TIM-3 regulates the proliferation by BDNF-mediated PI3K/AKT axis in the process of endometriosis.

BACKGROUND: T cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) initially discovered on the surface of Th1 cells, negatively regulates immune responses and mediates apoptosis of Th1 cells. An increasing number of studies have since shown that TIM-3 is crucial in the genesis and development of immune diseases, cancers, and chronic infectious illnesses. However, the effect of TIM-3 on endometriosis is still unknown. METHODS: Quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry were used to measure TIM-3 levels in endometriosis. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, colony-forming, Transwell® migration, Matrigel® invasion, and flow cytometry assays were used to explore the function of TIM-3 in vitro, and xenograft experiments in nude mice were used to assess its role in vivo. According to the RNA seq, brain-derived neurotrophic factor (BDNF) was screened. The involvement of specific proliferation-related signaling molecules was determined by transfecting a plasmid and adding an inhibitor in vivo and in vitro. RESULTS: TIM-3 mRNA and protein expression levels were significantly higher in eutopic and ectopic endometrial tissues than in normal endometrial tissues. By examining the effects of TIM-3 overexpression and knockdown on cell proliferation, migration, and invasion in vitro, and lesions formation in vivo, we found that the expression of TIM-3 was positively correlated with cell proliferation and clone formation in vitro, as well as lesions growth in nude mice. By adding the phosphatidylinositol 3 kinase/protein kinase B(PI3K/AKT) pathway inhibitor LY294002 and knocking down PI3K, we further verified that TIM-3 promotes proliferation in vivo and in vitro via the PI3K pathway. By transfecting the plasmid into ESC cells and gave inhibitors to endometriotic rats models, we tested that TIM-3 regulates the proliferation by BDNF-mediated PI3K/AKT axis. CONCLUSION: TIM-3 can promote the proliferation of endometriosis by BDNF-mediated PI3K/AKT axis in vivo and in vitro, which may provide a new therapeutic target for the treatment of endometriosis.

Exosomal miR-146a-5p derived from human umbilical cord mesenchymal stem cells can alleviate antiphospholipid antibody-induced trophoblast injury and placental dysfunction by regulating the TRAF6/NF-κB axis.

Exosomes originating from human umbilical cord mesenchymal stem cells (hucMSC-exos) have become a novel strategy for treating various diseases owing to their ability to regulate intercellular signal communication. However, the potential of hucMSC-exos to improve placental injury in obstetric antiphospholipid syndrome and its underlying mechanism remain unclear. Our objective was to explore the potential application of hucMSC-exos in the treatment of obstetric antiphospholipid syndrome and elucidate its underlying mechanism. In our study, hucMSC-exos ameliorated the functional impairment of trophoblasts caused by antiphospholipid antibodies in vitro and attenuated placental dysfunction in mice with obstetric antiphospholipid syndrome by delivering miR-146a-5p. Exosomal miR-146a-5p suppressed the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibited the activation of NF-κB signaling, leading to the down-regulation of IL-1ß and IL-18 to rescue inflammation and modulation of Cleaved-CASP3, BAX, and BCL2 to inhibit apoptosis in HTR8/SVneo cells and mice placenta. This study identified the potential molecular basis of how hucMSC-exos improved antiphospholipid antibody-induced placental injury and highlighted the functional importance of the miR-146a-5p/TRAF6 axis in the progression of obstetric antiphospholipid syndrome. More importantly, this study provided a fresh outlook on the promising use of hucMSC-exos as a novel and effective treatment approach in obstetric antiphospholipid syndrome.

Macrophages release IL11-containing filopodial tip vesicles and contribute to renal interstitial inflammation.

