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Updated immunization strategies are needed to address multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here we report interim results from an ongoing, open-label phase 2/3 trial evaluating the safety and immunogenicity of the bivalent Coronavirus Disease 2019 (COVID-19) vaccine candidate mRNA-1273.211, which contains equal mRNA amounts encoding the ancestral SARS-CoV-2 and Beta variant spike proteins, as 50-µg (n = 300) and 100-µg (n = 595) first booster doses administered approximately 8.7–9.7 months after the mRNA-1273 primary vaccine series (NCT04927065). The primary objectives were to evaluate the safety and reactogenicity of mRNA-1273.211 and to demonstrate non-inferior antibody responses compared to the mRNA-1273 100-µg primary series. Additionally, a pre-specified immunogenicity objective was to demonstrate superior antibody responses compared to the previously authorized mRNA-1273 50-µg booster. The mRNA-1273.211 booster doses (50-µg or 100-µg) 28 days after immunization elicited higher neutralizing antibody responses against the ancestral SARS-CoV-2 and Beta variant than those elicited 28 days after the second mRNA‑1273 dose of the primary series (NCT04470427). Antibody responses 28 days and 180 days after the 50-µg mRNA-1273.211 booster dose were also higher than those after a 50-µg mRNA-1273 booster dose (NCT04405076) against the ancestral SARS-CoV-2 and Beta, Omicron BA.1 and Delta variants, and all pre-specified immunogenicity objectives were met. The safety and reactogenicity profile of the bivalent mRNA-1273.211 booster (50-µg) was similar to the booster dose of mRNA-1273 (50-µg). Immunization with the primary series does not set a ceiling to the neutralizing antibody response, and a booster dose of the bivalent vaccine elicits a robust response with titers that are likely to be protective against COVID-19. These results indicate that bivalent booster vaccines can induce potent, durable and broad antibody responses against multiple variants, providing a new tool in response to emerging variants.

Sleep disturbances have been linked with Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) in observational studies, and the comorbidity of PD and ALS has been reported in clinical case reports, but the causalities remain unclear. This study aims to examine bidirectional causal relationships between sleep traits, PD and ALS.Bidirectional two sample Mendelian randomisation (MR) analyses were conducted, with data from individuals of mainly European ancestry. Genetic instruments were obtained from the largest published genome-wide association studies (GWAS) concerning various sleep traits, PD and ALS. MR estimates from each genetic instrument were combined by inverse variance weighted method, with alternate methods (eg, weighted median, MR Egger, MR-PRESSO) and statistical graphs to assess horizontal pleiotropy and remove outliers.MR analysis failed to observe any causal association between sleep disorders and PD, but found a possible causal effect of PD risk on ALS risk (odds ratio [OR] = 1.07; 95% CI: 1.01-1.14, P 0.01), albeit with a horizontal pleiotropy. Furthermore, MR analyses indicated that excessive daytime sleepiness (EDS) (OR = 2.29; 95% CI: 1.04-5.03, P = 0.04) contributed to a modest increase in risk of ALS, but the reverse causalities were not significant. Higher risk of ALS may be associated with being a "morning person" (OR = 1.03, P = 0.02), a longer sleep duration (OR = 1.01, P 0.01), and a mean of 9 h or more total sleep duration (β = 0.02, P = 0.04).Aided by large-scale GWAS, a shortage of evidence supporting causal relationships of sleep traits and PD risk, while significant evidence supports that EDS, higher PD risk may causally influence ALS risk. Future researches are required to explore the underlying pathological mechanism as well as the clinically significance, and replicate our findings using independent samples when data become available.

The study aimed to determine the association between cord plasma levels of apelin and vascular endothelial growth factor (VEGF) with respiratory distress syndrome (RDS) in preterm infants.This case-control study included 120 preterm infants admitted to the neonatal intensive care unit of our hospital between January 2019 and January 2020. The infants were divided into RDS (The plasma apelin levels in the RDS group were significantly higher than in the non-RDS group (158.9 ± 24.8 vs. 125.2 ± 18.2 pg/mL, respectively), whereas VEGF levels in the non-RDS group were significantly higher than in the RDS group (187.4 ± 28.5 vs. 245.1 ± 44.8 pg/mL, respectively) (bothDifferences in cord plasma apelin and VEGF levels may aid in the early diagnosis and treatment of RDS in preterm infants.

Objectives With advancing age, older drivers experience greater fatal crash risks due to age-related declines in cognitive and physical capabilities. Being informed of the age-related increased risks could help older drivers form compensatory strategies and determine when to seek further help to stay on the road safely for longer. Using a self-report assessment tool, the Attentional Failure during Driving Questionnaire (AFDQ), we examined older drivers’ experience of various attentional failures during daily driving and how the measures could predict their crash risks. Methods We used a new methodological approach distinguishing the occurrences of attentional failures during driving and the frequency of those occurrences. The individuals’ AFDQ occurrence and frequency scores were compared with prior driving outcomes and simulated driving performance. Results Unlike middle-aged drivers, frequency rather than occurrence of attentional failures was a significant predictor of prior traffic violations and crashes among older drivers. Also, attentional failures, but not chronological age, predicted older drivers’ crash risks. AFDQ frequency was also associated with older drivers’ poorer performance in simulated driving. Discussion The findings suggest that the self-report assessment for attention-related driving failures can predict older drivers’ crash risks. Furthermore, the two-part approach of AFDQ provides an opportunity to do a more comprehensive investigation of the associations between attentional declines and crash risks among older drivers.

Background: To investigate whether obesity with or without metabolic syndrome is prospectively associated with coronary artery calcium (CAC) progression and incident cardiovascular disease events. Methods: A total of 1730 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included (age, 40.1±3.6 years; 38.3% men), who completed computed tomography of CAC at baseline (year 15: 2000–2001) and follow-up (year 20 or 25). Metabolically healthy obesity (MHO) was defined as body mass index≥30 kg/m 2 without any metabolic syndrome components in our main analysis. Sensitivity analyses were conducted for several conditions characterizing 4 metabolic phenotypes. Results: During a mean follow-up of 9.1 years, 439 participants had CAC progression. MHO subjects had a significantly higher risk of CAC progression than their metabolically healthy normal weight counterparts (adjusted hazard ratios [95% CIs] from 1.761 [1.369–2.264] to 2.047 [1.380–3.036]) depending on the definition of MHO adopted. Obesity with unhealthy metabolic profile remained the highest significant risk of CAC progression and cardiovascular disease events whatever the definitions adopted for metabolically unhealthy status. Up to 60% of participants with MHO converted to metabolically unhealthy obesity from year 15 to year 20 or year 25. Further sensitivity analysis showed that MHO throughout carried a similar risk of incident cardiovascular disease events compared with metabolically healthy normal weight throughout. Conclusions: Different metabolic phenotypes of obesity beginning at a young age exhibit distinct risks of CAC progression and subsequent cardiovascular disease events in later midlife. MHO represents an intermediate phenotype between metabolically low- to high-risk obese individuals. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00005130.

