Nanobody-based strategy for rapid and accurate pathogen detection: A case of COVID-19 testing.

Antibody pairs-based immunoassay platforms served as essential and effective tools in the field of pathogen detection. However, the cumbersome preparation and limited detection sensitivity of antibody pairs challenge in establishment of a highly sensitive detection platform. In this study, using COVID-19 testing as a case, we utilized readily accessible nanobodies as detection antibodies and further proposed an accurate design concept with a more scientific and efficient screening strategy to obtain ultrasensitive antibody pairs. We employed nanobodies capable of binding different antigenic epitopes of the nucleocapsid (NP) or receptor-binding domain (RBD) antigens sandwich as substitutes for monoclonal antibodies (mAbs) sandwich in fast detection formats and utilized time-resolved fluorescence (TRF) microspheres as the signal probe. Consequently, we developed a multi-epitope nanobody sandwich-based fluorescence lateral flow immunoassay (FLFA) strip. Our results suggest that the NP antigen had a detection limit of 12.01pg/mL, while the RBD antigen had a limit of 6.51 pg/mL using our FLFA strip. Based on double mAb sandwiches, the values presented herein demonstrated 4 to 32-fold enhancements in sensitivity, and 32 to 256-fold enhancements compared to commercially available antigen lateral flow assay kits. Furthermore, we demonstrated the excellent characteristics of the proposed test strip, including its specificity, stability, accuracy, and repeatability, which underscores its the prospective utility. Indeed, these findings indicate that our established screening strategy along with the multi-epitope nanobody sandwich mode provides an optimized strategy in the field of pathogen detection.

A diagnostic model for differentiating tuberculous spondylodiscitis from pyogenic spondylodiscitis based on pathogen-confirmed patients.

OBJECTIVE: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed. METHODS: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed. RESULTS: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability. CONCLUSIONS: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS.

Association of the triglyceride-glucose index with all-cause and cause-specific mortality: a population-based cohort study of 3.5 million adults in China.

Background: The triglyceride-glucose (TyG) index has been recognized as a crucial risk factor for cardiovascular diseases. However, the association between the TyG index and mortality in the general population remains elusive. Methods: Participants were enrolled from the China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART), a nationwide prospective cohort study. The outcomes of interest were all-cause, cardiovascular, and cancer mortality. Restricted cubic splines and Cox regression models were used to assess the associations between the TyG index and outcomes. Findings: In total, 3,524,459 participants with a median follow-up of 4.6 (IQR, 3.1-5.8) years were included. The associations of the TyG index with all-cause and cardiovascular mortality were reverse L-shaped, with cut-off values of 9.75 for all-cause mortality and 9.85 for cardiovascular mortality. For each 1-unit increase in the TyG index, when below the cut-off values, the TyG index was not significantly associated with all-cause mortality (HR = 1.02, 95% CI: 1.00-1.03) and was only modestly associated with cardiovascular mortality (HR = 1.09, 95% CI: 1.06-1.11). Conversely, when the cut-off values were exceeded, the HRs (95% CI) were 2.10 (1.94-2.29) for all-cause mortality and 1.99 (1.72-2.30) for cardiovascular mortality. However, the association between the TyG index and cancer mortality was linearly negative (HR = 0.97, 95% CI: 0.94-0.99). Interpretation: The associations of the TyG index with all-cause and cardiovascular mortality displayed reverse L-shaped patterns, while an elevated TyG index showed a slight negative association with cancer mortality. We suggest that <9.75 could be the optimal TyG index cut-off value among the Chinese general population. Individuals at high risk of mortality might benefit from proper management of a high TyG index. Funding: The National High Level Hospital Clinical Research Funding (2023-GSP-ZD-2, 2023-GSP-RC-01), the Ministry of Finance of China and National Health Commission of China.

Longitudinal integrative cell-free DNA analysis in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) presents varied manifestations throughout pregnancy and poses a complex clinical challenge. High-depth cell-free DNA (cfDNA) sequencing analysis holds promise in advancing our understanding of GDM pathogenesis and prediction. In 299 women with GDM and 299 matched healthy pregnant women, distinct cfDNA fragment characteristics associated with GDM are identified throughout pregnancy. Integrating cfDNA profiles with lipidomic and single-cell transcriptomic data elucidates functional changes linked to altered lipid metabolism processes in GDM. Transcription start site (TSS) scores in 50 feature genes are used as the cfDNA signature to distinguish GDM cases from controls effectively. Notably, differential coverage of the islet acinar marker gene PRSS1 emerges as a valuable biomarker for GDM. A specialized neural network model is developed, predicting GDM occurrence and validated across two independent cohorts. This research underscores the high-depth cfDNA early prediction and characterization of GDM, offering insights into its molecular underpinnings and potential clinical applications.

