[The Research Progress in the Diagnosis and Treatment of Primary Intestinal Diffuse Large B-cell Lymphoma--Review].

Primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) is clinically rare, but in recent years, with the gradual maturity of pathology and molecular biology technology, its incidence rate and diagnosis rate have also increased. Due to the lack of specificity of the clinical symptoms of PI-DLBCL, it is easy to misdiagnose and miss the diagnosis, and there is no consensus on the best treatment of PI-DLBCL in clinical practice. Therefore, by retrieving the latest literature at home and abroad, this review systematically discusses the pathogenesis, clinical manifestations, diagnostic criteria, treatment and prognosis of PI-DLBCL, in order to improve the understanding of rare PI-DLBCL in hematology and oncology, and provide reference for basic research and clinical diagnosis and treatment of PI-DLBCL.

Analysis of Sex Hormones, Insulin Dosage, and Risk Factors Associated With Male Diabetic Patients.

The purpose of this study is to assess the influence of sex hormones and other indicators on risk factors for hypercoagulable states in male patients with type 2 diabetes mellitus. Ninety-two diabetic patients were divided into two groups based on testosterone levels: T1 group (testosterone <12 mmol/L) and T2 group (testosterone >12 mmol/L). Fifty-four non-diabetic patients were used as the control group. Sex hormone index, glucose, insulin, C-peptide, 24-h urinary free cortisol, thromboelastography, and insulin resistance index were measured by radioimmunoassay. Testosterone was lower in the diabetic men than in the control group (12.02 vs 14.77, p < .05), and was inversely related to blood coagulation status, blood glucose level, and cortisol level. Body mass index was positively correlated with estradiol and insulin resistance index. Testosterone was independently associated with the clotting process after controlling for age. Low testosterone is a risk factor for hypercoagulable state in diabetic men. Elevated estradiol and insulin resistance are influential factors for increased body mass index.

Changes in spectrum of biopsy-proven kidney diseases within decade: an analysis based on 10 199 cases from South China.

PURPOSE: To assess the regional epidemiological trends of kidney diseases over time in the South China using renal biopsy-proven cases. METHODS: This retrospective observational cohort study was conducted at the Institute of Nephrology, Second Xiangya Hospital of Central South University, and encompasses all patients diagnosed with kidney disease via biopsy from 2012 to 2021. RESULTS: The study sample consisted of 10 199 native kidneys, with a male-to-female ratio of 0.91:1 and an average age of 38.74 (±14.53) years. Primary glomerular nephropathy, systemic glomerular nephropathy (SGN), tubulointerstitial disease, and hereditary renal diseases accounted for 66.92 (6825)%, 24.49 (2498)%, 8.06 (822)%, and 0.53 (54)%, respectively. The leading pathologies of primary glomerular nephropathy remained the IgA nephropathy. The frequencies of IgA nephropathy and membranous nephropathy increased significantly, whereas the frequencies of minimal change disease and focal segmental glomerulosclerosis decreased (P < .001) between 2017 and 2021 than in the years 2012 and 2016. An earlier onset of membranous nephropathy was observed in the age group of 45-59 years compared to previous studies. The leading pathologies of SGN were found to be lupus nephritis (758 cases, 30.45%) and hypertension nephropathy (527 cases, 21.17%). The frequencies of hypertension nephropathy and diabetic nephropathy increased between 2017 and 2021 compared to 2012 and 2016 (P < .001), gradually becoming the leading pathological types of SGN. In elderly patients diagnosed with nephrotic syndrome, the frequencies of amyloidosis significantly increased (P < .01). CONCLUSION: Our study may provide insights for kidney disease prevention and public health strategies. What is already known on this topic The pathological spectrum of kidney diseases has undergone significant transformations in the past decade, driven by the escalating incidence of chronic diseases. Although there are studies exploring the renal biopsy findings from various regions in China which present both similarities and differences in epidemiology, few large-scale reports from the South China in recent decades were published. What this study adds Our findings reveal the following key observations: (i) increased proportion of middle-aged patients leading to the increasing average age at the time of biopsy；(ii) the frequencies of IgA nephropathy and membranous nephropathy (MN) increased significantly, whereas the frequencies of minimal change disease and focal segmental glomerulosclerosis decreased (P < .001) between 2017 and 2021 than in the years 2012 and 2016; (iii) earlier onset of MN in the age group of 45-59 years old was found in our study; and (iv) a higher frequency of hypertension nephropathy and DN presented over time, and frequency of amyloidosis increased in elderly patients diagnosed with NS. How this study might affect research, practice, or policy This single-center yet a large-scale study of the kidney disease spectrum in South China may provide a reference point for the diagnosis, treatment, and prevention of chronic kidney disease.

