Haematopoietic stem cell transplantation for hepatitis-associated aplastic anaemia and non-hepatitis-associated aplastic anaemia: A propensity score-matched analysis.

To validate the efficacy and safety of haematopoietic stem cell transplantation (HSCT) in hepatitis-associated aplastic anaemia (HAAA) patients, we reviewed 260 patients who underwent HSCT for acquired aplastic anaemia and eventually included 30 HAAA patients and 90 non-HAAA patients using propensity score matching. In the HAAA group, the estimated 5-year overall survival rate (75.8% vs. 86.5%, p = 0.409), failure-free survival (FFS) rate (74.0% vs. 83.2%, p = 0.485), graft-versus-host disease (GVHD)-free FFS rate (61.2% vs. 67.6%, p = 0.669) after HSCT were slightly lower but not statistically significant than those in the non-HAAA group. Both groups did not significantly differ in engraftment, post-transplant severe infection, cytomegalovirus (CMV) or Epstein-Barr virus viraemia, or GVHD incidences. The patterns of immune reconstitution were broadly consistent between the two groups. When stratifying HAAA patients according to donor type, no significant differences in survival, transplant-related mortality, or GVHD cumulative incidences were observed. CMV viraemia (68.7% vs 8.3%, p = 0.009) occurred more commonly in haploidentical donor (HID) transplants than in matched sibling donor transplants. However, early CMV disease incidence (5.6% vs. 0.0%, p = 1.000) was low. Overall, the post-transplant outcomes of HAAA patients were comparable to those of non-HAAA patients after balancing potential confounders, and HID-HSCT can offer an alternative curative option for HAAA.

Assessing the Quality of Metagenomic Next-Generation Sequencing for Pathogen Detection in Lower Respiratory Infections.

BACKGROUND: Laboratory-developed metagenomic next-generation sequencing (mNGS) assays are increasingly being used for the diagnosis of infectious disease. To ensure comparable results and advance the quality control for the mNGS assay, we initiated a large-scale multicenter quality assessment to scrutinize the ability of mNGS to detect pathogens in lower respiratory infections. METHODS: A reference panel containing artificial microbial communities and real clinical samples was used to assess the performance of 122 laboratories. We comprehensively evaluated the reliability, the source of false-positive and false-negative microbes, as well as the ability to interpret the results. RESULTS: A wide variety of weighted F1-scores was observed across 122 participants, with a range from 0.20 to 0.97. The majority of false positive microbes (68.56%, 399/582) were introduced from "wet lab." The loss of microbial sequence during wet labs was the chief cause (76.18%, 275/361) of false-negative errors. When the human context is 2 × 105 copies/mL, most DNA and RNA viruses at titers above 104 copies/mL could be detected by >80% of the participants, while >90% of the laboratories could detect bacteria and fungi at titers lower than 103 copies/mL. A total of 10.66% (13/122) to 38.52% (47/122) of the participants could detect the target pathogens but failed to reach a correct etiological diagnosis. CONCLUSIONS: This study clarified the sources of false-positive and false-negative results and evaluated the performance of interpreting the results. This study was valuable for clinical mNGS laboratories to improve method development, avoid erroneous results being reported, and implement regulatory quality controls in the clinic.

Risk factors and predictive model for acute kidney Injury Transition to acute kidney disease in patients following partial nephrectomy.

PURPOSE: Acute kidney disease (AKD) is believed to be involved in the transition from acute kidney injury (AKI) to chronic kidney disease in general populations, but little is understood about this possibility among kidney surgical populations. This study aimed to elucidate the incidence of AKD after partial nephrectomy and risk factors that promote the AKI to AKD transition. METHODS: From January 2010 to January 2020, this study retrospectively collected a dataset of consecutive patients with renal masses undergoing partial nephrectomy in 4 urological centers. Cox proportional regression analyses were adopted to identify risk factors that promoted the AKI to AKD transition. To avoid overfitting, the results were then verified by logistic least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then constructed and validated for AKI to AKD transition prediction. RESULTS: AKI and AKD occurred in 228 (21.4%) and 42 (3.9%) patients among a total of 1062 patients, respectively. In patients with AKI, multivariable Cox regression analysis and LASSO regression identified that age (HR 1.078, 1.029-1.112, p < 0.001), baseline eGFR (HR 1.015, 1.001-1.030, p < 0.001), RENAL score (HR1.612, 1.067-2.437, p = 0.023), ischemia time > 30 min (HR 7.284, 2.210-23.999, p = 0.001), and intraoperative blood loss > 300ml (HR 8.641, 2.751-27.171, p < 0.001) were risk factors for AKD transition. These five risk factors were then integrated into a nomogram. The nomogram showed excellent discrimination, calibration, and clinical net benefit ability. CONCLUSION: Around 3.9% patients following partial nephrectomy would transit from AKI to AKD. Intraoperative blood loss and ischemia time need to be diminished to avoid on-going functional decline. Our nomogram can accurately predict the transition from AKI to AKD.

