Grouper TIM-1 promotes nodavirus infection by inhibiting immune and inflammation response.

T-cell/transmembrane immunoglobulin and mucin domain-containing (TIM) protein family has attracted particular attention because of their broad immune functions and the response to viral infections. TIM-1, a member of the TIM family, has been demonstrated to play an important role in viral infections. However, its roles during fish nodavirus infection still remained largely unknown. In this study, a homolog of TIM-1 from orange-spotted grouper (Epinephelus coioides) (EcTIM-1) was identified, and characterized. EcTIM-1 encoded a 217-amino acids protein, containing one Immunoglobulin domain. Homology analysis showed that EcTIM-1 shared 98.62 % and 42.99 % identity to giant grouper (E. lanceolatus) and human (Homo sapiens). Quantitative Real-time PCR analyses indicated that EcTIM-1 was expressed in all examined tissues, with higher expression in liver, spleen, skin, and heart, and was significantly up-regulated in response to red-spotted grouper nervous necrosis virus (RGNNV) infection. EcTIM-1 was distributed in the cytoplasm, and partly co-localized with Golgi apparatus and lysosomes in vitro. The ectopic expression of EcTIM-1 promoted RGNNV replication by increasing the level of viral genes transcription and protein synthesis. Besides, overexpression of EcTIM-1 decreased the luciferase activity of type I interferon (IFN1), interferon stimulated response elements (ISRE) and nuclear factor kappa-B (NF-κB) promoters, as well as the transcription of pro-inflammatory factors and interferon related genes. EcTIM-1 significantly suppressed the luciferase activity of IFN1, ISRE and NF-κB promoters evoked by Epinephelus coioides melanoma differentiation-associated gene 5 (EcMDA5), mitochondrial antiviral signaling protein (EcMAVS), stimulator of IFN genes (EcSTING) or TANK-binding kinase 1 (EcTBK1). Collectively, EcTIM-1 negatively regulated interferon and inflammatory response to promote RGNNV infection. These results provide a basis for a better understanding of the innate immune response of TIM-1 in fish.

Latent class analysis of healthcare workers' knowledge, attitudes, and practice levels, and risk factors regarding associated with occupational exposure to antineoplastic drugs: A multicenter cross-sectional study.

The study investigated the health care workers' knowledge, attitudes, and practice levels regarding occupational protection against antineoplastic drugs (ADs) via analysis of latent classes and their influencing factors. A convenience sampling method was used to select healthcare workers from 7 hospitals in southern China between April and August 2023. A questionnaire based on literature analysis, brainstorming, and Delphi method was used to investigate the knowledge, practice, and attitudes of healthcare workers exposed to ADs for appropriate occupational protection intervention, followed by latent class analysis. The factors influencing latent classes were identified via single-factor analysis and multiple logistic regression. A total of 322 healthcare workers from departments using ADs were surveyed. The knowledge score associated with occupational protection against ADs was 31.95 ±â€…7.38. The attitude score was 21.08 ±â€…2.729, while the practice score was 36.54 ±â€…9.485. The overall score was 89.57 ±â€…15.497. The healthcare workers were divided into 4 latent classes based on their knowledge, attitude, and practice associated with occupational protection measures against ADs. Healthcare workers in the 4 categories showed significance differences based on professional title, marital status, educational background, and frequency of exposure to ADs (P < .05). The knowledge, attitude, and practice levels of healthcare workers engaged in ADs at work can be divided into 4 latent classes. Despite their increased awareness of the hazards associated with ADs and their attitudes toward protection, the healthcare workers displayed poor knowledge and implementation of occupational protection measures.

Once-daily upadacitinib versus placebo in adults with extensive non-segmental vitiligo: a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study.

