Cholecystectomy and risk of cardiovascular disease, all-cause and cause-specific mortality: a systematic review and updated meta-analysis.

Objective: Questions remain about the association among cholecystectomy, cardiovascular disease, all-cause and cause-specific mortality. We performed a systematic review and meta-analysis to clarify these associations. Methods: PubMed, Web of Science, Embase, and Cochrane Library databases were searched up to February 2024. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a DerSimonian-Laird random effects model. Results: We screened 16,595 articles and included 14 studies. No significant association was found between cholecystectomy and cardiovascular disease (CVD), with RR being 1.03 (95% CI [0.77-1.37], p = 0.848, I 2 = 99.6%), even in results with high heterogenous studies excluded (RR 1.20, 95% CI [0.97-1.49], p = 0.095, I 2 = 77.7%). Same result was proved in its subtype, coronary heart disease (RR 1.06, 95% CI [0.84-1.33], p = 0.633, I2 = 96.6%). Cholecystectomy increased CVD risk compared with healthy controls without gallstones (RR 1.19, 95% CI [1.05-1.35], p = 0.007, I 2 = 83.3%) and lowered CVD risk compared with gallstone carriers (RR 0.62, 95% CI [0.57-0.67], p < 0.001, I 2 = 82.1%). As for mortality, increase in the risk for all-cause (RR 1.17, 95% CI [1.03-1.34], p = 0.020, I 2 = 51.6%) and cardiovascular (RR 1.24, 95% CI [1.06-1.47], p = 0.009, I 2 = 20.7%) mortality, but not for cancer mortality (RR 1.18, 95% CI [0.95-1.47], p = 0.131, I 2 = 0.0%), were observed after cholecystectomy. Conclusion: Cholecystectomy may not be associated with the overall development of CVD, as well as CHD. Cholecystectomized patients showed increased CVD risk compared with healthy controls without gallstones, but decreased CVD risk compared with gallstone patients. Increased risk for all-cause and cardiovascular, but not cancer mortality was observed following cholecystectomy.

Abandonment Leads to Changes in Forest Structural and Soil Organic Carbon Stocks in Moso Bamboo Forests.

The important role of soil carbon pools in coping with climate change has become widely recognized. Moso bamboo (Phyllostachys pubescens) is an economically important bamboo species in South China; however, owing to factors such as rising labor costs and increasingly stringent environmental policies, Moso bamboo forests have recently been abandoned. The present study aimed to investigate the effects of abandonment on structural factors and soil organic carbon (SOC) stocks in Moso bamboo forests. We investigated Moso bamboo forests subjected to intensive management or abandonment for different durations and measured forest structural characteristics, mineral properties, soil nutrients, and other soil properties. Although abandonment did not significantly affect the height and diameter at breast height, it increased culm densities, biomass, and SOC stocks. The drivers of SOC stocks depended on soil depth and were mainly controlled by carbon decomposition mediated by soil properties. In the topsoil, mineral protection and soil total nitrogen (TN) exerted significant effects on SOC stocks; in the subsoil, soil TN was the main driver of SOC stocks. As the controlling factors of SOC stocks differed between the subsoil and topsoil, more attention should be paid to the subsoil. Overall, these findings refine our understanding of the structural characteristics and SOC stocks associated with Moso bamboo forest abandonment, serving as a reference for the follow-up management of these forests.

Algorithm of face anti-spoofing based on pseudo-negative features generation.

Introduction: Despite advancements in face anti-spoofing technology, attackers continue to pose challenges with their evolving deceptive methods. This is primarily due to the increased complexity of their attacks, coupled with a diversity in presentation modes, acquisition devices, and prosthetic materials. Furthermore, the scarcity of negative sample data exacerbates the situation by causing domain shift issues and impeding robust generalization. Hence, there is a pressing need for more effective cross-domain approaches to bolster the model's capability to generalize across different scenarios. Methods: This method improves the effectiveness of face anti-spoofing systems by analyzing pseudo-negative sample features, expanding the training dataset, and boosting cross-domain generalization. By generating pseudo-negative features with a new algorithm and aligning these features with the use of KL divergence loss, we enrich the negative sample dataset, aiding the training of a more robust feature classifier and broadening the range of attacks that the system can defend against. Results: Through experiments on four public datasets (MSU-MFSD, OULU-NPU, Replay-Attack, and CASIA-FASD), we assess the model's performance within and across datasets by controlling variables. Our method delivers positive results in multiple experiments, including those conducted on smaller datasets. Discussion: Through controlled experiments, we demonstrate the effectiveness of our method. Furthermore, our approach consistently yields favorable results in both intra-dataset and cross-dataset evaluations, thereby highlighting its excellent generalization capabilities. The superior performance on small datasets further underscores our method's remarkable ability to handle unseen data beyond the training set.

