tissue and the inflammatory response related to T-helper cell 1 (Th1) and T-helper cell 2 (Th2) cells. However, it did not affect Th17 cell-related inflammatory response.

Tumor-derived adenosine promotes macrophage proliferation in human hepatocellular carcinoma.

BACKGROUND & AIMS: Macrophages (Mϕ) represent a major component of tumor tissues and play an important role in both tumor progression and therapeutic response. Although tumor Mϕ are generally considered to be derived from circulating monocytes, emerging evidence indicates that tissue Mϕ pools can be maintained by self-renewal. We aimed to elucidate the contribution, phenotype, and regulatory mechanisms of proliferating Mϕ in human hepatocellular carcinoma (HCC). METHODS: Flow cytometry analyses were performed to examine the presence and phenotype of proliferating Mϕ in fresh HCC tissues. Dual immunofluorescence staining was applied to analyze the prognostic value of proliferating Mϕ. The underlying regulatory mechanisms were examined using human monocyte-derived Mϕ. RESULTS: Tumor-infiltrating Mϕ exhibited a significantly higher proliferative capacity than Mϕ in non-tumor tissues. A higher level of Mϕ proliferation was positively correlated with Mϕ density in the tumor and a poor prognosis in patients with HCC. Proliferating Mϕ were less differentiated (with increased CD206 expression) and were induced by the tumor cell-derived soluble small molecule, adenosine, but not proteins, lipids, or large peptides. Mechanistic studies demonstrated that autocrine granulocyte-macrophage colony-stimulating factor (GM-CSF) released by tumor-stimulated Mϕ could enhance A2A receptor expression on Mϕ and function synergistically with adenosine to elicit Mϕ proliferation in HCC. CONCLUSIONS: Local Mϕ proliferation is an important mechanism for Mϕ accumulation in HCC tissues. Tumor-derived adenosine functions synergistically with autocrine GM-CSF released from activated Mϕ, which promotes Mϕ proliferation. Thus, selective modulation of Mϕ accumulation at the source may provide a novel strategy for cancer therapy. LAY SUMMARY: Tumor-associated macrophages (TAMs) have been reported to play an essential role in both tumor progression and therapeutic response. A fundamental understanding of the mechanisms that regulate macrophage accumulation in tumors will undoubtedly lead to the development of strategies to target macrophages with high specificity and efficiency. The current study unveils a novel mechanism by which local proliferation is linked to macrophage accumulation in the tumor milieu, identifying potential targets for future immune-based anticancer therapies.

[Application of pelvic sentinel lymph node tracing technique in radical prostatectomy].

Pelvic lymph node dissection is an important step in radical prostatectomy (RP). Extended pelvic lymph node dissection (ePLND), currently employed for patients with intermediate- or high-risk PCa, may lead to overtreatment, prolong the operation time, and increase the risks of complications. Sentinel lymph node (SLN) is defined as the first metastasis lymph node from the primary tumor. In addition, SLN distribution is essential for overall lymph node dissection. However, due to the complex and diverse lymphatic drainage pathways and the inaccuracy of lymphatic tracing technology, SLN distribution and dissection have always been controversial. This review focuses on the application of pelvic SLN tracing technique in radical prostatectomy.

miR-200c overexpression inhibits the invasion and tumorigenicity of epithelial ovarian cancer cells by suppressing lncRNA HOTAIR in mice.

