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Spinal cord injury (SCI) has considerable impact on patient physical, mental, and financial health. Secondary SCI is associated with inflammation, vascular destruction, and subsequent permanent damage to the nervous system. Mesenchymal stem cells (MSCs) have anti-inflammatory properties, promoting vascular regeneration and the release neuro-nutrients, and are a promising strategy for the treatment of SCI. Preclinical studies have shown that MSCs promote sensory and motor function recovery in rats. In clinical trials, MSCs have been reported to improve the American Spinal Injury Association (ASIA) sensory and motor scores. However, the effectiveness of MSCs in treating patients with SCI remains controversial. MSCs promote tumorigenesis and ensuring the survival of MSCs in the hostile environment of SCI is challenging. In this article we examine the evidence on the pathophysiological changes occurring after SCI. We then review the underlying mechanisms of MSCs in the treatment of SCI and summarize the potential application of MSCs in clinical practice. Finally, we highlight the challenges surrounding the use of MSCs in the treatment of SCI and discuss future applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xia, Zhu, Yang, Wang, Li and Fu.)

Mesenchymal stem cell (MSC) chondrogenesis in three-dimensional (3D) culture involves dynamic changes in cytoskeleton architecture during mesenchymal condensation before morphogenesis. However, the mechanism linking dynamic mechanical properties of matrix to cytoskeletal changes during chondrogenesis remains unclear. Here, we investigated how viscoelasticity, a time-dependent mechanical property of collagen hydrogel, coordinates MSC cytoskeleton changes at different stages of chondrogenesis. The viscoelasticity of collagen hydrogel was modulated by controlling the gelling process without chemical cross-linking. In slower-relaxing hydrogels, although a disordered cortical actin promoted early chondrogenic differentiation, persistent myosin hyperactivation resulted in Rho-associated kinase (ROCK)-dependent apoptosis. Meanwhile, faster-relaxing hydrogels promoted cell-matrix interactions and eventually facilitated long-term chondrogenesis with mitigated myosin hyperactivation and cell apoptosis, similar to the effect of ROCK inhibitors. The current work not only reveals how matrix viscoelasticity coordinates MSC chondrogenesis and survival in a ROCK-dependent manner but also highlights viscoelasticity as a design parameter for biomaterials for chondrogenic 3D culture.

Background: The aim of the study was to explore the changes and the possible influencing factors of phosphorus excretion in chronic kidney disease (CKD) patients., Methods: A database with 204 patients who met the CKD diagnostic criteria was established. Clinical data, including 24-hour urine phosphorus excretion (24-hour UPE), were collected. The demographic and clinical characteristics of CKD patients in different stages and the changes in serum phosphorus (P) and 24-hour UPE with renal function were studied. After exploring the factors influencing 24-hour UPE by multiple linear regression analysis, the effects of gender on 24-hour UPE was assessed., Results: Among 204 patients, there were significant differences in serum calcium (Ca), P, 24-hour UPE, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D [25(OH)-VD] among different CKD stages. Twenty-four-hour UPE fluctuated greatly, but serum P was relatively stable, which was > 1.46 mmol/L at an estimated glomerular filtration rate (eGFR) < 10 mL/minute/1.73 m2. Male gender (β = 3.42, p < 0.00) and eGFR (β = 0.06, p < 0.00) were related to 24-hour UPE, while age, body weight, albumin (ALB), iPTH, and serum P were not related to 24-hour UPE according to regression analysis. There were significant differences in 24-hour UPE and serum P between males and females., Conclusions: Urinary phosphorus excretion decreased with decreasing renal function in CKD patients. Urinary phosphorus excretion might be affected by eGFR and gender.

Intervertebral disc degeneration (IVDD) is one of the leading causes of lower back pain. Although IVDD cannot directly cause death, it can cause pain, psychological burdens, and economic burdens to patients. Current conservative treatments for IVDD can relieve pain but cannot reverse the disease. Patients who cannot tolerate pain usually resort to a strategy of surgical resection of the degenerated disc. However, the surgical removal of IVDD can affect the stability of adjacent discs. Furthermore, the probability of the reherniation of the intervertebral disc (IVD) after surgery is as high as 21.2%. Strategies based on tissue engineering to deliver stem cells for the regeneration of nucleus purposes (NP) and annulus fibrosus (AF) have been extensively studied. The developed biomaterials not only locally withstand the pressure of the IVD but also lay the foundation for the survival of stem cells. However, the structure of IVDs does not provide sufficient nutrients for delivered stem cells. The role of immune mechanisms in IVDD has recently become clear. In IVDD, the IVD that was originally in immune privilege prevents the attack of immune cells (mainly effector T cells and macrophages) and aggravates the disease. Immune regulatory and inflammatory factors released by effector T cells, macrophages, and the IVD further aggravate IVDD. Reversing IVDD by regulating the inflammatory microenvironment is a potential approach for the treatment of the disease. However, the biological factors modulating the inflammatory microenvironment easily degrade in vivo . It makes it possible for different biomaterials to modulate the inflammatory microenvironment to repair IVDD. In this review, we have discussed the structures of IVDs and the immune mechanisms underlying IVDD. We have described the immune mechanisms elicited by different biological factors, including tumor necrosis factors, interleukins, transforming growth factors, hypoxia-inducible factors, and reactive oxygen species in IVDs. Finally, we have discussed the biomaterials used to modulate the inflammatory microenvironment to repair IVDD and their development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xia, Wang, Yang, Hou, Li, Zhu and Fu.)