Macrophage filopodia, which are dynamic nanotube-like protrusions, have mainly been studied in the context of pathogen clearance. The mechanisms by which they facilitate intercellular communication and mediate tissue inflammation remain poorly understood. Here, we show that macrophage filopodia produce a unique membrane structure called "filopodial tip vesicle" (FTV) that originate from the tip of macrophages filopodia. Filopodia tip-derived particles contain numerous internal-vesicles and function as cargo storage depots via nanotubular transport. Functional studies indicate that the shedding of FTV from filopodia tip allows the delivery of many molecular signalling molecules to fibroblasts. We observed that FTV derived from M1 macrophages and high glucose (HG)-stimulated macrophages (HG/M1-ftv) exhibit an enrichment of the chemokine IL11, which is critical for fibroblast transdifferentiation. HG/M1-ftv induce renal interstitial fibrosis in diabetic mice, while FTV inhibition or targeting FTV IL11- alleviates renal interstitial fibrosis, suggesting that the HG/M1-ftvIL11 pathway may be a novel mechanism underlying renal fibrosis in diabetic nephropathy. Collectively, FTV release could represent a novel function by which filopodia contribute to cell biological processes, and FTV is potentially associated with macrophage filopodia-related fibrotic diseases. Video Abstract.

Early diagnosis strategy of calciphylaxis in dialysis patients.

Calciphylaxis, a rapidly progressive and potentially life-threatening vascular calcification syndrome that clinically presents with persistently painful, ulcerative, or necrotizing skin lesions in multiple parts of the body, is predominantly observed in patients treated with dialysis. Early diagnosis of calciphylaxis is a key measure for reducing high disability and mortality. At present, there is no unified diagnostic standard for calciphylaxis, and there is a lack of effective early screening strategies. This paper summarized and discussed the diagnostic accuracy of calciphylaxis based on the latest research worldwide. We propose a modified strategy for the early diagnosis of calciphylaxis, which is suitable for dialysis patients to help clinicians better identify such disease and improve prognosis.

Vascular, valvular and kidney calcification manifested in mouse models of adenine-induced chronic kidney disease.

BACKGROUND: Ectopic calcification (EC) involves multiple organ systems in chronic kidney disease (CKD). Previous CKD-animal models primarily focused on a certain histological abnormality but did not show the correlation with calcified development among various tissues. This study compared calcified deposition in various tissues during CKD progression in mice. METHODS: Male 8-week-old C57BL/6J mice were randomly allocated to the seven groups: a basic, adenine, high-phosphorus, or adenine and high-phosphorus diet for 12-16 weeks (Ctl16, A12, P16, or AP16, respectively); an adenine diet for 4-6 weeks; and a high-phosphorus or adenine and high-phosphorus diet for 10-12 weeks (A6 + P10, A4 + P12, or A4 + AP12, respectively). RESULTS: Compared to the Ctl16 mice, the P16 mice only displayed a slight abnormality in serum calcium and phosphorus; the A12 mice had the most serious kidney impairment; the A4 + P12 and A6 + P10 mice had similar conditions of CKD, mineral abnormalities, and mild calcification in the kidney and aortic valves; the A4 + AP12 and AP16 groups had severe kidney impairment, mineral abnormalities and calcification in the kidneys, aortic valves and aortas. Furthermore, calcium-phosphate particles were deposited not only in the tubulointerstitial compartment but in the glomerular and tubular basement membrane. The elemental composition of EC in various tissues matched the calcification of human cardiovascular tissue as determined by energy dispersive spectroscopy. CONCLUSIONS: The severity of CKD was unparalleled with the progression of mineral metabolism disorder and EC. Calcification was closely related in different tissues and observed in the glomerular and tubular basement membranes.

Previous CKD-animal models primarily focused on a certain histological abnormality but lacked investigations of the interplay of EC in various tissues. This study compared calcified deposition in several tissues during CKD progression in mice, which was closely related. The severity of CKD was unparalleled with the development of ectopic calcification. Glomerular and tubular basement membrane calcification was detected in CKD mice, which has been considered extremely rare in clinical.

Association between insomnia and frailty in older population: A meta-analytic evaluation of the observational studies.

