Prediction of prognosis in patients with systemic sclerosis based on a machine-learning model.

OBJECTIVE: The clinical manifestations of systemic sclerosis (SSc) are highly variable, resulting in varied outcomes and complications. Diverse fibrosis of the skin and internal organs, vasculopathy, and dysregulated immune system lead to poor and varied prognoses in patients with SSc subtypes. Therefore, this study aimed to develop a personalized tool for predicting the prognosis of patients with SSc. METHODS: A cohort of 517 patients with SSc were recruited between January 2009 and November 2021 at Xijing Hospital in China, and 266 patients completed the follow-up and performed in the survival analysis. Risk factors for death were identified using Cox survival analysis and random survival forest-based machine-learning methods separately. The consistency index, area under the curve (AUC), and integrated Brier scores were used to compare the predictive performance of the different prognostic models. RESULTS: The results of Cox-based multivariate regression analysis suggested that pulmonary arterial hypertension, digital ulcer, and Modified Rodnan Skin Score (mRSS) were independent risk factors for poor prognosis in patients with SSc and significant risk factors in random survival forest (RSF) surveys. A nomogram was plotted to evaluate the prognostic risk to facilitate clinical assessment; the RSF model had better predictive performance than the Cox model, with 3- and 5-year AUCs of 0.74 and 0.78, respectively. CONCLUSION: Machine-learning models can help us better understand the prognosis of patients with SSc and comprehensively evaluate the clinical characteristics of each individual. The early identification of the characteristics of high-risk patients can improve the prognosis of those with SSc. Key Points • Regarding predictive performance, the random survival forest model was more effective than the Cox model and had unique advantages in analyzing nonlinear effects and variable importance. • Machine learning using the simple clinical features of patients with systemic sclerosis (SSc) to predict mortality can guide attending physicians, and the early identification of high-risk patients with SSc and referral to experts will assist rheumatologists in monitoring and management planning.

Biology of tongue coating in different disease stages of RA and its value in disease progression.

OBJECTIVE: To assess and compare the composition of tongue coating microbiota among patients at different stages of rheumatoid arthritis (RA). METHODS: A total of 47 patients diagnosed with RA, as per the American College of Rheumatology criteria, and 10 healthy individuals were enrolled in this study. The RA patients were stratified considering their Disease Activity Score 28 (DAS28), a composite measure based on the 28 tender and swollen joint count and erythrocyte sedimentation rate (ESR). The study population was further categorized into active phase group (LMH group) and inactive phase group (RE group) according to their DAS28 values. DNA extraction was extracted from tongue coating samples. Subsequently, the V3-V4 16S rDNA region was selectively amplified and sequenced through high-throughput 16S rDNA analysis. The resulting data were then utilized to ascertain the microbial contents. RESULTS: Significant variations were observed in the tongue coating microbiota of patients with RA during active and inactive phases, in comparison to healthy individuals (p < 0.05). At the genus level, the presence of Prevotellan, Veillonella, Rothia, and Neisseria in RA patients was notably more evident than in the healthy control (HC) group. These disparities find support in existing research on gut and oral microbiota. During the active phase of RA, the relative abundance of Veillonella, Rothia, and Neisseria in the tongue coating microbiota of patients was significantly higher than in those with inactive RA. These findings underscore the need for further and in-depth research on the potential impact of these microorganisms on the progression of RA disease. CONCLUSION: The results substantiate the hypothesis that tongue coating microbes actively contribute to the progression of RA.

Global prevalence and risk factors associated with Toxoplasma gondii infection in wild birds: A systematic review and meta-analysis.

A systematic review and meta-analysis were performed to identify the global prevalence and factors associated with Toxoplasma gondii infection in wild birds. Six bibliographic databases (Chinese National Knowledge Infrastructure, VIP Chinese Journal Database, Wanfang Data, PubMed, Web of science and ScienceDirect) were searched from inception to February 2023. The search yielded 1220 records of which 659 articles underwent full-text evaluation, which identified 49 eligible articles and 16,030 wild bird samples that were included in the meta-analysis. The estimated pooled global prevalence of T. gondii infection in wild birds was 16.6%. Out of the variables tested, publication year after 2020 and climate type were significantly associated with T. gondii infection (P<0.01). Our data indicate that the prevalence of T. gondii in wild birds can be influenced by epidemiological variables. Further research is needed to identify the biological, environmental, anthropogenic, and geographical risk factors which impact the ecology and prevalence of T. gondii in wild birds.

