Asymmetric Synthesis of ß-Hydroxyphosphonates via a Chemoenzymatic Cascade.

Chiral ß-hydroxyphosphonates are essential building blocks for organophosphorus compounds. However, the asymmetric synthesis of these units remains a significant challenge. Herein, we describe a one-pot chemoenzymatic cascade process to access chiral ß-hydroxyphosphonates, which combines photo-oxidative chemical reactions and bioreductions. The incorporation of photooxidation in the chemical reaction resulted in up to 92% yield and >99% enantiomeric excess (ee) of ß-hydroxyphosphonates in the cascade. In addition, the scale-up of diethyl (S)-(2-hydroxy-2-phenylethyl)phosphonate demonstrates the potential application of this strategy.

Cushing Syndrome due to a Pancreatic Neuroendocrine Tumor Treated With Radiofrequency Ablation.

Delayed diagnosis of Cushing syndrome (CS) results in advanced disease, treatment delays, and poor outcomes. We present a patient with ectopic ACTH syndrome (EAS) from a pancreatic neuroendocrine tumor (NET) whose care posed diagnostic and therapeutic challenges. A 59-year-old female with classic Cushing stigmata, biochemical evidence of ACTH-dependent hypercortisolism, and a 5-mm pituitary lesion presented for inferior petrosal sinus sampling, which was contraindicated due to non-ST elevation myocardial infarction and acute/subacute strokes. Whole-body computed tomography (CT) scan was unrevealing, but elevations in chromogranin A and proopiomelanocortin (POMC) concentrations suggested EAS. Positron emission tomography-CT with gallium 68-DOTATATE demonstrated a 7-mm pancreatic tail lesion, suspicious for a pancreatic NET. The patient was not a surgical candidate and treatment with ketoconazole was complicated by hepatoxicity. Endoscopic ultrasound-guided biopsy and radiofrequency ablation of the lesion was pursued. Pathology confirmed ACTH immunoreactive low-grade pancreatic NET. Post procedure, sustained normalization of ACTH and cortisol was achieved. This case supports the utility of POMC measurements in the differential diagnosis of CS and the use of advanced nuclear imaging for tumor localization. For patients with functional pancreatic NET who are poor surgical candidates or intolerant of pharmacotherapy, novel endoscopic ablation may offer a low-risk therapeutic option and should be further investigated.

Enzymolysis-based RNA pull-down identifies YTHDC2 as an inhibitor of antiviral innate response.

The innate immune response must be terminated in a timely manner at the late stage of infection to prevent unwanted inflammation. The role of m6A-modified RNAs and their binding partners in this process is not well known. Here, we develop an enzymolysis-based RNA pull-down (eRP) method that utilizes the immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) to fish out m6A-modified RNA-associated proteins. We apply eRP to capture the methylated single-stranded RNA (ssRNA) probe-associated proteins and identify YT521-B homology domain-containing 2 (YTHDC2) as the m6A-modified interferon ß (IFN-ß) mRNA-binding protein. YTHDC2, induced in macrophages at the late stage of virus infection, recruits IFN-stimulated exonuclease ISG20 (IFN-stimulated exonuclease gene 20) to degrade IFN-ß mRNA, consequently inhibiting antiviral innate immune response. In vitro and in vivo deficiency of YTHDC2 increases IFN-ß production at the late stage of viral infection. Our findings establish an eRP method to effectively identify RNA-protein interactions and add mechanistic insight to the termination of innate response for maintaining homeostasis.

First Report of Exserohilum rostratum Causing Leaf Blight on Broccoli (Brassica oleracea var. italica) in China.

