De novo germline mutation in the dual specificity phosphatase 10 gene accelerates autoimmune diabetes.

Insulin-dependent or type 1 diabetes (T1D) is a polygenic autoimmune disease. In humans, more than 60 loci carrying common variants that confer disease susceptibility have been identified by genome-wide association studies, with a low individual risk contribution for most variants excepting those of the major histocompatibility complex (MHC) region (40 to 50% of risk); hence the importance of missing heritability due in part to rare variants. Nonobese diabetic (NOD) mice recapitulate major features of the human disease including genetic aspects with a key role for the MHC haplotype and a series of Idd loci. Here we mapped in NOD mice rare variants arising from genetic drift and significantly impacting disease risk. To that aim we established by selective breeding two sublines of NOD mice from our inbred NOD/Nck colony exhibiting a significant difference in T1D incidence. Whole-genome sequencing of high (H)- and low (L)-incidence sublines (NOD/NckH and NOD/NckL) revealed a limited number of subline-specific variants. Treating age of diabetes onset as a quantitative trait in automated meiotic mapping (AMM), enhanced susceptibility in NOD/NckH mice was unambiguously attributed to a recessive missense mutation of Dusp10, which encodes a dual specificity phosphatase. The causative effect of the mutation was verified by targeting Dusp10 with CRISPR-Cas9 in NOD/NckL mice, a manipulation that significantly increased disease incidence. The Dusp10 mutation resulted in islet cell down-regulation of type I interferon signature genes, which may exert protective effects against autoimmune aggression. De novo mutations akin to rare human susceptibility variants can alter the T1D phenotype.

Direct Fabrication of Sub-10 nm Nanopores in WO3 Nanosheets Using Single Swift Heavy Ions.

Extending the fabrication methodology of solid-state nanopores in a wide range of materials is significant in the fields of single molecule detection, nanofluidic devices, and nanofiltration membranes. Here, we demonstrate a new method to directly fabricate size- and density-controllable sub-10 nm nanopores in WO3 nanosheets using single swift heavy ions (SHIs) without any chemical etching process. By selecting ions of different electronic energy losses (Se), nanopores with sizes from 1.8 to 7.4 nm can be created in WO3 nanosheets. The creation efficiency of nanopores achieves ∼100% for Se > 20 keV/nm, and there exists a critical thickness below which nanopores can be created. Combined with molecular dynamics simulations, we propose that the viscosity and surface tension of the transient molten phase caused by SHIs are the key factors for the formation of nanopores. This method paves a way to fabricate solid-state nanopores in materials with a low viscosity and surface tension.

The Effect of Social Isolation on Sarcopenia: A Longitudinal Study among the Middle-Aged and Older Population in China.

INTRODUCTION: Although social isolation is associated with premature death and somatic and mental diseases, evidence of its long-term effect on sarcopenia is scarce. This study aimed to examine the longitudinal association between social isolation and possible sarcopenia. METHODS: We extracted baseline and 4-year follow-up data from the China Health and Retirement Longitudinal Study and included participants aged 45 years or above. Social isolation was measured by factors including living alone, marital status, frequency of contact with adult children and friends, and participation in social activity. The change in social isolation from baseline to follow-up was classified into stable, progressive, and regressive groups. Possible sarcopenia was detected using the handgrip strength and five-time chair-stand test. Using mixed-effects logistic regression, we studied the effect of baseline isolation and the change in isolation status on possible sarcopenia at a 4-year follow-up. RESULTS: A total of 5,289 participants aged 45-90 years and without possible sarcopenia at baseline were included. After 4 years, possible sarcopenia was detected in 21.7% (1,146/5,289) of the participants. Compared with the low social isolation group, the middle (OR = 1.53, 95% confidence interval [CI] = 1.16-2.04, p = 0.003) and high social isolation groups (OR = 1.65, 95% CI = 1.26-2.18, p < 0.001) were associated with a higher risk of possible sarcopenia. Being not married/cohabiting (OR = 1.58, 95% CI = 1.19-2.10, p = 0.002), lack of contact with children (OR = 1.86, 95% CI = 1.21-2.85, p = 0.004), and lack of social activities (OR = 1.26, 95% CI = 1.04-1.53, p = 0.019) were associated with an increased risk of possible sarcopenia. Compared with the stable social isolation group, the progressive group was associated with a greater risk of possible sarcopenia (OR = 1.51, 95% CI = 1.17-1.95, p = 0.001). CONCLUSIONS: Social isolation is associated with an increased risk of possible sarcopenia. Progressive social isolation further elevates the risk. The most vulnerable groups are middle-aged and older people who live alone, are not socially active, and lack contact with their children.

