Fertility preservation in hematological cancer patients.

Among adolescents and young adults, hematological malignancies are the most common malignancies. Although the survival rate of hematological malignancies in young patients has been dramatically improved, due to the continuous improvement and development of tumor diagnosis and treatment options, cytotoxic therapies can significantly reduce a patient's reproductive capacity and cause irreversible infertility. The most two established solutions are embryo cryopreservation and oocyte cryopreservation which can be considered in single female. Sperm or testicular tissue cryopreservation in adult male are feasible approaches that must be considered before gonadotoxic therapy. A comprehensive consultation with reproductive specialists when once diagnosed is a significantly issue which would help those survivors who want to have children. In this article, we review germ cell toxicity, which happens during the treatment of hematological malignancies, and aims to propose safety, efficacy fertility preservation methods in younger patients with hematological malignancies.

Source-free active domain adaptation for diabetic retinopathy grading based on ultra-wide-field fundus images.

Domain adaptation (DA) is commonly employed in diabetic retinopathy (DR) grading using unannotated fundus images, allowing knowledge transfer from labeled color fundus images. Existing DAs often struggle with domain disparities, hindering DR grading performance compared to clinical diagnosis. A source-free active domain adaptation method (SFADA), which generates features of color fundus images by noise, selects valuable ultra-wide-field (UWF) fundus images through local representation matching, and adapts models using DR lesion prototypes, is proposed to upgrade DR diagnostic accuracy. Importantly, SFADA enhances data security and patient privacy by excluding source domain data. It reduces image resolution and boosts model training speed by modeling DR grade relationships directly. Experiments show SFADA significantly improves DR grading performance, increasing accuracy by 20.90% and quadratic weighted kappa by 18.63% over baseline, reaching 85.36% and 92.38%, respectively. This suggests SFADA's promise for real clinical applications.

Effects of occupational noise exposure on hearing loss: regulatory effect of Mediterranean diet.

OBJECTIVE: To assess regulatory effect of Mediterranean diet for occupational noise exposure and hearing loss. METHODS: This cross-sectional study included 4,757 individuals. Weighted logistic regression model was adopted to explore the association of occupational noise exposure and Mediterranean diet with hearing loss, and regulatory effects of the Mediterranean diet for the relationship of occupational noise exposure and hearing loss. RESULTS: Occupational noise exposure was associated with an increased odds of hearing loss. Under low adherence to the Mediterranean diet, the occupational noise exposure group was related to increased odds of hearing loss. Under high adherence to the Mediterranean diet, no significant difference was observed between occupational noise exposure and hearing loss, and adjusted effect size was reduced accordingly. CONCLUSION: Mediterranean diet may moderate this relationship of occupational noise exposure and hearing loss to some degree.

Effects of environmental enrichment on GLUT expression in the visual cortex of amblyopic rats.

OBJECTIVE: To investigate the potential changes of glucose metabolism and glucose transporter protein (GLUT) in the visual cortex of formally deprived amblyopic rats, as well as the effects of enriched environments on the levels of nerve conduction and glucose metabolism in the visual cortex of amblyopic rats. METHODS: 36 rats were randomly divided into three groups: CON + SE (n = 12), MD + SE (n = 12) and MD + EE (n = 12). The right eyelids of both MD + SE and MD + EE groups were sutured. After successful modelling, the MD + EE group was maintained in an enriched environment, and the other two groups were kept in the same environment. Pattern visual evoked potentials (PVEP) was used to confirm models' effect, glucose metabolism was analyzed by Micro-PET/CT (18F-FDG), and the protein as well as mRNA expression levels of GLUT were detected by Western Blot and quantitative RT-PCR (quantitative Reverse Transcription-Polymerase Chain Reaction) analyses, site of GLUT expression by immunofluorescence (IF). RESULTS: After suture modelling, both the MD + EE and MD + SE groups objective visual nerve conduction function decreased, the glucose metabolism in the visual cortex was markedly lower. After the enriched environment intervention, it recovered in the MD + EE group. The expression levels of GLUT1 and GLUT3 were increased in the MD + EE group in comparison with the MD + SE group. GLUT1 was primarily expressed on astrocytes and endothelial cells, but GLUT3 was mainly expressed on neurons. CONCLUSION: Enrichment of the environment exhibited a therapeutic effect on amblyopia, which could be related to the enhancement of glucose metabolism and GLUT expression in the visual cortex.

