The effect of active and passive smoking during pregnancy on birth outcomes: A cohort study in Shanghai.

INTRODUCTION: China is the largest tobacco consumer in the world, and tobacco poses a serious threat to the health of pregnant women. However, there are relatively few domestic studies on smoking during pregnancy and childbirth outcomes among pregnant women. The purpose of this study was to analyze the effect of active and passive smoking on pregnant women and their pregnancy outcomes, providing evidence and recommendations for intervention measures. METHODS: This was a cohort study in Shanghai from April 2021 to September 2023. According to the smoking status of pregnant women, they were divided into three groups: active smokers, passive smokers and non-smokers. A self-designed questionnaire was utilized to conduct the survey, and their pregnancy outcomes were tracked and followed up. RESULTS: A total of 3446 pregnant women were included in this study, among which 2.1% were active smokers, 43.5% were passive smokers, and 54.4% were non-smokers. The average age of the pregnant women was 29.9 years, and 41.2% had a university degree or higher. The education level of active smokers and passive smokers was significantly lower than that of non-smokers (p<0.05).The average gestational age of non-smokers was 38.6 weeks, and the birth weight was 3283.2 g, which was higher than those of active smokers and passive smokers (p<0.05). Logistic regression analysis showed that passive smoking increased the likelihood of preterm birth (AOR=1.38; 95% CI: 1.05-1.81), low birth weight (AOR=1.53; 95% CI: 1.10-2.12), and intrauterine growth restriction (AOR=1.35; 95% CI: 1.02-1.79), while active smoking increased the likelihood of preterm birth (AOR=2.98; 95% CI: 1.50-5.90), low birth weight (AOR=4.29; 95% CI: 2.07-8.88), intrauterine growth restriction (AOR=2.70; 95% CI: 1.37-5.33) , and birth defects (AOR=2.66; 95% CI: 1.00-6.97). CONCLUSIONS: Our findings illustrate that active and passive smoking can lead to adverse pregnancy outcomes. This study provides data on the relationship between smoking during pregnancy and delivery outcomes among pregnant women. In the future, we need more effective strategies to protect pregnant women from the harm of tobacco.

Ultrasonic Non-Destructive Detection Method for Residual Stress in Rotary Forging Aluminum Alloy Plates.

Aluminum alloy plates are widely used to manufacture large-scale integral structure parts in the field of aerospace. During the forming and processing of aluminum alloy plates, different degrees of residual stress are inevitably produced. Fast and accurate detection of residual stress is very essential to ensuring the quality of these plates. In this work, the longitudinal critically refracted (LCR) wave detection method based on a one-transmitter and double-receiver (OTDR) transducer and the finite element simulation were employed to obtain the residual stress. Aluminum alloy plates with different deformation amounts were fabricated by rotary forging to obtain different residual stress states. Results reveal that the plate formed by rotary forging is in a stress state of central tension and edge compression. As the deformation increases from 20% to 60%, the peak residual tensile stress increases from 156 MPa to 262 MPa, and there is no significant difference in the peak compressive stress. When the deformation reaches 60%, the difference in the residual stresses at different depths is less than 13%, which indicates that the plastic deformation zone basically penetrates the entire longitudinal cross-section of the plate. The maximum deviation between measurement and FE is 61 MPa, which means the experimental data are in good agreement with the FE results.

Biological significance of METTL5 in atherosclerosis: comprehensive analysis of single-cell and bulk RNA sequencing data.