Urinary organophosphate metabolite concentrations and birth sizes among women conceiving through in vitro fertilization in Shanghai, China.

BACKGROUND: Few studies have examined the adverse birth sizes of preconception exposure to organophosphate pesticides (OPs) in women undergoing in vitro fertilization (IVF). OBJECTIVES: We investigated the relationship of preconception OP exposure with birth sizes among Chinese women undergoing IVF. METHODS: This study included 302 couples seeking infertility treatment in the China National Birth Cohort Study, from Shanghai, China, who gave birth to singleton infants between 2018 and 2021. Clinical data were collected from medical records. We measured the concentrations of six nonspecific dialkyl phosphates (DAP) metabolites of OPs [diethylthiophosphate (DETP), diethylphosphate (DEP), diethyldithiophosphate (DEDTP), dimethyldithiophosphate (DMTP), dimethylphosphate (DMP), and dimethyldithiophosphate (DMDTP)] in maternal urine. DMDTP and DEDTP were precluded from further analyses due to the low detection rates. Generalized linear models (GLMs) and weighted quantile sum (WQS) regression analyses were performed to examine the individual and joint effects of OP exposures on gestational age, birth weight, body length, and ponderal index. Odder ratio (OR) of preterm birth were estimated using logistic regression models. RESULTS: Women in the highest as compared with lowest quartile of DEP had shorter gestational age (ß = - 0.68; 95% CI = -1.24, -0.11). The association was modified by sex, with boys showing larger decreases in gestational age (ß = - 0.86; 95% CI = -1.60, -0.13). No associations were found between other DAP metabolites and birth sizes. Results from linear models with individual DAP metabolites were corroborated by the WQS regression where DEP had the largest contribution to the overall mixture effect on gestational age (weight = 0.70). Moreover, DEP concentration was associated with an elevated risk of preterm birth (OR = 1.35, 95% CI = 1.11, 2.25). CONCLUSION: Preconception DEP concentration was associated with shortened gestational age and increased risk of preterm birth, and the association was more pronounced among boys than girls.

Sequential Ag+/biothiol and synchronous Ag+/Hg2+ biosensing with zwitterionic Cu2+-based metal-organic frameworks.

Zwitterionic metal-organic frameworks (MOFs) of {[Cu(Cbdcp)(Dps)(H2O)3]·6H2O}n (MOF 1) and [Cu4(Dcbb)4(Dps)2(H2O)2]n (MOF 2) (H3CbdcpBr = N-(4-carboxybenzyl)-(3,5-dicarboxyl)pyridinium bromide; H2DcbbBr = 1-(3,5-dicarboxybenzyl)-4,4'-bipyridinium bromide; Dps = 4,4'-dipyridyl sulfide) quench the fluorescence of cytosine-rich DNA tagged with 5-carboxytetramethylrhodamine (TAMRA, emission at 582 nm, denoted as C-rich P-DNA-1) and yield the corresponding P-DNA-1@MOF hybrids. Exposure of these hybrids to Ag+ results in the release of the P-DNA-1 strands from the MOF surfaces as double-stranded, hairpin-like C-AgI-C (ds-DNA-1@Ag+) with the restoration of TAMRA fluorescence. The ds-DNA-1@Ag+ formed on the surface of 1 can subsequently sense biothiols cysteine (Cys), glutathione (GSH), and homocysteine (Hcy) due to the stronger affinity of mercapto groups for Ag+ that serves to unfold the ds-DNA-1@Ag+ duplex, reforming P-DNA-1, which is re-adsorbed by MOF 1 accompanied by quenching of TAMRA emission. Meanwhile, MOF 2 is also capable of co-loading a thymine-rich probe DNA tagged with 5-carboxyfluorescein (FAM, emission at 518 nm, denoted as T-rich P-DNA-2) to achieve synchronous sensing of Ag+ and Hg2+, resulting from the simultaneous yet specific ds-DNA-1@Ag+ and T-HgII-T duplex (ds-DNA-2@Hg2+) formation, as well as the distinctive emission wavelengths of TAMRA and FAM. Detection limits are as low as 5.3 nM (Ag+), 14.2 nM (Cys), 13.5 nM (GSH), and 9.1 nM (Hcy) for MOF 1, and 7.5 nM (Ag+) and 2.6 nM (Hg2+) for MOF 2, respectively. The sequential sensing of Ag+ and biothiols by MOF 1, and the synchronous sensing of Ag+ and Hg2+ by MOF 2 are rapid and specific, even in the presence of other mono- and divalent metal cations or other biothiols at much higher concentrations. Molecular simulation studies provide insights regarding the molecular interactions that underpin these sensing processes.

