Ratiometric Electrochemiluminescence of Zirconium Metal-Organic Framework as a Single Luminophore for Sensitive Detection of HPV-16 DNA.

This study developed a new zirconium metal-organic framework (MOF) luminophore named Zr-DPA@TCPP with dual-emission electrochemiluminescence (ECL) characteristics at a resolved potential. First, Zr-DPA@TCPP with a core-shell structure was effectively synthesized through the self-assembly of 9,10-di(p-carboxyphenyl)anthracene (DPA) and 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP) as the respective organic ligands and the Zr cluster as the metal node. The reasonable integration of the two organic ligands DPA and TCPP with ECL properties into a single monomer, Zr-DPA@TCPP, successfully exhibited synchronous anodic and cathodic ECL signals. Besides, due to the impressively unique property of ferrocene (Fc), which can quench the anodic ECL but cannot affect the cathodic ECL signal, the ratiometric ECL biosensor was cleverly designed by using the cathode signal as an internal reference. Thus, combined with DNA recycle amplification reactions, the ECL biosensor realized sensitive ratiometric detection of HPV-16 DNA with the linear range of 1 fM-100 pM and the limit of detection (LOD) of 596 aM. The distinctive dual-emission properties of Zr-DPA@TCPP provided a new idea for the development of ECL luminophores and opened up an innovative avenue of fabricating the ratiometric ECL platform.

Coreactant-Free Zirconium Metal-Organic Framework with Dual Emission for Ratiometric Electrochemiluminescence Detection of HIV DNA.

Owing to the limitations of dual-signal luminescent materials and coreactants, constructing a ratiometric electrochemiluminescence (ECL) biosensor based on a single luminophore is a huge challenge. This work developed an excellent zirconium metal-organic framework (MOF) Zr-TBAPY as a single ECL luminophore, which simultaneously exhibited cathodic and anodic ECL without any additional coreactants. First, Zr-TBAPY was successfully prepared by a solvothermal method with 1,3,6,8-tetra(4-carboxyphenyl)pyrene (TBAPY) as the organic ligand and Zr4+ cluster as the metal node. The exploration of ECL mechanisms confirmed that the cathodic ECL of Zr-TBAPY originated from the pathway of reactive oxygen species (ROS) as the cathodic coreactant, which is generated by dissolved oxygen (O2), while the anodic ECL stemmed from the pathway of generated Zr-TBAPY radical itself as the anodic coreactant. Besides, N,N-diethylethylenediamine (DEDA) was developed as a regulator to ECL signals, which quenched the cathodic ECL and enhanced the anodic ECL, and the specific mechanisms of its dual action were also investigated. DEDA can act as the anodic coreactant while consuming the cathodic coreactant ROS. Therefore, the coreactant-free ratiometric ECL biosensor was skillfully constructed by combining the regulatory role of DEDA with the signal amplification reaction of catalytic hairpin assembly (CHA). The ECL biosensor realized the ultrasensitive ratio detection of HIV DNA. The linear range was 1 fM to 100 pM, and the limit of detection (LOD) was as low as 550 aM. The outstanding characteristic of Zr-TBAPY provided new thoughts for the development of ECL materials and developed a new way of fabricating the coreactant-free and single-luminophore ratiometric ECL platform.

3D hUC-MSCs spheroids exhibit superior resistance to autophagy and apoptosis of granulosa cells in POF rat model.

Premature ovarian failure (POF) is a common reproductive disease in women younger than 40 years old, and studies have demonstrated that the application of human umbilical cord mesenchymal stem cells (hUC-MSCs) is a promising therapy strategy for POF. Given the previously established therapeutic advantages of three-dimensional (3D) MSCs spheroids, and to evaluate their effectiveness, both 3D hUC-MSCs spheroids and monolayer-cultured hUC-MSCs were employed to treat cyclophosphamide (CTX)-induced POF rat model through orthotopic transplantation. The effects of these two forms on POF were subsequently assessed by examining apoptosis, autophagy, and oxidative damage in ovarian granulosa cells (GCs). The results indicated that hUC-MSCs spheroids exhibited superior treatment effects on resisting autophagy, apoptosis, and oxidative damage in GCs compared to monolayer-cultured hUC-MSCs. To further elucidate the impact of hUC-MSCs spheroids in vitro, a H2O2-induced KGN cells model was established and co-cultured with both forms of hUC-MSCs. As expected, the hUC-MSCs spheroids also exhibited superior effects in resisting apoptosis and autophagy caused by oxidative damage. Therefore, this study demonstrates that 3D hUC-MSCs spheroids have potential advantages in POF therapy; however, the detailed mechanisms need to be further investigated. Furthermore, this study will provide a reference for the clinical treatment strategy of POF.