The Experience of Cervical Cancer Patients Undergoing Hysterectomy: A Qualitative Study.

INTRODUCTION: Due to different social and cultural backgrounds, cervical cancer patients' experience of the treatment process and quality of life after treatment will be different. This study sought to gain in-depth understanding of the experiences of Chinese cervical cancer patients as regards their quality of life and physical symptoms. METHODOLOGY: Semi-structured interviews were used to collect data. We recruited 15 women with cervical cancer in eastern China for in-depth interviews. All data were entered into the NVivo 12 software program for analysis. RESULTS: Four themes emerged from the data: (a) uncertainty; (b) physical suffering; (c) psychological pressure; and (d) challenges of marriage and family. DISCUSSION: Cervical cancer patients showed concerns about the disease itself and the physical discomfort it causes, as well as changes in social relations. Health professionals need to talk about these issues and develop strategies to address them accordingly.

A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm with Orbital Tumor as the Initial Symptom.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. It is a rare and challenging clinical presentation. For decades, there has been no treatment course for managing BPDCN and its overall prognosis is poor. METHODS AND RESULTS: We report a 27-year-old man who was admitted to the hospital due to an orbital tumor as the first symptom. Progressive enlargement of the orbital tumor was accompanied by multiple purple circular nodules on the body trunk. Pathological confirmation of BPDCN after resection of the orbital mass. Bone marrow smear and flow cytometry on examination indicate AML-M5. Performance of chemotherapy and peripheral blood autologous stem cell transplantation. CONCLUSIONS: The clinical manifestations of blastic plasmacytoid dendritic cell neoplasms are diverse. The diagnosis of BPDCN can be difficult due to overlapping morphologic, immunophenotypic, and clinical features of other hematologic AML. Relapsed and refractory BPDCN remains an elusive therapeutic challenge. The future of new targeted therapeutic drugs is expected.

Relationship between blood cadmium levels and bone mineral density in adults: a cross-sectional study.

Introduction: Osteoporosis, a disease of reduced bone mass and microstructural deterioration leading to fragility fractures, is becoming more prevalent as aging progresses, significantly increasing the socioeconomic burden. In past studies, there has been a growing awareness of the harmful effects of heavy metals on bone, with cadmium being a significant exposure factor. The purpose of this study was to look into the association between adult bone mineral density(BMD) and blood cadmium levels. Methods: Based on information from the 2013-2014, 2017-2018 NHANES, weighted multiple regression, generalized weighted modeling, and smoothed curve fitting were utilized to investigate the association between blood cadmium and femur BMD. Furthermore, subgroup analyses were conducted to investigate any differences in the associations between age, sex, race, chronic kidney disease, and diabetes. Results: In 2,146 participants, blood cadmium levels and total femur [-0.02 (-0.03, -0.01), 0.0027], femoral neck [-0.01 (-0.02, -0.00), 0.0240], femoral trochanter [-0.01 (-0.02, -0.00), 0.0042], and intertrochanteric femoral trochanter [-0.02 (-0.03, -0.00), 0.0101] BMD were negatively correlated. Subgroup analyses showed that this association was more pronounced in women, non-Hispanic white people and other Hispanics, and those with chronic kidney disease and diabetes. Our results pointed to a negative relationship between femoral BMD and blood cadmium. This negative association varied by age, sex, race, diabetes, and chronic kidney disease. In particular, bone mineral density was more significantly negatively affected by blood cadmium levels in groups with diabetes and chronic kidney disease. Conclusion: Our findings demonstrated a significant negative association between blood cadmium levels and bone mineral density in a population of U.S. adults.

The longitudinal relationship between self-compassion and cancer patients' unmet supportive care needs.