Maternal preconception body mass index and time-to-pregnancy in Shanghai Women, China.

Previous studies suggested an association between female fertility and body size, but most of these studies were from Western countries and focused mainly on obesity. This study investigated the association between preconception body mass index (BMI) and time to pregnancy (TTP) in women planning to conceive from Shanghai, China. A total of 1,182 women aged 24-46 years were recruited from the Shanghai Birth Cohort between 2013 and 2015 and were followed up for 12 months. Preconception BMI was categorized as underweight, normal weight, and overweight/obesity according to the Chinese classification of BMI. Fecundability (FOR) and infertility (IOR) odds ratios were estimated using Cox (n = 1,092) and Logistic (n = 820) regression models, respectively. We found no differences in fecundability between underweight and overweight/obese women and normal-weight women. Furthermore, underweight and overweight/obese women did not have a higher risk of infertility compared with normal-weight women. Our findings suggest that non-optimal preconception BMI does not appear to influence female fecundability and infertility in Chinese women. These results should be interpreted with caution as they may be applicable only to women with demographic and anthropometric characteristics similar to our study population. Our findings need to be confirmed in other populations.

Successive and Specific Detection of Hg2+ and I- by a DNA@MOF Biosensor: Experimental and Simulation Studies.

A 2D metal-organic framework (MOF) of {[Cu(Dcbb)(Bpe)]·Cl} n (1, H2DcbbBr = 1-(3,5-dicarboxybenzyl)-4,4'-bipyridinium bromide, Bpe = trans-1,2-bis(4-pyridyl)ethylene)) has been prepared. MOF 1 associates with the thymine-rich (T-rich), single-stranded probe DNA (ss-DNA, denoted as P-DNA) labeled with fluorophore FAM (FAM = carboxyfluorescein) and quenches the FAM emission to give a nonemissive P-DNA@1 hybrid (off state). The P-DNA in the hybrid subsequently captures the Hg2+ to give a rigid double-stranded DNA featuring T-Hg2+-T motif (ds-DNA@Hg2+) and detach from MOF 1, triggering the recovery of the FAM fluorescence (on state). Upon subsequent addition of I-, Hg2+ was further sequestrated from the ds-DNA@Hg2+ duplex, driven by the stronger Hg-I coordination. The released P-DNA is resorbed by MOF 1 to regain the initial P-DNA@1 hybrid (off state). The P-DNA@1 sensor thus detects Hg2+ and I- sequentially via a fluorescence "off-on-off" mechanism. The sensor is highly selective and sensitive, yielding detection limits of 3.2 and 3.3 nM, respectively. The detection process was conformed by circular dichroism (CD) and the detection mechanism was verified by fluorescence anisotropy, binding constant, and simulation of the binding free energy at each stage.

Lanthanum-Based Metal-Organic Frameworks for Specific Detection of Sudan Virus RNA Conservative Sequences down to Single-Base Mismatch.

Reactions of La(NO3)3·6H2O with the polar, tritopic quaternized carboxylate ligands N-carboxymethyl-3,5-dicarboxylpyridinium bromide (H3CmdcpBr) and N-(4-carboxybenzyl)-3,5-dicarboxylpyridinium bromide (H3CbdcpBr) afford two water-stable metal-organic frameworks (MOFs) of {[La4(Cmdcp)6(H2O)9]}n (1, 3D) and {[La2(Cbdcp)3(H2O)10]}n (2, 2D). MOFs 1 and 2 absorb the carboxyfluorescein (FAM)-tagged probe DNA (P-DNA) and quench the fluorescence of FAM via a photoinduced electron transfer (PET) process. The nonemissive P-DNA@MOF hybrids thus formed in turn function as sensing platforms to distinguish conservative linear, single-stranded RNA sequences of Sudan virus with high selectivity and low detection limits of 112 and 67 pM, respectively (at a signal-to-noise ratio of 3). These hybrids also exhibit high specificity and discriminate down to single-base mismatch RNA sequences.

