Juvenile idiopathic arthritis presenting as diffuse alveolar hemorrhage at onset: A case series.

OBJECTIVE: The etiology of diffuse alveolar hemorrhage (DAH) in childhood is often unknown, and it may be an early manifestation of rheumatic disease. Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in children, but DAH as an onset manifestation of JIA is rare. This study summarizes the clinical characteristics of patients with JIA presenting as DAH. METHODS: We retrospectively analyzed the age of onset, clinical manifestations, imaging features, treatments, and prognosis of five cases of JIA presenting as DAH. RESULTS: Themedian age at DAH onset was 6 months (range, 2 months-3 years). Pallor was the most common manifestation of onset (5/5). Other symptoms included cough (2/5), tachypnea (2/5), hemoptysis (1/5), cyanosis (1/5), and fatigue (1/5). Imaging showed ground-glass opacity (GGO) (5/5), subpleural or intrapulmonary honeycombing (4/5), consolidation (3/5), interlobular septal thickening (2/5), and nodules (1/5). Anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) were positive in five children (5/5), and antinuclear antibody (ANA) was positive in four children (4/5). ANA in three children and ACPA/RF in one child were positive before the onset of joint symptoms. The median age at the onset of joint symptoms was 3 years and 9 months (2 years and 6 months-8 years). Joint symptoms were mainly characterized by joint swelling, pain, and difficulty walking, and the most commonly affected joints were the knees, ankles, and wrists. After the diagnosis of DAH, the five patients were treated with glucocorticoids. Alveolar hemorrhage was effectively controlled in three cases, but the other two patients still had anemia and poor improvements in chest imaging. After joint symptoms, the patients were treated with glucocorticoids combined with diclofenac, disease-modifying antirheumatic drugs, and biological agents. Alveolar hemorrhage was in remission, and joint symptoms were relieved in the five cases. CONCLUSION: DAH can be the first clinical manifestation of JIA, and joint involvement occurs 1-5 years later. Children with DAH who are positive for RF, ACPA, and/or ANA and have GGO accompanied by honeycombing on imaging should be concerned about their joint involvement in future.

The mediating and moderating effects of resilience between childhood trauma and geriatric depressive symptoms among Chinese community-dwelling older adults.

Objective: This study aims to examine the association between childhood traumatic events (CTEs), childhood trauma severity, and depressive symptoms, as well as to examine the mediating and moderating roles of resilience in these associations. Methods: We conducted a cross-sectional study of 1,091 community-dwelling older adults in Jinan, China. The trauma history questionnaire (THQ) was used to measure CTEs and childhood trauma severity. CTEs were defined as the number of traumatic events before the age of 18. We calculated childhood trauma severity by multiplying the number of CTEs by the participants' self-perceived impact level of the events from the THQ. We then applied the 15-item Geriatric Depression Scale and 10-item Connor-Davidson Resilience Scale to assess participants' depressive symptoms and resilience, respectively. Linear regression models were used to examine the associations, and structural equation modeling was used to examine the mediating and moderating roles of resilience. Results: Childhood traumatic events, childhood trauma severity, and resilience were all associated with depressive symptoms in older adults. Resilience mediated the relationship between childhood trauma severity and depressive symptoms (ß = 0.082, 95% CI = 0.045-0.123), accounting for 26.6% of the overall effect (ß = 0.308, 95% CI = 0.190-0.422). However, there was no evidence that resilience mediated the association between CTEs and depressive symptoms. In addition, we did not find that resilience played a moderating role in the associations of CTEs, childhood trauma severity with depressive symptoms. Conclusion: Resilience plays a mediating role in the relationship between childhood trauma severity and depressive symptoms. Intervention measures on improving resilience may reduce childhood trauma severity associated with depression risk in older Chinese adults.

Gauging urban resilience in the United States during the COVID-19 pandemic via social network analysis.