Safety and efficacy of microwave ablation for the treatment of low-risk papillary thyroid microcarcinoma: a prospective multicenter study.

OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.

Epsin1-mediated exosomal sorting of Dll4 modulates the tubular-macrophage crosstalk in diabetic nephropathy.

Tubular epithelial cells (TECs) play critical roles in the development of diabetic nephropathy (DN), and can activate macrophages through the secretion of exosomes. However, the mechanism(s) of TEC-exosomes in macrophage activation under DN remains unknown. By mass spectrometry, 1,644 differentially expressed proteins, especially Dll4, were detected in the urine exosomes of DN patients compared with controls, which was confirmed by western blot assay. Elevated Epsin1 and Dll4/N1ICD expression was observed in kidney tissues in both DN patients and db/db mice and was positively associated with tubulointerstitial damage. Exosomes from high glucose (HG)-treated tubular cells (HK-2) with Epsin1 knockdown (KD) ameliorated macrophage activation, TNF-α, and IL-6 expression, and tubulointerstitial damage in C57BL/6 mice in vivo. In an in vitro study, enriched Dll4 was confirmed in HK-2 cells stimulated with HG, which was captured by THP-1 cells and promoted M1 macrophage activation. In addition, Epsin1 modulated the content of Dll4 in TEC-exosomes stimulated with HG. TEC-exosomes with Epsin1-KD significantly inhibited N1ICD activation and iNOS expression in THP-1 cells compared with incubation with HG alone. These findings suggested that Epsin1 could modulate tubular-macrophage crosstalk in DN by mediating exosomal sorting of Dll4 and Notch1 activation.

The present status of metformin in fertility-preserving treatment in atypical endometrial hyperplasia and endometrioid endometrial cancer.

Progestin therapy is the main fertility-sparing treatment for women with endometrial cancer (EC) and atypical endometrial hyperplasia (AEH). However, still 15-25% of these women failed to achieve complete response (CR) and then lost their fertility after definitive surgery. Metformin has been demonstrated to play an anti-cancer role in multiple cancers including EC. Several studies also suggested metformin had potential benefit in improving the therapeutic outcome of fertility-preserving treatment alongside with progestin. This review has discussed existed evidence regarding the effect of metformin combined with progestin for women with AEH and EC who desire childbearing. Nevertheless, the therapeutic effect of metformin varied in different studies due to the high heterogeneity in the patient's characteristics, the inconsistency in dose and treatment duration of metformin, the combined use of hysteroscopy, the insufficient sample size and underpowered study-design. Therefore, care should be taken when interpreting the current results on this issue. Till now, there is still no strong evidence supporting the use of metformin in fertility-preserving treatment in AEH and EEC patients. Further research is needed to provide high-quality data to validate the role of metformin as adjunctive therapy alongside with progestin to preserve fertility for AEH and EEC patients.

LncRNA THOR promotes endometrial cancer progression through the AKT and ERK signaling pathways.