Epithelial ovarian cancer (EOC) is a common ovarian cancer in gynecological cancers today. It has been found that microRNAs and long-chain noncoding RNA (lncRNA) regulate the gene transcriptional expression in cells. However, it is not well understood that the upstream and downstream regulatory molecules of lncRNA HOX antisense intergenic RNA (HOTAIR). The effects of miR-200c overexpression on the invasion and nude mouse tumorigenicity, as well as lncRNA HOTAIR and snail expression of EOC SKOV3 cells, should be further explored. The expression of miR-200c and lncRNA HOTAIR was detected by reverse transcription PCR (RT-PCR) in EOC SKOV3 cells. The whole miR-200c gene fragment was cloned into a lentiviral plasmid vector. The miR-200c expression in transducted SKOV3 cells with reconstructed miR-200c lentivirus was significantly higher than the negative control (P < .01). The lentivirus-miR-200c-SKOV3 cells show that the invasion ability was significantly decreased compared with the negative control (P < .01). The nude mouse tumorigenicity was significantly decreased compared with that of the control group (P < .01). The snail protein expression in lentivirus-miR-200c-SKOV3 xenograft tumor was significantly decreased compared with the negative control lentivirus-SKOV3 group (P < .05). The miR-200c overexpression significantly decreased the expressions of lncRNA HOTAIR and snail, but increased E-cadherin expression in the lentivirus-miR-200c transducted SKOV3 cells of xenograft tumor, compared with the negative control (P < .05). The miR-200c overexpression in SKOV3 cells with transducted lentivirus-miR-200c can inhibit lncRNA HOTAIR expression, decrease snail, increase E-cadherin and significantly reduce the invasion and tumorigenicity of EOC SKOV3 cells. These results suggest that the miR-200c and lncRNA HOTAIR could be effective therapeutic targets for human epithelial ovarian cancer treatment.

[Effects of Targeting lncRNA HOTAIR on the Invasion and Nude Mouse Tumorigenicity of Epithelial Ovarian Cancer Cells].

OBJECTIVE: To explore the effects of shRNA-mediated downregulating lncRNA HOTAIR on the invasion,nude mouse tumorigenicity and snail expression of epithelial ovarian cancer SKOV3 cells. METHODS: The expression of lncRNA HOTAIR was detected by RT-PCR in SKOV3 cells. The shRNA targeting the lncRNA HOTAIR gene was cloned into RNA interference plasmid. The construction shHOTAIR vector was transfected into ovarian cancer SKOV3 cells by lipofectamine 2000,and the stably transfected cells were isolated by G418 and single clone selection. The downregulating expression of lncRNA HOTAIR was detected by quantitative real time PCR(qRT-PCR). The characteristics of shHOTAIR transfected SKOV3 cells were analyzed from the assays of invasion and nude mouse tumorigenicity,as well as the expression of snail and E-cadherin mRNA detected by qRT-PCR,and snail detected by immunohistochemistry and Western blot methods in xenograft tumor,respectively. RESULTS: The lncRNA HOTAIR expression was proved by RT-PCR in SKOV3 cells. The lncRNA HOTAIR expression in shHOTAIR transfected SKOV3 cells was significantly lower than the scramble control (P<0.01). The shHOTAIR transfected SKOV3 cells show that the invasion ability was significantly decreased compared with the scramble control (P<0.01). The nude mouse tumorigenicity,including tumorigenicity mouse number and tumor volume,was significantly decreased compared with the control group (P<0.01). The snail protein expression detected by IHC and Western blot in shHOTAIR-SKOV3 xenograft tumor was significantly decreased compared with the control scramble- SKOV3 group (P<0.05). The lncRNA HOTAIR low expression resulted in increasing E-cadherin and decreasing snail expression detected by qRT-PCR in the shHOTAIR transfected SKOV3 cells of xenograft tumor,compared with the scramble control (P<0.05). CONCLUSION: Targeting lncRNA HOTAIR expression in SKOV3 cells with RNA interference can decrease snail,increase E-cadherin and significantly reduce the invasion and tumorigenicity of epithelial ovarian cancer SKOV3 cells. These results suggest that the lncRNA HOTAIR could be an effective therapeutic target for human epithelial ovarian caner treatment.

c-Met identifies a population of matrix metalloproteinase 9-producing monocytes in peritumoural stroma of hepatocellular carcinoma.

Macrophages (Mϕ) are prominent components of solid tumours and exhibit distinct phenotypes in different microenvironments. Previously, we found that tumours could alter the normal developmental process of Mϕ to trigger transient activation of monocytes in the peritumoural stroma of human hepatocellular carcinoma (HCC). In the present study, we showed that a fraction of monocytes in the peritumoural stroma, but not in HCC cancer nests, expressed surface c-Met molecules. Monocytes exposed to tumours strongly expressed c-Met proteins with kinetics similar to their activation status, and significant correlations were found between c-Met levels and HLA-DR expression on tumour-infiltrating monocytes. NF-κB-mediated autocrine TNF-α stimulated the expression of c-Met on activated monocytes, and by interacting with its ligand hepatocyte growth factor (HGF), c-Met increased the motility and matrix metalloproteinase (MMP) 9-producing capacity of tumour-associated monocytes. The intensity of c-Met expression on tumour-infiltrating monocytes was associated with high mortality and reduced survival of patients with HCC. Therefore, the expression of c-Met on activated monocytes/Mϕ may represent a novel mechanism by which a tumour actively and precisely regulates the distribution and functions of these cells to facilitate disease progression.