Pleomorphic xanthoastrocytoma (PXA) is a rare tumor ranging from World Health Organization (WHO) grades 2-3 and can potentially recur and metastasize throughout the central nervous system (CNS). Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion is a frequent genomic alteration of PXA. Methylthioadenosine phosphorylase (MTAP) immunohistochemistry is a promising surrogate marker for CDKN2A homozygous deletion in different cancers but has not been examined in PXA. Therefore, we performed CDKN2A fluorescence in situ hybridization and MTAP immunohistochemistry on specimens from 23 patients with CNS WHO grades 2 (n = 10) and 3 (n = 13) PXAs, including specimens from primary and recurrent tumors, and determined whether MTAP immunohistochemistry correlated with CDKN2A homozygous deletion and clinicopathological features. CDKN2A homozygous deletion was detected in 30% (3/10) and 76.9% (10/13) of CNS WHO grades 2 and 3 PXAs, respectively. In addition, MTAP loss was inconsistent with CDKN2A homozygous deletion (sensitivity = 86.7%, specificity = 100%). Furthermore, CDKN2A homozygous deletion was correlated with WHO grade (p = 0.026) and the Ki-67 labeling index (p = 0.037). Therefore, MTAP immunostaining can be a suitable surrogate marker for CDKN2A homozygous deletions in PXAs, and CDKN2A homozygous deletions may be an important prognostic factor for PXAs., (© 2022. The Author(s), under exclusive licence to The Japan Society of Brain Tumor Pathology.)

Mercury is a heavy metal which causes irreversible toxicity to fish and is detected in aquatic environment around the world. We aimed to explore the relative mechanism of mercury exposure on the brain injury. In this study, high-throughput sequencing RNA-Seq technology was carried out to analyze the changes of gene expression of brain tissues exposed to mercury. A large number of differentially expressed genes were identified. And 366 genes were up-regulated and 688 genes were down-regulated. Gene Ontology (GO) functional enrichment analysis showed that DNA-templated and transport were highly enriched in the biological process. Membrane, nucleus, and cytoplasm were highly enriched in the cellular component, and metal ion binding and DNA binding were highly enriched in molecular function. The differential genes were enriched in ferroptosis, necroptosis, calcium signaling pathway, and ion channels. Real-time quantitative reverse transcription PCR (qRT-PCR) results demonstrated the selected genes exhibited the same trends with the RNA-Seq results, which indicates the transcriptome sequencing data is reliable. Our results may provide an insightful view for the toxic effects of mercury on brain injury of common carp., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite advances in cancer treatment, metastatic cancer is still the main cause of death in cancer patients. At present, the treatment of metastatic cancer is limited to palliative care. The abscopal effect is a rare phenomenon in which shrinkage of metastatic tumors occurs simultaneously with the shrinkage of a tumor receiving localized treatment, such as local radiotherapy or immunotherapy. Immunotherapy shows promise for cancer treatment, but it also leads to consequences such as low responsiveness and immune-related adverse events. As a promising target-based approach, intravenous or intratumoral injection of nanomaterials provides new opportunities for improving cancer immunotherapy. Chemically modified nanomaterials may be able to trigger the abscopal effect by regulating immune cells. This review discusses the use of nanomaterials in killing metastatic tumor cells through the regulation of immune cells and the prospects of such nanomaterials for clinical use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xia, Yang, Zhu, Wang, Li, Fan and Fu.)

Intervertebral disc degeneration (IVDD) is a main cause of lower back pain, leading to psychological and economic burdens to patients. Physical therapy only delays pain in patients but cannot eliminate the cause of IVDD. Surgery is required when the patient cannot tolerate pain or has severe neurological symptoms. Although surgical resection of IVD or decompression of the laminae eliminates the diseased segment, it damages adjacent normal IVD. There is also a risk of re-protrusion after IVD removal. Cell therapy has played a crucial role in the development of regenerative medicine. Cell transplantation promotes regeneration of degenerative tissue. However, owing to the lack of vascular structure in IVD, sufficient nutrients cannot be provided for transplanted mesenchymal stem cells (MSCs). In addition, dead cells release harmful substances that aggravate IVDD. Extracellular vesicles (EVs) have been extensively studied as an emerging therapeutic approach. EVs generated by paracrine MSCs retain the potential of MSCs and serve as carriers to deliver their contents to target cells to regulate target cell activity. Owing to their double-layered membrane structure, EVs have a low immunogenicity and no immune rejection. Therefore, EVs are considered an emerging therapeutic modality in IVDD. However, they are limited by mass production and low loading rates. In this review, the structure of IVD and advantages of EVs are introduced, and the application of MSC-EVs in IVDD is discussed. The current limitations of EVs and future applications are described., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xia, Yang, Hou, Wang, Li, Zhu and Fu.)

