Prediction of lymph node metastasis in T1 colorectal cancer based on combination of body composition and vascular invasion.

OBJECTIVES: Lymph node metastasis (LNM) in colorectal cancer (CRC) patients is not only associated with the tumor's local pathological characteristics but also with systemic factors. This study aims to assess the feasibility of using body composition and pathological features to predict LNM in early stage colorectal cancer (eCRC) patients. METHODS: A total of 192 patients with T1 CRC who underwent CT scans and surgical resection were retrospectively included in the study. The cross-sectional areas of skeletal muscle, subcutaneous fat, and visceral fat at the L3 vertebral body level in CT scans were measured using Image J software. Logistic regression analysis were conducted to identify the risk factors for LNM. The predictive accuracy and discriminative ability of the indicators were evaluated using receiver operating characteristic (ROC) curves. Delong test was applied to compare area under different ROC curves. RESULTS: LNM was observed in 32 out of 192 (16.7%) patients with eCRC. Multivariate analysis revealed that the ratio of skeletal muscle area to visceral fat area (SMA/VFA) (OR = 0.021, p = 0.007) and pathological indicators of vascular invasion (OR = 4.074, p = 0.020) were independent risk factors for LNM in eCRC patients. The AUROC for SMA/VFA was determined to be 0.740 (p < 0.001), while for vascular invasion, it was 0.641 (p = 0.012). Integrating both factors into a proposed predictive model resulted in an AUROC of 0.789 (p < 0.001), indicating a substantial improvement in predictive performance compared to relying on a single pathological indicator. CONCLUSION: The combination of the SMA/VFA ratio and vascular invasion provides better prediction of LNM in eCRC.

DDB2 promotes melanoma cell growth by transcriptionally regulating the expression of KMT2A and predicts a poor prognosis.

Identification of potential key targets of melanoma, a fatal skin malignancy, is critical to the development of new cancer therapies. Lysine methyltransferase 2A (KMT2A) promotes melanoma growth by activating the human telomerase reverse transcriptase (hTERT) signaling pathway; however, the exact mechanism remains elusive. This study aimed to reveal new molecular targets that regulate KMT2A expression and melanoma growth. Using biotin-streptavidin-agarose pull-down and proteomics, we identified Damage-specific DNA-binding protein 2 (DDB2) as a KMT2A promoter-binding protein in melanoma cells and validated its role as a regulator of KMT2A/hTERT signaling. DDB2 knockdown inhibited the expression of KMT2A and hTERT and inhibited the growth of melanoma cells in vitro. Conversely, overexpression of DDB2 activated the expression of KMT2A and promoted the growth of melanoma cells. Additionally, we demonstrated that DDB2 expression was higher in tumor tissues of patients with melanoma than in corresponding normal tissues and was positively correlated with KMT2A expression. Kaplan-Meier analysis showed a poor prognosis in patients with high levels of DDB2 and KMT2A. Overall, our data suggest that DDB2 promotes melanoma cell growth through the transcriptional regulation of KMT2A expression and predicts poor prognosis. Therefore, targeting DDB2 may regulate the effects of KMT2A on melanoma growth and progression, providing a new potential therapeutic strategy for melanoma.

Establishment and validation of a multivariate logistic model for risk factors of thyroid nodules using lasso regression screening.

Objective: This study aims to analyze the association between the occurrence of thyroid nodules and various factors and to establish a risk factor model for thyroid nodules. Methods: The study population was divided into two groups: a group with thyroid nodules and a group without thyroid nodules. Regression with the least absolute shrinkage and selection operator (Lasso) was applied to the complete dataset for variable selection. Binary logistic regression was used to analyze the relationship between various influencing factors and the prevalence of thyroid nodules. Results: Based on the screening results of Lasso regression and the subsequent establishment of the Binary Logistic Regression Model on the training dataset, it was found that advanced age (OR=1.046, 95% CI: 1.033-1.060), females (OR = 1.709, 95% CI: 1.342-2.181), overweight individuals (OR = 1.546, 95% CI: 1.165-2.058), individuals with impaired fasting glucose (OR = 1.590, 95% CI: 1.193-2.122), and those with dyslipidemia (OR = 1.588, 95% CI: 1.197-2.112) were potential risk factors for thyroid nodule disease (p<0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve for the Binary Logistic Regression Model is 0.68 (95% CI: 0.64-0.72). Conclusions: advanced age, females, overweight individuals, those with impaired fasting glucose, and individuals with dyslipidemia are potential risk factors for thyroid nodule disease.

