Effect of Post-transplant Dietary Restriction on Hematopoietic Reconstitution and Maintenance of Reconstitution Capacity of Hematopoietic Stem Cells.

Hematopoietic cell transplantation (HCT) is an important therapy for many hematological malignancies as well as some non-malignant diseases. Post-transplant hematopoiesis is affected by multiple factors, and the mechanisms of delayed post-transplant hematopoiesis remain poorly understood. Patients undergoing HCT often suffer from significantly reduced food intake due to complications induced by preconditioning treatments. Here, we used a dietary restriction (DR) mouse model to study the effect of post-transplant dietary reduction on hematopoiesis and hematopoietic stem cells (HSCs). We found that post-transplant DR significantly inhibited both lymphopoiesis and myelopoiesis in the primary recipient mice. However, when bone marrow cells (BMCs) from the primary recipient mice were serially transplanted into secondary and tertiary recipient mice, the HSCs derived from the primary recipient mice, which were exposed to post-transplant DR, exhibited a much higher reconstitution capacity. Transplantation experiments with purified HSCs showed that post-transplant DR greatly inhibited hematopoietic stem cell (HSC) expansion. Additionally, post-transplant DR reshaped the gut microbiotas of the recipient mice, which inhibited inflammatory responses and thus may have contributed to maintaining HSC function. Our findings may have important implications for clinical work because reduced food intake and problems with digestion and absorption are common in patients undergoing HCT.

Dietary restriction rescues 5-fluorouracil-induced lethal intestinal toxicity in old mice by blocking translocation of opportunistic pathogens.

Chemotherapy remains a major treatment for malignant tumors, yet the application of standard dose intensity chemotherapy is limited due to the side effects of cytotoxic drugs, especially in old populations. The underlying mechanisms of cytotoxicity and strategies to increase the safety and tolerance of chemotherapy remain to be explored. Using 5-fluorouracil (5-FU), a cornerstone chemotherapeutic drug, we demonstrate that the main cause of death in ad libitum (AL) fed mice after 5-FU chemotherapy was infection caused by translocation of intestinal opportunistic pathogens. We show that these opportunistic pathogens greatly increase in the intestine after chemotherapy, which was closely related to loss of intestinal lysozyme. Of note, two weeks of dietary restriction (DR) prior to chemotherapy significantly protected the loss of lysozyme and increased the content of the beneficial Lactobacillus genera, resulting in a substantial inhibition of intestinal opportunistic pathogens and their translocation. The rescue effect of DR could be mimicked by Lysozyme or Lactobacillus gavage. Our study provides the first evidence that DR achieved a comprehensive protection of the intestinal physical, biological and chemical barriers, which significantly improved the overall survival of 5-FU-treated mice. Importantly, the above findings were more prominent in old mice. Furthermore, we show that patients over 65 years old have enriched opportunistic pathogens in their gut microbiota, especially after 5-FU based chemotherapy. Our study reveals important mechanisms for the poor chemotherapy tolerance of the elderly population, which can be significantly improved by short-term DR. This study generates new insights into methods for improving the chemotherapeutic prognosis by increasing the chemotherapy tolerance and safety of patients with malignant tumors.

Energy Absorption Characteristics of Composite Material with Fiber-Foam Metal Sandwich Structure Subjected to Gas Explosion.

Based on the previous research on the energy absorption of foam metal materials with different structures, a composite blast-resistant energy-absorbing material with a flexible core layer was designed. The material is composed of three different fiber materials (carbon fiber, aramid fiber, and glass fiber) as the core layer and foamed iron-nickel metal as the front and rear panels. The energy absorption characteristics were tested using a self-built gas explosion tube network experimental platform, and the energy absorption effects of different combinations of blast-resistant materials were analyzed. The purpose of this paper is to evaluate the performance of blast-resistant materials designed with flexible fiber core layers. The experimental results show that the composite structure blast-resistant material with a flexible core layer has higher energy absorption performance. The work performed in this paper shows that the use of flexible core layer materials has great research potential and engineering research value for improving energy absorption performance, reducing the mass of blast-resistant materials, and reducing production costs. It also provides thoughts for the research of biomimetic energy-absorbing materials.