The long noncoding RNA (lncRNA) THOR is highly conserved and expressed in various human cancer tissues, although its potential role and underlying mechanism in endometrial cancer (EC) remain unknown. This study aims to explore THOR's biological function and molecular mechanism in EC progression. THOR expression in EC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR) and in situ hybridization (ISH). THOR expression based on The Cancer Genome Atlas (TCGA) and clinical sample analyses was significantly higher in EC tissues than normal tissues, and higher THOR levels were closely associated with poor overall survival in EC. Additionally, a positive correlation between ISH-detected THOR expression and pathological grade was observed. CCK-8, colony formation, and transwell migration and invasion assays revealed that THOR significantly enhances the proliferation, migration, and invasion abilities of EC cells. Moreover, IGF2BP1 protein expression and ERK and AKT protein phosphorylation levels in EC cells increased significantly with THOR overexpression in EC cells. In conclusion, our findings suggest that THOR promotes EC cell growth and invasion, and IGF2BP1-mediated AKT and ERK signaling pathways activation might be involved. Clinically, THOR is significantly expressed in EC, and high THOR expression correlates with poor prognosis, making it a potential prognostic marker for EC.

Identification of potential models for predicting progestin insensitivity in patients with endometrial atypical hyperplasia and endometrioid endometrial cancer based on ATAC-Seq and RNA-Seq integrated analysis.

Objective: The aim of this study was to establish predictive models based on the molecular profiles of endometrial lesions, which might help identify progestin-insensitive endometrial atypical hyperplasia (EAH) or endometrioid endometrial cancer (EEC) patients before progestin-based fertility-preserving treatment initiation. Methods: Endometrial lesions from progestin-sensitive (PS, n = 7) and progestin-insensitive (PIS, n = 7) patients were prospectively collected before progestin treatment and then analyzed by ATAC-Seq and RNA-Seq. Potential chromatin accessibility and expression profiles were compared between the PS and PIS groups. Candidate genes were identified by bioinformatics analyses and literature review. Then expanded samples (n = 35) were used for validating bioinformatics data and conducting model establishment. Results: ATAC-Seq and RNA-Seq data were separately analyzed and then integrated for the subsequent research. A total of 230 overlapping differentially expressed genes were acquired from ATAC-Seq and RNA-Seq integrated analysis. Further, based on GO analysis, REACTOME pathways, transcription factor prediction, motif enrichment, Cytoscape analysis and literature review, 25 candidate genes potentially associated with progestin insensitivity were identified. Finally, expanded samples were used for data verification, and based on these data, three predictive models comprising 9 genes (FOXO1, IRS2, PDGFC, DIO2, SOX9, BCL11A, APOE, FYN, and KLF4) were established with an overall predictive accuracy above 90%. Conclusion: This study provided potential predictive models that might help identify progestin-insensitive EAH and EEC patients before fertility-preserving treatment.

Efficacy of sentinel lymph node mapping in endometrial cancer with low- or high-intermediate risk.

BACKGROUND AND OBJECTIVES: This study was aimed to evaluate the efficacy of sentinel lymph node (SLN) mapping using indocyanine green (ICG) in Chinese women with endometrial cancer (EC). METHODS: Consecutive EC patients undergoing SLN mapping at Obstetrics and Gynecology Hospital of Fudan University were retrospectively reviewed. Overall and bilateral SLN detection rates and SLN locations were presented. Sensitivity, negative predictive value (NPV), and agreement rate were calculated and were compared between patients with low-intermediate (LIR) or high-intermediate risk (HIR). RESULTS: There were 454 patients screened, with SLN mapping with ICG performed in 428 patients and systematic lymphadenectomy performed in 159 patients. Overall and bilateral SLN detection rates were 96.50% and 82.71%, respectively. The sensitivity of SLN mapping was 80.00%, and the NPV was 97.76%. SLNs were most commonly located in obturator and external iliac regions. Efficacy of SLN mapping was higher in LIR patients than in HIR patients, with sensitivities of 100.00% and 75.00% (p > 0.05), NPVs of 100.00% and 90.00% (p = 0.002), and agreement rates of 100.00% and 92.31% (p = 0.007), respectively. CONCLUSION: SLN mapping with ICG had acceptable diagnostic efficacy in Chinese women with EC, but may cause more missed diagnoses in patients with HIR due to relatively low NPV and agreement rate.