Background: Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo. Methods: This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6 mg (UPA6), upadacitinib 11 mg (UPA11), upadacitinib 22 mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975. Findings: Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n = 49), UPA11 (n = 47), UPA22 (n = 43), or PBO (n = 46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was -7.60 (95% CI -22.18 to 6.97; p = 0.3037) for UPA6, -21.27 (95% CI -36.02 to -6.52; p = 0.0051) for UPA11, and -19.60 (95% CI -35.04 to -4.16; p = 0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was -7.45 (95% CI -16.86 to 1.96; p = 0.1198) for UPA6, -10.84 (95% CI -20.37 to -1.32; p = 0.0259) for UPA11 and -14.27 (95% CI -24.24 to -4.30; p = 0.0053) for UPA22. Ongoing treatment with upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n = 1)] and non-fatal ischemic stroke [UPA11 (n = 1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed. Interpretation: Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15 mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial. Funding: AbbVie Inc.

Association of cooking oil and incident of frailty in older adults: a cohort study.

BACKGROUND: Studies examining the potential association between cooking oil and frailty risk in older adults have produced conflicting outcomes. Therefore, our objective was to explore the relationship between cooking oil (vegetable and animal fat oils), changes in oil usage, and the risk of frailty in older adults. METHODS: We included 4,838 participants aged ≥ 65 years without frailty (frailty index < 0.25) from the 2011 wave of the Chinese Longitudinal Healthy Longevity Survey. Follow-up occurred in the 2014 and 2018 waves. Cox proportional hazard models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) to examine the association between cooking oil and frailty. Additionally, we evaluated the effect of switching cooking oil on frailty during the follow-up period. RESULTS: During a median follow-up of 3.0 (2.8-6.9) years, 1,348 individuals (27.9%) developed frailty. Compared to those using vegetable oil, users of animal fat oil had a lower risk of frailty (HR = 0.72, 95% CI: 0.61-0.85). Participants who switched from vegetable oil to animal fat oil, as well as those consistently using animal fat oil, had lower risks of frailty with HRs of 0.70 (0.52-0.95) and 0.63 (0.51-0.77) respectively, compared to those who consistently used vegetable oil. Conversely, individuals who switched from animal fat oil to vegetable oil experienced an increased risk of frailty (HR: 1.41, 95% CI: 1.01-1.97). CONCLUSIONS: The utilization of animal fat oil in cooking exhibited a reduced frailty risk among older adults. Conversely, transitioning from animal fat oil to vegetable oil may elevate the risk. These findings propose that substituting vegetable oil with animal fat oil in the diet may safeguard against frailty.

Synthesis and Evaluation of [18F]AlF-NOTA-c-DVAP: A Novel PET Probe for Imaging GRP78 in Cancer.

GRP78, a member of the HSP70 superfamily, is an endoplasmic reticulum chaperone protein overexpressed in various cancers, making it a promising target for cancer imaging and therapy. Positron emission tomography (PET) imaging offers unique advantages in real time, noninvasive tumor imaging, rendering it a suitable tool for targeting GRP78 in tumor imaging to guide targeted therapy. Several studies have reported successful tumor imaging using PET probes targeting GRP78. However, existing PET probes face challenges such as low tumor uptake, inadequate in vivo distribution, and high abdominal background signal. Therefore, this study introduces a novel peptide PET probe, [18F]AlF-NOTA-c-DVAP, for targeted tumor imaging of GRP78. [18F]AlF-NOTA-c-DVAP was radiolabeled with fluoride-18 using the aluminum-[18F]fluoride ([18F]AlF) method. The study assessed the partition coefficients, stability in vitro, and metabolic stability of [18F]AlF-NOTA-c-DVAP. Micro-PET imaging, pharmacokinetic analysis, and biodistribution studies were carried out in tumor-bearing mice to evaluate the probe's performance. Docking studies and pharmacokinetic analyses of [18F]AlF-NOTA-c-DVAP were also performed. Immunohistochemical and immunofluorescence analyses were conducted to confirm GRP78 expression in tumor tissues. The probe's binding affinity to GRP78 was analyzed by molecular docking simulation. [18F]AlF-NOTA-c-DVAP was radiolabeled in just 25 min with a high yield of 51 ± 16%, a radiochemical purity of 99%, and molar activity within the range of 20-50 GBq/µmol. [18F]AlF-NOTA-c-DVAP demonstrated high stability in vitro and in vivo, with a logD value of -3.41 ± 0.03. Dynamic PET imaging of [18F]AlF-NOTA-c-DVAP in tumors showed rapid uptake and sustained retention, with minimal background uptake. Biodistribution studies revealed rapid blood clearance and excretion through the kidneys following a single-compartment reversible metabolic model. In PET imaging, the T/M ratios for A549 tumors (high GRP78 expression), MDA-MB-231 tumors (medium expression), and HepG2 tumors (low expression) at 60 min postintravenous injection were 10.48 ± 1.39, 6.25 ± 0.47, and 3.15 ± 1.15% ID/g, respectively, indicating a positive correlation with GRP78 expression. This study demonstrates the feasibility of using [18F]AlF-NOTA-c-DVAP as a PET tracer for imaging GRP78 in tumors. The probe shows promising results in terms of stability, specificity, and tumor targeting. Further research may explore the clinical utility and potential therapeutic applications of this PET tracer for cancer diagnosis.