Advancing musculoskeletal tumor diagnosis: Automated segmentation and predictive classification using deep learning and radiomics.

OBJECTIVES: Musculoskeletal (MSK) tumors, given their high mortality rate and heterogeneity, necessitate precise examination and diagnosis to guide clinical treatment effectively. Magnetic resonance imaging (MRI) is pivotal in detecting MSK tumors, as it offers exceptional image contrast between bone and soft tissue. This study aims to enhance the speed of detection and the diagnostic accuracy of MSK tumors through automated segmentation and grading utilizing MRI. MATERIALS AND METHODS: The research included 170 patients (mean age, 58 years ±12 (standard deviation), 84 men) with MSK lesions, who underwent MRI scans from April 2021 to May 2023. We proposed a deep learning (DL) segmentation model MSAPN based on multi-scale attention and pixel-level reconstruction, and compared it with existing algorithms. Using MSAPN-segmented lesions to extract their radiomic features for the benign and malignant classification of tumors. RESULTS: Compared to the most advanced segmentation algorithms, MSAPN demonstrates better performance. The Dice similarity coefficients (DSC) are 0.871 and 0.815 in the testing set and independent validation set, respectively. The radiomics model for classifying benign and malignant lesions achieves an accuracy of 0.890. Moreover, there is no statistically significant difference between the radiomics model based on manual segmentation and MSAPN segmentation. CONCLUSION: This research contributes to the advancement of MSK tumor diagnosis through automated segmentation and predictive classification. The integration of DL algorithms and radiomics shows promising results, and the visualization analysis of feature maps enhances clinical interpretability.

Recent advances and clinical translation of liposomal delivery systems in cancer therapy.

The limitations of conventional cancer treatment are driving the emergence and development of nanomedicines. Research in liposomal nanomedicine for cancer therapy is rapidly increasing, opening up new horizons for cancer treatment. Liposomal nanomedicine, which focuses on targeted drug delivery to improve the therapeutic effect of cancer while reducing damage to normal tissues and cells, has great potential in the field of cancer therapy. This review aims to clarify the advantages of liposomal delivery systems in cancer therapy. We describe the recent understanding of spatiotemporal fate of liposomes in the organism after different routes of drug administration. Meanwhile, various types of liposome-based drug delivery systems that exert their respective advantages in cancer therapy while reducing side effects were discussed. Moreover, the combination of liposomal agents with other therapies (such as photodynamic therapy and photothermal therapy) has demonstrated enhanced tumor-targeting efficiency and therapeutic efficacy. Finally, the opportunities and challenges faced by the field of liposome nanoformulations for entering the clinical treatment of cancer are highlighted.

Nano-Brush Structure for Rapid Label-Free Differentiation of Alzheimer's Disease Stages and Direct Capture of Neuron-Derived Exosomes from Human Blood Plasma.

The measurement of the neurofilament light chain (NFL) in human blood plasma/serum is a promising liquid biopsy for Alzheimer's disease (AD) diagnosis, offering advantages over conventional neuroimaging techniques recommended in clinical guidelines. Here, a controllable nano-brush structure comprising upstanding silicon nanowires coated with indium tin oxide was employed as the sensing substrate. This nano-brush structure was modified with an NFL antibody (NFLAb) via silane coupling and then further connected as the extended gate in a field-effect transistor (EGFET). Notable signal differences emerged within a 2 min timeframe, enabling the label-free differentiation in human blood plasmas among four distinct cohorts: healthy controls, subjective cognitive decline, mild cognitive impairment, and dementia due to AD. Our study indicates that achieving a surface roughness exceeding 400 nm on the modified nano-brush structure enables the effective electrical sensing in our EGFETs. These distinct electrical responses measured via the NFLAb-modified nano-brush EGFETs can be attributed to the combined effects of the captured NFLs and NFL-specific neuron-derived exosomes (NDEs) found in dementia patients, as confirmed by electron spectroscopy for chemical analysis, atomic force microscopy, and scanning electron microscopy. Finally, the potential of quantitatively detecting NDEs on the NFLAb-modified nano-brush structure was demonstrated using spiked solutions containing NFL-specific NDEs from IMR-32 neuroblast cells, wherein concentration-dependent changes were observed in the EGFETs output signal. Our findings show that the NFLAb-modified nano-brush EGFET enables rapid, label-free differentiation between healthy individuals and patients at varying stages of AD.