Relationship between dietary macronutrients intake and biological aging: a cross-sectional analysis of NHANES data.

PURPOSE: This study aimed to investigate the association between macronutrient intake and biological age. METHODS: Data were collected from 26,381 adults who participated in the United States National Health and Nutrition Examination Survey (NHANES). Two biological ages were estimated using the Klemera-Doubal method (KDM) and PhenoAge algorithms. Biological age acceleration (AA) was computed as the difference between biological age and chronological age. The associations between macronutrient intakes and AA were investigated. RESULTS: After fully adjusting for confounding factors, negative associations were observed between AA and fiber intake (KDM-AA: ß - 0.53, 95% CI - 0.62, - 0.43, P < 0.05; PhenoAge acceleration: ß - 0.30, 95% CI - 0.35, - 0.25, P < 0.05). High-quality carbohydrate intake was associated with decreased AA (KDM-AA: ß - 0.57, 95% CI - 0.67, - 0.47, P < 0.05; PhenoAge acceleration: ß - 0.32, 95% CI - 0.37, - 0.26, P < 0.05), while low-quality carbohydrate was associated with increased AA (KDM-AA: ß 0.30, 95% CI 0.21, 0.38, P < 0.05; PhenoAge acceleration: ß 0.16, 95% CI 0.11, 0.21, P < 0.05). Plant protein was associated with decreased AA (KDM-AA: ß - 0.39, 95% CI - 0.51, - 0.27, P < 0.05; PhenoAge acceleration: ß - 0.21, 95% CI - 0.26, - 0.15, P < 0.05). Long-chain SFA intake increased AA (KDM-AA: ß 0.16, 95% CI 0.08, 0.24, P < 0.05; PhenoAge acceleration: ß 0.11, 95% CI 0.07, 0.15, P < 0.05). ω-3 PUFA was associated with decreased KDM-AA (ß - 0.18, 95% CI - 0.27, - 0.08, P < 0.05) and PhenoAge acceleration (ß - 0.09, 95% CI - 0.13, - 0.04, P < 0.05). CONCLUSION: Our findings suggest that dietary fiber, high-quality carbohydrate, plant protein, and ω-3 PUFA intake may have a protective effect against AA, while low-quality carbohydrate and long-chain SFA intake may increase AA. Therefore, dietary interventions aimed at modifying macronutrient intakes may be useful in preventing or delaying age-related disease and improving overall health.

A novel perspective on di-hexyl phthalate (2-ethylhexyl)-induced reproductive toxicity in females: Lipopolysaccharide synergizes with mono-2-ethylhexyl ester to cause inflammatory apoptosis rather than autophagy in ovarian granulosa cells.

Di-hexyl phthalate (2-ethylhexyl) (DEHP) has been confirmed to cause female reproductive toxicity in humans and model animals by affecting the survival of ovarian granulosa cells (GCs), but the interrelationships between DEHP's on autophagy, apoptosis, and inflammation in GCs are not clear. Our previous study demonstrated that DEHP exposure resulted in the disturbance of intestinal flora associated with serum LPS release, which in turn led to impaired ovarian function. LPS has also been shown to determine cell fate by modulating cellular autophagy, apoptosis, and inflammation. Therefore, this study investigated the role and link between LPS and autophagy, apoptosis, and inflammation of GCs in DEHP-induced ovarian injury. Here, we constructed an in vivo injury model by continuous gavage of 0-1500 mg/kg of DEHP in female mice for 30 days and an in vitro injury model by treatment of human ovarian granulosa cells (KGN) cells with mono-2- ethylhexyl ester (MEHP, an active metabolite of DEHP in vivo). In addition, the expression of relevant pathway molecules was detected by immunohistochemistry, immunofluorescence, qRT-PCR, and Western blotting after the addition of the autophagy inhibitor 3-methyladenine (3-MA), the apoptosis inhibitor Z-VAD- FMK and the NF-κB inhibitor BAY11-7082. The current study found that autophagy and apoptosis were significantly activated in GCs of DEHP-induced atretic follicles in vivo and found that MEHP-induced KGN cells autophagy and apoptosis were independent and potentially cytotoxic of each other in vitro. Further studies confirmed that DEHP exposure resulted in LPS release from the intestinal tract and entering the ovary, thereby participating in DEHP-induced inflammation of GCs. In addition, we found that exogenous LPS synergized with MEHP could activate the NF-κB signaling pathway to induce inflammation and apoptosis of GCs in a relatively prolonged exposure condition. Meanwhile, inhibition of inflammatory activation could rescue apoptosis and estrogen secretion function of GCs induced by MEHP combined with LPS. These results indicated that the increased LPS influenced by DEHP might cooperate with MEHP to induce inflammatory apoptosis of GCs, an important cause of ovarian injury in mice.

