Individualized Weight Management and Its Impact on Pregnancy Outcomes in Overweight/Obese Infertile Women: A Retrospective Study.

Background: Previous studies link overweight/obesity to reduced fertility, highlighting weight intervention as vital for better pregnancy outcomes. However, clarity on the role and efficacy of weight loss in enhancing pregnancy is inconsistent. Objective: This study aimed to assess the impact of individualized weight intervention on pregnancy among Chinese overweight/obese infertile women and explore body composition indexes influencing pregnancy outcomes. Methods: This retrospective study involved 363 overweight/obese infertile women admitted to the First Affiliated Hospital of Guangxi Medical University, Guangxi, China, from June 2017 to November 2020. Among them, 249 received personalized weight intervention (intervention group), while 114 did not (control group). Pregnancy outcomes were compared between the two groups, and changes in body composition before and after intervention were measured. Multivariate logistic regression was employed to analyze factors influencing pregnancy outcomes. Results: The intervention group exhibited significantly higher clinical pregnancy rates, natural pregnancy rates, assisted reproductive pregnancy rates, and induced ovulation (IO) pregnancy rates compared to the control group (all P < .05). Following weight intervention, there were significant decreases in body weight, body mass index (BMI), visceral fat area, and body fat (all P < .01). Logistic regression analysis identified polycystic ovary syndrome as the reason for infertility (OR=3.446, P = .016), ∆body weight %≥10% (OR=2.931, P = .014), and ∆visceral fat area% (OR=1.025, P = .047) as positive factors for a successful pregnancy. Conversely, age≥35 years old (OR=0.337, P = .001), BMI≥25 kg/m2 after intervention (OR=0.279, P < .001), and visceral fat area≥100 cm2 after intervention (OR=0.287, P = .007) were identified as negative factors. Conclusions: Individualized weight management enhances pregnancy outcomes in overweight/obese infertile women. Achieving a reduction in body weight by 10% or more, combined with effective control of visceral fat, proves important in improving pregnancy outcomes. Excess visceral fat emerges as an adverse factor impacting successful pregnancy.

Diagnostic performance of serum galactomannan and ß-D-glucan for invasive aspergillosis in suspected patients: A meta-analysis.

BACKGROUND: Serum galactomannan (GM) and ß-D-glucan (BG) are known markers of invasive aspergillosis (IA). The aim of this meta-analysis was to evaluate the efficiency of serum GM and BG as diagnostic markers of symptomatic IA infection and compare the performance of the combined tests with that of either test individually. METHODS: A literature search was carried out using PubMed, Web of Science, and EMBASE databases to include relevant studies published in English up to May 2023. The quality assessment was performed using Review Manager 5.3 software. A bivariate model was applied to pool diagnostic parameters using Stata 14.0 software. We used Cochrane I2 index to assess heterogeneity and identify the potential source of heterogeneity by meta-regression. Paired t tests were used to compare the value of GM and BG for IA diagnosis when used in combination or alone. RESULTS: Sixteen studies were eligible for inclusion in the meta-analysis. For proven or probable IA, serum GM and BG yielded a pooled sensitivity of 0.53 (95% CI 0.40-0.66) vs 0.72 (95% CI 0.61-0.81) and a pooled specificity of 0.94 (95% CI 0.91-0.97) vs 0.82 (95% CI 0.73-0.88). The area under the curve (AUC) of ROC was 0.90 (95% CI 0.87-0.92) vs 0.83 (95% CI 0.80-0.86) for all studies. The pooled sensitivity and specificity for IA diagnosis by combined GM and BG assays (GM/BG) were 0.84 (95% CI 0.69-0.86) and 0.76 (95% CI 0.69-0.81), respectively. The sensitivity of the combined GM/BG test to diagnose IA was higher than of the GM or BG test alone. CONCLUSION: Serum GM and BG tests had a relatively high accuracy for IA diagnosis in suspected patients. The diagnostic accuracy of both assays is comparable, and the diagnostic sensitivity is further improved by the combined detection of the 2 markers.

USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6.