BACKGROUND: N6-methyladenosine (m6A) methylation is involved in the pathogenesis of atherosclerosis (AS). Limited studies have examined the role of the m6A methyltransferase METTL5 in AS pathogenesis. METHODS: This study subjected the AS dataset to differential analysis and weighted gene co-expression network analysis to identify m6A methylation-associated differentially expressed genes (DEGs). Next, the m6A methylation-related DEGs were subjected to consensus clustering to categorize AS samples into distinct m6A subtypes. Single-cell RNA sequencing (scRNA-seq) analysis was performed to investigate the proportions of each cell type in AS and adjacent healthy tissues and the expression levels of key m6A regulators. The mRNA expression levels of METTL5 in AS and healthy tissues were determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RESULTS: AS samples were classified into two subtypes based on a five-m6A regulator-based model. scRNA-seq analysis revealed that the proportions of T cells, monocytes, and macrophages in AS tissues were significantly higher than those in healthy tissues. Additionally, the levels of m6A methylation were significantly different between AS and healthy tissues. METTL5 expression was upregulated in macrophages, smooth muscle cells (SMCs), and endothelial cells (ECs). qRT-PCR analysis demonstrated that the METTL5 mRNA level in AS tissues was downregulated when compared with that in healthy tissues. CONCLUSIONS: METTL5 is a potential diagnostic marker for AS subtypes. Macrophages, SMCs, and ECs, which exhibit METTL5 upregulation, may modulate AS progression by regulating m6A methylation levels.

Financial toxicity of informal caregivers of colorectal cancer patients: A cross-sectional study.

PURPOSE: To assess the level of financial toxicity of informal caregivers of colorectal cancer patients and explore the related key influencing factors. METHOD: A descriptive survey design was used in this study. Data were collected from 236 informal caregivers of colorectal cancer patients between March 2023 and July 2023 from a major hospital in central China (Henan province). Potential influence factors of financial toxicity, including basic information, perceived stress, and social support were analyzed using multivariate linear regression. RESULTS: The financial toxicity score of 236 caregivers of colorectal cancer patients was 19.42 ± 9.72. One hundred and fourteen caregivers (accounting for 48.31%) of colorectal cancer patients had high levels of financial toxicity. Financial toxicity scores of caregivers were negatively correlated with perceived stress (r = -0.421, P < 0.001) and positively correlated with social support (r = 0.416, P < 0.001). Our multivariate regression analysis identified some factors that directly affected caregivers' financial toxicity, including caregiver age (t = 2.105, P = 0.036), medical insurance (t = 2.462, P = 0.015), average household income (t = 2.995, P = 0.003), place of residence (t = 2.872, P = 0.004), perceived stress (t = -4.945, P < 0.001), and social support (t = 4.513, P < 0.001). CONCLUSIONS: Caregivers of colorectal cancer patients generally experience a higher level of financial toxicity, which could be eased by lower perceived stress and higher social support. In clinical practice, it is necessary to comprehensively assess the level of financial toxicity of particular caregivers and enact targeted interventions such as increasing communication and actively providing information to address the high medical costs, reducing the detrimental effects of financial toxicity, and improving the quality of colorectal cancer care.

Lactate promoted cisplatin resistance in NSCLC by modulating the m6A modification-mediated FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R axis.

BACKGROUND: Cisplatin resistance is one of the major obstacles in non-small cell lung cancer (NSCLC) treatment. Intriguingly, elevated lactate levels were observed in cisplatin-resistant cells, which spurred further investigation into their underlying biological mechanisms. METHODS: Lactate levels were measured by lactate detection kit. Cisplatin-resistance NSCLC cells were established using progressive concentration of cisplatin. Cell viability, proliferation, and apoptosis were detected by CCK-8, EdU, and flow cytometry, respectively. Cell proliferation in vivo was determined by immunohistochemistry of Ki67 and apoptotic cells were calculated by the TUNEL. MeRIP-PCR was used to measure FOXO3 m6A levels. The interactions of genes were analyzed via RIP, ChIP, Dual-luciferase reporter, and RNA pull-down, respectively. RESULTS: Elevated lactate levels were observed in both NSCLC patients and cisplatin-resistance cells. Lactate treatment increased cisplatin-resistance cell viability in vitro and promoted tumor growth in vivo. Mechanistically, lactate downregulated FOXO3 by YTHDF2-mediated m6A modification. FOXO3 transcriptionally reduced MAGI1-IT1 expression. FOXO3 overexpression inhibited the lactate-induced promotion of cisplatin resistance in NSCLC, which were reversed by MAGI1-IT1 overexpression. MAGI1-IT1 and IL6R competitively bound miR-664b-3p. FOXO3 overexpression or MAGI1-IT1 knockdown repressed lactate-mediated cisplatin resistance in vivo. CONCLUSION: Lactate promoted NSCLC cisplatin resistance through regulating FOXO3/MAGI1-IT1/miR-664b-3p/IL6R axis in YTHDF2-mediated m6A modification.

