The role of Testis-Specific Protein Y-encoded-Like 2 in kidney injury.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Recent findings suggest that Testis-Specific Protein Y-encoded-Like 2 (TSPYL2) plays a fibrogenic role in diabetes-associated renal injury. However, the role of TSPYL2 in IRI-induced kidney damage is not entirely clear. In this study, we found that the expression of TSPYL2 was upregulated in a mouse model of AKI and in the hypoxia/reoxygenation (H/R) cell model. Knockdown of TSPYL2 attenuated kidney injury after IRI. More specifically, the knockdown of TSPYL2 or aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) alleviated renal IRI-induced mitochondrial dysfunction and oxidative stress in vitro and in vivo. Further investigation showed that TSPYL2 regulated SREBP-2 acetylation by inhibiting SIRT1 and promoting p300 activity, thereby promoting the transcriptional activity of ACMSD. In conclusion, TSPYL2 was identified as a pivotal regulator of IRI-induced kidney damage by activating ACMSD, which may lead to NAD+ content and the damaging response in the kidney.

Novel non-invasive method for urine mapping: Deep-learning-enabled SERS spectroscopy for the rapid differential detection of kidney allograft injury.

The kidney allograft has been under continuous attack from diverse injuries since the very beginning of organ procurement, leading to a gradual decline in function, chronic fibrosis, and allograft loss. It is vital to routinely and precisely monitor the risk of injuries after renal transplantation, which is difficult to achieve because the traditional laboratory tests lack sensitivity and specificity, and graft biopsies are invasive with the risk of many complications and time-consuming. Herein, a novel method for the diagnosis of graft injury is demonstrated, using deep learning-assisted surface-enhanced Raman spectroscopy (SERS) of the urine analysis. Specifically, we developed a hybrid SERS substrate composed of gold and silver with high sensitivity to the urine composition under test, eliminating the need for labels, which makes measurements easy to perform and meanwhile results in extremely abundant and complex Raman vibrational bands. Deep learning algorithms were then developed to improve the interpretation of the SERS spectral fingerprints. The deep learning model was trained with SERS signals of urine samples of recipients with different injury types including delayed graft function (DGF), calcineurin-inhibitor toxicity (CNIT), T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), and BK virus nephropathy (BKVN), which explored the features of these types and achieved the injury differentiation with an overall accuracy of 93.03%. The results highlight the potential of combining label-free SERS spectroscopy with deep learning as a method for liquid biopsy of kidney allograft injuries, which can provide great potential to diagnose and evaluate allograft injuries, and thus extend the life of kidney allografts.

Ovarian leiomyoma accompanied by a neglected abdominal wall leiomyoma: A case report and literature review.

Ovarian leiomyoma and abdominal wall leiomyoma are both rare clinical entities. Here, we report the rare case with ovarian leiomyoma accompanied by a neglected abdominal wall leiomyoma to raise the awareness of clinicians of ovarian leiomyoma and multiple occurrences of benign leiomyoma for appropriate diagnosis.

Oral micronized progesterone versus vaginal progesterone for luteal phase support in fresh embryo transfer cycles: a multicenter, randomized, non-inferiority trial.