[Applicability of H2FPEF and HFA-PEFF Scores in Chinese Patients Suffering From Heart Failure With Preserved Ejection Fraction and Heart Failure With Preserved Ejection Fraction Complicated With Atrial Fibrillation].

Objective To analyze the diagnostic values of H2FPEF and HFA-PEFF scores for heart failure with preserved ejection fraction (HFpEF) and HFpEF complicated with atrial fibrillation (HFpEF-AF) in Chinese patients and explore the related factors. Methods A cross-sectional study was conducted.A total of 835 consecutive HFpEF patients treated in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from 2009 to 2020 were selected and assigned to a HFpEF-AF group (n=267) and a HFpEF group (n=568) according to the presence of AF or not.HFA-PEFF and H2FPEF scores were used for retrospective diagnosis and the diagnostic consistency of the two scores was assessed.One hundred and thirty-six healthy volunteers with age and sex matching the patients during the same period were selected as healthy controls.The receiver operating characteristic (ROC) curves were established for H2FPEF and HFA-PEFF scores in diagnosing HFpEF-AF and HFpEF,on the basis of which the diagnostic performance of the two scores was evaluated. Results There was no difference in the HFA-PEFF score between the two groups (P=0.070).However,the HFpEF-AF group had higher mean H2FPEF score and higher proportion of patients with the score no less than 6 than the HFpEF group (P<0.001).According to the ROC curves,HFA-PEFF and H2FPEF scores demonstrated high performance in diagnosing all HFpEF patients,with the area under the curve (AUC) of 0.892 and 0.922 and the optimal cut-offs of 4 and 4,respectively.The HFA-PEFF score showed similar performance in diagnosing HFpEF and HFpEF-AF,with the AUC of 0.899 and 0.911,respectively.The H2FPEF score had higher performance in diagnosing HFpEF-AF (AUC of approximately 1.000) and low performance in diagnosing HFpEF (AUC of 0.885). Conclusions The HFA-PEFF score is applicable in the diagnosis of both HFpEF and HFpEF-AF.The H2FPEF score may underestimate HFpEF in Chinese patients,and its applicability in the Chinese patients with HFpEF alone remains to be investigated.

Preoperative controlling nutritional status as an optimal prognostic nutritional index to predict the outcome for colorectal cancer.

BACKGROUND: The controlling nutritional status (CONUT) score effectively reflects a patient's nutritional status, which is closely related to cancer prognosis. This study investigated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer, and compared the predictive ability of the CONUT score with other indexes. AIM: To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection. METHODS: This retrospective analysis included 217 patients with newly diagnosed colorectal. The CONUT score was calculated based on the serum albumin level, total lymphocyte count, and total cholesterol level. The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve. The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: Using the cutoff value of the CONUT score, patients were stratified into CONUT low (n = 189) and CONUT high groups (n = 28). The CONUT high group had worse overall survival (OS) (P = 0.013) and relapse-free survival (RFS) (P = 0.015). The predictive performance of CONUT was superior to the modified Glasgow prognostic score, the prognostic nutritional index, and the neutrophil-to-lymphocyte ratio. Meanwhile, the predictive performances of CONUT + tumor node metastasis (TNM) stage for 3-year OS [area under the receiver operating characteristics curve (AUC) = 0.803] and 3-year RFS (AUC = 0.752) were no less than skeletal muscle mass index (SMI) + TNM stage. The CONUT score was negatively correlated with SMI (P < 0.01). CONCLUSION: As a nutritional indicator, the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer, and its predictive ability was superior to other indexes. The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.

Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis.

Background: Hashimoto thyroiditis (HT), a prevalent autoimmune disorder, is not yet thoroughly understood, especially when it comes to the influence of epigenetics in its pathogenesis. The primary goal of this research was to probe the DNAm profile across the genome in the whole blood derived from patients suffering from HT. Method: Using the Illumina 850K BeadChip, we conducted a genome-wide DNAm assessment on 10 matched pairs of HT sufferers and healthy individuals. Genes with differential methylation (DMGs) were identified and underwent functional annotation via the databases of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The transcriptional significance of potential epigenetic biomarker genes was corroborated through qRT-PCR. Results: The DNAm profiling across the genome indicated an overall reduction in methylation in HT subjects in comparison with their healthy counterparts. We detected 283 DMPs (adjusted P < 0.05 and |Δß| > 0.1), among which 152 exhibited hypomethylation and 131 demonstrated hypermethylation. Further analysis exposed a noteworthy concentration of hypermethylated DMPs in the 3´UTR, North Shore, and CpG islands, while there was a significant decrease in the Open Sea (all P < 0.001). The 283 DMPs were broadly distributed from chromosome 1 to 22, with chromosome 6 harboring the most DMPs (n = 51) and chromosome 12 carrying the most DMGs (n = 15). The SLFN12 gene, which presented with extreme hypomethylation in its promoter DMPs among HT patients, was identified as the epigenetic marker gene. Consequently, the SLFN12 mRNA expression was markedly upregulated in HT, displaying a negative relationship with its methylation levels. The area under curve (AUC) value for the SLFN12 gene among HT patients was 0.85 (sensitivity: 0.7, specificity: 0.7), a significant difference compared with healthy controls. The methylation levels of all DMPs in SLFN12 gene were negatively correlated with TSH and one CpG site (cg24470734) was positively assocciated with FT4. Conclusion: This investigation presents an initial comprehensive DNAm blueprint for individuals with HT, which permits clear differentiation between HT subjects and normal controls through an epigenetic lens. The SLFN12 gene plays a pivotal role in the onset of HT, suggesting that the methylation status of this gene could serve as a potential epigenetic indicator for HT.

Upregulation of FAM83F by c-Myc promotes cervical cancer growth and aerobic glycolysis via Wnt/ß-catenin signaling activation.

Cervical cancer (CC) seriously affects women's health. Therefore, elucidation of the exact mechanisms and identification of novel therapeutic targets are urgently needed. In this study, we identified FAM83F, which was highly expressed in CC cells and tissues, as a potential target. Our clinical data revealed that FAM83F protein expression was markedly elevated in CC tissues and was positively correlated with poor prognosis. Moreover, we observed that FAM83F knockdown significantly inhibited cell proliferation, induced apoptosis, and suppressed glycolysis in CC cells, while its overexpression displayed opposite effects. Mechanistically, FAM83F regulated CC cell growth and glycolysis by the modulation of Wnt/ß-catenin pathway. The enhancing effects of FAM83F overexpression on CC cell proliferation and glycolysis could be impaired by the Wnt/ß-catenin inhibitor XAV939. Moreover, we found that c-Myc bound to the FAM83F promoter and activated the transcription of FAM83F. Notably, knockdown of FAM83F impaired the enhancement of cell proliferation and glycolysis induced by ectopic c-Myc. Consistent with in vitro findings, results from a xenograft mouse model confirmed the promoting role of FAM83F. In summary, our study demonstrated that FAM83F promoted CC growth and glycolysis through regulating the Wnt/ß-catenin pathway, suggesting that FAM83F may be a potential molecular target for CC treatment. Schematic summary of c-Myc-activated FAM83F transcription to promote cervical cancer growth and glycolysis by targeting the Wnt/ß-catenin signal pathway.

