Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy. Short-chain fatty acids (SCFAs), prominent metabolites of the gut microbiota, have significant connections with various pregnancy complications, and some SCFAs hold potential for treating such complications. However, the metabolic profile of SCFAs in patients with ICP remains unclear. AIM: To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings. METHODS: Maternal serum and cord blood samples were collected from both patients with ICP (ICP group) and normal pregnant women (NP group). Targeted metabolomics was used to assess the SCFA levels in these samples. RESULTS: Significant differences in maternal SCFAs were observed between the ICP and NP groups. Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group, mirroring the pattern seen in maternal serum. Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs [r (Pearson) = 0.88, P = 7.93e-95]. In both maternal serum and cord blood, acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups (variable importance for the projection > 1). Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP, with caproic acid exhibiting the highest diagnostic efficacy (area under the curve = 0.97). CONCLUSION: Compared with the NP group, significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group, although they displayed distinct patterns of change. Furthermore, the SCFA levels in maternal serum and cord blood were significantly positively correlated. Notably, certain maternal serum SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP.

Detection of lard adulteration in 3 kinds of vegetable oils by liquid chromatography-mass spectrometry with porous graphite carbon column.

Liquid chromatography‒mass spectrometry employing porous graphite carbon columns and an n-octane-isopropanol mobile phase was utilized for the separation of triacylglycerols (TAGs) in various edible oils, aiming to identify lard adulteration in soybean, corn, and sunflower seed oils. Experiments were conducted using a Hypercarb column (2.1 mm × 100 mm, 5 µm) and an n-octane-isopropanol (70:30, V/V) mobile phase at a flow rate of 0.25 mL· min-1 and a column temperature of 60 °C. Detection was achieved through atmospheric pressure chemical ionization-mass spectrometry. Analysis of diverse edible oil samples revealed that oils of the same type shared similar TAG compositions, while different types exhibited distinct TAG profiles. Distinct variations in triglyceride composition were observed across different edible oils. Based on liquid chromatography‒mass spectrometry analysis, the characteristic component 1-stearic acid-2-palmitic acid-3-oleic acid glyceride (SPO), which may also include PSO, was identified in lard through principal component analysis and orthogonal partial least squares discriminant analysis. This component served as a marker for detecting as low as 0.1% lard adulteration in soybean, corn, and sunflower seed oils. The technique offers a precise and effective approach for the identification of lard adulteration in these edible oils.

Markers of intestinal barrier damage in patients with chronic insomnia disorder.

Objective: Insomnia disorder stands out as one of the prevalent clinical sleep and psychiatric disorders. Prior research has unequivocally demonstrated variations in the diversity and abundance of gut microbiota among individuals with insomnia disorder. These alterations may play a direct or indirect role in the onset and progression of insomnia disorder by compromising the integrity of the intestinal barrier. This study aims to evaluate the impairment of the intestinal barrier in individuals with insomnia disorder by scrutinizing the serum functionality of this barrier. Materials and methods: 45 patients with chronic insomnia disorder and 30 matched healthy volunteers were meticulously selected based on inclusion criteria. ELISA technology was employed to measure serum levels of diamine oxidase (DAO), D-lactic acid (D-LA), intestinal fatty acid binding protein (I-FABP), and endothelin (ET). Spearman correlation analysis was used to explore the relationship between intestinal mucosal markers and clinical characteristics. Data were analyzed using SPSS 26.0. Results: Compared to the healthy control group, the insomnia disorder group exhibited significantly elevated scores on subjective mood and sleep scales (GAD-7, PHQ-9, HAMA, HAMD, PSQI, and ISI) (P < 0.05). Overnight PSG indicated a notable increase in bed time, total wake time, sleep onset latency, and wake after sleep onset in individuals with insomnia disorder. Additionally, there was a decrease in sleep efficiency and alterations in sleep structure (increased proportion of N1 and N3 stages, prolonged N1 stage) (P < 0.05). The chronic insomnia disorder group displayed significantly reduced concentrations of serum DAO, D-LA, I-FABP, and ET (P < 0.05). Furthermore, significant positive correlations were identified between intestinal epithelial barrier markers and sleep efficiency, while negative correlations were found with wake after sleep onset, total wake time, PSQI, HAMA, and HAMD. Additionally, D-LA levels were significantly positively correlated with ET concentrations. Conclusion: Individuals with chronic insomnia disorder manifest disruptions in sleep structure, heightened susceptibility to anxiety and depressive moods, and impaired intestinal barrier function. These findings suggest that the occurrence and development of insomnia disorder may be linked to the impairment of the intestinal barrier.

