A comparative study between Dydrogesterone alone and combined with Non-Steroidal Anti-Inflammatory Drugs in the treatment of Mild Endometriosis.

Objective: To evaluate the clinical efficacy of dydrogesterone combined with non-steroidal anti-inflammatory drugs(NSAIDs) in the treatment of patients with mild endometriosis. Methods: This was a clinical comparative study. Eighty patients with mild endometriosis were recruited at Affiliated Hospital of Hebei University, randomly divided experimental group (n=40) and control group (n=40) from March 2022 to March 2023. Both groups started treatment with dydrogesterone on the 5th day of menstruation. Patients in the control group were treated with dydrogesterone monotherapy, while those in the experimental group were treated with mefenamic acid the basis of the therapy of the control group. The clinical efficacy, differences in the levels of humoral immune indexes, the levels of inflammatory factor and the incidence of adverse drug reactions of the two groups was compared and analyzed. Results: The efficacy of the experimental group was significantly higher than the control group, with a statistically significant difference(P=0.02). The levels of C3 and C4 in the experimental group after treatment were significantly lower than those in the control group, with a statistically significant difference(P=0.00). After treatment, TNF-a, CRP, IL-6 and other indexes in the experimental group were significantly lower than those in the control group, with statistically significant differences(P=0.00). The incidence of adverse reactions after treatment had no statistically significant difference(P=0.45). Conclusion: Dydrogesterone combined with non-steroidal anti-inflammatory drugs is a safe and effective treatment for patients with endometriosis. It can improve various obvious curative effects, such as marked relief of pain symptoms, reduction of complement and inflammatory factor levels without a significant increase in adverse reactions.

miR-29 family: A potential therapeutic target for cardiovascular disease.

Cardiovascular disease (CVD), including heart failure, myocardial fibrosis and myocardial infarction, etc, remains one of the leading causes of mortality worldwide. Evidence shows that miRNA plays an important role in the pathogenesis of CVD. miR-29 family is one of miRNA, and over the past decades, many studies have demonstrated that miR-29 is involved in maintaining the integrity of arteries and in the regulation of atherosclerosis, especially in the process of myocardial fibrosis. Besides, heart failure, myocardial fibrosis and myocardial infarction are inseparable from the regulatory role of miR-29. Here, we comprehensively review recent studies regarding miR-29 and CVD, illustrate the possibility of miR-29 as a potential marker for prevention, treatment and prognostic observation.

Macrophage 3D migration: A potential therapeutic target for inflammation and deleterious progression in diseases.

Macrophages are heterogeneous cells that have different physiological functions, such as chemotaxis, phagocytosis, endocytosis, and secretion of various factors. All physiological functions of macrophages are integral to homeostasis, immune defense and tissue repair. However, in several diseases, macrophages are recruited from the blood towards inflammatory sites. This process is called macrophage migration, which promotes deleterious disease progression. Macrophage migration is a key player in many inflammatory diseases, autoimmune diseases and cancers because it contributes to the accumulation of proinflammatory factors, the destruction of tissues and the development of tumors. Therefore, macrophage migration is proposed to be a potential therapeutic target. Macrophages migrate between two-dimensional (2D) and three-dimensional (3D) environments, implying that distinct migratory features and mechanisms are involved. Compared with the 2D migration of macrophages, 3D migration involves more complex variations in cellular morphology and dynamics. The structure of the extracellular matrix, a key factor, is modified in diseases that influence macrophage 3D migration. Macrophage 3D migration relates to disease pathology. Research that focuses on macrophage 3D migration is an emerging field and was reviewed in this article to indicate the molecular and cellular mechanisms of macrophage migration in 3D environments and to provide potential targets for controlling disease progression associated with this migration.

Suppression of macrophage migration by down-regulating Src/FAK/P130Cas activation contributed to the anti-inflammatory activity of sinomenine.