Background: Related studies have shown that it is safe for cancer patients to undergo assisted reproduction. However, studies on whether a history of cancer affects long-term reproductive outcomes in women who undergo assisted reproductive technology (ART) are scarce. In this study, we evaluated the long-term reproductive outcomes of patients with malignant tumors undergoing ART treatment and explored the impact of malignancy history on ART outcomes., Methods: This retrospective study analyzed the clinical outcomes of patients with malignant tumors undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles compared with those of age-matched healthy infertile women at Fujian Maternity and Child Health Hospital between January 2003 and October 2020. We evaluated ovarian stimulation outcome, the pregnancy rate, the live birth rate, the risk of adverse obstetric outcomes and birth outcomes., Results: This study included 59 patients in the cancer group for data analysis who had a history of malignancy. By matching, a total of 118 healthy infertile women were included in the control group. No statistically significant association was found in terms of age, duration of infertility, BMI, or insemination type between the two groups of patients. Thyroid cancer(45.8%) and gynecologic malignancies (44.07%) were the major cancer types in this study. There were statistically significant differences in the antral follicle count (AFC) (12.00 ± 7.86 vs. 14.90 ± 8.71, P=0.033), length of ovarian stimulation (9.98 ± 2.68 vs. 11.42 ± 2.43, P=0.033) and endometrial thickness on the trigger day (10.16 ± 3.11 vs. 10.84 ± 2.17, P<0.001) between the two groups. The total gonadotropin dose, number of oocytes retrieved, fertilization rate, cleavage rate, high-quality embryo rate, blastocyst rate and first-time embryo-transfer (ET) implantation rate were nonsignificantly lower in the cancer group than in the control group (P>0.05). There were no significant differences in the clinical pregnancy rate per ET cycle (32% vs. 40.39%, P=0.156), live birth rate per ET cycle (27% vs. 35.96%, P=0.119), miscarriage rate per ET cycle (5% vs. 4.43%, P=0.779), or preterm delivery rate per ET cycle (11.11% vs. 17.80%, P=0.547) between the two groups. Additionally, regression analysis showed that a history of malignancy was not a risk factor for reproductive outcomes., Conclusions: Overall, it is feasible for women with a history of cancer to conceive using ART is feasible and their long-term reproductive outcomes are similar to these of healthy infertile women. A history of cancer does not decrease the number of retrieved oocytes, increase the risk of adverse obstetric outcomes or affect birth outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Cai, Dong, Wang, Yang, Yu, Wei, Ke, Sun, Zheng and Sun.)

Purpose: We launched a retrospective cohort study to explore the interactions among serum uric acid (UA), urine UA, and stone types., Methods: Clinical characteristics of urolithiasis patients in Beijing Tsinghua Changgung Hospital from October 2015 to August 2017 were retrospectively collected. Participants were categorized according to the quartiles of SUA and UUA respectively. Logistic regression model was built to identify the relationship between stone composition and UA level. Cubic spline was fitted to explore the correlation between 24-h urine UA and serum UA., Results: 718 hospitalized patients (51.1 ± 14.3 years, male 63.4%) with urinary calculi were included. Higher serum UA is associated with male, alcohol use, multiple serum and urine electrolytes (e.g. potassium, chloride, calcium, phosphorus), and lower estimated glomerular filtration rate. The risk of UA stone and carbonate apatite stone was associated with serum UA while the risk of calcium oxalate (CaOx) stone and ammonium magnesium hexahydrate (AMH) was dependent on urine UA. In the unadjusted model (Model 1), higher risks of UA stones were observed in the third quartile (OR 3.26, 95% CIs 1.63-6.53, P = 0.001) and the fourth quartile (OR 3.55, 95% CIs 1.78-7.08, P < 0.001) of serum UA compared with the first quartile. The risks of carbonate apatite stone were lowered in the third (OR 0.48, 95% CIs 0.31-0.73, P = 0.001) and fourth quartile (OR 0.40, 95% CIs 0.42-0.98, P = 0.042) of serum UA. The risk of CaOx stone was increased in the fourth quartile (OR 2.14, 95% CIs 1.15-3.99, P = 0.017) while the risk of AMH stone was decreased in the third (OR 0.46, 95% CIs 0.22-0.94, P = 0.034) and fourth quartile (OR 0.35, 95% CIs 0.16-0.78, P = 0.009) of urine UA. The elevated risks of UA stones in high levels of serum UA were demonstrated in the adjusted model (Model 2). An M-shaped association was found between serum UA and urine UA in our population., Conclusions: Serum UA and urine UA might cast different impact on urinary calculus composition. Proper control of the parameters should be considered based on different predisposing factors in individual patients., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Aim: To explore the safety, effectiveness, and dialysis adequacy of simplified regional citrate anticoagulation hemodialysis (SRCA-HD) in hemodialysis patients with high risk of bleeding., Materials and Methods: From 64 hemodialysis patients, 400 cases of low blood flow (150 mL/min, dialysate flow 300 mL/min) SRCA-HD were retrospectively analyzed and subsequently referred to as the LBF-SRCA group. Then, a prospective cross-over study was performed in 24 hemodialysis patients with normal blood flow (200 mL/min, dialysate flow 500 mL/min) SRCA-HD, which was called the NBF-SRCA group. Citrate was pumped at the artery pipeline, and calcium-containing dialysate (A group: 1.25 mmol/L, B group: 1.5 mmol/L) was used. The differences in laboratory tests, pipeline and dialyzer clotting, adequacy of dialysis, and adverse events of the groups were compared., Results: 1) In the LBF-SRCA study, the correlation between citrate dosage and serum Ca 2+ level at 2 hours post-filter during dialysis was negative (r = -0.228, p < 0.05). Compared with the LBF-SRCA and NBF-SRCA-A group, the pump speed of citrate in the NBF-SRCA-B group was the highest, with 355.0 ± 19.5 mL/h, 396.3 ± 11.9 mL/h, and 407.7 ± 13.0 mL/h, respectively, p < 0.001. 2) The serum Ca 2+ at 2 and 4 hours post-filter during dialysis in the NBF-SRCA-B group was closer to the physiological level and significantly higher than in the A group, with 0.80 ± 0.06 vs. 0.68 ± 0.12 mmol/L, p < 0.001; 1.03 ± 0.11 vs. 0.93 ± 0.10 mmol/L, p = 0.005, respectively. 3) Both Kt/V of the NBF-SRCA-A (1.17 ± 0.24) and B (1.22 ± 0.23) group were significantly higher than that of the LBF-SRCA group (0.94 ± 0.02), p = 0.024 and p = 0.005, respectively. 4) The efficiency of anticoagulation was higher than 95% LBF-SRCA, NBF-SRCA-A and NBF-SRCA-B groups. The total clotting in the NBF-SRCA-B group (5/24) was significantly higher than that in the A group (3/24), p = 0.005., Conclusion: SRCA is safe, simple, and effective in hemodialysis. The dosage of citrate can be adjusted by monitoring serum Ca 2+ at 2 hours post-filter during dialysis. BFR of 200 mL/min, dialysate flow rate of 500 mL/min, and 1.5 mmol/L calcium dialysate are much safer in hemodialysis patients with a high-risk of bleeding.