Inhibition of ACSS2-mediated histone crotonylation alleviates kidney fibrosis via IL-1ß-dependent macrophage activation and tubular cell senescence.

Histone lysine crotonylation (Kcr), as a posttranslational modification, is widespread as acetylation (Kac); however, its roles are largely unknown in kidney fibrosis. In this study, we report that histone Kcr of tubular epithelial cells is abnormally elevated in fibrotic kidneys. By screening these crotonylated/acetylated factors, a crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) is found to remarkably increase histone 3 lysine 9 crotonylation (H3K9cr) level without influencing H3K9ac in kidneys and tubular epithelial cells. The integrated analysis of ChIP-seq and RNA-seq of fibrotic kidneys reveal that the hub proinflammatory cytokine IL-1ß, which is regulated by H3K9cr, play crucial roles in fibrogenesis. Furthermore, genetic and pharmacologic inhibition of ACSS2 both suppress H3K9cr-mediated IL-1ß expression, which thereby alleviate IL-1ß-dependent macrophage activation and tubular cell senescence to delay renal fibrosis. Collectively, our findings uncover that H3K9cr exerts a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive drug target to slow fibrotic kidney disease progression.

Protective effect of Xixin-Ganjiang herb pair for warming the lungs to dissolve phlegm in chronic obstructive pulmonary disease rats based on integrated network pharmacology and metabolomics.

Xixin-Ganjiang herb pair (XGHP) is a classic combination for warming the lungs to dissolve phlegm and is often used to treat a variety of chronic lung diseases; it can treat the syndrome of cold phlegm obstruction of lungs. First, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to examine the composition of XGHP, and network pharmacology was used to predict its potential core targets and signaling pathways in the current study. Second, a rat model of chronic obstructive pulmonary disease (COPD) was established for assessing the anti-COPD activity of XGHP, and metabolomics was used to explore the biomarkers and metabolic pathways. Finally, the sample was validated using molecular docking and Western blotting. The integration of metabolomics and network pharmacology results identified 11 targets, 3 biomarkers, 3 pathways, and 2 metabolic pathways. Western blotting showed that XGHP effectively regulated the expression of core proteins via multiple signaling pathways (downregulation of toll-like receptor 4 [TLR4] and upregulation of serine/threonine-protein kinase 1 [p-AKT1] and nitric oxide synthase 3 [NOS3]). Molecular docking results showed that the 10 potentially active components of XGHP have good affinity with tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase 9 (MMP-9), TLR4, p-AKT1, and NOS3. Our findings suggest that XGHP may regulate glucolipid metabolism, improve energy supply, and inhibit inflammatory responses (TNF-α, IL-6, and MMP-9) via the PI3K-Akt signaling pathway and HIF-1 signaling pathway in the management of COPD.

Tilletia horrida glycoside hydrolase family 128 protein, designated ThGhd_7, modulates plant immunity by blocking reactive oxygen species production.

Tilletia horrida is an important soilborne fungal pathogen that causes rice kernel smut worldwide. We found a glycoside hydrolase family 128 protein, designated ThGhd_7, caused cell death in Nicotiana benthamiana leaves. The predicted signal peptide (SP) of ThGhd_7 targets it for secretion. However, loss of the SP did not affect its ability to induce cell death. The 23-201 amino acid sequence of ThGhd_7 was sufficient to trigger cell death in N. benthamiana. ThGhd_7 expression was induced and upregulated during T. horrida infection. ThGhd_7 localised to both the cytoplasm and nucleus of plant cells, and nuclear localisation was required to induce cell death. The ability of ThGhd_7 to trigger cell death in N. benthamiana depends on RAR1 (required for Mla12 resistance), SGT1 (suppressor of G2 allele of Skp1), and BAK1/SERK3 (somatic embryogenesis receptor-like kinase 3). Heterologous overexpression of ThGhd_7 in rice reduced reactive oxygen species (ROS) production and enhanced susceptibility to T. horrida. Further research revealed that ThGhd_7 interacted with and destabilised OsSGT1, which is required for ROS production and is a positive regulator of rice resistance to T. horrida. Taken together, these findings suggest that T. horrida employs ThGhd_7 to disrupt ROS production and thereby promote infection.