Dual-emission Tb-based coordination polymer as a ratiometric fluorescence probe for the detection of phosphate.

A simple, sensitive dual-emission probe was developed for the detection of phosphate (Pi). The probe Tb-BTB/DPA was synthesized by mixing dual-ligand, 1,3,5-tri(4-carboxyphenyl) benzene (H3BTB) and dipicolinic acid (DPA), with metal ions Tb3+ in ethanol-water solution at 40℃ for 2 h. Tb-BTB/DPA exhibits two emission peaks, the emission at 362 nm is attributed to H3BTB, an energy transfer between Tb3+ nodes, and DPA further enhances the fluorescence of Tb3+ at 544 nm. Pi competes with ligand H3BTB to coordinate Tb3+, resulting in partial collapse of the Tb-BTB/DPA structure and interrupting the electron transfer between H3BTB and Tb3+. Therefore, the emission at 362 nm is enhanced, while the emission at 544 nm is unchanged, and a ratiometric fluorescence method is developed to detect Pi. Tb-BTB/DPA exhibits good linearity within the Pi concentration range (0.1-50 µmol/L), and the detection limit was 25.8 nmol/L. This study provides a new way to prepare probes with dual emission sensing properties.

Interaction of physical activity and low-level air pollution on cardiovascular disease: a prospective cohort study in UK Biobank.

To investigate the associations of physical activity (PA), low-level air pollution, and interaction on cardiovascular diseases (CVD) incidence based on the UK Biobank. PA was measured by the International Physical Activity Questionnaire and five air pollutants were estimated using Land Use Regression. All association estimates were based on Cox regression. Dose-response relationship was explored by restricted cubic spline, while multiplicative and additive interaction were examined by Pinteraction and relative excess risk due to interaction (RERI). As deviating proportional hazards assumption, we analyzed data as follow-up < 4 years and ≥ 4 years, separately. PA with 1000-4000 Metabolic Equivalent Task (MET) min/week showed the strongest protective impact on CVD incidence, while only low-level nitrogen dioxides (NO2) showed negative impact among five air pollutants and was considered for further analysis. Multiplicative interaction between PA and NO2 was observed during ≥ 4 years follow-up (Pinteraction = 0.049) while not during < 4 years (Pinteraction = 0.290). Positive additive interactions were found for high PA and low NO2 (< 20 µg/m3) group (RERI: 0.07, 95% confidence intervals: 0.02-0.11) during < 4 years, and for moderate PA with NO2 at 40- µg/m3 (0.07, 0.02-0.13) and < 20 µg/m3 (0.07, 0.02-0.12), while high PA showed similar results with NO2 at 40-, 20- and < 20 µg/m3 during ≥ 4 years. PA about 1000-4000 METs min/week showed the lowest CVD risk. Possibility of interaction with PA and NO2 is more likely to present with the increase in follow-up duration. We call for the optimal thresholds of PA, and exploring interaction thoroughly by considering types of PA.

High-Efficiency Aluminum-Metal Organic Framework/HEPES Electrochemiluminescence System for Ultrasensitive Detection of HBV DNA.

In this work, a novel aluminum metal-organic framework (Al-MOF)/N-2-hydroxyethylpiperazine-N'-ethane-sulfonic acid (HEPES) system with an excellent electrochemiluminescence (ECL) property was developed. First, Al-MOF was successfully synthesized through a one-pot solvothermal method by using 9,10-di(p-carboxyphenyl)anthracene (DPA) as the organic luminescence ligand and Al3+ as the metal node. Compared with DPA, Al-MOF showed high ECL intensity and excellent stability without an additional coreactant in the HEPES buffer. The corresponding ECL mechanism was studied in detail, verifying HEPES was not only the buffer in the system but also the coreactant of Al-MOF. In particular, the system of Al-MOF/HEPES showed a high ECL efficiency of 30.0%, taking the Ru(bpy)32+ system as the standard. In addition, the ECL signal of Al-MOF was effectively quenched by dopamine (DA). The biosensor for HBV DNA detection was constructed through the ECL signal on-off-on mode of DNA specific recognition integrated with the DNA walker signal amplification strategy. The ultrasensitive detection for HBV DNA was achieved with a linear range of 100 aM to 10 pM and a limit of detection (LOD) of 62.1 aM. This work proposed a high-efficiency Al-MOF/HEPES system, providing a new viewpoint for a coreactant-free system in the field of ECL.

