Aging alters histone H3 lysine 4 methylation in mouse germinal vesicle stage oocytes.

Decreasing oocyte competence with maternal aging is a major factor in mammalian infertility. One of the factors contributing to this infertility is changes to chromatin modifications, such as histone acetylation in old MII stage oocytes. Recent studies indicate that changes in histone acetylation at MII arise at the germinal vesicle (GV) stage. We hypothesised that histone methylation could also change in old GV oocytes. To test this hypothesis, we examined mono-, di- and trimethylation of histone H3 lysine 4 (H3K4 me1, me2 and me3, respectively) in young and older oocytes from 6-8- and 42-44-week-old mice, respectively. We found that H3K4 me2 and me3 decreased in older compared with young GV oocytes (100% vs. 81% and 100% vs. 87%, respectively; P<0.05). H3K4 me2 later increased in older MII oocytes (21% vs. 56%; P<0.05). We also examined the expression of genes encoding the H3K4 demethylases lysine (K)-specific demethylase 1A (Kdm1a) and retinol binding protein 2 (Rbp2). Expression of Kdm1a increased at both the mRNA and protein levels in older GV oocytes, but decreased in older MII oocytes (P<0.05), and was negatively correlated with H3K4 me2 levels. Conversely, expression of Rbp2 mRNA and protein decreased in older GV oocytes (P<0.05), and this was not correlated with H3K4 me3 levels. Finally, we showed that inhibition of Kdm1a of older oocytes at the GV stage restored levels of H3K4 me2 at the MII stage to those seen in 'young' oocytes (41% vs. 38%; P>0.05). These results suggest that changes in expression of H3K4 me2 and Kdm1a in older GV oocytes may represent a molecular mechanism underlying human infertility caused by aging.

Overall clinical course of indeterminate dendritic cell tumor patients without skin lesions: A rare case report.

BACKGROUND: Indeterminate dendritic cell tumor (IDCT) is a rare tumor of immune cells, and IDCT patients without skin lesions are rarely reported. Therefore, the clinical course in this type of patient is unclear, and further research on the underlying pathological mechanisms and appropriate treatments is needed. CASE SUMMARY: This study describes a female IDCT patient with bile duct lesions. The strong mimicry of IDCT lesions confused doctors, and consequently, this patient, who had no skin lesions, was first diagnosed with cholangiocarcinoma. Then, she presented with persistent abdominal distension without jaundice. Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination. However, no tumor cells or pathogens were found in the three subsequent ascites analyses. It took 2 years to reach the correct diagnosis, which was eventually obtained by performing surgery for biopsy of the patient's abdominal lymph nodes. However, by then, she was already in a cachexic state. Finally, she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases. CONCLUSION: For IDCT patients without skin lesions, early biopsy is the key to obtaining a correct diagnosis. Moreover, the collective management of IDCT patients is important. Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.

The association between vascular access satisfaction and all-cause mortality in maintenance hemodialysis patients.

BACKGROUND: The mortality is significantly higher in patients undergoing maintenance hemodialysis (MHD) than in the general population. It is well-known that vascular access (VA) is critical for MHD patients. But the association between VA satisfaction and all-cause mortality in MHD patients is still not clear. The aim of this study was to explore the relationship between VA satisfaction and all-cause mortality in MHD patients with a 30-month follow-up. METHODS: Two hundred twenty-nine MHD patients in two dialysis centers were enrolled in this observational prospective study. VA satisfaction was assessed using the Short Form Vascular Access Questionnaire (VAQ). Health-related quality of life (HRQoL) score was calculated with Short Form 36 (SF-36) questionnaire. Multiple logistic regression analysis was used to evaluate the influencing factors of all-cause mortality. RESULTS: During the 30-month follow-up period, 35 patients dropped out of the study. Among them, 31 patients died, and 4 patients stopped MHD treatment after renal transplantation. Multivariable analyses showed that the age, VAQ total score, social functioning score and dialysis-related complication score of the VAQ, the total score and MCS of the SF-36 were factors influencing all-cause mortality in MHD patients. The Kaplan-Meier curve further showed that the cumulative survival probability was significantly higher in the MHD patients with VAQ scores <7 at baseline than in patients with VAQ scores ⩾7 (p = 0.031). INCLUSION: The present study showed that VA satisfaction was significantly associated with all-cause mortality in MHD patients. These findings suggest that a holistic approach is required for VA choice.