Ischemic stroke (IS) is a dangerous cerebrovascular disorder with a significant incidence and death rate. Ubiquitin-specific peptidase 18 (USP18) has been proven to mitigate ischemic brain damage; however, its potential regulatory mechanisms remain unclear. In vivo and in vitro models of IS were established by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R). Neurocyte injury was detected by MTT, LDH, ROS level, mitochondrial membrane potential (Δψm), and flow cytometry. Molecular expression was evaluated by qPCR, Western blotting, and immunofluorescence staining. Molecular mechanisms were determined by Co-IP, RIP, and MeRIP. IS injury was determined by neurological behavior score and TTC staining. Mitophagy was observed by TEM. USP18 and fat mass and obesity-associated protein (FTO) expression declined after OGD/R. Dysfunctional mitochondrial and apoptosis in OGD/R-stimulated neurocytes were eliminated by USP18/FTO overexpression via mitophagy activation. USP18-mediated de-ubiquitination was responsible for increasing FTO protein stability. Up-regulation of FTO protein restrained m6A modification of sirtuin6 (SIRT6) in a YTHDF2-dependent manner to enhance SIRT6 expression and subsequent activation of AMPK/PGC-1α/AKT signaling. FTO induced mitophagy to ameliorate nerve cell damage through SIRT6/AMPK/PGC-1α/AKT pathway. Finally, USP18/FTO overexpression relieved IS in rats via triggering SIRT6/AMPK/PGC-1α/AKT axis-mediated mitophagy. USP18 increased FTO protein stability to trigger SIRT6-induced mitophagy, thus mitigating IS. Our data unravel the novel neuroprotective mechanism of USP18 and suggest its potential as a promising treatment target for IS.

Organophosphate flame retardants and their metabolites in the Pearl River Estuary: Occurrence, influencing factors, and ecological risk control strategies based on a mass balance model.

Estuaries serve as crucial filters for land-based pollutants to the open sea, but there is a lack of information on the migration and fate of organophosphate flame retardants (OPFRs) within estuaries. This study focused on the Pearl River Estuary (PRE) by examining the co-occurrence of OPFRs and their metabolites and quantifying their transport fluxes using a mass balance model. The seawater concentrations of OPFRs and their metabolites exhibited significant seasonal variations (p < 0.01), while the sediment concentrations of OPFRs reflected the long-term distributional equilibrium in the PRE. The concentration of Σ9OPFRs in seawater showed a relentless dilution from the entrance to the offshore region in the normal and wet seasons, which was significantly in accordance with the gradients of pH, dissolved oxygen (DO), and salinity (p < 0.05). Furthermore, horizontal migration dominated the transport of OPFRs, and the inventory assessment revealed that both the water column and sediment were important reservoirs in the PRE. According to the estimated fluxes from the mass balance model, riverine input emerged as the principal pathway for OPFR entry into the PRE (1.55 × 105, 6.28 × 104, and 9.00 × 104 kg/yr in the normal, dry and wet seasons, respectively), whereas outflow to the open sea predominantly determined the main fates of the OPFRs. The risk quotient (RQ) results showed that EHDPHP (0.835) in water posed medium ecological risk, while other OPFRs and metabolites presented relatively lower risk (RQ < 0.1). The risk control effects were evaluated through scenario simulations of mathematical fitting between controllable source factors and the RQ of risky OPFR. The risk of EHDPHP in the PRE could be effectively reduced by restricting its concentrations in entrance region (<9.31, 8.67, and 12.7 ng/L in the normal, dry and wet seasons, respectively) of the PRE. This research offers foundational insights into environmental management and pollution control strategies for emerging pollutants in estuaries.

First insights into the bioaccumulation, biotransformation and trophic transfer of typical tetrabromobisphenol A (TBBPA) analogues along a simulated aquatic food chain.