STUDY QUESTION: Does oral micronized progesterone result in a non-inferior ongoing pregnancy rate compared to vaginal progesterone gel as luteal phase support (LPS) in fresh embryo transfer cycles? SUMMARY ANSWER: The ongoing pregnancy rate in the group administered oral micronized progesterone 400 mg per day was non-inferior to that in the group administered vaginal progesterone gel 90 mg per day. WHAT IS KNOWN ALREADY: LPS is an integrated component of fresh IVF, for which an optimal treatment regimen is still lacking. The high cost and administration route of the commonly used vaginal progesterone make it less acceptable than oral micronized progesterone; however, the efficacy of oral micronized progesterone is unclear owing to concerns regarding its low bioavailability after the hepatic first pass. STUDY DESIGN, SIZE, DURATION: This non-inferiority randomized trial was conducted in eight academic fertility centers in China from November 2018 to November 2019. The follow-up was completed in April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1310 infertile women who underwent their first or second IVF cycles were enrolled. On the day of hCG administration, the patients were randomly assigned to one of three groups for LPS: oral micronized progesterone 400 mg/day (n = 430), oral micronized progesterone 600 mg/day (n = 440) or vaginal progesterone 90 mg/day (n = 440). LPS was started on the day of oocyte retrieval and continued till 11-12 weeks of gestation. The primary outcome was the rate of ongoing pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: In the intention-to-treat analysis, the rate of ongoing pregnancy in the oral micronized progesterone 400 mg/day group was non-inferior to that of the vaginal progesterone gel group [35.3% versus 38.0%, absolute difference (AD): -2.6%; 95% CI: -9.0% to 3.8%, P-value for non-inferiority test: 0.010]. There was insufficient evidence to support the non-inferiority in the rate of ongoing pregnancy between the oral micronized progesterone 600 mg/day group and the vaginal progesterone gel group (31.6% versus 38.0%, AD: -6.4%; 95% CI: -12.6% to -0.1%, P-value for non-inferiority test: 0.130). In addition, we did not observe a statistically significant difference in the rate of live births between the groups. LIMITATIONS, REASONS FOR CAUTION: The primary outcome of our trial was the ongoing pregnancy rate; however, the live birth rate may be of greater clinical interest. Although the results did not show a difference in the rate of live births, they should be confirmed by further trials with larger sample sizes. In addition, in this study, final oocyte maturation was triggered by hCG, and the findings may not be extrapolatable to cycles with gonadotropin-releasing hormone agonist triggers. WIDER IMPLICATIONS OF THE FINDINGS: Oral micronized progesterone 400 mg/day may be an alternative to vaginal progesterone gel in patients reluctant to accept the vaginal route of administration. However, whether a higher dose of oral micronized progesterone is associated with a poorer pregnancy rate or a higher rate of preterm delivery warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a grant from the National Natural Science Foundation of China (82071718). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the number ChiCTR1800015958. TRIAL REGISTRATION DATE: May 2018. DATE OF FIRST PATIENT'S ENROLMENT: November 2018.

SOCS3 inhibits the mesenchymal stromal cell secretory factor SDF-1-mediated improvement of islet function in non-obese diabetic mice.

BACKGROUND: Islet transplantation is used therapeutically in a minority of patients with type 1 diabetes (T1D). However, successful outcomes are hampered by early islet ß-cell loss caused by immune rejection and autoimmunity. Recent studies have demonstrated that mesenchymal stromal cells can enhance islet function both in vitro and in vivo by secreting ligands that activate islet G-protein coupled receptors (GPCRs). Stromal cell-derived factor 1 (SDF-1) is an MSC-secreted GPCR ligand, whereas the suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of STAT3-activating cytokines. Here, we determined whether improvement in islet function mediated by exogenous SDF-1 is impaired by SOCS3 in experimental models of T1D. METHODS: Isolated islets were cultured for 48 h with SDF-1. Cytokine-induced apoptosis was measured immediately. Islets from Socs3-/- mice were pre-cultured with exogenous SDF-1 and transplanted underneath the kidney capsule of C57BL/6 mice with streptozotocin-induced diabetes. Blood glucose levels were monitored for 28 days. AMD3100, an antagonist of the SDF-1 ligand CXCR4, was administered subcutaneously to islet transplanted mice to inhibit CXCR4 before and after transplantation. RESULTS: SDF-1 protected islet cells from cytokine-induced apoptosis in vitro. SOCS3-knockout (KO) islets pretreated with SDF-1 were effective in reducing blood glucose in non-obese diabetic mice in vivo. We found that SDF-1 elicits localized immunosuppression in transplanted SOCS3-KO islets. Immunomodulation was observed when SOCS-KO islets were preconditioned with SDF-1. Gene expression and flow cytometric analyses revealed significantly decreased immune cell infiltration, inflammatory cytokines, and concomitant increases in FOXP3+ regulatory T cells, alternatively activated M2 macrophages, and dendritic cell phenotypes. Administration of AMD3100 impaired the SDF-1-mediated improvement in SOCS3-KO islet function and local immune suppression. CONCLUSION: SDF-1 improves the function of islet grafts in autoimmune diabetes through regulation by CXCR4; however, the presence of SOCS3 reverses the protective effect of SDF-1 on islet grafts. These data reveal a molecular pathway that can elicit localized immunosuppression and delay graft destruction in transplanted islets.