Spinal cord injury (SCI) is a severe and traumatic disorder that ultimately results in the loss of motor, sensory, and autonomic nervous function. After SCI, local immune inflammatory response persists and does not weaken or disappear. The interference of local adverse immune factors after SCI brings great challenges to the repair of SCI. Among them, microglia, macrophages, neutrophils, lymphocytes, astrocytes, and the release of various cytokines, as well as the destruction of the extracellular matrix are mainly involved in the imbalance of the immune microenvironment. Studies have shown that immune remodeling after SCI significantly affects the survival and differentiation of stem cells after transplantation and the prognosis of SCI. Recently, immunological reconstruction strategies based on biomaterials have been widely explored and achieved good results. In this review, we discuss the important factors leading to immune dysfunction after SCI, such as immune cells, cytokines, and the destruction of the extracellular matrix. Additionally, the immunomodulatory strategies based on biomaterials are summarized, and the clinical application prospects of these immune reconstructs are evaluated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Xia, Li, Li and Fu.)

Cadmium (Cd) poisoning in humans and fish represents a significant global problem. Bacillus cereus (B. cereus) is a widely used probiotic in aquaculture. The objective of this study was to evaluate the potential of B. cereus in ameliorating Cd-induced toxicity in mirror carp. The biosorption rate of Zn for the B. cereus in 85.99% was significantly more than five strains. All fishes were exposed for 30 days to dietary ZnCl 2 (30mg/kg), waterborne Cd (1 mg/L), and/or dietary Zn-enriched B. cereus (Zn 30mg/kg and 10 7 cfu/g B. cereus). At 15 and 30 days, the fishes were sampled, and bioaccumulation, antioxidant activity, and intestinal microbiota were measured. Waterborne Cd exposure caused marked alterations in the composition of the microbiota. Dietary supplementation with Zn-enriched B. cereus can reduce the changes in the composition of intestinal microbiota in Cd exposure and decrease the pathogenic bacteria of Flavobacterium and Pseudomonas in Zn-enriched B. cereus groups. The results obtained indicate that Zn-enriched B. cereus can provide a significant protective effect on the toxicity of cadmium by inhibiting alterations in the levels of bioaccumulation and antioxidant enzyme including superoxide dismutase (SOD), catalase (CAT), total antioxidant (T-AOC), and malonaldehyde (MDA). Our results suggest that administration of Zn-enriched B. cereus has the potential to combat Cd toxicity in mirror carp., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mercury (Hg) is a global pollutant that affects the health of humans and ecosystems. Selenium (Se) is an essential trace element for many organisms including humans. Bacillus subtilis is one of the main probiotics used in aquaculture, and has a certain adsorption effect on heavy metals. The interaction between Hg and Se was rigorously studied, especially due to the observation of the protective effect of Se on Hg toxicity. The objective of this study was to research the effects of Hg, Se, and B. subtilis on inflammation and intestinal microbes in common carp. The common carp was exposed to Hg (0.03 mg/L), and 10 5  cfu/g Se-rich B. subtilis was added to the feed. After 30 days of feeding, samples were taken to evaluate the growth performance, serological response, inflammatory response, and intestinal microbial changes. In this study, when fish were exposed to Hg, the growth performance of the Se-rich B. subtilis plus 0.03 mg/L Hg fish group was lower than that of the control group and higher than 0.03 mg/L Hg; The levels of serum immunoglobulin M (IgM) and lysozyme (LZM) decreased, but after supplementation with Se-rich B. subtilis, the levels of LZM and IgM increased; Hg treatment significantly upregulated the mRNA expression of interleukin-1β (IL-1β), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and nuclear factor-kB (NF-κB P65), but downregulated the mRNA expression of interleukin-10 (IL-10), transforming growth factor-β (TGF-β) and NF-kappa-B inhibitor alpha (IkBα). However, compared with the Hg group, the Se-rich B. subtilis plus Hg group can significantly increase the mRNA expression levels of IL-1β, IL-8, TNF-α, and NF-κB P65, but reduce the regulation of IL-10, TGF-β, and IkBα expression. Through the analysis of the microbiological, we found that the Hg group was mainly composed of Aeromonas sobria and Aeromonas hydrophila. However, in the Se-rich B. subtilis treatment group, we found that Aeromonas sobria was significantly