Comparative efficacy of early TIPS, Non-early TIPS, and Standard treatment in patients with cirrhosis and acute variceal bleeding: a network meta-analysis.

BACKGROUND: Cirrhosis is a chronic disease characterized by chronic liver inflammation and diffuse fibrosis. A combination of vasoactive drugs, preventive antibiotics, and endoscopy is the recommended standard treatment for patients with acute variceal bleeding; however, this has been challenged. We compared the effects of early transjugular intrahepatic portosystemic shunt (TIPS), non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding. MATERIALS AND METHODS: The present network meta-analysis was conducted in accordance with the criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Assessing the methodological quality of systematic reviews guidelines. The review has been registered with the International Prospective Register of Systematic Reviews. The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and World Health Organization-approved trial registry databases were searched for randomized controlled trials (RCTs) evaluating early TIPS, non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding. RESULTS: Twenty-four RCTs (1894 patients) were included in the review. Compared with standard treatment, early TIPS [odds ratio (OR), 0.53; 95% credible interval (Cr), 0.30-0.94; surface under the cumulative ranking curve (SUCRA), 98.3] had a lower risk of all-cause mortality (moderate-to-high-quality evidence), and early TIPS (OR, 0.19; 95% CrI, 0.11-0.28; SUCRA, 98.2) and non-early TIPS (OR, 0.30; 95% CrI, 0.23-0.42; SUCRA, 1.8) were associated with a lower risk of rebleeding (moderate-to-high-quality evidence). Early TIPS was not associated with a reduced risk of hepatic encephalopathy, and non-early TIPS (OR, 2.78; 95% CrI, 1.89-4.23, SUCRA, 0) was associated with an increased incidence of hepatic encephalopathy (moderate-to-high-quality evidence). There was no difference in the incidence of new or worsening ascites (moderate-to-high-quality evidence) among the three interventions. CONCLUSION: Based on the moderate-to-high quality evidence presented in this study, early TIPS placement was associated with reduced all-cause mortality [with a median follow-up of 1.9 years (25th-75th percentile range 1.9-2.3 years)] and rebleeding compared to standard treatment and non-early TIPS. Although early TIPS and standard treatment had a comparable incidence of hepatic encephalopathy, early TIPS showed superiority over non-early TIPS in this aspect. Recent studies have also shown promising results in controlling TIPS-related hepatic encephalopathy. However, it is important to consider individual patient characteristics and weigh the potential benefits against the risks associated with early TIPS. Therefore, we recommend that clinicians carefully evaluate the patient's condition, considering factors such as severity of variceal bleeding, underlying liver disease, and overall clinical status, before making a treatment decision. Further well-designed RCTs comparing early TIPS with non-early TIPS are needed to validate these findings and provide more definitive guidance.

Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models.

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5+ BMSCs and Tek+ BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5+ TEK+ ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5+ BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition.

Allogeneic Hematopoietic Stem Cell Transplantation Can Improve Prognosis of Extramedullary Infiltration Positive t(8;21) Acute Myeloid Leukemia.