Globotriaosylsphingosine improves risk stratification of kidney progression in Fabry disease patients.

BACKGROUND: Kidney damage is common in patients with Fabry disease (FD), but more accurate information about the risk of progression to kidney failure is needed for clinical decision-making. In particular, FD patients with mild renal involvement often lack timely intervention and treatment. We aimed to utilize a model to predict the risk of renal progression in FD patients. METHODS: Between November 2011 and November 2019, ERT-naive patients with FD were recruited from three medical centers in China. To assess the risk of a 50% decline in the estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD), Cox proportional hazards models were utilized. The performance of these models was assessed using discrimination, calibration, and reclassification. RESULTS: A total of 117 individuals were enrolled. The mean follow-up time was 4.8 years, during which 35 patients (29.9 %) progressed to the composite renal outcomes. Male sex, baseline proteinuria, eGFR and globotriaosylsphingosine (Lyso-Gb3) were found to be independent risk factors for kidney progression by the Cox model, based on which a combined model containing those clinical variables and Lyso-Gb3 and clinical models including only clinical indicators were constructed. The two prediction models had relatively good performance, with similar model fit measured by R2 (59.8 % vs. 61.1 %) and AIC (51.54 vs. 50.08) and a slight increase in the C statistic (0.949 vs. 0.951). Calibration curves indicated closer alignment between predicted and actual renal outcomes in the combined model. Furthermore, subgroup analysis revealed that Lyso-Gb3 significantly improved the predictive performance of the combined model for kidney prognosis in low-risk patients with a baseline eGFR over 60 ml/min/1.73 m2 or proteinuria levels less than 1 g/d when compared to the clinical model. CONCLUSIONS: Lyso-Gb3 improves the prediction of kidney outcomes in FD patients with a low risk of progression, suggesting that these patients may benefit from early intervention to assist in clinical management. These findings need to be externally validated.

Surgical treatment for pelvic haemophilic pseudotumour: a retrospective analysis of 21 cases.

Background: Due to the rarity of pelvic haemophilic pseudotumour (PHPT) and demanding surgical technique for PHPT excision, no study reports the mid-term follow-up outcomes of surgical treatment of PHPT in a relatively large cohort. PHPT with varying degrees of bony pelvic involvement and infection status necessitates different operative procedures, yet there is currently no classification system for PHPT based on surgical practice. Methods: The study was conducted between June 25, 2004 and July 18, 2023, in Peking Union Medical College Hospital and Nanfang Hospital in China. We performed a retrospective analysis involving 21 patients with 24 PHPTs with a mean follow-up period of 7.1 years. The demographic information, PHPT characteristics, surgical data, and perioperative complications were analysed. Findings: 21 consecutive male patients with 24 PHPTs (21 primary PHPTs and three recurrent PHPTs) that underwent surgical treatment were involved in the study. A classification system including four subtypes was introduced as (I) PHPT confined to soft tissue; (II) PHPT involving bony pelvic without pelvic discontinuity; (III) PHPT causing pelvic discontinuity; (IV) Infectious PHPT. Of the 24 PHPTs, 11 (45.8%) were identified as Type I, five (20.8%) as Type II, three (12.5%) as Type III, and five (20.8%) as Type IV. At the time of surgery, the patients had a mean age of 37.0 ± 9.5 years (Range, 24-52 years). The mean maximum diameter of PHPTs upon surgery was 17.0 ± 7.7 cm (Range, 4.3-40.0 cm). The mean surgical duration was 192 ± 77 min (Range, 60-330 min) and the median intraoperative blood loss was 400 mL (IQR, 225-950 mL, Range, 100-3000 mL). One patient (4.8%) underwent intraoperative cardiopulmonary arrest and expired the following week. Four PHPTs (16.7%) presented postoperative wound infections and poor wound healing. During the follow-up period, five PHPTs (20.8%) experienced pseudotumour recurrence. Interpretation: Our findings suggest that surgical treatment for PHPTs is feasible and relatively safe. Symptomatic and progressive PHPTs should undergo surgical intervention as early as possible to minimise the surgical risks. Intraoperative use of abundant gelatin sponges in PHPT excision draws attention to severe embolism complications. Funding: There are no sources of funding for this manuscript.