Broccoli (Brassica oleracea var. italica) is not only an important crop worldwide with a large amount of production and consumption annually, but also rich in biologically active compounds (Surh et al., 2021). In November 2022, an unknown leaf blight was observed in the Broccoli planting area, Wenzhou City of Zhejiang Province (28.05 °N, 120.31 °E). Symptoms initially occurred at the leaf margin with yellow to gray lesions that were irregular and wilting. Approximately 10% of the surveyed plants were affected. To determine the pathogen, leaves with blight were collected randomly from five B. oleracea plants. Tissue blocks (3×3 mm) from diseased leaf portions were disinfected with 75% ethanol, rinsed three times with sterilized water, placed aseptically onto potato dextrose agar (PDA) medium, and incubated for 5 days at 28℃ in darkness. Seven fungal isolates with the same morphology were obtained using the spore method. The observed colonies were circular, taupe, pewter in color with light gray edging and many cottony aerial mycelia. Conidia were straight, curved or slightly bent, ellipsoidal to fusiform, and septate (typically 4-8 septa per conidium), with the size of 50.0-90.0 µm × 10.0-20.0 µm (n=30). The conidia had a slightly protruding and truncate hilum. These morphological characteristics were consistent with Exserohilum rostratum (Sharma et al., 2014). To further identify the pathogen, isolate WZU-XLH1 was chosen as a representative and the internal transcribed spacer (ITS) and glyceraldehyde-3-phosphate dehydrogenase-like (GAPDH) gene were amplified and sequenced using primer pairs ITS1/ITS4 (White et al., 1990) and Gpd1/Gpd2 (Berbee et al., 1999), respectively. The ITS and gpd gene sequences of isolate WZU-XLH1 were deposited in the GenBank database with accession numbers OQ750113 and OQ714500, respectively. BLASTn analysis showed matches of 568/571 (MH859108) and 547/547 (LT882549) with Exserohilum rostratum CBS 188.68. A neighbor-joining phylogenetic tree was constructed by combining the two sequenced loci, this isolate in the E. rostratum species complex clade at 71% bootstrap support.To verify the pathogenicity of the isolate, ten healthy Broccoli (cultivar 'You Xiu') seedlings with at least five leaves were divided into two groups: one group was inoculated with the isolate, while the other group served as a control. After surface disinfection with 75% ethanol and wiping with sterile water, tiny wounds were made on two leaves (two wounds in one leaf) using an inoculation needle. Fungal culture plugs cut from the isolate were placed on the wounds, while sterile PDA plugs served as the control. The leaves were sealed in wet airtight bags to retain moisture at room temperature with natural light (Cao et al., 2022). After five days, all leaves inoculated with isolate WZU-XLH1 showed symptoms identical to those observed in the field, with no symptoms present in the control group. The pathogenicity was confirmed by repeating the test in triplicate, and fungi re-isolated from symptomatic leaves were identified as E. rostratum by the morphological and molecular methods described above. To the best of our knowledge, this is the first report of E. rostratum causing leaf blight on broccoli in China. This study contributes to our understanding of B. oleracea leaf blight and establishes a basis for future studies on E. rostratum to develop management strategies.

Application of a specialist nurse-led multidisciplinary team model in the perioperative care of patients undergoing simultaneous pancreas and kidney transplantation: randomized controlled trial.

Background: Simultaneous pancreas and kidney transplantation (SPKT) is an effective treatment option for individuals who suffer from both diabetes mellitus and renal failure. However, experiments exploring nurse-led multidisciplinary team management during the perioperative management of patients undergoing SPKT are currently limited. This study aims to explore the clinical performance of a transplant nurse-led multidisciplinary team (MDT) in the perioperative management of SPKT patients. Methods: A total of 218 patients who underwent SPKT were randomly assigned to either a control group (n=116) receiving conventional care or an intervention group (n=102) managed through a transplant nurse-led MDT approach. The incidence of postoperative complications, hospital stay, total hospitalization cost, readmission rate, and postoperative nursing quality were compared between these 2 groups. Results: The intervention and control groups showed no significant differences in age, gender, and body mass index. Compared with the control group, the intervention group had a significantly lower incidence of postoperative pulmonary infection and gastrointestinal (GI) bleeding (27.6% vs. 14.7% and 31.0% vs. 15.7%, respectively, both P<0.05). Compared to the control group, the intervention group had significantly lower hospitalization costs, length of hospital stay, and readmission rate 30 days after discharge (32.98±9.10 vs. 36.78±15.36, 26.47±13.4 vs. 31.03±11.61 and 31.4% vs. 50.0%, respectively, all P<0.05). Additionally, the intervention group had significantly better quality of postoperative nursing care than the control group (11.61±0.69 vs. 9.64±1.42, P<0.01), the availability of infection control and prevention measures (11.74±0.61 vs. 10.53±1.11, P<0.01), the effectiveness of health education (11.73±0.61 vs. 10.41±1.06, P<0.01), the effectiveness of rehabilitation training (11.77±0.54 vs. 10.37±0.96, P<0.01), and the patient satisfaction with nursing care (11.83±0.42 vs. 10.81±1.08, P<0.01). Conclusions: The nurse-led MDT model for transplant patients can reduce complications, shorten hospital stays, and save costs. It also provides clear guidelines for nurses, improving care quality and aiding patient recovery. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900026543.