Evidence accumulation for value computation in the prefrontal cortex during decision making.

A key step of decision making is to determine the value associated with each option. The evaluation process often depends on the accumulation of evidence from multiple sources, which may arrive at different times. How evidence is accumulated for value computation in the brain during decision making has not been well studied. To address this problem, we trained rhesus monkeys to perform a decision-making task in which they had to make eye movement choices between two targets, whose reward probabilities had to be determined with the combined evidence from four sequentially presented visual stimuli. We studied the encoding of the reward probabilities associated with the stimuli and the eye movements in the orbitofrontal (OFC) and the dorsolateral prefrontal (DLPFC) cortices during the decision process. We found that the OFC neurons encoded the reward probability associated with individual pieces of evidence in the stimulus domain. Importantly, the representation of the reward probability in the OFC was transient, and the OFC did not encode the reward probability associated with the combined evidence from multiple stimuli. The computation of the combined reward probabilities was observed only in the DLPFC and only in the action domain. Furthermore, the reward probability encoding in the DLPFC exhibited an asymmetric pattern of mixed selectivity that supported the computation of the stimulus-to-action transition of reward information. Our results reveal that the OFC and the DLPFC play distinct roles in the value computation during evidence accumulation.

Is Anti-Reflux Anastomosis an Advantage in an Orthotopic Ileal Neobladder? A Systematic Review and Meta-Analysis.

INTRODUCTION: We conducted a systematic review and meta-analysis to assess the available literature regarding the postoperative effects of anti-reflux anastomosis and direct anastomosis in orthotopic ileal neobladder (ONB). METHODS: We searched PubMed, Embase, and the Cochrane Library in October 2021. We included 11 studies of patients with bladder cancer who underwent radical cystectomy and ONB as urinary diversion. Outcomes evaluated in this review were ureteroenteric anastomotic stricture (UEAS), vesicoureteral reflux, renal function (RFn) impairment, and pyelonephritis. All data were analyzed using Review Manager 5.4.4 and subgroup analyses were applied. RESULTS: A total of 11 studies were eligible for meta-analysis. The synthetic data suggested that anti-reflux anastomosis and direct anastomosis were comparable in terms of RFn impairment (odds ratio (OR) = 1.69; 95% confidence interval (CI): 0.18-15.6; p = 0.65, I2 = 69%) and pyelonephritis (OR = 1.13; 95% CI: 0.65-1.99; p = 0.66, I2 = 1%) without significant difference in each group statistically. The pooled study data showed a significantly higher incidence of UEAS (OR = 2.84; 95% CI: 1.75-4.61, p < 0.0001, I2 = 50%) and a lower incidence of vesicoureteral reflux (OR = 0.24; 95% CI: 0.10-0.59; p = 0.002, I2 = 75%) in anti-reflux anastomosis compared to direct anastomosis. In subgroup analysis, anti-reflux anastomosis was more likely to result in UEAS than direct anastomosis, especially when ureteral stent was removed within 14 days. CONCLUSION: Although meta-analysis showed that overall incidence of vesicoureteral reflux was higher with direct anastomosis than anti-reflux anastomosis, the rate of vesicoureteral reflux was not directly related to impairment of RFn. The anti-reflux mechanism of ONB was positively associated with a higher incidence of significant UEAS compared to the direct approach, which can lead to kidney damage and an increased risk of secondary surgical procedures.

Universal relation with regime transition for sediment transport in fine-grained rivers.