Multifunctional Injectable Microspheres Containing "Naturally-Derived" Photothermal Transducer for Synergistic Physical and Chemical Treating of Acute Osteomyelitis through Sequential Immunomodulation.

Osteomyelitis induced by Staphylococcus aureus (S. aureus) is a persistent and deep-seated infection that affects bone tissue. The main challenges in treating osteomyelitis include antibiotic resistance, systemic toxicity, and the need for multiple recurrent surgeries. An ideal therapeutic strategy involves the development of materials that combine physical, chemical, and immunomodulatory synergistic effects. In this work, we prepared injectable microspheres consisting of an interpenetrating network of ionic-cross-linked sodium alginate (SA) and genipin (Gp)-cross-linked gelatin (Gel) incorporated with tannic acid (TA) and copper ions (Cu2+). The Gp-cross-linked Gel acted as a "naturally-derived" photothermal therapy (PTT) agent. The results showed that the microspheres exhibited efficient and rapid bactericidal effects against both S. aureus and Escherichia coli (E. coli) under the irradiation of near-infrared light at 808 nm wavelength; moreover, the release of Cu2+ also induced sustained inhibitory effects against bacteria during the nonirradiation period. The in vitro cell culture results indicated that when combined with PTT, the microspheres could adaptively modulate macrophage M1 and M2 phenotypes in sequence. Additionally, these microspheres were found to enhance the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo studies conducted in a rat femur osteomyelitis model with bone defects showed that under multiple laser irradiation the microspheres effectively controlled bacterial infection, improved the pathological immune microenvironment, and significantly enhanced the repair and regeneration of bone tissues in the affected area.

Manganese regulation of COPII condensation controls circulating lipid homeostasis.

Precise control of circulating lipids is instrumental in health and disease. Bulk lipids, carried by specialized lipoproteins, are secreted into the circulation, initially via the coat protein complex II (COPII). How the universal COPII machinery accommodates the abundant yet unconventional lipoproteins remains unclear, let alone its therapeutic translation. Here we report that COPII uses manganese-tuning, self-constrained condensation to selectively drive lipoprotein delivery and set lipid homeostasis in vivo. Serendipitously, adenovirus hijacks the condensation-based transport mechanism, thus enabling the identification of cytosolic manganese as an unexpected control signal. Manganese directly binds the inner COPII coat and enhances its condensation, thereby shifting the assembly-versus-dynamics balance of the transport machinery. Manganese can be mobilized from mitochondria stores to signal COPII, and selectively controls lipoprotein secretion with a distinctive, bell-shaped function. Consequently, dietary titration of manganese enables tailored lipid management that counters pathological dyslipidaemia and atherosclerosis, implicating a condensation-targeting strategy with broad therapeutic potential for cardio-metabolic health.

Trade-offs between ligninase and cellulase and their effects on soil organic carbon in abandoned Moso bamboo forests in southeast China.

A vast expanse of Moso bamboo (Phyllostachys pubescens J.Houz.) forests in subtropical areas was once intensively managed but has been abandoned in recent years. However, the response of soil organic carbon (SOC) to abandonment management remains unclear, partly because how carbon-degrading enzymes vary with abandonment management and the role of this change in the soil carbon cycle are still poorly understood, which restricts the scientific evaluation of carbon sink benefits of these abandoned Moso bamboo forests. The results of the survey, based on 40 Moso bamboo forests, showed that compared with intensive management, abandonment management for 7-10 and 11-14 years exhibited a significant decrease in ligninase activities (a reduction of 12.14 % and 44.41 %, respectively) and a significant increase in SOC content (an increase of 49.39 % and 52.64 %, respectively). However, abandonment management did not affect cellulase activities or easily oxidizable organic carbon content (p > 0.05), but significantl increased non-easily oxidizable organic carbon (p < 0.05). Furthermore, the total nitrogen (TN) content and pH value increased with prolonged abandonment, and these trade-offs between ligninase and cellulase were primarily driven by pH and TN. The ligninase-to-cellulase activities ratio is the most key factor affecting NEOC and SOC changes in abandoned Moso bamboo forests. Together, these findings demonstrate the response of carbon-degrading enzyme trade-offs to abandonment management and highlight the role of these trade-offs in controlling SOC accumulation. In addition, the different responses of different SOC fractions to abandonment management deserve attention in future studies.

