Blockade of BLyS inhibits B-cell responses and antibody production for the prevention of chronic transplant rejection.

BACKGROUND: Chronic rejection, closely related to the activation of B cells and donor-specific antibody (DSA) production, has unsatisfactory therapeutic outcomes. B lymphocyte stimulator (BLyS) is a major regulatory factor that controls the activation and differentiation of B cells. However, it remains unclear whether BLyS blockade can regulate B and plasma cells in the transplantation setting and affect chronic rejection. Here, we investigated the efficacy of the BLyS inhibitors belimumab and telitacicept in controlling B-cell response and preventing chronic rejection. METHODS: The effects of belimumab and telitacicept on B-cell activation, differentiation, and antibody production in vitro were determined. A chronic rejection model in mouse was established by allogeneic cardiac transplantation with CTLA4-Ig treatment. Allograft survival, histology, DSA levels, and B-cell responses were analyzed to evaluate the chronic rejection-preventive effects of belimumab and telitacicept. RESULTS: In vitro experiments confirmed that belimumab and telitacicept inhibited B-cell activation and differentiation and reduced antibody production. In vivo experiments indicated that they significantly prolonged allograft survival, attenuated chronic rejection through significant suppression of myocardial ischemic necrosis and interstitial fibrosis, and reduced DSA-IgG levels, C4d deposition, and inflammatory cell infiltration. Furthermore, the frequencies of B cells, plasma cells, and IgG-producing cells in the recipients' spleen, lymph nodes, bone marrow, and blood were decreased after BLyS inhibitors treatment. CONCLUSIONS: This study demonstrated that belimumab and telitacicept inhibit B-cell responses and antibody production and alleviate chronic transplant rejection. Therefore, BLyS inhibitors are expected to be used for the prevention of chronic rejection in clinical practice.

Corrigendum: Dynamic risk prediction of BK polyomavirus reactivation after renal transplantation.

[This corrects the article DOI: 10.3389/fimmu.2022.971531.].

Therapeutic strategies against BK polyomavirus infection in kidney transplant recipients: Systematic review and meta-analysis.

BACKGROUND: The selection of antiviral therapy for BK polyomavirus (BKPyV) infection has been extensively debated. Our study aimed to assess the efficacy and safety of various treatments for BKPyV infection. METHODS: We searched PubMed, EMBASE, and Web of Science databases for relevant studies regarding drug treatments for BKPyV viremia/DNAemia published between January 1, 1970 and September 30, 2022. Two independent authors screened the published studies, extracted pertinent data, and evaluated their methodological quality. A meta-analysis was performed using the RevMan software version 4.2.2. RESULTS: A total of 33 published studies involving 986 patients were included in the meta-analysis. Overall, therapeutic interventions comprised immunosuppression reduction alone or in combination with leflunomide, intravenous immunoglobulin (IVIG), cidofovir, or mTOR inhibitor (mTORi) therapy. The meta-analysis revealed that the efficacy of immunosuppression reduction alone for serum BKPyV clearance was 68% (95% confidence interval [CI]: 0.58-0.77; I2 = 78%). Moreover, the efficacy of immunosuppression reduction in combination with leflunomide, cidofovir, IVIG, or mTORi therapy for serum BKPyV clearance was 61% (95% CI: 0.47-0.74; I2 = 83%), 71% (95% CI: 0.63-0.78; I2 = 0), 87% (95% CI: 0.82-0.93; I2 = 45%), and 80% (95% CI: 0.59-1.00; I2 = 58%), respectively. Compared to immunosuppression reduction alone, immunosuppression reduction combined with IVIG therapy offered a statistically significant benefit in serum BKPyV clearance (P < 0.01) with minimal adverse reactions, whereas other adjunctive drug treatments did not demonstrate considerable effects. CONCLUSIONS: Reducing immunosuppression remains the primary approach for treating BKPyV infection. Although the combination treatment with IVIG proved to be most effective, other agents might offer varied antiviral advantages of high heterogeneity, which should be substantiated in future long-term randomized controlled trials.

Microbiota of long-term indwelling hemodialysis catheters during renal transplantation perioperative period: a cross-sectional metagenomic microbial community analysis.