Social distancing policies and other restrictive measures have demonstrated efficacy in curbing the spread of the COVID-19 pandemic. However, these interventions have concurrently led to short- and long-term alterations in social connectedness. Comprehending the transformation in intracity social interactions is imperative for facilitating post-pandemic recovery and development. In this research, we employ social network analysis (SNA) to delve into the nuances of urban resilience. Specifically, we constructed intricate networks utilizing human mobility data to represent the impact of social interactions on the structural attributes of social networks while assessing urban resilience by examining the stability features of social connectedness. Our findings disclose a diverse array of responses to social distancing policies regarding social connectedness and varied social reactions across U.S. Metropolitan Statistical Areas (MSAs). Social networks generally exhibited a shift from dense to sparse configurations during restrictive orders, followed by a transition from sparse to dense arrangements upon relaxation of said orders. Furthermore, we analyzed the alterations in social connectedness as demonstrated by network centrality, which can presumably be attributed to the rigidity of policies and the inherent qualities of the examined MSAs. Our findings contribute valuable scientific insights to support informed decision-making for post-pandemic recovery and development initiatives.

Influence of duration of preoperative treatment with phenoxybenzamine and secretory phenotypes on perioperative hemodynamics and postoperative outcomes in pheochromocytoma and paraganglioma.

Objectives: Resection of pheochromocytoma and paraganglioma (PPGL) carries risks with perioperative hemodynamic instability. Phenoxybenzamine (PXB) is a commonly used α-blockade to prevent it. It is unclear whether lengthening the preoperative duration of PXB is better for hemodynamic stability and postoperative outcomes. Furthermore, different types of catecholamines have varying effects on perioperative hemodynamics. Thus, our study aimed to investigate the impact of the duration of preoperative preparation with PXB and secretory phenotypes of the patients on intraoperative hemodynamic stability and postoperative complications in PPGL. Methods: Between Dec 2014 and Jan 2022, 166 patients with PPGL were operated on by the same team at Sun Yat-sen Memorial Hospital. They were divided into group A(1-14d), Group B(15-21d), and Group C(>21d) based on the duration of management with PXB and into the adrenergic and the noradrenergic phenotype group based on secretory profiles. Data on intraoperative hemodynamics and postoperative outcomes were collected and compared among groups. Results: A total of 96 patients occurred intraoperative hemodynamic instability, and 24 patients had 29 postoperative complications related to the surgery. Among the 145 patients treated with PXB, no significant differences were found in the cumulative time outside the target blood pressure(6.67%[0-17.16%] vs. 5.97%[0-23.08%] vs. 1.22%[0-17.27%], p=0.736) or in the median total HI-score(42.00[30.00-91.00] vs. 89.00[30.00-113.00] vs. 49.00[30.00-93.00], p=0.150) among group A(n=45), B(n=51) and C(n=49). Multivariate analysis demonstrated that the level of plasma-free metanephrine(MN) was an independent risk factor for intraoperative hemodynamic instability. And the median cumulative time outside of the target blood pressure in the adrenergic phenotype group was significantly greater than that in the noradrenergic phenotype group(8.17%[0-26.22%] vs. 1.86%[0-11.74%], p=0.029). However, the median total HI-score(99.50[85.00-113.25] vs. 90.00[78.00-105.00], p=0.570) and postoperative outcomes showed no differences between the two groups. Conclusions: A preoperative duration of nearly 14 days with PXB is sufficient for ensuring intraoperative hemodynamic stability in PPGL. And lengthening the preparation duration may not provide additional benefits in the era of widespread application and advanced techniques of laparoscopic surgery. Additionally, patients with the adrenergic phenotype are more prone to intraoperative hemodynamic instability than the noradrenergic phenotype. Thus, more attention should be given to the adrenergic phenotype during surgery.

Exploratory factor analysis of shared and specific genetic associations in depression and anxiety.