Attenuated Salmonella typhimurium L forms suppress tumor growth and promote apoptosis in murine ovarian tumors.

To study the effects of attenuated Salmonella typhimurium L forms on the in vivo tumorigenicity and apoptosis of murine epithelial ovarian cancer cells, as well as the related mechanisms. Attenuated Salmonella typhimurium VNP20009 was induced into bacterial L forms by using antibiotic ceftriaxone. CCK-8 cell proliferation assay showed that attenuated S. typhimurium L forms can inhibit the proliferation of murine ovarian epithelial cancer ID8 cells. Attenuated ST L forms can induce apoptosis and inhibit invasion ability of epithelial ovarian cancer cells in vitro. TUNEL assay showed that attenuated ST L forms can induce apoptosis of ID8 cells in murine ovarian tumors. Meanwhile, attenuated ST L forms inhibit tumor growth in murine ovarian tumors. The tumorigenicity-related proteins of xenograft tumors detected by immunohistochemistry and fluorescence quantitative RT-PCR assays showed that attenuated ST L forms can reduce the expression of proteins that promote tumor growth and metastasis, such as Lgals9 and MMP9. This study confirmed that attenuated ST L forms can suppress tumor growth and promote apoptosis in murine ovarian tumors. Attenuated ST L forms may serve as a novel biological agent for bacterial-mediated tumor therapy in epithelial ovarian cancer.

The value of preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and red blood cell distribution width in predicting positive surgical margin after laparoscopic radical prostatectomy.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignant tumors in men, and laparoscopic radical prostatectomy (LRP) is commonly used to treat localized and advanced PCa. Positive surgical margin (PSM) is one of the most frequent problems faced by surgeons. AIMS: This study aimed to explore the value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) in predicting PSM after LRP. METHODS AND RESULTS: Three hundred and twenty patients with PCa were admitted and underwent LRP in Beijing Chaoyang Hospital from January 2017 to June 2023. Patients were randomly divided into a training set (225 cases) and a validation set (95 cases) in a 7:3 ratio. NLR, PLR, and RDW were significantly higher in the PSM group than in the negative surgical margins (NSM) group. In addition, the NLR, PLR, and RDW values correlated with clinical T stage, Gleason score, and seminal vesicle invasion in the PSM group. In training set, ROC curve analysis revealed that the optimal cutoff values of NLR, PLR, and RDW for predicting postoperative PSM in PCa were 2.31, 115.40, and 12.85%, respectively. Multivariate Logistic regression analysis showed NLR and RDW were the clinical independent predictors. The area under the curve (AUC, 0.770, 95% CI 0.709-0.831) for postoperative PSM was the highest when a combination of the three parameters was used, with sensitivity and specificity of 62.5% and 85.2%, respectively. In validation set, the AUC values for NLR, PLR, RDW and the three markers combined were 0.708, 0.675, 0.723, and 0.780, respectively. Correlation analysis showed that in the PSM group, NLR was positively correlated with PLR and RDW, and PLR was positively correlated with RDW. By contrast, in the NSM group, a positive association was only found between NLR and PLR. CONCLUSIONS: Higher preoperative NLR, PLR, and RDW values were associated with postoperative PSM. Additionally, the three markers combined may be useful to predict PSM.

Comparison of Cumulative Live Birth Rates between Flexible and Conventional Progestin-Primed Ovarian Stimulation Protocol in Poor Ovarian Response Patients According to POSEIDON Criteria: A Cohort Study.