In sufferers with nonalcoholic fatty liver disease (NAFLD), the differences of thyroid associated hormones and neutrophil to lymphocyte ratio (NLR) in different liver pathological groups have been compared.Patients with NAFLD diagnosed by liver biopsy in our hospital from July 2012 to February 2019 were selected. All subjects were divided into nonalcoholic steatohepatitis (NASH) team and non-NASH group, no/mild fibrosis group (F0-1) and significant fibrosis group (F2-4). The differences of thyroid related hormones and NLR in these groups were in contrast, respectively. For the TSH, we conducted further evaluation based on gender.The TSH and NLR in NASH patients were significantly higher than non-NASH patients, but there was no considerable difference in free triiodothyronine (FT3) and free thyroxine (FT4) between the 2 groups. In the gender-based subgroup analysis, the variations of TSH between the 2 groups were nonetheless statistically significant (P .05). The TSH and NLR in the significant fibrosis group were higher than these in the non/mild liver fibrosis group, and the differences were statistically significant (P .05), but there was no large difference in FT3 and FT4 between the 2 groups (P .05). In addition, in the gender-based subgroup analysis and further multivariable analysis, the variations of TSH between the 2 groups were still statistically significant (P .05).In this study, we found that serum thyroid stimulating hormone (TSH) and neutrophil to lymphocyte ratio (NLR) were closely associated to the severity of NAFLD, suggesting that this simple available laboratory index may additionally be incorporated into the future noninvasive diagnostic scoring model to predict the incidence of NASH and the degree of fibrosis.

ObjectiveThe study aimed to assess the associations of physical activity (PA) trajectories across a 25-year span with coronary artery calcium (CAC) progression, and subsequent risk of cardiovascular disease (CVD) events.MethodsWe included 2497 participants from the Coronary Artery Disease Risk Development in Young Adults study who had computed tomography-assessment of CAC at baseline (year 15: 2000–2001) and follow-up (year 20 or 25) and at least three measures of PA from year 0 to year 25. Long-term PA trajectories were determined by latent class modelling using a validated questionnaire.ResultsAmong the included participants, 1120 (44.9%) were men, 1418 (56.8%) were white, and the mean (SD) age was 40.4 (3.6) years. We identified three distinct PA trajectories based on PA average levels and change patterns: low (below PA guidelines, n=1332; 53.3%); moderate (meeting and slightly over PA guidelines, n=919; 36.8%) and high (about three times PA guidelines or more, n=246; 9.9%). During a mean (SD) follow-up of 8.9 (2.1) years, 640 (25.6%) participants had CAC progression. Participants in the high PA trajectory group had a higher risk of CAC progression than those in the low PA trajectory group after adjustment for traditional cardiovascular risk factors (HR 1.51; 95% CI 1.18 to 1.94). However, high PA trajectory was not associated with an increased risk of incident CVD events (HR 1.01; 95% CI 0.44 to 2.31) and the incidence of CVD events in participants with CAC progression was similar across all three PA trajectory groups (p=0.736).ConclusionLong-term PA about three times the guidelines or more is independently associated with CAC progression; however, no additional risk of incident CVD events could be detected.

There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC.This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non-inferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis.Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5-6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0-6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812-1.203; PThis non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

The purpose of this study was to analyze tear cytokine and complement levels in patients diagnosed with acute ocular graft-versus-host disease (oGVHD) and examine the consistency of these levels with the severity of clinical manifestations.Ten patients with acute oGVHD (20 eyes) were enrolled for the assessment of tear cytokine levels and ocular surface parameters, and 18 healthy people (36 eyes) were selected as the control group. The tear cytokine and complement levels were measured using microsphere-based immunoassay analysis.The main clinical manifestations of acute oGVHD include eye redness, a large amount of purulent exudate, eye pain, and even false membranes. The levels of intercellular cell adhesion molecule-1, interleukin 6 (IL-6), interleukin 1 beta (IL-1β), interleukin 8, epidermal growth factor (EGF), interleukin 7 (IL-7), B-cell activating factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), and complement in patients with acute oGVHD showed significant differences compared with those in normal people. Furthermore, the levels of IL-6, IL-1β, EGF, GM-CSF, IL-7, and C3a showed a stronger correlation with ocular surface parameters.Our study was the first to enroll patients with acute oGVHD to assess tear cytokine levels as a method contributing to the diagnosis of acute oGVHD. In addition, it has been demonstrated that certain tear cytokines, including intercellular cell adhesion molecule-1, IL-6, IL-1β, interleukin 8, B-cell activating factor, GM-CSF, IL-7, EGF, and complement, may be new diagnostic biomarkers for acute oGVHD.

Depression is a prevalent and disabling mental disorder that frequently co-occurs with a wide range of chronic conditions. Past evidence suggests that depression could be associated with the all-cause mortality and other disease mortality in Western populations, but little is known about the relationship in the Chinese population. Therefore, we investigated the associations between self-reported depression and all-cause and specific-cause mortality in Chinese adult populations.The Patient Health Questionnaire-9 (PHQ-9) was used to measure depressive symptoms among 8,151 adult participants drawn from the general population of Guizhou province, China. Participants death and cause of death were determined by linking with the official death records and certificates up to June 2021. Cause of death was coded according to ICD-10 then categorized as either cardiovascular disease (CVD, I00-I99), cancer (C00-C97) or other cause. Cox proportional hazard regression was used to examine the associations of self-reported depression with all-cause mortality and cause-specific mortality.With a median follow-up of 7.4 years, 8,151 participants (52.6% women) at baseline were included in the analysis. The multivariable cox hazard regression models showed that participants with moderate and major depression had the highest hazard ratio (HR) for risk of all-cause mortality (HR=5.65, 95% CI 3.09-10.33), CVD mortality (HR=5.66, 95% CI 2.02-15.84), and cancer mortality (HR=7.21, 95% CI 2.00-25.99), compared with participants had no or mild depression.Our findings suggested that depression was a risk factor for mortality, with greater risk for greater severity. Clinicians should be aware of the increased risk of mortality in populations with depression.

Background: Maternal smoking during pregnancy may be associated with low birth weight (LBW) in offspring and global risk estimates have not been summarized previously. We aimed to systematically explore evidence regarding maternal smoking and the LBW risk in offspring globally and examine possible causes of heterogeneity across relevant studies. Methods: Comprehensive search of PubMed, Ovid Embase, Ovid Medline (R), and Web of science from inception until October 2021 was carried out. A random-effects meta-analysis was used to estimate the pooled odds ratio (OR) and corresponding 95% confidence interval (CI). Restricted cubic spline analysis with four knots was used to further examine the dose-response relationship. Results: Literature searches yielded 4,940 articles, of which 53 met inclusion criteria (comprising 55 independent studies). Maternal smoking during pregnancy was significantly associated with the risk of LBW in offspring (OR=1.89 , 95% CI=1.80-1.98). Furthermore, an obvious dose–response relationship between the amount of cigarettes daily smoked in pregnancy and the risk of LBW in offspring was observed. The results of subgroup analyses indicated that the risk of maternal smoking on LBW was larger in more recently conducted studies (P = .020) and longer period of active smoking during pregnancy (P = .002). No evidence of publication bias was found. Conclusions: In summary, maternal smoking in pregnancy was significantly associated with a aternal smoking in pregnancy was significantly associated with a higher risk of LBW in offspring on a global scale. The risk of maternal smoking on infant higher risk of LBW in offspring on a global scale. The risk of maternal smoking on infant LBWLBW seems to be increasing over time, and was higher with seems to be increasing over time, and was higher with longer smoking duration longer smoking duration throughout pregnancy and more cigarettes smoked daily. throughout pregnancy and more cigarettes smoked daily.