Structural basis of nucleosomal H4K20 recognition and methylation by SUV420H1 methyltransferase.

Histone lysine methyltransferase SUV420H1, which is responsible for site-specific di-/tri-methylation of histone H4 lysine 20 (H4K20), has crucial roles in DNA-templated processes, including DNA replication, DNA damage repair, and chromatin compaction. Its mutations frequently occur in human cancers. Nucleosomes containing the histone variant H2A.Z enhance the catalytic activities of SUV420H1 on H4K20 di-methylation deposition, regulating early replication origins. However, the molecular mechanism by which SUV420H1 specifically recognizes and deposits H4K20 methyl marks on nucleosomes remains poorly understood. Here we report the cryo-electron microscopy structures of SUV420H1 associated with H2A-containing nucleosome core particles (NCPs), and H2A.Z-containing NCPs. We find that SUV420H1 makes extensive site-specific contacts with histone and DNA regions. SUV420H1 C-terminal domain recognizes the H2A-H2B acidic patch of NCPs through its two arginine anchors, thus enabling H4K20 insertion for catalysis specifically. We also identify important residues increasing the catalytic activities of SUV420H1 bound to H2A.Z NCPs. In vitro and in vivo functional analyses reveal that multiple disease-associated mutations at the interfaces are essential for its catalytic activity and chromatin state regulation. Together, our study provides molecular insights into the nucleosome-based recognition and methylation mechanisms of SUV420H1, and a structural basis for understanding SUV420H1-related human disease.

Nasal spray of an IgM-like ACE2 fusion protein HH-120 prevents SARS-CoV-2 infection: Two investigator-initiated postexposure prophylaxis trials.

HH-120, an IgM-like angiotensin converting enzyme 2 (ACE2) fusion protein, has been developed as a nasal spray against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently undergoing human trials. HH-120 nasal spray was assessed for postexposure prophylaxis (PEP) in two investigator-initiated (NS01 and NS02) trials with different risk levels of SARS-CoV-2 exposure. NS01 enrolled family caregiver participants who had continuous contacts with laboratory-confirmed index cases; NS02 enrolled participants who had general contacts (Part 1) or close contacts (Part 2) with index cases. The primary endpoints were safety and laboratory-confirmed and/or symptomatic SARS-CoV-2 infection. In NS01 trial (14 participants), the SARS-CoV-2 infection rates were 25% in the HH-120 group and 83.3% in the external control group (relative risk reduction [RRR]: 70.0%). In NS02-Part 1 (193 participants), the infection rates were 4% (HH-120) versus 11.3% (placebo), symptomatic infection rates were 0.8% versus 3.5%, hence with a RRR of 64.6% and 77.1%, respectively. In Part 2 (76 participants), the infection rates were 17.1% (HH-120) versus 30.4% (placebo), symptomatic infection rates were 7.5% versus 27.3%, with a RRR of 43.8% and 72.5%, respectively. No HH-120-related serious adverse effects were observed. The HH-120 nasal spray used as PEP was safe and effective in preventing laboratory-confirmed and symptomatic SARS-CoV-2 infection.

Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol.

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.

The Prevalence of Rodents Orientia tsutsugamushi in China During Two Decades: A Systematic Review and Meta-Analysis.