INTRODUCTION: Poor sleep quality has been suggested as a risk factor of frailty. However, previous studies that evaluated the association between insomnia and frailty in older population showed inconsistent results. We performed a meta-analysis to comprehensively evaluate the association. METHODS: Observational studies related to the aim of the meta-analysis were identified by search of PubMed, Embase, and Web of Science databases. A random-effect model incorporating the potential between-study heterogeneity was used to pool the results. RESULTS: Twelve studies including 16,895 old people contributed to the meta-analysis. Pooled results suggested a significant association between insomnia and frailty in the older population (odds ratio [OR]: 1.95, 95% confidence interval [CI]: 1.52-2.41, p < .001; I2  = 80%). Subgroup analyses showed consistent association between different symptoms of insomnia and frailty, including difficulty in falling asleep (OR: 1.45), difficulty in maintaining sleep (OR: 1.23), early morning awakening (OR: 1.21), and non-restorative sleep (OR: 1.84, p for subgroup difference = .15). Results were also consistent for subgroup analyses according to the study country, sample size, cutoffs of age for defining the older population, proportions of men, diagnostic criteria for frailty, adjustment of depression, and scores of study quality (p for subgroup difference all > .05). However, a stronger association was observed for insomnia detected with the Athens Insomnia Scale (OR: 2.92) than that with Pittsburgh Sleep Quality Index (OR: 1.30) or self-reporting (OR: 1.60, p for subgroup difference = .002). CONCLUSION: Insomnia is independently associated with frailty in the older population.

PEI-coated Prussian blue nanocubes as pH-Switchable nanozyme: Broad-pH-responsive immunoassay for illegal additive.

Nanozymes are commonly used in the construction of immunosensors, yet they are generally susceptible to pH condition, which greatly hindered their practical use. To break the limitation of pH conditions, polyethyleneimine-coated Prussian blue nanocubes (PBNCs@PEI) were synthesized as the pH-switchable nanozyme, which can show peroxidase-like and catalase-like activity in acidic and alkaline condition, respectively. Besides, the modification of PEI can largely improve the catalytic activity of PBNCs. Herein, the pH-switchable catalytic property of PBNCs@PEI was used to construct the dual-mode immunosensor for the detection of illegal additive, rosiglitazone. In acidic condition, PBNCs@PEI showed excellent peroxidase-like activity, which can trigger the colorimetric reaction of Au nanostars with TMB2+/CTAB. In alkaline condition, the catalase-like activity of PBNCs@PEI prevailed, thus the decomposition of H2O2 can generate O2 to initiate the aerobic oxidation of 4-chloro-1-naphthol (4-CN), which can decrease the fluorescence intensity of 4-CN. Based on the competitive immunoassay, both the localized surface plasmon resonance wavelength shift of Au nanostars and the fluorescence intensity change of 4-CN were quantitatively related with rosiglitazone concentration, thus shedding a new light on the construction of broad-pH-responsive immunosensor. Besides, a smart device was developed to transfer the chroma value of Au nanostars into the RSG concentration, making this sensor a promising method in on-site and point-of-care detection.

Long-term survivors demonstrate superior quality of life after haploidentical stem cell transplantation to matched sibling donor transplantation.

BACKGROUND: It has been well-documented that haplo-identical hematopoietic stem cell transplantation (HID-HSCT) can provide outcomes comparable to conventional matched sibling donor (MSD) HSCT, however, little is known about the effects on quality of life (QoL) in long-term survivors. This study is to investigate the differences in longitudinal performance of QoL between HID and MSD HSCT using a comprehensive assessment system. METHODS: This prospective study enrolled consecutive patients who had received allogenic-HSCT (allo-HSCT) between January 2018 and December 2019 in our center. All patients were informed to complete QoL questionnaires including the Mos 36-Item Short-Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT, version 4), using an online applet, before transplantation and at scheduled time points after transplantation. The linear mixed-effects model was used to analyze the variation trend of different dimensions of both SF-36 and FACT-BMT with different follow-up times. RESULTS: Of the 425 participants, recipients of HID and MSD who survived more than 1 year (n = 230) were included in the final analysis of QoL (median age [range]: 36, [15, 66]). The 3 year overall survival (OS) of HID and MSD was 82.42% and 86.46%, respectively. QoL was assessed using both SF-36 and FACT-BMT and there was longitudinal recovery with clinical significance in the cohort. Compared to MSD-HSCT patients, HID-HSCT recipients demonstrated superior QoL performance in some subscales describing physical and mental wellness. Specifically, the difference in physical performance is more remarkable using FACT-BMT whereas that in mental wellness is more significant using SF36. In the subsequent stratified analysis, patients with a history of aGVHD or CMV reactivation demonstrated inferior QoL. CONCLUSIONS: Long-term survivors of HID HSCT achieved better QoL in some sub-scales compared to MSD HSCT. In addition, SF-36 and FACT-BMT demonstrated different performance thus combination of both improved capacity of the evaluation system.