Prevalence of comorbid depression and associated factors among hospitalized patients with type 2 diabetes mellitus in Hunan, China.

BACKGROUND: Depression and diabetes are major health challenges, with heavy economic social burden, and comorbid depression in diabetes could lead to a wide range of poor health outcomes. Although many descriptive studies have highlighted the prevalence of comorbid depression and its associated factors, the situation in Hunan, China, remains unclear. Therefore, this study aimed to identify the prevalence of comorbid depression and associated factors among hospitalized type 2 diabetes mellitus (T2DM) patients in Hunan, China. METHODS: This cross-sectional study involved 496 patients with T2DM who were referred to the endocrinology inpatient department of Xiangya Hospital affiliated to Central South University, Hunan. Participants' data on socio-demographic status, lifestyle factors, T2DM-related characteristics, and social support were collected. Depression was evaluated using the Hospital Anxiety and Depression Scale-depression subscale. All statistical analyses were conducted using the R software version 4.2.1. RESULTS: The prevalence of comorbid depression among hospitalized T2DM patients in Hunan was 27.22% (95% Confidence Interval [CI]: 23.3-31.1%). Individuals with depression differed significantly from those without depression in age, educational level, per capita monthly household income, current work status, current smoking status, current drinking status, regular physical activity, duration of diabetes, hypertension, chronic kidney disease, stroke, fatty liver, diabetic nephropathy, diabetic retinopathy, insulin use, HbA1c, and social support. A multivariable logistic regression model showed that insulin users (adjusted OR = 1.86, 95% CI: 1.02-3.42) had a higher risk of depression, while those with regular physical activity (adjusted OR = 0.48, 95% CI: 0.30-0.77) or greater social support (adjusted OR = 0.20, 95% CI: 0.11-0.34) had a lower risk of depression. The area under the curve of the receiver operator characteristic based on this model was 0.741 with a sensitivity of 0.785 and specificity of 0.615. CONCLUSIONS: Depression was moderately prevalent among hospitalized T2DM patients in Hunan, China. Insulin treatment strategies, regular physical activity, and social support were significantly independently associated with depression, and the multivariable model based on these three factors demonstrated good predictivity, which could be applied in clinical practice.

Activation of the p62-Keap1-Nrf2 pathway protects against oxidative stress and excessive autophagy in ovarian granulosa cells to attenuate DEHP-induced ovarian impairment in mice.

Di-(2-ethylhexyl) phthalate (DEHP) is widely used in various plastics but has been demonstrated to cause female reproductive toxicity. However, the exact mechanism underlying the ovarian damage induced by DEHP remains unclear. In this study, DEHP was administered orally to 5-week-old female mice for 30 days at doses of 0, 250, 500, and 1000 mg/kg/day. The findings demonstrated that DEHP exposure disrupted ovarian function and follicular development as well as induced oxidative stress and autophagy in ovarian granulosa cells (GCs). Further, 200 µM mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP in vivo, induced autophagy in both human ovarian granulosa cells line (KGN) and mouse primary GCs within 24 h in vitro. However, it did not affect the p62-dependent autophagy flux. Furthermore, MEHP-induced autophagy was inhibited by the autophagy inhibitor 3-MA and exacerbated by the autophagy activator rapamycin, indicating that MEHP induces excessive autophagy in GCs. Subsequently, we found that MEHP-induced autophagic cell death was primarily attributed to oxidative damage from elevated intracellular ROS levels. Meanwhile, MEHP exposure induced nuclear translocation of erythroid-derived factor 2-related factor (Nrf2), a key regulator of antioxidant activity resulting in activating antioxidant effects. Interestingly, we also found that MEHP-induced increase in p62 competitively binds Keap1, thereby facilitating nuclear translocation of Nrf2 and establishing a positive feedback loop in antioxidant regulation. Therefore, this study demonstrated that inhibition of Nrf2 could aggravate oxidative damage and enhance excessive autophagy caused by MEHP, while activation of Nrf2 could reverse the trend. These findings have also been reinforced in studies of cultured ovaries in vitro. Our study suggests that the p62-Keap1-Nrf2 pathway may serve as a potential protective mechanism against DEHP-induced oxidative stress and excessive autophagy in mouse GCs.

