Albumin to globulin ratio (AGR) in systemic lupus erythematosus: correlation with disease activity.

OBJECTIVE: To investigate the role of albumin-to-globulin ratio (AGR) in systemic lupus erythematosus (SLE) and its relationship with disease activity. METHODS: This retrospective study consecutively selected patients with SLE and healthy controls. Patients were divided into three groups according to the SLE Disease Activity Index 2000 (SLEDAI-2K): group 1 (mild disease activity, SLEDAI-2K ≤ 6), group 2 (moderate disease activity, SLEDAI-2K 7-12) and group 3 (severe disease activity, SLEDAI-2K > 12). Predictors of SLE disease activity were analysed by ordinal logistical regression. RESULTS: A total of 101 Chinese patients with SLE and 75 healthy Chinese controls were included. Patients with SLE had lower AGR values than healthy individuals, and group 3 patients with SLE displayed lower AGR values than those in group 1, but similar values to group 2. AGR was inversely correlated with SLEDAI-2K (r = -0.543). Ordinal logistic regression analysis showed that lower AGR (ß = -1.319) and lower complement C4 (ß = -1.073) were independent risk factors for SLE disease activity. CONCLUSIONS: AGR was decreased in patients with SLE and may be utilized as a useful inflammatory biomarker for monitoring SLE disease activity.

LncRNA expression profiling in exosomes derived from synovial fluid of patients with rheumatoid arthritis.

OBJECTIVE: To identify the long non-coding RNA (lncRNA) expression profiling in exosomes derived from synovial fluid of rheumatoid arthritis (RA) patients, and carry out bioinformatics analysis on target genes of differentially expressed lncRNAs. METHODS: Exosomes were isolated from synovial fluid via ultracentrifugation. RNAs were extracted from exosomes by using HiPure Liquid RNA/miRNA kits, followed by lncRNA sequencing. Differentially expressed lncRNAs in RA were screened, and bioinformatics analysis of their target genes was carried out. qRT-PCR was used to verify the lncRNA expression levels. RESULTS: Compared with osteoarthritis (OA), 347 lncRNAs were found differentially expressed in RA. Compared with gout, 805 lncRNAs were found differentially expressed in RA. Compared with both OA and gout, 85 lncRNAs were found specially expressed in RA (65 were upregulated (including ENST00000433825.1)). Functional analysis of target genes of the specially expressed lncRNAs revealed significant enrichment of "autophagy" and "mTOR signaling pathway". The qRT-PCR results indicated that ENST00000433825.1 was highly expressed in RA, compared with both OA and gout (P < 0.05), which matched the lncRNA sequencing results. Correlation analysis showed that the level of ENST00000433825.1 in RA patients was significantly and positively correlated with the level of C-reactive protein (CRP) (P < 0.001). CONCLUSIONS: The lncRNA expression profiling in exosomes derived from synovial fluid of RA was significantly different from OA and gout. ENST00000433825.1 was highly and uniquely expressed in RA and significantly and positively correlated with CRP, which might provide a diagnostic and therapeutic biomarker for RA.

Azetidines Kill Multidrug-Resistant Mycobacterium tuberculosis without Detectable Resistance by Blocking Mycolate Assembly.

Tuberculosis (TB) is the leading cause of global morbidity and mortality resulting from infectious disease, with over 10.6 million new cases and 1.4 million deaths in 2021. This global emergency is exacerbated by the emergence of multidrug-resistant MDR-TB and extensively drug-resistant XDR-TB; therefore, new drugs and new drug targets are urgently required. From a whole cell phenotypic screen, a series of azetidines derivatives termed BGAz, which elicit potent bactericidal activity with MIC99 values <10 µM against drug-sensitive Mycobacterium tuberculosis and MDR-TB, were identified. These compounds demonstrate no detectable drug resistance. The mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with cell envelope biogenesis, specifically late-stage mycolic acid biosynthesis. Transcriptomic analysis demonstrates that the BGAz compounds tested display a mode of action distinct from the existing mycobacterial cell wall inhibitors. In addition, the compounds tested exhibit toxicological and PK/PD profiles that pave the way for their development as antitubercular chemotherapies.

Sema3A secreted by sensory nerve induces bone formation under mechanical loads.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.