Postvaccination serologic testing (PVST) is utilized to monitor the success or failure of vaccination against hepatitis B virus (HBV) infection in infants of hepatitis B surface antigen (HBsAg) positive mothers. This secondary analysis of 1255 infants of HBsAg-positive mothers at 7–14 months age included in two prospective studies aimed to determine the optimal interval for PVST after three hepatitis B vaccine doses. HBsAg and anti-HBs were quantitatively tested with microparticle enzyme immunoassay. The average PVST interval was 3.8 ± 2.2 months. Overall, 1.7% (21/1255) infants had anti-HBs

The most serious and common complication of the medication recommended by World Health Organization (WHO) for tuberculosis (TB) is anti-tuberculosis drugs-induced hepatotoxicity (ATDH). Pregnane X receptor (PXR) is a key factor of ATDH, while Hepatocyte nuclear factor 4α (HNF4α) and hepatocyte nuclear factor 4 alpha-antisense-1 (HNF4α-AS1) may have co-regulating relationship with PXR. This study aimed to explore whether the genetic variants of HNF4α and HNF4α-AS1 are associated with the predisposition of ATDH.TB patients diagnosed in West China Hospital between December 2014 and April 2018 were enrolled. TagSNPs in HNF4α and HNF4α-AS1 gene from the samples of the patients were genotyped with a custom-designed 2×48-plex SNP ScanTM Kit. The frequencies of the alleles, genotypes, genetic models and haplotype distribution of the variants were compared between the case and control groups. The association between SNP and ATDH risk was assessed by single factor logistic regression.Logistic regression analysis showed that none of the 15 genetic variants in HNF4α and HNF4α-AS1 genes were significantly associated with susceptibility to ATDH in the Chinese Han population after Bonferroni correction.A challenge has arisen to the promising application of SNPs in the HNF4α and HNF4α-AS1 genes as genetic markers for ATDH, and further study is needed with a larger sample size.

Purpose Accurate assessment of preoperative tumor burden contribute to formulate a scientific surgical plan for patients with pseudomyxoma peritonei (PMP). Present study aimed to assess whether the preoperative plasma D-Dimer level could reflect tumor burden for PMP patients. Methods A total of 253 PMP patients were included between June 1, 2013 and March 1, 2022. According to the peritoneal cancer index (PCI), all participants were divided into extensive (PCI ≥ 28) and none-extensive (PCI P value less than 0.05 is considered statistically significant. Results The level of D-Dimer (ng/ml) between extensive and none-extensive subgroup were 600 (328, 1268) vs. 339 (128, 598), Z = -5.425, p p Conclusion Preoperative plasma D-Dimer could moderately reflect tumor burden for PMP. In the future, a multivariate prediction model will be developed to help surgeons to formulate a more precise surgical plan for the PMP patients.

Background: Quantification of viral antigens and viral loads in human milk samples from mothers infected with hepatitis B virus is largely unknown. Research Aim: The aim of the study was to quantitatively measure the levels of viral antigens and deoxyribonucleic acid of hepatitis B virus in human milk from mothers infected with hepatitis B virus. Methods: Fifty-five pairs of milk and serum samples from mothers with positive hepatitis B surface antigen, including 11 hepatitis B e antigen positive, were quantitatively tested to measure viral antigens by microparticle enzyme immunoassay and viral loads by real-time polymerase chain reaction assay. Results: The median level of hepatitis B surface antigen in the human milk samples of mothers with positive or negative hepatitis B e antigen was each lower than that in the sera, respectively (1.10 vs. 4.32 log10 IU/ml, t = 10.693, p < .001; -0.77 vs. 2.53 log10 IU/ml, t = -25.135, p < .001). The titers of hepatitis B surface antigen or hepatitis B e antigen in the human milk samples were each correlated with that in maternal serum. The detectable level of deoxyribonucleic acid of hepatitis B virus in human milk ranged from 1.42–5.27 log10 IU/ml, whereas that in maternal sera was 1.44–8.66 log10 IU/ml. The viral level in human milk was not correlated with that in maternal circulation. Conclusion: The present study data illustrate the relatively low titers of viral markers in the milk of mothers with positive hepatitis B surface antigen.

The significant function of circRNAs in cancer was recognized in recent work, so a well-organized resource is required for characterizing the interactions between circRNAs and other functional molecules (such as microRNA and RNA-binding protein) in cancer. We previously developed cancer-specific circRNA database (CSCD), a comprehensive database for cancer-specific circRNAs, which is widely used in circRNA research. Here, we updated CSCD to CSCD2 (http://geneyun.net/CSCD2 or http://gb.whu.edu.cn/CSCD2), which includes significantly more cancer-specific circRNAs identified from a large number of human cancer and normal tissues/cell lines. CSCD2 contains >1000 samples (825 tissues and 288 cell lines) and identifies a large number of circRNAs: 1 013 461 cancer-specific circRNAs, 1 533 704 circRNAs from only normal samples and 354 422 circRNAs from both cancer and normal samples. In addition, CSCD2 predicts potential miRNA–circRNA and RBP–circRNA interactions using binding motifs from >200 RBPs and 2000 microRNAs. Furthermore, the potential full-length and open reading frame sequence of these circRNAs were also predicted. Collectively, CSCD2 provides a significantly enhanced resource for exploring the function and regulation of circRNAs in cancer.

Allicin, a chemical found in functional foods, has a variety of beneficial bioactivities but the unpleasent odor and unstability hinder its applications. Isolating products from cyclodextrin (CD) complexation, using β-CD and its derivatives, is usually a time and energy-consuming process. Herein, a high-efficiency and eco-friendly preparation method of an inclusion (allicin@α-CD) formed by allicin and α-CD was designed, which turned liquid allicin into crystal particles with high-speed stirring (10,000 r/min) at 25°C for 10 min in water. In vivo and in vitro masking evaluations showed that the inclusion particles could decrease the unpleasant odor of allicin. Molecular docking and experimental characterization results illustrated that the main reason of odor masking was due to the disulfide and thiocarbonyl groups of allicin being partially encapsulated by the cavity of α-CD. Compared with the physical mixture, the stability of allicin in allicin@α-CD at 60°C for 10 days was 33-fold improved. Overall, this efficient strategy of inclusion provided a promising approach for the industrialization of allicin-related formulations. PRACTICAL APPLICATION: In this study, an environmentally friendly method of α-CD inclusion without the use of organic reagents was designed to solidify and stabilize allicin, which effectively masked the unpleasant odor and taste of allicin. It has contributed greatly to improving the compliance of consumers and provided a new and effective approach to broaden the application of allicin.

Background Cisplatin has been a vital drug used for tumor treatment because of its excellent effect on numerous malignant solid cancers. Nonetheless, its nephrotoxicity is non-negligible in clinical practice. This study aims to provide a new understanding of the molecular mechanism of transient receptor potential ankyrin 1 (TRPA1) in cisplatin-induced renal apoptosis. Methods We evaluated the effect on apoptosis, TRPA1 expression, and intracellular calcium concentration of human kidney 2 (HK-2) cells induced by diamminedichloroplatinum (DDP). Additionally, we also assessed DDP-induced apoptosis, the expression of Bax, caspase3, cleaved-cas3, p53, Bcl-2 and intracellular calcium concentration combined with HC-030031 and/or pifithrin-α. The effect of FK506 on apoptosis of HK-2 cells induced by DDP and the expression of the nuclear factor of activated T cells (NFAT) protein treated with HC-030031, pifithrin-α, and/or FK506 were also explored. Results The results showed that apoptosis, TRPA1 expression, and intracellular calcium concentration of HK-2 cell induced by DDP were enhanced in a dose-dependent manner. HC-030031 and pifithrin-α relieved apoptosis, and intracellular calcium concentration and the expression of NFAT and phospho-NFAT (p-NFAT) were induced by DDP. HC-030031 combined with pifithrin-α further aggravated the above-mentioned tendency, including relieved apoptosis, intracellular calcium concentration, and NFAT and p-NFAT expression. HC-030031 and FK506 decelerated the apoptosis, and NFAT and p-NFAT expression of HK-2 cells was induced by DDP, while simultaneous treatment with HC-030031 and FK506 further decreased apoptosis and protein expression. However, the expression of Bcl-2 increased when HC-030031, pifithrin-α, or FK506 was used alone, and HC-030031 combined with pifithrin-α or FK506 further improved the expression of Bcl-2. Conclusions TRPA1 mediates cisplatin-induced apoptosis in renal tubular cells via the calcineurin-nuclear factor of activated T-cells-p53 signaling pathway.