A large number of macrophages in inflamed sites not only amplify the severity of inflammatory responses but also contribute to the deleterious progression of many chronic inflammatory diseases, autoimmune diseases and cancers. Macrophage migration is a prerequisite for their entry into inflammatory sites and their participation of macrophages in the pathologic processes. Inhibition of macrophage migration is therefore a potential anti-inflammatory mechanism. Moreover, alleviation of inflammation also prevents the macrophages infiltration. Sinomenine (SIN) is an alkaloid derived from the Chinese medicinal plant Sinomenium acutum. It has multiple pharmacological effects, including anti-inflammation, immunosuppression, and anti-arthritis. However, its anti-inflammatory molecular mechanisms and effect on macrophage migration are not fully understood. The purpose of this research was to investigate the pharmacological effects and the molecular mechanism of SIN on macrophage migration in vivo and in vitro as well as to elucidate its anti-inflammatory mechanisms associated with macrophage migration. Our results showed that SIN reduced the number of RAW264.7 cells migrating into inflammatory paws and blocked lipopolysaccharide (LPS)-induced RAW264.7 cells and bone marrow-derived macrophages (BMDMs) migration in vitro. Furthermore, SIN attenuated the 3D mesenchymal migration of BMDMs. The absence of macrophage migration after circulatory and periphery macrophages depletion led to a reduction in the severity of inflammatory response. In macrophages depleted (macrophages-/-) mice, as inflammatory severity decreased, RAW264.7 cells migration was suppressed. A non-obvious effect of SIN on the inflammatory response was found in macrophages-/- mice, while the inhibitory effect of SIN on RAW264.7 cells migration was still observed. Furthermore, the migration of RAW264.7 cells pre-treated with SIN was suppressed in normal mice. Finally, Src/focal adhesion kinase (FAK)/P130Cas axis activation, which supports macrophages mesenchymal migration, and iNOS expression, NO production, integrin αV and in integrin ß3 expressions, which promote Src/FAK/P130Cas activation, were down-regulated by SIN. However, SIN had no obvious effect on the expression of the monocyte chemoattractant protein-1 (MCP-1), which is an important chemokine for macrophage migration. These results indicated that SIN significantly inhibited macrophage mesenchymal migration by down-regulating on Src/FAK/P130Cas axis activation. There was a mutual regulatory correlation between the inflammatory response and macrophage migration, and the effects of SIN on macrophage migration were involved in its anti-inflammatory activity.

Correction to: Time to positivity of blood culture is a risk factor for clinical outcomes in Staphylococcus aureus bacteremia children: a retrospective study.

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Time to positivity of blood culture is a risk factor for clinical outcomes in Staphylococcus aureus bacteremia children: a retrospective study.

BACKGROUND: Staphylococcus aureus (S. aureus) is a common cause of bacteremia, which leads to significant morbidity and mortality. We investigated the relationship between time to positivity (TTP) and clinical outcomes in children with S.aureus bacteremia in the China. METHODS: A retrospective study of Staphylococcus aureus bacteremia inpatient was performed in Children's Hospital of Chongqing Medical University in China between 29 January 2014 and 29 August 2017. TTP and clinical parameters were determined and analyzed. The receiver operating characteristic (ROC) curves were plotted for optimal cut-off selection, multivariate logistic regression tests were performed to evaluate the association between TTP and clinical outcomes. RESULTS: Overall, 84 cases were enrolled. We stated that in-hospital mortality is significantly higher in the early TTP (≤17 h) than in the late TTP (> 17 h) group (57.14% vs 7.14%, P = 0.000). Septic shock occurred in 57.14% of patients with early TTP and in 18.57% of patients with late TTP (P = 0.002). Detailed multivariate and statistical analysis revealed that early TTP, need for vasoactive agent were independent risk factors of in-hospital mortality; early TTP, need for vasoactive agent and APACHE II score ≥ 15 were independent risk factors of septic shock incidence in S. aureus bacteremia children. CONCLUSIONS: Overall, TTP of ≤17 h appeared to correlate with the worse outcomes for S. aureus bacteremia children. These results have important implications in the assessments and management of pediatric S. aureus bacteremia in a clinical setting. TRIAL REGISTRATION: Retrospectively registered.