BACKGROUND: Previous genetic studies of anxiety and depression were mostly based on independent phenotypes. This study aims to investigate the shared and specific genetic structure between anxiety and depression. METHOD: To identify the underlying factors of Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and their combined scale (joint scale), we employed exploratory factor analysis (EFA) using the eigenvalue of parallel analysis. Subsequently, we conducted a genome-wide association study (GWAS) for these factors. In addition, we utilized LD Score Regression (LDSC) to determine the genetic correlations between the identified factors and four common mental disorders, three sleep phenotypes, and other traits that have been previously linked to anxiety and depression. RESULTS: The EFA uncovered two factors for the GAD-7 scale, namely nervousness and disturbance, two factors for the PHQ-9 scale, namely negative affect and sleep/appetite disturbance, and four factors for the joint scale, specifically nervousness, anhedonia, sleep/appetite disturbance, and fidget. We identified two genome-wide significant genomic loci, with overlap across GAD-7 factor 1 and joint scale factor 1: rs148579586 (PGAD-7 = 1.365 × 10-09, PJoint scale = 1.434 × 10-09) and rs201074060 (PGAD-7 = 3.672 × 10-09, PJoint scale = 3.824 × 10-09). Genetic correlations in factors ranged from 0.722 to 1.000 (all p < 1.786 × 10-03) with 27 of 28 correlations being significantly smaller than one. The genetic correlations with external phenotypes showed small variation across the eight factors. CONCLUSION: Unidimensional structures can provide more precise scores, which can aid in identifying the shared and specific genetic associations between anxiety and depression. This is a crucial step in characterizing the genetic structure of these conditions and their co-occurrence.

Sex disparity in cognitive aging related to later-life exposure to ambient air pollution.

BACKGROUND: Sex difference in the association between ambient air pollution and cognitive aging remained unclear. This current study aimed to assess the impacts of long-term exposure to major air pollutants on cognitive performance among Chinese middle-aged and older adults, and explore whether these associations could be modified by sex. METHODS: By deriving longitudinal data from four waves of the China Health and Retirement Longitudinal Study, we included 13,507 participants aged 45+ years who had at least two cognitive tests recorded from 2011 to 2018. We used a standardized questionnaire consisting of five domain-specific functions to measure global cognitive score. Based on well-validated spatiotemporal datasets, annual average concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) were assigned to each enrollee at prefectural city level and at the simulated residential addresses through Monte Carlo simulation approach. Linear mixed-effects models were applied to assess the impacts of major air pollutants on cognitive function with multiple adjustments. Sex-stratified analyses were performed to examine the potential effect modification on these associations. To enhance the interpretability of our results, we also compared the estimated effects of air pollutants with the effect of aging on cognitive function. RESULTS: We evaluated 38,950 records of cognitive function tests, of which 44.0% were from women. An increase of 10-µg/m3 in PM2.5, NO2 and O3 exposure were associated with 0.36 (95% confidence interval: -0.40, -0.31), 0.51 (-0.60, -0.43) and 0.26 (-0.47, -0.06) points decline in global cognitive score, respectively, equivalent to the effect of aging by 2.8-5.0 years. Sex-stratified analyses suggested significantly greater cognitive impairment associated with air pollutants in women than men. We found reversely J-shaped concentration-response relationships between ambient air pollutants and cognitive decline in both sexes. Main findings on sex-specific associations were robust to the adjustments for covariates, inclusion criteria, and co-pollutant analyses, as well as sensitivity analyses based on simulation-based exposure for PM2.5 and NO2. CONCLUSIONS: Later-life exposure to ambient air pollution may accelerate cognitive aging of middle-aged and older adults, suggesting significant sex disparity with higher vulnerability in women.

Outcomes of adult patients with type 1 primary refractory acute myeloid leukemia: a single center experience.

Adult patients with newly diagnosed de novo acute myeloid leukemia (AML), who had less than a 50% reduction in blast numbers and with > 15% residual blasts after first cycle of induction chemotherapy, defined as type 1 primary refractory (REF1), have grave prognosis. We retrospectively analyzed the data of 58 patients with REF1 who received salvage treatments with curative intension to evaluate the impact of salvage regimens with regard to response and overall survival (OS). Seventeen patients received intermediate- or high-dose cytarabine (ID/HD Ara-C) based intensive salvage chemotherapy, 36 patients received G-CSF primed less intensive chemotherapy and 5 patients received novel targeted drugs based low intensive therapy. The CR/CRi and MLFS rate was 6/17 and 2/17, 14/36 and 3/36, 3/5 and 0/5, respectively. The median OS for the whole cohort was 20.3 months. Median OS was comparable between the 3 arms. Overall, 42 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), 14 patients in the intensive arm, 24 patients in the less intensive arm and 4 patients in the low intensive arm. Median survival for allo-HSCT patients was significantly longer than for non-allo-HSCT patients (38.8 months vs. 2.1 months, p < 0.001). In multivariate analysis, achievement of CR/CRi after the salvage regimen were predictive of OS. We conclude that no significant difference in outcome among traditional salvage regimens in patients with REF1. G-CSF primed less intensive chemotherapy could serve as an alternative of ID/HD Ara-C based intensive chemotherapy and allo-HSCT is indispensable for long-term survival.