A retrospective study at a single center examining risk factors associated with central nervous system involvement in individuals diagnosed with diffuse large B-cell lymphoma.

OBJECTIVE: The aim of this study is to identify risk factors contributing to central nervous system (CNS) invasion and to validate the suitability of the Central Nervous System International Prognostic Index (CNS-IPI) for individuals afflicted with diffuse large B-cell lymphoma (DLBCL). METHODS: Based on the presence or absence of CNS invasion, 365 patients were stratified into two groups: the CNS group and the non-CNS group. The clinical data of the patients were retrospectively analyzed using univariate and multivariate analysis, and the differences in survival curves were compared. The dependent variable in this study was the presence or absence of CNS invasion, while the independent variables included age, stage, extranodal involvement, renal/adrenal involvement, and others. Statistical methods included the chi-squared test and Fisher's exact test for intergroup comparison and binary logistic regression for multi-factor analysis. The related risk factors were modeled using the Cox proportional hazards model. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was used to compare the differences between survival curves. The optimal cutoff value of beta-2 (ß2)-microglobulin was determined through the utilization of a receiver operating characteristic (ROC) curve. All P values were bidirectional, and P < 0.05 was considered statistically significant. Both SPSS 23.0 (IBM Inc., Armonk, NY, USA) and RStudio (R software version 4.0.2, R Project for Statistical Computing) software were used for data processing RESULTS: The five factors of the CNS-IPI were related to the prognosis of patients with CNS invasion. Bone involvement, albumin < 40 g/L, and P53 protein (+) were the risk factors for CNS invasion in patients with DLBCL. However, prognostic factors such as double strike, testicular involvement, breast involvement, uterine involvement, and bone marrow involvement did not apply to these patients. It was also discovered that elderly patients with DLBCL with reduced albumin levels were more susceptible to CNS invasion. Furthermore, extranodal involvement at multiple sites and elevated beta-2 (ß2) microglobulin were independent prognostic factors CONCLUSION: Patients older than 60 years with DLBCL and decreased albumin are at increased risk for CNS invasion. In addition to the five factors in the CNS-IPI, bone involvement, albumin levels < 40 g/L, and P53 protein expression are risk factors affecting the prognosis of CNS invasion in patients with DLBCL.

Learning implementation of a guideline based decision support system to improve hypertension treatment in primary care in China: pragmatic cluster randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of a clinical decision support system (CDSS) in improving the use of guideline accordant antihypertensive treatment in primary care settings in China. DESIGN: Pragmatic, open label, cluster randomised trial. SETTING: 94 primary care practices in four urban regions of China between August 2019 and July 2022: Luoyang (central China), Jining (east China), and Shenzhen (south China, including two regions). PARTICIPANTS: 94 practices were randomised (46 to CDSS, 48 to usual care). 12 137 participants with hypertension who used up to two classes of antihypertensives and had a systolic blood pressure <180 mm Hg and diastolic blood pressure <110 mm Hg were included. INTERVENTIONS: Primary care practices were randomised to use an electronic health record based CDSS, which recommended a specific guideline accordant regimen for initiation, titration, or switching of antihypertensive (the intervention), or to use the same electronic health record without CDSS and provide treatment as usual (control). MAIN OUTCOME MEASURES: The primary outcome was the proportion of hypertension related visits during which an appropriate (guideline accordant) treatment was provided. Secondary outcomes were the average reduction in systolic blood pressure and proportion of participants with controlled blood pressure (<140/90 mm Hg) at the last scheduled follow-up. Safety outcomes were patient reported antihypertensive treatment related events, including syncope, injurious fall, symptomatic hypotension or systolic blood pressure <90 mm Hg, and bradycardia. RESULTS: 5755 participants with 23 113 visits in the intervention group and 6382 participants with 27 868 visits in the control group were included. Mean age was 61 (standard deviation 13) years and 42.5% were women. During a median 11.6 months of follow-up, the proportion of visits at which appropriate treatment was given was higher in the intervention group than in the control group (77.8% (17 975/23 113) v 62.2% (17 328/27 868); absolute difference 15.2 percentage points (95% confidence interval (CI) 10.7 to 19.8); P<0.001; odds ratio 2.17 (95% CI 1.75 to 2.69); P<0.001). Compared with participants in the control group, those in the intervention group had a 1.6 mm Hg (95% CI -2.7 to -0.5) greater reduction in systolic blood pressure (-1.5 mm Hg v 0.3 mm Hg; P=0.006) and a 4.4 percentage point (95% CI -0.7 to 9.5) improvement in blood pressure control rate (69.0% (3415/4952) v 64.6% (3778/5845); P=0.07). Patient reported antihypertensive treatment related adverse effects were rare in both groups. CONCLUSIONS: Use of a CDSS in primary care in China improved the provision of guideline accordant antihypertensive treatment and led to a modest reduction in blood pressure. The CDSS offers a promising approach to delivering better care for hypertension, both safely and efficiently. TRIAL REGISTRATION: ClinicalTrials.gov NCT03636334.