Economic burden of systemic lupus erythematosus in Malaysia.

INTRODUCTION: Our cost-of-illness (COI) model adopted the perspective of both payer and society over a time horizon of 5 years to measure the economic burden of systemic lupus erythematosus (SLE) in Malaysia. METHODOLOGY: Our COI model utilized a prevalence-based model to estimate the costs and economic consequences of SLE in Malaysia. The clinical parameters were obtained from published literature and validated using the Delphi panel. Direct and indirect medical costs were measured, including disease management, transient events, and indirect costs. One-way sensitivity analysis was also performed. RESULTS: The number of target Malaysian patients with SLE in the COI model was 18,121. At diagnosis, the numbers of SLE patients with mild, moderate, and severe phenotypes were 2,582, 13,897, and 1,642, respectively. The total SLE cost in Malaysia over 5 years from both payer and society perspectives was estimated at MYR 678 million and 2 billion, respectively. The results showed a considerable cost burden due to productivity losses resulting from SLE-related morbidity and mortality. Over a 5-year time horizon, the costs per patient per year from the payer and society perspectives were MYR 7,484 ($4766) and 24,281($15,465), respectively. CONCLUSION: Our study demonstrated the substantial economic burden of SLE in Malaysia over a time horizon of 5 years. It affects adults of working age, in addition to the costs of SLE management and its consequences, such as flares, infection, and organ damage. Our COI model indicated that disease management costs among patients with higher disease severity were higher than those among patients with a mild phenotype. Hence, more attetion should be paid to limiting the progression of SLE and the occurrence of flares, with the need for further economic evaluation of novel treatments that could lead to better outcomes.

Integrated Genome Sequencing and Transcriptome Analysis Identifies Candidate Pathogenicity Genes from Ustilago crameri.

Ustilago crameri is a pathogenic basidiomycete fungus that causes foxtail millet kernel smut (FMKS), a devastating grain disease in most foxtail-millet-growing regions of the world. Here, we report an assembled high-quality genome sequence of U. crameri strain SCZ-6 isolated from the diseased grains of foxtail millet in Changzhi, Shanxi Province, China. The genome size is 19.55 Mb, consisting of 73 contigs (N50 = 840,209 bp) with a G + C content of 54.09%, and encoding 6576 predicted genes and 6486 genes supported by RNA-seq. Evolutionarily, U. crameri lies close to the barley smut U. hordei, and an obvious co-linearity was observed between these two smut fungi. We annotated the genome of U. crameri strain SCZ-6 using databases, identifying 1827 pathogen-host interaction (PHI)-associated genes, 1324 genes encoding fungal virulence factors, 259 CAZy-related genes, 80 genes encoding transporters, and 206 putative cytochrome P450 genes; their expression profiles at different inoculation time points were also detected. Additionally, 70 candidate pathogen effectors were identified according to their expression patterns and predicted functions. In summary, our results provide important insights into the pathogenic mechanisms of the pathogenesis-related genes of U. crameri and a robust foundation for further investigation.

Pleural effusion portends a poor prognosis in patients on continuous ambulatory peritoneal dialysis.