OBJECTIVES: Unmet supportive care needs are associated with psychological symptoms such as depression and anxiety. However, so far, few studies have explored the protective psychological factors of unmet needs. Therefore, this study intends to explore the protective effect of self-compassion on unmet needs of Chinese cancer patients and to examine the predictive role of self-compassion on these needs during treatment. METHODS: A longitudinal study was performed at Shaanxi Provincial Cancer Hospital in Xi'an, China. A total of 153 heterogeneous cancer patients were assessed after the first diagnosis (T1), at the beginning (T2) and end (T3) of medical treatment. Hierarchical linear regression analyses were used to examine the research questions. RESULTS: Cross-sectional regression analyses showed that self-compassion at T1 was significantly related to psychological needs at T1. Negative self-compassion at T1 was significantly related to total unmet needs, psychological needs, health system, and information and sexual needs. Longitudinal regression analyses showed that self-compassion at T1 significantly predicted total unmet needs; health system and information (HSI) needs at T2, psychological needs at T3, and negative self-compassion at T1 significantly predicted total unmet needs, HSI needs, physical needs, and patient care needs at T2 when controlling for unmet needs at T1. Positive self-compassion was not a predictor of unmet needs. CONCLUSIONS: Self-compassion can be a protective factor of unmet needs in cancer patients. Future intervention studies should focus on improving the overall level of self-compassion and reducing the level of negative self-compassion in cancer patients to reduce patients' unmet needs.

Multianticoagulant Pseudothrombocytopenia in a Patient with Primary Carcinoma of the Liver with Hypersplenism.

BACKGROUND: Pseudothrombocytopenia (PTCP) is a relatively rare phenomenon in vitro, the mechanism is not completely clear, and there is no unified solution for it. How to identify and solve PTCP accurately is a challenge for laboratory personnel. METHODS: According to the patient's clinical manifestations, thrombocytopenia caused by hypersplenism was excluded. PTCP was confirmed by platelet volume histograms, scattergrams and platelet clumps on the blood smears. Commonly used alternative anticoagulants such as sodium citrate or heparin were used for platelet counting. The corrective effect of the platelet count was not good, so non-anticoagulant blood was collected and tested immediately, and blood smears were used to count platelets manually. RESULTS: The PTCP of the patient could not be solved using sodium citrate and heparin anticoagulation. By collecting non-anticoagulant blood and testing immediately, the platelet count returned to normal (180 x 109/L), which is consistent with the results of manual counting on the patient's blood smears (175 x 109/L). CONCLUSIONS: When PTCP is confirmed, commonly used alternative anticoagulants can be used. If these do not work, non-anticoagulant blood can be collected and tested immediately, and blood smears can be used to count platelets manually.

Acute Myeloid Leukemia Secondary to Treatment with Oxaliplatin Combined with Capecitabine for Colorectal Cancer.

BACKGROUND: Treatment-related acute myeloid leukemia (t-AML) is often secondary to some cytotoxic drugs or occurs after radiotherapy and immunosuppression therapy. As commonly used drugs in colorectal cancer chemotherapy, oxaliplatin and capecitabine have obvious cytotoxicity, which may also be an important factor causing t-AML. METHODS: In this study, we report the development of treatment-related acute myeloid leukemia in a pT4NIMO colorectal cancer patient after an approximate 16-month latency period following treatment with 6 cycles of oxali-platin (190 mg on Day 1) plus capecitabine (1.5 g orally twice daily on Days 1 - 14) in combination with recombinant human granulocyte-colony stimulating factor treatment. The patient developed severe anemia with thrombocytopenia after treatment. After a peripheral blood smear and bone marrow biopsy, the diagnosis of AML-M2a was confirmed. RESULTS: The patient was diagnosed with t-AML approximately 16 months after treatment. Our case illustrates the possibility of some cytotoxic drugs inducing t-AML after colorectal cancer treatment. CONCLUSIONS: We suggest that clinicians conduct long-term epidemiological follow-up and epidemiological investigations on patients treated with oxaliplatin and capecitabine. In addition, clinicians should carefully check the complete blood cell count on routine follow-ups and observe the morphological changes of white blood cells in peripheral blood smears, even for asymptomatic patients who have undergone chemotherapy. In this way, we can observe the possibility of its development into secondary leukemia.

Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) promotes stress granule formation via YBX1 phosphorylation in ovarian cancer.