Background: Orientia tsutsugamushi is a zoonotic intracellular pathogen that requires parasitism in eukaryotic cells to reproduce. In recent years, tsutsugamushi disease reported in many places nationwide has crossed the Yangtze River, continuously, spreading to the North China. Now this phenomenon has aroused people's attention. Materials and Methods: In this study, meta-analysis was used to analyze the infection of rodents (vectors) in China, to clarify the transmission rule of O. tsutsugamushi. Results: This study included literature from six databases (PubMed, Web of Science, Science Direct, Wanfang, CNKI, and VIP). A total of 55 articles were included in the study from 610 retrieved articles. The total infection rate of O. tsutsugamushi in rodents was 5.5% (1206/20,620, 95% confidence interval [CI]: 0.0553-0.0617). The prevalence of O. tsutsugamushi in rodents before 2013 (7.73%, 95% CI: 4.11-12.37) was higher than after 2013 (2.11%, 95% CI: 0.64-4.41). O. tsutsugamushi spread among a variety of rodents, among which Rattus losea (13.3%, 95% CI: 4.33-26.26), Rattus tanezumi (5.69%, 95% CI: 1.37-12.72), and Apodemus agrarius (5.32%, 95% CI: 2.26-9.58) infection rate was higher. Kawasaki (8.32%, 95% CI: 1.42-20.17), Karp (7.36%, 95% CI: 2.62-14.22), Kato (2.54%, 95% CI: 0.08-8.28), and Gilliam (2.13%, 95% CI: 0.42-5.09) were the main prevalent genotypes in China. The prevalence of O. tsutsugamushi in rodents was seasonal, increasing gradually in summer (2.39%, 95% CI: 0.46-5.77), peaking in autumn (4.59%, 95% CI: 1.15-10.16), and then declining. The positive rate of immunofluorescence assay (25.07%, 95% CI: 8.44-46.88) was the highest among the detection methods, and it was statistically significant (p < 0.05). Based on the subgroup of geographical factors and climatic factors, the probability of O. tsutsugamushi infection in rodents was the highest when the temperature >19℃ (8.20%, 95% CI: 1.22-20.52), the altitude <100 millimeters (7.23%, 95% CI: 3.45-12.26), the precipitation >700 millimeters (12.22%, 95% CI: 6.45-19.50), and the humidity 60-70% (7.80%, 95% CI: 4.17-12.44). Conclusions: Studies have shown that rodents carrying O. tsutsugamushi are common. People should prevent and control rodents in life and monitor rodents carrying O. tsutsugamushi for a long time.

Nasal spray of an IgM-like ACE2 fusion protein HH-120 accelerates SARS-CoV-2 clearance: A single-center propensity score-matched cohort study.

HH-120, a recently developed IgM-like ACE2 fusion protein with broad-spectrum neutralizing activity against all ACE2-utilizing coronaviruses, has been developed as a nasal spray for use as an early treatment agent to reduce disease progression and airborne transmission. The objective of this study was to evaluate the safety and efficacy of the HH-120 nasal spray in SARS-CoV-2-infected subjects. Eligible symptomatic or asymptomatic SARS-CoV-2-infected participants were enrolled in a single-arm trial to receive the HH-120 nasal spray for no longer than 6 days or until viral clearance at a single hospital between August 3 and October 7, 2022. An external control was built from real-world data of SARS-CoV-2-infected subjects contemporaneously hospitalized in the same hospital using a propensity score matching (PSM) method. After PSM, 65 participants in the HH-120 group and 103 subjects with comparable baseline characteristics in the external control group were identified. The viral clearance time was significantly shorter in participants receiving the HH-120 nasal spray than that in subjects of the control group (median 8 days vs. 10 days, p < 0.001); the difference was more prominent in those subgroup subjects with higher baseline viral load (median 7.5 days vs. 10.5 days, p < 0.001). The incidence of treatment-emergent adverse events and treatment-related adverse events of HH-120 group were 35.1% (27/77) and 3.9% (3/77), respectively. All the adverse events observed were mild, being of CTCAE grade 1 or 2, and transient. The HH-120 nasal spray showed a favorable safety profile and promising antiviral efficacy in SARS-CoV-2-infected subjects. The results from this study warrant further assessment of the efficacy and safety of the HH-120 nasal spray in large-scale randomized controlled clinical trials.

Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice.

O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous post-translation modification occurring in both animals and plants. Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. Here, we report a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice. We first established the metabolic glycan labelling (MGL) strategy with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. A total of 1591 unambiguous O-GlcNAcylation sites distributed on 709 O-GlcNAcylated proteins were identified. Additionally, 102 O-GlcNAcylated proteins were identified with their O-GlcNAcylation sites located within serine/threonine-enriched peptides, causing ambiguous site assignment. The identified O-GlcNAcylated proteins are involved in multiple biological processes, such as transcription, translation and plant hormone signalling. Furthermore, we discovered two O-GlcNAc transferases (OsOGTs) in rice. By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants.

[Relationship between Asymptomatic Bacteriuria and Vaginal Colonization of Group B Streptococcus in the Third Trimester of Pregnancy].