Deep learning evolves into a new form of machine learning technology that is classified under artificial intelligence (AI), which has substantial potential for large-scale healthcare screening and may allow the determination of the most appropriate specific treatment for individual patients. Recent developments in diagnostic technologies facilitated studies on retinal conditions and ocular disease in metabolism and endocrinology. Globally, diabetic retinopathy (DR) is regarded as a major cause of vision loss. Deep learning systems are effective and accurate in the detection of DR from digital fundus photographs or optical coherence tomography. Thus, using AI techniques, systems with high accuracy and efficiency can be developed for diagnosing and screening DR at an early stage and without the resources that are only accessible in special clinics. Deep learning enables early diagnosis with high specificity and sensitivity, which makes decisions based on minimally handcrafted features paving the way for personalized DR progression real-time monitoring and in-time ophthalmic or endocrine therapies. This review will discuss cutting-edge AI algorithms, the automated detecting systems of DR stage grading and feature segmentation, the prediction of DR outcomes and therapeutics, and the ophthalmic indications of other systemic diseases revealed by AI.

BackgroundUpdated vaccination strategies against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern are needed. Interim results of the safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster candidate are presented.MethodsIn this ongoing, phase 2/3 trial, the 50-μg bivalent vaccine mRNA-1273.214 (25-μg each ancestral Wuhan-Hu-1 and omicron B.1.1.529 spike SARS-CoV-2 mRNAs) was compared to the authorized 50-μg mRNA-1273 booster in adults who previously received 2-dose primary series of 100-μg mRNA-1273 and a first booster dose of 50-μg mRNA-1273 at least 3 months prior. Primary objectives were safety and reactogenicity, and immunogenicity of 50-μg mRNA-1273.214 compared with 50-μg mRNA-1273. Immunogenicity data 28 days after the booster dose are presented.ResultsFour hundred thirty-seven and 377 participants received 50-μg of mRNA-1273.214, or mRNA-1273, respectively. Median time between first and second booster doses of mRNA-1273.214 and mRNA-1273 were similar (136 and 134 days, respectively). In participants with no prior SARS-CoV-2 infection, observed omicron neutralizing antibody geometric mean titers (GMTs [95% confidence interval]) after the mRNA-1273.214 and mRNA-1273 booster doses, were 2372.4 (2070.6−2718.2) and 1473.5 (1270.8−1708.4) respectively and the model-based GMT ratio (97.5% confidence interval) was 1.75 (1.49−2.04). All pre-specified non-inferiority (ancestral SARS-CoV-2 with D614G mutation [D614G] GMT ratio; ancestral SARS-CoV-2 [D614G] and omicron seroresponse rates difference) and superiority primary objectives (omicron GMT ratio) for mRNA-1273.214 compared to mRNA-1273 were met. Additionally, mRNA-1273.214 50-μg induced a potent neutralizing antibody response against omicron subvariants BA.4/BA.5 and higher binding antibody responses against alpha, beta, gamma, delta and omicron variants. Safety and reactogenicity profiles were similar and well-tolerated for both vaccines groups.ConclusionThe bivalent vaccine mRNA-1273.214 50-μg was well-tolerated and elicited a superior neutralizing antibody response against omicron, compared to mRNA-1273 50-μg, and a non-inferior neutralizing antibody response against the ancestral SARS-CoV-2 (D614G), 28 days after immunization, creating a new tool as we respond to emerging SARS-CoV-2 variants.

To investigate the carriage status ofThe stratified cluster sampling method was used to select 2 031 healthy children from seven kindergartens in Shunde District of Foshan in Guangdong, China. Nasal swabs were collected from all children for the isolation and identification ofThe carriage rates ofCo-carriage of

Background and AimsOral xerostomia remains one of the most common complications of differentiated thyroid carcinoma patients (DTC) after radioiodine therapy (RAI). Environmental factors in the etiology of xerostomia are largely unknown. We aimed to characterize the oral microbiota signatures and related biological functions associated with xerostomia and identify environmental factors affecting them.MethodsSaliva was collected from 30 DTC patients with xerostomia (XAs), 32 patients without xerostomia (indicated as non-XAs) following RAI after total thyroidectomy, and 40 healthy people (HCs) for 16S rRNA sequencing analysis.ResultsThe oral microbiota of XAs and non-XAs exhibited significant differences in α and β diversities and bacterial taxa. The abundance of porphyromonas, fusobacterium, and treponema_2 were significantly higher in XAs, while the abundance of the streptococcus was lower in the microbiota of non-XAs. Fusobacterium, and porphyromonas were negatively correlated with unstimulated/stimulated whole salivary secretion (USW)/(SWS), while fusobacterium, porphyromonas, and treponema_2 genera levels were positively associated with cumulative radioiodine dose. PICRUSt2 and BugBase suggested a significant difference in the expression of potentially_pathogenic, anaerobic, gram_negative, the arachidonic acid metabolism, and lipopolysaccharide (LPS) biosynthesis between XAs and non-XAs, possibly interdependent on radioiodine-induced inflammation. NetShift analysis revealed that porphyromonas genus might play as a key driver during the process of xerostomia. Five genera effectively distinguished XAs from non-XAs (AUC = 0.87).ConclusionOur study suggests for the first time that DTC patients with xerostomia after RAI display microbiota profiles and associated functional changes that may promote a pro-inflammatory environment. Dysbiosis of the oral microbiota may contribute to exacerbating the severity of xerostomia. Our results provide a research direction of the interaction mechanism between oral microbiota alteration and the progress of xerostomia.

Although osteo-inductive materials are regarded as promising candidates for critical-sized bone repair, their clinical application is limited by ambiguous mechanisms. The hypoxia-inducible factor (HIF)-1 signaling pathway, which responds to hypoxic conditions, is involved in both angiogenesis and osteogenesis. Strategies harnessing HIF-1 signaling to promote angiogenesis have been applied and have succeeded in repairing segmental bone defects. Meanwhile, macrophages have been shown to have important immunoregulatory effects on material-induced osteo-induction and correlate with HIF-1 activity. Thus, it is reasonable to assume that HIF-activated macrophages may also play important roles in the angiogenesis of material-induced osteo-induction. To verify this assumption, a classical type of osteo-inductive calcium phosphate (TCPs) was utilized. First, using RNA sequencing, we found that hypoxia activated the HIF signaling pathway in macrophages, which contributed to angiogenesis in TCPs. In addition, after treatment with a conditioned medium extracted from the co-culture system of macrophages and TCPs under hypoxic conditions, the migration and tube formation ability of human umbilical vein endothelial cells (HUVECs) significantly increased.