BACKGROUND In t(8;21) acute myeloid leukemia (AML), patients with extramedullary infiltration (EMI) tend to have worse survival outcomes than those without EMI. However, it is still unclear whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) benefits EMI-positive t(8;21) AML patients. MATERIAL AND METHODS This study retrospectively enrolled 651 t(8;21) AML patients, and analyzed 51 patients with EMI at diagnosis. Among the 51 patients, 15 patients received allo-HSCT. RESULTS The incidence of EMI in t(8;21) AML was 10.0%, and the first complete remission rate was 78.5% in EMI-positive t(8;21) AML patients. The central nervous system was the most frequently involved site (29.4%), followed by bones (15.7%), and skin (9.8%). In terms of karyotype, 19 (37.3%) patients were t(8;21) alone, 12 (23.5%) had additional loss of a sex chromosome, and 5 (9.8%) had complex karyotype. Significantly better overall survival was observed in patients with allo-HSCT compared to patients without allo-HSCT in both multivariable models (HR=0.32; P=0.0122) and the Kaplan-Meier curves (P=0.0157). CONCLUSIONS Allo-HSCT improved the survival of EMI-positive t(8;21) AML.

The Effects of Laughter Yoga on Perceived Stress, Positive Psychological Capital, and Exercise Capacity in Lung Cancer Chemotherapy Patients: A Pilot Randomized Trial.

BACKGROUND: Lung cancer is the malignant tumor with the highest morbidity and mortality rate in China. Although chemotherapy is effective in improving clinical symptoms, it causes a variety of acute and chronic side effects, seriously aggravating the psychological stress of patients. Laughter Yoga as a new type of aerobic exercise can effectively reduce stress levels and increase positive mood in patients. This study aimed to examine the effects of laughter yoga on perceived stress, positive psychological capital, and exercise capacity in lung cancer patients. METHODS: This study was a randomized, single-blind, parallel-group trial. The study enrolled 84 lung cancer chemotherapy patients from a general hospital in central China. These patients were randomly allocated to control and intervention groups (n = 42 per group) after baseline assessments. Patients in the control group received routine care and those in the intervention group received laughter yoga intervention. Perceived stress, positive psychological capital, and exercise capacity were assessed at baseline, immediately post-intervention. RESULTS: During the implementation of the study, there were 2 dropouts in each of the intervention and control groups. Ultimately, 80 patients in the control and intervention groups completed the trial. Patients who received laughter yoga intervention had significantly higher scores in positive psychological capital (P < .01, Cohen's d = 0.692) and exercise capacity (P < .01, Cohen's d = 0.659). Discernible differences were also observed in perceived stress (P < .01, Cohen's d = 1.087) between the 2 groups. CONCLUSIONS: The results of this study suggest that laughter yoga is an effective way and may produce beneficial effects on perceived stress, positive psychological capital and exercise capacity.

Comparative effectiveness and safety of laser, needle, and "quick fenestrater" in in situ fenestration during thoracic endovascular aortic repair.

Background: Special instruments are needed for the revascularization of aortic branches in in situ fenestration during thoracic endovascular aortic repair (TEVAR). This prospective study compared the effectiveness and safety of three currently used fenestraters: laser, needle, and Quick Fenestrater (QF). Methods: In all, 101 patients who underwent TEVAR for aortic disease (dissection, n = 62; aneurysm, n = 16, or ulcer, n = 23) were enrolled. All patients were randomly assigned to three groups: 34 were assigned to laser fenestration, 36 to needle fenestration, and 31 to QF fenestration. The epidemiological data, treatment, imaging findings, and follow-up outcomes were analyzed using data from the medical records. Results: The technical success rates of the laser, needle, and QF fenestration groups were 94.1%, 94.4%, and 100% (p > 0.05). After correction of mixed factors such as age and gender, it was showed the average operative time (Laser group: 130.01 ± 9.36 min/ Needle group: 149.80 ± 10.18 min vs. QF group: 101.10 ± 6.75 min, p < 0.001), fluoroscopy time (Laser group: 30.16 ± 9.81 min/ Needle group: 40.20 ± 9.91 min vs. QF group: 19.91 ± 5.42 min, p < 0.001), fenestration time (Laser group 5.50 ± 3.10 min / Needle group 3.50 ± 1.50 min vs. QF group 0.67 ± 0.06 min, p < 0.001), and guide wire passage time after fenestration (Laser group 5.10 ± 1.70 min / Needle group 4.28 ± 1.60 min vs. QF group 0.07 ± 0.01 min, p < 0.001) were all shorter with QF fenestration than with the other two tools. The overall perioperative complication rates of the laser, needle, and QF fenestration groups were 5.9%, 5.6%, and 0% (p > 0.05): One case of sheath thermal injury and one case of vertebral artery ischemia occurred in the laser fenestration group; one case each of access site hematoma and brachial artery thrombosis were reported in the needle fenestration group. 89 (88.1%, 89/101) patients were followed for a median of 12.6 ± 1.6 months. The overall postoperative complication rates of the laser, needle, and QF fenestration groups were 3.3%, 6.5%, and 0% (p > 0.05): In the laser fenestration group, there was one death due to postoperative ST-segment elevation myocardial infarction; in the needle fenestration group, one patient developed occlusion of the bridge stent; no complications occurred in the QF group. Conclusion: All three fenestration methods were effective in reconstructing supra-arch artery during TEVAR. QF fenestration required less contrast agent, with a shorter surgery duration and fewer complications than laser and needle fenestration.

