Retrospective analysis of patients with hepatocellular carcinoma complicated with human immunodeficiency virus infection after hepatectomy.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide, with a 5-year relative survival rate of approximately 18%. The similarity between incidence and mortality (830000 deaths per year) underscores the bleak prognosis associated with the disease. HCC is the fourth most common malignancy and the second leading cause of cancer death in China. Most patients with HCC have a history of chronic liver disease such as chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcoholism or alcoholic steatohepatitis, nonalcoholic fatty liver disease, or nonalcoholic steatohepatitis. Early diagnosis and effective treatment are the keys to improving the prognosis of patients with HCC. Although the total number of human immunodeficiency virus (HIV)-infected patients is declining globally the incidence of HCC is increasing in HIV-infected patients, especially those who are coinfected with HBV or HCV. As a result, people infected with HIV still face unique challenges in terms of their risk of developing HCC. AIM: To investigate the survival prognosis and clinical efficacy of surgical resection in patients with HCC complicated with HIV infection. METHODS: The clinical data of 56 patients with HCC complicated with HIV admitted to the Third Affiliated Hospital of Nantong University from January 2013 to December 2023 were retrospectively analyzed. Among these, 27 patients underwent hepatectomy (operation group) and 29 patients received conservative treatment (nonoperation group). All patients signed informed consents in line with the provisions of medical ethics. The general data, clinicopathological features and prognoses for the patients in the two groups were analyzed and the risk factors related to the prognoses of the patients in the operation group were identified. RESULTS: The median disease-free survival (DFS) and overall survival (OS) of HIV-HCC patients in the surgical group were 13 months and 17 months, respectively, and the median OS of patients in the nonsurgical group was 12 months. The OS of the surgical group was significantly longer than that of the control group (17 months vs 12 months, respectively; P < 0.05). The risk factors associated with DFS and OS in the surgical group were initial HIV diagnosis, postoperative microvascular invasion (MVI), a CD4+ T-cell count < 200/µL, Barcelona stage C-D, and men who have sex with men (MSM; P < 0.05). CONCLUSION: Hepatectomy can effectively prolong the survival of patients with HIV-HCC but MVI identified during postoperative pathological examination, late tumor detection, late BCLC stage, CD4+ T < 200/µL and MSM are risk factors affecting the survival and prognosis of patients undergoing hepatectomy. In addition, there were significant differences between the surgical group and the nonsurgical group in terms of the initial diagnosis of HIV, Child-Pugh score, alpha-fetoprotein measurement value, and HART-efficient antiretroviral therapy after the diagnosis of HIV (P < 0.05). Therefore, these factors may also affect the survival and prognosis of patients.

Intranasal esketamine versus esketamine-dexmedetomidine combination for premedication in pediatric patients undergoing strabismus surgery: a randomized controlled trial.

Background: Preoperative fear and anxiety are prevalent in children undergoing surgery. The combination of esketamine and dexmedetomidine has been proposed as a promising premedication for enhancing preoperative sedation and analgesia. This study compared the premedication efficacy of intranasal esketamine alone and esketamine-dexmedetomidine combination in pediatric patients undergoing strabismus surgery. Methods: One hundred and eighty preschool children aged 2-6 years scheduled for strabismus surgery were enrolled and randomly assigned to one of the three groups: intranasal premedication with esketamine 2 mg/kg (Group K), esketamine 1 mg/kg and dexmedetomidine 1 µg/kg (Group KD1), or esketamine 0.5 mg/kg and dexmedetomidine 2 µg/kg (Group KD2). The primary outcome was the level of sedation following the intervention, as measured by the modified Yale preoperative anxiety scale (mYPAS) and sedation scale (SS). Secondary outcomes included onset time of sedation, the successful rate of peripheral intravenous cannulation, parental separation anxiety scale (PSAS), mask acceptance scale (MAS), wake-up time, duration of stay in the post-anesthesia care unit (PACU), and premedication-related adverse effects. Results: After premedication, the mYPAS score gradually decreased in the three groups, with lower values in Group K than in Group KD1 and Group KD2 patients in 1, 5, and 10 min. SS in Group KD1 and Group KD2 steadily increased until 40 min after premedication, while SS in Group K increased in the first 5 min after premedication and maintained consistent levels during the remaining time. Sedation onset was substantially faster in Group K patients (11.4±7.8 min) than Group KD1 (18.1±7.5 min, P=0.006) and Group KD2 (18.4±6.8 min, P<0.001). PSAS, separation status, the successful rate of peripheral intravenous cannulation, and MAS were comparable among groups. There was no significant difference in terms of emergence time or duration of stay in the PACU among groups. More gastrointestinal events were observed in Group K (P<0.001). Conclusions: Intranasal premedication with 2 mg/kg esketamine produced a more rapid onset of sedation accompanied by more gastrointestinal reactions compared with a combination of esketamine and dexmedetomidine. Trial Registration: ClinicalTrials.gov identifier: NCT04757675.