RESEARCH QUESTION: To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible progestin-primed ovarian stimulation (fPPOS) regimen in poor ovarian response patients, according to POSEIDON criteria. DESIGN: Poor ovarian response women, according to POSEIDON criteria, who underwent the first PPOS protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between January 2018 and December 2020 were included. The fPPOS group involved 113 participants, and the cPPOS group included 1119 participants. In the cPPOS group, medroxyprogesterone acetate (MPA) (10 mg/d) was administrated on the gonadotropin injection the same day as gonadotropin injections in the cPPOS group, while MPA was started either on the day when the leading follicle with mean diameter > 12mm was present and/or serum E2 was >300 pg/mL in the fPPOS protocol group. The primary outcome was CLBR. RESULTS: The fPPOS protocol had higher CLBR per oocyte retrieval cycle compared to the cPPOS group, even without a statistically significant difference (29.6% vs. 24.9%, p = 0.365). The fPPOS group had fewer numbers of retrieved oocytes (2.87 ± 2.03 vs. 3.76 ± 2.32, p < 0.001) but a higher MII oocyte rate (89.8% vs. 84.7%, p = 0.016). In addition, the number of available embryos in the two groups was comparable (1.37 ± 1.24 vs. 1.63 ± 1.38, p = 0.095). There were five women in the fPPOS group, and 86 women in the cPPOS group had a premature LH surge (4.2% vs. 6.8%, p = 0.261). In the fPPOS group, there was one instance of premature ovulation, while in the cPPOS group, there were six occurrences of premature ovulation (0.8 vs. 0.5%, p = 1.000). CONCLUSION(S): The novel fPPOS protocol appears to achieve higher CLBR even without significant differences and with MPA consumption compared with cPPOS protocol in low-prognosis patients.

LncRNA HOTAIR down-expression inhibits the invasion and tumorigenicity of epithelial ovarian cancer cells by suppressing TGF-ß1 and ZEB1.

BACKGROUND: Epithelial ovarian cancer (EOC) is a pathological type with a higher mortality rate among gynecological cancers today. Long-chain noncoding RNAs (lncRNAs) can regulate the transcription and expression of cellular genes. However, the downstream molecules regulated by lncRNA HOTAIR have not been well studied. The effects of downregulated lncRNA HOTAIR on EOC invasiveness and tumorigenicity in nude mice, along with TGF- ß1 and ZEB1 in epithelial ovarian cancer cells, need to be investigated in further research. RESULTS: RT-qPCR was used to detect lncRNA HOTAIR and TGF-ß1 and ZEB1 mRNA expression in EOC SKOV3 cells. The expression of lncRNA HOTAIR in SKOV3 cells transfected with the recombinant shHOTAIR interference plasmid was significantly lower than that of the negative control. Compared with the negative control, the matrix gel invasion ability of shHOTAIR SKOV3 cells in vitro and their tumorigenicity in nude mice were significantly reduced. Moreover, compared with the control, the expression of ZEB1 protein in shHOTAIR-SKOV3 xenograft tumors was significantly reduced. Downregulation of lncRNA HOTAIR expression significantly reduced TGF-ß1 and ZEB1 mRNA expression, but increased the expression of E-cadherin mRNA. In summary, downregulated lncRNA HOTAIR in EOC SKOV3 cells transfected with shHOTAIR can inhibit TGF-ß1, reduce ZEB1, increase E-cadherin, and significantly reduce the invasiveness and tumorigenicity of ovarian epithelial cancer SKOV3 cells. CONCLUSIONS: These results suggest that the lncRNA HOTAIR may be an effective target for the treatment of human EOC.

Impact of growth hormone on IVF/ICSI outcomes and endometrial receptivity of patients undergoing GnRH antagonist protocol with fresh embryo transfer: a pilot study.