Gut Microbiota is an Impact Factor based on the Brain-Gut Axis to Alzheimer's Disease: A Systematic Review.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system. The pathogenesis of AD has been explained using cholinergic, ß-amyloid toxicity, tau protein hyperphosphorylation, and oxidative stress theories. However, an effective treatment method has not been developed. In recent years, with the discovery of the brain-gut axis (BGA) and breakthroughs made in Parkinson's disease, depression, autism, and other diseases, BGA has become a hotspot in AD research. Several studies have shown that gut microbiota can affect the brain and behavior of patients with AD, especially their cognitive function. Animal models, fecal microbiota transplantation, and probiotic intervention also provide evidence regarding the correlation between gut microbiota and AD. This article discusses the relationship and related mechanisms between gut microbiota and AD based on BGA to provide possible strategies for preventing or alleviating AD symptoms by regulating gut microbiota.

Characterization of an International High-Risk Escherichia coli ST410 Clone Coproducing NDM-5 and OXA-181 in a Food Market in China.

During a 2020 routine epidemiological investigation of carbapenem-resistant Enterobacterales at a local food market in Guangzhou, China, two Escherichia coli ST410 isolates coproducing NDM-5 and OXA-181 were obtained from environmental samples. Antimicrobial susceptibility testing, whole-genome sequencing, and conjugation assays were applied to identify their resistance phenotypes, phylogenetic relatedness, and genetic characteristics. Phylogenetic analysis showed that the two isolates were clonally related with only one core-genome single-nucleotide polymorphism (SNP) difference and clustered into a branch with 87 E. coli ST410 isolates deposited in GenBank. These 89 ST410 isolates were closely related (≤51 SNPs), and most were from humans in Southeast Asian countries (n = 47). A Vietnamese clinical isolate collected in 2017 showed the strongest epidemiological link (seven SNPs) to the two ST410 isolates detected in this study. Complete-genome analysis revealed that the carbapenem resistance determinants blaNDM-5 and blaOXA-181 were located on an IncF1:A1:B49-IncQ1 plasmid and IncX3 plasmid, respectively. Conjugation experiments confirmed that the IncX3 plasmid was self-transmissible while the IncF1:A1:B49-IncQ1 plasmid was nonconjugative. BLASTn analysis indicated that the two plasmids showed high similarity to other blaNDM-5-bearing IncF1:A1:B49-IncQ1 and blaOXA-181-bearing IncX3 plasmids from other countries. Altogether, the high similarity of the core genomes and plasmids between the ST410 isolates found in this study and those human source isolates from foreign countries suggested the clonal spread of E. coli ST410 strains and horizontal transmission of blaOXA-181-bearing IncX3 plasmids across Southeast Asian countries. Stringent sanitary management of food markets is important to prevent the dissemination of high-risk clones to the public. IMPORTANCE This is the first report of an Escherichia coli ST410 clone that coproduces NDM-5 and OXA-181 in China. The high similarity of the core genomes and plasmids between the ST410 isolates characterized in this study and human source isolates from foreign countries strongly suggests that this ST410 lineage is an international high-risk clone, highlighting the need for continuous global surveillance of ST410 clones.

Mechanistic Insight into Electron Transfer from Fe(II)-Bearing Clay Minerals to Fe (Hydr)oxides.