Epidemiological trends and burden analysis of cervical cancer attributable to unsafe sex: A population-based study from 1990 to 2019.

BACKGROUND: Unsafe sex is recognized as an important risk factor for cervical cancer (CC). Understanding the global disease burden of CC attributable to unsafe sex can assist policymakers in allocating healthcare resources. METHODS: Data were obtained from the 2019 global burden of disease database (GBD). We examined global, regional, and national levels of CC mortality, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) caused by unsafe sex. ASRs were evaluated using estimated annual percentage changes (EAPCs). RESULTS: Attributable to unsafe sex, there were 280,479 CC-related deaths in 2019 and 8,955,013 CC-related DALYs. In the period 1990-2019, the global ASRs of CC due to unsafe sex decreased around the world; for age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR), the EAPCs were -0.93 and -0.95. The highest ASMRs and ASDRs were found in central sub-Saharan Africa and the lowest in Australasia. CONCLUSION: In the past few decades, the ASMR and ASDR of CC caused by unsafe sexual practices have decreased over time, with significant variations observed among different countries and regions. Increased focus is needed on spreading awareness about sexual health and promoting CC prevention and screening, particularly in low- and middle-income nations.

AI-Based multimodal Multi-tasks analysis reveals tumor molecular heterogeneity, predicts preoperative lymph node metastasis and prognosis in papillary thyroid carcinoma: A retrospective study.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the predominant form of thyroid cancer globally, especially when lymph node metastasis (LNM) occurs. Molecular heterogeneity, driven by genetic alterations and tumor microenvironment components, contributes to the complexity of PTC. Understanding these complexities is essential for precise risk stratification and therapeutic decisions. METHODS: This study involved a comprehensive analysis of 521 patients with PTC from our hospital and 499 patients from The Cancer Genome Atlas (TCGA). The real-world cohort 1 comprised 256 patients with stage I-III PTC. Tissues from 252 patients were analyzed by DNA-based next-generation sequencing, and tissues from four patients were analyzed by single-cell RNA sequencing (scRNA-seq). Additionally, 586 PTC pathological sections were collected from TCGA, and 275 PTC pathological sections were collected from the real-world cohort 2. A deep learning multimodal model was developed using matched histopathology images, genomic, transcriptomic, and immune cell data to predict LNM and disease-free survival (DFS). RESULTS: This study included a total of 1,011 PTC patients, comprising 256 patients from cohort 1, 275 patients from cohort 2, and 499 patients from TCGA. In cohort 1, we categorized PTC into four molecular subtypes based on BRAF, RAS, RET, and other mutations. BRAF mutations were significantly associated with LNM and impacted DFS. ScRNA-seq identified distinct T cell subtypes and reduced B cell diversity in BRAF-mutated PTC with LNM. The study also explored cancer-associated fibroblasts and macrophages, highlighting their associations with LNM. The deep learning model was trained using 405 pathology slides and RNA sequences from 328 PTC patients and validated with 181 slides and RNA sequences from 140 PTC patients in the TCGA cohort. It achieved high accuracy, with an AUC of 0.86 in the training cohort, 0.84 in the validation cohort, and 0.83 in the real-world cohort 2. High-risk patients in the training cohort had significantly lower DFS rates (P<0.001). Model AUCs were 0.91 at 1 year, 0.93 at 3 years, and 0.87 at 5 years. In the validation cohort, high-risk patients also had lower DFS (P<0.001); the AUCs were 0.89, 0.87, and 0.80 at 1, 3, and 5 years. We utilized the GradCAM algorithm to generate heatmaps from pathology-based deep learning models, which visually highlighted high-risk tumor areas in PTC patients. This enhanced clinicians' understanding of the model's predictions and improved diagnostic accuracy, especially in cases with lymph node metastasis. CONCLUSION: The AI-based analysis uncovered vital insights into PTC molecular heterogeneity, emphasizing BRAF mutations' impact. The integrated deep learning model shows promise in predicting metastasis, offering valuable contributions to improved diagnostic and therapeutic strategies.