less than the Hg group. Se-rich B. subtilis improves Hg-induced intestinal microbial changes, alleviates the abundance of Aeromonas, and alleviates the inflammation of the fish. The results of this study show that Se-rich B. subtilis dietary supplements can effectively protect common carp against Hg toxicity., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Fluorine is an environmental toxicant and exposure of fluorine could induce various health disorders. Gut microbiota has been known to be involved in maintaining animal or human health. Therefore, in the present study, we aimed to evaluate the relationship between fluorine exposure and gut microbiota in common carp. Gut microbiota composition was detected by 16S rRNA gene sequencing. Intestinal structural integrity was assessed by hematoxylin-eosin staining and tight junction protection detection. The results showed that exposure of carp to fluorine led to the injury of intestinal tissues. And compared to the control group, the expression of tight junction protein ZO-1 and occludin was decreased. Meanwhile, the gut microbial diversity and composition were changed by fluorine exposure. At the phylum level, the abundance of Fusobacteria and Firmicutes increased significantly, and the abundance of Actinobacteria decreased markedly after treatment of fluorine. At the genus level, interestingly, we found the abundance of Plesiomonas, an important pathogenic bacteria, increased significantly by the treatment of fluorine. And the abundance of Akkermansia, a critical probiotics, was markedly inhibited by the treatment of fluorine. In conclusion, the results suggested fluorine exposure changed the gut microbiome composition and led to the damage of intestinal structural integrity.

Introduction: Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) are rare tumors, mainly encountered in the gastroenteropancreatic tract. Based on the limited available data, MiNEN is usually a highly aggressive neoplasm combining a high-grade neuroendocrine and a non-neuroendocrine component, associated with a poor prognostic outlook. Deficient DNA mismatch repair (MMR) results in microsatellite instability, which is a useful screening marker for identifying patients with Lynch syndrome and a prognostic factor for chemotherapeutic interventions. Little information on MMR status in MiNEN is available in published studies. Therefore, the purpose of this study was to explore the status and putative role of MMR on MiNEN., Methods: We investigated the MMR status in 44 cases and characterized their clinicopathological features and prognoses. Immunohistochemistry was performed for four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2)., Results: Mean age at diagnosis was 61 years, and 75% of the patients were male. Lymph node metastases were observed in 14 (35.9%) patients. The most common tumor localizations were gastric (28 patients, 63.6%). Lack of immunohistochemical expression of MMR proteins was shown in 38.6% of cases. The common deletion rates of one or more proteins were 29.4% (5/17) for MLH1/PMS2 and 23.5% (4/17) for MLH1. Correlation between clinicopathological parameters showed that MMR deficiency was significantly associated with early TNM stage and better prognoses in patients with MiNEN., Conclusion: MiNENs showed frequent losses of MMR protein expression, which contributes to the knowledge of the pathological and clinical aspects of MiNEN tumors., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Cadmium (Cd) is a hazardous pollutant known to exert various toxic effects and other sublethal effects on aquatic organisms, and induce a variety of adverse effects on human health, and can be commonly found in environment. The aim of this study was to explore the effects of waterborne Cd exposure on the intestinal microbiota, and Cd accumulation and oxidative response in Carassius auratus gibelio (C. gibelio). The fish were exposed to waterborne Cd at 0, 1, 2, and 4 mg/L for 30 days. Waterborne Cd exposure resulted marked alterations in the composition of microbiota. At the genus level, Bacteroides, Aeromonas, Akkermansia, Acinetobacter, Chryseobacterium, Shinella, Cetobacterium and Bacillus were significantly changed in Cd groups. The results obtained indicate that Cd exposure significantly increased the bioaccumulation level of Cd and profoundly affected antioxidant enzyme including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), total antioxidant (T-AOC), malonaldehyde (MDA), and glutathione-S-transferase (GST). The present findings may provide a new framework for the role of gut microbiota in the response to environmental chemical contamination and in the pathogenesis of body disorders.