Integrated fecal microbiome and metabolome analysis explore the link between polystyrene nanoplastics exposure and male reproductive toxicity in mice.

Microplastics (MPs) and nanoplastics (NPs) are novel environmental pollutants that are ubiquitous in the environment and everyday life. NPs can easily enter the tissues and have more significant potential health risks due to their smaller diameter. Previous studies have shown that NPs can induce male reproductive toxicity, but the detailed mechanisms remain uncertain. In this study, intragastric administration treated mice with polystyrene NPs (PS-NPs, 50, and 90 nm) at 3 and 15 mg/mL/day doses for 30 days. Then, the fresh fecal samples were collected from those mice that the exposure doses of 50 nm PS-NPs at 3 mg/mL/day and 90 nm at 15 mg/mL/day for subsequent investigations of 16S rRNA and metabolomics according to significant toxicological effects (Sperm number, viability, abnormality, and testosterone level). The conjoint analysis findings indicated that PS-NPs disrupted the homeostasis of the gut microbiota, metabolism, and male reproduction, suggesting that abnormal gut microbiota-metabolite pathways may be important in PS-NPs-induced male reproductive toxicity. Meanwhile, the common differential metabolites such as 4-deoxy-Erythronic acid, 8-iso-15-keto-PGE2, apo-10'-violaxanthin, beta-D-glucosamine, isokobusone, oleamide, oxoadipic acid, sphingosine induced by 50 and 90 nm PS-NPs might be used as biomarkers to explore PS-NPs-induced male reproductive toxicity. In addition, this study systematically demonstrated that nano-scale PS-NPs induced male reproductive toxicity via the crosstalk of gut microbiota and metabolites. It also provided valuable insights into the toxicity of PS-NPs, which was conducive to reproductive health risk assessment for public health prevention and treatment.

Prevalence of Anxiety and Associated Factors Among Inpatients with Type 2 Diabetes Mellitus in China: A Cross-Sectional Study.

This study aimed to investigate the prevalence of anxiety and its associated factors among inpatients with type 2 diabetes mellitus (T2DM) in China. This study was a cross-sectional study. Inpatients with T2DM admitted to the Endocrinology Department of Xiangya Hospital, Central South University in Hunan Province of China from March 2021 to December 2021 were consecutively included in this study. Participants were interviewed to obtain the data on socio-demographic characteristics, lifestyle characteristics, T2DM-related information, and social support. Anxiety was measured using the Hospital Anxiety and Depression Scale-anxiety subscale by experienced physicians. Multivariable logistic regression analysis was used to estimate the independent contribution of each independent variable to anxiety. A total of 496 inpatients with T2DM were included in this study. The prevalence of anxiety was 21.8% (95% confidence interval [CI]: 18.1%-25.4%). The results of multivariable logistic regression analysis indicated that age of at least 60 (adjusted odd ratio [aOR] = 1.79, 95% CI: 1.04-3.08), and having diabetes specific complications (aOR = 4.78, 95% CI: 1.02-22.44) were risk factors for anxiety, and an educational level of high school or above (aOR = 0.55, 95% CI: 0.31-0.99), regular physical activity (aOR = 0.36, 95% CI: 0.22-0.58), and high social support (aOR = 0.30, 95% CI: 0.17-0.53) were protective factors for anxiety. A predictive model based on these five variables showed good performance (area under the curve = 0.80). Almost one in five inpatients with T2DM suffered from anxiety in China. Age, educational level, regular physical activity, diabetes specific complications, and social support were independently associated with anxiety.

Trial-level characteristics associate with treatment effect estimates: a systematic review of meta-epidemiological studies.