TOTEM: a multi-cancer detection and localization approach using circulating tumor DNA methylation markers.

BACKGROUND: Detection of cancer and identification of tumor origin at an early stage improve the survival and prognosis of patients. Herein, we proposed a plasma cfDNA-based approach called TOTEM to detect and trace the cancer signal origin (CSO) through methylation markers. METHODS: We performed enzymatic conversion-based targeted methylation sequencing on plasma cfDNA samples collected from a clinical cohort of 500 healthy controls and 733 cancer patients with seven types of cancer (breast, colorectum, esophagus, stomach, liver, lung, and pancreas) and randomly divided these samples into a training cohort and a testing cohort. An independent validation cohort of 143 healthy controls, 79 liver cancer patients and 100 stomach cancer patients were recruited to validate the generalizability of our approach. RESULTS: A total of 57 multi-cancer diagnostic markers and 873 CSO markers were selected for model development. The binary diagnostic model achieved an area under the curve (AUC) of 0.907, 0.908 and 0.868 in the training, testing and independent validation cohorts, respectively. With a training specificity of 98%, the specificities in the testing and independent validation cohorts were 100% and 98.6%, respectively. Overall sensitivity across all cancer stages was 65.5%, 67.3% and 55.9% in the training, testing and independent validation cohorts, respectively. Early-stage (I and II) sensitivity was 50.3% and 45.7% in the training and testing cohorts, respectively. For cancer patients correctly identified by the binary classifier, the top 1 and top 2 CSO accuracies were 77.7% and 86.5% in the testing cohort (n = 148) and 76.0% and 84.0% in the independent validation cohort (n = 100). Notably, performance was maintained with only 21 diagnostic and 214 CSO markers, achieving a training AUC of 0.865, a testing AUC of 0.866, and an integrated top 2 accuracy of 83.1% in the testing cohort. CONCLUSIONS: TOTEM demonstrates promising potential for accurate multi-cancer detection and localization by profiling plasma methylation markers. The real-world clinical performance of our approach needs to be investigated in a much larger prospective cohort.

Are recyclable plastics eco-friendly? Recycled PVC microplastics show higher toxicity than pristine PVC on Vallisneria natans, regardless of Cadmium.

As environmental awareness increases, the use of recyclable plastics has risen. However, it is currently unclear whether recycled microplastics (MPs) pose a lesser or greater environmental risk than pristine MPs. Cadmium (Cd), known for its toxicity to most organisms, can bind with MPs and accumulate in sediments. Few studies have explored the environmental risks posed by the coexistence of recycled MPs and pristine MPs with Cd to rooted macrophytes. We investigated the effects of recycled PVC MPs (R-PVC-MPs) and pristine PVC MPs (PVC-MPs) on Vallisneria natans in the presence and absence of Cd. Results showed that at moderate and high Cd levels, R-PVC-MPs reduced plant Cd enrichment. Despite this, the fresh weight of V. natans exposed to R-PVC-MPs was significantly lower than those exposed to PVC-MPs. Furthermore, R-PVC-MPs had more negative impacts on the physiological traits of V. natans than PVC-MPs, as chlorophyll was significantly reduced across all Cd levels. At high Cd levels, both R-PVC-MPs and PVC-MPs caused significantly high oxidative stress, with no significant differences observed. The PCoA plot showed that different MPs cause noticeable variations within the same Cd concentration. The trait network diagrams illustrated strong interactions among traits, with R-PVC-MPs showing the highest complexity. Lower average degree and decreased edge density indicate that traits of plants with R-PVC-MPs addition are more independent of each other. Our findings suggest that recycled PVC MPs pose a greater environmental risk than pristine PVC MPs, offering reference for assessing the risks of recycled plastics in freshwater ecosystems.