A Review of Off-On Fluorescent Nanoprobes: Mechanisms, Properties, and Applications.

With the development of nanomaterials, fluorescent nanoprobes have attracted enormous attention in the fields of chemical sensing, optical materials, and biological detection. In this paper, the advantages of "off-on" fluorescent nanoprobes in disease detection, such as high sensitivity and short response time, are attentively highlighted. The characteristics, sensing mechanisms, and classifications of disease-related target substances, along with applications of these nanoprobes in cancer diagnosis and therapy are summarized systematically. In addition, the prospects of "off-on" fluorescent nanoprobe in disease detection are predicted. In this review, we presented information from all the papers published in the last 5 years discussing "off-on" fluorescent nanoprobes. This review was written in the hopes of being useful to researchers who are interested in further developing fluorescent nanoprobes. The characteristics of these nanoprobes are explained systematically, and data references and supports for biological analysis, clinical drug improvement, and disease detection have been provided appropriately.

Clinical features related to lymphatic metastasis in grade 3 endometroid endometrial cancer: a retrospective cross-sectional study.

BACKGROUND: Endometrial cancer (EC) has been one of the most general cancers with respect to gynecological malignancies; however, there are debates on clinical strategies concerning treatments especially for patients with grade 3 (G3) endometroid endometrial cancer (EEC). Present study aimed to evaluate the lymphatic metastasis (LM) related factors and figure out the necessity of lymphadenectomy for G3 EEC patients. METHODS: From January 2009 to April 2019, 3751 EC patients were admitted to Obstetrics and Gynecology Hospital of Fudan University. Clinical characteristics include age, grade, stage, and clinical pathological features. A total of 1235 EEC patients were involved in the multivariable analysis. Three hundred and eighty-one patients were involved in the survival analysis and the data attributed to sufficient follow-up information. Kaplan-Meier curve and log-rank test were utilized to analyze the survival rate. RESULTS: Among the 1235 EEC patients, 181 (14.7%) were categorized as G3 and 1054 (85.3%) were grade 1 to grade 2 (G1-2). Multivariate analysis demonstrated that lymphovascular space invasion, adnexal involvement, and cervical stroma involvement were independent risk factors of LM in G3 cohort with odds ratio 3.4, 5.8, and 8.9; 95% confidence interval 1.1-10.6, 1.5-22.4, and 2.8-28.0, respectively. LM rates increased from 3.3% (3/92) to 75% (9/12) for G3 EEC cohort as related factor numbers increased from one to three. There were no differences between G3 and G1-2 EEC in overall survival and progression free survival. Additionally, no survival advantage was observed for G3 EEC patients at early stage with different plans of adjuvant treatment. CONCLUSIONS: For G3 EEC patients without other pathological positive factor, the LM rate is lower than those with other pathological positive factor. Survival analysis showed no difference between G3 cohort and G1-2 cohort. Also, different adjuvant treatments had no impact on the overall survival for G3 EEC patients.

Sentinel lymph Node mapping versus systematic pelvic lymphadenectomy on the prognosis for patients with intermediate-high-risk Endometrial Cancer confined to the uterus before surgery: trial protocol for a non-inferiority randomized controlled trial (SNEC trial).

BACKGROUND: Sentinel lymph node (SLN) mapping has been recommended as an alternative staging approach to lymphadenectomy for apparent uterine-confined endometrial cancer (EC). However, the prognostic value of SLN mapping alone instead of systematic lymphadenectomy on EC patients remains unclear. METHODS: A multi-center, open label, non-inferiority randomized controlled trial has been designed to identify if SLN mapping alone is not inferior to pelvic lymphadenectomy on prognosis of patients with intermediate-high-risk EC clinically confined to uterus. Eligible patients will be 1:1 randomly assigned to accept SLN mapping or pelvic lymphadenectomy. The primary endpoint is the 2-year progression-free survival (PFS). The second points are the 5-year PFS, 5-year overall survival, surgery-related adverse events and life quality. A total of 780 patients will be enrolled from 6 hospitals in China within 3-year period and followed up for 5 years. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04276532.