Fine-grained sediment (grain size under 2,000 µm) builds floodplains and deltas, and shapes the coastlines where much of humanity lives. However, a universal, physically based predictor of sediment flux for fine-grained rivers remains to be developed. Herein, a comprehensive sediment load database for fine-grained channels, ranging from small experimental flumes to megarivers, is used to find a predictive algorithm. Two distinct transport regimes emerge, separated by a discontinuous transition for median bed grain size within the very fine sand range (81 to 154 µm), whereby sediment flux decreases by up to 100-fold for coarser sand-bedded rivers compared to river with silt and very fine sand beds. Evidence suggests that the discontinuous change in sediment load originates from a transition of transport mode between mixed suspended bed load transport and suspension-dominated transport. Events that alter bed sediment size near the transition may significantly affect fluviocoastal morphology by drastically changing sediment flux, as shown by data from the Yellow River, China, which, over time, transitioned back and forth 3 times between states of high and low transport efficiency in response to anthropic activities.

Comparison of porcine ALG and rabbit ATG on outcomes of HLA-haploidentical hematopoietic stem cell transplantation for patients with acquired aplastic anemia.

OBJECTIVE: To evaluate the efficacy and safety of P-ALG (porcine anti-lymphocyte globulin) and R-ATG (rabbit anti-thymocyte globulin) in the conditioning regime for patients with acquired aplastic anemia who underwent HLA-haploidentical hematopoietic stem cell transplantation (halpo-HSCT). METHODS: A total of 91 patients with acquired aplastic anemia who received haplo-HSCT at our center between January 2014 and December 2020 were retrospectively reviewed. Twenty-eight patients were in the P-ALG group while sixty-three patients were in the R-ATG group. RESULTS: The median time was 11 versus 13 days (P = 0.294) for myeloid engraftment and 12.5 versus 15 days (P = 0.465) for platelet engraftment in the P-ALG and R-ATG groups, respectively. There were no significant difference in 5-year overall survival (74.83% ± 8.24% vs 72.29% ± 6.26%, P = 0.830), GVHD-free, failure-free survival (71.05% ± 8.65% vs 62.71% ± 6.22%, P = 0.662), failure-free survival (74.83% ± 8.24% vs 66.09% ± 5.84%, P = 0.647) and transplantation-related mortality (25.17% ± 8.24% vs 26.29% ± 6.22%, P = 0.708) between the two groups. The incidence of aGVHD (acute graft versus host disease) (65.39% ± 9.33% vs 62.71% ± 6.30%, P = 0.653), II-IV aGVHD (38.46% ± 9.54% vs 35.64% ± 6.24%, P = 0.695), III-IV aGVHD (19.23% ± 7.73% vs 10.53% ± 4.07%, P = 0.291), cGVHD (chronic graft versus host disease) (22.22% ± 12.25% vs 22.31% ± 6.30%, P = 0.915), and moderate to severe cGVHD (5.56% ± 5.40% vs 9.28% ± 4.46%, P = 0.993) were not significantly different. Similar outcomes were observed between the P-ALG and R-ATG groups for severe bacterial infection (17.9% vs 25.4%, P = 0.431), invasive fungal diseases (3.6% vs 9.5%, P = 0.577) and graft rejection (0% vs 9.5%, P = 0.218). However, the incidence of cytomegalovirus infection and Epstein-Barr virus infection was significantly lower in the P-ALG group (46.4% vs 71.4%, P = 0.022; 3.6% vs 25.4%, P = 0.014). CONCLUSION: The efficacy and safety of P-ALG were similar with R-ATG in the setting of haplo-HSCT for patients with acquired aplastic anemia patients. P-ALG could be an alternative for R-ATG.

Targeting MYC and BCL2 by a natural compound for "double-hit" lymphoma.

Concurrent translocations of MYC and BCL2 lead to abnormal expression of both oncoproteins, which contribute to the aggressive clinical characteristics of double-hit lymphoma (DHL). An effective therapy for DHL remains an unmet clinical need. In this study, we showed that both Ca2+ /calmodulin-dependent protein kinase II δ (CAMKIIδ) and γ (CAMKIIγ) were highly expressed in DHL. Both isoforms of CAMKII stabilize c-Myc protein by phosphorylating it at Ser62, increase BCL2 expression, and promote DHL tumor growth. Inhibition of CAMKIIδ and CAMKIIγ by either berbamine (BBM) or one of its derivatives (PA4) led to the down regulation of c-Myc and BCL2 proteins. BBM/PA4 also exhibited anti-tumor efficacy in DHL cell lines and NSG xenograft models. Altogether, CAMKIIδ and CAMKIIγ appear to be critical for DHL tumor development and are promising therapeutic targets for DHL.