APE1 is an essential gene involved in DNA damage repair, the redox regulation of transcriptional factors (TFs) and RNA processing. APE1 overexpression is common in cancers and correlates with poor patient survival. Stress granules (SGs) are phase-separated cytoplasmic assemblies that cells form in response to environmental stresses. Precise regulation of SGs is pivotal to cell survival, whereas their dysregulation is increasingly linked to diseases. Whether APE1 engages in modulating SG dynamics is worthy of investigation. In this study, we demonstrate that APE1 colocalizes with SGs and promotes their formation. Through phosphoproteome profiling, we discover that APE1 significantly alters the phosphorylation landscape of ovarian cancer cells, particularly the phosphoprofile of SG proteins. Notably, APE1 promotes the phosphorylation of Y-Box binding protein 1 (YBX1) at S174 and S176, leading to enhanced SG formation and cell survival. Moreover, expression of the phosphomutant YBX1 S174/176E mimicking hyperphosphorylation in APE1-knockdown cells recovered the impaired SG formation. These findings shed light on the functional importance of APE1 in SG regulation and highlight the importance of YBX1 phosphorylation in SG dynamics.

Secondary metabolites and their bioactivities from Paecilomyces gunnii YMF1.00003.

Four new polyketides (1-4) and seven known compounds (5-11) including three polyketides and four sterols were isolated from the fermented extracts of Paecilomyces gunnii YMF1.00003. The new chemical structures were determined through the analysis of the nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry, and their configurations were subsequently confirmed by nuclear overhauser effect spectroscopy, the calculated electronic circular dichroism (ECD) spectra, and quantum chemical calculations of the NMR data (qcc NMR). Based on the results of pre-activity screening and compound structure target prediction, certain metabolites were assayed to evaluate their cytotoxic and protein kinase Cα inhibitory activities. Results indicated that 3ß-hydroxy-7α-methoxy-5α,6α-epoxy-8(14),22E-dien-ergosta (8) exhibited potent cytotoxic activity, with half-maximal inhibitory concentration values of 3.00 ± 0.27 to 15.69 ± 0.61 µM against five tumor cells, respectively. The new compound gunniiol A (1) showed weak cytotoxic activity at a concentration of 40 µM. At a concentration of 20 µg/mL, compounds 1, 6, and 7 exhibited protein kinase Cα inhibition by 43.63, 40.93, and 57.66%, respectively. This study is the first to report steroids demonstrating good cytotoxicity and polyketides exhibiting inhibitory activity against protein kinase Cα from the extracts of P. gunnii.

LATS2 degradation promoted fibrosis damage and rescued by vitamin K3 in lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). The limited treatment options for LN increase the economic burdens on patients. Because fibrotic progression leads to irreversible renal damage in LN patients and further progresses to chronic kidney disease (CKD) and the end stage of renal disease (ESRD), developing new targets to prevent LN fibrotic progression could lead to a feasible treatment strategy for LN patients. METHODS: In this study, we examined YAP activation and LATS2 downregulation in LN kidney biopsy samples (LN: n = 8, normal: n = 2) and lupus-prone MRL/lpr mice (n = 8 for each disease stage). The function of LATS2 was further investigated by in situ injection of Ad-LATS2 into mice with LN (n = 6 mice per group). We examined the role of SIAH2-LATS2 regulation by IP-MS and co-IP, and the protective effect of the SIAH2 inhibitor was investigated in mice with LN. RESULTS: Restoring LATS2 by an adenovirus in vivo alleviated renal fibrotic damage in mice with LN. Moreover, we found that LATS2 was degraded by a K48 ubiquitination-proteasome pathway mediated by SIAH2 and promoted YAP activation to worsen fibrosis progression in LN. The H150 region of the substrate binding domain (SBD) is an important site for SIAH2-LATS2 binding. The SIAH2-specific inhibitor vitamin K3 protected against LN-associated fibrotic damage in vivo. CONCLUSION: In summary, we identified the SIAH2-LATS2 axis as an attractive intervention target in LN to alter the resistance to fibrosis.

A case of POEMS syndrome comprising of a complicated diagnostic procedure: Case report.