Lactic acid fermentation improves rehydration and emulsifying properties of spray-dried egg yolk powder.

In this study, we investigated the protein structures, powder characteristics, as well as rehydration and emulsifying properties of spray-dried egg yolk powder after short-time lactic acid fermentation (3.5 h). Results indicate that fermentation improved the rehydration and emulsifying properties of yolk powder. Limosilactobacillus reuteri-fermented yolk powder exhibited better wettability due to the porous structure of particles and higher hydrophilicity. Lacticaseibacillus rhamnosus-fermented yolk powder had an enhanced coefficient of stability due to its smaller particles and higher surface charge. The higher water solubility of fermented yolk powder samples is mainly attributed to their lower hydrophobicity and higher zeta potential. The enhanced emulsifying activity of fermented yolk powder samples is primarily related to their increased ß-turn structure and better solubility. Furthermore, fermentation treatment altered powder moisture content and bulk densities, while not affecting its flow behavior and thermal stability. This study provides an effective approach to improving the quality of yolk powder.

The global burden of cardiovascular disease attributable to diet low in fiber among people aged 60 years and older, 1990-2019: an age-period-cohort analysis of the global burden of disease study.

OBJECTIVES: This study aimed to quantify the global cardiovascular disease (CVD) burden attributable to diet low in fiber among adults aged 60 years and older using data from the Global Burden of Disease (GBD) Study 2019. METHODS: We extracted data on CVD mortality, disability-adjusted life-years (DALYs), and risk-factor exposures from the GBD 2019 study for people aged 60 and older. Age-period-cohort models were used to estimate the overall annual percentage change in mortality and DALY rate (net drift, % per year), mortality and DALY rate for each age group from 1990 to 2019 (local drift, % per year), longitudinal age-specific rate corrected for period bias (age effect), and mortality and Daly rate for each age group from 1990 to 2019 (local drift, % per year). And period/cohort relative risk (period/cohort effect). RESULTS: From 1990 to 2019, global age-standardized cardiovascular disease (CVD) mortality rates attributable to low dietary fiber intake decreased by 2.37% per year, while disability-adjusted life years (DALYs) fell by 2.48% annually. Decreases were observed across all sociodemographic index regions, with fastest declines in high and high-middle SDI areas. CVD mortality and DALY rates attributable to low fiber increased exponentially with age, peaking at 85-89 years, and were higher in men than women. Regarding period effects, mortality and DALY rates declined since 2000, reaching nadirs in 2015-2019. For birth cohort patterns, risks attributable to low fiber intake peaked among early 1900s births and subsequently fell, with more pronounced reductions over time in women. CONCLUSIONS: Low dietary fiber intake is a leading contributor to the global cardiovascular disease burden, accounting for substantial mortality and disability specifically among older adults over recent decades.

Application of superb microvascular imaging technology in clinical disease activity of rheumatoid arthritis.