High CENPA expression in papillary renal cell carcinoma tissues is associated with poor prognosis.

OBJECTIVE: This work focused on investigating the relation of centromeric protein A (CENPA) gene expression with prognosis of papillary renal cell carcinoma (PRCC). METHODS: We obtained data from PRCC cases in TCGA. Thereafter, CENPA levels between the paired PRCC and matched non-carcinoma samples were analyzed by Wilcoxon rank-sum test, while the relations of clinicopathological characteristics with CENPA level were examined by logistic regression and Wilcoxon rank-sum test. The prognostic value of CENPA was assessed by plotting the receiver operating feature curve (ROC) and calculating the value of area under curve (AUC). In addition, relations between clinicopathological characteristics and PRCC survival were analyzed through Kaplan-Meier (KM) and Cox regression analyses. After dividing the total number of patients into the trial cohort and the validation cohort in a ratio of 7:3, we constructed a nomogram in trial cohort according to multivariate Cox regression results for predicting how CENPA affected patient survival and used the calibration curve to verify its accuracy in both cohorts. We also determined CENPA levels within cancer and matched non-carcinoma samples through immunohistochemistry (IHC). Finally, we utilized functional enrichment for identifying key pathways related to differentially expressed genes (DEGs) between PRCC cases with CENPA up-regulation and down-regulation. RESULTS: CENPA expression enhanced in PRCC tissues compared with healthy counterparts (P < 0.001). CENPA up-regulation was related to pathological TNM stage and clinical stage (P < 0.05). Meanwhile, the ROC curves indicated that CENPA had a remarkable diagnostic capacity for PRCC, and the expression of CENPA can significantly improve the predictive accuracy of pathological TNM stage and clinical stage for PRCC. As revealed by KM curves, PRCC cases with CENPA up-regulation were associated with poor survival compared with those with CENPA down-regulation (Risk ratio, RR = 3.07, 95% CI: 1.58-5.97, P = 0.001). In the meantime, univariate as well as multivariate analysis showed an independent association of CENPA with overall survival (OS, P < 0.05) and the nomogram demonstrated superior predictive ability in both cohorts. IHC analysis indicated that PRCC cases showed an increased CENPA positive rate compared with controls. As revealed by functional annotations, CENPA was enriched into pathways associated with neuroactive ligand receptor interactions, cytokine receptor interactions, extracellular matrix regulators, extracellular matrix glycoproteins and nuclear matrisome. CONCLUSION: CENPA expression increases within PRCC samples, which predicts dismal PRCC survival. CENPA may become a molecular prognostic marker and therapeutic target for PRCC patients.

Clinical characteristics and prognosis of pediatric myelin oligodendrocyte glycoprotein antibody-associated diseases in China.

BACKGROUND: Research on myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD) among Chinese children is relatively rare. Therefore, this study aimed to explore and analyze the clinical characteristics and prognoses of Chinese children with acquired demyelinating syndromes (ADSs) who tested positive or negative for MOG-Ab. METHODS: The clinical data of children with MOGAD who were treated in the Department of Neurology at Shanghai Children's Hospital from January 2017 to October 2021 were retrospectively collected. RESULTS: Among 90 children with ADSs, 30 were MOG-Ab-positive, and 60 were MOG-Ab-negative. MOG-Ab-positive children experienced more prodromal infections than did MOG-Ab-negative children (P < 0.05). Acute disseminated encephalomyelitis was the most common ADSs in both groups. There were ten cases of a rebound increase in MOG-Ab titers. There were significant differences in the MOG titer-related prognosis and disease time course between the disease relapse group and the non-relapse group (P < 0.01). Among the MOG-Ab-positive patients, the most affected brain areas detected via magnetic resonance imaging (MRI) were the temporal lobe, cerebellar hemispheres, brainstem, and periventricular lesions. The most common shapes of the lesions were commas, triangles, or patches. The average improvement time based on brain MRI was much longer in MOG-Ab-positive than in MOG-Ab-negative children (P < 0.05). The initial treatment time correlated with the disease time course, and the prognosis may be affected by the disease time course and serum MOG-Ab titer (P < 0.05). CONCLUSION: The clinical characteristics and imaging features of ADSs differed between MOG-Ab-positive and MOG-Ab-negative children. In addition to existing treatment plans, additional diagnoses and treatment plans should be developed to reduce recurrence and improve the prognoses of children with MOGAD.