Background: Catheter-related infection (CRI) is a major complication in patients undergoing hemodialysis. The lack of high-throughput research on catheter-related microbiota makes it difficult to predict the occurrence of CRI. Thus, this study aimed to delineate the microbial structure and diversity landscape of hemodialysis catheter tips among patients during the perioperative period of kidney transplantation (KTx) and provide insights into predicting the occurrence of CRI.Methods: Forty patients at the Department of Transplantation undergoing hemodialysis catheter removal were prospectively included. Samples, including catheter tip, catheter outlet skin swab, catheter blood, peripheral blood, oropharynx swab, and midstream urine, from the separate pre- and post-KTx groups were collected and analyzed using metagenomic next-generation sequencing (mNGS). All the catheter tips and blood samples were cultured conventionally.Results: The positive detection rates for bacteria using mNGS and traditional culture were 97.09% (200/206) and 2.65% (3/113), respectively. Low antibiotic-sensitivity biofilms with colonized bacteria were detected at the catheter tip. In asymptomatic patients, no statistically significant difference was observed in the catheter tip microbial composition and diversity between the pre- and post-KTx group. The catheter tip microbial composition and diversity were associated with fasting blood glucose levels. Microorganisms at the catheter tip most likely originated from catheter outlet skin and peripheral blood.Conclusions: The long-term colonization microbiota at the catheter tip is in a relatively stable state and is not readily influenced by KTx. It does not act as the source of infection in all CRIs, but could reflect hematogenous infection to some extent.

Fatal BK polyomavirus-associated pneumonia: report of two cases with literature review.

BACKGROUND: In immunocompromised populations, such as patients with AIDS and recipients of solid organ and hematopoietic stem cell transplants, BK polyomavirus (BKPyV) can reactivate and cause several diseases, which can lead to death in their severe forms. Unlike hemorrhagic cystitis and BKPyV-associated nephropathy, BKPyV-associated pneumonia is rare, with only seven known cases worldwide. However, the disease can rapidly progress with extremely high mortality. CASE PRESENTATION: Herein, we report two cases of BKPyV-associated pneumonia following hematopoietic stem cell transplantation. Both patients had consistent infectious pneumonia and graft-versus-host disease after stem cell transplantation. The diagnosis of BKPyV-associated pneumonia was confirmed by metagenomic next-generation sequencing and polymerase chain reaction after the sudden worsening of the pulmonary infection signs and symptoms concomitant with renal dysfunction and systemic immune weakening. Both patients eventually died of systemic multi-organ failure caused by severe pneumonia. CONCLUSIONS: Currently, BKPyV reactivation cannot be effectively prevented. Immunocompromised patients must actively manage their primary lung infections, pay close attention to pulmonary signs and imaging changes. Especially during and after steroid pulse therapy or immunosuppressive therapy for graft versus host diseases, BKPyV load in blood/urine needs to be regularly measured, and the immunosuppressive intensity should be adjusted properly after the BKPyV reactivation diagnosis. Clinical trials of new antiviral drugs and therapies for BKPyV are urgently needed.

Dynamic viral integration patterns actively participate in the progression of BK polyomavirus-associated diseases after renal transplantation.

The classical lytic infection theory along with large T antigen-mediated oncogenesis cannot explain the BK polyomavirus (BKPyV)-associated tumor secondary to BKPyV-associated nephropathy (BKVAN), viremia/DNAemia, and viruria after renal transplantation. This study performed virome capture sequencing and pathological examination on regularly collected urine sediment and peripheral blood samples, and BKVAN and tumor biopsy tissues of 20 patients with BKPyV-associated diseases of different stages. In the early noncancerous stages, well-amplified integration sites were visualized by in situ polymerase chain reaction, simultaneously with BKPyV inclusion bodies and capsid protein expression. The integration intensity, the proportion of microhomology-mediated end-joining integration, and host PARP-1 and POLQ gene expression levels increased with disease progression. Furthermore, multiomics analysis was performed on BKPyV-associated urothelial carcinoma tissues, identifying tandem-like structures of BKPyV integration using long-read genome sequencing. The carcinogenicity of BKPyV integration was proven to disturb host gene expression and increase viral oncoprotein expression. Fallible DNA double-strand break repair pathways were significantly activated in the parenchyma of BKPyV-associated tumors. Olaparib showed an antitumor activity dose-response effect in the tumor organoids without BRCA1/2 genes mutation. In conclusion, the dynamic viral integration patterns actively participate in the progression of BKPyV-associated diseases and thus could be a potential target for disease monitoring and intervention.