Deepm6A-MT: A deep learning-based method for identifying RNA N6-methyladenosine sites in multiple tissues.

N6-methyladenosine (m6A) is the most prevalent, abundant, and conserved internal modification in the eukaryotic messenger RNA (mRNAs) and plays a crucial role in the cellular process. Although more than ten methods were developed for m6A detection over the past decades, there were rooms left to improve the predictive accuracy and the efficiency. In this paper, we proposed an improved method for predicting m6A modification sites, which was based on bi-directional gated recurrent unit (Bi-GRU) and convolutional neural networks (CNN), called Deepm6A-MT. The Deepm6A-MT has two input channels. One is to use an embedding layer followed by the Bi-GRU and then by the CNN, and another is to use one-hot encoding, dinucleotide one-hot encoding, and nucleotide chemical property codes. We trained and evaluated the Deepm6A-MT both by the 5-fold cross-validation and the independent test. The empirical tests showed that the Deepm6A-MT achieved the state of the art performance. In addition, we also conducted the cross-species and the cross-tissues tests to further verify the Deepm6A-MT for effectiveness and efficiency. Finally, for the convenience of academic research, we deployed the Deepm6A-MT to the web server, which is accessed at the URL http://www.biolscience.cn/Deepm6A-MT/.

The antiviral role of largemouth bass STING against iridovirus infection.

Stimulator of interferon gene (STING) plays a crucial role in the innate immune response against viral and bacterial pathogens. However, its function in largemouth bass iridovirus (LMBV) infection remains uncertain. Here, a STING homolog (MsSTING) from largemouth bass (Micropterus salmoides) was cloned and characterized. MsSTING encoded a 407-amino-acid polypeptide, which shared 84.08% and 41.45% identity with golden perch (Perca flavescens) and human (Homo sapiens) homologs, respectively. MsSTING contained four transmembrane domains and a conserved C-terminal domain. The mRNA level of MsSTING was significantly increased in response to LMBV infection in vitro. Subcellular localization observation indicated that MsSTING encoded a cytoplasmic protein, which co-localized predominantly with endoplasmic reticulum (ER) and partially with mitochondria. Moreover, its accurate localization was dependent on the N-terminal transmembrane motif (TM) domains. MsSTING was able to activate interferon (IFN) response, evidenced by the activation of IFN1, IFN3 and ISRE promoters by its overexpression in vitro. Mutant analysis showed that both the N-terminal and C-terminal domain of MsSTING were essential for its activation on IFN response. In addition, overexpression of MsSTING inhibited the transcription and protein levels of viral core genes, indicating that MsSTING exerted antiviral action against LMBV. Consistently, the inhibitory effects were significantly attenuated when the N-terminal or C-terminal domains of MsSTING was deleted. Furthermore, MsSTING overexpression upregulated the transcriptions of interferon-related genes and pro-inflammatory factors, including TANK-binding kinase 1(TBK1), interferon regulatory factor 3 (IRF3), interferon regulatory factor 7 (IRF7), interferon stimulated exonuclease gene 20 (ISG20), interferon-induced transmembrane protein 1(IFITM1), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6). Together, MsSTING exerted antiviral action upon LMBV infection through positive regulation the innate immune response.