AIMS: Pleural effusion is not an infrequent complication in patients undergoing continuous ambulatory peritoneal dialysis. However, there is not adequate data to evaluate pleural effusion and prognosis in clinical practice. In this study, we validated this potential association by a multicenter cohort. METHODS: We screened 1,162 patients who met the inclusion criteria with PD. According to the existence of pleural effusion on stable dialysis (4-8 weeks after dialysis initiation), the participants were divided into pleural effusion and non-pleural effusion groups. The hazard ratios (HRs) of all-cause and cause-specific death were estimated with adjustment for demographic characteristics and multiple potential clinical confounders. Subgroup analysis and propensity score matching (PSM) were used to further verify the robustness of the correlation between hydrothorax and prognosis. RESULTS: Pleural effusion was found in 8.9% (104/1162) of PD individuals. After adjusting for the confounding factors, patients with pleural effusion had significantly increased HRs for all-cause death was 3.06 (2.36-3.96) and cardiovascular death was 3.78 (2.67-5.35) compared to those without pleural effusion. However, it was not associated with infectious and other causes of death. After PSM, the HR of all-cause mortality was 3.56 (2.28-5.56). The association trends were consistent in the subgroup sensitivity analysis. CONCLUSION: Pleural effusion is not rare in PD, and is significantly associated with overall and cardiovascular mortality, which is independent of underlying diseases and clinically relevant indicators.

Semi-Supervised Learning for Multi-Label Cardiovascular Diseases Prediction: A Multi-Dataset Study.

Electrocardiography (ECG) is a non-invasive tool for predicting cardiovascular diseases (CVDs). Current ECG-based diagnosis systems show promising performance owing to the rapid development of deep learning techniques. However, the label scarcity problem, the co-occurrence of multiple CVDs and the poor performance on unseen datasets greatly hinder the widespread application of deep learning-based models. Addressing them in a unified framework remains a significant challenge. To this end, we propose a multi-label semi-supervised model (ECGMatch) to recognize multiple CVDs simultaneously with limited supervision. In the ECGMatch, an ECGAugment module is developed for weak and strong ECG data augmentation, which generates diverse samples for model training. Subsequently, a hyperparameter-efficient framework with neighbor agreement modeling and knowledge distillation is designed for pseudo-label generation and refinement, which mitigates the label scarcity problem. Finally, a label correlation alignment module is proposed to capture the co-occurrence information of different CVDs within labeled samples and propagate this information to unlabeled samples. Extensive experiments on four datasets and three protocols demonstrate the effectiveness and stability of the proposed model, especially on unseen datasets. As such, this model can pave the way for diagnostic systems that achieve robust performance on multi-label CVDs prediction with limited supervision.

Repeated intravenous thrombolysis in recurrent ischemic stroke within 3 months: a systematic review.

BACKGROUND: Repeated intravenous thrombolysis (RIVT) within 3 months is an off-guideline therapy, however, may be an effective and safe way to treat early recurrent ischemic stroke. This study was conducted to assess the potential influencing factors on the efficacy and safety of RIVT in recurrent ischemic stroke within 3 months and to explore the strategy of RIVT within 3 months. METHODS: PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang Database were searched for cases of RIVT in recurrent ischemic stroke within 3 months up to February 1, 2023. Clinical characteristics were compared and analyzed between the good-outcome and poor-outcome groups and between the symptomatic intracranial hemorrhage (sICH) and non-sICH groups respectively. RESULTS: A total of 16 studies including 24 cases of RIVT within 3 months were retrospectively analyzed in the present study. The patients' ages ranged from 42 to 87 years (median 73.5 years) and the intervals between thrombolysis were from 0.25 to 90 days (median 9.5 days). Comparing the clinical characteristics between the good-outcome group and the poor-outcome group, no statistically significant differences were found (P > 0.05), but the differences in baseline National Institutes of Health stroke scale (NIHSS) score of the recurrent stroke (P = 0.056) and good outcome after the previous IVT (P = 0.054) nearly reached statistical significance. Comparing the data between the non-sICH group and the sICH group, statistically significant differences were found in terms of the proportion of cardiogenic embolism (P = 0.036), baseline NIHSS score in the recurrent stroke (P = 0.007) and the interval between thrombolysis (P = 0.041), but no significant difference was found by regression analysis. CONCLUSION: In patients with recurrent ischemic stroke within 3 months, those with a good outcome after the previous IVT and a low baseline NIHSS score in the recurrent stroke may be considered for RIVT, whereas those with a high baseline NIHSS score, a short interval between thrombolysis, and cardiogenic embolism may suffer a higher risk of sICH. Due to sample size and publication bias, more studies with larger sample sizes and more rigorous designs are needed to confirm this conclusion.