The Value of Mean Platelet Volume for Prognosis of Patients with Acute Cerebral Infarction.

BACKGROUND: The purpose of this study was to investigate the value of mean platelet volume (MPV) for prognosis of patients with acute cerebral infarction (ACI). METHODS: One hundred ACI patients and 80 healthy volunteers acting as healthy controls (HCs) were consecutively included in this study. Their baseline clinical and laboratory characteristics were extracted from an electroniccase system. ACI patients were followed for 90 days to collect the main study endpoints including poor prognosis, death due to cardiovascular causes, and the recurrence of stroke. ACI patients were evaluated after 7 days in the hospital using the National Institute of Health Stroke Scale (NIHSS) score to evaluate stroke severity on admission and using the modified Rankin Scale (mRS) to evaluate functional disorders. Receiver operating characteristic (ROC) curve analysis was used to estimate the predictive value of MPV on ACI. Kaplan-Meier survival analysis and Cox regression models were used to analyse the value of MPV as a predictor of ACI. RESULTS: This study suggested that MPV and rate of hypertension were higher in ACI patients than in the HC group. In the follow-up period, 32 ACI patients suffered study endpoints; they had higher average MPV, NIHSS scores, longer ACI onset times, and shorter event-free survival time compared to control patients. ROC curves showed that MPV was an index for prognosis of ACI patients with an AUC of MPV of 0.82 (95% confidence interval (CI): 0.74 - 0.90), and the best cutoff was 10.05 fL. MPV, NHISS scores, age, and TG were independent risk factors for endpoints of ACI patients. MPV with hazard ratio (HR) was 1.94 (95% CI, 1.37 - 2.72, p = 0.000), NIHSS score with HR was 1.22 (95% CI, 1.03 - 1.44, p = 0.021), age with HR was 1.06 (95% CI, 1.00 - 1.11, p = 0.038), and TG HR was 0.60 (95% CI, 0.36 - 1.00, p = 0.048) using Cox regression models. P  0.05 for all groups was considered statistically significant. CONCLUSIONS: Mean platelet volume was an independent risk factor and serves as a sensitive index for the prognosis of ACI patients.

Therapeutic effects of mifepristone combined with Gestrinone on patients with endometriosis.

OBJECTIVE: To evaluate the clinical therapeutic effects of mifepristone combined with gestrinone on patients with endometriosis. METHODS: A total of 150 endometriotic patients treated in our hospital between January 2014 and December 2015 were randomly divided into a control group and a treatment group (n=75). The control group began to orally take gestrinone capsules on the second day after menstruation started (2.5 mg/time, twice/week). The treatment group orally took mifepristone tablets (12.5 mg/time, once/day), and the dosage and administration of gestrinone capsules were the same as those of the control group. After 24 weeks of consecutive treatment, the clinical therapeutic effects of the two groups were assessed, and the pelvic symptom score, clinical sign score, serum sex hormone levels and pregnancy outcomes were compared. RESULTS: The total effective rates of control and treatment groups were 77.3% and 90.7% respectively, between which the difference was statistically significant (P<0.05). After treatment, the scores of pelvic symptoms (dysmenorrhea, dyspareunia, pelvic pain) and clinical signs (pelvic tenderness, induration) significantly reduced (P<0.05). Each score of the treatment group decreased more significantly than that of the control group did (P<0.05). The serum follicle hormone, luteinizing hormone, estrogen and progesterone levels were significantly lower than those before treatment (P<0.05). Each level of the treatment group dropped more significantly than that of the control group did (P<0.05). The pregnancy rates in the 6th and 12th months of follow-up were 28.0% and 13.3% in the control group respectively, and 42.7% and 29.3% in the treatment group respectively. Such rates of the two groups were significantly different at each follow-up time point (P<0.05). CONCLUSION: Mifepristone combined with gestrinone had satisfactory clinical therapeutic effects on endometriosis by reducing hormone levels and improving pregnancy outcomes. Therefore, this regimen is worthy of promotion and application in clinical practice.