Prevalence and Clinical Characteristics of Calciphylaxis in Chinese Hemodialysis Patients.

Background: Calciphylaxis is a grievous life-threatening vascular disease that commonly affects dialysis population. This is the first epidemiological survey of calciphylaxis initiated in China. Methods: In the cross-sectional survey, a stratified sampling method was used to select 24 dialysis centers in Jiangsu Province. The participants were all adult patients in each center who had been on hemodialysis for more than 6 months. Calciphylaxis patients were uniformly diagnosed based on characteristic skin lesions and histopathological features. Results: A total of 3,867 hemodialysis patients (average age of 55.33 ± 13.89 years; 61.81% of males) were included. Forty eight cases were diagnosed with calciphylaxis, and prevalence was 1.24%. Among calciphylaxis patients, 33 cases were male, and the average age and median dialysis duration were 53.85 ± 15.17 years and 84.00 (48.00, 138.75) months, respectively. Skin biopsy was performed in 70.83% of calciphylaxis patients, and positive rate was 64.71%. Meanwhile, the positive rate of bone scintigraphy in the diagnosis of calciphylaxis was 62.5%. The prevalence of hyperparathyroidism in case group was as high as 72.92% with longer duration, and 42.86% had undergone parathyroidectomy. Multivariate analysis indicated that increased BMI, prolonged dialysis duration, warfarin therapy, hyperparathyroidism, diabetes, tumors, low serum albumin and high serum alkaline phosphatase levels were high-risk factors for calciphylaxis. Conclusions: The prevalence of calciphylaxis in Chinese hemodialysis patients was 1.24% according to regional epidemiological survey, but its actual prevalence would be presumably far beyond present data. It's urgent to improve clinical understanding of calciphylaxis, and multifaceted diagnostic methods should be applied for early screening.

Use of the optimized sodium thiosulfate regimen for the treatment of calciphylaxis in Chinese patients.

BACKGROUND: Sodium thiosulfate (STS) can be used to treat patients diagnosed with calciphylaxis, which is a rare life-threatening syndrome. However, our patients treated with the recommended STS regimen presented with serious adverse events, resulting in treatment withdrawal. Then an optimized STS regimen was used to increase the tolerance of patients to STS and improve treatment continuation. The curative effect of the new regimen is not yet definite. Therefore, this study aimed to evaluate the response to the use of the optimized STS regimen for the treatment of calciphylaxis in Chinese patients during the first three courses of treatment. METHODS: Demographic, clinical, and laboratory data were retrospectively collected on 31 calciphylaxis patients with chronic kidney disease (CKD) or end-stage kidney disease (ESKD) treated with the optimized STS regimen. The primary outcome was a clinical improvement. The secondary outcomes included survival rate and adverse events. RESULTS: Twenty-five patients (over 80%) achieved clinical improvement considering improvement or nonspecific changes of skin lesions (80.65%) and pain relief (100%). Furthermore, 54.84% of patients did not experience any adverse events and none died from complications. During a median follow-up of 9 months (interquartile range 4‒19), 27 patients (87.10%) survived; additionally, 13 patients (41.94%) survived after a one-year follow-up period. CONCLUSION: The optimized STS regimen is relatively safe, associated with satisfactory outcomes, and well tolerated by patients for short to medium treatment duration. Hence, it is a promising approach for the treatment of patients diagnosed with calciphylaxis.

TRIM27 regulates the expression of PDCD4 by the ubiquitin­proteasome pathway in ovarian and endometrial cancer cells.