XBP1 modulates endoplasmic reticulum and mitochondria crosstalk via regulating NLRP3 in renal ischemia/reperfusion injury.

The functional status of mitochondria and the endoplasmic reticulum are central to renal ischemia/reperfusion injury (IRI). X-box binding protein 1 (XBP1) is an important transcription factor in endoplasmic reticulum stress. NLR family pyrin domain containing-3 (NLRP3) inflammatory bodies are closely related to renal IRI. In vivo and in vitro, we examined the molecular mechanisms and functions of XBP1-NLRP3 signaling in renal IRI, which influences ER-mitochondrial crosstalk. In this study, mice were subjected to 45 min of unilateral renal warm ischemia, the other kidney resected, and reperfusion was performed for 24 h in vivo. In vitro, murine renal tubular epithelial cells (TCMK-1) were exposed to hypoxia for 24 h and reoxygenation for 2 h. Tissue or cell damage was evaluated by measuring blood urea nitrogen and creatinine levels, histological staining, flow cytometry, terminal deoxynucleotidyl transferase-mediated nick-end labeling, diethylene glycol staining, and transmission electron microscopy (TEM). Western blotting, immunofluorescence staining, and ELISA were used to analyze protein expression. Whether XBP1 regulates the NLRP3 promoter was evaluated using a luciferase reporter assay. Kidney damage was reduced with decreasing blood urea nitrogen, creatinine, interleukin-1ß, and interleukin-18 levels. XBP1 deficiency reduced tissue damage and cell apoptosis, protecting the mitochondria. Disruption of XBP1 was associated with reduced NLRP3 and cleaved caspase-1 levels and markedly improved survival. In vitro in TCMK-1 cells, XBP1 interference inhibited caspase-1-dependent mitochondrial damage and reduced the production of mitochondrial reactive oxygen species. The luciferase assay showed that spliced XBP1 isoforms enhanced the activity of the NLRP3 promoter. These findings reveal that XBP1 downregulation suppresses the expression of NLRP3, a potential regulator of endoplasmic reticulum mitochondrial crosstalk in nephritic injury and a potential therapeutic target in XBP1-mediated aseptic nephritis.

The impact of angiotensin converting enzyme insertion/deletion gene polymorphism on diabetic kidney disease: A debatable issue.

OBJECTIVE: The objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk. METHODS: All eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software. RESULTS: In overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR=1.316, 95% CI: 1.213-1.427, P=0.000; DD versus ID+II: OR=1.414, 95% CI: 1.253-1.595, P=0.000; II versus DD+ID: OR=0.750, 95% CI: 0.647-0.869, P=0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR=1.361, 95% CI: 1.243-1.490, P=0.000; DD versus ID+II: OR=1.503, 95% CI: 1.310-1.726, P=0.000; II versus DD+ID: OR=0.738, 95% CI: 0.626 -0.870, P=0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients. CONCLUSION: ACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD.

A single-center analysis of genotype-phenotype characteristics of Chinese patients with autosomal dominant polycystic kidney disease by targeted exome sequencing.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by PKD1 and PKD2 mutations. However, only a few studies have investigated the genotype and phenotype characteristics of Asian patients with ADPKD. This study aimed to investigate the relationship between the natural course of ADPKD genotype and phenotype. Methods: Genetic studies of PKD1/2 genes of Chinese patients with ADPKD in a single center were performed using targeted exome sequencing and next-generation sequencing on peripheral blood DNA. Results: Among the 140 patients analyzed, 80.00% (n = 112) harbored PKD1 mutations, 11.43% (n = 16) harbored PKD2 mutations, and 8.57% (n = 12) harbored neither PKD1 nor PKD2 mutations. The average age at dialysis was 52.60 ± 11.36, 60.67 ± 5.64, and 52.11 ± 14.63 years, respectively. The renal survival rate of ADPKD patients with PKD1 mutations (77/112) was significantly lower than that of those with PKD2 mutations (9/16), leading to an earlier onset of end-stage renal disease (ESRD). Renal prognosis was poor for those with nonsense mutations, and they required earlier renal replacement therapy. Conclusions: The genotype and phenotype characteristics of ADPKD patients potentially vary across ethnic groups. Our findings supplement the genetic profiles of Chinese ADPKD patients, could serve as a guide for therapy monitoring and prognosis assessment of ADPKD, and may improve the clinical diagnosis.