Molecular interactions between gold nanoparticles and model cell membranes.

The interactions between nanoparticles (NPs) and cells are of huge interest because NPs have been extensively researched for biomedical applications. For the cellular entry of NPs, it remains unclear how the cell membrane molecules respond to the exposure of NPs due to a lack of appropriate surface/interface-sensitive techniques to study NP-cell membrane interactions in situ in real time. In this study, sum frequency generation (SFG) vibrational spectroscopy was employed to examine the interactions between lipid bilayers (serving as model mammalian cell membranes) and Au NPs of four different sizes with the same mass, or the same NP number, or the same NP surface area. It was found that lipid flip-flop was induced by Au NPs of all four sizes. Interestingly, the lipid flip-flop rate was found to increase as the Au NP size increased with respect to the same particle number or the same NP surface area. However, the induced lipid flip-flop rate was the same for Au NPs with different sizes with the same mass, which was interpreted by the same "effective surface contact area" between Au NPs and the model cell membrane. We believe that this study provided the first direct observation of the lipid flip-flop induced by the interactions between Au NPs and the model mammalian cell membrane.

[TLR-4 involvement in pyroptosis of mice with pulmonary inflammation infected by Actinobacillus pleuropneumoniae].

OBJECTIVE: Pyroptosis is a caspase-1 dependent programmed cell death and involves pathogenesis of infectious diseases by releasing many pro-inflammatory cytokines to induced inflammation. TLR-4 plays an important role in mediating pathogenesis of some infectious diseases. In this study, we detected the expression of TLR-4 and some molecules (e. g caspase-1, TNF-α, IL-1ß, IL-6, IL-18 ) related with pyroptosis to determine its involvement and mechanisms of pulmonary inflammation in mice infected by A. pleuropneumoniae. METHODS: Mice were intranasally infected by A. pleuropneumoniae and killed 48 hours post infection. Pulmonary gross lesion and histological pathology by H-E were observed. Expression levels of caspase-1 , caspase-3, TNF-α, IL-1ß, IL-6, IL-18, and TLR-4 in lung of mice were detected by RT-PCR and qPCR. RESULTS: Serious pulmonary hemorrhage and inflammation in infected mice were observed. Expression levels of caspase-1, caspase-3, TNF-α, IL-1ß, IL-6, IL-18 and TLR-4 increased, and expression levels of caspase-3 were not changed in lung of infected mice. CONCLUSION: TLR-4 might be involved in pulmonary inflammation of mice infected by A. pleuropneumoniae. After induced by activated TLR-4 some cells in this lesion expressed pro-inflammatory cytokines. These cytokines would induce pulmonary inflammation. This lesion might involve pyroptosis with caspase-1 expression.

Low dose of dexamethasone combined with netupitant and palonosetron in preventing nausea and vomiting in breast cancer patients induced by anthracycline drugs.

BACKGROUND: To study the effects of various courses of dexamethasone (DEX) combined with 5-HT3 receptor antagonists (RA) and NK-1 RA in suppressing high-grade nausea and vomiting (CINV) caused by anthracycline and cyclophosphamide chemotherapy regimens (AC or EC) in breast cancer (BC) patients. PATIENTS AND METHODS: A prospective study was performed with 252 BC patients who received AC between January, 2019 and June, 2022 in our hospital. Patients were randomly separated into control Group (N = 130) who received DEX 12 mg on day 1 and 8 mg per dose on day 2-4 and observation group (N = 122) treated with DEX 5 mg per dose on days 1-4. The response was monitored. Primary study endpoint was complete resolution (CR) of patients nausea or vomiting; secondary study endpoints included acute CR and delayed CR; and complete control (CC), acute CC, delayed CC, and safety. RESULTS: All patients underwent six rounds of chemotherapy, and no difference was found in the clinical data. CR of acute/delayed phase was (94.3%/88.5%, P > 0.05), (89.3%/90.8%, P > 0.05); total CR was (80.3%/81.5%, P > 0.05); CC was (56.6%/59.2%, P > 0.05), (64.8%/67.7%, P > 0.05); total CR was (48.4%/53.1%, P > 0.05). CONCLUSIONS: The preventive antiemetic effects of NEPA, a fixed-dose combination of netupitant and palonosetron combined with DEX 5 mg per dose on days 1-4, can be similar to DEX 12 mg on day 1 and 8 mg per dose on days 2-4, low-dose hormone with better safety, which is beneficial.