Background: Femoral nerve palsy can cause loss in quadriceps function and knee extension disability, which may lead to severe lower extremity impairment. The obturator nerve trunk transfer in the pelvic, the obturator nerve mortal branches transfer out of the pelvic, along with nerve graft, was introduced years ago to restore femoral nerve function. However, the outcomes of these procedures have never been compared. The aims of this study were to give our experiences in surgical reconstruction for femoral nerve injury and to compare the outcomes of different approaches., Methods: Nine patients with complete femoral nerve injury have been enrolled in this study between March 2012 and July 2016. All patients were followed up for at least 2 years after surgical intervention for sural nerve graft (n = 3), obturator trunk transfer in the pelvic (n = 2), or obturator nerve mortal branches transfer out of the pelvic (n = 4)., Results: All patients gained satisfactory quadriceps Medical Research Council grade (M3-M4+) after more than 2 years of follow-up. The sural nerve graft led to the earliest recovery on average, followed by obturator nerve mortal branches transfer in the thigh level and then obturator nerve trunk transfer in the pelvic. The functional outcomes, demonstrated by Lower Extremity Functional Scale and Femoral Nerve Motor Function Scale scores, also showed that the sural nerve graft was the best on average, followed by obturator nerve trunk transfer in the pelvic and then obturator nerve mortal branches transfer in the thigh level., Conclusions: Our results indicate that all these 3 procedures are safe and reliable ways to reconstruct femoral nerve function and can be applied to patients with different kinds of injuries. The sural nerve graft should be considered in the first place and the obturator nerve transfer at different level (trunk transfer in the pelvic or mortal branches transfer out of the pelvic) can be performed as the alternative.

Cadmium (Cd) is the most common heavy metal and is easily detected in aquatic environments on a global scale. Vitamin C was a widely used vitamin in aquaculture. The aim of this study was to explore the potential of vitamin C in ameliorating Cd-induced toxicity in grass carp kidney (CIK) cells. Cell viability, oxidative response, metallothionein (MT), and immune-related gene expression was analyzed in the present study. The results show that cell viability was significantly reduced following Cd exposure, but the vitamin C supplementation attenuated the increased in cell viability. In addition, vitamin C supplementation can increase the antioxidation response and MT and immune-related gene expression. These results indicate that vitamin C has the potential to alleviate the effects of Cd toxicity in CIK cells.

Cadmium (Cd) is the most abundant heavy metal in aquatic environments and is easily detected on a global scale. Carassius auratus gibelio is a common aquaculture species. The aim of this study was to explore the toxic effects of 1, 2, and 4 mg/L Cd on the energy metabolism, growth performance, and neurological responses of C. gibelio. After 30 days of exposure, Cd concentrations in the liver and brain were significantly increased in Cd-exposed groups. Low-level Cd exposure (1 mg/L) increased weight and length gains, as well as food intake, in the fish. Acetylcholinesterase activity decreased significantly in the Cd-exposed groups. Energy metabolism levels (as reflected by oxygen consumption, ammonia excretion rate, and swimming activity), as well as serum T3 and T4 levels, increased significantly in the fish exposed to 1 mg/L Cd. However, energy metabolism and serum T3/T4 levels decreased significantly in the 4-mg/L Cd group. Neuropeptide gene expression levels in brain were consistent with the observed changes in food intake. In the Cd-exposed groups, the expression levels of neuropeptide Y (NPY), apelin, and metallothionein (MT) increased significantly, while those of pro-opinmelanocortin (POMC), ghrelin, and corticotrophin-releasing factor (CRF) decreased significantly. Our data suggested that in fish, low doses of Cd might increase food intake, as well as weight and length gains, but high doses of Cd might have the opposite effect. These effects might be a result of neurohumoral regulation. Long-term exposure to low doses of Cd might cause weight gain and affect food intake.

Osteosarcoma (OS) is one of the most common malignant bone tumors among children and young adults. Furowanin A (Fur A), one of the active ingredients of Millettia pachycarpa Benth, has been found to exert pro-apoptotic activity in human leukemia cells. This study is designed to evaluate the efficacy of Fur A against OS. The effect of Fur A on cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Western blotting and quantitative real-time PCR (qRT-PCR) were performed to determine the protein and mRNA level of sphingosine kinase 1 (SphK1), respectively. To validate the role of SphK1 in the pro-apoptotic activity of Fur A, overexpressing SphK1 vector and siRNA targeting SphK1 were utilized to transfect OS cells. Moreover, an OS xenograft murine model was used to analyze the therapeutic efficacy of Fur A in vivo. Fur A treatment led to a dose-dependent decrease in the number of viable cells. It also exhibited antiproliferative activity and significantly promoted apoptotic cell death in OS cell lines. Our results showed that the anticancer activity of Fur A was associated with downregulation of SphK1 and inactivation of its downstream signaling. The mediatory role of SphK1 was validated when the pro-apoptotic activity of Fur A was significantly blocked by SphK1 overexpression, while SphK1 knockdown sensitized the OS cells to Fur A. We concluded that Fur A can exhibit anti-growth and pro-apoptotic activities in vitro and in vivo in OS by downregulating SphK1. Our study highlights the possibility of utilizing Fur A as a chemotherapeutic agent in the treatment of OS. Anat Rec, 302:1941-1949, 2019. © 2019 American Association for Anatomy., (© 2019 American Association for Anatomy.)