Myocardial bridging in obstructive hypertrophic cardiomyopathy: a risk factor for myocardial fibrosis.

BACKGROUND: Myocardial bridging (MB) is common in patients with hypertrophic cardiomyopathy (HCM). There are sparse data on the impact of MB on myocardial fibrosis in HCM. This study was designed to evaluate the relationship between MB and myocardial fibrosis in patients with obstructive HCM. METHODS: In this cohort study, retrospective data were collected from a high-volume HCM center. Patients with obstructive HCM who underwent septal myectomy and preoperative cardiac magnetic resonance (CMR) were screened from 2011 to 2018. RESULTS: Finally, 492 patients were included in this study, with an average age of 45.7 years. Of these patients, 76 patients had MB. MB occurred mostly in the left anterior descending artery (73/76). The global extent of late gadolinium enhancement (LGE) was correlated with the degree of systolic compression (r = 0.33, p = 0.003). Multivariable linear regression analysis revealed that the degree of systolic compression was an independent risk factor for LGE (ß = 0.292, p = 0.007). The LGE fraction of basal and mid anteroseptal segments in patients with severe MB (compression ratio ≥ 80%) was significantly greater than that in patients with mild to moderate MB (compression ratio < 80%). During a median follow-up of 28 (IQR: 15-52) months, 15 patients died. Kaplan-Meier analysis did not identify differences in all-cause death (log-rank p = 0.63) or cardiovascular death (log-rank p = 0.72) between patients undergoing MB-related surgery and those without MB. CONCLUSIONS: MB with severe systolic compression was significantly associated with a high extent of fibrosis in patients with obstructive HCM. Concomitant myotomy or coronary artery bypass grafting might provide excellent survival similar to that of patients without MB. Identification of patients with severe MB and providing comprehensive management might help improve the prognosis of patients with HCM.

A formula for instability-related bone loss: estimating glenoid width and redefining bare spot.

PURPOSE: The aim of the study reveals a new intuitive method for preoperatively assessing defect ratio in glenoid deficiency based on the native glenoid width and the bare spot. METHODS: A linear relationship, i.e. the rh formula, between the native glenoid width (2r) and height (h) was revealed by a cadaver cohort (n = 204). To validate the reliability of the rh formula, 280 3D-CT images of intact glenoids were recruited. To evaluate the accuracy of rh formula in estimating glenoid defect, the 65 anterior-inferior defect models were artificially established based on the 3D-CT images of intact glenoids. Moreover, a clinically common anterior-posterior (AP) method was compared with the rh formula, to verify the technical superiority of rh formula. RESULTS: The regression analysis indicated a linear relationship between the width and height of intact glenoid: 2r = 0.768 × h - 1.222 mm (R2 = 0.820, p < 0.001). An excellent reliability was found between the formula prediction and model width (ICC = 0.911, p = 0.266). An excellent agreement was found between the predicted values and model parameters (glenoid width, ICCrh = 0.967, prh = 0.778; defect ratio, prh = 0.572, ICCrh = 0.997). And, it is of higher accuracy compared to the AP method (glenoid width, ICCAP = 0.933, pAP = 0.001; defect ratio, ICCAP = 0.911, pAP = 0.033). CONCLUSION: Applying the cadaver-based formula on 3D-CT scans accurately predicts native glenoid width and redefines bare spot for preoperatively determining glenoid bone loss.

Automatic segmentation of ameloblastoma on ct images using deep learning with limited data.