Dynamic risk prediction of BK polyomavirus reactivation after renal transplantation.

Purpose: To construct a dynamic prediction model for BK polyomavirus (BKV) reactivation during the early period after renal transplantation and to provide a statistical basis for the identification of and intervention for high-risk populations. Methods: A retrospective study of 312 first renal allograft recipients with strictly punctual follow-ups was conducted between January 2015 and March 2022. The covariates were screened using univariable time-dependent Cox regression, and those with P<0.1 were included in the dynamic and static analyses. We constructed a prediction model for BKV reactivation from 2.5 to 8.5 months after renal transplantation using dynamic Cox regression based on the landmarking method and evaluated its performance using the area under the curve (AUC) value and Brier score. Monte-Carlo cross-validation was done to avoid overfitting. The above evaluation and validation process were repeated in the static model (Cox regression model) to compare the performance. Two patients were presented to illustrate the application of the dynamic model. Results: We constructed a dynamic prediction model with 18 covariates that could predict the probability of BKV reactivation from 2.5 to 8.5 months after renal transplantation. Elder age, basiliximab combined with cyclophosphamide for immune induction, acute graft rejection, higher body mass index, estimated glomerular filtration rate, urinary protein level, urinary leukocyte level, and blood neutrophil count were positively correlated with BKV reactivation, whereas male sex, higher serum albumin level, and platelet count served as protective factors. The AUC value and Brier score of the static model were 0.64 and 0.14, respectively, whereas those of the dynamic model were 0.79 ± 0.05 and 0.08 ± 0.01, respectively. In the cross-validation, the AUC values of the static and dynamic models decreased to 0.63 and 0.70 ± 0.03, respectively, whereas the Brier score changed to 0.11 and 0.09 ± 0.01, respectively. Conclusion: Dynamic Cox regression based on the landmarking method is effective in the assessment of the risk of BKV reactivation in the early period after renal transplantation and serves as a guide for clinical intervention.

The impact of angiotensin converting enzyme insertion/deletion gene polymorphism on diabetic kidney disease: A debatable issue / El impacto del polimorfismo del gen de inserción/deleción de la enzima convertidora de la angiotensina en la enfermedad renal diabética: una cuestión discutible

Objective: The objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk.MethodsAll eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software.ResultsIn overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR=1.316, 95% CI: 1.213–1.427, P=0.000; DD versus ID+II: OR=1.414, 95% CI: 1.253–1.595, P=0.000; II versus DD+ID: OR=0.750, 95% CI: 0.647–0.869, P=0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR=1.361, 95% CI: 1.243–1.490, P=0.000; DD versus ID+II: OR=1.503, 95% CI: 1.310–1.726, P=0.000; II versus DD+ID: OR=0.738, 95% CI: 0.626 –0.870, P=0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients.ConclusionACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD. (AU)