OBJECTIVES: Detection of synovitis is essential for assessing the activity and predicting the prognosis of rheumatoid arthritis (RA). The aim of this study was to investigate the diagnostic performance of superb microvascular imaging (SMI) in RA patients with high, moderate, and low activity. METHODS: One hundred four patients with active RA were selected from the hospital between May 2022 and August 2023. The study observed the correlation between bone erosion of the carpal joint, joint cavity effusion, thickness of synovial hyperplasia of the carpal joint, positivity rate of synovial blood vessels, and their semiquantitative scores with the clinical disease activity of RA using SMI examination. RESULTS: The detection of synovial hyperplasia thickness and joint effusion in the high-activity group was higher than that in the low-activity group, and the difference was statistically significant (P < 0.05). The quantitative SMI test demonstrated that the synovial blood flow grading and semiquantitative grade increased gradually with activity level (P<0.05). During the high, moderate, and low-activity groups, the vascular index (VI) value of the hyperplastic synovial membrane decreased gradually, showing statistical significance both between and within the groups (P<0.05). CONCLUSION: SMI technology exhibited high sensitivity and accuracy in assessing disease activity in RA. It holds significant clinical application value as a reliable auxiliary tool for assessing disease activity in RA and treatment. Key Points • Super micro-vascular imaging (SMI) demonstrated higher detection rates of microvessels in RA patients with high disease activity compared to those with low activity, showing statistical significance. • The quantitative SMI test revealed a clear correlation between synovial blood flow grading and disease activity levels in RA patients, highlighting the potential of SMI as a valuable tool for disease activity and treatment of rheumatoid arthritis.

Participation in Multidisciplinary Teams Among Healthcare Professionals: A Discrete Choice Experiment in Tertiary Public Hospitals in China.

Purpose: Healthcare professionals' participation is crucial for the efficient implementation of multidisciplinary team (MDT) collaboration models. We identified the key factors influencing healthcare professionals' preference to participate in MDTs in tertiary hospitals. Methods: To clarify the attributes and levels of the discrete choice experiment (DCE), we conducted a targeted literature review and conducted in-depth interviews with MDT service providers. Following this, a DCE was designed to evaluate healthcare professionals' preferences for MDT participation, and the influence of factors such as salary subsidies, leadership attention, patient participation, quality assessment, working intensity, and case complexity. A conditional logit model estimated the utility of each attribute. Willingness-to-pay estimates were derived by taking the negative ratio of the coefficients of non-economic and economic attributes. A series of policy simulation analyses were conducted. Results: Two hundred healthcare professionals completed the questionnaire, with 180 valid responses used for analysis. All attributes were statistically significant. Leadership attention and working intensity were the primary factors influencing staff willingness to participate in MDTs, followed by quality assessment and salary subsidies. Significant preference differences were observed between respondents; compared with mid-level staff, senior-level healthcare professionals believed patient engagement would be more helpful in boosting participation. The policy simulation showed that changing leadership attention from "neglect" to "emphasis" would increase the probability of staff choosing to participate in MDTs from 24.4% to 66.98%. Conclusion: Leadership attention was the primary concern for healthcare professionals in MDTs. To effectively motivate staff participation in MDTs, policymakers should adopt a holistic approach that considers work motivation and individual backgrounds, including competitive salary packages and a positive work environment. They should concurrently introduce MDT case complexity measurement tools to optimize resource allocation. Addressing staff members' unique needs and career aspirations by creating targeted training programs, pathways for advancement, and personalized career development plans are also crucial.

Impact of inpatient self-efficacy and trust in physicians on inpatient satisfaction with medical services: the mediating role of patient participation in medical decision-making.