Tetrabromobisphenol A (TBBPA) analogues have been investigated for their prevalent occurrence in environments and potential hazardous effects to humans and wildlife; however, there is still limited knowledge regarding their toxicokinetics and trophic transfer in aquatic food chains. Using a developed toxicokinetic model framework, we quantified the bioaccumulation, biotransformation and trophic transfer of tetrabromobisphenol S (TBBPS) and tetrabromobisphenol A di(allyl ether) (TBBPA-DAE) during trophic transfer from brine shrimp (Artemia salina) to zebrafish (Danio rerio). The results showed that the two TBBPA analogues could be readily accumulated by brine shrimp, and the estimated bioconcentration factor (BCF) value of TBBPS (5.68 L kg-1 ww) was higher than that of TBBPA-DAE (1.04 L kg-1 ww). The assimilation efficiency (AE) of TBBPA-DAE in zebrafish fed brine shrimp was calculated to be 16.3%, resulting in a low whole-body biomagnification factor (BMF) in fish (0.684 g g-1 ww). Based on the transformation products screened using ultra-high-performance liquid chromatograph-high resolution mass spectrometry (UPLC-HRMS), oxidative debromination and hydrolysis were identified as the major transformation pathways of TBBPS, while the biotransformation of TBBPA-DAE mainly took place through ether bond breaking and phase-II metabolism. Lower accumulation of TBBPA as a metabolite than its parent chemical was observed in both brine shrimp and zebrafish, with metabolite parent concentration factors (MPCFs) < 1. The investigated BCFs for shrimp of the two TBBPA analogues were only 3.77 × 10-10 - 5.59 × 10-3 times of the theoretical Kshrimp-water based on the polyparameter linear free energy relationships (pp-LFERs) model, and the BMF of TBBPA-DAE for fish was 0.299 times of the predicted Kshrimp-fish. Overall, these results indicated the potential of the trophic transfer in bioaccumulation of specific TBBPA analogues in higher trophic-level aquatic organisms and pointed out biotransformation as an important mechanism in regulating their bioaccumulation processes. ENVIRONMENTAL IMPLICATION: The internal concentration of a pollutant in the body determines its toxicity to organisms, while bioaccumulation and trophic transfer play important roles in elucidating its risks to ecosystems. Tetrabromobisphenol A (TBBPA) analogues have been extensively investigated for their adverse effects on humans and wildlife; however, there is still limited knowledge regarding their toxicokinetics and trophic transfer in aquatic food chains. This study investigated the bioaccumulation, biotransformation and trophic transfer of TBBPS and TBBPA-DAE in a simulated di-trophic food chain. This state-of-art study will provide a reference for further research on this kind of emerging pollutant in aquatic environments.

BMSC-derived exosomal miR-148b-3p attenuates OGD/R-induced HMC3 cell activation by targeting DLL4 and Notch1.

Bone mesenchymal stem cell (BMSC)-derived exosome (BMSC-Exo) could be a treatment method for ischemic injury. In ischemic cerebrovascular disease (IC), microglia is pivotal in neuronal damage and remodeling. This study explores the mechanisms of BMSC-Exo miR-148b-3p in regulating oxygen-glucose deprivation/reoxygenation (OGD/R)-induced human microglial clone 3 (HMC3) cell activation. Transmission electron microscopy (TEM) and qNano were used to assess BMSC-Exo features. The functions of BMSC-Exo miR-148 b-3p in OGD/R-induced HMC3 cell activation were explored via MTT assay, flow cytometry, scratch, transwell, and enzyme-linked immunosorbent assay (ELISA) assays. A dual-luciferase reporter assay was performed to determine the relationship between miR-148b-3p and Delta-like ligand 4(DDL4) or neurogenic locus notch homolog protein 1 (Notch1). OGD/R decreased miR-148b-3p expression in HMC3 cells. After BMSC-Exo treatment, miR-148b-3p expression was upregulated, cell viability and migration were inhibited, cell cycles remained in the G0/G1 phase, and proinflammatory cytokines were decreased in OGD/R-induced HMC3 cells. More importantly, BMSC-Exo miR-148b-3p could further strengthen BMSC-Exo effects. DDL4 and Notch1 are direct targets of miR-148b-3p, respectively. Moreover, the knockdown of DLL4 or Notch1 could inhibit OGD/R-induced HMC3 cell activation. BMSC-Exo miR-148b-3p inhibited OGD/R-induced HMC3 cell activation via inhibiting DLL4 and Notch1 expression, which provided a new strategy for treating cerebral ischemia.

New insight into the bioaccumulation and trophic transfer of free and conjugated antibiotics in an estuarine food web based on multimedia fate and model simulation.