RATIONALE: This article presents the case of a patient with recurrent chronic diarrhea and cachexia who was misdiagnosed, followed by a literature review to summarize the reasons for misdiagnosis of POEMS syndrome and the treatment strategies. PATIENT CONCERNS: The diagnosis and treatment of this patient suggest that with the improvement of M-protein detection levels, the diagnosis of patients with low M-protein levels, such as those with POEMS syndrome, has been greatly aided. DIAGNOSES: POEMS syndrome requires polyneuropathy and monoclonal plasma cell proliferation as mandatory diagnostic criteria. Therefore, patients presenting with polyneuropathy should routinely undergo M-protein testing and consider the possibility of POEMS syndrome. INTERVENTIONS: The patient, in this case, was treated primarily with relatively conservative immunomodulatory agents. OUTCOMES: During follow-up after treatment, the patient's diarrhea and malnutrition showed significant improvement. LESSONS SUBSECTIONS: POEMS syndrome has low clinical specificity and a high rate of misdiagnosis. However, once a definitive diagnosis is made, the treatment outcome is favorable.

Synthesis and Characterization of a [1,2,6]Diazaphosphonine Oxide: An Example of a Photoswitchable Phosphorus-Containing Cyclic Azobenzene.

We report herein the synthesis and characterization of a phosphorus-containing cyclic azobenzene as a new photoswitchable scaffold. This backbone reveals high bidirectional photoswitching yields and high thermal stability for both isomers, with t1/2 > 90 days at 60 °C. Both E- and Z-isomers have been characterized by UV-vis spectroscopy and X-ray crystallography.

Predictors of amputation in patients with diabetic foot ulcers: a multi-centre retrospective cohort study.

PURPOSE: Investigating risk factors for amputation in patients with diabetic foot ulcer (DFU) and developing a nomogram prediction model. METHODS: We gathered case data of DFU patients from five medical institutions in Anhui Province, China. Following eligibility criteria, a retrospective case-control study was performed on data from 526 patients. RESULTS: Among the 526 patients (mean age: 63.32 ± 12.14), 179 were female, and 347 were male; 264 underwent amputation. Univariate analysis identified several predictors for amputation, including Blood type-B, Ambulation, history of amputation (Hx. Of amputation), Bacterial culture-positive, Wagner grade, peripheral arterial disease (PAD), and laboratory parameters (HbA1c, Hb, CRP, ALB, FIB, PLT, Protein). In the multivariate regression, six variables emerged as independent predictors: Blood type-B (OR = 2.332, 95%CI [1.488-3.657], p < 0.001), Hx. Of amputation (2.298 [1.348-3.917], p = 0.002), Bacterial culture-positive (2.490 [1.618-3.830], p <0.001), Wagner 3 (1.787 [1.049-3.046], p = 0.033), Wagner 4-5 (4.272 [2.444-7.468], p <0.001), PAD (1.554 [1.030-2.345], p = 0.036). We developed a nomogram prediction model utilizing the aforementioned independent risk factors. The model demonstrated a favorable predictive ability for amputation risk, as evidenced by its area under the receiver operating characteristics (ROC) curve of 0.756 and the well-fitted corrected nomogram calibration curve. CONCLUSION: Our findings underscore Blood type-B, Hx. Of amputation, Bacterial culture-positive, Wagner 3-5, and PAD as independent risk factors for amputation in DFU patients. The resultant nomogram exhibits substantial accuracy in predicting amputation occurrence. Timely identification of these risk factors can reduce DFU-related amputation rates.

Protocol for induction of human kidney cell fibrosis.

Here, we present a protocol for inducing fibrosis in human kidney-2 (HK2) cells followed by quantitative real-time PCR analysis of fibrosis-related genes. We describe steps for growing and expanding cells, inducing HK2 fibrosis, and collecting cells for downstream applications. Given the limited cell quantity in culture flasks and the challenges of cell collection, we utilized 10-cm Petri dishes for cell harvesting, with each experimental group comprising five replicate samples. For complete details on the use and execution of this protocol, please refer to Zhang et al.1.

A dual-signal amplification strategy based on rolling circle amplification and APE1-assisted amplification for highly sensitive and specific miRNA analysis for early diagnosis of alzheimer's disease.