Electron transfer (ET) is the essence of most biogeochemical processes related to element cycling and contaminant attenuation, whereas ET between different minerals and the controlling mechanism remain elusive. Here, we used surface-associated Fe(II) as a proxy to explore ET between reduced nontronite NAu-2 (rNAu-2) and Fe (hydr)oxides in their coexisting systems. Results showed that ET could occur from rNAu-2 to ferrihydrite but not to goethite, and the ET amount was determined by the number of reactive sites and the reduction potential difference between rNAu-2 and ferrihydrite. ET proceeded mainly through the mineral-mineral interface, with a negligible contribution of dissolved Fe2+/Fe3+. Control experiments by adding K+ and increasing salinity together with characterizations by X-ray diffraction, scanning electron microscopy/energy-dispersive spectrometry, and atomic force microscopy suggested that ferrihydrite nanoparticles inserted the interlayer space in rNAu-2 where structural Fe(II) in rNAu-2 transferred electrons mainly through the basal plane to ferrihydrite. This study implicates the occurrence of ET between different redox-active minerals through the mineral-mineral interface. As minerals at different reduction potentials often coexist in soils/sediments, the mineral-mineral ET may play an important role in subsurface biogeochemical processes.

The STAT3 inhibitor stattic overcome bortezomib-resistance in multiple myeloma via decreasing PSMB6.

Bortezomib, an FDA approved drug in 2003 for newly diagnosed and relapsed/refractory MM, had showed great efficacy in different clinical settings. However, many patients still developed resistance to Bortezomib, and the mechanism of action remains unelucidated. Here, we showed that Bortezomib resistance can be partially overcome by targeting a different subunit of 20 S complex - PSMB6. PSMB6 knock down by shRNA increased sensitivity to Bortezomib in resistant and sensitive cell line. Interestingly, a STAT3 inhibitor, Stattic, is shown to selectively inhibit PSMB6 and induce apoptosis in Bortezomib resistant and sensitive MM cells, even with IL-6 induction. Therefore, PSMB6 is a novel target for Bortezomib resistance and Stattic may offer a potential therapeutic strategy.

Insight into Accelerating Polysulfides Redox Kinetics by BN@MXene Heterostructure for Li-S Batteries.

Sluggish redox kinetics and shuttle effect of polysulfides hinder the extensive application of the lithium-sulfur batteries (LSBs). Herein a functional heterostructure of boron nitride (BN) and MXene with an alternately layered structure (BN@MXene) is designed as separator interlayer. High efficiency Li+ transmission, uniform lithium deposition, strong adsorption, and efficient catalytic conversion activities of lithium polysulfides (LiPSs) realized by this heterostructure are confirmed by experiments and theoretical calculations. The alternately layered structure provides unblocked ion transmission channels and abundant active sites to accelerate the polysulfides redox kinetics with reduced energy barriers of oxidation and reduction reactions. As a result, the LSBs deliver an initial discharge capacity of up to 1273.9 mAh g-1 at 0.2 °C and a low decay of 0.058% per cycle in long-term cycling up to 700 cycles at 1 °C. This work provides an effective designing strategy to accelerate the polysulfides redox kinetics for advanced Li-S electrochemical system.

Combined use of autologous sustained-release scaffold of adipokines and acellular adipose matrix to construct highly vascularized, mature, engineered adipose tissue.

BACKGROUND: Adipose tissue engineering plays a key role in the reconstruction of soft tissue defects. The acellular adipose matrix (AAM) is a promising biomaterial for the construction of engineered adipose tissue. However, AAM lacks sufficient adipo-induction potency owing to the abundant loss of matrix-bound adipokines during decellularization. METHODS: An adipose-derived extracellular matrix (ECM) collagen scaffold, "adipose collagen fragment" (ACF), was prepared using a novel mechanical method that provides sustained release of adipokines. Here, we used label-free proteomics methods to detect the protein components in AAM and ACF. In vivo , ACF was incorporated into AAM or acellular dermal matrix (ADM) and implanted into nude mice to evaluate adipogenesis. Neo-adipocytes, neo-vessels and corresponding gene expression were evaluated. The effects of ACF on adipogenic differentiation of human adipose-derived stem cells (ADSCs) and tube formation by human umbilical vein endothelial cells were tested in vitro . RESULTS: Proteomics analysis showed that ACF contains diverse adipogenic and angiogenic proteins. ACF can release diverse adipokines and induce highly vascularized, mature adipose tissue in AAM, and even in non-adipogenic ADM. Higher expression of adipogenic markers PPAR-γ and CEBP-α and greater numbers of tubule structures were observed in ACF-treated groups in vitro . CONCLUSION: The combination of ACF and AAM could serve as a novel and promising strategy to construct mature, vascularized adipose tissue for soft tissue reconstruction.