Long non-coding RNA LINC01116 acts as an oncogene in prostate cancer cells through regulation of miR-744-5p/UBE2L3 axis.

BACKGROUND: Long non-coding RNA (lncRNA) has been confirmed to exert a critical effect on the progression of tumors, including prostate cancer. Previous literature has demonstrated LINC01116 involves in activities of multiple cancers. However, the underlying role of LINC01116 in prostate cancer remains unclear. METHODS: qRT-PCR measured the expression of LINC01116 in prostate cancer cells. EdU experiment was used to detect cell proliferation. Transwell assays detected cell migration and invasion. Immunofluorescence staining and western blot assays were utilized to measure EMT progress. The binding relationship between RNAs was confirmed by a series of mechanism assays. In addition, rescue experiments were conducted to verify the relationship among RNAs. RESULTS: LINC01116 was found to be highly expressed in prostate cancer cells. Functional assays indicated that inhibition of LINC01116 could suppress cell proliferation, migration, invasion and EMT progress. Also, miR-744-5p was proven to bind with LINC01116. Moreover, UBE2L3 was verified as the target gene of miR-744-5p. In rescue assays, we discovered that inhibited miR-744-5p or overexpressed UBE2L3 could offset the suppressive influence of silencing LINC01116 on prostate cancer cells. CONCLUSION: Our study suggested that lncRNA LINC01116 acted as an oncogene in prostate cancer and accelerated prostate cancer cell growth through regulating miR-744-5p/UBE2L3 axis.

Primary breast double-hit lymphoma management and outcomes: a real-world multicentre experience.

BACKGROUND: Primary breast double-hit lymphoma (PB-DHL) is a rare, highly aggressive malignancy that poses challenges regarding accurate diagnosis and selecting optimal treatment regimens. METHODS: We retrospectively reviewed 48 cases of patients diagnosed with PB-DHL in six academic centres between June 2014 and June 2020 in China. Study-specific data were recorded, including treatment options, therapeutic evaluation, prognostic factors and relapse patterns, and the overall survival (OS) and progression-free survival (PFS) were evaluated. RESULTS: In total, 48 patients were enrolled, with 14 patients treated with DA-EPOCH-R/MA (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, alternating with high-dose methotrexate and cytarabine), 18 patients treated with DA-EPOCH-R (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and 16 patients treated with R-HyperCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate). The overall 5-year OS and PFS rates were 41.7% (95% confidence interval [CI], 27.6-56.8%) and 37.5% (95% CI, 24.0-52.6%), respectively. Of the three treatment regimens, the 5-year OS was higher in DA-EPOCH-R/MA group than in the DA-EPOCH-R or R-HyperCVAD subgroups (57.1% vs. 38.9% vs. 31.3%; P = 0.016), as was the 5-year PFS (50.0% vs. 38.9% vs. 25.0%; P = 0.035). Autologous stem cell transplantation (ASCT) prolonged the OS and PFS compared with non-ASCT patients (5-year OS: 72.2% vs. 23.3%; P < 0.001; 5-year PFS: 72.2% vs. 16.7 %, P < 0.001). Multivariate analysis identified tumour size, risk stratification, treatment with DA-EPOCH-R/MA, breast irradiation, and ASCT as significant prognostic factors. CONCLUSIONS: DA-EPOCH-R/MA is a promising regimen for PB-DHL, and breast irradiation yields complementary benefits for prognosis. ASCT significantly decreased disease relapse, providing a potential curative PB-DHL intervention and justifying ASCT as first-line therapy for young patients. More effective treatment strategies for PB-DHL patients remain encouraging.