Effects of nitrification and urease inhibitors on ammonia-oxidizing microorganisms, denitrifying bacteria, and greenhouse gas emissions in greenhouse vegetable fields.

Soil microorganisms and N cycling are important components of biogeochemical cycling processes. In addition, the study of the effects of nitrification and urease inhibitors on N and microorganisms in greenhouse vegetable fields is essential to reducing N loss and greenhouse gas emissions. The effects of nitrification inhibitors [2-chloro-6-(trichloromethyl) pyridine (CP), dicyandiamide (DCD)], and urease inhibitor [N-(n-butyl) thiophosphoric triamide (NBPT)] on soil inorganic N (NH4+-N, NO2--N and NO3--N) concentrations and the production rates of greenhouse gases (N2O, CH4, and CO2) in greenhouse vegetable fields were investigated via indoor incubation experiments. Polymerase chain reaction amplification and high-throughput sequencing technology (Illumina Miseq) were used to explore the community structure and abundance changes of ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), and denitrifying bacteria (nirK and nirS). The results showed that CP and DCD obviously inhibited NH4+-N conversion, and NO2--N, and NO3--N accumulation, NBPT slowed down urea hydrolysis and NH4+-N production, and the apparent nitrification rates of soil were in the following order: NBPT > DCD > DCD + NBPT > CP + NBPT > CP. Compared with urea treatment, the peak N2O production rate of inhibitor treatment decreased by 73.30-99.30%, and the production rate of CH4 and CO2 decreased by more than 66.16%. DCD and CP reduced the abundance of AOA and AOB, respectively. Furthermore, NBPT hindered the growth of ammonia-oxidizing microorganisms and nirS-type denitrifying bacteria, and urea and nitrification inhibitors were detrimental to the growth of Ensifer and Sinorhizobium in the nirK community. Nitrification and urease inhibitors can effectively slow down nitrification and greenhouse gas emissions, reduce N loss and improve soil quality by inhibiting the growth of ammonia-oxidizing microorganisms and denitrifying bacteria.

Eriodictyol regulated ferroptosis, mitochondrial dysfunction, and cell viability via Nrf2/HO-1/NQO1 signaling pathway in ovarian cancer cells.