BioThings Explorer: a query engine for a federated knowledge graph of biomedical APIs.

Knowledge graphs are an increasingly common data structure for representing biomedical information. These knowledge graphs can easily represent heterogeneous types of information, and many algorithms and tools exist for querying and analyzing graphs. Biomedical knowledge graphs have been used in a variety of applications, including drug repurposing, identification of drug targets, prediction of drug side effects, and clinical decision support. Typically, knowledge graphs are constructed by centralization and integration of data from multiple disparate sources. Here, we describe BioThings Explorer, an application that can query a virtual, federated knowledge graph derived from the aggregated information in a network of biomedical web services. BioThings Explorer leverages semantically precise annotations of the inputs and outputs for each resource, and automates the chaining of web service calls to execute multi-step graph queries. Because there is no large, centralized knowledge graph to maintain, BioThing Explorer is distributed as a lightweight application that dynamically retrieves information at query time. More information can be found at https://explorer.biothings.io, and code is available at https://github.com/biothings/biothings_explorer.

[Effectiveness analysis of "tail compression fixation+suture bridge" technology under shoulder arthroscopy for treating primary tear in medial enthesis of rotator cuff].

Objective: To investigate the feasibility and effectiveness of "tail compression fixation+suture bridge" technology under shoulder arthroscopy for treating primary tear in medial enthesis of rotator cuff. Methods: The clinical data of 11 patients with primary tear in medial enthesis of rotator cuff who met the selection criteria between October 2020 and October 2022 were retrospectively analyzed, including 3 males and 8 females, aged 39-79 years, with an average of 61.0 years. Rotator cuff injury was caused by traumatic fall in 8 cases, and the time from injury to admission was 1-4 months, with an average of 2.0 months; the remaining 3 cases had no obvious inducement. The active range of motion of the affected shoulder was limited, with an active forward flexion range of motion of (64.1±10.9)°, abduction of (78.1±6.4)°, internal rotation of (48.2±6.6)°, and external rotation of (41.8±10.5)°; 5 cases had shoulder stiffness. The preoperative visual analogue scale (VAS) score was 7.8±0.8 and the American Society of Shoulder and Elbow Surgeons (ASES) score was 23.9±6.4. The patients were treated with "tail compression fixation+suture bridge" technology under shoulder arthroscopy, and the pain and functional recovery were evaluated by VAS score, ASES score, and active range of motion of shoulder joint at last follow-up; MRI was performed after operation, and the integrity of rotator cuff was evaluated by Sugaya classification system. Results: All the 11 patients were followed up 2-22 months, with an average of 13.5 months. All incisions healed by first intention, and there was no complication such as infection, rotator cuff re-tear, and anchor falling off. At last follow-up, the VAS score was 0.8±0.7 and the ASES score was 93.5±4.2, which significantly improved when compared with those before operation ( P<0.05). All 11 patients had no significant swelling in the shoulders, and the active range of motion was (165.1±8.8)° in flexion, (75.3±8.4)° in abduction, (56.6±5.5)° in internal rotation, and (51.8±4.0)° in external rotation, which significantly improved when compared with those before operation ( P<0.05). Shoulder MRI showed adequate tendon thickness and good continuity in 9 cases, including 4 cases with partial high signal area; and 2 cases with inadequate tendon thickness but high continuity and partial high signal area. According to Sugaya classification system, there were 4 cases of type 1 (36.4%), 5 cases of type 2 (45.5%), and 2 cases of type 3 (18.1%). Conclusion: For the patients with primary tear in medial enthesis of rotator cuff, the "tail compression fixation+suture bridge" technology under shoulder arthroscopy is simple and effective.