The Development and Application of Vegetable Genomics Increase the Efficiency of Exploring New Gene Resources for Vegetables.

Vegetables, as indispensable non-staple foods in people's daily diet, provide a variety of essential vitamins, minerals, and other nutrients, as well as special phytochemicals, which are recognized as functional components for human nutritional balance or medicinal purposes [...].

Cardiovascular adverse events associated with immune checkpoint inhibitors: a meta-analysis.

Objective: To evaluate the cardiovascular safety of anticancer drug immune checkpoint inhibitors (ICIs) used in patients with malignant tumors. Methods: Four clinical research databases that have been completed since their establishment were searched, and the odds ratios and 95% confidence intervals of each indicator were statistically calculated. Results: 62 randomized controlled trial and controlled trials were included. In single drug treatment ICIs group, the overall risk of cardio cerebral Vascular disease at all levels was higher than that in the placebo/chemotherapy group. Especially in all grades of Myocarditis and above grade 3 compared with normal controls, except for pericardial lesions, other indicators have no obvious side effects. Conclusion: Single drug use of an anti-tumor ICIs may increase cardiovascular side effects risk in cancer patients, so we need to strengthen monitoring, identification and management, and timely intervention to manage ICI induced adverse events.

Integrated cell wall and transcriptomic analysis revealed the mechanism underlying zinc-induced alleviation of cadmium toxicity in Cosmos bipinnatus.

Plant growth is severely harmed by cadmium (Cd) contamination, while the addition of zinc (Zn) can reduce the toxic effects of Cd. However, the interaction between Cd and Zn on the molecular mechanism and cell wall of Cosmosbipinnatus is unclear. In this study, a transcriptome was constructed using RNA-sequencing. In C. bipinnatus root transcriptome data, the expression of 996, 2765, and 3023 unigenes were significantly affected by Cd, Zn, and Cd + Zn treatments, respectively, indicating different expression patterns of some metal transporters among the Cd, Zn, and Cd + Zn treatments. With the addition of Zn, the damage to the cell wall was reduced, both the proportion and content of polysaccharides in the cell wall were changed, and Cd accumulation was decreased by 32.34%. In addition, we found that Cd and Zn mainly accumulated in pectins, the content of which increased by 30.79% and 61.4% compared to the CK treatment. Thus, Zn could alleviate the toxicity of Cd to C. bipinnatus. This study revealed the interaction between Cd and Zn at the physiological and molecular levels, broadening our understanding of the mechanisms of tolerance to Cd and Zn stress in cosmos.

Low-Density Lipoprotein Cholesterol, Cardiovascular Disease Risk, and Mortality in China.

Importance: Limited evidence supports the association between low-density lipoprotein cholesterol (LDL-C) and mortality across different atherosclerotic cardiovascular disease (ASCVD) risk stratifications. Objective: To explore the associations between LDL-C levels and mortality and to identify the optimal ranges of LDL-C with the lowest risk of mortality in populations with diverse ASCVD risk profiles. Design, Setting, and Participants: The ChinaHEART project is a prospective cohort study that recruited residents aged 35 to 75 years from 31 provinces in mainland China between November 2014 and December 2022. Participants were categorized into low-risk, primary prevention, and secondary prevention cohorts on the basis of their medical history and ASCVD risk. Data analysis was performed from December 2022 to October 2023. Main Outcomes and Measures: The primary end point was all-cause mortality, and secondary end points included cause-specific mortality. Mortality data were collected from the National Mortality Surveillance System and Vital Registration. The association between LDL-C levels and mortality was assessed by using Cox proportional hazard regression models with various adjusted variables. Results: A total of 4 379 252 individuals were recruited, and 3 789 025 (2 271 699 women [60.0%]; mean [SD] age, 56.1 [10.0] years) were included in the current study. The median (IQR) LDL-C concentration was 93.1 (70.9-117.3) mg/dL overall at baseline. During a median (IQR) follow-up of 4.6 (3.1-5.8) years, 92 888 deaths were recorded, including 38 627 cardiovascular deaths. The association between LDL-C concentration and all-cause or cardiovascular disease (CVD) mortality was U-shaped in both the low-risk cohort (2 838 354 participants) and the primary prevention cohort (829 567 participants), whereas it was J-shaped in the secondary prevention cohort (121 104 participants). The LDL-C levels corresponding to the lowest CVD mortality were 117.8 mg/dL in the low-risk group, 106.0 mg/dL in the primary prevention cohort, and 55.8 mg/dL in the secondary prevention cohort. The LDL-C concentration associated with the lowest all-cause mortality (90.9 mg/dL vs 117.0 mg/dL) and CVD mortality (87 mg/dL vs 114.6 mg/dL) were both lower in individuals with diabetes than in individuals without diabetes in the overall cohort. Conclusions and Relevance: This study found that the association between LDL-C and mortality varied among different ASCVD risk cohorts, suggesting that stricter lipid control targets may be needed for individuals with higher ASCVD risk and those with diabetes.