Jagged1 contained in MSC-derived small extracellular vesicles promotes squamous differentiation of cervical cancer by activating NOTCH pathway.

PURPOSE: Cervical cancer is the fourth most common cancer in women and poses a major threat to women's health, urgently requiring new treatment methods. METHODS: This study first successfully extracted and identified small extracellular vesicles secreted by human umbilical cord-derived mesenchymal stem cells. We studied the effects of MSC-sEV on the squamous differentiation levels of cervical cancer CaSki cells in vitro, and explored the effects of MSC-sEV on the NOTCH pathway, the growth, proliferation, migration abilities and squamous differentiation levels of cervical cancer cells. The roles of MSC-sEV were also verified in human keratinocyte HaCaT cells. RESULTS: The results showed that Jagged1 protein on MSC-sEV can bind to NOTCH1 on cervical cancer cells, activate NOTCH signaling, and promote squamous differentiation levels in CaSki cells, thus inhibiting the growth, proliferation and migration abilities of CaSki cells. MSC-sEV can also activate the NOTCH pathway in HaCaT cells, but promote the viability of HaCaT cells. CONCLUSION: MSC-sEV can activate the NOTCH pathway to promote squamous differentiation of CaSki cells and inhibit the growth proliferation and migration abilities of CaSki cells which may be a new mechanism for cervical cancer treatment.

Relationship Between Gestational Diabetes Mellitus and Postpartum Diastasis Recti Abdominis in Women in the First Year Postdelivery.

OBJECTIVE: Postpartum diastasis recti abdominis (DRA) influences women's appearance and health. Gestational diabetes mellitus (GDM) can affect the structure of the rectus abdominis muscles. However, the relationship between GDM and postpartum DRA is unknown. The objective of this study was to investigate the relationship between GDM and postpartum DRA. METHODS: This retrospective cohort study included 241 women in the first year postdelivery. Women with GDM were matched with those without GDM using propensity score matching. They underwent an oral glucose tolerance test during pregnancy and a random blood glucose test before delivery. At follow-up, DRA was diagnosed by palpation, and interrectus distance was measured using ultrasound to evaluate the severity of DRA. The strength of the rectus abdominis was evaluated using the manual muscle testing method. RESULTS: Among the 241 participants, 174 (72.2%) had postpartum DRA, and 46 women with GDM were matched with 46 women without GDM on the basis of propensity scores. Women with GDM had higher odds of experiencing postpartum DRA (adjusted odds ratio = 4.792; 95% CI = 1.672 to 13.736) and larger interrectus distance values at the upper part of the rectus abdominis than those without GDM. There was a weak and positive correlation between the fasting oral glucose tolerance test level and the interrectus distance values (0.267 ≤ r ≤ 0.367). CONCLUSION: GDM was associated with postpartum DRA in women in the first year of delivery. Women with GDM had larger interrectus distance values at the upper part of the rectus abdominis than those without GDM. The fasting oral glucose tolerance test level showed a positive and weak correlation with the severity of postpartum DRA. IMPACT: Women with GDM have higher odds of experiencing postpartum DRA than those without GDM. The upper part of the rectus abdominis deserves increased focus during and after rehabilitation. Controlling the fasting oral glucose tolerance test level may help reduce the severity of postpartum DRA.

A study of programmed death-1/programmed death ligand and iodine-induced autoimmune thyroiditis in NOD.H-2h4 mice.