ObjectiveTo investigate the relations of Triglyceride glucose (TyG) index with cerebral small vessel disease (CSVD) burden and cognitive function in aged patients with type 2 diabetes mellitus (T2DM).MethodsA total of 308 elderly patients with T2DM were included in this retrospective study. The standardized Chinese version of Mini-Mental State Examination was used to assess cognitive function. The total CSVD burden score was assessed by combining four imaging markers of CSVD, including the presence of white matter hyperintensity, cerebral microbleeds in the deep, lacunes and enlarged perivascular spaces in the basal ganglia. The TyG index was calculated as the formula of ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. We used logistic regression analysis and mediation analysis to investigate the relations of TyG index with CSVD and cognitive function.ResultsMultivariate binary logistic regression analysis showed that increased TyG index (OR: 2.241; 95% Confidence Interval(CI): 1.439 to 3.490; P <0.001), or severe CSVD burden (OR: 2.198; 95% CI: 1.283 to 3.763; P = 0.004) was associated with an increased risk of cognitive impairment in elderly patients with T2DM after adjusting for potential confounders. In addition, TyG index was an independent risk factor of severe CSVD burden (OR: 1.472; 95% CI: 1.003 to 2.160; P = 0.048) after controlling for potential confounders. Compared with the lowest TyG index tertile, the multivariable-adjusted OR of the highest tertile was 3.298 (95% CI: 1.685 to 6.452; P for trend P for trend = 0.047) for severe CSVD burden. Mediation analysis found a significant moderating effect of the severe CSVD burden on the association between higher TyG index levels and cognitive impairment.ConclusionsThe increased TyG index is an independent risk factor for cognitive impairment and severe CSVD burden in clinical practice. A proportion of the effect of increased TyG index on cognitive impairment may be due to the aggravation of CSVD burden.

Despite recent preclinical progress with oncolytic bacteria in cancer therapy, dose-limiting toxicity has been a long-standing challenge for clinical application. Genetic and chemical modifications for enhancing the bacterial tumor-targeting ability have been unable to establish a balance between increasing its specificity and effectiveness while decreasing side effects. Herein, we report a simple, highly efficient method for rapidly self-assembling a clinically used lipid on bacterium and for reducing its minimum effective dose and toxicity to normal organs. The resultant bacteria present the ability to reverse-charge between neutral and acidic solutions, thus enabling weak interactions with the negatively charged normal cells, hence increasing their biocompatibility with blood cells and with the immune system. Additionally, the lipid-coated bacteria exhibit a longer blood circulation lifetime and low tissue trapping compared with the wild-type strains. Thereby, the engineered bacteria show enhanced tumor specificity and effectiveness even at low doses. Multiple visualization techniques are used for vividly demonstrating the time course of bacterial circulation in the blood and normal organs after intravenous administration. We believe that these methods for biointerfacial lipid self-assembly and evaluation of bacterial systemic circulation possess vast potential in exquisitely fabricating engineered bacteria for cancer therapy in the future., This research was supported by the National Natural Science Foundation of China (grant no. 81971726), the Natural Science Foundation of Jiangsu Province (grant no. BK20191351), the China Postdoctoral Science Foundation (grant no. 2020M670091ZX), and the Nanjing Healthcare Science and Technology Development Special Funded Project (YKK20191)., info:eu-repo/semantics/publishedVersion

Longdan Xiegan (LDXG) decoction, an ancient Chinese herbal formula, has been widely used in treating herpes zoster. This meta-analysis aimed to evaluate whether LDXG formula as adjuvant therapy had additional benefits in acute herpes zoster patients. Two authors independently searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wanfang database from their inception to July 31, 2021. Relevant randomized controlled trials (RCTs) that investigated the add-on effects of LDXG formula (decoction, capsule, or pill) in the management of acute herpes zoster were included. Nine RCTs with 821 patients were identified. A random effect model meta-analyses showed that LDXG formula plus conventional therapy significantly reduced the time to blister resolution (weighted mean difference [WMD] -1.31 days; 95% confidence intervals [CI] -1.56 to -1.06), time to crust formation (WMD -1.91 days; 95% CI -2.31 to -1.50), time to pain resolution (WMD -2.13 days; 95% CI -2.65 to -1.60), pain intensity assessed by visual analogue scale (WMD -1.13; 95% CI -2.03 to -0.24), and incidence of persistent pain (risk ratio [RR] 0.28; 95% CI 0.15-0.50) compared with the conventional therapy alone. However, the overall certainty of evidence was very low to moderate. LDXG formula as adjuvant therapy may achieve additional benefits in terms of accelerating skin healing process, relieving pain symptoms, and preventing persistent pain in acute herpes zoster patients. However, interpretation of these findings should be considered the presence of statistical heterogeneity and/or unclear risk of bias.

To evaluate the value of the β- d -glucan (BDG) testing of intraocular fluid for the diagnosis of fungal endophthalmitis (FE).Twenty patients (22 eyes) with FE were diagnosed using both culture and nonculture methods. Intraocular fluid was collected for BDG testing, including 22 eyes of FE and 55 eyes of control group. Under different BDG cutoff points as the test-positives, the BDG sensitivity, specificity, positive predictive value, and negative predictive value for FE were analyzed.The BDG testing value was 1,022.78 ± 1,362.40 pg/mL in the FE group, significantly higher than that of the control group (105.0 ± 180.80 pg/mL, P0.001). The area under the receiver operating characteristic (ROC) curve was 0.885 (95% confidence interval, 0.793-0.978; P0.001). With the prespecified BDG cutoff 107.83 pg/ml as the test-positive, sensitivity was 81.8%, specificity was 87.5%, and the Youden index was 0.693. When the BDG cutoff was depicted as 202.05 pg/mL, sensitivity reduced to 77.3%, specificity increased at 95.8%, and the Youden index reached the highest value of 0.731.β- d -glucan testing of intraocular fluid demonstrated good sensitivity and specificity regarding the diagnosis of FE, which can provide earlier diagnosis to achieve better outcomes.

Metastasis is a major cause of breast cancer mortality and the current study found histone demethylase, KDM2A, expression to be negatively correlated with breast cancer metastasis. KDM2A knockdown greatly promoted migration and invasion of breast cancer cells. The histone demethylase activity of KDM2A downregulated EGF transcription and suppressed the EGF-TSPAN8 pathway. Inhibition of breast cancer cell migration was also dependent on the histone demethylase activity of KDM2A. A novel mechanism of KDM2A-suppression of the EGF-TSPAN8 pathway which inhibited breast cancer cell migration and invasion is reported.

Background: Remnant cholesterol (RC) contributes to residual risk of atherosclerotic cardiovascular disease, but population-based evidence on the prospective relationship between RC and coronary artery calcium (CAC) progression is rare. Methods: We pooled data obtained from 6544 atherosclerotic cardiovascular disease–free individuals from the CARDIA study (Coronary Artery Risk Development in Young Adults; n=2635) and MESA (Multi-Ethnic Study of Atherosclerosis; n=3909), with a mean±SD age of 47.2±19.8 years; 3019 (46.1%) were men who completed computed tomography of CAC at baseline. RC was measured as total cholesterol minus HDL (high-density lipoprotein) cholesterol minus calculated LDL (low-density lipoprotein) cholesterol (LDL-C) estimated by using the Martin/Hopkins equation. Adjusted Cox models were used to assess the relationships between RC levels and CAC progression. We also performed discordance analyses examining the risk of CAC progression in RC versus LDL-C discordant/concordant groups using median cut points and clinically relevant LDL-C targets. Results: During a median follow-up of 8.6 years, 2778 (42.5%) participants had CAC progression. After multivariable adjustment for demographics and cardiovascular risk factors, a 1-mg/dL increase in RC levels was associated with a 1.3% higher risk of CAC progression (hazard ratio, 1.013 [95% CI, 1.008–1.017]). Results were similar when we categorized individuals by RC quartiles. Furthermore, the discordant high RC/low LDL-C group had a significantly higher risk of CAC progression than the concordant low RC/LDL-C group regarding their medians (hazard ratio, 1.195 [95% CI, 1.063–1.343]) or when setting the clinical LDL-C cut points at 100 and 130 but not 70 mg/dL. The association remained robust across a series of sensitivity analyses. Conclusions: Elevated RC levels were associated with an increased risk of CAC progression independent of traditional cardiovascular risk factors, even in individuals with optimal LDL-C levels. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT00005130 (CARDIA) and NCT00005487 (MESA).