Ambient PM2.5, ozone and mortality in Chinese older adults: A nationwide cohort analysis (2005-2018).

BACKGROUND: Cohort evidence linking long-term survival with exposure to multiple air pollutants (e.g., fine particulate matter [PM2.5] and ozone) was extensively sparse in low- and middle-income countries, especially among older adults. This study aimed to investigate potential associations of long-term exposures to PM2.5 and ozone with all-cause mortality in Chinese older adults. METHODS: A dynamic nationwide prospective cohort comprising 20,352 adults aged ≥65 years were enrolled from the Chinese Longitudinal Healthy Longevity Study and followed up through 2005-2018. Participants' annual exposures to warm-season ozone and year-round PM2.5 were assigned using satellite-derived spatiotemporal estimates. A directed acyclic graph (DAG) was developed to identify confounding variables. Associations of annual mean exposures to PM2.5 and ozone with mortality were evaluated using single- and two-pollutant Cox proportional hazards models, adjusting for time-dependent individual risk factors and ambient temperature. RESULTS: During 100 thousand person-years of follow-up (median: 3.6 years), a total of 14,313 death events occurred. The participants were averagely aged 87.1 years at baseline and exposed to a wide range of annual average concentrations of warm-season maximum 8-hour ozone (mean, 54.4 ppb; range, 23.3-81.6 ppb) and year-round PM2.5 (mean, 65.5 µg/m3; range, 10.1-162.9 µg/m3). Approximately linear concentration-response relationship was identified for ozone, whereas significant increases in PM2.5-associated mortality risks were observed only when concentrations were above 60 µg/m3. Rises of 10 ppb in ozone and 10 µg/m3 in PM2.5 above 60 µg/m3 were associated with increases in all-cause mortality of 13.2% (95% confidence interval [CI]: 10.2-16.2%) and 6.2% (95% CI: 4.6-7.7%) in DAG-based single-pollutant model, and of 9.7% (95% CI: 6.6-13.0%) and 5.3% (95% CI: 3.7-6.9%) in DAG-based two-pollutant model, respectively. We detected significant effect modification by temperature in associations of mortality with ozone (P <0.001 for interaction), suggesting greater ozone-related risks among participants in warmer locations. CONCLUSIONS: This study provided longitudinal evidence that long-term exposure to ambient PM2.5 and ozone significantly and independently contributed to elevated risks of all-cause mortality among older adults in China.

Effects of Stool Sample Preservation Methods on Gut Microbiota Biodiversity: New Original Data and Systematic Review with Meta-Analysis.

Here, we aimed to compare the effects of different preservation methods on outcomes of fecal microbiota. We evaluated the effects of different preservation methods using stool sample preservation experiments for up to 1 year. The stool samples from feces of healthy volunteers were grouped based on whether absolute ethanol was added and whether they were hypothermically preserved. Besides, we performed a systematic review to combine current fecal microbiota preservation evidence. We found that Proteobacteria changed significantly and Veillonellaceae decreased significantly in the 12th month in the room temperature + absolute ethanol group. The four cryopreservation groups have more similarities with fresh sample in the 12 months; however, different cryopreservation methods have different effects on several phyla, families, and genera. A systematic review showed that the Shannon diversity and Simpson index of samples stored in RNAlater for 1 month were not statistically significant compared with those stored immediately at -80°C (P = 0.220 and P = 0.123, respectively). The -80°C refrigerator and liquid nitrogen cryopreservation with 10% glycerine can both maintain stable microbiota of stool samples for long-term preservation. The addition of absolute ethanol to cryopreserved samples had no significant difference in the effect of preserving fecal microbial characteristics. Our study provides empirical insights into preservation details for future studies of the long-term preservation of fecal microbiota. Systematic review and meta-analysis found that the gut microbiota structure, composition, and diversity of samples preserved by storage methods, such as preservation solution, are relatively stable, which were suitable for short-term storage at room temperature. IMPORTANCE The study of gut bacteria has become increasingly popular, and fecal sample preservation methods and times need to be standardized. Here, we detail a 12-month study of fecal sample preservation, and our study provides an empirical reference about experimental details for long-term high-quality storage of fecal samples in the field of gut microbiology research. The results showed that the combination of -80°C/liquid nitrogen deep cryopreservation and 10% glycerol was the most effective method for the preservation of stool samples, which is suitable for long-term storage for at least 12 months. The addition of anhydrous ethanol to the deep cryopreserved samples did not make a significant difference in the preservation of fecal microbiological characteristics. Combined with the results of systematic reviews and meta-analyses, we believe that, when researchers preserve fecal specimens, it is essential to select the proper preservation method and time period in accordance with the goal of the study.