The substantial utilization of antibiotics causes their "pseudo-persistence" in offshore environments. Published studies on antibiotic surveillance in food webs have primarily emphasized on parent forms; however, the compositions and concentrations of conjugated antibiotics in aquatic organisms remain largely unexplored. This study systematically examined the distribution characteristics and trophodynamics of free antibiotics and their conjugated forms in an estuarine food web. Total antibiotic levels differed insignificantly between the surface and bottom waters. The total mean values of free antibiotics in crabs, fish, shrimps, sea cucumbers, and snails varied from 0.77 to 1.4 ng/g (wet weight). The numbers and values of antibiotics rose in these biological samples after enzymatic hydrolysis. Conjugated antibiotics accounted for 23.8-76.9% of the total antibiotics in the biological samples, revealing that conjugated forms play a non-negligible role in aquatic organisms. More number of antibiotics exhibited bioaccumulation capabilities after enzymatic hydrolysis. In the food web, the free forms of anhydroerythromycin and conjugated forms of trimethoprim and ciprofloxacin underwent trophic dilution, whereas the free forms of trimethoprim and conjugated forms of ofloxacin underwent trophic amplification. The present work provides new insights into the bioaccumulation and trophic transfer of free and conjugated antibiotics in food webs.

Role of Gastrointestinal Microbiota from Crucian Carp in Microbial Transformation and Estrogenicity Modification of Novel Plastic Additives.

Ingestion is a major exposure route for hydrophobic organic pollutants in fish, but the microbial transformation and estrogenic modification of the novel plastic additives by the gut microbiota of fish remain obscure. Using an in vitro approach, we provide evidence that structure-related transformation of various plastic additives by the gastric and intestinal (GI) microbiota from crucian carp, with the degradation ratio of bisphenols and triphenyl phosphate faster than those of brominated compounds. The degradation kinetics for these pollutants could be limited by oxygen and cometabolic substrates (i.e., glucose). The fish GI microbiota could utilize the vast majority of carbon sources in a Biolog EcoPlate, suggesting their high metabolic potential and ability to transform various organic compounds. Unique microorganisms associated with transformation of the plastic additives including genera of Citrobacter, Klebsiella, and some unclassified genera in Enterobacteriaceae were identified by combining high-throughput genetic analyses and metagenomic analyses. Through identification of anaerobic transformation products by high-resolution mass spectrometry, alkyl-cleavage was found the common transformation mechanism, and hydrolysis was the major pathway for ester-containing pollutants. After anaerobic incubation, the estrogenic activities of triphenyl phosphate and bisphenols A, F, and AF declined, whereas that of bisphenol AP increased.

Free and conjugated forms of metabolites are indispensable components of steroids: The first evidence from an estuarine food web.

Steroids have attracted particular attention as environmental contaminants because of their severe endocrine-disrupting effects. Previous studies have predominantly focused on parent steroids; however, the levels and proportions of the free and conjugated forms of their metabolites remain largely unclear, especially in food webs. Here, we first characterized the free and conjugated forms of parent steroids and their metabolites in 26 species in an estuarine food web. The steroids were dominated by their metabolites in water samples, whereas parent compounds were predominant in sediment samples. The total mean steroid concentrations in the biota samples that underwent non-enzymatic hydrolysis decreased in the following order: crabs (27 ng/g) > fish (5.9 ng/g) > snails (3.4 ng/g) > shrimps and sea cucumbers (1.2 ng/g); and those in the biota samples that underwent enzymatic hydrolysis decreased in the following order: crabs (57 ng/g) > snails (9.2 ng/g) > fish (7.9 ng/g) > shrimps and sea cucumbers (3.5 ng/g). The proportion of metabolites in the enzymatic hydrolysis biota samples was higher (38-79%) than that (2.9-65%) in non-enzymatic ones, indicating that the free and conjugated forms of metabolites in aquatic organisms were not negligible. Most synthetic steroids were either bioaccumulative or highly bioaccumulative. Importantly, in the invertebrate food web, 17α-methyltestosterone was biomagnified, while 17ß-boldenone underwent trophic dilution. Although the estuarine water had a median ecological risk level, the health risks via aquatic product consumption were very low. This study provides novel insights into the composition and trophic transfer of steroids in an estuarine food web for the first time and highlights that free and conjugated metabolites should receive more attention, particularly in biota samples.

Bioaccumulation and Trophic Transfer of Organophosphate Flame Retardants and Their Metabolites in the Estuarine Food Web of the Pearl River, China.