Programmed cell death 4 (PDCD4) is regarded as an important tumor suppressor that is lowly expressed or deleted in numerous human types of cancer, including ovarian and endometrial cancer. Tripartite motif­containing 27 (TRIM27) is closely related to the occurrence and development of tumors and is highly expressed in numerous types of cancer such as ovarian and endometrial cancer. PDCD4 can be degraded through ubiquitination, while TRIM27 has the E3 ubiquitin ligase activity. However, whether TRIM27 may regulate the expression of PDCD4 by ubiquitination effect remains unclear. In the present study, the expression of PDCD4 and TRIM27 in different ovarian and endometrial cancer cell lines was detected by reverse transcription­quantitative PCR (RT­qPCR), western blotting and immunocytochemistry. The impact of TRIM27 overexpression and knockdown on PDCD4 expression and the effective mechanism of TRIM27 regulating PDCD4 expression were also investigated in vitro by RT­qPCR, western blotting, co­immunoprecipitation assay, Transwell migration and Matrigel invasion assays. The results showed that the expression of TRIM27 and PDCD4 had a negative association at the protein level, and the distribution of TRIM27 and PDCD4 proteins had a phenomenon of co­localization in different ovarian and endometrial cancer cell lines. TRIM27 promoted the degradation of PDCD4 through the ubiquitin­proteasome pathway. To sum up, TRIM27 could increase the migration and invasion of ovarian and endometrial cancer cells by promoting the ubiquitination and degradation of PDCD4. The present findings may provide a new target for the treatment of ovarian and endometrial cancer.

Identifying subcutaneous tissue microcalcification by Fluo-3 AM imaging in cutaneous calciphylaxis.

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is typically characterized by subcutaneous tissue calcification and excruciatingly painful cutaneous lesions with high mortality. It is critical for dermatologists to make early diagnosis and appropriate management, yet currently only 56% of calciphylaxis cases are correctly diagnosed by conventional histological stain1. Specially, the identification of subtle calcium deposits of subcutaneous can be challenging but is believed crucial for early diagnosis of calciphylaxis2. More sensitive calcification staining is in high demand. In this study, Fluo-3 AM was found to be a rapid, sensitive and reliable fluorescent probe for the detection of calcium deposits and could be a promising diagnostic tool for calciphylaxis.

Layered manganese dioxide nanoflowers with Cu2+and Bi3+ intercalation as high-performance cathode for aqueous zinc-ion battery.

For aqueous zinc ion batteries (AZIBs), birnessite MnO2 (δ-MnO2) has been intensively used as one of the most potential cathode materials due to its layered structure, which is conducive to reversible insertion/extraction of zinc ions. However, δ-MnO2 has not been attained for zinc ion storage performance because of its inferior conductivity as well as the undesirable structural degradation upon charge/discharge cycling. Herein, we have designed two kinds of cathode materials of Cu0.06MnO2·1.7H2O (CuMO) and Bi0.09MnO2·1.5H2O (BiMO) with nanoflower structure for the first time by a facile one-step hydrothermal method, which will be applied for high-performance AZIBs.The pre-intercalated metal ions and water molecules serve as pillars to sustain the layered structures, improving the stability of these materials. Particularly, the CuMO may experience a replacement reaction except the zinc ion insertion/extraction to form metallic Cu during the cycling process, which can enhance the diffusion rate of Zn2+, thus resulting in an excellent electronic conductivity and exhibiting remarkable specific capacities. Furthermore, a pseudo-capacitance that is derived from the surface-adsorbed Cu2+and Bi3+ also contributes to the improved electrochemical performances. The reversible capacity of CuMO is estimated as 350 mAh g-1 at 0.5 A g-1, which is much higher than that of pure δ-MnO2 (190 mAh g-1 at 0.5 A g-1). However, BiMO demonstrates long-term cycling stability, maintaining a capacity of 114.5 mAh g-1 even after 1100 charged-discharged cycles at 1 A g-1. The capacity retention is found to be as high as 98.6%, which is much higher than that of pure δ-MnO2 (53.8%). This can contribute to the development of high-performance AZIBs and the application of metal ion pre-intercalation methods in other areas.

Radiomics-based method for diagnosis of calciphylaxis in patients with chronic kidney disease using computed tomography.