Lead (Pb), a heavy metal and an environmental stressor, may affect many physiological processes, including the serum index and the immune response. The aim of this study was to explore the toxic effects of Pb on the serum index and the immune response of Carassius auratus gibelio (C. gibelio) fed 0, 120, or 240 mg/kg Pb, and 10 9  cfu/g Bacillus subtilis (B. subtilis). After 15 and 30 days of dietary exposure, the serum indices and the immune responses of the fish were assessed. Dietary Pb exposure significantly affected various components of the serum index, including calcium, magnesium, glucose, cholesterol, total protein, glutamic-pyruvic transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). However, sIgA activity in the gut increased significantly following B. subtilis supplementation. Notable changes were also observed in the expression levels of immune-related genes, including HSP70, IgM, HSP90, IL-1β, IL-6, and TNF-α. B. subtilis supplementation effectively attenuated the effects of dietary Pb exposure.

Lead (Pb) is one of the most ubiquitous and toxic elements in the aquatic environment. Bacillus subtilis (B. subtilis) is a widely used probiotic in aquaculture. The aim of this study was to explore the toxic effects on bioaccumulation, hematological parameters, and antioxidant responses of Carassius auratus gibelio (C. gibelio) exposed to dietary lead at 0, 120, and 240 mg/kg and/or B. subtilis at 10 9  cfu/g. At 15 and 30 days, the fish were sampled and bioaccumulation, hematological parameters, and antioxidant responses were assessed. The result showed that B. subtilis administration can provide a significant protection against lead toxicity by reducing lead bioaccumulation in tissues, increasing the antioxidant enzymes activity, recovering δ-aminolevulinic acid dehydratase activity and optimizing the hematological parameters. Our results suggested that administration of B. subtilis (109 cfu/g) has the potential to combat dietary lead toxicity in C. gibelio.

The T-cell response and tolerance in non-lymph tissues differs from those in lymph tissues such as the spleen and thymus. The distribution and composition of the TCR repertoires in non-lymph tissues and how they differ and associate with their counterparts in lymph tissue remain unclear. Thus, we studied the thymus, spleen, blood, liver and small intestine of BALB/c mice at the ages of one, three and five months to carry out a preliminary analysis of the spatial-temporal homogeneity and heterogeneity of the total TCR β chain CDR3 repertoire using high-throughput sequencing technology and immune bioinformatics approaches. The data show that the diversity of the CDR3 repertoires was decreased as the mouse age increased, except in the small intestine. The number of low-expanded clones in the CDR3 repertoires was greatest in the thymus, followed by the spleen, blood, liver and small intestine, and highly expanded clones had an opposite trend in the different mice ages. The thymus and the spleen showed the greatest overlap of CDR3 sequences with the other tissues across the different mice ages. The distribution of the CDR3 repertoire length was normal, with a median of 14 aa in all the mouse tissues, except the small intestine of the one-month-old mice had a median of 12 aa. In summary, the composition and characteristics of the CDR3 repertoires in the thymus were similar to those in the spleen, and repertoires in the blood were similar to those in the liver; only the small intestine showed a unique composition. These results offer a novel method to explore the source, differentiation, proliferation and response of distinct T cells in different tissues at different mice ages., Competing Interests: None.

The aim of this study was to explore the effects of lead exposure on the antioxidant and immune responses of Crucian carp. Three hundred sixty healthy Crucian carp were randomly grouped into four groups and exposed to different doses of lead (0, 0.05, 0.5, and 1 mg/L). Fish were sampled at 30 and 60 days, respectively, and antioxidant capability, immune parameters, ALAD activity, and immune-related genes were assessed. The results showed that T-AOC and GSH activities of the liver were significantly increased in 60 days (P < 0.05); the activities of SOD, CAT, T-AOC, and GSH were significantly increased (P < 0.05) compared to the control in the kidney in 60 days. With an increase in Pb dose, the activity and expression of lysozyme and the content of immunoglobulin M were significantly decreased compared to the control. Compared with the control group, the activity of ALAD in the lead-exposed group decreased significantly (P < 0.05). The expression of the HSP70, tumor necrosis factor-α (TNF-α), interleukins (IL-10), and immunoglobulin M genes was all enhanced in lead-exposed group, whereas lysozyme gene expression was decreased. The results indicated that lead induced oxidative stress and had immunotoxic effects on Crucian carp.