Introduction: Gonadotropin-releasing hormone antagonist (GnRH-ant) protocol is widely used in the world for controlled ovarian hyperstimulation (COH). However, previous studies have shown that pregnancy outcomes of fresh embryo transfer with GnRH-ant protocol are not ideal. Current studies have demonstrated the value of growth hormone (GH) in improving the pregnancy outcome of elderly women and patients with diminished ovarian reserve, but no prospective studies have confirmed the efficacy of GH in fresh embryo transfer with GnRH-ant protocol, and its potential mechanism is still unclear. This study intends to evaluate the impact of GH on IVF/ICSI outcomes and endometrial receptivity of patients undergoing GnRH-ant protocol with fresh embryo transfer, and preliminarily explore the possible mechanism. Methods: We designed a randomized controlled trial of 120 infertile patients with normal ovarian response (NOR) who will undergo IVF/ICSI from April 2023 to April 2025, at Department of Reproductive Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The patients will be divided into the depot gonadotropin-releasing hormone agonist (GnRH-a) protocol group, GnRH-ant protocol control group, and GnRH-ant protocol plus GH intervention group at a ratio of 1:1:1 by block randomization design. Patients will be followed on enrollment day, trigger day, embryo transfer day, 7 days after oocytes pick-up, 15 days after embryo transfer, 28 days after embryo transfer, and 12 weeks of gestation. The primary outcome is the ongoing pregnancy rate. Secondary outcomes include the gonadotropin dosage, duration of COH, endometrial thickness and pattern, luteinizing hormone, estradiol, progesterone level on trigger day, numbers of retrieved oocytes, high-quality embryo rate, biochemical pregnancy rate, clinical pregnancy rate, implantation rate, ectopic pregnancy rate, early miscarriage rate, multiple pregnancy rate and incidence of moderate and severe ovarian hyperstimulation syndrome. The endometrium of certain patients will be collected and tested for endometrial receptivity. Ethics and dissemination: The study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology [approval number: TJ-IRB20230236; approval date: February 10, 2023]. The research results will be presented at scientific/medical conferences and published in academic journals. Clinical trial registration: Chinese Clinical Trial Registry; identifier: ChiCTR2300069397.

The Effect of Latent Tuberculosis Infection on Ovarian Reserve and Pregnancy Outcomes among Infertile Women Undergoing Intrauterine Insemination: A Retrospective Cohort Study with Propensity Score Matching.

Latent tuberculosis infection (LTBI) widely exists in patients with unexplained infertility, and whether LTBI would affect the ovarian reserve and pregnancy outcome of infertile women undergoing intrauterine insemination (IUI) is still unknown. A single-center, retrospective, cohort study was designed that included infertile women undergoing IUI at the Department of Reproductive Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, from January 2018 to December 2020. The primary outcomes of this study were ovarian reserve and live birth rate. Secondary outcomes included pregnancy outcomes and maternal and neonatal complications. As a result, 3066 IUI cycles were eventually enrolled in this study. Of these women, 9.6% (295/3066) had LTBI evidence. After propensity score matching (PSM), there was no significant difference in the baseline between the LTBI and non-LTBI groups. The data showed that women who had LTBI had trends toward lower biochemical pregnancy rates (12.9% vs. 17.7%, p-value 0.068), lower clinical pregnancy rates (10.8% vs. 15.1%, p-value 0.082) and lower live birth rates (8.1% vs. 12.1%, p-value 0.076), with no significant differences. There were also no significant differences in ovarian reserve and other secondary outcomes between the two groups. In conclusion, there were no significant differences in ovarian reserve, perinatal or neonatal complications between women with and without LTBI. Women with LTBI tended to have worse pregnancy outcomes after receiving IUI, but the difference was not significant.

Case Report: Analysis of four cases of metastatic bladder masses after radical prostatectomy.

Objective: The aim of this study is to investigate the clinical characteristics and diagnostic and therapeutic methods of bladder metastasis after radical prostatectomy and to improve its diagnosis and treatment. Methods: The clinical data of four patients with bladder metastasis after radical prostatectomy were retrospectively analyzed from January 2011 to December 2021. Three cases suffered from intermittent gross hematuria, and only one case was found to have an elevated prostate-specific antigen (PSA) value. Transurethral resection of bladder tumor was performed in four cases, in which one case also underwent resection of urethral mass. Three cases received endocrine therapy, one of which added intravesical instillation and radiation therapy. Another case received chemotherapy based on comprehensive treatment. Results: According to the pathological and immunohistochemical results, three cases were acinar adenocarcinoma of the prostate with Gleason score of 9, and all cases were PSA positive and negative for cytokeratin 7 (CK7) and GATA binding protein 3 (GATA-3). One case was small cell neuroendocrine carcinoma of the prostate and was positive for chromogranin A (CGA), synaptophysin (SYN), and cluster of differentiation 56 (CD56). During the follow-up period of 4 to 13 months, one case was lost to follow-up and three cases were alive. Conclusion: Bladder metastasis after radical prostatectomy is rare, and pathology combined with immunohistochemistry is the gold standard for its diagnosis. Pathological type determines its treatment. Systemic treatment is essential, and local treatment is the most palliative means. Early diagnosis and treatment is significant for better prognosis.