Calciphylaxis is a rare, life-threatening condition that affects patients with chronic kidney disease (CKD) undergoing dialysis. Skin biopsy as the gold standard causes ulceration, bleeding, or infection. This study aimed to develop radiomic methods using CT as a noninvasive method for calciphylaxis diagnosis. The confirmed calciphylaxis patients (Group I), pathologically confirmed non-calciphylaxis patients (Group II), and CKD patients (Group III) from October 1, 2017, to November 30, 2019, were enrolled. Training: 70% of patients of Group I and all Group III. Test: 30% of patients of Group I and all Group II. ROI was set at the skin lesion including the soft tissue. First-order and texture features were extracted from each lesion unit. CT-based radiomic models were on the basis of logistic regression (LR) and support vector machine (SVM). Additionally, model performance was evaluated in the test dataset and compared with the plain radiography and bone scintigraphy. In total, 124 lesions and 38 lesions were identified in training and test datasets. Radiomic models were effective in detecting calciphylaxis in patients with CKD, with AUCs of 0.93 (95% CI: 0.924-0.953) and 0.93 (95% CI: 0.921-0.953) (SVM and LR) in test. The SVM model manifested a sensitivity and specificity of 0.89 and 0.8, and 0.78 and 0.90, at high-sensitivity and high-specificity operating points, respectively. Similar performance was found in the LR model. Radiomic models were more effective than plain radiography and bone scintigraphy (Delong test, P<0.05). Verification studies showed the features which manifested the real variability of lesions. In this research, it primarily developed a radiomic method for noninvasive detection of calciphylaxis in patients with CKD. Through this method, calciphylaxis can be detected when invasive procedures are not feasible.

Oral Treponema denticola Infection Induces Aß1-40 and Aß1-42 Accumulation in the Hippocampus of C57BL/6 Mice.

Accumulation of amyloid-ß (Aß) in the brain is a central component of pathology in Alzheimer's disease. A growing volume of evidence demonstrates close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aß remain to be unclear. In this study, we demonstrated that T. denticola was able to enter the brain and act directly on nerve cells resulting in intra- and extracellular Aß1-40 and Aß1-42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both ß-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of ß-secretase, as well as DAPT, an inhibitor of γ- secretase, were found to be able to inhibit the effect of T. denticola on Aß accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aß1-42 and Aß1-40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and presenilin 1.

Risk factors for calciphylaxis in Chinese hemodialysis patients: a matched case-control study.

INTRODUCTION: Calciphylaxis is a rare but potentially fatal disease commonly occurred in dialysis patients. Despite some previous studies on risk factors for calciphylaxis, there is still a lack of data from Chinese population. METHODS: The retrospective matched case-control study about calciphylaxis was performed in Zhongda Hospital affiliated to Southeast University. The case group involved 20 hemodialysis patients who were newly diagnosed with calciphylaxis from October 2017 to December 2018. The 40 noncalciphylaxis patients undergoing dialysis with the same age and duration of dialysis were randomly selected as controls. RESULTS: Most of calciphylaxis patients were male and elderly, while overweight people were more susceptible to the disease. Although incidence of secondary hyperparathyroidism was higher in calciphylaxis patients, the differences in duration of elevated serum intact parathyroid hormone (iPTH) and its highest value did not reach statistical significance compared with controls. No significant difference in warfarin therapy was discernible between two groups. The univariate regression analysis indicated that male, score of use of activated vitamin D and its analogues, corrected serum calcium level, serum phosphate, Ca × P product, iPTH, albumin, and alkaline phosphatase (ALP) level were significantly associated with calciphylaxis. Elevated levels of serum phosphate (OR 4.584, p = 0.027) and ALP (OR 1.179, p = 0.036), decreased level of serum albumin (OR 1.330, p = 0.013) were independent risk factors after multivariate analysis. CONCLUSION: This is the first report of risk factors associated with calciphylaxis in China. Increased levels of serum phosphate and ALP, decreased level of serum albumin were vital high-risk factors for calciphylaxis in Chinese hemodialysis population.

Potential effect of sodium thiosulfate in calciphylaxis: remission of intractable pain.