Joint Association of Sleep Onset Time and Sleep Duration With Cardiometabolic Health Outcome.

BACKGROUND: The association of sleep onset time and duration with cardiometabolic health is not well characterized. METHODS AND RESULTS: This study included 6696 adults aged 20 to 80 years from the NHANES (National Health and Nutrition Examination Study) 2015 to 2018. Participants were categorized into 9 groups according to the cross-tabulation of sleep onset time (<22:00 [early], 22:00-23:59 [optimal], and ≥24:00 [late]) and duration (<7 hours [insufficient], 7-8 hours [sufficient], and ≥9 hours [excessive]), with optimal sleep onset time and sufficient duration as the reference. The primary outcomes included hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, hyperglycemia, central obesity, and metabolic syndrome. Inappropriate sleep onset time and sleep duration were associated with increased odds of hypertension, hypertriglyceridemia, and metabolic syndrome, especially among participants aged 40 to 59 years. Compared with men reporting optimal onset and sufficient duration, men reporting optimal onset with excessive duration (odds ratio [OR]: 2.01 [95% CI, 1.12-3.58]) and late onset with insufficient duration (OR, 1.74 [95% CI, 1.13-2.68]) had higher odds of metabolic syndrome. Compared with women reporting optimal onset and sufficient duration, women reporting optimal onset and insufficient duration (OR, 1.61 [95% CI, 1.11-2.32]) and early onset and excessive duration (OR, 2.16 [95% CI, 1.30-3.57]) had higher odds of hypertension, and women reporting late onset and excessive duration (OR, 5.64 [95% CI, 1.28-6.77]) were at the highest odds of hypertriglyceridemia. CONCLUSIONS: Late sleep onset as well as insufficient or excessive sleep duration are associated with adverse cardiometabolic outcomes, particularly in participants aged 40 to 59 years.

Schottky barrier reduction on optoelectronic responses in heavy ion irradiated WSe2 memtransistors.

Two-dimensional transition metal dichalcogenide-based memtransistors provide simulation, sensing, and storage capabilities for applications in a remotely operated aerospace environment. Swift heavy ion (SHI) irradiation technology is a common method to simulate the influences of radiation ions on electronic devices in space environments. Here, SHI irradiation technology under different conditions was utilized to produce complex defects in WSe2-based memtransistors. Low-resistance state to low-resistance state (LRS-LRS) switching behaviors under light illumination were achieved and photocurrent responses with different spike trains were observed in SHI-irradiated memtransistors, which facilitated the design of devices with enriched analog functions. Reduction of the Schottky barrier height due to the introduced defects at the metal/WSe2 interface was confirmed to be the major factor responsible for the observed behaviors. 1T phase and concentric circle-type vacancies were also created in the SHI-irradiated 2H-WSe2 channel besides the amorphous structure; these complex defects could seriously affect the transport properties of the devices. We believe that this work serves as a foundation for aerospace radiation applications of all-in-one devices. It also opens a new application field of heavy ion irradiation technology for the development of multiterminal memtransistor-based optoelectronic artificial synapses for neuromorphic computing.

A systematic and comprehensive analysis of T cell exhaustion related to therapy in lung adenocarcinoma tumor microenvironment.

Background: T cell exhaustion (TEX) is an important immune escape mechanism, and an in-depth understanding of it can help improve cancer immunotherapy. However, the prognostic role of TEX in malignant lung adenocarcinoma (LUAD) remains unclear. Methods: Through TCGA and GEO datasets, we enrolled a total of 498 LUAD patients. The patients in TCGA-LUAD were unsupervised clustered into four clusters according to TEX signaling pathway. WGCNA analysis, survival random forest analysis and lasso regression analysis were used to select five differentially expressed genes among different clusters to construct a TEX risk model. The risk model was subsequently validated with GEO31210. By analyzing signaling pathways, immune cells and immune checkpoints using GSEA, GSVA and Cibersortx, the relationship between TEX risk score and these variables was evaluated. In addition, we further analyzed the expression of CCL20 at the level of single-cell RNA-seq and verified it in cell experiments. Results: According to TEX signaling pathway, people with better prognosis can be distinguished. The risk model constructed by CD109, CCL20, DKK1, TNS4, and TRIM29 genes could further accurately identify the population with poor prognosis. Subsequently, it was found that dendritic cells, CD44 and risk score were closely related. The final single-cell sequencing suggested that CCL2O is a potential therapeutic target of TEX, and the interaction between TEX and CD8 + T is closely related. Conclusion: The classification of T cell depletion plays a crucial role in the clinical decision-making of lung adenocarcinoma and needs to be further deepened.