This study aimed to investigate the antitumor effect and the underlying molecular mechanism of eriodictyol on ovarian cancer cells. CaoV3 and A2780 were exposed to eriodictyol at different concentrations of 0-800 µM. Cell apoptosis and viability were determined by TdT-mediated dUTP Nick-End Labeling (TUNEL) assay and Cell Counting Kit-8 (CCK-8) assay, respectively. Mitochondrial membrane potential was evaluated by flow cytometers with a JC-1 detection kit. Fe2+ content was evaluated using an iron assay kit. The section of tumor tissues was observed using hematoxylin-eosin (H&E) staining and nuclear factor erythroid 2-related factor 2 (Nrf2) expression was detected by immunohistochemistry (IHC) staining. Eriodictyol suppressed cell viability and induced cell apoptosis of CaoV3 and A2780 cells. Half maximal inhibitory concentration (IC50 ) value of CaoV3 at 24 and 48 h was (229.74 ± 5.13) µM and (38.44 ± 4.68) µM, and IC50 value of A2780 at 24 and 48 h was (248.32 ± 2.54) µM and (64.28 ± 3.19) µM. Fe2+ content and reactive oxygen species production were increased and protein levels of SLC7A11 and GPX4 were decreased by eriodictyol. Besides, eriodictyol reduced the ratio of JC-1 fluorescence ratio, glutathione and malondialdehyde contents but elevated Cytochrome C level. Nrf2 phosphorylation were obviously downregulated by eriodictyol. Finally, eriodictyol suppressed tumor growth, aggravated mitochondrial dysfunction and downregulated Nrf2 expression in tumor tissue in mice. Eriodictyol regulated ferroptosis, mitochondrial dysfunction and cell viability via Nrf2/HO-1/NQO1 signaling pathway in ovarian cancer.

Analysis and evaluation of different sequencing depths from 5 to 20 million reads in shotgun metagenomic sequencing, with optimal minimum depth being recommended.

Our study was to analyze and evaluate the impact of different shotgun metagenomic sequencing depths from 5 to 20 million in metagenome-wide association studies (MWASs), and to determine the optimal minimum sequencing depth. We included a set of 200 previously published gut microbial shotgun metagenomic sequencing data on obesity (100 obese vs. 100 non-obese). The reads with original sequencing depths >20 million were downsized into seven experimental groups with depths from 5 to 20 million (interval 2.5 million). Using both integrated gene cluster (IGC) and metagenomic phylogenetic analysis 2 (MetaPhlAn2), we obtained and analyzed the read matching rates, gene count, species richness and abundance, diversity, and clinical biomarkers of the experimental groups with the original depth as the control group. An additional set of 100 published data from a colorectal cancer (CRC) study was included for validation (50 CRC vs. 50 CRC-free). Our results showed that more genes and species were identified following the increase in sequencing depths. When it reached 15 million or higher, the species richness became more stable with changing rate of 5% or lower, and the species composition more stable with ICC intraclass correlation coefficient (ICC) higher than 0.75. In terms of species abundance, 81% and 97% of species showed significant differences in IGC and MetaPhlAn2 among all groups with p < 0.05. Diversity showed significant differences across all groups, with decreasing differences of diversity between the experimental and the control groups following the increase in sequencing depth. The area under a receiver operating characteristic curve, AUC, of the obesity classifier for running the obesity testing samples showed an increasing trend following the increase in sequencing depth (τ = 0.29). The validation results were consistent with the above results. Our study found that the higher the sequencing depth is, the more the microbial information in structure and composition it provides. We also found that when sequencing depth was 15 million or higher, we obtained more stable species compositions and disease classifiers with good performance. Therefore, we recommend 15 million as the optimal minimum sequencing depth for an MWAS.

Tumor necrosis factor-stimulated gene-6-a new serum identification marker to identify severe and symptomatic carotid artery stenosis.