Objective To reveal the relationship between asymptomatic bacteriuria (ASB) and vaginal colonization of group B Streptococcus in the third trimester of pregnancy.Methods A total of 4287 pregnant women who were followed up from January 2018 to June 2021 were enrolled in this study.The pregnant women with ASB were assigned as the observation group,and those without ASB were matched at a ratio of 1∶4 as the control group.Results Among the 4287 pregnant women,158 (3.69%) pregnant women had ASB,including 28 (17.72%) with group B Streptococcus colonization in the third trimester.Among the 632 pregnant women without ASB (control),44 cases (6.96%) had vaginal colonization of group B Streptococcus in the third trimester.The colonization rate of group B Streptococcus in the pregnant women with ASB was significantly higher than that in the pregnant women without ASB (χ2=17.666,P<0.001).Logistic regression showed that ASB was positively correlated with the vaginal colonization of group B Streptococcus in the third trimester of pregnancy (OR=2.577,95%CI=1.509-4.402,P=0.001).Conclusions ASB is positively correlated with the vaginal colonization of group B Streptococcus in the third trimester.The screening,prevention,and control of ASB in the early trimester is of great significance to reduce the vaginal colonization of group B Streptococcus in the third trimester.

Antidepressant-like effect of ginsenoside Rb1 on potentiating synaptic plasticity via the miR-134-mediated BDNF signaling pathway in a mouse model of chronic stress-induced depression.

Background: Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) plays a critical role in the pathogenesis of depression by modulating synaptic structural remodeling and functional transmission. Previously, we have demonstrated that the ginsenoside Rb1 (Rb1) presents a novel antidepressant-like effect via BDNF-TrkB signaling in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed mice. However, the underlying mechanism through which Rb1 counteracts stress-induced aberrant hippocampal synaptic plasticity via BDNF-TrkB signaling remains elusive. Methods: We focused on hippocampal microRNAs (miRNAs) that could directly bind to BDNF and are regulated by Rb1 to explore the possible synaptic plasticity-dependent mechanism of Rb1, which affords protection against CUMS-induced depression-like effects. Results: Herein, we observed that brain-specific miRNA-134 (miR-134) could directly bind to BDNF 3'UTR and was markedly downregulated by Rb1 in the hippocampus of CUMS-exposed mice. Furthermore, the hippocampus-targeted miR-134 overexpression substantially blocked the antidepressant-like effects of Rb1 during behavioral tests, attenuating the effects on neuronal nuclei-immunoreactive neurons, the density of dendritic spines, synaptic ultrastructure, long-term potentiation, and expression of synapse-associated proteins and BDNF-TrkB signaling proteins in the hippocampus of CUMS-exposed mice. Conclusion: These data provide strong evidence that Rb1 rescued CUMS-induced depression-like effects by modulating hippocampal synaptic plasticity via the miR-134-mediated BDNF signaling pathway.

Quercetin exerts antidepressant and cardioprotective effects in estrogen receptor α-deficient female mice via BDNF-AKT/ERK1/2 signaling.

Brain-derived neurotrophic factor (BDNF) is the potential link between depression and cardiovascular disease and estrogen receptor α (ERα), an estrogen-mediated major regulator, plays an important role in protecting against depression and cardiovascular disease. However, the relationship between BDNF and ERα remains obscure. Herein, quercetin (QUE), a kind of plant flavonoids and existed in many vegetables and fruits, was found to simultaneously reverse ERα-/--induced depression-like and cardiac dysfunction by reducing immobility time in the tail suspension test (TST) and forced swimming test (FST), and decreasing systolic blood pressure and activating the apoptosis-related proteins, BDNF, tropomyosin-related kinase B (TrkB), protein kinase B (AKT), and extracellular regulatory protein kinase (ERK1/2) in the hippocampal and cardiac tissues of female mice. These findings suggested that ERα might be involved in the regulation of BDNF activity, thereby regulating depression-like and cardiovascular responses in female mice, and QUE exerted significant antidepressant and cardioprotective effects, at least in part, through BDNF-TrkB-AKT/ERK1/2 to effectively inhibit ERα-/--induced hippocampal and cardiac dysfunction.

Double-edged role of radiotherapy in patients with pulmonary large-cell neuroendocrine carcinoma.