The accumulation and trophodynamics of organophosphate flame retardants (OPFRs) and their metabolites were investigated in the estuarine food web of the Pearl River, China. The mean ∑OPFR concentration among the investigated species increased in the following order: fish [431 ± 346 ng/g lipid weight (lw)] < snail (1310 ± 621 ng/g lw) < shrimp (1581 ± 1134 ng/g lw) < crab (1744 ± 1397 ng/g lw). The di-alkyl phosphates (DAPs) of di-(n-butyl) phosphate (DNBP), bis(2-butoxyethyl) phosphate (BBOEP), and diphenyl phosphate (DPHP) were the most abundant metabolites, with concentrations same as or even higher than their corresponding parent compounds. The log bioaccumulation factors for most OPFRs were lower than 3.70, and significant biomagnification was only found for trisphenyl phosphate [TPHP, with the trophic magnification factors (TMFs) > 1]. The TMFs of OPFRs, except for TPHP and tributyl phosphate had a positive correlation with lipophilicity (log KOW, p ≤ 0.05) and a negative correlation with the biotransformation rate (log KM, p ≤ 0.05). The mean TMF > 1 was observed for all of the OPFR metabolites based on the bootstrap regression method. The "pseudo-biomagnification" of OPFR metabolites might be attributed to the biotransformation of OPFRs in organisms at high trophic levels.

The incidence of post-traumatic stress disorder following traumatic childbirth: A systematic review and meta-analysis.

BACKGROUND: Although birth trauma may be a risk factor for postpartum post-traumatic stress disorder (PTSD), no systematic review regarding the incidence of postpartum PTSD in women with traumatic childbirth has been reported. OBJECTIVE: To estimate the incidence of PTSD in women following traumatic childbirth by systematically reviewing and synthesizing all available evidence. SEARCH STRATEGY: Six databases were searched using a combination of related terms for birth trauma and PTSD. SELECTION CRITERIA: Cohort and cross-sectional studies that were related to traumatic childbirth and PTSD were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened potentially relevant studies and extracted key data elements. A series of meta-analyses were conducted using STATA 17.0 software, with pooled incidence rates estimated using random effects models. MAIN RESULTS: A total of nine studies were included in this study. The pooled incidence of PTSD after traumatic childbirth was 19.4% (95% confidence interval 11.9%-26.5%). The incidence of PTSD varied with the scales used to assess traumatic birth and PTSD, evaluation times of PTSD after childbirth, and types of study participants. CONCLUSIONS: The incidence of PTSD in women with traumatic childbirth is about 19%, higher than the general obstetric population, suggesting that trauma-related care for them should be enhanced.

The probability and possible influence factors of intermittent ovarian function recovery in patients with premature ovarian insufficiency.

RESEARCH QUESTION: What are the probability and underlying influence factors of intermittent ovarian function recovery in patients with idiopathic premature ovarian insufficiency (POI)? DESIGN: This was a retrospective cohort study conducted in tertiary hospitals recruiting 162 patients diagnosed with POI based on European Society of Human Reproduction and Embryology criteria from June 2015 to March 2022. The incidence of intermittent ovarian function recovery was evaluated, and the possible influence factors were investigated by univariate and multivariate analysis. RESULTS: Among 162 POI patients, 48 (29.63%) presented intermittent ovarian function recovery, and 11 (6.79%) were natural pregnancies; 114 (70.37%) patients failed to show ovarian function recovery. No association was found between initial clinical features and intermittent ovarian function recovery. In contrast, the variables of FSH, LH, oestradiol, anti-Müllerian hormone (AMH), ovarian volume, passive smoking and weekly exercise time after diagnosis were correlated with intermittent ovarian function recovery in patients with POI and further analysis indicated that FSH concentration at diagnosis (odds ratio [OR] 0.964, 95% confidence interval [CI] 0.934-0.995, P = 0.023), passive smoking (OR 0.369, 95% CI 0.141-0.963, P = 0.042) and weekly exercise time after diagnosis (OR 5.592, 95% CI 1.83-17.088, P = 0.003) were influence factors of intermittent ovarian function recovery in POI patients. CONCLUSIONS: The incidence of intermittent ovarian function recovery in patients with idiopathic POI was 29.63%, and the natural pregnancy rate was 6.79%. Lower FSH concentration at diagnosis, no passive smoking and a weekly exercise time ≥1.5 h after the diagnosis may be beneficial for intermittent ovarian function recovery in POI patients.