Objective: Patient satisfaction reflects the social benefits of hospitals and is an important indicator of hospital performance. This study explores the mechanism through which inpatients' trust in physicians, self-efficacy, and participation in medical decision-making impact their satisfaction with medical services. Methods: A questionnaire was administered to 814 inpatients in 10 randomly selected tertiary hospitals and 10 randomly selected secondary hospitals in Hangzhou, China. A correlation analysis and hierarchical linear regression were conducted to analyze the factors influencing inpatient satisfaction. Results: The outcome measures of trust in physicians and participation in medical decision-making behaviors had significant positive effects on inpatient satisfaction.Trust in physicians was shown to directly influence inpatient satisfaction, while inpatient participation in decision-making partially mediated this relationship. Inpatient participation in medical decision-making fully mediated the relationship between self-efficacy and inpatient satisfaction. Conclusion: While inpatients were relatively satisfied, there is room for improvement. Healthcare providers should improve patient trust by actively listening to their needs and providing feedback, establishing effective communication mechanisms. Patient self-efficacy can be enhanced through health education, special lectures, and case sharing. Patients should also be encouraged to actively participate in medical decision-making. Practical implications: Based on inpatient feedback during a preliminary survey, we refined this study's questionnaire to enhance its feasibility for future research. This article shares key findings for healthcare managers and providers, advising that patient satisfaction can be enhanced through trust, self-efficacy, and participation.

Association of Molar Incisor Hypomineralization with Hypomineralized Second Primary Molars: An Updated Systematic Review with a Meta-Analysis and Trial Sequential Analysis.

INTRODUCTION: There is a correlation between molar incisor hypomineralization (MIH) and hypomineralized second primary molars (HSPM), but this relationship has not been definitively confirmed. The purpose of this systematic review and meta-analysis was to reevaluate whether children with HSPM are more affected by MIH than non-HSPM children. METHODS: A systematic search was conducted in four databases (PubMed, Embase, Web of Science, and the Cochrane Library) for literature, published up to December 2022. Two independent reviewers conducted the study search and screening, quality assessment, and data extraction according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The risk-of-bias assessment of all included cohort studies and case-control studies was assessed by the Newcastle-Ottawa Scale (NOS), and cross-sectional studies were assessed using the Agency for Healthcare Research Quality (AHRQ) scale. RevMan 5.4 software was used for all data analyses, with odds ratios (ORs) and 95% confidence intervals (CIs) as the effect measures. Sensitivity and subgroup analyses were conducted to identify the potential sources of heterogeneity among the studies. Publication bias was tested and corrected by funnel plots and Egger's test. Trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software to control for type-1 and type-2 errors. RESULTS: A total of 12 studies involving 8,944 children were included in this meta-analysis. Compared with the non-HSPM group, the HSPM group had an increased likelihood of MIH (OR = 10.90, 95% CI = 4.59-25.89, p < 0.05). All the included studies were of moderate-to-high quality. TSA and sensitivity analyses suggested the robustness of this outcome. CONCLUSION: This systematic review demonstrated a certain correlation between HSPM and MIH, suggesting that HSPM can play a predictive role in the occurrence of MIH. Further high-quality, multicenter, and large-sample longitudinal studies are highly recommended.

Target-Triggered Multiple-Polarity-Switchable Multiplexed Photoelectrochemical Platform.

Convenient and accurate quantification of disease-relevant multitargets is essential for community disease screening. However, in the field of photoelectrochemical (PEC) sensors for multisubstance detection, research on the continuous detection of multiple targets using a polarity-switching mode is scarce. In this study, a multiplexed PEC bioassay was developed based on a target-triggered "anodic-cathodic-anodic" multiple-polarity-switchable mode. Employing miRNA-21 and miRNA-141 as model analytes, the photosensitive material combinations of Cu2O/gold nanoparticles (AuNPs)/TiO2 and CdS/AuNPs/TiO2 were successively formed through the specific binding of different whisker branches of Whisker-DNA to Cu2O-H1 and the CdS-tripod DNA ring, respectively. This process reverses the photocurrent polarity from anodic to cathodic and then back to anodic upon detecting different targets, resulting in the high-sensitivity quantification of various biological targets with reduced interference. To enhance the device's utility and affordability in community disease screening, integrating a capacitor and a multimeter-smartphone connection simplifies the assembly and reduces costs. In developing the PEC sensor, the device demonstrated linear detection ranges for miRNA-21 and miRNA-141 from 0.01 fM to 10 nM. Detection limits for miRNA-21 and miRNA-141 were established at 3.2 and 4.3 aM, respectively. The innovative target-triggered multiple-polarity-switchable mode offers adaptability for other multitarget detections by simply modifying the structure of the whisker branches and the combination of photosensitive materials.