Impacts of androgen deprivation therapy on the risks and outcomes of SARS-CoV-2 infection in patients with prostate cancer.

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.

Correlation Analysis between Tibial Tuberosity-Trochlear Groove Distance and Other Patellar Stability Parameters in Young and Middle-aged Populations.

OBJECTIVE: The exact mechanism of patellofemoral instability has not been clearly clarified. The current study aims to explore the correlation between the tibial tuberosity-trochlear groove (TT-TG) distance and other patellar stability parameters. METHODS: A total of 60 individuals aged 18 to 40 years who underwent knee computed tomography (CT) examination between September 2014 and December 2017 were retrospectively recruited. Five reference sites were selected on the femoral trochlear articular surface in every CT image. The TT-TG distance and the trochlear groove angles (TGA) at the five reference sites were measured. The patellar ligament length (PLL), patellar length (PL), medial patellar retinaculum length (MPRL) and lateral patellar retinaculum length (LPRL) were quantitatively analyzed. The TT-TG distances on different knee sides or in different sexes were compared. The relationships between the TT-TG distance and TGA, PLL/PL, MPRL, and LPRL were analyzed by Spearman's method. Comparison analysis among patellar stability parameters was analyzed using ANOVA or two-tailed Student's t test. RESULTS: Variance analysis revealed no significant differences in the TT-TG distances among the five positions of the femoral trochlea (F = 0.67, P = 0.62) but significant differences among the five femoral TGAs at the five reference sites (F = 380.37, P < 0.01). Notably, an increasing tendency of the TT-TG distance was observed in the sexes (male, range 16.61-19.68 mm; female, range 14.37-17.38 mm) and knee sides (left knee, range 14.37-18.43 mm; right knee, range 15.80-19.68 mm). The TGA at site 1 of the femoral trochlear cartilage was the largest, with an angle of 151.97° ± 10.4°, and then gradually decreased to the smallest when the cartilage disappeared at site 5, with an angle of 92.05° ± 10.01°. Interestingly, there was a positive relationship between the TT-TG distance at site 1 and TGA in the right knees of males (r = 0.490, P = 0.033) as well as LPRL in the left knees of males (r = -0.420; P = 0.046). There were no correlations between the TT-TG distance and the other patellar stability parameters, including TGA, PLL/PL, MPRL, and LPRL. CONCLUSION: Among young and middle-aged populations, patella surgeries should be carefully determined based on the comprehensive consideration of these patellar stability parameters rather than the TT-TG distance alone. Differences in sex and knee side should also be considered.

Highly Efficient Electrochemiluminescence of MnS:CdS@ZnS Core-Shell Quantum Dots for Ultrasensitive Detection of MicroRNA.