Blood unconjugated bilirubin and tacrolimus are negative predictors of specific cellular immunity in kidney transplant recipients after SAR-CoV-2 inactivated vaccination.

The immunogenicity of SARS-CoV-2 vaccines is poor in kidney transplant recipients (KTRs). The factors related to poor immunogenicity to vaccination in KTRs are not well defined. Here, observational study demonstrated no severe adverse effects were observed in KTRs and healthy participants (HPs) after first or second dose of SARS-CoV-2 inactivated vaccine. Different from HPs with excellent immunity against SARS-CoV-2, IgG antibodies against S1 subunit of spike protein, receptor-binding domain, and nucleocapsid protein were not effectively induced in a majority of KTRs after the second dose of inactivated vaccine. Specific T cell immunity response was detectable in 40% KTRs after the second dose of inactivated vaccine. KTRs who developed specific T cell immunity were more likely to be female, and have lower levels of total bilirubin, unconjugated bilirubin, and blood tacrolimus concentrations. Multivariate logistic regression analysis found that blood unconjugated bilirubin and tacrolimus concentration were significantly negatively associated with SARS-CoV-2 specific T cell immunity response in KTRs. Altogether, these data suggest compared to humoral immunity, SARS-CoV-2 specific T cell immunity response are more likely to be induced in KTRs after administration of inactivated vaccine. Reduction of unconjugated bilirubin and tacrolimus concentration might benefit specific cellular immunity response in KTRs following vaccination.

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.

Neoxanthin alleviates the chronic renal failure-induced aging and fibrosis by regulating inflammatory process.

Chronic renal failure (CRF) refers to progressive renal damage caused by chronic kidney diseases (CKD). Dialysis therapy and kidney transplantation are the important treatment for CRF. However, due to the limitation of conditions, they cannot be widely utilized. At present, the treatment of renal failure is a worldwide problem in clinic. Therefore, in the current study, we investigated the potential therapeutic effects of neoxanthin on CFR-caused aging and fibrosis. In this work, the effects of neoxanthin on CRF were studied using experimental techniques such as biochemistry, immunohistochemistry and molecular biology. In vitro, neoxanthin alleviated the aging and oxidative damage of kidney cells. In vivo, we found that Neoxanthin could alleviate adenine-induced CRF. Neoxanthin also inhibited CRF-caused renal aging, fibrosis, oxidative stress and inflammation. These findings indicate that neoxanthin could delay the progression of CRF and alleviate CRF-induced aging and fibrosis. Collectively, we found that neoxanthin shows good potential to inhibit CRF-caused kidney aging and fibrosis, suggesting that neoxanthin may be used as a drug (or a functional food) for the treatment of CRF-related diseases.

Mesenchymal stem cells-derived HIF-1α-overexpressed extracellular vesicles ameliorate hypoxia-induced pancreatic ß cell apoptosis and senescence through activating YTHDF1-mediated protective autophagy.