BACKGROUND: Ameloblastoma, a common benign tumor found in the jaw bone, necessitates accurate localization and segmentation for effective diagnosis and treatment. However, the traditional manual segmentation method is plagued with inefficiencies and drawbacks. Hence, the implementation of an AI-based automatic segmentation approach is crucial to enhance clinical diagnosis and treatment procedures. METHODS: We collected CT images from 79 patients diagnosed with ameloblastoma and employed a deep learning neural network model for training and testing purposes. Specifically, we utilized the Mask R-CNN neural network structure and implemented image preprocessing and enhancement techniques. During the testing phase, cross-validation methods were employed for evaluation, and the experimental results were verified using an external validation set. Finally, we obtained an additional dataset comprising 200 CT images of ameloblastoma from a different dental center to evaluate the model's generalization performance. RESULTS: During extensive testing and evaluation, our model successfully demonstrated the capability to automatically segment ameloblastoma. The DICE index achieved an impressive value of 0.874. Moreover, when the IoU threshold ranged from 0.5 to 0.95, the model's AP was 0.741. For a specific IoU threshold of 0.5, the model achieved an AP of 0.914, and for another IoU threshold of 0.75, the AP was 0.826. Our validation using external data confirms the model's strong generalization performance. CONCLUSION: In this study, we successfully applied a neural network model based on deep learning that effectively performs automatic segmentation of ameloblastoma. The proposed method offers notable advantages in terms of efficiency, accuracy, and speed, rendering it a promising tool for clinical diagnosis and treatment.

Development and validation of an individualized angiogenesis and tumor-infiltrating lymphocytes prognostic signature in nasopharyngeal carcinoma.

In recent years, targeted therapy and immunotherapy have become ideal choices for the treatment of advanced, metastatic, recurrent, and drug-resistant nasopharyngeal carcinoma (NPC), but the lack of understanding of the relationship and mechanism between TILs and angiogenic factors hinders therapeutic development and optimization. In this study, the expression of angiogenesis-related markers (VEGF-A,VEGFR-2) and TILs (CD4+T,CD8+T) was studied by using immunohistochemistry (IHC). Then we constructed an immunohistochemical scoring model for the co-expression of angiogenesis-related markers and TILs (COV+TIL score)in the training (n = 124) and validated the accuracy and reliability of the scoring system in the validation cohorts (n = 114), respectively We established the COV+TIL score model and stratified patients into different risk level in the training cohorts according to COV+TIL score (cut-off value=28). Patients in the high-risk group had worse prognosis in the training cohorts five-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) was lower than that of patients in the low-risk group, and this result was validated in the validation cohorts ( 5-year OS in the high-risk and the low-risk group 46.8% vs. 83.4%, HR: 3.42, 95%CI: 1.77-6.61, p < 0.001); ( 5-year PFS 45.9% vs. 81.2%, HR: 3.22, 95%CI: 1.71-6.06, p < 0.001); ( 5-year LRRFS 74.6% vs. 87.5%, HR: 3.22, 95%CI: 1.16-8.93, p = 0.027); and ( 5-year DMFS79.2% vs. 93.2%, HR: 2.22, 95%CI: 0.91-5.39, p = 0.086). Upon multivariable analysis, COV+TIL score emerged as an independent prognostic indicator for defining survival in the training cohorts and the validation cohorts. Combining the COV+TIL score and TNM stage improved the prediction ability of the survival. In conclusion, NPC patients with high COV+TIL score showed worse prognosis.

THSD7A as a Promising Biomarker for Membranous Nephrosis.

Membranous nephropathy (MN) is an autoimmune disease of the kidney glomerulus and one of the leading causes of nephrotic syndrome. The disease exhibits heterogeneous outcomes with approximately 30% of cases progressing to end-stage renal disease. Traditionally, the standard approach of diagnosing MN involves performing a kidney biopsy. Nevertheless, kidney biopsy is an invasive procedure that poses risks for the patient including bleeding and pain, and bears greater costs for the health system. The clinical management of MN has steadily advanced owing to the identification of autoantibodies to the phospholipase A2 receptor (PLA2R) in 2009 and thrombospondin domain-containing 7A (THSD7A) in 2014 on the podocyte surface. At present, serum anti-PLA2R antibody detection and glomerular PLA2R antigen staining have been used for clinical diagnosis and prognosis, but the related detection of THSD7A has not been widely used in clinical practice. Here, we summarized the emerging knowledge regarding the roles THSD7A plays in MN and its clinical implications as diagnostic, prognostic, and therapeutic response as well as Methods for detecting serum THSD7A antibodies.

Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis.

We aimed to investigate the clinical efficacy of blood purification technology based on cytokine adsorption in the treatment of sepsis. Sixty patients with sepsis were randomly divided into control (n = 30) and experimental (n = 30) groups. Both groups were given routine treatment and continuous venovenous hemofiltration, and on this basis, the experimental group received acrylonitrile/sodium methacrylate (AN69ST) blood purification. The levels of C-reactive protein, procalcitonin, white blood cell count, albumin, platelets, total bilirubin, creatinine, lactic acid, and APACE II score, as well as secretion of inflammatory factors interleukin (IL)-6 and tumor necrosis factor (TNF-α) were compared. The hospitalization time, mechanical ventilation (MV) time, drug use time, and mortality were analyzed. After treatment, the secretion levels of IL-6 and TNF-α were decreased, and other indicators were significantly improved compared with those before treatment (P < 0.05), especially in the experimental group (P < 0.05). The hospitalization time, MV time, and drug use time in the experimental group were significantly lower than those of the control group (P < 0.05), and the mortality was lower than that in the control group (P < 0.05). In conclusion, blood purification technology based on cytokine adsorption can significantly improve various indicators of sepsis patients, reduce hospitalization time, reduce mortality, and improve the prognosis.

Mitral Valve Prolapse in Obstructive Hypertrophic Cardiomyopathy.

Obstructive hypertrophic cardiomyopathy (oHCM) and mitral valve (MV) prolapse (MVP) are the 2 conditions which could cause symptomatic heart failure and sudden cardiac death. The clinical characteristics and surgical outcomes of patients with oHCM and MVP have not been well reported. From April 2012 to February 2018, 84 patients with oHCM (28 patients with MVP and 56 gender- and age-matched patients without MVP) who underwent septal myectomy at our institution were enrolled in this study. Information on clinical characteristics and outcomes was obtained from electronic medical records and follow-up surveys. Compared with those without MVP, patients with MVP were more symptomatic (New York Heart Association class III to IV; 96% vs 77%), more often moderate-to-severe mitral regurgitation (86% vs 48%), atrial fibrillation (39% vs 11%) and higher incidence of nonsustained ventricular tachycardia (44% vs 15%). Twenty (71%) had MV repair and 8 (29%) had MV replacement. Compared with patients without MVP, those with MVP had a longer postoperative hospital stay (10.9 ± 6.4 vs 7.8 ± 2.8 days). None of the 84 study patients died during hospital or follow-up. At the most recent echocardiographic evaluation, left ventricular outflow tract gradient significantly decreased from 69.7 ± 35.4 millimeters of mercury to 7.3 ± 5.1 millimeters of mercury and the degree of mitral valve regurgitation improved from grade 2.43 ± 0.69 to grade 0.5 ± 0.69. In conclusion, MVP occurs rarely in oHCM, and was related to atrial fibrillation, ventricular arrhythmia and mitral regurgitation. Mitral valve surgery in combination with myectomy is effective and safe for patients with oHCM and MVP, relieving substantially left ventricular outflow tract gradients and mitral regurgitation.

The meta-analysis of sister chromatid exchange as a biomarker in healthcare workers with occupational exposure to antineoplastic drugs.

BACKGROUND: Sister chromatid exchange (SCE) can be used to identify early occupational health status in health care workers. Our aim is to comprehensively assess the relationship between long-term exposure to antineoplastic drugs (ADs) and SCE in health care workers via meta-analysis. METHODS: Five databases were systematically searched for relevant articles published from inception to November 30, 2022. Literature data are expressed as mean difference and 95% confidence intervals (CI) or relative risk and 95% CI. For I2 > 50% trials, random effect model is used for statistical analysis, otherwise fixed effect model is used. This review was registered in the International Prospective Register of Systematic Reviews (identifier CRD42023399914). RESULTS: Fourteen studies were included in this study. Results showed the level of SCE in healthcare workers exposed to ADs was significantly higher than in controls. The mean difference of the SCE trial was 0.53 (95% CI: 0.10-0.95, P = .01) under a random-effects model. CONCLUSIONS: The findings suggested a significant correlation between occupational exposure to ADs in health care workers and SCE, requiring the attention of health care workers in general.