Objetivo: El objetivo de este estudio fue evaluar la influencia de los polimorfismos del gen I/D de la ECA en el riesgo de enfermedad renal diabética (ERD).MétodosSe identificaron todas las investigaciones elegibles, se revisó el número de varios genotipos en el grupo de casos y controles. El análisis combinado se realizó con el software Stata.ResultadosEn el conjunto de los sujetos, se incluyeron 24.321 participantes con 12.961 casos y 11.360 controles. El análisis combinado mostró una relación significativa entre el alelo D, el genotipo DD o II y el riesgo de DKD (D frente a I: OR=1,316, IC del 95%: 1,213–1,427, P=0,000; DD frente a ID+II: OR=1,414, IC del 95%: 1,253-1,595, P=0,000; II frente a DD+ID: OR=0,750, 95% CI: 0,647-0,869, P=0,000). El análisis de subgrupos mostró que el polimorfismo del gen I/D de la ECA se correlacionaba con la DMD tanto en la población asiática como en la china. Además, el polimorfismo del gen I/D de la ECA se correlacionó con la DKD de tipo 2 (D frente a I: OR=1,361, IC del 95%: 1,243-1,490, P=0,000; DD frente a ID+II: OR=1,503, IC del 95%: 1,310-1,726, P=0,000; II frente a DD+ID: OR=0,738, 95% CI: 0,626 -0,870, P=0,000). Sin embargo, no hubo una correlación evidente en los sujetos caucásicos y en los pacientes diabéticos de tipo 1.ConclusiónLos polimorfismos I/D de la ECA se correlacionaron con la DKD en poblaciones asiáticas y diabéticas de tipo 2. El alelo D de la ECA/genotipo DD podría ser un factor de riesgo, mientras que el genotipo II de la ECA podría ser un factor de protección para la DKD. (AU)

Relationship between controlled attenuated parameter and magnetic resonance imaging-proton density fat fraction for evaluating hepatic steatosis in patients with NAFLD.

We used cross-sectional and longitudinal studies to comprehensively compare hepatic steatosis measurements obtained with magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and controlled attenuated parameter (CAP) in hepatic steatosis in adults with nonalcoholic fatty liver disease (NAFLD). A total of 185 participants with NAFLD and 12 non-NAFLD controls were recruited. CAP and MRI-PDFF data were collected at baseline from all participants and from 95 patients included in the longitudinal study after 24 weeks of drug or placebo intervention. Pearson correlation, linear regression, and piecewise linear regression analyses were used to evaluate the relationship between the two modalities. Linear analysis suggested a positive correlation between CAP and MRI-PDFF (r = 0.577, p < 0.0001); however, piecewise linear regression showed no correlation when CAP was ≥331 dB/m (p = 0.535). In the longitudinal study, both the absolute and relative change measurements were correlated between the two modalities; however, the correlation was stronger for the relative change (relative r = 0.598, absolute r = 0.492; p < 0.0001). Piecewise linear regression analysis revealed no correlation when CAP was reduced by more than 53 dB/m (p = 0.193). Conclusions: We found a correlation between CAP and MRI-PDFF measurements for grading hepatic steatosis when CAP was <331 dB/m. While the measured absolute change and relative change were correlated, it was stronger for the relative change. These findings have implications for the clinical utility of CAP or MRI-PDFF in the clinical diagnosis and assessment of NAFLD.

Acute transient thyroid swelling after fine-needle aspiration biopsy: A case report of a rare complication and a literature review.

Fine-needle aspiration biopsy (FNAB) is a safe and effective thyroid examination method with rare complications. Herein, we report a rare case of acute transient thyroid swelling that occurred after ultrasound-guided FNAB. The patient experienced acute pain with rapid thyroid swelling. Ultrasound imaging revealed a nodule with a linear, hypoechoic, and "patch-like" appearance, indicating edema without hemorrhage. After receiving anti-anaphylaxis and detumescence therapy for 1 day, the swelling regressed. Acute transient thyroid swelling is an extremely rare event that occurs shortly after FNAB and may frighten patients; therefore, clinicians should be aware of this complication in this context.

The Influence of ACE Insertion/Deletion Gene Polymorphism on the Risk of IgA Nephropathy: A Debatable Topic.