Improving Pretrained Language Model Fine-Tuning With Noise Stability Regularization.

The advent of large-scale pretrained language models (PLMs) has contributed greatly to the progress in natural language processing (NLP). Despite its recent success and wide adoption, fine-tuning a PLM often suffers from overfitting, which leads to poor generalizability due to the extremely high complexity of the model and the limited training samples from downstream tasks. To address this problem, we propose a novel and effective fine-tuning framework, named layerwise noise stability regularization (LNSR). Specifically, our method perturbs the input of neural networks with the standard Gaussian or in-manifold noise in the representation space and regularizes each layer's output of the language model. We provide theoretical and experimental analyses to prove the effectiveness of our method. The empirical results show that our proposed method outperforms several state-of-the-art algorithms, such as [Formula: see text] norm and start point (L2-SP), Mixout, FreeLB, and smoothness inducing adversarial regularization and Bregman proximal point optimization (SMART). In addition to evaluating the proposed method on relatively simple text classification tasks, similar to the prior works, we further evaluate the effectiveness of our method on more challenging question-answering (QA) tasks. These tasks present a higher level of difficulty, and they provide a larger amount of training examples for tuning a well-generalized model. Furthermore, the empirical results indicate that our proposed method can improve the ability of language models to domain generalization.

Identifying NFKB1, STAT3, and CDKN1A as Baicalein's Potential Hub Targets in Parkinson's Disease-related α-synuclein-mediated Pathways by Integrated Bioinformatics Strategies.

BACKGROUND: The overexpression, accumulation, and cell-to-cell transmission of α-synuclein leads to the deterioration of Parkinson's disease (PD). Previous studies suggest that Baicalein (BAI) can bind to α-synuclein and inhibit α-synuclein aggregation and secretion. However, it is still unclear whether BAI can intervene with the pathogenic molecules in α-synuclein-mediated PD pathways beyond directly targeting α-synuclein per se. METHODS: This study aimed to systematically investigate BAI's potential targets in PD-related A53T mutant α-synuclein-mediated pathways by integrating data mining, network pharmacological analysis, and molecular docking simulation techniques. RESULTS: The results suggest that BAI may target genes that are dysregulated in synaptic transmission, vesicle trafficking, gene transcription, protein binding, extracellular matrix formation, and kinase activity in α-synucleinmediated pathways. NFKB1, STAT3, and CDKN1A are BAI's potential hub targets in these pathways. CONCLUSION: Our findings highlight BAI's potentiality to modulate α-synuclein-mediated pathways beyond directly targeting α-synuclein per se.

The interplay between the nerves and skeleton: a 30-year bibliometric analysis.

Background: The mechanisms and effects of the interplay between the nerves and skeleton remain a popular research topic. This study aimed to analyze and evaluate publications on nerve-bone interactions using bibliometrics and to identify the state of the art of current research, hotspots, and future directions. Methods: This study included 1989 articles and reviews from the Web of Science Core Collection (WoSCC) published from January 1, 1991, to June 22, 2022. The Bibliometrix package of R 4.2.0 (The R Foundation for Statistical Computing, Vienna, Austria) was used to analyze basic information about the publications, including the annual number of publications, institution analysis, author influence analysis, journal analysis, and the national cooperation network. We also used CiteSpace 5.8.R3 for bibliometric analysis, including co-occurrence, co-citation, and cluster analysis. Results: We discovered a significant increase in the number of articles on nerve-bone interactions published over the last 10 years. The most active country and institution were the United States and the University of Minnesota, respectively. In terms of journals and cocited journals, Bone was ranked highest with respect to the number of publications, while Journal of Bone and Mineral Research was ranked highest among cited journals. Wang Lei was the author with the most publications, and Bjurholm A was the most cited author. The analysis of references and keywords revealed that the impact of nerve- and neuromodulation-related factors on stem cell differentiation was a persistently hot topic. Osteoarthritis, neuropeptide Y, and osteoclastogenic process are likely to be the next era of research hotspots. The neurovascular crosstalk within bone has received great attention, especially in skeletal diseases, which may provide potential targets for future treatments. Conclusions: We used a bibliometric method to provide an efficient, objective, and comprehensive assessment of existing research about the interplay between the skeletal and nervous systems and to accurately identify hotspots and research frontiers, providing valuable information for future research.