Excess iodine will trigger the occurrence of autoimmune thyroiditis (AIT), and programmed death-1 (PD-1)/programmed death ligand (PD-L) will also contribute to the development of AIT. The purpose of this study was to explore the role that negative regulatory signals mediated by PD-1/PD-L play in the development of spontaneous autoimmune thyroiditis (SAT) in NOD.H-2h4 mice when they are exposed to iodine. Programmed death ligand 1 (PD-L1) antibody was administered intraperitoneally to NOD.H-2h4 mice. The relevant indicators were determined by flow cytometry, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry, pathological hematoxylin and eosin staining, and arsenic-cerium catalytic spectrophotometry. Results showed that the level of urinary iodine, the level of thyroid lymphocyte infiltration, the level of thyroglobulin antibodies (TgAb) and interferon (IFN-γ)/tumor necrosis factor (TNF-α)/interleukin (IL-2)/IL-17, and the relative expression of PD-1/PD-L1/programmed death-2 (PD-L2) increased with the intervention of excess iodine. After the intervention of the PD-L1 antibody, the expression of PD-1/PD-L1/PD-L2 in different degrees was inhibited, but the level of thyroid lymphocyte infiltration and serum TgAb/IFN-γ/TNF-α/ IL-2/IL-17 did not decrease. Collectively, although PD-1/PD-L participates in the occurrence of SAT and induces inflammation, administration of the PD-L1 antibody does not effectively improve the pathological process of SAT. More research is needed to determine whether PD-1/PD-L intervention can treat autoimmune thyroid disease.

Distribution of iodine concentration in drinking water in China mainland and influence factors of its variation.

OBJECTIVE: To identify the current spatial distribution of iodine concentration in drinking water (dWIC) at the township-level across China and its influencing factors through visualization and spatial statistical analysis by the geographic information system. METHODS: The dWIC for each township was used to describe the distribution by ArcGIS 10.7. The spatial aggregation characteristics were analyzed by spatial auto-correlation analysis. The inverse distance weight method was used to predict the dWIC at nonsampling sites. The correlation between the dWIC and the distance from each township to the Yellow River as well as the depth of tube wells were analyzed by ordinary least squares and geographically weighted regression, respectively. RESULTS: A total of 37,541 townships were included in this study. dWIC ranged from 0 to 1113.7 µg/L, and the median was 3.3 µg/L. There were 35,606 townships < 40 µg/L (94.85 % of surveyed townships), 40 µg/L ≤ 1015 townships ≤100 µg/L (2.70 % of surveyed townships), and 920 townships > 100 µg/L (2.45 % of surveyed townships). The results were statistically significant of global autocorrelation analysis (Moran's I = 0.43, Z = 922.15, P < 0.01). Local Moran's I showed that 3128 townships (8.33 % of surveyed townships) belong to H-H cluster areas. The dWIC was partially negatively correlated with the distance from each township to the Yellow River, as well as positively correlated with the depth of tube wells in partial areas. CONCLUSIONS: The dWIC varied widely across mainland China (from 0 µg/L to 1113.7 µg/L). 94.85 % of surveyed townships were below 40 µg/L and 2.45 % of surveyed townships were exceeding 100 µg/L. Moreover, the distance from each township to the Yellow River may be one of the geneses of iodine-excess areas. Finally, this study has provided a visible reference of dWIC for the precise control strategy and focused monitoring in China.

Effects of different iodine levels on the DNA methylation of intrinsic apoptosis-associated genes and analysis of gene-environment interactions in patients with autoimmune thyroiditis.

Iodine is an essential nutrient that may change the occurrence of autoimmune thyroiditis (AIT). Apoptosis and DNA methylation participate in the pathogenesis and destructive mechanism of AIT. We detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG, ING4, BRSK2 and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine. 176 adult patients with AIT in Shandong Province, China, were included. The MethylTargetTM assay was used to verify the levels of methylation. We used PCR to detect the mRNA levels of the candidate genes. Interactions between methylation levels of the candidate genes and iodine levels were evaluated with multiplicative and addictive interaction models and GMDR. In the AIT group, YWHAG_1 and six CpG sites and BRSK2_1 and eight CpG sites were hypermethylated, whereas ING4_1 and one CpG site were hypomethylated. A negative correlation was found between methylation levels of YWHAG and mRNA expression. The combination of iodine fortification, YWHAG_1 hypermethylation and BRSK2_1 hypermethylation was significantly associated with elevated AIT risk. A four-locus model (YWHAG_1 × ING4_1 × BRSK2_1 × iodine level) was found to be the best model of the gene-environment interactions. We identified abnormal changes in the methylation status of YWHAG, ING4 and BRSK2 in patients with AIT in different iodine levels. Iodine fortification not only affected the methylation levels of YWHAG and BRSK2 but also interacted with the methylation levels of these genes and may ultimately increase the risk of AIT.