BACKGROUND: The main pathological change causing carotid artery stenosis is atherosclerosis, and studies suggest that tumor necrosis factor-stimulated gene-6 (TSG-6) has an anti-atherogenic effect and may be a new target for the diagnosis of carotid artery stenosis disease. We hypothesized that serum TSG-6 levels might also be associated with carotid artery stenosis. The aim of this study was to evaluate the diagnostic significance and potential predictive value of serum TSG-6 levels in patients with severe carotid artery stenosis and symptomatic stenosis. METHODS: Serum TSG-6 levels were measured in 96 patients with carotid stenosis and 40 sex and age matched control healthy subjects. The expression of TSG-6 in carotid plaques (4 severe stenoses, 4 moderate stenoses, and 4 mild stenoses) and 4 superficial temporal artery vascular tissues of 12 patients with carotid stenosis who underwent endarterectomy at our hospital were detected by Western blot. Histological analysis of carotid plaque and superficial temporal artery tissues was also performed. RESULTS: Compared with controls, serum TSG-6 levels were higher in patients with carotid stenosis, TSG-6 expression was increased in tissues with moderate and severe stenosis, and TSG-6 expression was significantly higher in the fibrous cap component of the plaque than in the non-fibrous cap component. Serum TSG-6 levels were higher in patients with symptomatic stenosis than in patients with asymptomatic stenosis. Tissue TSG-6 staining levels and serum TSG-6 levels were positively correlated (r = 0.694, p < 0.05) and tissue TSG-6 staining levels were positively correlated with macrophage staining levels (r = 0.932, p < 0.05). Logistic regression analysis showed that serum TSG-6 was an independent factor for the presence of severe carotid stenosis and symptomatic stenosis in patients (p < 0.001). Serum TSG-6 levels were more diagnostically efficient than other indices in identifying severe and symptomatic carotid stenosis (p < 0.05), especially in identifying symptomatic stenosis (p < 0.01). We further significantly increased the diagnostic power of symptomatic stenosis using a combined model of serum TSG-6 and homocysteine (p < 0.05). CONCLUSIONS: Serum TSG-6 may serve as a new non-invasive and easily measured biomarker to better screen people with severe and symptomatic carotid stenosis in clinical practice.

Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox.

Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular calcification often occurs with osteoporosis, a contradictory association called "calcification paradox". Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861.

Pre-operative predictive factors of residual varus on the mechanical axis after Oxford unicompartmental knee arthroplasty.

Background: Residual varus after Oxford unicompartmental knee arthroplasty (UKA) happens frequently. This study aims to evaluate the pre-operative contributing factors of residual varus. Methods: A total of 1,002 knees (880 patients, 201 patients were male, and 679 were female) underwent Oxford UKA in the Orthopedic Surgery Department of the Beijing Jishuitan Hospital from March 2018 to April 2021. The mean age of the patient was 64.7 ± 7.7 years. To assess residual varus, the full-length lower extremity is placed upright for EOS imaging, with the knee fully extended. The angle of post-operative residual varus was measured as described by Noyes et al. Of the knees studied, they were either categorized into an under-corrected group (post-operative Noyes angle >5°) or a corrected group (post-operative Noyes angle ≤5°). Age, gender, body mass index (BMI), range of motion (ROM), Clinical American Knee Society Score (Clinical AKSS), and Function American Knee Society Score (Function AKSS) were compared. The following additional parameters were measured: pre-operative Noyes angle, lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), the posterior slope of the proximal tibia angle (PPTA), joint line converge angle (JLCA), and fixed flexion deformity (FFD). Results: There was no statistically significant difference between the two groups in regards to gender (p = 0.428), surgical leg (p = 0.937), age (p = 0.851), BMI (p = 0.064), pre-operative Clinical AKSS (p = 0.206) and Function AKSS (p = 0.100). However, pre-operative ROM statistically differed between the two groups (p < 0.001). The contributing factors of post-operative residual varus were determined to be the following parameters: pre-operative MPTA (p < 0.001, OR = 4.522, 95% CI: 2.927-6.984), pre-operative Noyes (p < 0.001, OR = 3.262, 95% CI: 1.802-5.907) and pre-operative FFD (p = 0.007, OR = 1.862, 95% CI: 1.182-2.934). The effects of pre-operative LDFA (p = 0.146), JLCA (p = 0.942), and pre-operative PPTA (p = 0.899) on the post-operative mechanical axis did not show statistical significance. Conclusions: Patients with severe pre-operative varus, particularly varus deformity mainly from the tibial side or pre-operative FFD, are more prone to get extremity mechanical axis residual varus after UKA with Oxford.

Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway.

BACKGROUND: Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients. METHODS: In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital. RESULTS: Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. CONCLUSION: Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.