The mouse model of hepatic veno-occlusive disease.

With the application of hematopoietic stem cell transplantation, Subacute or acute increase in the incidence of hepatic veno-occlusive disease (HVOD) becomes more common and it can lead to fatal complications. This article characterizes a mouse model of HVOD induced by monocrotaline. After gavage with monocrotaline was performed on BALB/c mice, On the 3rd, 4th, 6th, 8th and 10th days, mice were anesthetized, blood was collected and the liver was removed. Liver slices were processed by HE stain, Masson's trichrome stain or immunohistochemical stain. From days 3 through 4, histopathology and cytokine changes were determined as severe, early HVOD. From days 6 through 8, the changes were considered to represent late HVOD. On the 10th day, the above changes showed that late HVOD gradually improved.

Squamous cell carcinoma of the renal parenchyma presenting as hydronephrosis: a case report and review of the recent literature.

BACKGROUND: Primary squamous cell carcinoma of the renal parenchyma is extremely rare, only 5 cases were reported. CASE PRESENTATION: We probably report the fifth case of primary Squamous cell carcinoma (SCC) of the renal parenchyma in a 61-year-old female presenting with intermittent distending pain for 2 months. Contrast-enhanced computed tomography (CECT) revealed hydronephrosis of the right kidney, but a tumor cannot be excluded completely. Finally, nephrectomy was performed, and histological analysis determined that the diagnosis was kidney parenchyma squamous cell carcinoma involving perinephric adipose tissue. CONCLUSIONS: The present case emphasizes that it is difficult to make an accurate preoperative diagnosis with the presentation of hidden malignancy, such as hydronephrosis.

A Combination of the Mayo Adhesive Probability Score and the RENAL Score to Predict Intraoperative Complications in Small Renal Masses.

INTRODUCTION: To evaluate the potential predictive value of the Mayo Adhesive Probability (MAP) score combined with the RENAL score for intraoperative outcomes in retroperitoneal laparoscopic nephron-sparing surgery (NSS) in an Eastern Asian population. METHODS: An initial of 388 patients undergoing retroperitoneal laparoscopic NSS were identified. MAP and RENAL scores were calculated according to CT and a logistic regression model was adopted as a combination of the RENAL score and the MAP score. RESULTS: A total of 293 patients were included. The overall intraoperative complication rate was 7.5% (21 cases). The MAP score was found to correlate with operation time (OT; r = 0.169), estimated blood loss (EBL; r = 0.318), and intraoperative complications (r = 0.242). The RENAL score was correlated with warm is-chemia time (r = 0.503), OT (r = 0.334), intraoperative complications (r = 0.178), and EBL (r = 0.218). The MAP score and the RENAL score were reliable predictors of overall intraoperative complications, with areas under the curve (AUC) of 0.728 and 0.759, respectively. After combination of these 2 scores, the AUC of overall intra-operative complications was improved with statistical significance (AUC = 0.847, combination vs. RENAL score: p = 0.044 < 0.05; combination vs. MAP score: p = 0.005 < 0.05). CONCLUSION: The MAP score is an important predictor of EBL, OT, and intraoperative complications in retroperitoneal laparoscopic NSS and its combination with the RENAL score showed a superior predictive value compared to a single score in overall intraoperative complications. The MAP score might be considered in preoperative radiologic aspects as regularly as the RENAL score.

The Handling of Oxalate in the Body and the Origin of Oxalate in Calcium Oxalate Stones.

Urolithiasis is one of the most common urologic diseases in industrialized societies. More than 80% of renal stones are composed of calcium oxalate, and small changes in urinary oxalate concentrations affect the risk of stone formation. Elucidation of the source of oxalate and its mechanism of transport is crucial for understanding the etiology of urolithiasis. Sources of oxalate can be both endogenous and exogenous. With regard to oxalate transport, tests were carried out to prove the function of solute-linked carrier 4 (SLC4) and SLC26. The molecular mechanism of urolithiasis caused by SLC4 and SLC26 is still unclear. The growing number of studies on the molecular physiology of SLC4 and SLC26, together with knockout genetic mouse model experiments, suggest that SLC4 and SLC26 may be a contributing element to urolithiasis. This review summarizes recent research on the sources of oxalate and characterization of the oxalate transport ionic exchangers SLC4 and SLC26, with an emphasis on different physiological defects in knockout mouse models including kidney stone formation. Furthermore, SLC4 and SLC26 exchangers provide new insight into urolithiasis and may be a novel therapeutic target for modification of urinary oxalate excretion.