Proximal femoral nail antirotation versus InterTan nail for the treatment of intertrochanteric fractures: A systematic review and meta-analysis.

PURPOSE: This meta-analysis compared the efficacy and safety of Proximal Femoral Nail Antirotation (PFNA) and InterTan Nail in the treatment of intertrochanteric fractures. Given the high incidence of femoral intertrochanteric fractures in the elderly population and its impact on quality of life, choosing the most effective and safest surgical option is crucial. PFNA and InterTan are currently two commonly used techniques, but there is a lack of systematic evaluation comparing their safety and effectiveness. This study aims to fill this knowledge gap through Meta-analysis, providing clinicians with evidence-based treatment recommendations. MATERIALS AND METHODS: A computer search was used to search for published literature on PFNA and InterTan in the treatment of intertrochanteric fractures in PubMed (Medline), Web of Science, Embase, Cochrane Library (CENTRAL), Cinahl, CBM, and CNKI.A total of 853 related literatures were retrieved, and 15 literatures were finally included. Newcastle-Ottawa-Scale and Cochrane systematic review methodologies were used to assess the quality of the literature. Meta-analysis was performed using Review Manager 5.4 software, following data extraction. RESULTS: The comparison found that during the surgical treatment of intertrochanteric fractures, the operation time, fluoroscopy time, and blood loss in the PFNA group were significantly shorter than those in the InterTan group, and the difference was statistically significant. In terms of postoperative complication rates, the InterTan group had a significant advantage over the PFNA group. Shaft fracture, varus collapse, cut out, screw migration, and pain of hip and thigh were the most likely to occur in the PFNA group, and the differences were all statistically significant. In terms of postoperative efficacy, the results of the PFNA group and the InterTan group were comparable, and there was no significant differences. CONCLUSIONS: When selecting surgical techniques for the treatment of femoral intertrochanteric fractures, it is necessary to conduct individualized assessments based on the patient's overall health status, surgical tolerance, and post-operative recovery needs. For patients who cannot tolerate long-term surgery or are in poor physical condition, PFNA may be more appropriate. While for patients who can tolerate long-term surgery or have more complex conditions, InterTan may be more suitable.

Familial mesial temporal lobe epilepsy phenotype is associated with novel LGI1 variants: A report of two families.

OBJECTIVE: To expand the clinical phenotype and mutation spectrum of familial mesial temporal lobe epilepsy (FMTLE) and provide a new perspective for exploring the pathological mechanisms of epilepsy caused by leucine-rich glioma inactivated 1 (LGI1) variants. METHODS: We reported clinical data from two families with FMTLE and screened patients for variants in the LGI1 gene using Whole-exome sequencing and Sanger sequencing. The clinical features of FMTLE were analysed. The pathogenicity of the causative loci was assessed according to the American College of Medical Genetics and Genomics guidelines, and potential pathogenic mechanisms were predicted through multiple bioinformatics and molecular dynamics software. RESULTS: We identified two novel LGI1 truncating variants within two large families with FMTLE: LGI1 (c.1174C>T, p.Q392X) and LGI1 (c.703C>T, p.Q235X). Compared to previous reports, we found that focal to bilateral tonic-clonic seizures are a common type of seizure in FMTLE. The clinical phenotypes of patients with FMTLE caused by LGI1 variants were relatively mild, and all patients responded well to valproic acid. Bioinformatics analyses and molecular dynamics simulations showed that protein structure and interactions were considerably weakened or damaged as a result of both variants. CONCLUSION: This study presents the first report identifying LGI1 as a potential novel pathogenic gene within FMTLE families, thereby broadening the mutation spectrum associated with FMTLE. The findings of this study offer novel insights and avenues for understanding the intricate molecular mechanisms underlying LGI1 variants and their correlations with patient phenotypes. This study proposes the possibility of familial focal epilepsy syndromes overlapping.