Calciphylaxis, a rare disease mainly seen in patients with chronic kidney disease, is characterised by ischaemic skin damages and excruciating pain. Calciphylaxis has poor prognosis which often results in amputation and high mortality. Although guidelines for the management of calciphylaxis are not available, sodium thiosulfate has shown efficacy in many clinical reports. We report the case of a 64-year-old advanced calciphylaxis male patient who had two amputations due to intolerable pain manifested as deteriorating ulcer. After he was treated with intravenous sodium thiosulfate (STS), his pain was significantly relieved with a healing trend of the big wound. One more amputation for the remission of intractable pain was avoided. The treatment experience indicates that sodium thiosulfate is of great value in quick pain relief and reducing suffering of calciphylaxis patients.

TIPE2 inhibits the migration and invasion of endometrial cells by targeting ß-catenin to reverse epithelial-mesenchymal transition.

STUDY QUESTION: Do changes in tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TIPE2) levels in endometrium of patients with adenomyosis alter the proliferation, migration and invasion ability of endometrial cells? SUMMARY ANSWER: TIPE2 expression levels were low in eutopic and ectopic endometrium of adenomyosis patients, and TIPE2 inhibited the migration and invasion of endometrial cells, mainly by targeting ß-catenin, to reverse the epithelial-mesenchymal transition (EMT). WHAT IS KNOWN ALREADY: Adenomyosis is a benign disease, but it has some pathophysiological characteristics similar to the malignant tumor. TIPE2 is a novel negative immune regulatory molecule, and it also participates in the development of malignant tumors. STUDY DESIGN, SIZE, DURATION: Control endometrium (n = 48 women with non-endometrial diseases) and eutopic/ectopic endometrium from patients with adenomyosis (n = 50), human endometrial cancer cell lines, and primary endometrial cells from the eutopic endometrium of adenomyosis patients were used in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: The expression level of TIPE2 mRNA and protein in the eutopic/ectopic endometrial tissues of adenomyosis patients and control endometrium was determined by quantitative RT-PCR (qRT-PCR), western blot and immunohistochemistry. The effects of TIPE2 overexpression and knockdown on the proliferation, migration and invasion of endometrial cell lines and primary adenomyotic endometrial cells were determined using a cell counting kit-8, 5-ethynyl-2'-deoxyuridine assay, colony-forming assay, transwell migration assay and matrigel invasion assay. The expression of EMT-related markers and signal molecules was detected by western blot. The interaction between TIPE2 and ß-catenin was detected by co-immunoprecipitation and laser confocal microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: The mRNA and protein expression levels of TIPE2 in the eutopic and ectopic endometrial tissues of adenomyosis patients were significantly downregulated compared with the control endometrium (P Ë‚ 0.01). TIPE2 could bind to ß-catenin and inhibit the nuclear translocation of ß-catenin, downregulate the expression of stromal cell markers, upregulate the expression of glandular epithelial cell markers, decrease the occurrence of epithelial-mesenchymal transition (EMT) and suppress the migration and invasion of endometrial cells (P Ë‚ 0.01). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, the experiments were performed only in eutopic and ectopic endometrial tissues, endometrial cancer cell lines and primary adenomyotic endometrial cells. A mouse model of adenomyosis will be constructed to detect the effects of TIPE2 in vivo. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that TIPE2 is involved in the development of adenomyosis, which provides a potential new diagnostic and therapeutic strategy for the treatment of adenomyosis. STUDY FUNDINGS/COMPETING INTEREST(S): This present study was supported by grants from the National Natural Science Foundation of China (81471437, 81771554), Natural Science Foundation of Shandong (ZR2018MH013), Science and technology development plan provided by Health and Family Planning Committee in Shandong (2014-25). The authors declare that they have no conflicts of interest.

A Case of Early Calciphylaxis Diagnosed by Bone Scan.

Calcium uremic aortic disease (calciphylaxis) has long been considered as a rare, life-threatening small vessel disease. The diagnosis of calciphylaxis depends mainly on clinical symptoms and high risk factors, and skin biopsy can be used to confirm the diagnosis. However, noninvasive testing methods are still the focus of exploration currently. There is increasing evidence that bone scintigraphy is helpful in the diagnosis of calciphylaxis, especially for assessing the involvement of muscles and internal organs. Here, we describe a pathology-proven case of calciphylaxis case and the corresponding imaging findings on Tc-99 m MDP bone scan imaging.