Ocean acidification may alleviate the toxicity of zinc to the macroalga, Ulva lactuca.

We investigated the toxic effects of different zinc (Zn) concentrations (natural seawater, 25 µg/L, and 100 µg/L) under two CO2 concentrations (410 ppmv, and 1000 ppmv) on Ulva lactuca. A significant decrease in the relative growth rate of U. lactuca was observed with an increase in Zn concentration under the low CO2 treatment condition, and we observed a notable decrease at 100 µg/L Zn under the high CO2 treatment condition. Moreover, the net photosynthetic rate increased when thalli were cultured under 25 and 100 µg/L Zn under the high CO2 treatment condition. The concentrations of chlorophyll a and b were significantly increased under 100 µg/L Zn and the high CO2 treatment conditions. Malondialdehyde content decreased under high CO2 treatment conditions, compared with the low CO2 treatment conditions, regardless of the Zn concentration. These findings suggest that ocean acidification may alleviate the toxic effects of Zn pollution on U. lactuca.

Global, regional, national epidemiology and trends of neglected tropical diseases in youths and young adults aged 15-39 years from 1990 to 2019: findings from the global burden of disease study 2019.

BACKGROUND: In recent years, the escalating concern for neglected tropical diseases (NTDs) has been recognized as a pressing global health issue. This concern is acutely manifested in low- and middle-income countries, where there is an escalating prevalence among adolescents and young adults. The burgeoning of these conditions threatens to impair patients' occupational capabilities and overall life quality. Despite the considerable global impact of NTDs, comprehensive studies focusing on their impact in younger populations remain scarce. Our study aims to describe the global prevalence of neglected tropical diseases among people aged 15 to 39 years over the 30-year period from 1990 to 2019, and to project the disease burden of the disease up to 2040. METHODS: Annual data on incident cases, mortality, and disability-adjusted life years (DALYs) for NTDs were procured from the Global Burden of Disease Study 2019 (GBD 2019). These data were stratified by global and regional distribution, country, social development index (SDI), age, and sex. We computed age-standardized rates (ASRs) and the numbers of incident cases, mortalities, and DALYs from 1990 to 2019. The estimated annual percentage change (EAPC) in the ASRs was calculated to evaluate evolving trends. RESULTS: In 2019, it was estimated that there were approximately 552 million NTD cases globally (95% Uncertainty Interval [UI]: 519.9 million to 586.3 million), a 29% decrease since 1990. South Asia reported the highest NTD prevalence, with an estimated 171.7 million cases (95% UI: 150.4 million to 198.6 million). Among the five SDI categories, the prevalence of NTDs was highest in the moderate and low SDI regions in 1990 (approximately 270.5 million cases) and 2019 (approximately 176.5 million cases). Sub-Saharan Africa recorded the most significant decline in NTD cases over the past three decades. Overall, there was a significant inverse correlation between the disease burden of NTDs and SDI. CONCLUSION: NTDs imposed over half a billion incident cases and 10.8 million DALYs lost globally in 2019-exerting an immense toll rivaling major infectious and non-communicable diseases. Encouraging declines in prevalence and disability burdens over the past three decades spotlight the potential to accelerate progress through evidence-based allocation of resources. Such strategic integration could substantially enhance public awareness about risk factors and available treatment options.

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.

Visual detection of fungicide resistance by combining RPA and CRISPR/Cas12a in peach Brown rot fungus Monilinia fructicola.