A comprehensive assessment of heavy metal(loid) contamination in leafy vegetables grown in two mining areas in Yunnan, China-a focus on bioaccumulation of cadmium in Malabar spinach.

Contamination of leafy vegetables grown in heavy metal(loid)-polluted mining areas pose serious health risks. This study aimed to explore the heavy metal(loid) contamination of leafy vegetables near two mining areas, by collecting samples from 14 different leafy vegetable species in Yunnan Province, China. The lead (Pb), cadmium (Cd), arsenic (As), and copper (Cu) contents of the samples were determined, and risks to human health were calculated using the hazard quotient and hazard index (HI). Moreover, Malabar spinach was identified as a leafy vegetable that exhibits low accumulation of heavy metal(loid)s. The accumulation capacity of different Malabar spinach varieties was verified, and a Cd soil safety threshold was determined using a pot experiment. Overall, Pb and Cd were the main soil and vegetable contaminants found in both study sites. The HI values for all leafy vegetables, apart from Malabar spinach, were greater than 1, indicating the presence of risks to human health; moreover, the health risks were greater for children than adults. The Malabar spinach pot experiment results showed that only some Cd forms exceeded China's maximum permissible standards. Furthermore, Malabar spinach varieties A (instant Malabar spinach), C (extra-large leaf green vine Malabar spinach), and F (large leaf Malabar spinach) displayed the lowest Cd accumulation. We calculated Cd total and bioavailable soil safety thresholds of 4.75 and 0.77 mg kg-1, respectively. However, further research is required to validate soil heavy metal safety thresholds for different vegetables. Ultimately, the heavy metal(loid) contamination of leafy vegetables described here was more serious than anticipated. Finally, the results of this study can inform residents living near these mining areas of a low-risk leafy vegetable, which will reduce the harm caused by heavy metal(loid) contamination in the area.

Integrated Spatial Modulation and STBC-VBLAST Design toward Efficient MIMO Transmission.

In this contribution, the concept of spatial modulation (SM) is firstly integrated into the structure of space-time block codes (STBC)-aided vertical Bell-labs layered space-time (VBLAST) systems, in order to strike a balanced tradeoff among bit error ratio (BER), spectral efficiency and computational complexity. First of all, in order to enhance the BER performance of STBC-VBLAST, we advocate an effective transmit power allocation (TPA) scheme with negligible implementation costs, while dividing the STBC and VBLAST layers with alleviated interference, so as to facilitate combination with SM. Then, we further utilize the unique structure of SM for enhancing the spectral efficiency of original STBC-VBLAST, wherein the information is conveyed by not only the amplitude/phase modulation (APM) symbols but also the antenna indices. In addition, constellation sets of STBC symbols are specifically designed to be rotated to make full use of the degrees of freedom. Finally, the performance advantages of the above-mentioned structures over traditional STBC-VBLAST are demonstrated by the theoretical derivation of a closed-form expression for the union bound on the bit error probability for various spectral efficiencies, and they are supported by simulation results.

Enhanced PDGFR/Wnt/ß-catenin activity of mesenchymal stem cells with high migration ability rescue bone loss of osteoporosis.

Osteoporosis is a widespread disease characterized by bone mass loss and microarchitectural deterioration. The side effects of clinical drugs make mesenchymal stem cells (MSCs)-based therapy gain increasing focus in the treatment of osteoporosis. MSCs need to migrate to the site of damage and undergo differentiation in order to participate in the subsequent bone repair process. Therefore, the homing ability of MSCs may be related to the repair ability. Here, we proposed a novel method to screen MSCs with high migration capacity and confirmed that these MSCs exhibited higher osteogenic differentiation ability both in vivo and in vitro. Further results indicated that MSCs with high migration ability could partly rescue the bone loss of ovarectomized (OVX) rats. Higher expression of Platelet-derived growth factors receptor ß- (PDGFRß) and more nuclear transduction of ß-catenin in MSCs with high migration ability may be responsible for biological functions. This article may provide a method to improve the efficacy of MSCs-based therapy in the clinic.