Purpose: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is classified as non-small-cell lung cancer, but has characteristics similar to small-cell lung cancer. This study was performed to evaluate the effect of surgery and radiotherapy on patients with LCNEC. Materials and Methods: We analyzed 1,619 patients with stage I-III LCNEC, identified from the Surveillance, Epidemiology, and End Results database, diagnosed from 2000 to 2013. The Kaplan-Meier analysis and the Cox proportional hazard model were used to study patient prognosis. Results: Overall, 869 (53.7%) stage I LCNEC patients, 203 (12.5%) stage II patients, and 547 (33.8%) stage III patients were included in the analysis. Various surgery types were all associated with higher overall survival (OS) and lung cancer-specific survival (LCSS) than no surgery, with the following HRs: 0.334 (OS) and 0.279 (LCSS) for lobectomy, 0.468 (OS) and 0.416 (LCSS) for partial/wedge/segmental resection, and 0.593 (OS) and 0.522 (LCSS) for pneumonectomy (all p < 0.05). OS and LCSS of stage I and II LCNEC patients were not improved by radiotherapy (stage I: OS p = 0.719, LCSS p = 0.557; stage II: OS p = 0.136, LCSS p = 0.697). However, in stage III patients, radiotherapy significantly improved both OS and LCSS (p < 0.001). Following multivariate analysis, increased age, male patients, radiotherapy and diagnosed at stage II or III were all independent risk factors for LCNEC (all p < 0.05). Conclusion: Lobectomy had the best outcome for OS and LCSS in stage I-II LCNEC. For stage III LCNEC patients, radiotherapy can significantly improve survival time. However, in LCNEC patients undergoing surgery, radiotherapy may reduce survival time.

Rb1, the Primary Active Ingredient in Panax ginseng C.A. Meyer, Exerts Antidepressant-Like Effects via the BDNF-Trkb-CREB Pathway.

Panax ginseng C.A. Meyer (Araliaceae), a popular tonic and dietetic herbal medicine, has been traditionally prescribed in China and other countries to treat affective disorders. The medicinal parts of ginseng, the roots and flower buds, have become increasingly popular as dietary supplements due to the current holistic healthcare trend. We have investigated for the first time the antidepressive actions of the different medicinal parts, namely, the main roots, fibrous roots, and flower buds (in water extract and powder), of garden-cultivated ginseng through behavioral and drug-induced tests in mice. The water extracts, but not the powders of ginseng fibrous roots, flower buds, and main roots (1.5 g of crude drug per kilogram, p.o.), significantly reduced the immobility time in the forced swim test (FST) and tail suspension test (TST); moreover, the water extracts enhanced the 5-hydroxytryptophan (5-HTP)-induced head-twitch response and antagonized the action of reserpine in the mouse. We then explored the antidepressive mechanism of action of the ginsenoside Rb1 (Rb1) related to the brain-derived neurotrophic factor (BDNF) and its downstream proteins in mice exposed to chronic unpredictable mild stress (CUMS). Treatment with Rb1 (20 mg/kg, p.o.) for 21 days significantly attenuated the CUMS-induced decrease in the activities of BDNF, tropomyosin-related kinase B (TrkB), protein kinase B (AKT), extracellular regulatory protein kinase (ERK), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) in the mouse hippocampal CA3 region and prefrontal cortex (PFC). Interestingly, treatment with the novel TrkB antagonist ANA-12 (0.5 mg/kg, i.p.) did not alter the level of BDNF but significantly blocked the antidepressive effects of Rb1 on proteins downstream of BDNF in CUMS-treated mice. These results suggest that BDNF-TrkB-CREB signaling may be involved in the antidepressive mechanism of the action of Rb1.

The effectiveness and safety of electromyography biofeedback therapy for motor dysfunction of children with cerebral palsy: A protocol for systematic review and meta-analysis.

INTRODUCTION: To investigate the effectiveness and safety of electromyography (EMG) biofeedback therapy in improving motor dysfunction among children with cerebral palsy (CP). METHODS AND ANALYSIS: The following databases will be searched: PubMed, EMBASE, ScienceDirect, the Cochrane Library, China National Knowledge infrastructure (CNKI), Technology Periodical Database (VIP), WanFang Data and China Biology Medicine (CBM) from inception to June 2019. All relevant randomized controlled trials (RCTs) utilizing EMG biofeedback therapy for CP will be included. The main outcome is the Gross Motor Function Measure (GMFM). Additional outcomes such as the Modified Ashworth Scale (MAS), Integral Electromyogram (iEMG), Composite Spasticity Scale (CSS), passive range of motion (PROM) or other related outcomes will be included, adverse effects of EMG biofeedback therapy and comparators will also be included. Two reviewers will screen studies, extract data and assess quality independently. Review Manager 5.3 will be used to assess the risk of bias, data synthesis, and subgroup analysis. ETHICS AND DISSEMINATION: This systematic review does not require formal ethical approval because all data will be analyzed anonymously. Results will provide a general overview and evidence concerning the effectiveness and safety of EMG biofeedback therapy for children with CP. The findings of this systematic review will be disseminated through peer-reviewed publications or conference presentations.