Pancreatic islet transplantation is an ideal treatment strategy for type 1 diabetes mellitus (T1DM), but hypoxia-induced pancreatic ß cell death after islet transplantation is the huge obstacle that causes failure of this therapy. Thus, it become necessary to improve pancreatic ß cell viability under hypoxic conditions. In the present study, we designed mesenchymal stem cells (MSCs)-derived hypoxia-inducible factor 1α (HIF-1α)-overexpressed extracellular vesicle (EVs) (HIF-1α-EVs) and found that HIF-1α-EVs was effectively to promote cell viability and autophagy, and suppress cell apoptosis and senescence in the hypoxia-treated pancreatic ß cells. In addition, blockage of autophagy by its inhibitor 3-methyladenine (3-MA) abrogated the rescuing effects of HIF-1α-EVs on hypoxia-induced pancreatic ß cell death. Then, the potential underlying mechanisms by which HIF-1α-EVs triggered protective autophagy were uncovered, and we found that HIF-1α-EVs upregulated YTHDF1, resulting in the upregulation of autophagy-associated proteins (ATG5, ATG2A and ATG14), which were abrogated by deleting m6A writer METTL3. Finally, we verified that HIF-1α-EVs rescued cell viability, and reversed hypoxia-induced pancreatic ß cell apoptosis and senescence in a YTHDF1-dependent manner. Collectively, we concluded that MSCs-derived HIF-1α-EVs activated YTHDF1-mediated protective autophagy to promote pancreatic ß cell survival under hypoxic conditions, and HIF-1α-EVs could be used as candidate treatment strategy to increase the success rate of islet transplantation.

Effects of Long Noncoding RNA HOXA-AS2 on the Proliferation and Migration of Gallbladder Cancer Cells.

To explore the function and mechanism of lncRNA HOXA-AS2 in cancer-associated fibroblasts (CAFs)-derived exosomes in gallbladder cancer metastasis, and provide new research targets for the treatment of gallbladder cancer. At the same time, in order to clarify the early predictive value of lncRNA HOXA-AS2 for gallbladder cancer metastasis, and to provide a theoretical basis for clinical individualized treatment of gallbladder cancer. Methods. In our previous work, we used TCGA database analysis to find that lncRNA HOXA-AS2 was highly expressed in gallbladder cancer tissues compared with normal tissues. In this study, the expression levels of HOXA-AS2 in gallbladder cancer cell lines and control cells were first verified by QPCR and Western blot methods. Then, lentiviral tools were used to construct knockdown vectors (RNAi#1, RNAi#2) and negative control vectors targeting two different sites of HOXA-AS2, and the vectors were transfected into NOZ and OCUG-1 cells, respectively. Real-time PCR was used to detect knockdown efficiency. Then, the effects of silencing HOXA-AS2 on the proliferation, cell viability, cell migration, and invasion ability of gallbladder cancer cells were detected by MTT, plate cloning assay, Transwell migration chamber assay, and Transwell invasion chamber assay. Finally, the interaction between HOXA-AS2 and miR-6867 and the 3'UTR of YAP1 protein was detected by luciferase reporter gene. The results showed that the expression level of HOXA-AS2 in gallbladder cancer cell lines was higher than that in control cells. The expression of HOXA-AS2 in gallbladder carcinoma tissues was significantly higher than that in adjacent tissues (p < 0.05). After successful knockout of HOXA-AS2 by lentiviral transfection, the expression of HOXA-AS2 in gallbladder cancer cell lines was significantly decreased. Through cell proliferation and plate clone detection, it was found that silencing HOXA-AS2 inhibited cell proliferation and invasion. Through software prediction and fluorescein reporter gene detection, it was found that HOXA-AS2 has a binding site with miR-6867, and the two are negatively correlated, that is, the expression of miR-6867 is enhanced after the expression of HOXA-AS2 is downregulated. And the 3'UTR of YAP1 protein in the Hippo signaling pathway binds to miR-6867. Therefore, HOXA-AS2 may affect the expression of YAP1 protein by regulating miR-6867, thereby inhibiting the Hippo signaling pathway and promoting the proliferation and metastasis of gallbladder cancer cells. HOXA-AS2 is abnormally expressed in gallbladder cancer cells. HOXA-AS2 may promote the migration and invasion of gallbladder cancer cells by regulating the Hippo signaling pathway through miR-6867. HOXA-AS2 may serve as a potential diagnostic and therapeutic target for gallbladder cancer in clinic.

Ex vivo removal of stones in donor kidneys by pyelotomy prior to renal transplantation: a single-center case series.