Organophosphate esters, airway inflammation, and lung function among U.S. participants: A nationally representative cross-sectional study from NHANES, 2011-2012.

BACKGROUND: Human beings are widespread exposed to organophosphate esters (OPEs), but little is known about their effects on respiratory health. OBJECTIVES: To investigate the associations of exposure to OPEs with lung function and airway inflammation among U.S. participants from NHANES, 2011-2012. METHODS: A total of 1636 participants aged 6-79 years were included. Concentrations of OPE metabolites were measured in urine and lung function was assessed with spirometry. Fractional exhaled nitric oxide (FeNO) and blood eosinophils (B-Eos), two important inflammatory biomarkers, were also measured. Linear regression was performed to examine the relationships of OPEs with FeNO, B-Eos and lung function. Bayesian kernel machine regression (BKMR) was used to evaluate the joint associations between OPEs mixtures and lung function. RESULTS: Three of seven OPE metabolites had detection frequencies > 80 %, including diphenyl phosphate (DPHP), bis (1,3-dichloro-2-propyl) phosphate (BDCPP), bis-2-chloroethyl phosphate (BCEP). A 10-fold increase in DPHP concentrations were associated with 1.02 mL decreases in FEV1 (ß = -0.01, 95 % CIs = -0.02, -0.003) and FVC (ß = -0.01, 95 % CIs = -0.02, -0.003), respectively, and the similar, modest decreases were seen for BDCPP. For each 10-fold increase in BCEP concentration, FVC was also reduced by 1.02 mL (ß = -0.01, 95 % CIs = -0.02, -0.002). Moreover, the negative associations were only found in non-smokers aged >35 years. The aforementioned associations were confirmed by BKMR, but we cannot definitively identify a constituent driving this association. B-Eos was negatively associated with FEV1 and FEV1/FVC, but not with OPEs. No associations were found of FeNO with OPEs and lung function. CONCLUSIONS: Exposure to OPEs was associated with modest decrements in lung function, although the observed decrease in FVC and FEV1 is unlikely to be of real clinical relevance for the majority of subjects in this series. Moreover, those associations presented age and smoking status-dependent pattern. Unexpectedly, the adverse effect was not mediated by FeNO/B-Eos.

Assessment of right ventricular structure and systolic function in amateur marathon runners using three-dimensional speckle tracking echocardiography.

Prolonged high-intensity endurance exercise has been reported to have adverse effects on the heart, which are further correlated with exercise dose. However, its effect on the right ventricle (RV) of amateur runners is unknown. This study aimed was to evaluate the early right ventricular structure and systolic function of amateur marathon runners by three-dimensional speckle tracking echocardiography (3D-STE), and to further analyze the correlation between relevant parameters and the amount of training. A total of 30 amateur marathon runners (marathon group) and 27 healthy volunteers (control group) were enrolled. Conventional echocardiography combined with 3D-STE was performed in all subjects, and the marathon group was screened by echocardiography a week before a marathon (V1), within 1 h post-marathon (V2), and 4 days post-marathon (V3). RV global longitudinal strain (GLS) and RV end-diastolic volume (EDV) increased significantly in the marathon group compared to the control group (P < 0.05). RV GLS was significantly decreased in the marathon group within 1 h post-marathon (V1: - 26.2 ± 2.5% vs V2: - 23.0 ± 1.6% vs V3: - 25.6 ± 2.6%, P < 0.001). However, there was no significant difference in RV ejection fraction (RVEF) (P > 0.05). The results of the correlation analysis showed that RV EDV and RV end-systolic volume (ESV) were positively correlated with the average training volume (P < 0.001). Multivariate linear regression analysis showed that average training volume was an independent predictor of RV EDV in amateur marathoners (ß = 0.642, P < 0.001). The systolic function of the RV was enhanced in amateur marathon runners in the early stage, manifested by an increase in RV EDV. After a long period of high-intensity endurance exercise, RV systolic function will temporarily be reduced. 3D-STE can identify this subclinical change with high sensitivity and provide valuable information to assess the structure and function of RV in amateur marathon runners.