HDACs alters negatively to the tumor immune microenvironment in gynecologic cancers.

The role of histone deacetylases (HDACs) in the tumor immune microenvironment of gynecologic tumors remains unexplored. We integrated data from The Cancer Genome Atlas and Human Protein Atlas to examine HDAC expression in breast, cervical, ovarian, and endometrial cancers. Elevated HDAC expression correlated with poor prognosis and highly malignant cancer subtypes. Gene Set Enrichment Analysis revealed positive associations between HDAC expression and tumor proliferation signature, while negative associations were found with tumor inflammation signature. Increased HDAC expression was linked to reduced infiltration of natural killer (NK), NKT, and CD8+ T cells, along with negative associations with the expression of PSMB10, NKG7, CCL5, CD27, HLA-DQA1, and HLA-DQB1. In a murine 4T1 breast cancer model, treatment with suberoylanilide hydroxamic acid (SAHA; HDAC inhibitor) and PD-1 antibody significantly inhibited tumor growth and infiltration of CD3+ and CD8+ T cells. Real-time polymerase chain reaction revealed upregulated expressions of Psmb10, Nkg7, Ccl5, Cd8a, Cxcr6, and Cxcl9 genes, while Ctnnb1 and Myc genes were inhibited, indicating tumor suppression and immune microenvironment activation. Our study revealed that HDACs play tumor-promoting and immunosuppressive roles in gynecologic cancers, suggesting HDAC inhibitors as potential therapeutic agents for these cancers.

Cumulative live birth rates and birth outcomes after IVF/ICSI treatment cycles in young POSEIDON patients: A real-world study.

Objective: The aim of this study was to describe the cumulative live birth rates (CLBRs) of young women with or without low prognosis according to the POSEIDON criteria after IVF/ICSI cycles and to investigate whether the diagnosis of low prognosis increases the risk of abnormal birth outcomes. Design: Retrospective study. Setting: A single reproductive medicine center. Population: From January 2016 to October 2020, there were 17,893 patients (<35 years) involved. After screening, 4,105 women were included in POSEIDON group 1, 1,375 women were included in POSEIDON group 3, and 11,876 women were defined as non-POSEIDON. Interventions: Baseline serum AMH level was measured on the D2-D3 of menstrual cycle before IVF/ICSI treatment. Main outcome measures: Cumulative live birth rate (CLBR), birth outcomes. Results: After four stimulation cycles, the CLBRs in POSEIDON group 1, POSEIDON group 3, and non-POSEIDON group reached 67.9% (95% CI, 66.5%-69.3%), 51.9% (95% CI, 49.2%-54.5%), and 79.6% (95% CI, 78.9%-80.3%), respectively. There was no difference in gestational age, preterm delivery, cesarean delivery, and low birth weight infants between the three groups, but macrosomia was significantly higher in non-POSEIDON group, after adjusting for maternal age and BMI. Conclusions: The POSEIDON group shows lower CLBRs than the non-POSEIDON group in young women, while the risk of abnormal birth outcomes in the POSEIDON group will not increase.

Splenic Metastatic Choriocarcinoma with Nontraumatic Splenic Rupture: A Case Report and Literature Review.

Choriocarcinoma is a highly malignant trophoblastic tumor that occurs mostly in women of childbearing age. The main mode of metastasis is hematogenous metastasis. The most common sites of metastasis are the lung, vagina and brain, while splenic metastasis is rare. Because of its rapid development, extensive metastasis can occur in a short period, and some patients only show metastatic symptoms, which are often missed or misdiagnosed as ectopic pregnancy or other diseases. We describe a rare case of splenic metastatic choriocarcinoma with acute abdominal pain caused by nontraumatic splenic rupture. In addition, we review the previous literature on splenic metastasis of choriocarcinoma and summarize the clinical manifestations, management measures and prognoses. Our case and literature review indicate that splenic metastatic choriocarcinoma is rare and difficult to distinguish from splenic ectopic pregnancy and other diseases. Clinicians should strengthen their understanding of this disease and avoid misdiagnosis.