Renovascular Disease Induces Senescence in Renal Scattered Tubular-Like Cells and Impairs Their Reparative Potency.

Scattered tubular-like cells (STCs), dedifferentiated renal tubular epithelial cells, contribute to renal self-healing, but severe injury might blunt their effectiveness. We hypothesized that ischemic renovascular disease (RVD) induces senescence in STC and impairs their reparative potency. CD24+/CD133+ STCs were isolated from swine kidneys after 16 weeks of RVD or healthy controls. To test their reparative capabilities in injured kidneys, control or RVD-STC (5×105) were prelabeled and injected into the aorta of 2 kidneys, 1-clip (2k,1c) mice 2 weeks after surgery. Murine renal function and oxygenation were studied in vivo 2 weeks after injection using micro-magnetic resonance imaging, and fibrosis, tubulointerstitial injury, capillary density, and expression of profibrotic and inflammatory genes ex vivo. STC isolated from swine RVD kidneys showed increased gene expression of senescence and senescence-associated secretory phenotype markers and positive SA-ß-gal staining. Delivery of normal pig STCs in 2k,1c mice improved murine renal perfusion, blood flow, and glomerular filtration rate, and downregulated profibrotic and inflammatory gene expression. These renoprotective effects were blunted using STC harvested from RVD kidneys, which also failed to attenuate hypoxia, fibrosis, tubular injury, and capillary loss in injured mouse 2k,1c kidneys. Hence, RVD may induce senescence in endogenous STC and impair their reparative capacity. These observations implicate cellular senescence in the pathophysiology of ischemic kidney disease and support senolytic therapy to permit self-healing of senescent kidneys.

Novel insight from the first lung transplant of a COVID-19 patient.

BACKGROUND: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient. MATERIALS AND METHODS: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1ß and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS: Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.

Rare imaging findings of hypersensitivity pneumonitis: A case report.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an immune-mediated syndrome caused by allergen inhalation. High-resolution computed tomography (HRCT) of HP may show diffuse ground-glass opacity, centrilobular ground-glass nodules, areas of air-trapping, thin-walled cysts, or fibrotic changes. CASE SUMMARY: A 47-year-old male patient went to the hospital complaining of cough and gradual aggravation of shortness of breath. HRCT of the lung showed that multiple nodules and ground-glass high-density shadows were present in both lungs. In addition, circular high-density shadows of various sizes were widely distributed in both lungs with relatively normal lung markings inside them. But other tests did not have a positive finding that can clarify the cause. Therefore, the patient underwent a lung biopsy. The pathological results showed that the lesions tended to be HP. After 4 mo of follow-up, the lesions in the patient's lungs were absorbed spontaneously, and the symptoms of cough and shortness of breath have disappeared. The review results suggested that the patient's disease was self-healing, which was consistent with the characteristics of HP. CONCLUSION: For some patients with HP, abnormal HRCT findings, such as the lesions in the lungs, can be absorbed on their own, which is an important clue in the diagnosis of the disease. Early diagnosis by lung biopsy is necessary when antigen exposure is unknown.

Human umbilical cord-derived mesenchymal stem cells and human cord blood mononuclear cells protect against cisplatin-induced acute kidney injury in rat models.