Association of perfluoroalkyl substances with pulmonary function in adolescents (NHANES 2007-2012).

Perfluoroalkyl substances (PFASs) constitute an environmentally persistent and widespread class of anthropogenic chemicals that have been used in industrial and commercial applications in the USA and around the world. Animal studies suggested its toxic impact on lung development, but the adverse effect of PFAS exposure on childhood pulmonary function has not been clearly determined. We investigated the potential cross-sectional association of environmental PFAS exposures with pulmonary function in 765 adolescents aged 12-19 years from the US National Health and Nutrition Examination Survey (NHANES) 2007-2012. Exposure to PFASs was estimated by measuring serum concentrations, and pulmonary function was assessed by spirometry. Linear regression and weighted quantile sum (WQS) regression were performed to estimate the associations of individual chemicals and chemical mixtures with pulmonary function. Median concentrations of PFOA, PFOS, PFNA, and PFHxS (detection frequencies > 90%) were 2.70, 6.40, 0.98, and 1.51 ng/mL, respectively. No associations were found between the four individual congeners and Σ4PFASs and the pulmonary function measures in total adolescents. Sensitive analyses were further conducted stratified by age (12-15 and 16-19 years) and sex (boys and girls). In adolescents aged 12-15 years, PFNA was negatively associated with FEV1:FVC (p-trend = 0.007) and FEF25-75% (p-trend = 0.03) among girls, while PFNA was positively associated with FEV1: FVC (p-trend = 0.018) among boys. No associations were found among adolescents aged 16-19 years, either boys or girls. The aforementioned associations were confirmed when further applying WQS models, and PFNA was identified to be the most heavily weighing chemical. Our results suggested that environmental exposure to PFNA may affect pulmonary function among adolescents aged 12-15 years. Given the cross-sectional analysis and less consistent results, further replications of the association in large prospective cohort studies are warranted.

Coaxial radiography guided puncture technique for percutaneous transforaminal endoscopic lumbar discectomy: A randomized control trial.

BACKGROUND: The coaxial radiography-guided puncture technique (CR-PT) is a novel technique for endoscopic lumbar discectomy. As the X-ray beam and the puncturing needle are maintained in a parallel and coaxial direction, the X-ray beam can be used to guide the trajectory angle, facilitating the choice of the puncture site and providing real-time guidance. This puncture technique offers numerous advantages over the conventional anterior-posterior and lateral radiography-guided puncture technique (AP-PT), especially in cases of herniated lumbar discs with a hypertrophied transverse process or articular process, high iliac crest, and narrowed intervertebral foramen. AIM: To confirm whether CR-PT is a superior approach to percutaneous transforaminal endoscopic lumbar discectomy compared to AP-PT. METHODS: In this parallel, controlled, randomized clinical trial, herniated lumbar disc patients appointed to receive percutaneous endoscopic lumbar discectomy treatment were recruited from the Pain Management Department of the Affiliated Hospital of Xuzhou Medical University and Nantong Hospital of Traditional Chinese Medicine. Sixty-five participants were enrolled and divided into either a CR-PT group or an AP-PT group. The CR-PT group underwent CR-PT, and the AP-PT group underwent AP-PT. The number of fluoroscopies during puncturing, puncture duration (min), surgery duration (min), VAS score during puncturing, and puncture success rate were recorded. RESULTS: Sixty-five participants were included, with 31 participants in the CR-PT group and 34 in the AP-PT group. One participant in the AP-PT group dropped out due to unsuccessful puncturing. The number of fluoroscopies [median (P25, P75)] was 12 (11, 14) in the CR-PT group vs 16 (12, 23) in the AP-PT group, while the puncture duration (mean ± SD) was 20.42 ± 5.78 vs 25.06 ± 5.46, respectively. The VAS score was 3 (2, 4) in the CR-PT group vs 3 (3, 4) in the AP-PT group. Further subgroup analysis was performed, considering only the participants with L5/S1 segment herniation: 9 patients underwent CR-PT, and 9 underwent AP-PT. The number of fluoroscopies was 11.56 ± 0.88 vs 25.22 ± 5.33; the puncture duration was 13.89 ± 1.45 vs 28.89 ± 3.76; the surgery duration was 105 (99.5, 120) vs 149 (125, 157.5); and the VAS score was 2.11 ± 0.93 vs 3.89 ± 0.6, respectively. All the above outcomes demonstrated statistical significance (P < 0.05), favoring the CR-PT treatment. CONCLUSION: CR-PT is a novel and effective technique. As opposed to conventional AP-PT, this technique significantly improves puncture accuracy, shortens puncture time and operation time, and reduces pain intensity during puncturing.