In this work, a novel electrochemiluminescence (ECL) biosensor was developed for ultrasensitive detection of microRNA let-7a (miRNA let-7a) based on MnS:CdS@ZnS core-shell quantum dots (QDs) as ECL luminophores with high ECL efficiency. Impressively, compared to the CdS:Mn@ZnS QDs prepared by ionic doping with ECL efficiency of 0.87%, MnS:CdS@ZnS QDs synthesized by bimetallic clusters (Cd2Mn2O4) doping exhibited high ECL efficiency of up to 15.84% with S2O82- as cathodic coreactant due to the elimination of the dopants size mismatch and "self-purification" effect, which could achieve the surface defect passivation of MnS:CdS@ZnS QDs for effectively improving the ECL emission. Furthermore, with the help of strand displacement amplification (SDA), the trace target miRNA let-7a was able to be converted to a number of output DNA labeled with ferrocene (Fc) to construct an ultrasensitive ECL biosensor. The well-designed ECL biosensor for miRNA let-7a exhibited high stability and excellent sensitivity of a concentration variation from 10 aM to 1 nM and a low detection limit of 4.1 aM, which was further applied to the analysis of miRNA let-7a from cancer cell (MCF-7) lysate. Thus, this strategy provides a novel method to prepare high-efficient ECL emitters for the construction of ECL biosensing platforms in biological fields and clinical diagnosis.

The High Expression of Minichromosome Maintenance Complex Component 5 Is an Adverse Prognostic Factor in Lung Adenocarcinoma.

Background: Minichromosome maintenance (MCM) genes are crucial for genomic DNA replication and are important biomarkers in tumor biology. In this study, we aimed to identify the diagnostic, therapeutic, and prognostic value of the MCM2-10 genes in patients with lung cancer. Methods: We examined the expression levels, gene networks, and protein networks of lung cancer using data from the ONCOMINE, GeneMANIA, and STRING databases. We conducted a functional enrichment analysis of MCM2-10 using the clusterProfiler package using TCGA data. The correlation between the MCM2-10 expression and lung cancer prognosis was evaluated using Cox regression analysis. The influence of clinical variables on overall survival (OS) was evaluated using univariate and multivariate analyses. The TIMER database was used to evaluate the correlation between tumor infiltrating levels and lung cancer. Kaplan-Meier Plotter pan-cancer RNA sequencing was used to estimate the correlation between the MCM5 expression and OS in different immune cell subgroups in patients with lung adenocarcinoma (LUAD). Finally, the 1-, 3-, and 5-year predictions of LUAD were performed using nomogram and calibration analysis. Results: The expression of MCM2, 3, 4, 5, 6, 7, 8, and 10 in lung cancer was higher than that for normal samples. The MCM5 expression was associated with poor OS in patients with LUAD, and prognosis was related to TNM stage, smoking status, and pathological stage. The MCM5 expression is correlated with immune invasion in LUAD and may affect prognosis due to immune infiltration. Conclusion: MCM5 may serve as a molecular biomarker for LUAD prognosis.

Exosomes as smart drug delivery vehicles for cancer immunotherapy.

Exosomes (Exos) as drug delivery vehicles have been widely used for cancer immunotherapy owing to their good biocompatibility, low toxicity, and low immunogenicity. Some Exos-based cancer immunotherapy strategies such as tuning of immunosuppressive tumor microenvironment, immune checkpoint blockades, and cancer vaccines have also been investigated in recent years, which all showed excellent therapeutic effects for malignant tumor. Furthermore, some Exos-based drug delivery systems (DDSs) for cancer immunotherapy have also undergone clinic trails, indicating that Exos are a promising drug delivery carrier. In this review, in order to promote the development of Exos-based DDSs in cancer immunotherapy, the biogenesis and composition of Exos, and Exos as drug delivery vehicles for cancer immunotherapy are summarized. Meanwhile, their clinical translation and challenges are also discussed. We hope this review will provide a good guidance for Exos as drug delivery vehicles for cancer immunotherapy.

Clinical value of MRI in evaluating and diagnosing of humeral lateral condyle fracture in children.