Neuroprotective Strategies for Stroke by Natural Products: Advances and Perspectives.

Cerebral ischemic stroke is a disease with high prevalence and incidence. Its management focuses on rapid reperfusion with intravenous thrombolysis and endovascular thrombectomy. Both therapeutic strategies reduce disability, but the therapy time window is short, and the risk of bleeding is high. Natural products (NPs) have played a key role in drug discovery, especially for cancer and infectious diseases. However, they have made little progress in clinical translation and pose challenges to the treatment of stroke. Recently, with the investigation of precise mechanisms in cerebral ischemic stroke and the technological development of NP-based drug discovery, NPs are addressing these challenges and opening up new opportunities in cerebral stroke. Thus, in this review, we first summarize the structure and function of diverse NPs, including flavonoids, phenols, terpenes, lactones, quinones, alkaloids, and glycosides. Then we propose the comprehensive neuroprotective mechanism of NPs in cerebral ischemic stroke, which involves complex cascade processes of oxidative stress, mitochondrial damage, apoptosis or ferroptosis-related cell death, inflammatory response, and disruption of the blood-brain barrier (BBB). Overall, we stress the neuroprotective effect of NPs and their mechanism on cerebral ischemic stroke for a better understanding of the advances and perspective in NPs application that may provide a rationale for the development of innovative therapeutic regimens in ischemic stroke.

Tooth loss, denture use, and all-cause and cause-specific mortality in older adults: a community cohort study.

Objectives: The available evidence on the connections between tooth loss, denture use, and mortality from all causes or specific causes among older adults is inconclusive. Therefore, we aimed to investigate the association between tooth loss, denture use, and all-cause and cause-specific mortality in older adults. Methods: A cohort of 5,403 participants aged 65 and older were recruited in the 2014 Chinese Longitudinal Healthy Longevity Survey wave and followed up in the 2018 wave. Cox proportional hazard models were used to examine the association between the number of natural teeth, denture use, and all-cause and cause-specific mortality. Results: During a mean (SD) follow-up of 3.1 years (1.3), 2,126 deaths (39.3%) occurred. Individuals with 0 and 1-9 teeth had higher mortality due to all-cause, cardiovascular disease (CVD), cancer, and other causes (all p-trend <0.05) than those with 20+ teeth. At the same time, no association was found with respiratory disease mortality. Participants who used dentures had lower mortality due to all causes [hazard ratios (HR) 0.79, 95% confidence intervals (CI) 0.71-0.88], CVD (HR 0.80, 95% CI 0.64-1.00), respiratory disease (HR 0.66, 95% CI 0.48-0.92), and other causes (HR 0.77, 95% CI 0.68-0.88) than those without dentures. Joint analysis revealed that older adults with fewer natural teeth and no dentures had higher mortality. Additionally, interaction analyses showed that the effects of the number of natural teeth on all-cause mortality were more pronounced in older adults aged <80 years (p-value for interaction = 0.03). Conclusion: Having fewer natural teeth, particularly less than 10 teeth, is linked to an increased risk of mortality from all causes, including CVD, cancer, and other causes, but not respiratory disease. The use of dentures would mitigate the adverse impact of tooth loss on all-cause and some cause-specific mortality.

Influence of occupational exposure to antineoplastic agents on adverse pregnancy outcomes among nurses: A meta-analysis.