[Brachial-basilic arteriovenous fistula versus arteriovenous graft in vascular access for maintenance hemodialysis patients].

OBJECTIVE: To compared the outcomes of autogenous brachial-basilic arteriovenous fistula (BBAVF) and AV graft (AVG) in patients undergoing long-term hemodialysis. METHODS: Approved by Zhong Da hospital ethics committee, we analyzed 61 complex patients, 30 randomized to receive AVG and 31 received BBAVF. We compared patency rates of BBAVF and AVG in 3 months, 1 year, 2 years, 3 years, and complication rates. RESULTS: Patency rates of BBAVF in 3 months, 1 year, 2 years, 3 years were 100%, 96.8%, 90.3%, 87.1%, 3 years accumulative total infection rate was 3.2%, thrombosis rate was 3.2%. Patency rates of AVG in 3 months, 1 year, 2 years, 3 years were 96.7%, 50.0%, 36.7%, 33.3%, 3 years accumulative total infection rate was 26.7%, thrombosis rate was 33.3%. Patency rates of BBAVF in 1 year, 2 years, 3 years were higher than patency rates of AVG. The complication rates of infection and thrombosis were significantly lower for BBAVF than for AVG (P < 0.05, respectively). CONCLUSIONS: BBAVF has the advantage of a higher patency rate, a lower complication rates of infection and thrombosis, should be served as a favourable choice in building the vascular access in maintenance hemodialysis patients.

The impact of vascular access satisfaction on health-related quality of life in patients receiving maintenance hemodialysis: A 2-year follow-up study.

BACKGROUND: Health-related quality of life (HRQoL) has been demonstrated to predict mortality in patients receiving maintenance hemodialysis (MHD). Vascular access (VA) is critical for MHD patients. The aim of this study was to investigate the change in HRQoL among MHD patients with a 2-year follow-up and to explore the impact of VA satisfaction on HRQoL in this population. METHODS: 229 MHD patients in two dialysis centers were included in this observational prospective study. VA satisfaction was assessed using the Vascular Access Questionnaire (VAQ). The 36 Item Short-Form Health Survey (SF-36) questionnaire was employed to evaluate HRQoL scores. Multiple logistic regression analysis was used to evaluate the influencing factors of HRQoL. RESULTS: A total of 229 MHD patients were enrolled in the study, and 198 individuals (86.46%) completed the 2-year follow-up. HRQoL decreased statistically significantly from baseline to the 2-year follow-up across all dimensions. Multivariable analyses showed that the overall score, social functioning score, dialysis-related complication score of VAQ influenced HRQoL in the study population. Furthermore, HRQoL total scores and scores on the physical component summary (PCS) and mental component summary (MCS) domains were significantly higher in the satisfied VA group than in the dissatisfied group at baseline. After the 2-year follow-up, patients with a higher level of VA satisfaction reported higher HRQoL than patients with lower VA satisfaction. CONCLUSION: Our data suggested that VA satisfaction was significantly associated with HRQoL in MHD patients. These findings imply that surgeons and nephrologists should incorporate patient satisfaction into VA surgical decision-making.

NanoSIMS sulfur isotopic analysis at 100 nm scale by imaging technique.