Itch sensation provokes the scratch reflex to protect us from harmful stimuli in the skin. Although scratching transiently relieves acute itch through activation of mechanoreceptors, it propagates the vicious itch-scratch cycle in chronic itch by further aggravating itch over time. Although well recognized clinically, the peripheral mechanisms underlying the itch-scratch cycle remain poorly understood. Here, we show that mechanical stimulation of the skin results in activation of the Piezo2 channels on Merkel cells that pathologically promotes spontaneous itch in experimental dry skin. Three-dimensional reconstruction and immunoelectron microscopy revealed structural alteration of MRGPRA3 + pruriceptor nerve endings directed toward Merkel cells in the setting of dry skin. Our results uncover a functional miswiring mechanism under pathologic conditions, resulting in touch receptors triggering the firing of pruriceptors in the skin to drive the itch-scratch cycle.

Nrf2 (nuclear factor E2-related factor 2, encoded by Nfe2l2) acts as a master transcriptional regulator in mediating antioxidant, detoxification and cytoprotective responses against oxidative, electrophilic and metabolic stress, but also plays a crucial role in cancer metabolism and multiple oncogenic pathways, whereas the redox sensor Keap1 functions as a predominant inhibitor of Nrf2 and hence changes in its expression abundance directly affect the Nrf2 stability and transcriptional activity. However, nuanced functional isoforms of Keap1α and β have rarely been identified to date. Herein, we have established four distinct cell models stably expressing Keap1-/-, Keap1β (Keap1Δ1-31), Keap1-Restored and Keap1α-Restored, aiming to gain a better understanding of similarities and differences of two Keap1 isoforms between their distinct regulatory profiles. Our experimental evidence revealed that although Keap1 and its isoforms are still localized in the cytoplasmic compartments, they elicited differential inhibitory effects on Nrf2 and its target HO-1. Furtherly, transcriptome sequencing unraveled that they possess similar but different functions. Such functions were further determined by multiple experiments in vivo (i.e. subcutaneous tumour formation in nude mice) and in vitro (e.g., cell cloning, infection, migration, wound healing, cell cycle, apoptosis, CAT enzymatic activity and intracellular GSH levels). Of note, the results obtained from tumorigenesis experiments in xenograft model mice were verified based on the prominent changes in the PTEN signaling to the PI3K-AKT-mTOR pathways, in addition to substantially aberrant expression patterns of those typical genes involved in the EMT (epithelial-mesenchymal transition), cell cycle and apoptosis.

Background Via counting the different kinds of white blood cells (WBCs), a good quantitative description of a person’s health status is obtained, thus forming the critical aspects for the early treatment of several diseases. Thereby, correct classification of WBCs is crucial. Unfortunately, the manual microscopic evaluation is complicated, time-consuming, and subjective, so its statistical reliability becomes limited. Hence, the automatic and accurate identification of WBCs is of great benefit. However, the similarity between WBC samples and the imbalance and insufficiency of samples in the field of medical computer vision bring challenges to intelligent and accurate classification of WBCs. To tackle these challenges, this study proposes a deep learning framework by coupling the pre-trained ResNet and DenseNet with SCAM (spatial and channel attention module) for accurately classifying WBCs. Results In the proposed network, ResNet and DenseNet enables information reusage and new information exploration, respectively, which are both important and compatible for learning good representations. Meanwhile, the SCAM module sequentially infers attention maps from two separate dimensions of space and channel to emphasize important information or suppress unnecessary information, further enhancing the representation power of our model for WBCs to overcome the limitation of sample similarity. Moreover, the data augmentation and transfer learning techniques are used to handle the data of imbalance and insufficiency. In addition, the mixup approach is adopted for modeling the vicinity relation across training samples of different categories to increase the generalizability of the model. By comparing with five representative networks on our developed LDWBC dataset and the publicly available LISC, BCCD, and Raabin WBC datasets, our model achieves the best overall performance. We also implement the occlusion testing by the gradient-weighted class activation mapping (Grad-CAM) algorithm to improve the interpretability of our model. Conclusion The proposed method has great potential for application in intelligent and accurate classification of WBCs.

This study aimed to explore the efficacy of trypsin inhibitors in the treatment of severe pancreatitis (SP) by meta-analysis.The Boolean logic retrieval method was adopted to recruit the relevant literature. Chinese and English databases were respectively searched using a combination of the following search terms: "trypsin inhibitor", "acute pancreatitis", and "severe pancreatitis". The trypsin-treated SP group was set as the experimental group, and the blank control was set as the control group. Meta-analysis was performed using RevMan 5.3 software provided by the Cochrane system.A total of 12 references were included. The meta-analysis suggested that the heterogeneity test results of pancreatic infection incidence were Chi2 =0.51, degrees of freedom (df) =7, I2=0%50%, and P=1.000.01, with risk ratio (RR): 0.80, 95% confidence interval (CI): (0.64, 1.01), Z=1.88, and P=0.06. The heterogeneity test results of extra-pancreatic infection incidence were Chi2 =0.20, df =5, I2=0%50%, and P=1.000.01, with RR: 0.81, 95% CI: (0.62, 1.05), Z=1.60, and P=0.11. The heterogeneity test results of the length of hospital stay were Tau2 =65.69, Chi2 =75.05, df =6, I2=92%50%, and P0.0001. The length of hospital stay of the experimental group was shorter than that of the control group, with mean difference (MD): -23.31 and the 95% CI: (-29.60, -17.02), and the difference was statistically significant (Z=7.26, P0.0001). The heterogeneity test results of the inflammatory factor tumor necrosis factor-α (TNF-α) level were Chi2 =67.28, df =3, I2=96%50%, and P0.0001. The level of TNF-α in the experimental group was lower than that in the control group, with MD: -11.69, 95% CI: (-12.51, -10.87), and the difference was statistically significant (Z=27.88, P0.0001). The heterogeneity test results of the mortality rate were Chi2 =2.52, df =5, I2=0%50%, and P=0.770.01. The mortality rate of the experimental group was lower than that of the control group, with RR: 0.27 and 95% CI: (0.19, 0.40), and the difference was notable (Z=6.75, P0.0001).The meta-analysis performed in this study confirmed that trypsin inhibitors can inhibit the release of inflammatory factors and reduce mortality rate of SP patients.

BACKGROUND Isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) are the four most common drugs for the first-line treatment of tuberculosis (TB). Although chemotherapy drugs are widely used in the treatment of TB, and achieved good results, but the side effects, especially anti-tuberculosis drug-induced liver injury (ATDILI), cannot be overlooked. Many researchers have made efforts to uncover the association of cytochrome P450 (CYP) enzyme genetic polymorphisms with ATDILI. In this study, we systematically reviewed and meta-analyzed the relationship between CYP polymorphism and susceptibility to ATDILI. METHODS We carried out literature searches of PubMed, Ovid, the Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI). Medical Subject Headings (MeSH) terms including "cytochrome P450 enzyme", "drug-induced liver injury", "polymorphism", "tuberculosis", and "hepatotoxicity" were used as keywords for our searches. RESULTS The pooled odds ratio (OR) of all studies for CYP2E1 to the risk of ATDILI was 1.18 [95% confidence interval (CI): 0.82-1.71]. The articles in this meta-analysis were observed to be mildly heterogeneous. Further subgroup analysis revealed that the patients who receiving a four-drug protocol (INH + RIF + PZA + EMB) or three-drug protocol (INH + RIF + PZA) regimens showed a higher risk of ATDILI than those who receiving INH alone. However, subgroup analyses according to participants' ethnic origin, study type, and the definition of ATDILI produced no statistically significant results. Associations between other genes in the CYP family and ATDILI were indistinct and equivocal. DISCUSSION Our meta-analysis has uncovered an association between CYP2E1 RsaI/PstI polymorphisms and ATDILI, especially among patients who receive a four-drug (INH + RIF + PZA + EMB) or three-drug (INH + RIF + PZA) anti-TB treatment regimen.