Rapid and ultrasensitive detection of acute kidney injury biomarkers CH3L1 and L-FABP using surface-enhanced Raman spectroscopy.

Chitinase 3-like 1 (CH3L1) and liver fatty acid binding protein (L-FABP) are promising biomarkers for the early diagnosis of acute kidney injury (AKI). Here, a highly sensitive method for the quantitative detection of CH3L1 and L-FABP by surface-enhanced Raman spectroscopy (SERS) based on graphene oxide/gold and silver core-shell nanoparticles (GO/Au@Ag NPs) was proposed. The results showed that such GO/Au@Ag substrate can achieve rapid sensing of CH3L1 and L-FABP with a wide response range (2 × 10-1 to 2 × 10-8 mg/mL and 1.2 × 10-1 to 1.2 × 10-8 mg/mL, respectively) and high sensitivity. The detection limits of CH3L1 and L-FABP were 1.21 × 10-8 mg/mL and 0.62 × 10-8 mg/mL, respectively. In addition, the simultaneous detection of the two biomarkers in serum was demonstrated, showing the feasibility of this method in the complex biological environment. The detection of CH3L1 and L-FABP will greatly improve the early diagnosis and intervention of AKI.

Transcriptomic Analysis Revealed an Important Role of Peroxisome-Proliferator-Activated Receptor Alpha Signaling in Src Homology Region 2 Domain-Containing Phosphatase-1 Insufficiency Leading to the Development of Renal Ischemia-Reperfusion Injury.

In kidney transplantation, the donor kidney inevitably undergoes ischemia-reperfusion injury (IRI). It is of great importance to study the pathogenesis of IRI and find effective measures to attenuate acute injury of renal tubules after ischemia-reperfusion. Our previous study found that Src homology region 2 domain-containing phosphatase-1 (SHP-1) insufficiency aggravates renal IRI. In this study, we systematically analyzed differences in the expression profiles of SHP-1 (encoded by Ptpn6)-insufficient mice and wild-type mice by RNA-seq. We found that a total of 161 genes showed at least a twofold change, with a false discovery rate <0.05 in Ptpn6 +/mev mice after IRI and 42 genes showing more than a fourfold change. Of the eight genes encoding proteins with immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that bind to Ptpn6, three were upregulated, and five were downregulated. We found that for the differentially expressed genes (DEGs) with a fold change >2, the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were the cell division pathway and peroxisome-proliferator activated receptor PPARα signaling pathways. Furthermore, the downregulated genes of the PPARα signaling pathway were mainly related to fatty acid absorption and degradation. Using an agonist of the PPARα signaling pathway, fenofibrate, we found that renal IRI was significantly attenuated in Ptpn6 +/mev mice. In summary, our results show that insufficiency of SHP-1 inhibits the expression of genes in the PPARα signaling pathway, thereby leading to increased reactive oxygen species (ROS) and exacerbating the renal IRI. The PPARα signaling agonist fenofibrate partially attenuates renal IRI induced by SHP-1 insufficiency.

Colistin sulfate for decontamination of preservation fluid in kidney transplantation to decrease the incidence of donor-derived infections caused by multidrug-resistant Gram-negative bacteria.

BACKGROUND: Preservation fluid (PF) contamination, especially by multidrug-resistant (MDR) Gram-negative bacteria (GNB), poses a high risk of donor-derived infection (DDI) and severe clinical outcomes. We sought to determine whether the use of colistin sulfate to decontaminate PF in kidney transplantation can decrease the incidence of probable DDI (p-DDI) caused by MDR GNB. METHODS: In a retrospective study of 916 recipients who received deceased donation, 864 PF samples were collected and cultured, and microbiological contaminants were recorded with the recipients' clinical data and outcomes. From March 2016 to May 2019, 624 samples were decontaminated with ceftizoxime, and from June 2019 to March 2021, 240 samples were decontaminated with colistin sulfate. Between-group comparisons were performed to assess the ability of the two decontamination regimens to decrease the incidence of p-DDI, especially MDR GNB-related infection. RESULTS: The overall PF contamination rate was 54.51% (471/864), and 80 samples were positive for MDR GNB contamination. All p-DDIs occurred in the ceftizoxime group (p < 0.001), and 67.65% of p-DDIs were MDR GNB-related. In the ceftizoxime group, 23 of 61 cases of MDR GNB contamination led to related p-DDIs, while none occurred in the colistin sulfate group (p = 0.002). Among the 23 patients with p-DDIs, 5 died due to severe infection, and 2 experienced graft loss. CONCLUSIONS: The goal of decontamination should be to decrease the risk of MDR GNB-related p-DDI, and colistin sulfate could be an effective and feasible option.