Novel Brominated Flame Retardants (NBFRs) in a Tropical Marine Food Web from the South China Sea: The Influence of Hydrophobicity and Biotransformation on Structure-Related Trophodynamics.

The increasing discharge and ubiquitous occurrence of novel brominated flame retardants (NBFRs) in aquatic environments have initiated intense global concerns; however, little information is available regarding their structure-related trophodynamics in marine food webs. In this study, a tropical marine food web including 29 species (18 fish and 11 invertebrate species) was collected from coral reef waters of the Xisha Islands, the South China Sea, for an analysis of 11 representative NBFRs. The mean ∑NBFR concentrations generally increased in the following sequence: sea cucumbers (0.330 ng/g lw) < crabs (0.380 ng/g lw) < shells (2.10 ng/g lw) < herbivorous fishes (2.30 ng/g lw) < carnivorous fishes (4.13 ng/g lw), with decabromodiphenyl ethane (DBDPE) and hexabromobenzene (HBB) as the predominant components. Trophic magnification was observed for all of the investigated NBFRs, with trophic magnification factors (TMFs) ranging from 1.53 (tetrabromobisphenol A bis(dibromopropyl ether)) to 5.32 (HBB). Significant negative correlations were also found between the TMFs and the tested in vitro transformation clearance rates (CLin vitro) for the target NBFRs except for bis(2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate (TBPH) (p < 0.05). Multiple linear regression analysis confirmed that the transformation rate is a more powerful predictor for TMFs than the hydrophobicity of NBFRs in this marine food web.

GATA3 improves the protective effects of bone marrow-derived mesenchymal stem cells against ischemic stroke induced injury by regulating autophagy through CREG.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) transplantation has been demonstrated to benefit functional recovery after ischemic stroke, however, the low survival rate of BMSCs in ischemic microenvironment largely limits its use. METHODS: Rat BMSCs (rBMSCs) were isolated from SD rats and treated with oxygen glucose deprivation/reoxygenation (OGD) to mimic ischemic microenvironment in vitro. Expression of mRNAs and proteins were assessed by qRT-PCR and western blot, respectively. Cell viability was detected using MTT. ROS level was evaluated by DCFH-DA Assay Kit. TUNEL and flow cytometry analysis were adopted to detect cell apoptosis. Immunofluorescence analysis was used to examine LC3 expression. Dual-luciferase reporter and ChIP assays were employed to determine the interaction between CREG and GATA3. Middle cerebral artery occlusion (MCAO) model was established to mimic ischemic stroke in vivo. TTC staining was used to measure the infarcts area in the brain of MCAO rats. Nissl staining was used to examine the quantity of neurons, and mNSS test was applied to compare behavioral functions of animals. RESULTS: The rBMSCs were successfully isolated from SD rats. OGD exposure decreased the expression of GATA3 in rBMSCs, GATA3 overexpression alleviated OGD-induced cell injury and enhanced autophagy. Treatment with autophagy inhibitor (3-MA) abolished the protective effects of GATA3 against OGD-induced cell injury. GATA3 targeted the promoter of CREG and positively regulated its expression. The protective effect of GATA3 overexpression on autophagy during OGD exposure was reversed by CREG knockdown. Moreover, GATA3 overexpression improved the therapeutic effects of BMSCs transplantation on ischemic stroke in vivo. CONCLUSION: Our results indicated that GATA3 overexpression improved the therapeutic effects of rBMSCs transplantation against ischemic stroke induced injury by regulating autophagy through CREG.

Identification and characterization of pulmonary mesenchymal stem cells derived from rat fetal lung tissue.

Pulmonary mesenchymal stem cells (PMSCs) have great potential in lung tissue repair and regeneration, which have been isolated from some mammalian species, including mice, bovine and pig. However, the isolation, characteristics and differentiation potential of rat PMSCs have not been reported. In this study, we successfully isolated PMSCs from Sprague-Dawley rat fetal lung tissue in vitro for the first time and attempted to evaluate its multilineage differentiation potentials. The cultured PMSCs showed typical spindle-shaped morphology and high proliferative potential, and could be passaged for at least 13 passages and maintained high hereditary stability with more than 93.6 % of cells were diploid (2n = 42) by G-banding analysis. Furthermore, the PMSCs could express mesenchymal markers Sca-1, CD29, CD44, CD73 and CD90, but not hematopoietic markers CD34 and CD45. Besides, the expression of cell markers of AT2 (SFTPC), AT1 (PDPN) and macrophage (CD11b) were also negative. Cell cycle examination revealed majority of the PMSCs were in G0/G1 phase, which are similar with previously reported pig PMSCs. In addition, the PMSCs were multipotent and could differentiated into osteocytes, adipocytes, hepatocytes and neurons in vitro. Together, the present study demonstrated the stemness and multi-differentiation potentials of rat PMSCs, which conferred a potential regenerative cell resource for cell regenerative therapy of lung injury.