Optical imaging has played a vital role in development of biomedicine and image-guided theragnostic. Nevertheless, the clinical translation of optical molecular imaging for deep-tissue visualization is still limited by poor signal-to-background ratio and low penetration depth owing to light scattering and tissue autofluorescence. Hence, to facilitate precise diagnosis and accurate surgery excision in clinical practices, the responsive optical probes (ROPs) are broadly designed for specific reaction with biological analytes or disease biomarkers via chemical/physical interactions for photoacoustic and second near-infrared fluorescence (NIR-II, 900–1700 nm) fluorescence imaging. Herein, the recent advances in the development of ROPs including molecular design principles, activated mechanisms and treatment responses for photoacoustic and NIR-II fluorescence imaging are reviewed. Furthermore, the present challenges and future perspectives of ROPs for deep-tissue imaging are also discussed.

Background Intradialytic hypotension (IDH) remains the most frequent severe side effect of hemodialysis (HD) and increases patient morbidity and mortality. Excessive ultrafiltration (UF) is considered the leading cause of IDH. This study developed a suitable prescription of UF to reduce the incidences of IDH episodes. Methods A retrospective study was performed to analyze 33,224 HD/hemodiafiltration (HDF) treatments in 312 patients. The prescription of UF were determined following the International Society of Peritoneal Dialysis (ISPD) guideline. The Pearson's method was used to study the correlation between relative variables. The receiver operating characteristic (ROC) curve was used to predict the value of the UF/weight ratio (UF/Wt) for IDH in all patients to establish a diagnostic cut-off point. Univariate and multivariate logistic regression analyses were applied to study the risk factors of IDH. Results Twelve thousand five hundred and fifty-eight sessions of IDH (38.7%) were identified, among which 1,224 (3.6%) were recorded with intervention against IDH. Both the systolic blood pressure (SBP) and mean arterial pressure (MAP) of the hemodialytic patients were positively correlated with the UF quantity and the UF/Wt, but negatively correlated with blood flow. The ROC curve showed that UF/Wt =0.04 was the cut-off point for IDH. Age [per 10-year increment, odds ratio (OR) =1.005, 95% confidence interval (CI): 1.004 to 1.007, P=0.000], diabetes mellitus (OR =1.209, 95% CI: 1.122 to 1.303, P=0.000), and UF/Wt >0.04 (OR =1.605, 95% CI: 1.532 to 1.682, P=0.000) were all independently associated with higher incidences of IDH. Conclusions IDH commonly occurs during HD in Chinese patients. Unchangeable factors such as diabetes and age, and modifiable factors including UF were associated with IDH. A UF/Wt threshold more than 0.04 may be a potential alert for avoiding IDH, especially in the elderly and diabetic patients.

BACKGROUND/AIMS To explore risk factors of acute kidney injury (AKI) and its severity after liver transplantation. MATERIALS AND METHODS This was a retrospective cohort of consecutive adults undergoing orthotopic liver transplantation (OLT) at a referral hospital. Risk factors for AKI from 1week post-liver transplantation and 4-week outcomes were analysed. Further analyses of factors that influenced the severity of AKI were also performed. RESULTS A total of 204 patients were included. AKI was found in 55.4% of patients in the first week after OLT. Risk factors for AKI were recipient's sex, BMI, preoperative creatinine, preoperative hepatic encephalopathy, cold ischaemia time, duration of surgery, duration of inferior vena clamping, postoperative peak lactate and postoperative peak AST, which were higher in the AKI group. Four weeks after liver transplantation, 20.4% of AKI patients still had abnormal renal function and a mortality rate of 3.6%, and these values were significantly higher than those of patients without AKI (P

Host-modulation therapy is generally accepted as a novel promising method for diabetic periodontitis (DP) treatment and screening an appropriate drug model is the key to success. Resveratrol (RSV), because of its viable antioxidative and anti-inflammatory properties and its ability to control glucose metabolism, is considered a potential candidate. However, poor water solubility, rapid decomposition and short serum half-life period significantly limit its application. Therefore, in this study, we designed a RSV-grafted mesoporous silica nanoparticle (MSN-RSV) drug carrier system to enhance RSV's stability effectively and prolong its duration. Further analyses have verified the indispensable role of MSNs in improving the bioavailability of RSV, which could result in a more favorable therapeutic efficacy in DP related to regulating the polarization of the macrophage. The reason for this could be explained by activating the SIRT1/AMPK signaling pathway and inhibiting the NF

Pain emanating from the female reproductive tract is notoriously difficult to treat, and the prevalence of transient pelvic pain has been placed as high as 70%-80% in women surveyed. Although sex hormones, especially estrogen, are thought to underlie enhanced pain perception in females, the underlying molecular and cellular mechanisms are not completely understood. Here, we showed that the pain-initiating TRPA1 channel was required for pain-related behaviors in a mouse model of estrogen-induced uterine pain in ovariectomized female mice. Surprisingly, 2- and 4-hydroxylated estrogen metabolites (2- and 4-HEMs) in the estrogen hydroxylation pathway, but not estrone, estradiol, or 16-HEMs, directly increased nociceptor hyperactivity through TRPA1 and TRPV1 channels, and picomolar concentrations of 2- and 4-hydroxylation estrone (2- or 4-OHE1) could sensitize TRPA1 channel function. Moreover, both TRPA1 and TRPV1 were expressed in uterine-innervating primary nociceptors, and their expression was increased in the estrogen-induced uterine pain model. Importantly, pretreatment with 2- or 4-OHE1 recapitulated estrogen-induced uterine pain-like behaviors, and intraplantar injections of 2- and 4-OHE1 directly produced a TRPA1-dependent mechanical hypersensitivity. Our findings demonstrated that TRPA1 is critically involved in estrogen-induced uterine pain-like behaviors, which may provide a potential drug target for treating female reproductive tract pain.

This study was carried out to assess the association of dehydroepiandrosterone (DHEA) with diabetic nephropathy (DN) in patients with type 2 diabetes mellitus to better predict the progression of diabetic nephropathy.A total of 1,082 patients with type 2 diabetes mellitus in the Department of Endocrinology and Metabolism of Tianjin Medical University General Hospital were enrolled in this study, and grouped for comparison. The effect of serum DHEA on DN was evaluated by multivariate logistic regression analysis, and receiver operating characteristic curves were established to explore the optimal concentration of DHEA in patients with DN and non-DN.DHEA was significantly decreased in patients with DN (P 0.001). The prevalence of DN was significantly higher in the low DHEA quartile than in the other quartiles (P 0.001). Spearman-related analysis showed that DHEA levels were negatively correlated with patient age, course of diabetes, systolic blood pressure, blood creatinine, uric acid, urine albumin-to-creatinine ratio, 24-h urine microalbumin, 24-h urine protein quantification and glomerular filtration rate, and positively correlated with body mass index, total cholesterol and low density lipoprotein. Logistic regression analysis showed that the effect of DHEA on DN was statistically significant (P 0.001). The receiver operating characteristic curve showed that the sensitivity was 81.4%, the specificity was 70% and the area under the curve was 0.812 when the optimal cut-off value was 1,640 (pg/mL).DHEA is significantly associated with DN and might be a protective factor for DN, and is important for the prediction of DN.