Simultaneous and ultra-sensitive SERS detection of SLPI and IL-18 for the assessment of donor kidney quality using black phosphorus/gold nanohybrids.

Due to the global challenge of donor kidney shortage, expanding the pool of deceased donors has been proposed to include expanded criteria donors. However, the lack of methods to precisely measure donor kidney injury and predict the outcome still leads to high discard rates and recipient complications. As such, evaluation of deceased donor kidney quality is critical prior to transplantation. Biomarkers from donor urine or serum provide potential advantages for the precise measure of kidney quality. Herein, simultaneous detection of secretory leukocyte peptidase inhibitor (SLPI) and interleukin 18 (IL-18), two important kidney injury biomarkers, has been achieved, for the first time, with an ultra-high sensitivity using surface enhanced Raman scattering (SERS). Specifically, black phosphorus/gold (BP/Au) nanohybrids synthesized by depositing Au nanoparticles (NPs) onto the BP nanosheets serve as SERS-active substrates, which offer a high-density of inherent and accessible hot-spots. Meanwhile, the nanohybrids possess biocompatible surfaces for the enrichment of target biomarkers through the affinity with BP nanosheets. Quantitative detection of SLPI and IL-18 were then achieved by characterizing SERS signals of these two biomarkers. The results indicate high sensitivity and excellent reproducibility of this method. The limits of detection reach down to 1.53×10-8 mg/mL for SLPI and 0.23×10-8 mg/mL for IL-18. The limits of quantification are 5.10×10-8 mg/mL and 7.67×10-9 mg/mL for SLPI and IL-18. In addition, simultaneous detection of these biomarkers in serum was investigated, which proves the feasibility in biologic environment. More importantly, this method is powerful for detecting multiple analytes inheriting from excellent multiplexing ability of SERS. Giving that the combined assessment of SLPI and IL-18 expression level serves as an indicator of donor kidney quality and can be rapidly and reproducibly conducted, this SERS-based method holds great prospective in clinical practice.

SIRT3 protects kidneys from ischemia-reperfusion injury by modulating the DRP1 pathway to induce mitochondrial autophagy.

Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) and may influence renal graft survival. In this study, we investigate the involvement of SIRT3 and DRP1 in mitochondrial autophagy and AKI in a mouse model of IRI. Autophagy was detected in the absence of SIRT3, and hypoxic reoxygenation (H/R) experiments using renal tubular epithelial cells NRK52E were performed in vitro to validate these results. We found that autophagosomes increased following IRI and that the expression of autophagy-related genes was up-regulated. The inhibition of autophagy with 3-methyladenine exacerbated IRI, whereas the DRP1 inhibitor Mdivi-1 reversed this inhibition. Mdivi-1 did not reverse the inhibition of autophagy in the absence of SIRT3. During IRI, Mdivi-1 reduced autophagy and DRP1 expression, whereas SIRT3 overexpression attenuated this condition. Rescue experiment showed that autophagy was increased when both SIRT3 or DRP1 were over- or under-expressed or just DRP1 was under-expressed but expression was reduced when just SIRT3 was under-expressed. However, the expression of DRP1-related molecules was reduced when SIRT3 was overexpressed and when DRP1 was under-expressed. Taken together, these findings indicate that SIRT3 protects against kidney damage from IRI by modulating the DRP1 pathway to induce mitochondrial autophagy.

CIRBP promotes ferroptosis by interacting with ELAVL1 and activating ferritinophagy during renal ischaemia-reperfusion injury.