BACKGROUND: Humeral lateral condyle fractures (HLCFs) are common paediatric fractures. Radiographs are hard to accurately evaluate and diagnose the damage of articular epiphyseal cartilage in HLCFs. METHODS: 60 children who should be suspected to be HLCFs in clinical practice from Dec 2015 to Nov 2017 were continuously included as the first part patients. Subsequently, 35 HLCFs patients with complete follow-up information who had no obvious displacement on radiograph were the second part patients. The sensitivity and specificity of radiograph and MRI in diagnosing of HLCFs and their stability were calculated respectively. Calculated the sensitivity and specificity of each scan sequence of MRI in diagnosing of HLCFs osteochondral fractures. The degree of fracture displacement was measured respectively. Compared the ratio of surgical treatment, secondary fracture displacement and complications between the stable fracture group and the unstable fracture group on MRI in part 2 patients. RESULTS: Sensitivity of diagnosing HLCFs by MRI was significantly higher than radiograph (100.00% vs. 89.09%, P = 0.03). Sensitivity of diagnosing integrity of trochlear cartilage chain by MRI was 96.30%, which was significantly higher than that by radiograph (62.96%, P < 0.01). The sensitivity of cartilage sensitive sequence (3D-FS-FSPGR/3D-FSPGR) was different with FS-PDWI and FS-T2WI (P = 0.01 and P = 0.02, respectively). The degree of HLCFs displacement by MRI was higher than radiograph (P < 0.05). In the unstable fracture group, 5 cases (45.45%) had a fracture displacement of more than 2 mm on MRI, which was significantly higher than that in stable fracture group (0.00%, P < 0.01). CONCLUSIONS: MRI is superior to the radiograph of elbow joint in evaluating and diagnosing children HLCFs and their stability. The coronal 3D-FS-FSPGR/3D-FSPGR sequence is a significant sequence for diagnosing osteochondral fractures in HLCFs. MRI can provide important clinical value for treatment decisions of HLCFs without significant displacement.

Predictive Value of Preoperative Positive Urine Cytology for Development of Bladder Cancer After Nephroureterectomy in Patients With Upper Urinary Tract Urothelial Carcinoma: A Prognostic Nomogram Based on a Retrospective Multicenter Cohort Study and Systematic Meta-Analysis.

BACKGROUND: Upper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence (IVR) in patients with UUT-UC. However, the results of these studies are controversial or even contradictory, and investigations with UUT-UC patients in northeast China are rare. METHODS: We first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 231 UUT-UC patients (training cohort = 142, validation cohort = 89) after radical nephroureterectomy (RNU) by the nomogram model. Subsequently, we quantitatively combined our results with the published data after searching several databases to assess whether preoperative positive urine cytology was associated with poor intravesical recurrence-free survival and a high risk of tumor malignant biological behavior. RESULTS: Firstly, the multicenter retrospective cohort study demonstrated that preoperative positive urine cytology correlated with poor intravesical recurrence-free survival and can serve as significant independent predictors of IVR by Kaplan-Meier curves and Cox regression analysis. The construction of the nomogram demonstrated that predictive efficacy and accuracy were significantly improved when preoperative urine cytology was combined. Meanwhile, meta-analysis showed that preoperative positive urine cytology was associated with a 49% increased risk of IVR. In the subgroup analysis by region, study type, and sample size, the pooled hazard ratios (HRs) were statistically significant for the Japan subgroup (HR 1.32), China subgroup (HR 1.88), cohort study subgroup (HR 1.45), and the single-arm study subgroup (HR 1.63). CONCLUSIONS: Preoperative urine cytology was validated as a potential predictor of intravesical recurrence in patients with UUT-UC after RNU, although these results need to be generalized with caution. Large, prospective trials are required to further confirm its significance in prognosis and tumor malignant biological behavior.

Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment.

Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa (P=0.175). Stratified analyses of sex showed that aspirin intake did not lead to a lower risk of BCa in female patients (P=0.063). However, the male population who regularly took aspirin had a lower incidence of BCa (OR=0.748, 95% CI= 0.584-0.958, P=0.021). Subgroup analyses stratified by smoking found a significant reduction in the risk of BCa in current smokers with aspirin intake (OR=0.522, 95% CI=0.342-0.797, P=0.002). In terms of prognosis of BCa, patients with a history of aspirin intake did not had a markedly longer OS or RFS than those with no history of aspirin intake by Kaplan-Meier curves. Stratified analysis by sex showed no correlation between aspirin intake and the recurrence or survival of BCa for either male or female patients. However, in people younger than 68, aspirin intake seemed to have prolonged effects for overall survival (HR=3.876; 95% CI=1.326-11.325, P=0.019). Then, we performed a meta-analysis and the combined results from 19 articles and our study involving more than 39524 BCa cases indicated that aspirin intake was not associated with the occurrence of BCa (P=0.671). Subgroup analysis by whether regular use of aspirin, by the mean duration of use of aspirin, by sex, by smoking exposure, by research region and by study type also supported the above results. In terms of the impact of aspirin intake on the prognosis of patients with BCa, 11 articles and our study involving 8825 BCa cases were eligible. The combined results showed that patients with aspirin intake did not have significantly influence on survival, recurrence, progression and metastasis than those without aspirin intake. On the whole, both our retrospective study and literature meta-analysis suggested a lack of a strong relevant association between the use of aspirin and the incidence or prognosis of BCa. Thus, additional long-term follow-up prospective research is warranted to clarify the association of aspirin with BCa incidence and prognosis.

Interleukin-1ß-Treated Mesenchymal Stem Cells Inhibit Inflammation in Hippocampal Astrocytes Through Exosome-Activated Nrf-2 Signaling.

BACKGROUND: Interleukin-1ß (IL-1)-treated mesenchymal stem cells (MSCs) and IL-1-MSCs-conditioned medium (CM) exert anti-inflammatory roles. Astrocytes are essential for the modulation of synaptic activity and neuronal homeostasis in the brain. Exosomes are the critical mediators in intercellular communication. However, the mechanism underlying the anti-inflammatory effect of IL-1-treated MSCs remains unknown. METHODS: In this study, exosomes (IL-1-Exo) were isolated from IL-1-treated MSCs. In addition, lipopolysaccharide (LPS)-treated hippocampal astrocytes and status epilepticus (SE) mice were treated with IL-1-Exo. Inflammatory activity, astrogliosis, and cognitive performance were measured to determine the effect of IL-1-Exo on inflammation. RESULTS: The results revealed that IL-1-Exo significantly inhibited LPS-induced astrogliosis and inflammatory responses of astrocytes. Also, IL-1-Exo reversed the LPS-induced effect on calcium signaling. The Nrf2 signaling pathway was associated with the effect of IL-1-Exo in LPS-treated astrocytes. Furthermore, IL-1-Exo reduced the inflammatory response and improved the cognitive performance of SE mice. CONCLUSION: The results suggest that IL-1-Exo inhibited LPS-induced inflammatory responses in astrocytes and SE mice and that the effect of IL-1-Exo was primarily mediated through the Nrf-2 signaling pathway. This study provides a new understanding of the molecular mechanism of inflammation-associated brain diseases and an avenue to develop nanotherapeutic agents for the treatment of inflammatory conditions in the brain.

Decrease of an intracellular organic osmolyte contributes to the cytotoxicity of organophosphate in neuroblastoma cells in vitro.

Organophosphorus compounds (OP) causes prominent delayed neuropathy in vivo and cytotoxicity to neuronal cells in vitro. The primary target protein of OP's neurotoxicity is neuropathy target esterase (NTE), which can convert phosphatidylcholine (PC) to glycerophosphocholine (GPC). Recent studies reveal that autophagic cell death is important for the initiation and progression of OP-induced neurotoxicity both in vivo and in vitro. However, the mechanism of how OP induces autophagic cell death is unknown. Here it is found that GPC is an important organic osmolyte in the neuroblastoma cells, and treatment with tri-o-cresyl phosphate (TOCP), a representative OP, leads to the decrease of GPC and imbalance of extracellular and intracellular osmolality. Knockdown of GPC metabolizing enzyme glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) reverses TOCP-induced autophagic cell death, which further supports the notion that the reduced GPC level leads to the autophagic cell death. Furthermore, it is found that autophagic cell death is due to the induction of reactive oxygen species (ROS) and mitochondrial damage by imbalance of osmolality with TOCP treatment. In summary, this study reveals that TOCP treatment decreases GPC level and intracellular osmolality, which induces ROS and mitochondrial damage and leads to the cell death and neurite degradation by autophagy. This study lays the foundation for further investigations on the potential therapeutic approaches for OP neurotoxicity or NTE mutation-related neurological diseases.