NanoSIMS has been widely used for in-situ sulfur isotopic analysis (32S and 34S) of micron-sized grains or complex zoning in sulfide in terrestrial and extraterrestrial samples. However, the conventional spot mode analysis is restricted by depth effects at the spatial resolution < 0.5-1 µm. Thus sufficient signal amount cannot be achieved due to limited analytical depths, resulting in low analytical precision (1.5‰). Here we report a new method that simultaneously improves spatial resolution and precision of sulfur isotopic analysis based on the NanoSIMS imaging mode. This method uses a long acquisition time (e.g., 3 h) for each analytical area to obtain sufficient signal amount, rastered with the Cs+ primary beam of ∼100 nm in diameter. Due to the high acquisition time, primary ion beam (FCP) intensity drifting and quasi-simultaneous arrival (QSA) significantly affects the sulfur isotopic measurement of secondary ion images. Therefore, the interpolation correction was used to eliminate the effect of FCP intensity variation, and the coefficients for the QSA correction were determined with sulfide isotopic standards. Then, the sulfur isotopic composition was acquired by the segmentation and calculation of the calibrated isotopic images. The optimal spatial resolution of ∼ 100 nm (Sampling volume of 5 nm × 1.5 µm2) for sulfur isotopic analysis can be implemented with an analytical precision of ∼1‰ (1SD). Our study demonstrates that imaging analysis is superior to spot-mode analysis in irregular analytical areas where relatively high spatial resolution and precision are required and may be widely applied to other isotopic analyses.

Exploration of chemotherapy-free regimen after multi-line chemotherapy-induced renal impairment in recurrent ovarian cancer: Case report and literature review.

Introduction: Platinum-based combination chemotherapy is recommended first choice for relapsed ovarian cancer. However, many of the chemotherapeutic agents are nephrotoxic and can promote kidney dysfunction, which affect the efficacy of cancer treatment and the survival of the patient. There is a need to explore long-term treatments of chemotherapy-free regimen of chronic kidney disease in recurrent ovarian cancer. Case presentation: A 41-year-old female patient was presented with stage IIIC well-differentiated ovarian serous papillary adenocarcinoma in 2009. The patient had recurrence of platinum resistance after secondary cytoreductive surgery, and it was difficult to continue chemotherapy after multiple lines of chemotherapy due to myelosuppression, renal impairment and other factors. The patient accepted Niraparib-based treatment regimen after multi-line chemotherapy-induced stage 4 chronic kidney disease. Niraparib combined with anlotinib achieved median PFS of 11 months, disease re-progression, and the patient was switched to niraparib combined with letrozole from October 2021. No evidence of tumor progression was observed till date and the renal toxicity is acceptable. Conclusions: In patients with relapsed ovarian cancer, treatment becomes increasingly challenging to subsequent therapies because of renal impairment and emerging drug resistance. Niraparib-based treatment regimen may be a good choice for patients with well-differentiated serous adenocarcinoma of the ovary who are intolerant to chemotherapy.

The association between vascular access satisfaction and quality of life and depression in maintained hemodialysis patients.

BACKGROUND: Vascular access (VA) is known to be critical for the survival of patients on maintained hemodialysis (MHD) treatment. However, the association between VA satisfaction and psychiatric state in MHD patients is still not fully elucidated. Thus, the aim of this study is to evaluate the relationship among VA satisfaction, health-related quality of life (HRQOL) and depression in MHD patients with different VA types. METHODS: This cross-sectional study was conducted at two dialysis centers with MHD-dependent patients. The Short Form Vascular Access Questionnaire (VAQ) was administered to estimate the level of MHD patients' satisfaction with their VA. HRQOL was assessed using the Short Form 36 (SF-36) questionnaire. Depression was assessed using the Zung's self-rating depression scale (SDS). RESULTS: Of the total 252 patients, AVF was used by 84.13%, AVG was used by 2.78%, and TCC was used by 13.09%. There was no significant difference in satisfaction and SDS scores by access type in patients with AVF, AVG, and TCC. However, HRQOL was worst in patients with TCC, and highest in the AVF group. Further analysis showed that VAQ scores in the domains of overall and dialysis-related complications exhibited a negative correlation with HRQOL. And SF-36 HRQOL scores, including the total score, PCS and MCS, were all negatively correlated with SDS scores (p < 0.05). The results of multivariable analyses found that VAQ scores in the domains of overall score and physical symptom, and total score of HRQOL influenced the depression. CONCLUSIONS: In the present study, no significant difference in satisfaction scores by access type was found in patients with AVF, AVG, and TCC. The HRQOL score was higher in patients with AVF than in those with AVG or TCC. And the result suggested a negative association between HRQOL and depression. Vascular access satisfaction and HRQOL might be risk factors for the presence of depression in MHD patients.