Microbial pathways driving stable soil organic carbon change in abandoned Moso bamboo forests in southeast China.

Mineral-associated organic carbon (MOC) is a stable component of the soil carbon (C) pool, critical to realize carbon sequestration and coping with climate change. Many Moso bamboo (Phyllostachys edulis) forests in subtropical and tropical areas that used to be intensively managed have been left unmanaged. Still, studies on MOC changes occurring during the transition from intensive management to unmanagement are lacking. Besides, the understanding of the role of microorganisms in MOC accumulation is far from satisfactory. Based on the combination of field investigation and laboratory analysis of 40 Moso bamboo forest sampling plots with different unmanaged chronosequence's in southeast China, we observed the MOC content in Moso bamboo forests left unmanaged for 2-5 years had decreased, whereas that in forests left unmanaged for 11-14 years had increased compared with that in intensively managed forests. Specifically, the MOC contents in forests left unmanaged for 11-14 years were significantly higher than in those under intensive management or unmanaged for 2-5 years. Moreover, we found that microorganisms drove MOC change through two different pathways: (i) more microorganisms led to more soil nutrients, which led to more amino sugars, ultimately resulting in the accumulation of MOC, and (ii) microorganisms promoted the accumulation of MOC by influencing the content of metal oxides (poorly crystalline aluminum oxides and free aluminum oxides). We believe that ignoring the interaction between microorganisms and metal oxides may lead to uncertainty in evaluating the relative contribution of microbial residues to MOC.

Comparative Transcriptome Analysis Revealing the Potential Mechanism of Low-Temperature Stress in Machilus microcarpa.

Machilus microcarpa is a rare national tree species in China and possesses important ornamental and ecological value. M. microcarpa can be planted in low-temperature areas, depending on whether its seedlings can withstand the harm. To face this problem, the annual seedlings of M. microcarpa were subjected to five temperature treatments, and eight physiological indicators were measured. Furthermore, comparative transcriptome analysis was performed between M. microcarpa leaves treated at 25°C and -2.8°C. A total of 9,385 differentially expressed genes (DEGs) were involved in low-temperature stress in M. microcarpa. An upregulated (cobA) and five downregulated (HEM, CHLM, CRD, CLH, and PORA) genes associated with the porphyrin and chlorophyll metabolism pathway may reduce chlorophyll synthesis under low-temperature stress. Upregulation of six DEGs (two GAPDHs, PFK, PGAM, PDC, and PK) involved in the glycolysis/gluconeogenesis pathway provided energy for M. microcarpa under adverse cold conditions. Thirteen upregulated and seven downregulated genes related to antioxidant enzymes were also observed under low-temperature stress. Candidate transcription factors (TFs) played key roles in signal transduction under low-temperature stress in M. microcarpa, and quantitative real-time PCR (qRT-PCR) analysis validated the RNA-seq data. The results provide valuable information for further studies on the cold response mechanisms for low-temperature stress in M. microcarpa.

Variations in rhizosphere soil total phosphorus and bioavailable phosphorus with respect to the stand age in Pinus massoniana Lamb.

Phosphorus (P) is a nutrient limiting plant growth in subtropical regions. However, our understanding of how soil P responds to an increase in stand age is rather poor. In particular, little is known about how bioavailable P pools (soluble P, exchangeable P, hydrolyzable P, and ligand P) shift with a change in stand age. Moreover, the P cycle in rhizosphere soil has the most direct and significant influence on plants. The aim of the present study was to determine the concentrations of total P in various rhizosphere soil bioavailable P fractions in 5-, 9-, 19-, 29-, and 35-year-old stands of Pinus massoniana Lamb. According to the results, total P (TP) concentration and N:P ratio in rhizosphere soil first decreased, and then increased with an increase in stand age. Soluble P concentration decreased first, and then increased with an increase in stand age; exchangeable P and ligand P decreased first, and then tended to be stable with an increase in stand age, whereas hydrolyzable P increased first, and then decreased. Structural Equation Model results suggested that ligand P and soluble P were the major factor affecting the TP. In addition, soil microorganisms and acid phosphatase-driven hydrolyzable P play a crucial role in soil bioavailable P cycling. Overall, the results of our study provide a mechanistic understanding of soil bioavailable P cycling under low available P conditions, and a basis for an effective P management strategy for the sustainable development of P. massoniana plantations.