Background: Donors with incidentally discovered asymptomatic renal stones was considered a relative contraindication to the kidney donation because of a potential increased morbidity risk for renal transplant recipients. Stone clearance from the donors should be done before donation to ensure safety of the recipient. This study aimed to observe the safety and efficacy of kidney transplantation from donors with nephrolithiasis who received pyelolithotomy before transplantation. Methods: Between January 2015 and March 2021, 14 deceased organ donors at The Second Affiliated Hospital of Guangzhou Medical University were found to have kidney stones during predonation evaluation. After donor kidney repair, all of the donor kidneys underwent ex vivo pyelolithotomy. Then the organs were transplanted to the right iliac fossa of 17 patients with end-stage renal failure. Data were analyzed for technical feasibility, intraoperative and postoperative complications, and stone clearance. Ultrasonography and urinal routine were followed at the 1-, 3-, and 6-month postoperatively. Results: The stones were successfully removed ex vivo by pyelotomy with an average time of 41.0±12.8 minutes. Seventeen recipients successfully underwent renal transplantation, and their renal function recovered well. Slight gross hematuria occurred in 12 cases after operation, and hematuria disappeared after conservative treatment. Ureteral stents were removed within two months after the procedure. There were no complications such as delayed recovery of renal function, acute rejection, ureteral necrosis, and urinary fistula. The serum creatinine of 17 patients 1 month after the operation was 136.8±26.7 µmol/L. None of the 17 patients included in the study suffered from stone recurrence or graft dysfunction in the follow-up period. Conclusions: Ex vivo removal of stones by pyelotomy was a technically feasible means of safely and efficiency rendering a stone-bearing donor kidney stone-free. The procedure obtained good early-middle outcomes in kidney transplantation and is therefore worthy of clinical application.

Ketoreductase Catalyzed (Dynamic) Kinetic Resolution for Biomanufacturing of Chiral Chemicals.

Biocatalyzed asymmetric reduction of ketones is an environmentally friendly approach and one of the most cost-effective routes for producing chiral alcohols. In comparison with the well-studied reduction of prochiral ketones to generate chiral alcohols with one chiral center, resolution of racemates by ketoreductases (KREDs) to produce chiral compounds with at least two chiral centers is also an important strategy in asymmetric synthesis. The development of protein engineering and the combination with chemo-catalysts further enhanced the application of KREDs in the efficient production of chiral alcohols with high stereoselectivity. This review discusses the advances in the research area of KRED catalyzed asymmetric synthesis for biomanufacturing of chiral chemicals with at least two chiral centers through the kinetic resolution (KR) approach and the dynamic kinetic resolution (DKR) approach.

Nursing of acute graft-versus-host disease after simultaneous pancreas-kidney transplantation: a case series study.

Background: This paper aimed to summarize our experience in the nursing of acute graft-versus-host disease (aGVHD) after simultaneous pancreas-kidney transplantation (SPK). Methods: We retrospectively collected and analyzed the demographic characteristics, preoperative evaluation, donor evaluation, screening, and surgical methods of patients with aGVHD after SPK in our center from September 2016 to September 2019. Results: One patient developed intractable diarrhea with decline in platelet (PLT), white blood cell (WBC), and red blood cell (RBC) counts. Meanwhile, the other two patients experienced facial and trunk rashes, hepatic impairment, as well as decreased PLT, WBC, and RBC counts. We took the following nursing interventions: establishing an intensive care team and close monitoring of changes in the condition; protective isolation to minimize exogenous infections; nursing of pulmonary infections; and nutritional support. However, despite careful treatment and nursing, the conditions of the three patients subsequently worsened rapidly and became uncontrollable, and all died. Conclusions: aGVHD is extremely rare after SPK, and no literature exists concerning nursing care or management related to this condition. Clinical manifestations and histopathology are helpful for diagnosis; however, treatment outcomes might be unsatisfactory and the prognosis is poor. Early detection, diagnosis, and intervention have a positive impact on the prognosis of aGVHD, and proper nursing can benefit patients.

Penthorum Chinense Pursh Extract Alleviates Aflatoxin B1-Induced Liver Injury and Oxidative Stress Through Mitochondrial Pathways in Broilers.