Association between an insertion/deletion polymorphism within 3'UTR of SGSM3 and risk of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy, and multiple host genetic factors are believed to contribute to HCC development. The small G protein signaling modulator 3 (SGSM3) has been shown to be associated with small G protein coupled receptor signal transduction pathway, suggesting a potential role in HCC susceptibility. We carried out a case-control study in a Chinese population (502 cases and 513 controls) to determine whether the 4-bp insertion/deletion polymorphism (rs56228771) in 3' untranslated region of SGSM3 could affect HCC susceptibility. Logistic regression analysis showed that compared with the del/del genotype, the ins/del genotype of rs56228771 was associated with a significantly decreased risk of HCC [adjusted odd ratio = 0.55, 95% confidence interval (CI) = 0.42-0.73, P = 1.93 × 10(-5)]. The combined ins/del + ins/ins genotypes contributed to a 45% decreased HCC risk (95% CI = 0.42-0.73, P = 1.03 × 10(-5)). This protective trend was more prominent in the HBsAg-negative subgroup. Furthermore, in vivo experiments showed that mRNA levels of SGSM3 from HCC tumor tissues and adjacent non-HCC tissues were correlated with rs56228771 genotypes. Tissue samples with ins/ins genotype have the highest level of SGSM3, which are 2.85-3.00-fold and 1.46-1.57-fold higher than that with ins/del and del/del genotype, respectively. Similar results were also observed with four common hepatoma cell lines in vitro. In addition, compared with HCC tissues, significantly higher SGSM3 expression was observed in adjacent non-HCC tissues (fold change = 2.48), implying its tumor suppressor roles in HCC. Bioinformatics prediction showed that the insertion allele disrupted a binding site for microRNA (miRNA)-151-5p, which would upregulate SGSM3. Taken together, we provided initial evidence that rs56228771 may contribute to hepatocarcinogenesis, possibly by affecting SGSM3 expression through a miRNA-mediated regulation. The replication of our studies in other populations and functional analysis will further strengthen the underlining mechanism.

Diverse animal models for Chlamydia infections: unraveling pathogenesis through the genital and gastrointestinal tracts.

Chlamydia trachomatis is responsible for infections in various mucosal tissues, including the eyes, urogenital, respiratory, and gastrointestinal tracts. Chronic infections can result in severe consequences such as blindness, ectopic pregnancy, and infertility. The underlying mechanisms leading to these diseases involve sustained inflammatory responses, yet thorough comprehension of the underlying mechanisms remains elusive. Chlamydial biologists employ in multiple methods, integrating biochemistry, cell biology, and genetic tools to identify bacterial factors crucial for host cell interactions. While numerous animal models exist to study chlamydial pathogenesis and assess vaccine efficacy, selecting appropriate models for biologically and clinically relevant insights remains a challenge. Genital infection models in animals have been pivotal in unraveling host-microbe dynamics, identifying potential chlamydial virulence factors influencing genital pathogenicity. However, the transferability of this knowledge to human pathogenic mechanisms remains uncertain. Many putative virulence factors lack assessment in optimal animal tissue microenvironments, despite the diverse chlamydial infection models available. Given the propensity of genital Chlamydia to spread to the gastrointestinal tract, investigations into the pathogenicity and immunological impact of gut Chlamydia become imperative. Notably, the gut emerges as a promising site for both chlamydial infection vaccination and pathogenesis. This review elucidates the pathogenesis of Chlamydia infections and delineates unique features of prevalent animal model systems. The primary focus of this review is to consolidate and summarize current animal models utilized in Chlamydia researches, presenting findings, discussions on their contributions, and suggesting potential directions for further studies.

Different biopsy techniques for different pancreas graft locations after homolateral simultaneous pancreas-kidney transplantation.