Gastric microbiota: an emerging player in gastric cancer.

Gastric cancer (GC) is a common cancer worldwide with a high mortality rate. Many microbial factors influence GC, of which the most widely accepted one is Helicobacter pylori (H. pylori) infection. H. pylori causes inflammation, immune reactions and activation of multiple signaling pathways, leading to acid deficiency, epithelial atrophy, dysplasia and ultimately GC. It has been proved that complex microbial populations exist in the human stomach. H. pylori can affect the abundance and diversity of other bacteria. The interactions among gastric microbiota are collectively implicated in the onset of GC. Certain intervention strategies may regulate gastric homeostasis and mitigate gastric disorders. Probiotics, dietary fiber, and microbiota transplantation can potentially restore healthy microbiota. In this review, we elucidate the specific role of the gastric microbiota in GC and hope these data can facilitate the development of effective prevention and therapeutic approaches for GC.

Alteration of Lipid Profile Between Subclinical Hypothyroidism and Well-Matched Controls: A Meta-Analysis.

In previous studies, subclinical hypothyroidism (SCH) has been associated with altered lipid profiles. However, since the discrepancy between these study results may reside in the great heterogeneity of the populations studied, this relationship is controversial. This study aimed to explore the changes in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) between subclinical hypothyroidism (SCH) and well-matched euthyroid (EU) groups. Multiple databases were searched for publications before December 1, 2021, including cross-sectional studies on the association between SCH and lipid profile matched by age, gender, and BMI. Twenty-five articles with 3347 participants were included for meta-analysis. The results showed that the TC, TG, and LDL-c levels of the SCH groups were higher than the EU groups (TC, SMD=0.49, 95% CI 0.27, 0.71, p<0.001) (TG, SMD=0.43, 95% CI 0.21, 0.64, p<0.05 ) (LDL-c, SMD=0.75, 95% CI 0.46, 1.03, p<0.001 ). The HDL-c levels of the SCH group were lower than the control group (SMD=-0.53, 95% CI -0.81, -0.25, p<0.05). SCH has a larger impact on LDL-c than the other three indicators. After subgroup analyses, there was a larger impact on lipid alteration in the subgroup of TSH>10 µIU/ml, especially on LDL-c. This study found that SCH was associated with altered lipid profiles. Appropriate clinical treatment may be needed to prevent dyslipidemia and related diseases.

Serum thyroglobulin as a biomarker of iodine excess and thyroid disease occurrence in adults.

BACKGROUND: Thyroglobulin (Tg) is considered a sensitive indicator of iodine deficiency. However, the usefulness of Tg as a biomarker of excess iodine is uncertain. The present study aimed to determine the influence of different iodine intake on serum Tg levels, evaluate the influence of thyroid diseases on the distribution of Tg, and identify the factors that may affect Tg levels. METHODS: A cross-sectional survey with a total of 1208 adults was conducted in different water iodine areas in China. Urinary iodine concentration (UIC), water iodine concentration (WIC), serum Tg, thyroid-stimulating hormone (TSH), and thyroid antibodies were measured. The thyroid volumes and nodules were measured by B-scan ultrasound. RESULTS: Based on the WIC data, subjects were divided into three groups. Based on the median urinary iodine concentration (MUIC) data, the iodine levels were adequate, more than adequate, and excess for the WIC < 10 µg/L group, 10 µg/L ≤ WIC ≤ 100 µg/L g, and WIC > 100 µg/L groups, respectively. The median Tg was significantly higher in the excess iodine group than in the adequate iodine group and the more than adequate iodine group (14.6 µg/L vs.12.7 µg/L, P = 0.042; 14.6 µg/L vs.12.5 µg/L, P = 0.004). Multiple linear regression analysis showed that excess iodine intake, goitre, thyroid nodules, and hypothyroidism were significantly related to higher serum Tg levels. CONCLUSION: Serum Tg level can be a promising biomarker of excessive iodine intake, but other factors, especially the presence of thyroid disease, should be considered when using this parameter.