Fine-Root Decomposition and Nutrient Return in Moso Bamboo (Phyllostachys pubescens J.Houz.) Plantations in Southeast China.

Plant fine-root decomposition is an important pathway for the reentry of nutrients into the soil. Studies have mainly focused on the loss of fine-root mass and the release characteristics of major elements, including, C, N, and P, but there are few reports on trace elements. In this study, in situ decomposition experiments were conducted to study the dynamic characteristics of mass loss and residual rates of 10 mineral elements in two diameter classes (<2 mm and 2-5 mm) of moso bamboo in the process of fine-root decomposition. The results of the year-long experiment reported herein showed that: (1) fine roots with diameters of less than 2 mm decomposed faster than those with diameters of 2-5 mm; (2) C, N, P, K, Ca, and Mg were released, whereas Fe, Mn, Zn, and Cu were enriched or changed little; (3) decomposition time and root diameter had significant effects on the remaining percentages of C, N, K, Ca, Mg, Mn, Zn, and Cu, and there were interactions among the elements (P < 0.05). The remaining percentages of P and Fe were only affected by decomposition time. This is the first comprehensive report on the variation in 10 elements during the fine-root decomposition of moso bamboo. The study expands our understanding of the release of mineral nutrients during fine-root decomposition, laying a solid theoretical foundation for further research on fine-root decomposition and plant-soil nutrient cycling.

Surgical treatment for patients with hemophilic pseudotumor-related femoral fracture: a retrospective study.

BACKGROUND: Hemophilic pseudotumor (HPT)-related fracture is a rare but severe complication in patients with HPTs. These fractures often occur in femurs. There is no consensus on the standard surgical protocol for HPT-related femoral fracture. The present retrospective study evaluated the outcomes of these patients treated with surgical interventions. METHODS: Ten patients with HPT-related femoral fractures who were treated with 14 surgical procedures due to 11 fractures in our hospital from January 2014 to April 2020 were evaluated retrospectively. Demographic data, fracture location, complications after surgery, and follow-up outcomes were recorded and analyzed. The mean follow-up period was 39.7 months. RESULTS: The mean age at surgery was 31 years. Closed reduction external fixation (CREF) was originally performed in 2 patients, open reduction internal fixation (ORIF) was performed in 4 patients, screw fixation alone was performed in 1 patient, brace immobilization was performed in 1 patient, and amputation was performed in 3 patients. Bone union was observed in 5 patients, and an adequate callus was visible in 2 patients. Both patients with CREF had pin infections. Nonunion combined with external fixation (EF) failure occurred in 1 patient, and the plate was broken after ORIF. Three patients underwent autogenous or allogeneic cortical strut grafting. Three patients had HPT recurrence. CONCLUSIONS: It is necessary to perform surgery in patients with HPT-related femoral fractures. Surgical treatments must consider fracture stabilization and HPT resection. Internal fixation is preferable, and EF should only be used for temporary fixation. If the HPT erodes more than one third of the bone diameter, strut grafts are necessary for mechanical stability. Amputation is an appropriate curative method in certain situations.

Treatment of pelvic haemophilic pseudotumour: A retrospective study.

BACKGROUND: The incidence of a pelvic haemophilic pseudotumour is very low and is rarely seen in the clinic. Due to the lack of clear treatment standards, patients often suffer from the condition over a protracted period. The aim of this retrospective study was to present our institutional experience in the treatment of pelvic haemophilic pseudotumours over the past 8 years. METHODS: We retrospectively analysed patients with a pelvic haemophilic pseudotumour who were treated in the Nanfang hospital between February 2012 and December 2019. The type and severity of haemophilia, the presence of inhibitors, comorbidities, pseudotumour imaging data, treatment and follow-up results were recorded and analysed. RESULTS: Pelvic pseudotumours were identified in seven patients with haemophilia. Three patients had severe haemophilia, three had moderate haemophilia, one had mild haemophilia and inhibitors were present in two patients. Transfusion-related infectious diseases were noted in three patients. Spontaneous rupture and infection of the pseudotumour occurred in five patients. In addition, five patients underwent surgical treatment, two of whom healed well, two patients suffered recurrence of the pseudotumour, and one patient developed a postoperative haematoma twice. Two patients were treated conservatively, one of whom was unable to walk because of progression of the disease, while the other died from severe bleeding and infection. CONCLUSIONS: Once a pelvic haemophilic pseudotumour is diagnosed, surgical resection should be performed as soon as possible. A delay in diagnosis and suboptimal treatment may lead to complications of the pelvic haemophilic pseudotumour.