Induced Pluripotent Stem Cells Attenuate Acute Lung Injury Induced by Ischemia Reperfusion via Suppressing the High Mobility Group Box-1.

Pulmonary endothelial cell injury is a hallmark of acute lung injury. High-mobility group box 1 (HMGB1) can modulate the inflammatory response via endothelial cell activation and release of inflammatory molecules. Thus, we tested whether induced pluripotent stem cells (iPSCs) can alleviate ischemia/reperfusion (I/R) induced lung injury, and, if so, whether HMGB1 mediates the effect in a male C57BL/6 mouse model. Intravenously injected iPSCs into mice 2 h after I/R showed a significant attenuation of lung injury (assessed by lung mechanics, edema, and histology) 24 h after reperfusion (compared with controls), along with decreases in HMGB1, phosphorylated nuclear factor-κB, inflammatory cytokines [interleukin (IL)1ß, IL6 and tumor necrosis factor-α], and the activation of endothelial cells. Furthermore, these effects of iPSCs can be mimicked by blocking HMGB1 with an inhibitor in vivo and in vitro. We conclude that iPSCs can be a potential therapy for I/R-induced lung injury. These cells may exert therapeutic effects through blocking HMGB1 and inflammatory cytokines.

Diminished expression of major histocompatibility complex facilitates the use of human induced pluripotent stem cells in monkey.

BACKGROUND: Stem cells, including induced pluripotent stem cells (iPSCs), have tremendous potential in health care, though with several significant limitations. Each of the limitations, including immunogenicity, may block most of the therapeutic potentials. Beta2 microglobulin (B2M) and MHC II transactivator (CIITA) are critical for MHC I and II, respectively. MHCs are responsible for immunogenic recognition. METHODS: B2M and CIITA were knocked out from human iPSCs, either separately or simultaneously. The effects of single or dual knockout of B2M and CIITA on iPSC properties were evaluated in a xenogeneic model of human-to-monkey transplantation. RESULTS: B2M or CIITA knockout in human induced pluripotent stem cells (iPSCs) diminishes the expression of MHC I or II alleles, respectively, without changing iPSC pluripotency. Dual knockout was better than either single knockout in preserving the ability of human iPSCs to reduce infiltration of T and B lymphocytes, survive, and promote wound healing in monkey wound lesions. The knockouts did not affect the xenogeneic iPSC-induced infiltration of macrophages and natural killer cells. They, however, decreased the iPSC-promoted proliferation of allogeneic peripheral blood mononuclear cells and T lymphocytes in vitro, although not so for B lymphocytes isolated from healthy human donors. Although the dual knockout cells survived long enough for suiting therapeutic needs, the cells eventually died, possibly due to innate immune response against them, thereby eliminating long-term risks. CONCLUSIONS: Having these iPSCs with diminished immunogenicity-recognizable to allogeneic recipient may provide unlimited reproducible, universal, standardized "ready-to-use" iPSCs and relevant derivatives for clinical applications.

RSK4: a new prognostic factor in glioma.

Glioma is the most common and fatal brain tumour and has a poor prognosis. Ribosomal S6 protein kinase 4 (RSK4) has been found to be involved in multiple tumour types; however, the role of RSK4 in gliomas and its clinical relevance remain unclear. In the present study, RSK4 expression was found to be significantly increased in glioma tissues compared with matched adjunct non-noncancerous tissues. Moreover, the expression of RSK4 was significantly higher in high-grade (III and IV) glioma tissues than in low-grade (I and II) glioma tissues. The data showed that the expression of RSK4 was significantly correlated with WHO grade, three-year survival rate and five-year survival rate. Kaplan-Meier analyses showed that patients with high RSK4 expression had poor overall survival. In addition, multivariate Cox regression analysis showed that RSK4 might be an independent prognostic factor in glioma patients. Collectively, these results suggest that RSK4 may be a new prognostic factor in glioma patients, and RSK4 is expected to be a potential biomarker and a potential target for glioma therapy.