Serum Zonula Occludens-1 and Claudin-5 Levels in Patients with Insomnia Disorder: A Pilot Study.

Purpose: This research aimed to investigate serum Zonula occludens-1 (ZO-1) and Claudin-5 (CLDN5) levels to show whether or not their eventual changes in patients with insomnia disorder could have etiopathogenetic importance. There was no research investigating serum ZO-1 and CLDN5 concentrations in insomnia disorder. Patients and Methods: This study included 60 insomnia disorder patients and 45 normal controls. None of the patients received drugs for insomnia. The patients completed Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI), and Polysomnography (PSG) to score the insomnia disorder symptoms. Venous blood samples were collected, and serum ZO-1 and claudin-5 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Results: Serum ZO-1 level was significantly higher without a significant difference between age, sex, and body mass index, whereas the difference in serum claudin-5 level between the two groups was not statistically significant. In addition, ZO-1 levels were positively correlated with ISI and PSQI and negatively with N1 and N1_perc. We also demonstrated a positive correlation between the levels of CLDN5 and HAMA, and a negative correlation with total sleep time (TST), N1 and N1_perc. Conclusion: Our findings suggest an association between these intestinal and brain endothelial permeability markers and insomnia disorders. However, these remain modest and preliminary and need more extensive studies, including long-term follow-up populations and involving gut microbes, to further validate and explore the mechanisms involved.

Differences of airborne and mural microorganisms in a 1,500-year-old Xu Xianxiu's Tomb, Taiyuan, China.

Background: Microbial colonization represents one of the main threats to the conservation of subterranean cultural heritage sites. Recently, the microbial colonization on murals in tombs has gradually attracted attention. Methods: In this study, a total of 33 samples, including 27 aerosol samples and 6 mural painting samples, were collected from different sites of Xu Xianxiu's Tomb and analyzed using culture-dependent methods. We compared the diversities of culturable bacteria and fungi isolated from the air and murals and explored the potential impacts of microorganisms on the biodeterioration of the murals. Results: Phylogenetic analyses revealed that the culturable bacteria belonged to Bacillus, Microbacterium, Lysobacter and Arthrobacter. And the most of fungal belonged to the Penicillium, Cladosporium and Aspergillus genera. The composition and structure of airborne bacteria and fungi outside the tomb were both significantly different from that inside the tomb. The variation trends of airborne bacterial and fungal concentrations at different sampling sites were remarkably similar. Bacillus frigoritolerans, Bacillus halotolerans, Bacillus safensis, Exiguobacterium mexicanum, Microbacterium trichothecenolyticum, and Micrococcus yunnanensis were bacterial species commonly isolated from both the mural and air environments. Fungal species commonly isolated from aerosol samples and mural painting samples were Alternaria alternata, Cladosporium cladosporioides, Penicillium brevicompactum, and Peyronellaea glomerata. The prediction of the ecological functions of the bacteria revealed that chemoheterotrophy or aerobic_chemoheterotrophy accounted for substantial relative proportions in all sample types. Conclusion: These results suggest that the aerosol circulation between the inside and outside environments of the tomb was weak and that the outside environment had yet to have an impact on the air microbial community inside the tomb. Selective colonization of microorganisms, which is mediated by interaction between microorganisms and special microenvironmental factors, is an important reason for the biodeterioration of murals.

Prognostic significance of the Gustave Roussy immune (GRIm) score in cancer patients: a meta-analysis.