BACKGROUND: To summarize the up-to-date empirical evidence on trial-level characteristics of randomized controlled trials associated with treatment effect estimates. METHODS: A systematic review searched three databases up to August 2020. Meta-epidemiological (ME) studies of randomized controlled trials on intervention effect were eligible. We assessed the methodological quality of ME studies using a self-developed criterion. Associations between treatment effect estimates and trial-level characteristics were presented using forest plots. RESULTS: Eighty ME studies were included, with 25/80 (31%) being published after 2015. Less than one-third ME studies critically appraised the included studies (26/80, 33%), published a protocol (23/80, 29%), and provided a list of excluded studies with justifications (12/80, 15%). Trials with high or unclear (versus low) risk of bias on sequence generation (3/14 for binary outcome and 1/6 for continuous outcome), allocation concealment (11/18 and 1/6), double blinding (5/15 and 2/4) and smaller sample size (4/5 and 2/2) significantly associated with larger treatment effect estimates. Associations between high or unclear risk of bias on allocation concealment (5/6 for binary outcome and 1/3 for continuous outcome), double blinding (4/5 and 1/3) and larger treatment effect estimates were more frequently observed for subjective outcomes. The associations between treatment effect estimates and non-blinding of outcome assessors were removed in trials using multiple observers to reach consensus for both binary and continuous outcomes. Some trial characteristics in the Cochrane risk-of-bias (RoB2) tool have not been covered by the included ME studies, including using validated method for outcome measures and selection of the reported results from multiple outcome measures or multiple analysis based on results (e.g., significance of the results). CONCLUSIONS: Consistently significant associations between larger treatment effect estimates and high or unclear risk of bias on sequence generation, allocation concealment, double blinding and smaller sample size were found. The impact of allocation concealment and double blinding were more consistent for subjective outcomes. The methodological and reporting quality of included ME studies were dissatisfactory. Future ME studies should follow the corresponding reporting guideline. Specific guidelines for conducting and critically appraising ME studies are needed.

Metformin ameliorates polycystic ovary syndrome in a rat model by decreasing excessive autophagy in ovarian granulosa cells via the PI3K/AKT/mTOR pathway.

Polycystic ovary syndrome (PCOS) is a common gynecological disease accompanied by a variety of clinical features, including anovulation, hyperandrogenism, and ovarian abnormalities, resulting in infertility. PCOS affects approximately 6%-15% of all reproductive-age women worldwide. Metformin, a popular drug used to treat PCOS in patients, has beneficial effects in reducing hyperandrogenism and inducing ovulation; however, the mechanisms by which metformin ameliorates PCOS are not clear. Hence, we aimed to explore the mechanisms of metformin in treating PCOS. In the present study, we first treated a letrozole-induced PCOS rat model with metformin, detected the pathological recovery of PCOS, and then assessed the effects of metformin on H2O2-induced autophagy in ovarian granulosa cells (GCs) by detecting the level of oxidative stress and the expression of autophagy-associated proteins and key proteins in the PI3K/AKT/mTOR pathway. We demonstrated that metformin ameliorated PCOS in a rat model by downregulating autophagy in GCs, and metformin decreased the levels of oxidative stress and autophagy in H2O2-induced GCs and affected the PI3K/AKT/mTOR signaling pathway. Taken together, our results indicate that metformin ameliorates PCOS in a rat model by decreasing excessive autophagy in GCs via the PI3K/AKT/mTOR pathway, and this study provides evidence for targeted reduction of excessive autophagy of ovarian granulosa cells and improvement of PCOS.

Prevalence of Moderate to Severe Anxiety Symptoms among Patients with Myocardial Infarction: a Meta-Analysis.

This study attempted to synthesize the evidence on the prevalence of moderate to severe anxiety symptoms among myocardial infarction (MI) patients to offer a reliable and accurate estimate on the number of MI patients suffering from moderate to severe anxiety symptoms. Comprehensive electronic searches (PubMed, Embase and Web of Science) were performed from their inception to February 2021. Between-study heterogeneity was analyzed using the Cochran's Q test and [Formula: see text] statistic, and if it was high across the eligible studies, meta-regression and subgroup analyses were conducted to examine the source of heterogeneity. Publication bias and the robustness of the pooled results were also examined. A total of 18 eligible studies covering 8,532 MI patients were included, of which 3,443 were identified with moderate to severe anxiety symptoms. Between-study heterogeneity was high ([Formula: see text]=98.8%) with the reported prevalence ranging from 9.6% to 69.17%, and the pooled prevalence was 38.08% (95% confidence interval: 28.82-47.81%) by a random-effects model. Meta-regression analyses indicated that publication year (ß = -0.014) was significant moderators contributing 16.11% to the heterogeneity. Subgroup analyses indicated that studies using the anxiety subscale of Brief Symptom Inventory to assess anxiety were homogenous ([Formula: see text]=0.0). Furthermore, the pooled prevalence of moderate to severe anxiety symptoms varied significantly by geographic region, instrument used to assess anxiety, methodological quality, sex, education level, a history of previous MI and hypercholesterolemia. Additionally, the results of Egger's linear test (t = -0.630) and Begg's rank test (z = -0.190) indicated no evidence of publication bias, and the sensitivity of the pooled results was low. Nearly two fifth of MI patients suffered from moderate to severe anxiety symptoms, which emphasizes the importance of early identification of anxiety symptoms after MI, as well as the need of implementing psychological interventions for those with elevated anxiety symptoms.