AIM: This study aimed to explore the relationship between nurses' occupational exposure to antineoplastic agents and adverse pregnancy outcomes. DESIGN: Meta-analysis. METHODS: Data were retrieved from studies published before April 2022 in PubMed, the Cochrane Library, the Web of Science, Embase databases, the China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), China Science and Technology Journal databases (VIP) and Wan Fang databases (WF). Stata MP (Version 17.0) was used to conduct this meta-analysis. RESULTS: The current evidence shows that occupational exposure to antineoplastic agents increases nurses' risk of spontaneous abortions, stillbirths, and congenital abnormalities. It is necessary to pay attention to occupational exposures caused by antineoplastic agents, especially for female nurses of reproductive age. Managers should take timely and effective countermeasures to ensure their occupational safety and reduce the risk of adverse pregnancy outcomes.

3D MRI PD-SPACE-COR Predicting Safety Margin for Coracoid Transfer.

OBJECTIVE: The maximum bone length available for coracoid process transfer varies among individuals, while no preoperative guideline has been developed for predicting the safety margin (SM) in Latarjet shoulder reconstruction. The aim of the study was to evaluate the 3D MRI proton density (PD)-weighted sampling perfection with application-optimized contrasts using different flip-angle evolution (SPACE) sequence in preoperatively predicting SM for coracoid transfer. METHODS: The post-multiplanar reconstructed images were obtained from 24 volunteers (17 males, seven females) to determine the clarity and sensitivity of the PD-SPACE-COR and PD-SPACE-FS-COR protocols. Furthermore, the distance from the coracoid tip to the lateral edge of the attachment of trapezoid ligament (TL) was measured. To evaluate the accuracy of 3D MRI prediction, a cadaveric cohort has been launched in 32 shoulders (nine males, seven females). The distance between the tip of coracoid process and the outmost edge of TL footprint, namely, the SM, was measured. RESULTS: A better sensitivity was found in PD-SPACE-COR in detecting coracoclavicular ligaments (CCLs), including TL and conoid ligament (CL), compared to PD-SPACE-FS-COR by ranking, McNemar test (P = 0.001), and kappa coefficients (κ = 0.51, P = 0.43). The SM determined by the PD-SPACE-COR protocol was 24.28 ± 2.17 mm while that by cadaveric morphometry was 25.53 ± 2.84 mm. No difference was found between measurements (P = 0.78). CONCLUSION: This research provides new insights for preoperatively geometrical planning coracoid transfer by 3D MRI PD-SPACE-COR, which motivates personalized medicine in orthopedics.

The meta-analysis of cytogenetic biomarkers as an assessment of occupational risk for healthcare workers exposed to antineoplastic drugs.

OBJECTIVE: Antineoplastic drugs (ADs) are widely used in clinical practice and have been demonstrated to be effective in treating malignant tumors. However, they carry a risk of cytogenotoxicity for healthcare workers. Studies have reported that genotoxic biomarkers can be applied to assess the occupational health status of healthcare workers at an early stage, but results of different studies are variable. The objectives of the review were examine the association between long-term exposure to ADs and cytogenetic damage to healthcare workers. METHODS: We systematically reviewed studies between 2005 and 2021 using PubMed, Embase and Web of Science databases that used cytogenetic biomarkers to assess occupational exposure to ADs in healthcare workers. We used RevMan5.4 to analyze the tail length parameters of the DNA, frequency of the chromosomal aberrations, sister chromatid exchanges and micronuclei. A total of 16 studies were included in our study. The studies evaluate the quality of the literature through the Agency for Healthcare Research and Quality. RESULTS: The results revealed that under the random-effects model, the estimated standard deviation was 2.37 (95% confidence interval [CI] 0.92-3.81, P = 0.001) for the tail length parameters of the DNA, 1.48 (95% CI 0.71-2.25, P = 0.0002) for the frequency of chromosomal aberrations, 1.74 (95% CI 0.49-2.99, P = 0.006) for the frequency of sister chromatid exchanges and 1.64 (95% CI 0.83-2.45, P < 0.0001) for the frequency of micronuclei. CONCLUSIONS: The results indicate that there is a significant association between occupational exposure to ADs and cytogenetic damage, to which healthcare workers should be alerted.