Background: Biopsy of a transplanted pancreas is sometimes necessary in patients who have undergone simultaneous pancreas-kidney (SPK) transplantation and have elevated serum lipase and amylase concentrations. However, the risks associated with pancreatic graft biopsy are high, and the best biopsy technique for different location of pancreatic graft remains unclear. Methods: Depending on the anatomical location of the transplanted pancreas, percutaneous computed tomography (CT) combined with color Doppler-guided puncture biopsy or laparoscopic biopsy was used to obtain samples of transplanted pancreatic tissue that were shallow and deep, respectively. Results: After SPK transplantation, 4 patients developed abnormal serum lipase and amylase concentrations and underwent pancreas graft biopsy, 1 patient underwent percutaneous CT combined with color Doppler-guided puncture biopsy, 2 patients underwent laparoscopic wedge biopsy, and 1 patient underwent laparoscopic and puncture biopsy. All biopsies were performed successfully, with no intra- or postoperative complications (e.g., bleeding, pancreatic leakage, intestinal leakage). Biopsy sampling was effective in 3 patients, including 1 case of acute pancreatic rejection, 1 case of pancreatitis, and 1 case of pancreatic plasmablastic lymphoma. Biopsy failed to retrieve samples in 1 patient with a deep pancreatic graft who underwent laparoscopic wedge biopsy. Conclusions: Pancreas graft biopsy is safe and feasible after SPK transplantation. In addition to the two biopsy methods mentioned, other methods can also be used. Different biopsy strategies should be formulated according to the anatomical location of the transplanted pancreas.

Mediation of exciton concentration on magnetic field effects in NPB : Alq3-based heterojunction OLEDs.

Organic light-emitting diodes (OLEDs) are considered one of the most promising new display technologies owing to their advantages, such as all-solid-state, high color gamut, and wide viewing angle. However, in terms of special fields, the brightness, lifetime, and stability of the devices need further improvement. Therefore, heterojunction devices with different concentrations were prepared to regulate device brightness. The brightness of the bulk heterojunction device is enhanced by 9740 cd m-2, with a growth rate of about 26.8%. The impact of various temperatures and various exciton concentrations on the device magneto-conductance (MC) and magneto-electroluminescence (MEL) was investigated. Experimental results demonstrate that the exciton concentration inside the device can be tuned to improve optoelectronic properties and organic magnetic effects. The complex spin mixing process inside the bulk heterojunction device is deeply investigated, which provides a reliable basis for the design of bulk heterojunction devices.

Development of a novel prognostic assessment model for hepatitis B virus-related acute-on-chronic liver failure based on reexamination results.

Acute-on-chronic liver failure (ACLF) is a common clinical emergency and critical illness with rapid progression and poor prognosis. This study aims to establish a more efficient system for the prognostic assessment of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), which will provide a guiding scheme for subsequent treatment and improve the survival rate of patients. Data on 623 patients with HBV-ACLF were recorded. Univariate and multivariate analyses were performed to determine the discriminative abilities of the novel prognostic assessment model in predicting 90-day mortality. The area under the receiver operating characteristic curve was used to evaluate the accuracy of the models. Patients were divided into high- and low-scoring groups based on the best critical values, and survival rates were analyzed using Kaplan-Meier survival analysis and compared by applying log-rank tests. The area under the curve of the new scoring system established using the results of the first reexamination, the results of the first examination, the mean daily change in these results (MDCR) and the results of other first examinations were 0.911 (95% confidence interval [CI]: 0.889, 0.933), 0.893 (95% CI: 0.868, 0.917), and 0.895 (95% CI: 0.871, 0.919), respectively. The final prognostic scoring system established using the results of the first reexamination was chosen as a novel prognostic assessment model, and patients with lower scores (first reexamination results [FRER] score ≤ 3.65) had longer survival times (P < .001). The prognostic scoring system established using the FRER combined with other examination results can better assess the prognosis of HBV-ACLF at 90 days.

Tubular Numb promotes renal interstitial fibrosis via modulating HIF-1α protein stability.