Cold temperature mediated nitrate removal pathways in electrolysis-assisted constructed wetland systems under different influent C/N ratios and anode materials.

Electrolysis had proven to be useful for the enhanced performance in constructed wetlands (CWs). While at cold temperature, the nitrate removal pathways, plant physiological characteristics and microbial community structure in electrolysis-assisted CWs were unclear. Therefore, the purification performance of three electrolysis-assisted horizontal subsurface-flow constructed wetlands (E-HSCWs) with different anodes and a control system in cold seasons were evaluated in this study. E-HSCWs showed a 2.02-83.21% increase of total nitrogen (TN) removal when compared to control, and the gaps were enlarged with increasing C/N (chemical oxygen demand/total nitrogen, COD/TN) ratios. Nitrite accumulation in E-HSCWs presented a first increase then went down trend with increasing C/N ratios, compared to a steady increase in control system. The optimum C/N ratio was 8 in E-HSCWs for both TN and COD removal. Moreover, Ti|IrO2-Ta2O5 (Ti) anode showed the highest potential for TN and COD removal. Less root weight, shorter root length and reduced TN and total phosphorus (TP) contents in roots were observed in wetland plants (Iris sibirica) of E-HSCWs. In E-HSCWs with Fe and C anodes, the nitrate removal was mainly accomplished by autotrophic denitrifier Hydrogenophaga. While in E-HSCWs with Ti anode, the synergistic effect of autotrophic denitrifier Hydrogenophaga and heterotrophic denitrifiers Acidovorax, Simplicispira, Zoogloea accounted for the nitrate removal. These results showed that E-HSCWs at proper C/N ratio of 8 would be promising for nitrate removal at cold temperature.

Vertical-flow constructed wetland based on pyrite intensification: Mixotrophic denitrification performance and mechanism.

Deep nitrogen removal from low-carbon wastewater is a pressing water treatment challenge as of yet. Eight sets of vertical-flow constructed wetland (VFCW) intensified by pyrite were designed and applied to treat with low C/N ratio wastewater in this research. The results showed that the addition of pyrite (100% added) significantly promoted TN removal with an efficiency higher than 27.05% under low C/N ratio conditions, indicating that mixotrophic denitrification was achieved in VFCW. Microbial analysis showed that the community structure and diversity of microorganisms were changed significantly, and the growth of autotrophic (Thiobacillus) and heterotrophic bacteria (Thauera) concomitantly enhanced. It is recommended that the addition amount of pyrite is 75% of the wetland volume, meantime, mixing evenly with 25% high porosity substrate (such as activated carbon, volcanic stone, etc.), which could enhance the effective adhesion of microorganisms and their contact area with pyrite, ultimately improve the denitrification capacity of the VFCW.

Triclosan weakens the nitrification process of activated sludge and increases the risk of the spread of antibiotic resistance genes.

The usage of triclosan (TCS) may rise rapidly due to the COVID-19 pandemic. TCS usually sinks in the activated sludge. However, the effects of TCS in activated sludge remain largely unknown. The changes in nitrogen cycles and the abundances of antibiotic resistance genes (ARGs) caused by TCS were investigated in this study. The addition of 1000 µg/L TCS significantly inhibited nitrification since the ammonia conversion rate and the abundance of nitrification functional genes decreased by 12.14%. The other nitrogen cycle genes involved in nitrogen fixation and denitrification were also suppressed. The microbial community shifted towards tolerance and degradation of phenols. The addition of 100 µg/L TCS remarkably increased the total abundance of ARGs and mobile genetic elements by 33.1%, and notably, the tetracycline and multidrug resistance genes increased by 54.75% and 103.42%, respectively. The co-occurrence network revealed that Flavobacterium might have played a key role in the spread of ARGs. The abundance of this genus increased 92-fold under the addition of 1000 µg/L TCS, indicating that Flavobacterium is potent in the tolerance and degradation of TCS. This work would help to better understand the effects of TCS in activated sludge and provide comprehensive insight into TCS management during the pandemic era.