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are a promising tool to attenuate cisplatin (CP)-induced acute kidney injury (AKI). However, whether the transplantation of human cord blood mononuclear cells (hCBMNCs) exhibits similar protective effects and their potential underlying mechanisms of action remain unclear. The present study aimed to determine the protective effects of hUCMSCs and hCBMNCs transplantation therapies on an established CP-induced rat model and explore their underlying mechanisms of action. A total of 24 Sprague-Dawley rats, selected based on body weight, were randomly assigned into 4 groups: i) normal control; ii) model (CP); iii) hCBMNCs (CP + hCBMNCs); and iv) hUCMSCs (CP + hUCMSCs). hUCMSCs (2.0x106 cells) and hCBMNCs (2.0x106 cells) were injected into the femoral vein of rats 24 h after CP (8 mg/kg) treatment. To determine the effects of hCBMNCs and hUCMSCs on CP-induced rats, renal function assessment and histological evaluations were performed. Expression levels of high mobility group box 1 (HMGB1) and the ratio of Bax/Bcl2 in renal tissues were detected to elucidate their underlying molecular mechanisms of action. The results demonstrated that transplantation of hUCMSCs and hCBMNCs significantly improved renal function in CP-induced AKI rats, as evidenced by the enhancement of renal morphology; decreased concentrations of blood urea nitrogen and serum creatinine; and a lower percentage of apoptotic renal tubular cells. The expression of HMGB1 and the ratio of Bax/Bcl-2 were significantly reduced in the hUCMSCs and hCBMNCs groups compared with CP group. In conclusion, the present study indicated that hCBMNCs exert similar protective effects to hUCMSCs on CP-induced AKI. hUCMSCs and hCBMNCs protect against CP-induced AKI by suppressing HMGB1 expression and preventing cell apoptosis.

Osteoclastic activity was associated with the development of steroid-induced osteonecrosis of femoral head.

This study is focussed on evaluating and comparing two mediators of osteoclast, osteoprotegerin (OPG) and nuclear factor-κB ligand (RANKL), in plasma and tissue levels in patients with steroid-induced osteonecrosis of femoral head (SIONFH). Subjects were included in this cross-sectional case-control study in 2016. Bone histomorphology, immunohistochemistry, Western blotting, OPG and RANKL plasma levels, post-hoc statistical power and receiver-operating characteristic (ROC) curves were evaluated. Eighty-six patients diagnosed with SIONFH and 51 healthy subjects were included. OPG expression levels in bone samples increased with ARCO stage, and RANKL expression levels decreased with ARCO stages. Plasma OPG and RANKL levels were significantly higher in the SIONFH group compared with the healthy control group. The plasma OPG level and ratio of OPG and RANKL were positively associated with ARCO stages and significantly higher in stages III and IV. Plasma RANKL levels were negatively associated with ARCO stage and were significantly higher in ARCO stages II and III. Plasma OPG and RANKL may represent potential biomarkers during SIONFH at different stages. Higher plasma OPG levels indicated late-stage SIONFH, and higher plasma RANKL levels indicated early stage. Our findings may provide a clue for the development of diagnostic tools and therapies for SIONFH.

Adjunctive mesenchymal stem/stromal cells augment microvascular function in poststenotic kidneys treated with low-energy shockwave therapy.

Effective therapeutic strategies are needed to preserve renal function in patients with atherosclerotic renal artery stenosis (ARAS). Low-energy shockwave therapy (SW) and adipose tissue-derived mesenchymal stem/stromal cells (MSCs) both stimulate angiogenesis repair of stenotic kidney injury. This study tested the hypothesis that intrarenal delivery of adipose tissue-derived MSCs would enhance the capability of SW to preserve stenotic kidney function and structure. Twenty-two pigs were studied after 16 weeks of ARAS, ARAS treated with a SW regimen (bi-weekly for 3 weeks) with or without subsequent intrarenal delivery of adipose tissue-derived MSCs and controls. Four weeks after treatment, single-kidney renal blood flow (RBF) before and after infusion of acetylcholine, glomerular filtration rate (GFR), and oxygenation were assessed in vivo and the renal microcirculation, fibrosis, and oxidative stress ex vivo. Mean arterial pressure remained higher in ARAS, ARAS + SW, and ARAS + SW + MSC compared with normal. Both SW and SW + MSC similarly elevated the decreased stenotic kidney GFR and RBF observed in ARAS to normal levels. Yet, SW + MSC significantly improved RBF response to acetylcholine in ARAS, and attenuated capillary loss and oxidative stress more than SW alone. Density of larger microvessels was similarly increased by both interventions. Therefore, although significant changes in functional outcomes were not observed in a short period of time, adjunct MSCs enhanced pro-angiogenic effect of SW to improve renal microvascular outcomes, suggesting this as an effective stratege for long-term management of renovascular disease.