Renal ischaemia-reperfusion (IR) is a major cause of acute kidney injury (AKI). Cold-inducible RNA-binding protein (CIRBP) may contribute to AKI because its deficiency protects against renal IR injury in a mechanism believed to involve ferroptosis. We aimed to investigate whether ferroptosis is associated with CIRBP-mediated renal damage. The differential expression of CIRBP was examined in tubular epithelial (HK2) cells during hypoxia-reoxygenation (HR) or in response to erastin, an inducer of ferroptosis. CIRBP expression was increased in response to HR or erastin in HK2 cells but the silencing of CIRBP inhibited HR and erastin-induced ferroptosis together with ferritinophagy. We discovered an interaction between CIRBP and ELAVL1 using STRING software, which was verified through co-immunoprecipitation and fluorescence colocalization assays. We found that ELAVL1 is a critical regulator in the activation of ferritinophagy and the promotion of ferroptosis. HR or erastin also induced the expression of ELAVL1. An autophagy inhibitor (hydroxychloroquine) or si-ELAVL1 transfection reversed CIRBP-enhanced ferritinophagy activation and ferroptosis in HK2 cells under HR. Injection of anti-CIRBP antibody into a mouse model of IR inhibited ferroptosis and decreased renal IR injury in vivo. In summary, our results provide evidence that ferritinophagy-mediated ferroptosis could be responsible for CIRBP-enhanced renal IR injury.

SHP-1 inhibits renal ischemia reperfusion injury via dephosphorylating ASK1 and suppressing apoptosis.

Apoptosis of tubular epithelium cells (TECs) plays critical roles in renal ischemia reperfusion (I/R) injury, but the molecular regulatory mechanisms of apoptosis still require further investigation. Recently, phosphatase family members have been suggested to regulate multiple aspects of the injury and regeneration response. However, the roles of SHP-1, an important protein-tyrosine phosphatase, in the regulation of renal I/R injury remain unknown. Here, we found that SHP-1 knockdown in vivo significantly increased renal I/R injury and aggravated the apoptosis of TECs. Consistently, after SHP-1 knockdown in TECs in vitro, a sharp increase of apoptosis induced by cobalt dichloride was found. The protective role of SHP-1 was also validated in a TEC cell line stably overexpressing SHP-1. Mechanistically, the ASK1/MKK4/JNK pro-apoptosis signal was over activated after SHP-1 knockdown, and SHP-1 could bind to and dephosphorylate ASK1 to inhibit its activation, thus repressing apoptosis.

SIRT3 Protects Against Acute Kidney Injury via AMPK/mTOR-Regulated Autophagy.

Acute kidney injury (AKI), which involves the loss of kidney function caused by damage to renal tubular cells, is an important public health concern. We previously showed that sirtuin (SIRT)3 protects the kidneys against mitochondrial damage by inhibiting the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, attenuating oxidative stress, and downregulating proinflammatory cytokines. In this article, we investigated the role of autophagy, mediated by a mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), in the protective effect of SIRT3, against sepsis-induced AKI, in a mouse model of cecal ligation and puncture (CLP). The AKI in CLP mice was associated with the upregulation of autophagy markers; this effect was abolished in SIRT3- mice in parallel with the downregulation of phospho (p)-AMPK and the upregulation of p-mTOR. Pretreatment with the autophagy inhibitor 3-methyladenine (3-MA) or AMPK inhibitor compound isotonic saline (C), exacerbated AKI. SIRT3 overexpression promoted autophagy, upregulated p-AMPK and downregulated p-mTOR in CLP mice, attenuating sepsis-induced AKI, tubular cell apoptosis, and inflammatory cytokine accumulation in the kidneys. The blockage of autophagy induction largely abolished the protective effect of SIRT3 in sepsis-induced AKI. These findings indicate that SIRT3 protects against CLP-induced AKI by inducing autophagy through regulation of the AMPK/mTOR pathway.

Misdiagnosis Analysis of Cervical Minimal Deviation Adenocarcinoma: a Report of Three Rare Cases and Literature Review.