Tubulointerstitial fibrosis is the ultimate common pathway of all manners of chronic kidney disease. We previously demonstrated that specific deletion of Numb in proximal tubular cells (PTCs) prevented G2/M arrest and attenuated renal fibrosis. However, how Numb modulates cell cycle arrest remains unclear. Here, we showed that Numb overexpression significantly increased the protein level of hypoxia-inducible factor-1α (HIF-1α). Numb overexpression-induced G2/M arrest was blocked by silencing endogenous HIF-1α, subsequently downregulated the expression of cyclin G1 which is an atypical cyclin to promote G2/M arrest of PTCs. Further analysis revealed that Numb-augmented HIF-1α protein was blocked by simultaneously overexpressing MDM2. Moreover, silencing Numb decreased TGF-ß1-induceded HIF-1α protein expression. While endogenous MDM2 was knocked down this reduction was reversed, indicating that Numb stabilized HIF-1α protein via interfering MDM2-mediated HIF-1α protein degradation. Interestingly, HIF-1α overexpression significantly upregulated the expression of Numb and silencing endogenous HIF-1α blocked CoCl2 or TGF-ß1-induced Numb expression. Chromatin immunoprecipitation (ChIP) assays demonstrated that HIF-1α binded to the promoter region of Numb. This binding was significantly increased by TGF-ß1. Collectively, these data indicate that Numb and HIF-1α cooperates to promote G2/M arrest of PTCs, and thus aggravates tubulointerstitial fibrosis. Numb might be a potential target for the therapy of tubulointerstitial fibrosis.

Correlation Between Fe/S/As Speciation Transformation and Depth Distribution of Acidithiobacillus ferrooxidans and Acidiphilium acidophilum in Simulated Acidic Water Column.

It is well known that speciation transformations of As(III) vs. As(V) in acid mine drainage (AMD) are mainly driven by microbially mediated redox reactions of Fe and S. However, these processes are rarely investigated. In this study, columns containing mine water were inoculated with two typical acidophilic Fe/S-oxidizing/reducing bacteria [the chemoautotrophic Acidithiobacillus (At.) ferrooxidans and the heterotrophic Acidiphilium (Aph.) acidophilum], and three typical energy substrates (Fe2+, S0, and glucose) and two concentrations of As(III) (2.0 and 4.5 mM) were added. The correlation between Fe/S/As speciation transformation and bacterial depth distribution at three different depths, i.e., 15, 55, and 105 cm from the top of the columns, was comparatively investigated. The results show that the cell growth at the top and in the middle of the columns was much more significantly inhibited by the additions of As(III) than at the bottom, where the cell growth was promoted even on days 24-44. At. ferrooxidans dominated over Aph. acidophilum in most samples collected from the three depths, but the elevated proportions of Aph. acidophilum were observed in the top and bottom column samples when 4.5 mM As(III) was added. Fe2+ bio-oxidation and Fe3+ reduction coupled to As(III) oxidation occurred for all three column depths. At the column top surfaces, jarosites were formed, and the addition of As(III) could lead to the formation of the amorphous FeAsO4⋅2H2O. Furthermore, the higher As(III) concentration could inhibit Fe2+ bio-oxidation and the formation of FeAsO4⋅2H2O and jarosites. S oxidation coupled to Fe3+ reduction occurred at the bottom of the columns, with the formations of FeAsO4⋅2H2O precipitate and S intermediates. The formed FeAsO4⋅2H2O and jarosites at the top and bottom of the columns could adsorb to and coprecipitate with As(III) and As(V), resulting in the transfer of As from solution to solid phases, thus further affecting As speciation transformation. The distribution difference of Fe/S energy substrates could apparently affect Fe/S/As speciation transformation and bacterial depth distribution between the top and bottom of the water columns. These findings are valuable for elucidating As fate and toxicity mediated by microbially driven Fe/S redox in AMD environments.

Sex Differences in Fecal Microbiota Correlation With Physiological and Biochemical Indices Associated With End-Stage Renal Disease Caused by Immunoglobulin a Nephropathy or Diabetes.