Acute Kidney Disease Increases the Risk of Post-Kidney Biopsy Bleeding Complications.

INTRODUCTION: Kidney biopsy, providing the insightful information for most kidney diseases, is an invasive diagnostic tool with certain risks ranging from the least severe macroscopic hematuria to the most severe life-threatening bleeding necessitating renal artery embolization. We aimed to compare the postbiopsy bleeding complications between 2 common methods and to further explore the risk factors of bleeding complications in patients using the negative pressure suction puncture (NPS) method. METHODS: We retrospectively collected the data from percutaneous native kidney biopsies in 2016. The clinical, laboratory tests, pathological findings, and the occurrence of bleeding complications following kidney biopsy were analyzed. The kidney biopsy was performed in our center by experienced nephrologists with 2 different methods, namely, NPS method and real-time ultrasound-guided needle (RTU) method. We compared rates of complications between 2 methods and evaluated univariate and multivariate association of risk factors with bleeding complications in the NPS group. RESULTS: 626 kidney biopsies were performed between January 2016 and December 2016. There were 83.2% (521/626) participants in the NPS group and 16.8% (105/626) in the RTU group. There were more participants in the RTU group needing >1 needle pass during biopsy than those in the NPS group (61.0 vs. 14.7%, p < 0.001). Acute kidney disease (AKD) occurred before the procedure of kidney biopsy accounted for 13.8% (72/521) in the NPS group and 1.9% (2/105) in the RTU group. The renal pathological findings revealed higher number of glomeruli in the NPS group than in the RTU group (26.8 ± 13.0 vs. 17.2 ± 8.6, p < 0.001). The incidence of bleeding complications in the NPS group was lower than that in the RTU group (9.2 vs. 21.9%, p < 0.01). Logistic multivariate regression showed that AKD was independently associated with bleeding complications after kidney biopsy in the NPS group. CONCLUSION: Regarding the bleeding risk, there was noninferiority of NPS over RTU. AKD contributes to higher risks of bleeding complications after kidney biopsy.

[Mechanism and surgical treatment of acetabular roof column fractures with external iliac arterial injury: analysis of 4 cases].

Pelvic arterial injuries caused by pelvic or acetabular fractures are rare (15%-20%), and the complication by external iliac artery (EIA) injuries is even rarer, which can result in a mortality rate as high as 75%-83%. The mechanism of major artery damage caused by pelvic or acetabular fractures remains unclear. We report our experience with surgical treatment of 4 patients with acetabular roof column fracture and EIA injury. All the 4 patients underwent injury control resuscitation and surgery after admission. One patient died of multiple organ dysfunction syndrome (MODS), and the other 3 patients recovered smoothly. In these cases, as we presume, the occurrence of acetabular roof column fracture caused the EIA, which was connected to the iliopsoas muscle through soft tissues such as the iliac fascia, to be pulled into the fracture space along with the iliopsoas muscle and was cut directly by the fracture end; the EIA may also be punctured during transport and fracture reduction. Although acetabular roof column fractures with EIA injuries rarely occur, the consequences can be fatal. In such cases, clinicians should be highly vigilant about the possibility of large vessel injuries, and its early detection using threedimensional vascular reconstruction based on CT vessels or arterial interventional angiography can be critical for implementation of early treatment to save the limbs.

Clinical significance of plasma globotriaosylsphingosine levels in Chinese patients with Fabry disease.