Human umbilical cord mesenchymal stem cells derived extracellular vesicles alleviate salpingitis by promoting M1-to-M2 transformation.

Background: With an increasing number of patients experiencing infertility due to chronic salpingitis after Chlamydia trachomatis (CT) infection, there is an unmet need for tissue repair or regeneration therapies. Treatment with human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EV) provides an attractive cell-free therapeutic approach. Methods: In this study, we investigated the alleviating effect of hucMSC-EV on tubal inflammatory infertility caused by CT using in vivo animal experiments. Furthermore, we examined the effect of hucMSC-EV on inducing macrophage polarization to explore the molecular mechanism. Results: Our results showed that tubal inflammatory infertility caused by Chlamydia infection was significantly alleviated in the hucMSC-EV treatment group compared with the control group. Further mechanistic experiments showed that the application of hucMSC-EV induced macrophage polarization from the M1 to the M2 type via the NF-κB signaling pathway, improved the local inflammatory microenvironment of fallopian tubes and inhibited tube inflammation. Conclusion: We conclude that this approach represents a promising cell-free avenue to ameliorate infertility due to chronic salpingitis.

Environment and chronic disease in rural areas of Heilongjiang, China (ECDRAHC).

PURPOSE: Environmental factors such as long-term exposure to cold can increase the risk of chronic diseases. However, few studies have focused on the impact of environmental factors and lifestyle changes on chronic diseases. To fully explore the association between exposure to environmental factors and the prevalent risk of various chronic diseases, we conducted a large cohort study (Environment and Chronic Disease in Rural Areas of Heilongjiang, China (ECDRAHC)). The ECDRAHC collected detailed questionnaire data covering 10 sections, physical measurements and blood and urine samples. In this study, we describe the design and implementation of the cohort study and present the findings for the first 10 000 participants. PARTICIPANTS: The ECDRAHC study was carried out in rural areas where the annual average temperature is 2.9°C, and aimed to recruit 40 000 participants who are long-term residents aged 35-74 years. The participants will be followed up every 5 years. Currently, ECDRAHC has reached 26.7% (n=10 694) of the targeted population. FINDINGS TO DATE: A total of 10 694 adults aged 35-74 years were recruited, including 61.7% women. The prevalence of current smokers was 46.8% in men and 35.4% in women. The mean blood pressure was 140.2/89.9 mm Hg and 135.7/85.0 mm Hg in men and women, respectively. The mean body mass index was 24.74 kg/m2 in men and 24.65 kg/m2 in women, with >7.3% being obese (>30 kg/m2). The main non-communicable diseases found in phase 1 were hypertension, diabetes, hypertriglyceridaemia and metabolic syndrome, with a higher prevalence of 51.0%, 21.6%, 46.8% and 42.6%, respectively. FUTURE PLANS: We plan to complete the follow-up for the first phase of the ECDRAHC in 2024. The second and third phase of the cohort will be carried out steadily, as planned. This cohort will be used to investigate the relationship between environmental factors, lifestyle, and genetic and common chronic diseases.

Ultra-dense plasmonic nanogap arrays for reorientable molecular fluorescence enhancement and spectrum reshaping.