This study investigated the sex-specific differences in the correlation between intestinal microbiota and end-stage renal disease. Here, we compared the differences in the gut microbiota of male and female healthy controls (HC) and patients with end-stage renal disease (ESRD) caused by immunoglobulin A (IgA) nephropathy (ESRD-IgAN) or type-2 diabetes mellitus (ESRD-T2DM) using high-throughput sequencing of the 16S rRNA gene. We also analyzed the correlation between gut microbiota and clinical immune indicators. We assigned 8, 10, 5, 7, 11, and 20 volunteers to female HC, ESRD-IgAN, and ESRD-T2DM, and male HC, ESRD-IgAN, and ESRD-T2DM, respectively. The results showed sex-specific differences in both physiological and biochemical indices and intestinal microbiota composition, as well as the correlation between them. The correlations between physiological and biochemical indices in men were significantly lower than those in women, especially for indices related to immunity, blood glucose, and cardiac color sonography. Urine output, lymphocyte ratio, serum albumin, blood calcium, dialysis status, serum urea nitrogen, urine protein, and diabetes significantly correlated with male fecal microbiota composition, whereas only creatinine and 2-h post-prandial blood glucose significantly correlated with female fecal microbiota composition. The top 50 dominant operational taxonomic units showed a stronger correlation with physiological and biochemical indices in samples obtained from females than from males. These differences highlight sex-specific differences in the effectiveness of ESRD prevention and treatments via regulating intestinal microbiota.

EZH2-inhibitor DZNep enhances apoptosis of renal tubular epithelial cells in presence and absence of cisplatin.

BACKGROUND: The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and induces the trimethylation of histone H3 lysine 27 (H3K27me3) in the promoter of many key genes; EZH2 acts as a transcriptional repressor and is an epigenetic regulator for several cancers. However, the role of EZH2 in nonneoplastic diseases, such as kidney diseases, is unknown and has been investigated. MATERIALS AND METHOD: NRK-52E cells were treated with DZNep, a potent inhibitor of EZH2, with different concentrations and for different times to evaluate the apoptosis level of NRK-52E cells by Western blot and Flow cytometry analysis. The binding of EZH2 to the Deptor promoter was determined by ChIP assay. RESULTS: The inhibition of EZH2 with 3-deazaneplanocin A (DZNep), a specific inhibitor of EZH2, led to the apoptosis of NRK-52E cells and the inhibition of mTORC1 and mTORC2 activity. A ChIP assay demonstrated that EZH2 bound the promoter region of Deptor, an endogenous inhibitor of mTORC1 and mTORC2, and regulated the transcription of Deptor by modulating H3K27me3 in its promoter region. Further experiments were performed to examine the effects of EZH2 inhibition on cisplatin-induced injured cells. Cisplatin induced the activation of mTORC1 and mTORC2 and apoptosis in NRK-52E cells, and DZNep inhibited mTORC1 and mTORC2 activity and aggravated cell apoptosis. CONCLUSIONS: These data suggested that EZH2 inhibition increased the transcription of Deptor by modifying H3K27me3 in its promoter region, subsequently inhibited mTORC1 and mTORC2 activities, downregulated the expression of apoptosis suppressor genes, and finally led to apoptosis in renal tubular cells. The inhibition of EZH2 aggravated the cisplatin-induced injury in renal tubular cells by inactivating the mTOR complexes. The present study provides new insight into renal protection and suggests that EZH2 might be a target.

Impact of the use of vasoactive drugs in cardiac death donors on the early postoperative renal function and related complications in renal transplant recipients.