Chaperone-mediated Autophagy Regulates Cell Growth by Targeting SMAD3 in Glioma.

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

Antidote or Trojan horse for submerged macrophytes: Role of microplastics in copper toxicity in aquatic environments.

Due to their unique surface structures and physicochemical properties, microplastics (MPs) can adsorb other contaminants, thus impacting their toxicity and fate in aquatic ecosystems. In the present study, the adsorption and transportation of copper ions (Cu2+) in polyethylene (PE, 5 and 150 µm) and their combined effects on four submerged macrophyte species were assessed. Results demonstrated that the addition of PE reduced the Cu2+ concentration in copper sulfate (CuSO4) solution and the adsorption of Cu2+ in PE (10 mg/L) increased with CuSO4 concentration (100-600 µmol/L). PE alone exhibited no inhibitory effects on macrophytes, while Cu2+ showed fatal toxicity toward the macrophytes. However, the combination of PE and Cu2+ showed lower inhibitory effects on macrophytes and the toxicity attenuation varied among species. Additionally, PE may act as a carrier (like a Trojan horse) for the environmental transfer of Cu2+, thereby hosting Cu2+ toxicity against macrophytes in the imported environment. Our findings indicate that PE acts as both an antidote to and carrier of Cu2+ toxicity in macrophytes. This study should help in clarifying the combined effects and risk assessments of MPs and heavy metals in future studies.

Diagnostic validity of different gonial angle segmentation for the assessment of mandibular growth direction: A retrospective study.

BACKGROUND: The development of the mandible largely determines the sagittal and vertical lateral appearance. The gonial angle (Articulare-Gonion-Menton, Ar-Go'-Me), as a composite indicator, represents the growth direction of the mandible. We proposed a method based on the Frankfort horizontal (FH) plane and its vertical plane (VFH) to divide the gonial angle into sagittal and vertical components (Articulare-Gonion-VFH / Menton-Gonion-FH, Ar-Go'-VFH / Me-Go'-FH) and to compare the accuracy of diagnosing the development of the mandible and maxillofacial structures with other methods. METHODS: Lateral cephalometric films from 736 volunteers aged 6-30 years were collected and analyzed for cephalometric measurements. Four groups of segmentation-based angle, including the FH-based segmentation (Ar-Go'-VFH / Me-Go'-FH), the SN-based segmentation (Articulare-Gonion- Sellion-Nasion plane' vertical plane/ Menton-Gonion- Sellion-Nasion plane, Ar-Go'-VSN / Me-Go'-SN), the Go'-S based segmentation(Articulare-Gonion-Sellion / Menton-Gonion-Sellion, Ar-Go'-S / Me-Go'-S), and the Go'-N based segmentation (Articulare-Gonion-Nasion / Menton-Gonion-Nasion, Ar-Go'-N / Me-Go'-N), as well as commonly used sagittal and vertical indices were measured. Pearson correlation analysis was used to show the representativeness of different segmentation methods on the mandibular growth direction. RESULTS: As the gonial angle decreased with age, all the segmentation-based metrics decreased. The plane-based segmentation metrics, including Ar-Go'-VFH / Me-Go'-FH, Ar-Go'-VSN / Me-Go'-SN, were superior to the point-based segmentation metrics (Ar-Go'-S / Me-Go'-S, and Ar-Go'-N / Me-Go '-N) in evaluating vertical and sagittal development of the mandible. The sagittal indicators displayed alteration of ramus and condyle, while these vertical indicators responded to the alteration of the mandibular corpus and gonial angle. CONCLUSIONS: The gonial angle should be clinically segmented with planes (including SN plane and FH plane) rather than points (including Go'-S and Go'-N) to assess mandibular development. The FH plane-based segmentation method facilitated chair-side diagnosis of the mandibular growth direction.

Nitrogen-Doped Hierarchical Porous Activated Carbon Derived from Paddy for High-Performance Supercapacitors.