Metabolomic differentiation of benign vs malignant pulmonary nodules with high specificity via high-resolution mass spectrometry analysis of patient sera.

Differential diagnosis of pulmonary nodules detected by computed tomography (CT) remains a challenge in clinical practice. Here, we characterize the global metabolomes of 480 serum samples including healthy controls, benign pulmonary nodules, and stage I lung adenocarcinoma. The adenocarcinoma demonstrates a distinct metabolomic signature, whereas benign nodules and healthy controls share major similarities in metabolomic profiles. A panel of 27 metabolites is identified in the discovery cohort (n = 306) to distinguish between benign and malignant nodules. The discriminant model achieves an AUC of 0.915 and 0.945 in the internal validation (n = 104) and external validation cohort (n = 111), respectively. Pathway analysis reveals elevation in glycolytic metabolites associated with decreased tryptophan in serum of lung adenocarcinoma vs benign nodules and healthy controls, and demonstrates that uptake of tryptophan promotes glycolysis in lung cancer cells. Our study highlights the value of the serum metabolite biomarkers in risk assessment of pulmonary nodules detected by CT screening.

[Study on Factors Affecting Hemolytic Properties of Cyanoacrylate Glues for Surgical Use].

This study aims to discuss the factors affecting the hemolytic properties of α-cyanoacrylate glues for surgical use. The results showed that the different extractions, test methods, pH value, rapid solidification and the extract ratio were the main factors affecting the hemolytic properties. The choose of PBS as the extraction for haemolysis test maybe was more suitable than physiological saline. It was recommended that using both direct contact methods and indirect contact methods should be more comprehensive for hemolytic evaluation.

Zanthoxylum bungeanum seed oil inhibits tumorigenesis of human melanoma A375 by regulating CDC25A/CyclinB1/CDK1 signaling pathways in vitro and in vivo.

Background: Zanthoxylum bungeanum seed oil (ZBSO) is extracted from the seeds of the traditional Chinese medicine Z. bungeanum Maxim, which has been shown to have anti-melanoma effects. However, the specific mechanisms are not illustrated adequately. Aims: To further investigate the mechanism by which ZBSO inhibits melanoma and to provide scientific evidence to support ZBSO as a potential melanoma therapeutic candidate. Methods: CCK-8 assays were used to detect the function of ZBSO on A375 cells. Based on transcriptomics analyses, Western blot analysis was applied to determine whether an association existed in ZBSO with the CDC25A/CyclinB1/CDK1 signaling pathway. In addition, RT-qPCR and immunohistochemistry analysis validated that ZBSO has the anti-melanoma effect in a nude mouse xenograft model of human melanoma. Then, 16S rRNA sequencing was used to detect the regulation of gut microbes. Results: Cellular assays revealed that ZBSO could inhibit A375 cell viability by regulating the cell cycle pathway. Further studies presented that ZBSO could constrain CDC25A/CyclinB1/CDK1 signaling pathway in vitro and in vivo models of melanoma. ZBSO did not produce toxicity in mice, and significantly reduced tumor volume in xenotransplants of A375 cells. Genome analysis indicated that ZBSO successfully altered specific gut microbes. Conclusion: ZBSO inhibited the growth of A375 cells by regulating CDC25A/cyclinB1/CDK1 signaling pathway both in vitro and in vivo, suggesting that ZBSO may be a novel potential therapeutic agent.