A dried sweat spot paper (DSSP) method based on novel mass spectrometry probe labeling for detection and resolution of DL-lactate enantiomers as potential biomarkers for diabetes mellitus.

BACKGROUND: Human sweat can be collected non-invasively with low infectivity; however, its application as a determination method has been challenged due to the presence of trace amounts of chiral metabolites. Moreover, its application as a biological fluid for disease diagnosis has not been previously reported. In this study, the human dried sweat spot paper (DSSP) method was proposed for the derivatization of a novel mass spectrometric chiral probe, N-[1-Oxo-5-(triphenylphosphonium) pentyl]-(S)-3-aminopyrrolidine (OTPA), determination and resolution of DL-lactic acid (DL-LA) enantiomers in human elbow sweat. RESULTS: The methodological validation revealed the resolution (Rs) as 1.78, the limit of detection (S/N = 3) as 20.83 fmol, good linearity (R2 ≥ 0.9996), and the intra-day and intra-day stability with RSD ranging from 0.53 to 10.85 %, while the average recovery rate of D-LA and L-LA were 104.00 % ± 4.68 % and 107.41 % ± 8.34 %, respectively, with high accuracy. In addition, the method was applied for the determination of DL-LA in the sweat on elbow of 10 healthy volunteers and 30 diabetic patients. The results demonstrated that the D/L ratio and L/D ratio were significantly different (p < 0.0001). In addition, a moderate positive linear correlation between the D/L-LA ratio in human sweat and fasting blood glucose level (r = 0.7744, p < 0.0001) was observed, thereby suggesting that the D/L ratio of lactate in human sweat correlate the glucose level in human fasting blood. SIGNIFICANCE AND NOVELTY: The D/L lactate ratio in human sweat could be used as a potential biomarker for diabetes screening. The method can be used to screen for diabetes by providing a dry sweat paper to test equipment and has the potential to be a non-invasive early-warning diagnostic tool for diabetes.

4,5-Dimethoxycanthin-6-one Inhibits Glioblastoma Stem Cell and Tumor Growth by Inhibiting TSPAN1 Interaction with TM4SF1.

Glioblastoma stem cells (GSCs) have been implicated in the self-renewal and treatment resistance of glioblastoma (GBM). Our previous study found that 4,5-dimethoxycanthin-6-one has the potential to inhibit GBM cell proliferation. This current study aims to elucidate the molecular mechanism underlying the effects of 4,5-dimethoxycanthin-6-one in GBM development. The effect of 4,5-dimethoxycanthin-6-one on GSC formation and differentiation was explored in human GBM cell lines U251 and U87. Subsequently, 4,5-dimethoxycanthin-6-one binding to tetraspanin 1 (TSPAN1) / transmembrane 4 L six family member 1 (TM4SF1) was analyzed by molecular simulation docking. Co-immunoprecipitation (Co-IP) and immunofluorescence (IF) were used to assess the interactions between TSPAN1 and TM4SF1 in GSCs. Cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assay. To evaluate cell migration, invasion and apoptosis, we employed wound healing assay, transwell and flow cytometry, respectively. Furthermore, subcutaneous xenograft tumor models in nude mice were constructed to evaluate the impact of 4,5-dimethoxycanthin-6-one on GSCs in vivo by examining tumor growth and histological characteristics. 4,5-Dimethoxycanthin-6-one inhibited GSC formation and promoted stem cell differentiation in a concentration-dependent manner. Molecular docking models of 4,5-dimethoxycanthin-6-one with TM4SF1 and TSPAN1 were constructed. Then, the interaction between TSPAN1 and TM4SF1 in GSC was clarified. Moreover, 4,5-dimethoxycanthin-6-one significantly inhibited the expressions of TM4SF1 and TSPAN1 in vitro and in vivo. Overexpression of TSPAN1 partially reversed the inhibitory effects of 4,5-dimethoxycanthin-6-one on GSC formation, proliferation, migration and invasion. 4,5-Dimethoxycanthin-6-one inhibited GBM progression by inhibiting TSPAN1/TM4SF1 axis. 4,5-Dimethoxycanthin-6-one might be a novel and effective drug for the treatment of GBM.