BACKGROUND: The prognostic value of the Gustave Roussy immune (GRIm) score in cancer patients has been widely reported but remains inconsistent. The aim of this study is to systematically investigate the relationship between the GRIm score and survival outcomes in cancer patients. METHODS: Relevant literature was identified using electronic databases including Web of Science, PubMed, and Embase from the inception to March 2023. The primary endpoints were long-term oncological outcomes. Subgroup analysis and sensitivity analysis were conducted during the meta-analysis. RESULTS: Fifteen studies (20 cohorts) including 4997 cancer patients were enrolled. The combined results revealed that patients in the high GRIm group had a deteriorated overall survival (HR = 2.07 95%CI: 1.73-2.48; p < 0.0001; I2 = 62%) and progression-free survival (HR = 1.42; 95%CI: 1.22-1.66; p < 0.0001; I2 = 36%). The prognostic values of GRIm on overall survival and progression-free survival were observed across various tumour types and tumour stages. Sensitivity analysis supported the stability and reliability of the above results. CONCLUSION: Our evidence suggested that the GRIm score could be a valuable prognostic marker in cancer patients, which can be used by clinicians to stratify patients and formulate individualized treatment plans.

Serum vascular endothelial growth factor and cortisol expression to predict prognosis of patients with hypertensive cerebral hemorrhage.

BACKGROUND: Cerebral hemorrhage is a common and severe complication of hypertension in middle-aged and elderly men. AIM: To investigate the correlation between vascular endothelial growth factor (VEGF) and cortisol (Cor) and the prognosis of patients with hypertensive cerebral hemorrhage. METHODS: A hundred patients with hypertensive intracerebral hemorrhage were enrolled from January 2020 to December 2022 and assigned to the hypertensive intracerebral hemorrhage group. Another 100 healthy people who were examined at our hospital during the same period were selected and assigned to the healthy group. Peripheral venous blood was collected, and serum Cor and VGEF levels were measured through enzyme linked immunosorbent assay. RESULTS: A statistically significant difference in serum Cor and VGEF levels was observed among patients with varying degrees of neurological impairment (P < 0.05). Serum Cor and VGEF levels were significantly higher in the severe group than in the mild-to-moderate group. Cor and VEGF levels were significantly higher in patients with poor prognoses than in those with good prognoses. Multiple logistic regression analysis revealed that serum Cor and VGEF levels were independent factors affecting hypertensive intracerebral hemorrhage (P < 0.05). CONCLUSION: Cor and VGEF are associated with the occurrence and development of hypertensive cerebral hemorrhage and are significantly associated with neurological impairment and prognosis of patients.

E3 ubiquitin ligase STUB1 affects the mTORC1 pathway through p62 and participates in regulating the differentiation of follicular helper T cells in rheumatoid arthritis.

OBJECTIVE: The abnormal expansion of Tfh cells plays a key role in chronic inflammation of RA joint. We speculated that STUB1 is an important regulatory factor in promoting the differentiation of Tfh cells in RA. CONTENT AND METHODS: The proportion of Tfh cells and the level of STUB1 in Tfh cells was measured. CD4+T cells were isolated from PBMCs of RA patients, and the percentage of Tfh cells was detected after up- or down-regulating the expression of STUB1. The levels of mTORC1 pathway activator p-mTOR and p-S6K were measured by Western blot. The ubiquitination of p62 by STUB1 and its ubiquitination type as well as the activation of mTORC1 was detected in vitro, and the activation of the mTORC1 and the differentiation of Tfh cells was detected in STUB1-upregulated CD4+ T cells with overexpressed p62. RESULTS: The level of STUB1 is elevated in Tfh cells of patients. Up-regulation of STUB1 can promote the differentiation of Tfh cells. STUB1 promotes the degradation of p62 via K48-linked ubiquitination and promotes the activation of mTORC1. Overexpression of p62 can reverse the promoting effect of STUB1 on the differentiation of Tfh cells and the activation of mTORC1. CONCLUSION: STUB1 can promote the differentiation of Tfh cells in RA by mediating the activation of mTORC1 pathway through ubiquitination of p62.

Comparative efficacy and safety of six non-ergot dopamine-receptor agonists in early Parkinson's disease: a systematic review and network meta-analysis.