Background: The connection between angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphisms and IgA nephropathy (IgAN) was conflicting. This pooled analysis was performed to explore this issue. Methods: All eligible investigations were identified from various electronic databases, and the pooled analysis was evaluated using Stata software. Results: 27 studies with 2538 IgAN cases and 3592 controls were included. In overall subjects, ACE D allele, DD, and II genotype were associated with IgAN susceptibility (D vs. I: OR = 1.21, 95% CI: 1.10-1.32, P < 0.001; DD vs. ID + II: OR = 1.38, 95% CI: 1.20-1.60, P < 0.001; and II vs. DD + ID: OR = 0.83, 95% CI: 0.73-0.95, P=0.007). In Asian and Chinese patients, ACE I/D gene polymorphism was also correlated with IgAN vulnerability. Moreover, ACE D allele, DD, and II genotype were correlated with the progression of IgAN (D vs. I: OR = 1.37, 95% CI: 1.09-1.73, P=0.008; DD vs. ID + II: OR = 1.57, 95% CI: 1.06-2.31, P=0.024; and II vs. DD + ID: OR = 0.69, 95% CI: 0.49-0.99, P=0.045). Conversely, in Caucasian subjects, there was no link between ACE I/D gene polymorphism and the risk of IgAN. Conclusion: ACE I/D gene polymorphism was correlated with the vulnerability and progression of IgAN in Asian and Chinese patients, and ACE D allele and DD homozygote genotype could be adverse factors for IgAN, while the II homozygote genotype could be an advantage factor. But, no significant association was found between ACE I/D gene polymorphism and IgAN in Caucasians.

Heterogeneity of cell composition and origin identified by single-cell transcriptomics in renal cysts of patients with autosomal dominant polycystic kidney disease.

Rationale: Renal cysts in patients with autosomal dominant polycystic kidney disease (ADPKD) can originate from any nephron segments, including proximal tubules (PT), the loop of Henle (LOH), distal tubules (DT), and collecting ducts (CD). Previous studies mostly used limited cell markers and failed to identify cells negative for these markers. Therefore, the cell composition and origin of ADPKD cyst are still unclear, and mechanisms of cystogenesis of different origins await further exploration. Methods: We performed single-cell RNA sequencing for the normal kidney tissue and seven cysts derived from superficial or deep layers of the polycystic kidney from an ADPKD patient. Results: Twelve cell types were identified and analyzed. We found that a renal cyst could be derived either from CD or both PT and LOH. Gene set variation analysis (GSVA) showed that epithelial mesenchymal transition (EMT), TNFA signaling via the NFKB pathways, and xenobiotic metabolism were significantly activated in PT-derived cyst epithelial cells while robust expression of genes involved in G2M Checkpoint, mTORC1 signaling, E2F Targets, MYC Targets V1, MYC Targets V2 were observed in CD-derived cells. Conclusion: Our results revealed that a single cyst could originate from CD or both PT and LOH, suggesting heterogeneity of polycystic composition and origin. Furthermore, cyst epithelial cells with different origins have different gene set activation.

Case Report: Malacoplakia Due to E. coli With Cryptococcus albidus Infection of a Transplanted Kidney in a Patient With Recurrent Urinary Tract Infection.

Background: Colonization of Cryptococcus rarely occurs in a graft. This study reports a case of malacoplakia and cryptococcoma caused by E. coli and Cryptococcus albidus in a transplanted kidney, with detailed pathology and metagenome sequencing analysis. Case Presentation: We presented a case of cryptococcoma and malacoplakia in the genitourinary system including the transplant kidney, bladder, prostate, and seminal vesicles caused by Cryptococcus albidus and Escherichia coli in a renal-transplant recipient. Metagenome sequencing was conducted on a series of samples obtained from the patient at three different time points, which we termed Phase I (at the diagnosis of cryptococcoma), Phase II (during perioperative period of graftectomy, 3 months after the diagnosis), and Phase III (2 months after graftectomy). Sequencing study in the Phase I detected two and four sequences of C. albidus respectively in cerebrospinal fluid (CSF) and feces, with resistant Escherichia coli 09-02E presented in urine and renal mass. A 3-month antibiotic treatment yielded a smaller bladder lesion but an enlarged allograft lesion, leading to a nephrectomy. In the Phase II, two sequences of C. albidus were detected in CSF, while the E. coli 09-02E continued as before. In the Phase III, the lesions were generally reduced, with one C. albidus sequence in feces only. Conclusions: The existence and clearance of Cryptococcus sequences in CSF without central nervous system symptoms may be related to the distribution of infection foci in vivo, the microbial load, and the body's immunity. Overall, this study highlights the need for enhanced vigilance against uncommon types of Cryptococcus infections in immunocompromised populations and increased concern about the potential correlation between E. coli and Cryptococcus infections.