MicroRNA (miRNA) is involved in the progression of Alzheimer's disease (AD) and emerges as a promising AD biomarker and therapeutic target. Therefore, there is an urgent need to develop convenient and precise miRNA detection methods for AD diagnosis. Herein, a dual-signal amplification strategy based on rolling circle amplification and APE1-assisted amplification for miRNA analysis for early diagnosis of AD was proposed. The strategy consisted of dumbbell-shaped probe (DP) as amplification template and a reporter probe (RP) with an AP site modification. In the presence of the target miRNA, the miRNAs bound to the toehold domain of DP and DP was activated into a circular template. Then, RCA reaction was triggered, producing a large number of long-stranded products containing repeated sequences. After RCA, APE1 enzyme recognized and removed AP site in the complex of RCA/RP products. By coupling RCA with APE1-assisted amplification, this method has high sensitivity with the limit of detection (LOD) of 1.82 fM. Moreover, by using DP as template for RCA reaction, high specificity can be achieved. By detecting miR-206 in serum using this method, the expression of miR-206 can be accurately distinguished between AD patients and healthy individuals, indicating that this method has broad application prospects in clinical diagnosis.

Bisphenol S, bisphenol F, bisphenol a exposure and body composition in US adults.

Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used to replace bisphenol A (BPA), an endocrine-disrupting chemical with putative obesogenic properties; whether and how BPS and BPF affect adiposity in humans remains to be determined. Therefore, we examined the association of BPA, BPS， and BPF with body composition among US adults. We included 1787 participants aged 20-59 years old in the National Health and Nutrition Examination Survey 2013-2016 who had information on urinary BPA, BPS, and BPF concentrations, and body composition measured using dual-energy x-ray absorptiometry. After full adjustment for potential confounders in linear regression models, BPA was significantly associated with the % body fat of the whole body, arm, and leg, with the ß (95% CI) for the highest quartile vs. the lowest quartile of 1.34 (95%CI [0.11, 2.58], P = 0.03), 1.60 (95%CI [0.20, 3.00], P = 0.03), and 1.63 (95%CI [0.24, 3.02], P = 0.02), respectively. No association between BPA and lean mass was found. For BPS, significant associations were found for % body fat of the whole body (ß [95% CI] = 1.42 [0.49, 2.36], P = 0.004), trunk (ß[95% CI] = 1.92 [0.86, 2.97], P = 0.001), and arm (ß [95% CI] = 1.60 [0.49, 2.70], P = 0.01), as well as lean mass of the whole body (ß [95% CI] = 2610.6 [1324.3, 3896.8], P < 0.001), trunk (ß [95% CI] = 1467.0 [745.3, 2188.7], P < 0.001), arm (ß [95% CI] = 113.4 [10.3, 216.5], P = 0.03), and leg (ß [95% CI] = 431.5 [219.6, 643.4], P < 0.001), comparing the third quartile vs. the lowest quartile. No significant association was observed between BPF and % body fat and lean mass. Results suggest that higher BPA levels were significantly associated with greater % body fat of the whole body and limbs, and there was suggestive evidence that BPS levels were associated with both % body fat and lean mass of the whole body and body parts in a nonmonotonic relationship.

Exosomes Derived from Adipose Stem Cells Enhance Angiogenesis in Diabetic Wound Via miR-146a-5p/JAZF1 Axis.

Chronic trauma in diabetes is a leading cause of disability and mortality. Exosomes show promise in tissue regeneration. This study investigates the role of exosomes derived from adipose stem cells (ADSC-Exos) in angiogenesis. MiRNA-seq analysis revealed significant changes in 47 genes in human umbilical vein endothelial cells (HUVECs) treated with ADSC-Exos, with miR-146a-5p highly expressed. MiR-146a-5p mimics enhanced the pro-angiogenic effects of ADSC-Exos, while inhibitors had the opposite effect. JAZF1 was identified as a direct downstream target of miR-146a-5p through bioinformatics, qRT-PCR, and dual luciferase assay. Overexpress of JAZF1 resulted in decreased proliferation, migration, and angiogenic capacity of HUVECs, and reduced VEGFA expression. This study proposes that ADSC-Exos regulate angiogenesis partly via the miR-146a-5p/JAZF1 axis.