LncRNA HOTTIP promotes the proliferation and invasion of ovarian cancer cells by activating the MEK/ERK pathway.

Recent studies have revealed that long non­coding RNAs (lncRNAs) serve important roles in carcinogenesis and that this type of gene may be used as biomarkers in cancer. A high level of lncRNA HOXA distal transcript antisense RNA (HOTTIP) is associated with unfavorable prognosis for patients with ovarian cancer (OC), but the mechanism of HOTTIP involved in OC development remains to be elucidated. The present study aimed to investigate the mechanism of HOTTIP in metastasis­associated OC cell behaviors. HOTTIP levels in ovarian cells were quantified by reverse transcription­quantitative PCR, cell proliferation was analyzed by colony formation assay, and apoptosis was assessed by flow cytometry. Cell migratory and invasive abilities were evaluated by wound healing and Transwell assays, respectively. The expression levels of mitogen­activated protein kinase kinase (MEK)/ERK pathway­associated proteins were detected by western blotting. The results demonstrated that knockdown of HOTTIP in OC cells significantly reduced the phosphorylation levels of MEK and ERK, inhibited the proliferation and invasion of OC cells and promoted their apoptosis. Furthermore, the effects of HOTTIP on cell migration and invasion were partly associated with the epithelial­mesenchymal transition (EMT) process. Proliferation, invasion and EMT of OC cells were enhanced following overexpression of HOTTIP; however, these effects were reversed by the MEK/ERK pathway inhibitor U0126. In conclusion, HOTTIP was demonstrated to promote the proliferation, migration and invasion of OC cells by activating the MEK/ERK pathway. Therefore, HOTTIP may serve as a potential therapeutic target for OC.

Dynamic patterns of histone H3 lysine 4 methyltransferases and demethylases during mouse preimplantation development.

Extensive and dynamic chromatin remodeling occurs after fertilization, including DNA methylation and histone modifications. These changes underlie the transition from gametic to embryonic chromatin and are thought to facilitate early embryonic development. Histone H3 lysine 4 methylation (H3K4me) is an important epigenetic mechanism that associates with gene-specific activation and functions in development. However, dynamic regulation of H3K4me during early embryonic development remains unclear. Herein, the authors examined the dynamic changes of H3K4me and its key regulators (Ash1l, Ash2l, Kmt2a, Kmt2b, Kmt2c, Setd1a, Setd7, Kdm1a, Kdm1b, Kdm5a, Kdm5b, Kdm5c, and Kdm5d) in mouse oocytes and preimplantation embryos. An increase in levels of H3K4me2 and me3 was observed at the one- to two-cell stages (P < 0.05), corresponding to the period of embryonic genome activation (EGA). Subsequently, the H3K4me2 level dramatically decreased at the four-cell stage and remained at low level until the blastocyst stage (P < 0.05), whereas the H3K4me3 level transiently decreased in the four-cell embryos but steadily increased to the peak in the blastocysts (P < 0.05). The high level of H3K4me2 during the EGA was coinciding with a peak expression of its methyltransferase, ASH2L, which may stabilize this methylation level during this period. Correspondingly, a concomitant decrease in levels of its demethylases, KDM5B and KDM1A, was observed. H3K4me3 was correlated to the expression of its methyltransferase (KMT2B) and demethylase (KDM5A). Thus, these enzymes may function for the EGA and the first lineage segregation in preimplantation mouse embryos.