The impact of angiotensin converting enzyme insertion/deletion gene polymorphism on diabetic kidney disease: A debatable issue.

OBJECTIVE: The objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk. METHODS: All eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software. RESULTS: In overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR=1.316, 95% CI: 1.213-1.427, P=0.000; DD versus ID+II: OR=1.414, 95% CI: 1.253-1.595, P=0.000; II versus DD+ID: OR=0.750, 95% CI: 0.647-0.869, P=0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR=1.361, 95% CI: 1.243-1.490, P=0.000; DD versus ID+II: OR=1.503, 95% CI: 1.310-1.726, P=0.000; II versus DD+ID: OR=0.738, 95% CI: 0.626 -0.870, P=0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients. CONCLUSION: ACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD.

[Prognostic value of preoperative serum albumin in patients with non-muscle-invasive bladder cancer undergoing transurethral resection of bladder tumor].

OBJECTIVE: To assess the value of preoperative serum albumin level in predicting the survival of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing transurethral resection of bladder tumor (TURBT). METHODS: Two hundred and sixteen newly diagnosed patients with NMIBC who underwent TURBT between January, 2007 and April, 2012 were retrospectively analyzed. The patients were categorized into low albumin (<40 g/L) and normal albumin (≥40 g/L) groups. The patient survival was estimated using the Kaplan-Meier method, and univariate and multivariate Cox proportional analyses were used to determine the hazard ratios (HRs) for the overall survival (OS). RESULTS: Of the patients with available data, 82 (39%) and 127 (61%) patients were classified into low albumin (<40 g/L) and normal albumin (≥40 g/L) groups, respectively. Kaplan-Meier analysis showed a significantly worse 5-year OS in low albumin group than in normal albumin group (P=0.017). In the multivariate Cox regression analysis, after adjusting for confounding variables, the preoperative albumin level remained as an independent predictor for 5-year OS (HR: 3.102, 95%CI: 1.200-8.020, P=0.020). CONCLUSION: A low preoperative albumin level predicts a poor 5-year OS in patients with NMIBC who underwent TURBT. Preoperative serum albumin can be a good prognostic factor for predicting survival of the patients with NMIBC treated with TURBT.

Expression of HERC4 in lung cancer and its correlation with clinicopathological parameters.

BACKGROUND: Growing evidence suggests that the members of the ubiquitin-proteasome system (UPS) are important for tumorigenesis. HERC4, one component, is a recently identified ubiqutin ligase. However, the expression level and function role of HERC4 in lung cancer remain unknown. Our objective was to investigate any correlation between HERC4 and development of lung cancer and its clinical significance. MATERIALS AND METHODS: To determine HERC4 expression in lung cancer, an immunohistochemistry analysis of a tissue microarray containing samples of 10 lung normal tissues, 15 pulmonary neuroendocrine carcinomas, 45 squamous epithelial cancers and 50 adenocarcinomas was conducted. Receiver operating characteristic (ROC) curve analysis was applied to obtain a cut-off point of 52.5%, above which the expression of HERC4 was regarded as "positive". RESULTS: On the basis of ROC curve analysis, positive expression of HERC4 was detected in 0/10 (0.0%) of lung normal tissues, in 4/15 (26.7%) of pulmonary neuroendocrine carcinomas, in 13/45 (28.9%) of squamous epithelial cancers and in 19/50 (38.0%) of adenocarcinomas. It showed that lung tumors expressed more HERC4 protein than adjacent normal tissues (χ2=4.675, p=0.031). Furthermore, HERC4 positive expression had positive correlation with pT status (χ2=44.894, p=0.000), pN status (χ2=43.628, p=0.000), histological grade (χ2=7.083, p=0.029) and clinical stage (χ2=72.484, p=0.000), but not age (χ2=0.910, p=0.340). CONCLUSIONS: Our analysis suggested that HERC4 is likely to be a diagnostic biomarker for lung cancer.