BACKGROUND: Peach brown rot caused by Monilinia fructicola severely affects the quality and yield of peach, resulting in large economic losses worldwide. Methyl benzimidazole carbamate (MBC) fungicides and sterol demethylation inhibitor (DMI) fungicides are among the most applied chemical classes used to control the disease but resistance in the target pathogen has made them risky choices. Timely monitoring of resistance to these fungicides in orchards could prevent control failure in practice. RESULTS: In the current study, we developed methods based on recombinase polymerase amplification (RPA) and CRISPR/Cas12a systems to detect MBC and DMI resistance based on the E198A mutation in the ß-tubulin (MfTub2) gene and the presence of the Mona element in the upstream region of the MfCYP51, respectively. For MBC resistance, RPA primers were designed that artificially incorporated PAM sites to facilitate the CRISPR/Cas12a reaction. Subsequently, specific tcrRNAs were designed based on the E198A mutation site. For the detection of the Mona element, we designed RPA primers M-DMI-F2/M-DMI-R1 that in combination with crRNA1 detected 'Mona' and distinguished resistant from sensitive strains. CONCLUSION: Both methods exhibited high sensitivity and specificity, requiring only a simple isothermal device to obtain results within 1 h at 37 °C. The FQ-reporter enabled visualization with a handheld UV or white light flashlight. This method was successfully used with purified DNA from lab cultures and crude DNA from symptomatic fruit tissue, highlighting its potential for on-site detection of resistant strains in orchards. © 2024 Society of Chemical Industry.

Prediction of Drug-Induced Liver Injury: From Molecular Physicochemical Properties and Scaffold Architectures to Machine Learning Approaches.

The process of developing new drugs is widely acknowledged as being time-intensive and requiring substantial financial investment. Despite ongoing efforts to reduce time and expenses in drug development, ensuring medication safety remains an urgent problem. One of the major problems involved in drug development is hepatotoxicity, specifically known as drug-induced liver injury (DILI). The popularity of new drugs often poses a significant barrier during development and frequently leads to their recall after launch. In silico methods have many advantages compared with traditional in vivo and in vitro assays. To establish a more precise and reliable prediction model, it is necessary to utilize an extensive and high-quality database consisting of information on drug molecule properties and structural patterns. In addition, we should also carefully select appropriate molecular descriptors that can be used to accurately depict compound characteristics. The aim of this study was to conduct a comprehensive investigation into the prediction of DILI. First, we conducted a comparative analysis of the physicochemical properties of extensively well-prepared DILI-positive and DILI-negative compounds. Then, we used classic substructure dissection methods to identify structural pattern differences between these two different types of chemical molecules. These findings indicate that it is not feasible to establish property or substructure-based rules for distinguishing between DILI-positive and DILI-negative compounds. Finally, we developed quantitative classification models for predicting DILI using the naïve Bayes classifier (NBC) and recursive partitioning (RP) machine learning techniques. The optimal DILI prediction model was obtained using NBC, which combines 21 physicochemical properties, the VolSurf descriptors and the LCFP_10 fingerprint set. This model achieved a global accuracy (GA) of 0.855 and an area under the curve (AUC) of 0.704 for the training set, while the corresponding values were 0.619 and 0.674 for the test set, respectively. Moreover, indicative substructural fragments favorable or unfavorable for DILI were identified from the best naïve Bayesian classification model. These findings may help prioritize lead compounds in the early stage of drug development pipelines.

Double strain-release enables formal C-O/C-F and C-N/C-F ring-opening metathesis.

Metathesis reactions have been established as a powerful tool in organic synthesis. While great advances were achieved in double-bond metathesis, like olefin metathesis and carbonyl metathesis, single-bond metathesis has received less attention in the past decade. Herein, we describe the first C(sp3)-O/C(sp3)-F bond formal cross metathesis reaction between gem-difluorinated cyclopropanes (gem-DFCPs) and epoxides under rhodium catalysis. The reaction involves the formation of a highly electrophilic fluoroallyl rhodium intermediate, which is capable of reacting with the oxygen atom in epoxides as weak nucleophiles followed by C-F bond reconstruction. The use of two strained ring substrates is the key to the success of the formal cross metathesis, in which the double strain release accounts for the driving force of the transformation. Additionally, azetidine also proves to be a suitable substrate for this transformation. The reaction offers a novel approach for the metathesis of C(sp3)-O and C(sp3)-N bonds, presenting new opportunities for single-bond metathesis.