Di-(2-ethylhexyl) phthalate exposure induces female reproductive toxicity and alters the intestinal microbiota community structure and fecal metabolite profile in mice.

Di-(2-ethylhexyl) phthalate (DEHP) is one of the most commonly used plasticizers, and it is widely applied in various plastic products. DEHP is an endocrine-disrupting chemical (EDC) that has been shown to disrupt the function of reproductive system in females. Although many studies have shown that DEHP potentially causes female reproductive toxicity, including depletion of the primordial follicle and decreased sex hormone production, the specific mechanisms by which DEHP affects female reproduction remain unknown. In recent years, research focused on the intestinal flora has provided an idea to eliminate our confusion, and gut bacterial dysbiosis may contribute to female reproductive toxicity. In the present study, the feces of DEHP-exposed mice were collected and analyzed using 16S rRNA amplicon sequencing and untargeted global metabolite profiling of metabolomics. DEHP obviously causes reproductive toxicity, including the ovarian organ coefficient, estradiol level, histological features of the ovary and estrus. Furthermore, DEHP exposure alters the structure of the intestinal microbiota community and fecal metabolite profile in mice, suggesting that the reproductive toxicity may be caused by gut bacterial dysbiosis and altered metabolites, such as changes in the levels of short-chain fatty acid (SCFA). Additionally, it is well known that changes in gut microbiota and fecal metabolites cause inflammation and tissue oxidative stress, expectedly, we found oxidative stress in the ovary and systemic inflammation in DEHP exposed mice. Thus, based on our findings, DEHP exposure may cause gut bacterial dysbiosis and altered metabolite profiles, particularly SCFA profiles, leading to oxidative stress in the ovary and systemic inflammation to ultimately induce female reproductive toxicity.

Blood Pressure Variability and Outcomes in End-Stage Renal Disease Patients on Dialysis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Previous studies have suggested that blood pressure variability (BPV) is associated with an increased risk of mortality and cardiovascular events in patients on dialysis. However, the results are inconsistent. A comprehensive literature review was conducted to analyze the association between BPV and outcomes in patients on dialysis. METHODS: Articles in Embase, Medline, and Web of Science from the date of inception through January 1, 2020, were identified. The outcomes were all-cause and cardiovascular mortality and cardiovascular events. The risk of bias was assessed using the Newcastle-Ottawa scale tool. Random effects models were used to pool the overall effect sizes. Two reviewers extracted the data independently. Meta-regression and subgroup analyses were performed to explore potential heterogeneity. RESULTS: Fifteen eligible studies were included, and all enrolled hemodialysis recipients only. The overall risk of bias for the included studies was low. A 1-SD increase in systolic BPV was associated with higher risks of all-cause mortality (HR = 1.18; 95% CI 1.11-1.26, I2 = 53.8%), cardiovascular mortality (HR = 1.23; 95% CI 1.10-1.37, I2 = 57.2%), and cardiovascular events (HR = 1.27; 95% CI 1.07-1.51, I2 = 69.3%). Likewise, a 1-SD increase in diastolic BPV was associated with higher HR for all-cause and cardiovascular mortality (HR = 1.14; 95% CI 1.05-1.23, I2 = 0.0%, and HR = 1.14; 95% CI 0.94-1.38, I2 = 0.0%, respectively). CONCLUSIONS: A greater BPV is associated with higher risks of cardiovascular and mortality outcomes in patients on hemodialysis. Further research is required to determine whether BPV may be useful either as a marker enabling individualized treatment of cardiovascular risk or as a treatment target in its own right.

Development and validation of a preoperative prediction model for follicular thyroid carcinoma.