Background: Non-ergot dopamine agonists (NEDAs) have been used as monotherapy or as an adjunctive therapy to levodopa for many years. Novel long-acting formulations of NEDAs including pramipexole extended-release (ER), ropinirole prolonged-release (PR), and rotigotine transdermal patch have been developed. However, there is no strong evidence that a given NEDA is more potent than another. We performed a systematic review and network meta-analysis to evaluate the efficacy, tolerability and safety of six commonly used NEDAs in early Parkinson's disease (PD). Methods: Six NEDAs including piribedil, rotigotine transdermal patch, pramipexole immediate-release (IR)/ER, and ropinirole IR/PR were investigated. The efficacy outcomes including Unified Parkinson's Disease Rating Scale activities in daily life (UPDRS-II), motor function (UPDRS-III), and their subtotal (UPDRS-II + III), tolerability and safety outcomes were analyzed. Results: A total of 20 RCTs (5,355 patients) were included in the current study. The result indicated that compared with placebo, all six investigated drugs had statistically significant differences in the improvement of UPDRS-II, UPDRS-III, and UPDRS-II + III (except ropinirole PR in UPDRS-II). There were no statistically significant differences between six NEDAs for the UPDRS-II and UPDRS-III. For UPDRS-II + III, the improvement of ropinirole IR/PR and piribedil were higher than that of rotigotine transdermal patch, and piribedil was higher than that of pramipexole IR. The surface under the cumulative ranking curve (SUCRA) indicated that piribedil resulted in best improvement in UPDRS-II and UPDRS-III (0.717 and 0.861, respectively). For UPDRS-II + III, piribedil and ropinirole PR exhibited similar improvement and both had high rates (0.858 and 0.878, respectively). Furthermore, piribedil performed better as monotherapy, ranking first in the improvement of UPDRS-II, III, and II + III (0.922, 0.960, and 0.941, separately). With regard to tolerability, there was a significant increase in overall withdrawals with pramipexole ER (0.937). In addition, the incidence of adverse reaction of ropinirole IR was relatively high (nausea: 0.678; somnolence: 0.752; dizziness: 0.758; fatigue: 0.890). Conclusions: In this systematic review and network meta-analysis of six NEDAs, piribedil exhibited better efficacy, especially as monotherapy, and ropinirole IR was associated with a higher incidence of adverse events in patients with early PD.

Decreased lymphocyte count before conditioning is associated with BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: BK virus-associated hemorrhagic cystitis (BKV-HC) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It can cause morbidity and may increase treatment-related mortality. Previous studies showed that the occurrence of BKV-HC was related to various factors. However, there are still many controversial factors. It is not clear whether BKV-HC will affect the long-term prognosis of patients. OBJECTIVE: We aimed to identify risk factors for BKV-HC after allo-HSCT and evaluate the effect of BKV-HC on overall survival (OS) and progression- free survival (PFS) of patients. STUDY DESIGN: We retrospectively analyzed the clinical data of 93 patients who underwent allo-HSCT. Univariate and multivariate analysis were used to identify risk factors for BKV-HC. The Kaplan-Meier method was used to estimate OS and PFS. A difference was considered statistically significant if P < 0.05. RESULTS: A total of 24 patients developed BKV-HC. The median occurrence time of BKV-HC was 30 (range:8-89) days after transplantation, and the median duration was 25.5 (range:6-50) days. Multivariate logistic regression analysis indicated that peripheral blood lymphocyte count <1 × 109/L before conditioning (OR = 4.705, P = 0.007) and haploidentical transplantation (OR = 13.161, P = 0.018) were independent risk factors for BKV-HC. The 3-year OS rate was 85.9% (95%CI:62.1%-95.2%) in the BKV-HC group and 73.1% (95%CI: 58.2%-88.0%) in the non-BKV-HC group. There was no significant difference between the two groups (P = 0.516). The 3-year PFS rate was 76.3% (95%CI: 57.9%-94.7%) in the BKV-HC group and 58.1% (95%CI: 39.5%-76.7%) in the non-BKV-HC group. There was no significant difference in the two groups (P = 0.459). The severity of BKV-HC was not related to the OS and PFS of the patients (P value was 0.816 and 0.501, respectively). CONCLUSION: Haploidentical transplantation and decreased peripheral blood lymphocyte count before conditioning increased the risk of BKV-HC after allo-HSCT. The occurrence of BKV-HC after allo-HSCT and the severity of which did not affect OS and PFS of the patients.