Cervical minimal deviation adenocarcinoma (MDA) is a rare variant of cervical adenocarcinoma that is difficult to diagnose due to the deep location, endogenous growth pattern, deceptively benign appearance of tumor cells, and lack of connection to human papillomavirus (HPV). Cytological evaluation and biopsies offer suboptimal detection and transvaginal sonography or Magnetic Resonance Imaging (MRI) only reveal multiple lesions that mimic multiple benign nabothian cysts. Besides, standard screening, diagnostic tools, and treatments are not established. Thus, MDA tends to be misdiagnosed with other gynecological diseases. In this study, we examine three cases with extensive abdominal metastasis and adhesions, which are not initially associated clinically with HPV and cervical malignancies. All cases were misdiagnosed as nabothian cysts, endometrial adenocarcinoma or ovarian cancer, though finally diagnosed as MDA by postoperative pathology. Delay in diagnosis and treatment can result in irreversible outcomes. Misdiagnoses are analyzed and suggestions for improving early detection are discussed with a brief review of the literature.

Establishment of specific cytotoxic T lymphocyte culture system and its inhibitory effect on ovarian cancer.

The present study aimed to establish a novel method for efficiently inducing cytotoxic T lymphocytes (CTLs) in vitro, in order to develop an immune-based therapy for suppressing and killing ovarian cancer cells with a high safety and efficacy. Peripheral blood mononuclear cells (PBMCs) were stimulated with CpG oligodeoxynucleotide (CpGODN) and ginsenoside Rg1, which were united as an immune adjuvant, and human epidermal growth factor receptor 2 (HER2/neu) antigen peptide, in order to establish a specific CTL culture system in vitro. Chromosome karyotype analysis, growth curve construction and flow cytometric analysis of immune phenotypes, including cluster of differentiation (CD)3, CD4 and CD8, were performed to characterize the stimulated PBMCs in vitro. Subsequently, SKOV3 ovarian cancer cells were treated with the specific CTL culture system in vitro, and MTT assays were performed to test the inhibitory and lethal effects of the CTLs on SKOV3 cells. The number of CTLs was significantly increased from day 7 of stimulation with the specific mixture (CpGODN, ginsenoside Rg1 and HER2/neu) (P<0.01), and plateaued on day 19. Following activation, the number of CD3+, CD3+CD4+ and CD3+CD8+ cells was significantly increased (P<0.01). The lymphocyte karyotype did not change following exposure to antigen. After treatment with the specific CTL system, the number of SKOV3 cells in the experimental group was significantly reduced compared with that in the control group (P<0.01). The results of the present study suggested that two novel immune adjuvants, CpGODN and ginsenoside Rg1, could be combined with the HER2/neu antigen peptide to establish a specific CTL culture system in vitro. This system demonstrated a high antigen specificity, safety and proliferative ability, and exerted significant lethal and inhibitory effects on SKOV3 cells in vitro.

Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury.

Acute kidney injury (AKI) is a rapid loss of kidney function characterized by damage to renal tubular cells driven by mitochondrial dysregulation and oxidative stress. Here, we used a murine caecal ligation and puncture (CLP) model of sepsis-induced AKI to study the role of sirtuin 3 (SIRT3), a NAD(+) dependent deacetylase critical for the maintenance of mitochondrial viability, in AKI-related renal tubular cell damage and explored the underlying mechanisms. CLP induced alterations in kidney function and morphology were associated with SIRT3 downregulation, and SIRT3 deletion exacerbated CLP-induced kidney dysfunction, renal tubular cell injury and apoptosis, mitochondrial alterations, and ROS production in a knockout mouse model. SIRT3 deletion increased the CLP-induced upregulation of the NLRP3 inflammasome and apoptosis-associated speck-like protein, resulting in the activation of oxidative stress, increased production of the proinflammatory cytokines interleukin (IL)-1ß and IL-18, and the enhancement of apoptosis, and these effects were reversed by antioxidant NAC. Our results suggest that SIRT3 plays a protective role against mitochondrial damage in the kidney by attenuating ROS production, inhibiting the NRLP3 inflammasome, attenuating oxidative stress, and downregulating IL-1ß and IL-18.

Cotyledonoid dissecting leiomyoma of the uterus: A report of four cases and a review of the literature.