Polydatin improves osteogenic differentiation of human bone mesenchymal stem cells by stimulating TAZ expression via BMP2-Wnt/ß-catenin signaling pathway.

OBJECTIVES: Polydatin (PD), extracted from Polygonum cuspidatum, has shown potential therapeutic applications due to its antiosteoporotic and anti-inflammatory activities. Our previous study suggested that PD promotes the osteogenesis of human bone marrow stromal cells (hBMSCs) via the BMP2-Wnt/ß-catenin pathway. The aim of our present study was to further explore the role of PD-mediated regulation of Tafazzin (TAZ), a transcriptional coactivator with a PDZ-binding motif, in osteogenesis. MATERIALS AND METHODS: hBMSCs were isolated and treated with PD at various concentrations. Alizarin red staining and RT-qPCR were performed to identify calcium complex deposition in hBMSCs as well as the expression of specific osteoblast-related markers, respectively, in each group. Next, TAZ-silenced hBMSCs were generated by lentivirus-produced TAZ shRNA. After treatment with PD, the osteogenic abilities of the TAZ-silenced and control hBMSCs were estimated by ALP activity assay, and expression of the TAZ protein was detected by Western blot analysis and immunofluorescence staining. In vitro, an ovariectomized (OVX) mouse model was established and used to evaluate the effect of PD on bone destruction by micro-CT, immunohistochemistry, and ELISA. RESULTS: In vitro, 30 µM PD significantly improved the proliferation and calcium deposition of hBMSCs and markedly stimulated the expression of the mRNAs RUNX2, Osteopontin, DLX5, ß-catenin, TAZ, and Osteocalcin (OCN). Osteogenic differentiation induced by PD was blocked by lentivirus-mediated TAZ shRNA. Furthermore, Noggin (a regulator of bone morphogenic protein 2 (BMP2)) and DKK1 (an inhibitor of the Wnt/ß-catenin pathway) were found to inhibit the increase in TAZ expression induced by PD. In vivo, PD prevented estrogen deficiency-induced bone loss in the OVX mouse model. CONCLUSION: Taken together, our findings suggest that PD improved the osteogenic differentiation of hBMSCs and maintained the bone matrix in the OVX mouse model through the activation of TAZ, a potential target gene of the BMP2-Wnt/ß-catenin pathway.

MicroRNA-148b enhances the radiosensitivity of B-cell lymphoma cells by targeting Bcl-w to promote apoptosis.

Lymphoma is a malignant disease of the hematopoietic system that typically affects B cells. The up-regulation of miR-148b is associated with radiosensitization in B-cell lymphoma (BCL). This study aimed to explore the role of miR-148b in regulating the radiosensitivity of BCL cells and to investigate the underlying mechanism. miR-148b directly targeted Bcl-w, decreased the cell viability and colony formation, while promoted apoptosis, in irradiated BCL cells. These changes were accompanied by decreased mitochondrial membrane potential, release of cytochrome C, increased levels of the cleaved caspase 9 and caspase 3, and increased expression of other proteins related to the mitochondrial apoptosis pathway. These effects of miR-148b were effectively inhibited by Bcl-w. In addition, miR-148b inhibited the growth of tumors in nude mice implanted with xenografts of irradiated Raji cells. In patients with BCL, levels of miR-148b were downregulated, while levels of Bcl-w were upregulated; a significant negative correlation between levels of miR-148b and Bcl-w was confirmed. Taken together, these experiments showed that miR-148b promoted radiation-induced apoptosis in BCL cells by targeting anti-apoptotic Bcl-w. miR-148b might be used as a marker to predict the radiosensitivity of BCL.