Consistently, the high metastasis of cancer cells is the bottleneck in the process of tumor treatment. In this process of metastasis, a pivotal role is executed by epithelial–mesenchymal transition (EMT). The epithelial-to-mesenchymal transformation was first proposed to occur during embryonic development. Later, its important role in explaining embryonic developmental processes was widely reported. Recently, EMT and its intermediate state were also identified as crucial drivers in tumor progression with the gradual deepening of research. To gain insights into the potential mechanism, increasing attention has been focused on the EMT-related transcription factors. Correspondingly, miRNAs target transcription factors to control the EMT process of tumor cells in different types of cancers, while there are still many exciting and challenging questions about the phenomenon of microRNA regulation of cancer EMT. We describe the relevant mechanisms of miRNAs regulating EMT, and trace the regulatory roles and functions of major EMT-related transcription factors, including Snail, Twist, zinc finger E-box-binding homeobox (ZEB), and other families. In addition, on the basis of the complex regulatory network, we hope that the exploration of the regulatory relationship of non-transcription factors will provide a better understanding of EMT and cancer metastasis. The identification of the mechanism leading to the activation of EMT programs during diverse disease processes also provides a new protocol for the plasticity of distinct cellular phenotypes and possible therapeutic interventions. Here, we summarize the recent progress in this direction, with a promising path for further insight into this fast-moving field.

Dopamine (DA) is an important neurotransmitter; however, any excess or deficiency of DA will cause several diseases in humans. To monitor DA efficiently and conveniently, a Ag nanozyme strengthened by bioactive folic acid (FA@AgNPs) was developed by homogeneous redox assembly. After the microstructure and performance were characterized in detail, it was noted that the proposed FA@AgNPs possessed superior peroxidase-like activity due to the ultra-small Ag nanoparticles and multiple amino, hydroxyl, and aromatic rings in FA. FA@AgNPs accelerated the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with a low Michaelis constant (K

Background Infrapatellar fat pad (IPFP) is regarded as an essential knee tissue involved in osteoarthritis (OA) for its potential structural-related or metabolism-related function. This cross-sectional study aims to identify which part is more related to OA. Methods Patients with knee OA ( n = 53) and healthy controls ( n = 54) were prospectively recruited. Based on high-resolution magnetic resonance imaging with a slice thickness of only 0.35 mm, IPFP structural-related parameters (volume and maximal area), metabolism-related parameter (signal), degeneration indicators, and patellar maltracking indicators (patellar translation, patellofemoral angle, and Insall-Salvati ratio) were measured. IPFP volume (maximal area, and signal) was compared between healthy controls and OA patients. The level of significance for all comparisons was set as .05. Results OA patients had higher IPFP signal (672.9 ± 136.9 vs 567.3 ± 63.6, p = .009), but no significant difference in IPFP volume or maximal area compared with healthy controls. In healthy controls, IPFP signal was positively associated with age ( β = 1.481; 95% CI: 0.286–2.676; p = .018); IPFP maximal area was positively related to Insall-Salvati ratio ( β = 0.001; 95% CI: 0.0003–0.0017; p = .039), but not associated with patellar translation and patellofemoral angle. In OA patients, IPFP signal was positively associated with cartilage loss ( β = 0.005; 95% CI: 0.003–0.007; p = .013); no correlation between knee pain and IPFP volume or maximal area was observed. Conclusions The metabolism-related function of IPFP, which can be reflected by the IPFP signal, might play a more critical role in OA progression than its structural function.

Heavy metals (HMs) pose serious threats to both human and environmental health and therefore, effective and low-cost techniques to remove HMs are urgently required. Here we report a facile Fe-tannin coating method for zero-valent iron (ZVI) including nanoparticles (nZVI) and foam (Fe

There have been recent extensive studies and rapid advancement on the pathogenesis underlying idiopathic pulmonary fibrosis (IPF), and intricate pathogenesis of IPF has been suggested. The purpose of this study was to clarify the logical relationship between these mechanisms. An extensive search was undertaken of the PubMed using the following keywords: “etiology,” “pathogenesis,” “alveolar epithelial cell (AEC),” “fibroblast,” “lymphocyte,” “macrophage,” “epigenomics,” “histone,” acetylation,” “methylation,” “endoplasmic reticulum stress,” “mitochondrial dysfunction,” “telomerase,” “proteases,” “plasminogen,” “epithelial-mesenchymal transition,” “oxidative stress,” “inflammation,” “apoptosis,” and “idiopathic pulmonary fibrosis.” This search covered relevant research articles published up to April 30, 2020. Original articles, reviews, and other articles were searched and reviewed for content; 240 highly relevant studies were obtained after screening. IPF is likely the result of complex interactions between environmental, genetic, and epigenetic factors: environmental exposures affect epigenetic marks; epigenetic processes translate environmental exposures into the regulation of chromatin; epigenetic processes shape gene expression profiles; in turn, an individual's genetic background determines epigenetic marks; finally, these genetic and epigenetic factors act in concert to dysregulate gene expression in IPF lung tissue. The pathogenesis of IPF involves various imbalances including endoplasmic reticulum, telomere length homeostasis, mitochondrial dysfunction, oxidant/antioxidant imbalance, Th1/Th2 imbalance, M1–M2 polarization of macrophages, protease/antiprotease imbalance, and plasminogen activation/inhibition imbalance. These affect each other, promote each other, and ultimately promote AEC/fibroblast apoptosis imbalance directly or indirectly. Excessive AEC apoptosis and impaired apoptosis of fibroblasts contribute to fibrosis. IPF is likely the result of complex interactions between environmental, genetic, and epigenetic factors. The pathogenesis of IPF involves various imbalances centered on AEC/fibroblast apoptosis imbalance.

Background:. The low accuracy of equations predicting 24-h urinary sodium excretion using a single spot urine sample contributed to the misclassification of individual sodium intake levels. The application of single spot urine sample is limited by a lack of representativity of urinary sodium excretion, possibly due to the circadian rhythm in urinary excretion. This study aimed to explore the circadian rhythm, characteristics, and parameters in a healthy young adult Chinese population as a theoretical foundation for developing new approaches. Methods:. Eighty-five participants (mean age 32.4 years) completed the 24-h urine collection by successively collecting each of the single-voided specimens within 24 h. The concentrations of the urinary sodium, potassium, and creatinine for each voided specimen were measured. Cosinor analysis was applied to explore the circadian rhythm of the urinary sodium, potassium, and creatinine excretion. The excretion per hour was computed for analyzing the change over time with repeated-measures analysis of variance and a cubic spline model. Results:. The metabolism of urinary sodium, potassium, and creatinine showed different patterns of circadian rhythm, although the urinary sodium excretion showed non-significant parameters in the cosinor model. A significant circadian rhythm of urinary creatinine excretion was observed, while the circadian rhythm of sodium was less significant than that of potassium. The circadian rhythm of urinary sodium and creatinine excretion showed synchronization to some extent, which had a nocturnal peak and fell to the lowest around noon to afternoon. In contrast, the peak of potassium was observed in the morning and dropped to the lowest point in the evening. The hourly urinary excretion followed a similar circadian rhythm. Conclusion:. It is necessary to consider the circadian rhythm of urinary sodium, potassium, and creatinine excretion in adults while exploring the estimation model for 24-h urinary sodium excretion using spot urine.