Cotyledonoid dissecting leiomyoma (CDL), also termed Sternberg tumor, is a variant of uterine leiomyoma that is rarely diagnosed by clinical evaluation. At present, ~43 cases of CDL have been reported in the literature written in the English language. Due to the distinctive grapelike gross appearance of an exophytic mass resembles placental tissue, CDL is often misdiagnosed clinically as an ovarian tumor or uterine sarcoma. Therefore, an awareness of the features of the disease is important to prevent misdiagnosis and overtreatment. The present study reports 4 cases of CDL of the uterus that were treated at the Second Hospital of Jilin University between January 2009 and December 2011. All 4 patients in the current study presented with a palpable asymptomatic pelvic mass, which was detected during physical examinations, and cancer antigen 125 tumor marker levels that were within the normal range. The exploratory laparotomy of the 4 patients revealed lobulated tumors with a grapelike appearance extending from the lateral uterine wall into the ligament or the adjacent tissues. The frozen section and postoperative pathology were diagnosed as CDL. A total abdominal hysterectomy was performed in the first case of a 55-year-old woman that had been in menopause for 7 years. The patient was well and showed no evidence of disease subsequent to 48 months of follow-up. A total abdominal hysterectomy and right salpingo-oophorectomy were performed in the second case of a 43-year-old woman, who was well and showed no evidence of disease subsequent to 26 months of follow-up. A subtotal abdominal hysterectomy and bilateral salpingectomy were performed in the third case of a 37-year-old woman, who was well and showed no evidence of disease subsequent to 27 months of follow-up. A total abdominal hysterectomy and right-salpingectomy were performed with the removal of a retroperitoneal fibroid extension in the fourth case of a 48-year-old woman, who was well and showed no evidence of disease subsequent to 32 months of follow-up.

Optimizing the utilization of kidneys from small pediatric deceased donors under 15 kg by choosing pediatric recipients.

Currently, most kidneys from small pediatric deceased donors are transplanted into adult recipients (i.e., PTA). However, due to the weight mismatch, there is a high discard rate and a high ratio of EBKTs if adopting PTA. Here, we sought both to optimize utilization of these challenging but scarce donor grafts by selecting pediatric recipients and to characterize the feasibility and efficacy of this PTP allocation strategy. From February 2012 to October 2014, kidneys from 27 infant donors ≤ 15 kg were procured and distributed to 38 pediatric candidates in our center. The grafts were utilized for EBKT if the donor weighed 2.5-5 kg and for SKT if the donor weighed 5-15 kg, leading to 10 EBKTs and 28 SKTs. The overall utilization rate from small pediatric deceased donors was 94.12%. After a follow-up of 3-26 months, the graft survival rate was 89.47%, with four graft losses due to vascular thrombosis. Kidneys from low-body-weight donors should be applied to pediatric recipients, and the kidneys from infant donors ≥ 5 kg can be used in single-kidney-transplant procedures at experienced centers to optimize utilization.

Tri-iodothyronine preconditioning protects against liver ischemia reperfusion injury through the regulation of autophagy by the MEK/ERK/mTORC1 axis.

BACKGROUND AND OBJECTIVES: The autophagy pathway has previously been suggested as an important protective factor in liver injury. The purpose of this study is to demonstrate the protective, autophagy-modulating effect of tri-iodothyronine (T3) on liver ischemia reperfusion injury. METHODS: Liver ischemia reperfusion was induced in male C57BL/6 mice after T3 administration. Liver function, histological damage, inflammatory infiltration, cytokine production, oxidative stress, antioxidant capacity, autophagy changing, and autophagy-associated intracellular signaling pathway were assessed to evaluate the impact of antecedent T3 treatment on ischemia reperfusion induced liver injury. RESULTS: After 70% liver ischemia reperfusion injury, mice that were preconditioned with appropriate T3 displayed significantly preserved liver function, less histological damage, less apoptosis, and enhanced antioxidant capacity. Further studies revealed that mice which were preconditioned with T3 before IR induction exhibited an increased level of autophagy mediated by MEK/ERK/mTORC1. CONCLUSIONS: Our results provide the first line of evidence indicating that antecedent T3 injection can provide protection for the liver against ischemia reperfusion induced injury by enhancing autophagy. Therefore, T3 preconditioning could be a potential therapeutic approach to prevent liver IR injury related to various clinical conditions.