Extrinsic Adenomyosis Is Associated With Postoperative Recurrence of Ovarian Endometrioma.

Objective: To determine whether endometrioma recurrence is closely related to the presence of extrinsic adenomyosis, which was demonstrated by magnetic resonance imaging (MRI). Design: Observational crosssectional study involving patients with the recurrence of ovarian endometrioma (OMA). Correlations of endometrioma recurrence and adenomyosis subtypes shown by MRI were analyzed. Method: Between January 2018 and December 2020, a total of 233 patients with recurrence of OMA after ovarian cystectomy were administered for surgery at our institution. All patients were divided into subtype II (Group A), subtype I+IV (Group B), and nonadenomyosis (Group C) groups at preoperative MRI imaging. The correlations of endometrioma recurrence with clinical features, imaging appearance, and surgical findings were retrospectively analyzed. Results: We found 112 (48.07%) patients of endometrioma recurrence combined with subtype II adenomyosis, 8 (3.43%) subtype I adenomyosis, 47 (20.17%) subtype IV adenomyosis, 66 (28.32%) nonadenomyosis. The mean time of OMA recurrence (44.28 ± 8.37, vs. 63.96 ± 10.28, vs. 69.36 ± 9.34 mon), rate of pain symptoms (85.71, vs. 69.10, vs. 18.18%), and primary infertility (31.25, vs. 14.55, vs. 10.77%) were higher in Group A. Uterine volume (257.37± 42.61, vs. 203.14 ± 33.52, vs. 100.85 ± 26.67 cm3), and mean OMA size (4.97 ± 2.25, vs. 4.36 ± 2.38, vs. 4.46 ± 2.70 cm) were significantly larger in Group A. The rate of DIE (83.93, vs. 45.45, vs. 40.91%), the number of DIE (3.6 ± 1.8 vs. 2.3 ± 1.5 vs. 2.2 ± 1.3), the mean total revised American Society for Reproductive Medicine score (rASRM, 103.14 ± 23.89 vs. 74.23 ± 16.72 vs. 36.51 ± 14.23) were significantly higher in Group A. After a multiple logistic regression analysis, extrinsic adenomyosis (OR 2.5, 95% CI 1.2-3.4), DIE lesions (OR 2.1, 95% CI 1.4-2.8), and primary infertility (OR 1.8, 95% CI 1.3-4.3) were significantly associated with early recurrence (in 3-year) of OMA. Conclusions: Extrinsic adenomyosis was associated with postoperative recurrence of OMA. In addition, a pathogenic link between extrinsic adenomyosis and pelvic endometriosis needs to be clarified.

[Downregulation of SND1 Expression Accelerates Cell Senescence of Human Diploid Fibroblasts 2BS via Modulating the SASP].