A facile and environmentally friendly fabrication is proposed to prepare nitrogen-doped hierarchical porous activated carbon via normal-pressure popping, one-pot activation and nitrogen-doping process. The method adopts paddy as carbon precursor, KHCO3 and dicyandiamide as the safe activating agent and nitrogen dopant. The as-prepared activated carbon presents a large specific surface area of 3025 m2·g-1 resulting from the synergistic effect of KHCO3 and dicyandiamide. As an electrode material, it shows a maximum specific capacitance of 417 F·g-1 at a current density of 1 A·g-1 and very good rate performance. Furthermore, the assembled symmetric supercapacitor presents a large specific capacitance of 314.6 F·g-1 and a high energy density of 15.7 Wh·Kg-1 at 1 A·g-1, maintaining 14.4 Wh·Kg-1 even at 20 A·g-1 with the energy density retention of 91.7%. This research demonstrates that nitrogen-doped hierarchical porous activated carbon derived from paddy has a significant potential for developing a high-performance renewable supercapacitor and provides a new route for economical and large-scale production in supercapacitor application.

The effect of revenue diversification on bank profitability and risk during the COVID-19 pandemic.

Banks can potentially reduce the variability of their revenue by diversifying beyond traditional lending activities into noninterest revenue sources. We investigate the effect of the COVID-19 pandemic on the relation between the use of noninterest income and bank profit and risk. The economic effect of the pandemic resulted in tightened credit standards and reduced demand for many types of loans. We find that noninterest revenue sources are positively related to performance but inversely related to risk. These results are consistent with a beneficial diversification effect during the pandemic from banks expanding beyond traditional lending sources of revenue.

Improving Adversarial Robustness via Attention and Adversarial Logit Pairing.

Though deep neural networks have achieved the state of the art performance in visual classification, recent studies have shown that they are all vulnerable to the attack of adversarial examples. In this paper, we develop improved techniques for defending against adversarial examples. First, we propose an enhanced defense technique denoted Attention and Adversarial Logit Pairing (AT + ALP), which encourages both attention map and logit for the pairs of examples to be similar. When being applied to clean examples and their adversarial counterparts, AT + ALP improves accuracy on adversarial examples over adversarial training. We show that AT + ALP can effectively increase the average activations of adversarial examples in the key area and demonstrate that it focuses on discriminate features to improve the robustness of the model. Finally, we conduct extensive experiments using a wide range of datasets and the experiment results show that our AT + ALP achieves the state of the art defense performance. For example, on 17 Flower Category Database, under strong 200-iteration Projected Gradient Descent (PGD) gray-box and black-box attacks where prior art has 34 and 39% accuracy, our method achieves 50 and 51%. Compared with previous work, our work is evaluated under highly challenging PGD attack: the maximum perturbation ϵ ∈ {0.25, 0.5} i.e. L ∞ ∈ {0.25, 0.5} with 10-200 attack iterations. To the best of our knowledge, such a strong attack has not been previously explored on a wide range of datasets.

Aniline-containing derivatives of parthenolide: Synthesis and anti-chronic lymphocytic leukaemia activity.

Parthenolide exhibits anti-leukaemia activity, whilst its synthetic modification to impart improve drug-like properties, including 1,4-conjugate addition of primary and secondary amines, have previously been used, 1,4-addition of aniline derivatives to parthenolide has not been fully explored. A protocol for such additions to parthenolide is outlined herein. Reaction conditions were determined using tulipane as a model Michael acceptor. Subsequently, aniline-containing parthenolide derivatives were prepared under the optimised conditions and single crystal X-ray diffraction structures were resolved for three of the compounds synthesised. The synthesised derivatives, along with compounds resulting from a side reaction, were tested for their in vitro anti-leukaemia activity using the chronic lymphocytic leukaemia (CLL) MEC1 cell line. Computational studies with the 2RAM protein structure suggested that the activity of the derivatives was independent of their in silico ability to dock with the Cys38 residue of NF-κB.

Tau knockout exacerbates degeneration of parvalbumin-positive neurons in substantia nigra pars reticulata in Parkinson's disease-related α-synuclein A53T mice.