The risk of cancer in patients with connective tissue diseases but without dermatomyositis or polymyositis: A multicenter cohort study conducted over 15 years in China.

OBJECTIVES: To investigate the relative risk of cancer in Chinese patients with connective tissue diseases (CTD) associated with and without dermatomyositis or polymyositis. METHODS: A retrospective, multicenter cohort study investigated 32,380 CTD patients (2334 diagnosed with dermatomyositis or polymyositis) without a history of malignancies treated from January 1, 1997, to December 31, 2011. Standardized incidence ratios (SIR) of cancers determined the incidence of malignancies during follow-up. The data was compared with the cancer morbidity of the general population from the Chinese Cancer Registry Annual Report of National Central Cancer Registry. RESULT: A total of 113 patients (348.98 per 100,000) developed cancer during follow-up, 75 (249.62 per 100,000) were patients with CTD without dermatomyositis or polymyositis. The risk of cancer among patients with CTD was increased (SIR=1.45, 95% confidence interval [CI] 1.22-1.71), and this risk increased with age (<40 years: SIR=1.00 [95%CI 0.45-2.21]; 41-60 years: SIR=1.53 [95%CI 1.17-2.00]; and >60 years SIR=2.34 (95%CI 0.93-2.77]) and the time of follow-up (<1year: SIR=1.22 [95%CI 0.88-1.70]; 1-5 years: SIR=1.14 [95%CI 0.79-1.65]; and 6-10 years SIR=1.70 [95%CI 1.34-2.85]), but was similar between genders (male SIR=1.60 [95%CI 1.10-2.31] and female SIR=1.25 [95%CI 1.01-1.55]). The cancer risk among CTD patients without dermatomyositis or polymyositis was not affected (SIR=0.93, 95%CI 0.75-1.16), regardless of gender, age, or follow-up. CONCLUSION: The cancer risk for patients with CTD without dermatomyositis or polymyositis was not increased or decreased, but it was increased when patients with dermatomyositis or polymyositis were included.

Ubpy controls the stability of the ESCRT-0 subunit Hrs in development.

Ubiquitylated developmental membrane signaling proteins are often internalized for endocytic trafficking, through which endosomal sorting complexes required for transport (ESCRT) act sequentially to deliver internalized cargos to lysosomes. The ESCRT function in endocytic sorting is well established; however, it is not fully understood how the sorting machinery itself is regulated. Here, we show that Ubiquitin isopeptidase Y (Ubpy) plays a conserved role in vivo in the homeostasis of an essential ESCRT-0 complex component Hrs. We find that, in the absence of Drosophila Ubpy, multiple membrane proteins that are essential components of important signaling pathways accumulate in enlarged, aberrant endosomes. We further demonstrate that this phenotype results from endocytic pathway defects. We provide evidence that Ubpy interacts with and deubiquitylates Hrs. In Ubpy-null cells, Hrs becomes ubiquitylated and degraded in lysosomes, thus disrupting the integrity of ESCRT sorting machinery. Lastly, we find that signaling proteins are enriched in enlarged endosomes when Hrs activity is abolished. Together, our data support a model in which Ubpy plays a dual role in both cargo deubiquitylation and the ESCRT-0 stability during development.

Is selenium deficiency really the cause of Keshan disease?

Keshan disease (KD) is a dilated cardiomyopathy closely related with a diet deficient in the mineral selenium. It is named for the northeastern Chinese county Keshan, where the disease prevalence is high because of selenium-deficient soil. KD is a gene-environment interaction disease. Here, we used stepwise multiple regression analysis to analyze the risk factors of the disease and the main clinical features in 71 KD patients and 290 controls. The variables analyzed included age, sex, family history of KD, blood selenium level, glutathione peroxidase-1 (GPx-1) activity, variance at codon198 in GPx-1 gene, residence in an endemic area, abnormal electrocardiography (ECG) findings, and cardiothoracic (CT) ratio. The main risk factors found were low GPx-1 activity, family history of KD and living in an endemic area. The main clinical features were increased cardiac load on ECG and increased CT ratio and Tei index. Public health and clinical prevention efforts could focus on increasing GPx-1 activity to address KD. Is selenium deficiency really the certain cause of KD? This is not at all a settled question. And further study is promptly required to investigate the etiology of KD.