Understanding interactions between molecular transition and intense electromagnetic fields confined by plasmon nanostructures is of great significance due to their huge potential in fundamental cavity quantum electrodynamics and practical applications. Here, we report reorientable plasmon-enhanced fluorescence leveraging the flexibilities in densely-packed gold nanogap arrays by template-assisted depositions. By finely adjusting the symmetry of the unit structure, arrays of nanogaps along two nearly-orthogonal axes can be tailored collectively with spacing down to sub-10 nm on a single chip, facilitating distinct "inter-cell" and "intra-cell" plasmon couplings. Through engineering two sets of nanogaps, the varying hybridization-induced plasmonic bonding modes lead to adjustable splitting of the fluorescence emission peak with a width up to 81 nm and narrowing of linewidths up to a factor of 3. Besides, polarization anisotropy with a ratio up to 63% is obtained on the basis of spectrally separated local hotspots with discrepant oscillation directions. The developed plasmonic nanogap array is envisaged to provide a promising chip-scale, cost-effective platform for advancing fluorescence-based detection and emission technologies in both classical and quantum regimes.

The effect and mechanism of excessive iodine on the endothelial function of human umbilical vein endothelial cells.

Iodine excess (IE) can cause thyroid dysfunction, thyroid diseases can adversely affect cardiovascular function. Accordingly, this study was to explore the direct and indirect effects of IE on endothelial function. Nthy-ori 3-1 and HUVECs cells were treated with potassium iodide (KI). CCK-8, LDH leakage, Elisa, RT-PCR and Western blotting were used to detect relevant indicators. Results showed that a certain level of KI can directly and indirectly reduce the viability of HUVECs and increase cytotoxicity. KI decreased the expression of ET-1 and VWF in HUVECs, inhibited the secretion of ET-1 in culture medium, and increased the expression of IL-6 and TNFα in HUVECs or Nthy-ori 3-1 cells alone. In the co-culture system, KI decreased the expression of ET-1 and THBD and increased the expression of TNFα and IL-6. Collectively, IE can directly and indirectly inhibit endothelial function of endothelial cells, which may be related to its induced inflammatory response.

Effects of Excessive Iodine on the BDNF-TrkB Signaling Pathway and Related Genes in Offspring of EAT Rats.

Excess iodine can cause autoimmune thyroiditis (AIT) in women, but it is unclear whether this has any implications for neurodevelopmental mechanisms in offspring. We studied the effects of experimental autoimmune thyroiditis (EAT) rats with different amounts of iodine intake on offspring brain development via the brain-derived neurotrophic factor (BDNF)-tropomycin receptor kinase B (TrkB) signaling pathway, because BDNF plays an important role in neurodevelopment. Rats in three thyroglobulin (Tg) immunized groups with varying iodine intakes (Tg (100 µg/L iodine), Tg + High-iodine I group (Tg + HI, 20 mg/L iodine), and Tg + High-iodine II group (Tg + HII, 200 mg/L iodine)) were injected with 800 µg Tg once every 2 weeks for 3 times. Rats in the control group (NI, 100 µg/L iodine) were immunized with saline. Arsenic-cerium catalytic spectrophotometry was used to measure urine iodine levels. The lymphocytic infiltration in the thyroids was observed by histopathological studies. Thyroid autoantibodies levels were measured using radioimmunoassay. The norepinephrine (NE) contents were measured by an enzyme-linked immunosorbent assay. The levels of the BDNF-TrkB signaling pathway and related genes were measured by quantitative real-time PCR and Western blot. Urinary iodine levels increased as iodine intake increased. Lymphocytes were significantly aggravated in Tg-immunized rats. Serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) levels were clearly elevated in Tg-immunized rats. Tg-immune groups had significantly lower NE levels. The BDNF-TrkB signaling pathway and related gene mRNA and protein levels were found to be significantly lower in Tg-immune groups with higher iodine levels. Maternal AIT may reduce the levels of certain neurodevelopmental mechanisms in the offspring, such as the BDNF-TrkB signaling pathway and related factors, while excessive iodine consumption by the mother may exacerbate this effect.