Although plasma globotriaosylsphingosine (lyso-Gb3) is a promising biomarker of Fabry disease (FD), few studies have assessed the impact of lyso-Gb3 in patients with FD. A total of 38 patients diagnosed with FD at Ruijin Hospital between January 2012 and December 2014 were recruited in the current study. An additional 120 unrelated healthy individuals were selected as healthy controls. A simplified liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was performed to determine lyso-Gb3 levels in plasma. Protein precipitation and glycolipid extraction were conducted using acetone/methanol. Clinical performance, including diagnostic value and disease surveillance, were compared between plasma lyso-Gb3 levels and α-galactosidase A (α-gal A) enzyme activity. The overall coefficient of variation values between inter- and intra-days varied between 2.8 and 18.9% and linearity correlation coefficients were ≥0.99 for all assays. Therefore, the effectiveness of the LC-MS/MS method was validated. Furthermore, a cut-off value of 0.81 ng/ml plasma lyso-Gb3 was able to separate patients with FD from healthy individuals. The sensitivity of this cut-off was 94.7% and the specificity was 100%. Compared with α-gal A enzyme activity, the diagnostic rate of patients assessed using plasma lyso-Gb3 levels was similar; however, there was a tighter correlation between plasma lyso-Gb3 levels and the mainz severity score index score in male patients (r=0.711 vs. r=-0.687). The sensitivity of plasma lyso-Gb3 in diagnosing female patients with FD was higher than α-gal A enzyme activity (82.4 vs. 23.5%). To the best of our knowledge, the present study is the first to report the effectiveness of plasma lyso-Gb3 levels in diagnosing Chinese patients with FD. Using α-gal A activity as a reference, the results of current study indicated that plasma lyso-Gb3 levels are more useful at diagnosing female patients with FD. Furthermore, plasma lyso-Gb3 levels are more suitable at determining overall disease severity in male patients.

Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease.

Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients.

Inhibitor of DNA Binding 1 Is Induced during Kidney Ischemia-Reperfusion and Is Critical for the Induction of Hypoxia-Inducible Factor-1α.

In this study, rat models of acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) and HK-2 cell models of hypoxia-reoxygenation (H/R) were established to investigate the expression of inhibitor of DNA binding 1 (ID1) in AKI, and the regulation relationship between ID1 and hypoxia-inducible factor 1 alpha (HIF-1α). Through western blot, quantitative real-time PCR, immunohistochemistry, and other experiment methods, the induction of ID1 after renal I/R in vivo was observed, which was expressed mainly in renal tubular epithelial cells (TECs). ID1 expression was upregulated in in vitro H/R models at both the protein and mRNA levels. Via RNAi, it was found that ID1 induction was inhibited with silencing of HIF-1α. Moreover, the suppression of ID1 mRNA expression could lead to decreased expression and transcription of HIF-1α during hypoxia and reoxygenation. In addition, it was demonstrated that both ID1 and HIF-1α can regulate the transcription of twist. This study demonstrated that ID1 is induced in renal TECs during I/R and can regulate the transcription and expression of HIF-1α.

Successful Treatment of Idiopathic Eosinophilic Peritonitis by Oral Corticosteroid Therapy in a Continuous Ambulatory Peritoneal Dialysis Patient.

Eosinophilic peritonitis is a well-described complication of peritoneal dialysis and is often associated with either a reaction to the dialysis system constituent (tubing, sterilant or solution) or an underlying bacterial or fungal reaction. We report a case of eosinophilic peritonitis, which is treated by oral prednisone acetate therapy. A 43-year-old female patient developed end-stage renal disease and underwent continuous ambulatory peritoneal dialysis for 2.5 years. The patient received 2,000 ml of 1.5% dialysis solution (PD2) with three exchanges daily and 2,000 ml of 2.5% PDF overnight (PD2). She went to the consultation because of a constant turbid peritoneal dialysis effluent for 3 months without abdominal pain. Repeated peritoneal effluent samples showed an elevated white blood cell count of 500 cells/mm(3), with 87% eosinophils. The peripheral blood test revealed a white blood cell count of 3.8 × 10(9)/l, with 32.2% eosinophils. Etiology like bacterial and fungal infection was excluded by peritoneal fluid culture. Turbidness persisted in spite of diagnostic antibiotic treatment. Given the fact that we found a significant elevation of eosinophils in the peripheral blood and an absolute increase in the eosinophil count of >30/mm(3) in dialysis fluid (up to 400/mm(3) in our patient), obvious dialysate effluent turbidness, negative results of repeated peritoneal fluid cultures, inefficacy of antibiotic therapy, and negativity of serum tumor and immunological markers, we drew the conclusion that the patient had idiopathic eosinophilic peritonitis. Oral corticosteroid was administered at once (20 mg prednisone acetate daily), which was gradually weaned off and stopped over an 8-week period. Afterwards, the dialysis effluent became clear, and the cytological analysis showed that the white blood cell count decreased to 1 × 10(6)/l, with no eosinophils. This case reminds us that the diagnosis of eosinophilic peritonitis should be considered when repeated cultures are always negative and the turbidness of peritoneal dialysis effluent persists in spite of an antibiotic therapy.