BACKGROUND: To explore the impact of the use of vasoactive drugs in donation after cardiac death (DCD) donors on graft function, with an attempt to guide the clinical practices of organ preservation and DCD kidney transplantation. METHODS: The clinical data of 187 DCD donors and 304 recipients who were operated on in our center from February 2018 to May 2019 were retrospectively analyzed. Based on whether vasoactive drugs were used for maintaining blood pressure in DCD donors, the renal donors and recipients were divided into a high-dose group (norepinephrine ≥1.3 µg/kg/min or in combination with dopamine), a low-dose group (norepinephrine <1.3 µg/kg/min or in conjunction with dopamine), and a no-medication group (without the use of vasoactive drugs). The clinical features, post-transplant renal function, and complications were compared among these three groups. RESULTS: The early renal function 1 and 7 days after surgery was significantly superior in the high-dose group and no-medication group (P<0.05) but showed no significant difference between the low-dose group and the no-medication group (P>0.05). Blood urea nitrogen (BUN) on the 1st postoperative days was significantly higher in the high-dose group than in the low-dose group and the no-medication group (P<0.05). Renal function indicators, including serum creatinine (CRE), BUN, and blood uric acid (UA) on the 30th postoperative day, showed no significant difference among these three groups (P>0.05). The incidence of delayed graft function (DGF) after renal transplantation was significantly higher in the high-dose group than in the low-dose group and the no-medication group (P<0.05), whereas there was no significant difference between the groups in the incidences of graft rejection and infections (P>0.05). CONCLUSIONS: The use of vasoactive drugs in DCD donors can affect the early recovery of renal function in renal transplant recipients, particularly for those donors who are administered a high dose of vasoactive drugs. Therefore, donor maintenance should be performed cautiously with vasoactive drugs.

Reconstruction of the hepatic artery using the superior mesenteric artery for liver transplantation.

BACKGROUND: To investigate the application of the superior mesenteric artery (SMA) for the in vitro reconstruction of the hepatic artery for liver transplantation, and to improve the success rate and safety of donor liver transplantation. METHODS: The donor liver and the pancreas were obtained, and the SMA and its branches were used to reconstruct the hepatic artery. Liver transplantation was performed after reconstruction to understand the intraoperative situation after donor liver opening, as well as postoperative liver function. Color Doppler ultrasound of the transplanted liver was also performed. RESULTS: During the period from September 2016 to March 2020, a total of 98 pancreases were obtained. The common hepatic artery and gastroduodenal artery loop (CHA-GDA) were preserved to the donor pancreas, and only the proper hepatic artery (PHA) or left/right hepatic artery (LHA/RHA) were preserved to the donor liver. If the PHA of the donor liver was short or absent, the SMA was used for lengthening the PHA or in vitro reconstruction of the LHA/RHA, followed by implantation of the donor liver after reconstruction. A total of 17 cases of this type of donor liver required mesenteric artery lengthening or reconstruction. After opening, the donor liver was well-filled, bile secretion was normal, and liver function recovered as scheduled after surgery. Color Doppler ultrasound and CT angiography (CTA) of the transplanted liver revealed that hepatic arteries were normal without complications such as hepatic artery embolism. CONCLUSIONS: In vitro reconstruction of the hepatic artery with the SMA is an effective new method of vascular reconstruction, which ensures the blood flow of the hepatic artery, reduces the anastomosis difficulty of the arteries of the donor liver, and reduces the occurrence of vascular complications.

Pancreas allograft biopsies procedure in the management of pancreas transplant recipients.

Pancreas transplantation is an effective therapy for diabetic patients, which can significantly improve the survival rate and quality of life of diabetic patients. According to the international registration of pancreas transplantation center, the global total pancreas transplantation has reached more than 80,000 cases by 2017, including pure pancreas transplantation and simultaneous pancreas-kidney transplantation (SPK). With the development and application of a new type of immunosuppressant, with the gradual maturity of organ preservation technology and surgical technology, the pancreas transplantation has rapidly on a global scale. However, pancreas transplantation still has more problems than limit its development compared with other organ transplantation. For example, the early diagnosis and treatment of pancreatic rejection are of considerable significance to the prognosis of pancreas transplantation. Some surveillance methods of diagnosis have been used increasingly, among which the histopathological diagnosis is particularly important. The first Banff schema for the histological diagnosis of pancreas rejection has been published, which primarily dealt with the diagnosis of acute T-cell-mediated rejection (ACMR). In recent years, antibody-mediated rejection (AMR) has been more emphasized as the primary cause of graft failure. The Banff pancreas allograft rejection grading schema was updated in 2011 by a broad-based multidisciplinary panel, presenting comprehensive guidelines for the diagnosis of AMR.