Aflatoxin is an important toxicant of the fungal origin and poses a threat to the poultry industry. This study was designed to reveal the underlying mechanism and protective methods against aflatoxin B1 (AFB1)-induced liver injury, oxidative stress, and apoptosis using a Traditional Chinese medicine, Penthorum chinense Pursh extract (PCPE), in broilers. A total of 164 (day-old) broilers were equally allocated to the control, AFB1 (3 mg/kg feed), positive drug (Yin-Chen-Hao Tang extract, 10 ml/kg feed), PCPE (2 g PCPE/kg), and PCPE low, medium, and high dose groups (1 g, 2 g, 3 g PCPE/kg feed, respectively). AFB1 significantly decreased the growth performance and serum immunoglobulin level, altered normal serum biochemical parameters and antioxidant activities, and induced histopathological lesions in the liver as compared to control group. Additionally, AFB1 significantly up-regulated the mRNA expression levels of apoptosis-related genes such as Bax, Bak, caspase-9, caspase-3, and p53, whereas it down-regulated the expression levels of BCL2 in the liver of broilers. The supplementation of different doses of PCPE to AFB1-affected birds significantly eased AFB1 negative effects by improving growth performance, immunoglobulin level, and oxidative capacity, and reversed oxidative stress and pathological lesions in liver. Furthermore, supplementation of PCPE to the AFB1 group reversed apoptosis by significantly down-regulating the mRNA expression levels of Bax, Bak, caspase-9, caspase-3, and p53 and up-regulating the expression levels of BCL2 in the liver of broilers. Based on these results, we conclude that supplementation of PCPE is protective and safe against oxidative stress, is anti-apoptotic, and reverses the liver damage caused by AFB1 in broilers.

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.

Simultaneous antegrade urography of the upper urinary tract and retrograde cystography combined with computed tomography imaging in the management of ureteral complications after renal transplantation.

BACKGROUND: To investigate the significance of simultaneous urography of the upper and lower urinary tract of transplanted kidneys combined with computed tomography urography (CTU), computed tomography arteriography (CTA), and computed tomography venography imaging in the planning of open surgery performed to treat any ureteral complications of a transplanted kidney. METHODS: In all, 24 patients with ureteral complications after renal transplantation were admitted, 12 of whom had renal graft ostomy during open surgery. Simultaneous antegrade urography of the upper urinary tract and retrograde cystography of the transplanted kidneys were performed on the patients. With the use of computed tomography imaging results, surgical planning was carried out. RESULTS: All surgeries were successfully completed according to preoperative planning. Three patients underwent end-to-end anastomosis of the ureter and bladder muscle flap, 8 patients underwent ureterocystostomy, and 1 patient underwent an end-to-end ureteral anastomosis. After the follow-up up to now, all the patients had stable renal function, and no complications such as ureteral stenosis or urine leakage have thus far reoccurred in the transplanted kidneys. CONCLUSIONS: When open surgery is required to treat any ureteral complications following renal transplantation, preoperative multiangle imaging can be used to better understand the condition of the transplanted urinary tract and thus aid considerably in surgical planning.

Autologous bone marrow-derived mesenchymal stem cells for interstitial fibrosis and tubular atrophy: a pilot study.

BACKGROUND: Mesenchymal stem cells (MSCs)-based therapy has shown promising results for renal injury. In this study, the efficacy and safety of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating nonspecific interstitial fibrosis and tubular atrophy (IFTA) were evaluated. METHODS: From March 2011 to January 2013, 11 renal transplanted patients with IFTA were recruited. At baseline, patients were given one intra-arterial infusion of BM-MSCs; 7 days and 1 month later, another two intravenous infusions of cells were followed. Serum creatinine, creatinine clearance rate, and serum cystatin-C at baseline and 7 days, 1 month, 3 months, 6 months, and 12 months after the intra-arterial infusion of BM-MSCs were used to assess renal function. At baseline and 6 months, histological examination based on hematoxylin-eosin, Masson's trichrome and periodic acid-Schiff staining and immunohistochemistry for transforming growth factor ß1 (TGF-ß1) and connective tissue growth factor (CTGF) was performed. Adverse events were recorded to evaluate the safety of BM-MSCs treatment. RESULTS: At 12 months, the renal function of 6 patients (54.5%) was improved, 3 (27.3%) were stable and 2 (18.2%) were worsened. At 6 months, the mean IFTA scores of all participators were similar with the baseline (1.73 ± 0.41 vs.1.50 ± 0.0.77, p = 0.242); however, it was significantly decreased when only 6 patients with improved renal function were analyzed (1.67 ± 0.41 vs. 1.08 ± 0.20, p = 0.013). Besides, decreased expression of TGF-ß1 and CTGF were also observed at 6 months. During 1 year follow-up period, only two minor complications including infection and allergy were observed. CONCLUSION: Our results demonstrated that autologous BM-MSCs are safe and beneficial for IFTA patients. Abbreviations: MSCs: mesenchymal stem cells; BM-MSCs: marrow-derived mesenchymal stem cells; IFTA: interstitial fibrosis and tubular atrophy; CAN: chronic allograft nephropathy; CNIs: calcineurin inhibitors; Scr: serum creatinine; CCr: creatinine clearance rate; Cys-C: cystatin-C; TGF-ß1: transforming growth factor ß1; CTGF: connective tissue growth factor.