α-Synuclein (α-syn)-induced neurotoxicity has been generally accepted as a key step in the pathogenesis of Parkinson's disease (PD). Microtubule-associated protein tau, which is considered second only to α-syn, has been repeatedly linked with PD in association studies. However, the underlying interaction between these two PD-related proteins in vivo remains unclear. To investigate how the expression of tau affects α-syn-induced neurodegeneration in vivo, we generated triple transgenic mice that overexpressed α-syn A53T mutation in the midbrain dopaminergic neurons (mDANs) with different expression levels of tau. Here, we found that tau had no significant effect on the A53T α-syn-mediated mDANs degeneration. However, tau knockout could modestly promote the formation of α-syn aggregates, accelerate the severe and progressive degeneration of parvalbumin-positive (PV+) neurons in substantia nigra pars reticulata (SNR), accompanied with anxiety-like behavior in aged PD-related α-syn A53T mice. The mechanisms may be associated with A53T α-syn-mediated specifically successive impairment of N-methyl-d-aspartate receptor subunit 2B (NR2B), postsynaptic density-95 (PSD-95) and microtubule-associated protein 1A (MAP1A) in PV+ neurons. Our study indicates that MAP1A may play a beneficial role in preserving the survival of PV+ neurons, and that inhibition of the impairment of NR2B/PSD-95/MAP1A pathway, may be a novel and preferential option to ameliorate α-syn-induced neurodegeneration.

Analysis of Cerebrospinal Fluid Soluble TREM2 and Polymorphisms in Sporadic Parkinson's Disease in a Chinese Population.

BACKGROUND: Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor that mediates the degradation disorder of amyloid ß (Aß) in Alzheimer's disease. However, the role of TREM2 in Parkinson's disease (PD) and α-Synclein (α-Syn) degradation is largely unknown. METHODS: In this case-control study on Chinese population, we sequenced for polymorphisms in exon 2 of the TREM2 gene in 1,292 individuals, PD cases (n = 612), healthy controls (n = 680) by Sanger sequence, and compared the distribution of allelic frequencies between the two groups by the Fisher's exact test. Additionally, we developed and used the enzyme-linked immunosorbent assay to evaluated soluble TREM2 (sTREM2) levels in the cerebrospinal fluid (CSF), and plasma in partial of sequenced groups (55 PD and 40 healthy controls) analyzed their relationship with total a-syn (t-a-Syn). RESULTS: Two novel variants were detected in exon 2 of the TREM2 gene, namely, p.S81 N, p.G58D; however, these were not significantly associated with PD (612 PD and 680 healthy controls). sTREM2 in CSF was significantly upregulated in PD patients compared to healthy controls (433.1 ± 24.7 pg/mL vs. 275.2 ± 17.9 pg/mL, p < 0.0001), but not in plasma (281.7 ± 29.3 pg/mL vs. 257.8 ± 16.5 pg/mL, p = 0.805). In PD patients, sTREM2 was positively correlated with t-α-syn (r = 0.62, p = 0.0001) in CSF, but not in plasma (r = 0.02, p = 0.89). CONCLUSIONS: Although it may not indicate that exon 2 polymorphisms of TREM2 play a role in the pathogenesis of PD in the Chinese population, our findings described above highlight the relevance of CSF sTREM2 as a promising biomarker and are extremely possible to the therapeutic target for PD in the future.

Complex pulmonary arteriovenous fistula in mother and daughter: Case report.

RATIONALE: Complex pulmonary arteriovenous fistula (PAVF) is unusual, and even rarer in 2 members of a family. PAVF may not appear on chest X-ray or computed tomography imaging, especially in asymptomatic patients, and therapy is limited. Herein, PAVFs occurring in a mother and daughter are described, with the current standard methods of diagnosis and treatment of PAVF. PATIENT CONCERNS: A 34-year-old woman and her 13-year-old daughter presented with light cyanosis of the nail beds but were otherwise asymptomatic, and physical examination was unremarkable. Their arterial oxygen saturation levels were low (80-85%). DIAGNOSES: Angiography led to a diagnosis of PAVF involving the bilateral lung in both women. INTERVENTIONS: The combined use of coils with occluder (patent ductus arteriosus, or PDA) to obstruct the fistula. OUTCOMES: After interventional treatment, the patients' arterial oxygen saturation improved rapidly (90-95%). At 6-month follow-up, the patients' symptoms and oxygen saturation were normal. LESSONS: PAVF is an autosomal dominant disease. Here, the characteristics of the 2 patients were very similar. Using detachable coils and then a PDA occluder is a highly efficient method for treating complex PAVFs.