OBJECTIVE: The low pre- and intraoperative diagnostic rates in follicular thyroid carcinoma (FTC) often lead to inadequate surgical resection and necessitate further completion surgery. Therefore, the preoperative prediction of FTC in thyroid nodules is essential. DESIGN AND PATIENT: Patients were categorized into two data sets: the modelling data set, which included 3649 patients admitted to our centre between January 2014 and December 2016, and the validation data set, which included 1253 patients admitted between January and December 2017. Patient data from the FTC and non-FTC groups were initially included in a modelling data set to establish a preoperative prediction model. This model was subsequently employed in a validation data set for external validation of the predictive value. The positivity rate for FTC predicted by the model was compared with that of the intraoperative frozen sections. RESULTS: The preoperative serum thyroglobulin level, nodule diameter, calcification status, solidity and blood supply were selected as predictors for the model. The regression equation was as follows: Y = 0.010 × (thyroglobulin level) + 0.556 × (nodule diameter) + 0.675 × (calcification status) + 2.355 × (nodule component) + 1.072*(blood flow) - 9.787. The model positively predicted FTC at values of Y ≥ -4.11. The accuracy, sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of the prediction model were 89.2%, 90.2%, 87.7%, 39.2 and 0.11, respectively. External validation of the model demonstrated acceptable results. The positive prediction rate of the model was 90.7% (78/86), which was significantly higher than that of the intraoperative frozen sections (10.5% [9/86]; P < 0.0001). CONCLUSIONS: We successfully established and validated a simple and reliable preoperative prediction model for FTC using the preoperative thyroglobulin level and ultrasonographic features of the thyroid nodules. This model may improve the preoperative evaluation of FTC in clinical settings and facilitate the development of a reasonable surgical programme for FTC.

Downregulation of Gabarapl1 significantly attenuates antibody binding to porcine aortic endothelial cells.

After hyperacute rejection in pig-to-primate xenotransplantation had been overcome by the introduction of α1,3-galactosyltransferase gene-knockout (GTKO) pigs, acute and chronic antibody-mediated rejection became one of the major barriers to long-term graft survival. This was associated with exposure of non-Gal antigens to the recipient's immune system and indicated that further genetic engineering of the pigs would be necessary. We here report that Gabarapl1, a regulator of tumorigenesis, plays a role in the regulation of immunogenicity of porcine aortic endothelial cells (PAECs). Knockdown of Gabarapl1 in PAECs results in a remarkable reduction in binding of serum antibody from PAEC-immunized monkeys, associated with decreased serum cytotoxicity of pig cells. Expression of swine leukocyte antigens (SLA) II DR was downregulated by Gabarapl1 knockdown. However, suppression of expression of SLA II is associated with less reduction of antibody binding than achieved by Gabarapl1 knockdown, suggesting that other Gabarapl1-regulated xenoantigens may be more important. These findings indicate a hitherto unknown relationship between Gabarapl1 and xenoimmunogenicity, suggesting a potential new strategy to reduce rejection initiated by the presence of non-Gal antigens.

Application of Continuous and Intermittent Intraoperative Nerve Monitoring in Thyroid Surgery.

BACKGROUND: Whether continuous intraoperative nerve monitoring (C-IONM) can further reduce the incidence of recurrent laryngeal nerve injury compared with intermittent intraoperative nerve monitoring (I-IONM) in high-risk thyroid surgery is still controversial. This observational study aimed to evaluate the incidence of vocal cord paralysis (VCP) in high-risk thyroid surgeries performed with I-IONM and C-IONM. MATERIALS AND METHODS: High-risk thyroid surgical patients operated with I-IONM or C-IONM by the same group of surgeons in the thyroid surgery department of our institution between January 2014 and February 2018 were analyzed. Differences in the incidence rates of temporary and permanent VCP between the two groups were compared. A P-value < 0.05 was considered statistically significant. RESULTS: A total of 344 patients who underwent high-risk thyroid surgery (550 nerves at risk [NARs]) were observed, with 238 patients (374 NARs) operated with I-IONM and 106 patients (173 NARs) operated with C-IONM. The incidence of temporary and permanent VCP was 1.9% (7/374) and 0.8% (3/374) in the I-IONM group and 1.2% (2/173) and 0% (0/173) in the C-IONM group, respectively, showing no statistical difference (P = 0.726 and P = 0.555). The incidence rate of impending recurrent laryngeal nerve injuries successfully prevented in the C-IONM group was 5.2% (9/173). CONCLUSIONS: Both I-IONM and C-IONM are equally safe and effective in high-risk thyroid surgery. C-IONM can help predict impending recurrent laryngeal nerve injury in real time and has a good warning feature, thereby minimizing critical maneuvers in high-risk thyroid surgery.