A Systematic Review and Meta-Analysis of Autoantibodies for Diagnosis and Prognosis in Patients With Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Objectives: To review the available evidence on sensitivity and specificity of anti-NF155 antibody detection in diagnosing a specific subset of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to calculate the frequencies of different autoantibodies to paranodal proteins. Background: Diagnosis of CIDP relies on clinical and neurophysiologic criteria and lacks useful diagnostic biomarkers. A subset of CIDP patients exhibit atypical clinical phenotypes and impaired response to conventional treatments. These patients were reported as having autoantibodies targeting paranodal protein neurofascin isoform 155 (NF155), contactin-1 (CNTN1), and contactin-associated protein-1 (CASPR1). Here, we conducted a meta-analysis to summarize evidence on the diagnostic and prognostic value of these autoantibodies, especially for anti-NF155 antibody. Methods: We searched the following electronic bibliographic databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science. Eligible studies provided information to calculate the frequencies of anti-NF155 antibody and anti-CNTN1 antibody, the sensitivity and specificity of anti-NF155 antibody, and the incidence of improvement and deterioration among anti-NF155 antibody seropositive CIDP patients. Heterogeneity was assessed using Q and I 2 statistics. Results: The pooled frequency of anti-NF155 autoantibody across 14 studies was 7% [95% confidence interval (CI): 0.05-0.10] with high heterogeneity; the overall pooled sensitivity and specificity of anti-NF155 antibody for the diagnosis of a specific subgroup of CIDP patients were 0.45 (95% CI: 0.29-0.63) and 0.93 (95% CI: 0.86-0.97), respectively. Conclusions: For diagnosing of a specific subset of CIDP characterized by poor response to intravenous immunoglobulin (IVIg), we found a moderate sensitivity and a high specificity. The anti-NF155 antibody test should be used as a confirmatory test rather than a screening test. Systematic Review Registration: PROSPERO, identifier: CRD42020203385 and CRD42020190789.

A systematic review of the correlation between serum asymmetric dimethylarginine, carotid atherosclerosis and ischaemic stroke.

OBJECTIVE: To investigate the correlation between serum asymmetric dimethylarginine (ADMA) and the risk of ischaemic stroke and carotid atherosclerosis in adults. METHODS: We systematically searched PubMed, EMBASE, Web of Science and other databases for relevant studies on serum ADMA and ischaemic stroke or carotid atherosclerosis, which were published from December 1980 to December 2019. The quality of the included studies was evaluated according to the Cochrane system evaluation standard. The difference in serum ADMA level between ischaemic stroke and control group was selected as the effect size (standardized mean difference, SMD). The pooled analysis was performed using Review Manager (V.5.3). RESULTS: According to the selection criteria, thirteen studies were included in the meta-analysis after screening. Nine studies compared ADMA levels between the ischaemic stroke group and healthy control group, involving a total of 1315 and 880 subjects in the two groups, respectively. Pooled effect sizes were calculated using the random-effects model due to the high heterogeneity (I2  = 93%, P < .00001). The level of serum ADMA in patients with ischaemic stroke was significantly higher than that in healthy people (SDM = 0.69, 95% CI [0.32, 1.06], P = .0002). Seven of the thirteen articles compared ADMA levels between the carotid arteriosclerosis group and the healthy control group, with 559 and 330 subjects in the two groups, respectively. The random-effects model was applied due to the high heterogeneity (I2  = 91%, P < .00001). The level of serum ADMA in patients with carotid arteriosclerosis was significantly higher than that in healthy people (SDM = 1.03, 95% CI [0.49, 1.57], P = .0002). CONCLUSION: The serum ADMA may be related to ischaemic stroke, and it is a risk factor for carotid atherosclerosis.

Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in patients with laryngeal cancer: a systematic review and meta-analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been shown to be associated with the progression of laryngeal cancer (LC), but studies have reported inconsistent results. We systematically evaluated the effect of the pretreatment NLR on the prognosis of LC in the meta-analysis. METHOD: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched from January 1, 2000 to September 10, 2019, to identify studies investigating the relationship between the NLR and outcomes in LC patients. The fixed-effects model was used to assess the pooled hazard ratio (HR), along with the 95% confidence interval (95% CI). RESULTS: A total of 105 records were obtained through the databases and 12 studies enrolling 3710 patients were included in the meta-analysis. The pooled overall survival (OS, HR = 1.76, 95% CI 1.53-2.03, P < 0.001), progression-free survival (PFS, HR = 1.72, 95% CI 1.38-2.13, P < 0.001) and disease-free survival (DFS, HR = 1.66, 95% CI 1.33-2.07, P < 0.001) indicated that a higher NLR led to a poorer prognosis for patients with LC. In terms of publication year, country, cutoff value, cutoff method, treatment modality, statistical model and NOS score, subgroup analyses consistently showed a worse OS in patients with an elevated NLR. Additionally, there was no significant difference among the subgroups (all P for heterogeneity > 0.05). CONCLUSION: An elevated pretreatment NLR is significantly associated with poorer prognosis in patients with LC. NLR values are easily obtained from routinely collected blood samples and could assist clinicians in determining the prognosis of LC patients.

Distinguish CIDP with autoantibody from that without autoantibody: pathogenesis, histopathology, and clinical features.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is considered to be an immune-mediated heterogeneous disease involving cellular and humoral immunity. In recent years, autoantibodies against nodal/paranodal protein neurofascin155 (NF155), neurofascin186 (NF186), contactin-1 (CNTN1), and contactin-associated protein 1 (CASPR1) have been identified in a small subset of patients with CIDP, which disrupt axo-glial interactions at nodes/paranodes. Although CIDP electrodiagnosis was made in patients with anti-nodal/paranodal component autoantibodies, macrophage-induced demyelination, the characteristic of typical CIDP, was not observed. Apart from specific histopathology, the pathogenic mechanisms and clinical manifestations of CIDP with autoantibody are also distinct. We herein compared pathogenesis, histopathology, clinical manifestations, and therapeutic response in CIDP with autoantibody vs. CIDP without autoantibody. CIDP with autoantibodies should be considered as an independent disease entity, not a subtype of CIDP due to many differences. They possibly should be classified as CIDP-like chronic nodo-paranodopathy, which can better characterize these disorders, help diagnose and make the most effective therapeutic decisions.

Prednisone improves pregnancy outcome in repeated implantation failure by enhance regulatory T cells bias.

OBJECTIVE: Repeated implantation failure (RIF) has been shown related to maternal immune imbalance. Many studies suggested that prednisone promoted the Th17/Treg balance shift to the direction of immune tolerance. Our study aimed to evaluate the role of prednisone in Th17/Treg balance and pregnancy outcome in RIF patients. STUDY DESIGN AND MAIN OUTCOME MEASURES: Peripheral blood of healthy fertile controls and RIF patients were collected at the late proliferation phase. The population of Treg and Th17 cells, the expression of Foxp3 and RORC mRNA and the concentration of IL-17A, IL-23 and IL-10 were detected by flow cytometry, qRT-PCR and enzyme-linked immunosorbent assay. RIF patients were given oral prednisone 10 mg daily from the late proliferation phase of the cycle before FET. After one month of treatment, the above immune indicators were tested, and natural cycle frozen embryo transfer was performed. RESULTS: The Treg cells proportion and IL-10 concentration in peripheral blood of RIF patients was lower than that of NF group, while the proportion of Th17 cells and concentration of proinflammatory cytokine were significantly higher. After prednisone treatment, the indicators related to immune tolerance increased significantly. Five out of 19 RIF patients were successful pregnancy after FET, in which, one had an early miscarriage and four live births. No pregnancy complications and fetal abnormalities were observed. CONCLUSIONS: We report the beneficial effect of prednisone on RIF patients. The underlying mechanism may attribute to shift the Treg/Th17 immune balance to a Treg bias, and enhance embryo implantation, ultimately improve pregnancy outcomes.