Effect of disseminated intravascular coagulation on donation after citizens' death donor kidneys.

BACKGROUND: To investigate the effect of disseminated intravascular coagulation (DIC) on donor kidney in donation after citizens' death (DCD) donors. METHODS: The clinical and laboratory data of 159 DCD donors obtained by our center in 2018 were retrospectively analyzed. The DIC diagnosis was performed according to the Chinese DIC scoring system (CDSS). The donors were divided into two groups: DIC (+) and DIC (-). The difference between kidney rejection rate and zero puncture glomerular microthrombus formation rate were compared. RESULTS: Among the 159 DCD donors, 11 were discarded (accounting for 6.91%). The reasons for the discarded cases included 5 cases (3.14%) for moderate and severe glomerular microthrombus formation in the renal zero puncture pathology; 2 cases (1.26%) for glomerular sclerosis ratio over 50%; 2 cases (1.26%) for long-term low blood pressure before pregnancy and significantly increased serum creatinine level and no urine; 1 case (0.73%) for kidney stones and stagnant water; 1 case (0.63%) for malignant tumor. The donor rejection rate of the DIC (+) group was higher than that of the DIC (-) group, and the difference was statistically significant (P<0.05). Among all donors, 10 cases (6.29%) were found to have glomerular microthrombus at zero puncture, and the microthrombotic rate in the DIC (+) group was significantly higher than that in the DIC (-) group (P<0.05). Of the 10 microthrombotic donors, 5 donors with severe glomerular microthrombus were discarded. CONCLUSIONS: Donor-induced DIC can easily cause renal glomerular microthrombus formation, and the donor kidney rejection rate has increased.

Identification of a novel immune-related microRNA prognostic model in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer, and one of the most common malignant tumors. Many studies have shown that certain microRNAs (miRNAs) play an important role in the occurrence and development of ccRCC. Nevertheless, the prognosis of ccRCC patients is very rarely based on these "immuno-miRs". Our aim was thus to determine the relationship between immune-related miRNA signatures and ccRCC. METHODS: We downloaded the miRNA expression data from 521 KIRC and 71 normal tissues in The Cancer Genome Atlas (TCGA). We used "limma" package and univariate Cox regression analysis to identify differentially expressed miRNAs (DEMs) that related to overall survival (OS). We applied lasso and multivariate Cox regression analyses to construct a prognostic model based on immuno-miRs. We evaluated the performance of model by using the Kaplan-Meier method. Furthermore, Cox regression analysis was used to determine independent prognostic signatures in ccRCC. RESULTS: A total of 59 significant immuno-miRs were identified. We use univariate Cox regression analysis to acquire 18 immune-related miRNAs which were markedly related to OS of ccRCC patients in the training set. We then constructed the 9-immune-related-miRNA prognostic model (miR-21, miR-342, miR-149, miR-130b, miR-223, miR-365a, miR-9-1, and miR-146b) by using lasso and multivariate Cox regression. Further analysis suggested that the immune-related prognostic model could be an independent prognostic indicator for patients with ccRCC. The prognostic performance of the 9-immune-related-miRNA prognostic model was further validated successfully in the testing set. CONCLUSIONS: We established a novel immune-based prognostic model of ccRCC based on potential prognostic immune-related miRNAs. Our results indicated that the 9-miRNA signature could be a practical and reliable prognostic tool for ccRCC.

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.