Esophageal squamous cell carcinoma (ESCC) is generally known to be a highly fatal cancer, and thus novel molecular targets are needed to improve its diagnosis and treatment. AJUBA has been shown to regulate cell cycle, adhesion, proliferation, apoptosis, and migration in many malignant tumors. However, the clinical significance of AJUBA in ESCC tumor metastasis remains unclear. In this study, we explored the role of AJUBA, Yes-associated protein 1 (YAP1), and matrix metalloproteinase 14 (MMP14) in the clinical presentation and survival of ESCC. Immunohistochemical staining showed higher expression of these proteins in cancer tissues than in paired adjacent tissues, and this upregulation was differently related to lymph node metastasis and TNM stage. AJUBA expression was positively correlated with that of YAP1. High expression of MMP14 was associated with reduced survival. In general, our findings reveal that AJUBA, YAP1, and MMP14 might function as oncoproteins and contribute to novel targeted therapy in ESCC., Competing Interests: None., (IJCEP Copyright © 2018.)

Sterigmatocystin (ST) is generally recognized as a potential carcinogen, mutagen and teratogen. Studies showed that ST could induce adenocarcinoma of lung in mice in vivo and DNA damage, cell cycle arrest in a human immortalized bronchial epithelial cell line (BEAS-2B cells) and a human lung cancer cell line (A549 cells) in vitro. Besides, ST could induce G 2 arrest (cell cycle arrest in G 2 phase) in several other cells. Cell cycle arrest may be one of the common toxic effects of ST. As cells may undergo apoptosis or death due to cell cycle arrest, we wondered whether apoptosis is another common effect of ST in different cells in vitro. In the present study, we studied the effects of ST on proliferation and apoptosis in A549 cells and BEAS-2B cells with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis (FCM). The MTT results showed that proliferation inhibition following ST treatment for 24h was observed in both A549 and BEAS-2B cells in vitro. And increased apoptosis by FCM was also found after ST treatment. Down-regulation of Bcl-2, up-regulation of Bax and the activation of caspase-3 after ST treatment were detected by western blotting analyses. The results in the present study are consistent with our previous results, which indicated that inducing apoptosis may be a common effect of ST in different cells in vitro., (Copyright © 2017. Published by Elsevier GmbH.)

Objective: To define the outcomes and risk predictors of fetal and maternal consequences of pregnancy in lupus nephritis (LN) patients., Methods: Maternal and fetal outcomes of pregnancy in 52 systemic lupus erythematosus (SLE) patients were observed. Patients were allocated into two groups according to the presence or absence of LN., Results: LN patients were subject to a higher risk of fetal complications, including fetal loss (7/24, 29.2 %, P = 0.001), lower birth weight (2548.2 ± 540.8 vs. 2949.1 ± 592.6 g, P = 0.028) and a higher frequency of small for gestational age births (33.3 vs. 10.7 %, P = 0.002). Higher rates of lupus flares (83.3 vs. 21.4 %, P = 0.001) and increased LAI-P scores (0.65 ± 0.36 vs. 0.21 ± 0.27, P = 0.001) during pregnancy were observed in LN patients. Multivariate analysis showed that increased SLE activity (P = 0.02, OR 4.2, 95 % CI 1.2-14.5), renal damage (P = 0.001, OR 8.4, 95 % CI 2.2-31.8), hypocomplementemia (P = 0.05, OR 3.23, 95 % CI 1.0-10.7), hypoalbuminemia (P = 0.011, OR 5.62, 95 % CI 1.4-23.0) and hypertension (P = 0.021, OR 6.0, 95 % CI 1.5-24.2) during pregnancy were predictors of adverse fetal outcomes., Conclusions: Pregnancy in LN patients should be monitored before and during pregnancy because of poor fetal and maternal outcomes. Increased LAI-P scores, renal damage, hypocomplementemia, hypoalbuminemia and hypertension are predictors of adverse fetal outcomes for SLE patients.

Objective: Research was done on the possible roles of beta-catenin, p53 and proliferating cell nuclear antigen (PCNA) in the carcinogenesis of colorectal adenoma (CRA)., Methods: beta-catenin and p53 and PCNA expressions were studied with immunohistochemical stain in 77 specimens of CRA together with mild epithelial dysplasia (CRA-MD), CRA with moderate/severe epithelial dysplasia (CRA-D/SD) and CRA with cancerous changes (CRA-C)., Results: The percentage of abnormal expression of beta-catenin increased during the transition from CRA-MD to CRA-D/SD to CRA-C (P < 0.01). The nuclear expressions of beta-catenin in CRA-D/SD and CRA-C were all significantly higher than that in CRA-MD. Expression of p53 and PCNA were increased from CRA-MD to CRA-D/SD to CRA-C, with the positive rates in these three groups of 10.3%, 43.8%, 75.0% for p53 and 17.2%, 62.5%, 87.5% for PCNA, respectively. 69.7% of cases with positive nuclear beta-catenin expression showed strong PCNA positivity which was much higher than the 36.4% of cases without nuclear beta-catenin expression (P < 0.05). The percentage of strong PCNA expression in the p53 positive cases was significant higher than that in cases with negative p53 expression (72.4% vs 37.5%, P < 0.05). Nuclear beta-catenin and p53 co-expression rates in CRA-C reached 50%., Conclusion: beta-catenin, p53 and PCNA may play important roles in the carcinogenesis of colorectal adenoma.