Performance of Imaging Techniques in Non-invasive Diagnosis of Non-alcoholic Fatty Liver Disease in Children: A Systematic Review and Meta-Analysis.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. With the continuous emergence of various non-invasive diagnostic methods, imaging techniques have always been considered as potential alternative methods to liver biopsy. This study aimed to evaluate the diagnostic performance of imaging techniques so as to search for the most promising technology. Methods: We searched English and Chinese databases. English databases included Cochran library, Embase, PubMed, and Web of Science, while Chinese databases included the Wanfang database and China National Knowledge Internet. Results: Finally, 11 articles were included (12 studies, one of which included studies on both fibrosis and steatosis). Further, 26.2% of the participants had mild steatosis, 34.1% had moderate steatosis, and 34.9% had severe steatosis. Also, 64.0% had any fibrosis, 29.1% had significant fibrosis, 13.8% had advanced fibrosis, and 2.8% had cirrhosis. Irrespective of the grade of fibrosis, transient elastography (TE) had higher sensitivity (97-100%), whereas magnetic resonance elastography (MRE) had the lowest sensitivity (58-63%). The pooled sensitivity and specificity of imaging techniques in diagnosing steatosis were 89% (95% CI, 71-96) and 89% (95% CI, 72-96), and AUROC 0.95 (95% CI, 93-97), multifrequency magnetic resonance elastography-hepatic fat fraction (mMRE-HFF) had the highest sensitivity (87%, 95% CI 77-97), ultrasonography (US) had the lowest specificity (96%, 95% CI 92-98%). Conclusion: Imaging techniques have a good diagnostic performance for children with NAFLD, especially the diagnosis of liver fibrosis based on ultrasound or magnetic resonance elastography. Compared with different imaging techniques, TE has the best performance in diagnosing significant fibrosis. Liver stiffness measurement (LSM) is expected to become a biological indicator for routine screening, dynamic monitoring of disease changes, and prognostic evaluation.

Protective autophagy alleviates neurotoxin-gelsenicine induced apoptosis through PERK signaling pathway in Neuro-2a cells.

Gelsemium elegans Benth. (G. elegans) showed significant biological activities, but it has the side effects of neurotoxicity, predominantly in the form of respiratory depression. Gelsenicine is the main toxic constituent of G. elegans which is highly neurotoxic to humans and animals. Although the acute neurotoxicity of gelsenicine has been widely reported, but neurotoxicity mechanisms have not been elucidated and its direct effect on nerve cells remains poorly characterized. In this study, Neuro-2a cells were used to be our object of study for determining the mechanism by which gelsenicine induced neurotoxicity. We found that gelsenicine is neurotoxic to Neuro-2a cells; indeed cell proliferation was inhibited and apoptosis was induced in a dose-dependent manner. Meanwhile, gelsenicine markedly promoted autophagy and activated autophagic flux. Additionally, promoting autophagy with rapamycin decreased apoptosis, whereas blocking autophagy with 3-methyladenine (3-MA) increased apoptosis. Furthermore, the protein kinase ribose nucleic acid (RNA)-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2α)/activating transcription factor 4 (ATF4) signaling pathway was involved in the induction of protective autophagy in Neuro-2a cells. Inhibition of PERK using small interfering RNA (siRNA) inhibited gelsenicine-induced autophagy and aggravated apoptosis. These data indicate that gelsenicine not only exhibited cytotoxicity and induced apoptosis, but it also induced protective autophagy via PERK signaling pathway to alleviate gelsenicine-mediated apoptosis in Neuro-2a cells.