OBJECTIVE: To investigate the effect of down-regulation of SND1 expression on senescence of human diploid fibroblasts. METHODS: Western blot and immunohistochemistry were used to detect the expression of SND1 in young or senescent 2BS cells and aged tissues. Immunofluorescence was conducted to detect the localization of SND1 in young 2BS cells. CCK8 and EDU were performed to detect the proliferation of 2BS. Colony formation analysis was used to evaluate the capacity of colony formation of 2BS. Expression chip and RT-qPCR analysis were performed to detect the change of SASP expression level. ß-galactosidase staining was employed to indicate the senescent 2BS cells. RESULTS: The expression of SND1 in the senescent 2BS cells was significantly down-regulated compared with in the younger 2BS cells, and in human colon adenomas, its expression was also significantly down-regulated compared with in non-lesion colon tissues. In young 2BS, knockdown of SND1 inhibited the proliferation and colony formation of 2BS, and led to stronger senescence-associated beta-galactosidase staining (SA-ß-gal). Expression chip and RT-qPCR analysis indicated that knockdown of SND1 up-regulated the expression of senescence-associated secretory phenotype components (SASP). CONCLUSIONS: Our data indicated that down-regulation of SND1 regulated human diploid cell senescence by up-regulating the expression of SASP components.

Contrast-Induced Encephalopathy Resulting From Use of Ioversol and Iopromide.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare disease, whose etiology and risk factors remain unclear and need investigation. METHODS: We collected 7 CIE cases from 2646 patients injected with ioversol and 5 CIE cases from 526 patients injected with iopromide, all of whom underwent neurointervention surgery in our regional centers. The incidence of CIE, its characteristics, and risks were analyzed in both groups. RESULTS: The overall incidence of CIE was 0.38%, specifically 0.95% and 0.26% in the iopromide and ioversol groups, respectively; the former incidence was significantly higher than the latter (P = 0.029). The risk of CIE with iopromide was 3.567 to 3.618 times higher than that with ioversol (single-factor analysis odds ratio [OR], 3.618; 95% confidence interval [CI], 1.144-11.443; P = 0.029; multifactor analysis OR, 3.567 (95% CI, 0.827-15.379); P = 0.088). Moreover, acute cerebral infarction was an independent risk factor for CIE (OR, 4.024; 95% CI, 1.137-14.236; P = 0.031). Contrast-induced encephalopathy could occur within 5 minutes after injecting contrast media. The CIE characteristics differed according to the medium. In the ioversol group, the most common characteristic was visual disorder (71.43%), whereas in the iopromide group, the most common characteristic was delirium (100%). CONCLUSIONS: Compared with ioversol, iopromide appeared more likely to lead to CIE. Acute cerebral infarction was an independent risk factor for CIE. The earliest CIE onset was within 5 minutes after injecting contrast. The characteristics of CIE varied significantly for different contrast media.

Whole-Exome Sequencing Reveals New Potential Mutations Genes for Primary Mucosa-Associated Lymphoid Tissue Lymphoma Arising From the Kidney.

Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas involving the kidney were extremely rare, genetic alteration or molecular features was not yet explored, which may lead to limited choices for postoperative adjuvant or targeted. Whole-exome sequencing based tumor mutation profiling was performed on the tumor sample from a 77-year-old female presenting with discomfort at the waist was pathologically diagnosed as MALT lymphomas in the right kidney. We identified 101 somatic SNVs, and the majority of the identified SNVs were located in CDS and intronic regions. A total of 190 gain counts of CNVs with a total size of 488,744,073 was also investigated. After filtering with the CGC database, seven predisposing genes (ARID4A, COL2A1, FANCL, ABL2, HSP90AB1, FANCA, and DIS3) were found in renal MALT specimen. Furthermore, we compared somatic variation with known driver genes and validated three mutational driver genes including ACSL3, PHOX2B, and ADCY1. Sanger sequencing of germline DNA revealed the presence of a mutant base T of PHOX2B and a mutant base C of ADCY1 in the sequence, which were discovered for the first time in MALT lymphomas involving the kidney. Moreover, immunohistochemical analysis revealed that tumor cells were positive for CD20, CD79a, PAX5, CD21, and CD23, and expression of CD3, CD5, and CD8 were observed in reactive T lymphocytes surrounding tumor cells. These findings illustrated that concurrent aberrant PHOX2B and ADCY1 signaling may be a catastrophic event resulting in disease progression and inhibition of the putative driver mutations may be alternative adjuvant therapy for MALT lymphoma in the kidney which warrants further clinical investigation.