Total tubeless versus standard percutaneous nephrolithotomy: a meta-analysis.

To compare the safety and efficacy of total tubeless percutaneous nephrolithotomy (PCNL) with standard PCNL for the treatment of upper urinary calculi. PubMed, EMBASE, Cochrane Library and ScienceDirect were searched for collecting related literature on the two procedures. All compared studies, including randomized controlled trials (RCT), cohort studies (CS) and case-control studies (CCS), were included. Totally, 14 studies were included. Pooled data demonstrated that patients who underwent total tubeless PCNL were associated with significantly shorter operation time [weighted mean difference (WMD): -3.41, P = 0.004], shorter hospital stay (WMD: -1.54, P < 0.00001). It seemed that significantly less postoperative analgesic requirement could be found in the total tubeless PCNL group according to subgroup analysis. However, no significant differences could be found between the two groups in stone-free rate [risk ratio (RR): 1.03, P = 0.26], hemoglobin drop (WMD: -0.03, P = 0.85), and rates of postoperative fever (RR: 0.53, P = 0.11) and transfusion (RR: 0.79, P = 0.41). Sensitivity analysis after excluding CCS revealed results similar to previous findings. Total tubeless PCNL would be superior to standard PCNL in reducing operation time, hospital stay and postoperative analgesic requirement without significantly more adverse events.

The Effect of Daily Fluid Management and Beverages Consumption on the Risk of Bladder Cancer: A Meta-analysis of Observational Study.

Epidemiological studies have evaluated the risk of bladder cancer (BCa) in relation to total fluid intake, as well as specific type of beverages consumption, with controversial results. The aim of this study was to further explore the potential relationship by conducting a meta-analysis. Fifty-four articles involving more than 43,000 BCa patients were included in this meta-analysis. A positive, though not statistically significant, association was found between total fluid intake and risk of BCa comparing the highest with lowest intake (SRRE: 1.16, 95%CI: 1.00-1.36). By conducting dose-response meta-analysis, we found that each 500 ml/day increase in total fluid intake was associated with 3.3% increased risk of BCa (RR: 1.03, 95%CI: 1.00-1.07). Pronounced increase in risk of BCa was detected when total fluid intake was more than 3000 ml/day. Meta-analyses of specific type of beverages showed increasing intake of coffee (RR: 1.03, 95%CI: 1.02-1.05) were risk factors for BCa. On the contrary, increasing intake of milk appeared to be a potential protective factor for BCa (RR: 0.90, 95%CI: 0.83-0.98). The risk of BCa was not significantly related to intake of water (RR: 1.01, 95%CI: 0.98-1.03), alcohol (RR: 1.01, 95%CI: 0.97-1.05), tea (RR: 1.01, 95%CI: 0.97-1.05) and soft drinks (RR: 1.04, 95%CI: 0.96-1.11).

A novel compound heterozygous mutation of the L2HGDH gene in a Chinese boy with L-2-hydroxyglutaric aciduria: case report and literature review.

OBJECTIVE: L-2-hydroxyglutaric aciduria is a genetic metabolic disorder. Its clinical features include elevated levels of hydroxyglutaric acid in body fluids and abnormal magnetic resonance imaging (MRI) in the subcortical white matter, which are affected by the accumulation of L-2-hydroxyglutaric acid. METHOD: A boy with psychomotor retardation and progressive ataxia accompanied by abnormal brain MRI findings was tested using whole-exome sequencing. RESULTS: Next-generation sequencing (NGS) revealed two novel compound heterozygous frameshift mutations, c.407 del A (p.K136SfsTer3) and c.699_c700 ins A (p.D234RfsTer42), in the L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene, leading to premature termination codons and truncated FAD/NAD(P)-binding domain of L2HGDH protein. Further laboratory testing revealed an increase in the 2-hydroxyglutaric acid level in the urine. CONCLUSION: The results suggested that NGS could provide clues for identifying patients with abnormal neuroradiological findings in the subcortical white matter.