Mechanical Property, Efficacy, and User Experience of an Innovative Wearable Device in Preventing Fall-Induced Injuries.

Background and Objectives: With the global population aging at an unprecedented pace, the imminent surge in falls and fall-induced injuries necessitates urgent attention. Innovative assistive technologies are crucial in addressing this daunting challenge. This study aimed to evaluate the mechanical properties, efficacy, safety, and user experience of the Intelligent Bone Protection Vest (IBPV), a novel, reusable, non-airbag wearable device. Research Design and Methods: The IBPV integrates a machine learning-based algorithm for real-time monitoring of wearer motion and a unique honeycomb-structured foldable cushion for fall impact attenuation. We evaluated the impact attenuation capabilities of the IBPV and conducted 2 human subject studies to assess its efficacy and safety. Additionally, semistructured interviews were conducted to qualitatively explore its usability, safety, and opportunities for enhancement. Results: The compression tests confirmed the energy absorption capacity of the honeycomb-structured foldable cushion. In over 800 fall tests involving 14 young and middle-aged subjects using a touchdown fall test, as well as 7 older subjects using a novel fall simulation test, the IBPV demonstrated an overall protection rate exceeding 84%. Discussion and Implications: These results underscored the potential of the IBPV in reducing fall-induced injuries by mitigating the impact force on the hip during falls. Future studies with more rigorous design are needed to confirm whether this active wearable device may serve as a dependable fall protection product.

Global, regional, and national burden of ischemic stroke, 1990-2021: an analysis of data from the global burden of disease study 2021.

Background: Ischemic stroke remains a major contributor to global mortality and morbidity. This study aims to provide an updated assessment of rates in ischemic stroke prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021, specifically focusing on including prevalence investigation alongside other measures. The analysis is stratified by sex, age, and socio-demographic index (SDI) at global, regional, and national levels. Methods: Data for this study was obtained from the 2021 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). To quantify temporal patterns and assess trends in age-standardized rates of ischemic stroke prevalence (ASPR), incidence (ASIR), mortality (ASDR), and DALYs, estimated annual percentage changes (EAPCs) were computed over the study period. The analyses were disaggregated by gender, 20 age categories, 21 GBD regions, 204 nations/territories, and 5 SDI quintiles. R statistical package V 4.4.2 was performed for statistical analyses and plot illustrations. Findings: In 2021, the global burden of ischemic stroke remained substantial, with a total of 69,944,884.8 cases with an ASPR of 819.5 cases per 100,000 individuals (95% UI: 760.3-878.7). The ASIR was 92.4 per 100,000 people (95% UI: 79.8-105.8), while the ASDR was 44.2 per 100,000 persons (95% UI: 39.3-47.8). Additionally, the age-standardized DALY rate was 837.4 per 100,000 individuals (95% UI: 763.7-905). Regionally, areas with high-middle SDI exhibited the greatest ASPR, ASIR, ASDR, and age-standardized DALY rates, whereas high SDI regions had the lowest rates. Geospatially, Southern Sub-Saharan Africa had the highest ASPR, while Eastern Europe showed the highest ASIR. The greatest ASDR and age-standardized DALY rates were observed in Eastern Europe, Central Asia, as well as North Africa, and the Middle East. Among countries, Ghana had the highest ASPR, and North Macedonia had both the highest ASIR and ASDR. Furthermore, North Macedonia also exhibited the highest age-standardized DALY rate. Interpretation: Regions with high-middle and middle SDI continued to experience elevated ASPR, ASIR, ASDR and age-standardized DALY rates. The highest ischemic stroke burden was observed in Southern Sub-Saharan Africa, Central Asia, Eastern Europe, and the Middle East. Funding: None.

[Correlation of lipid metabolism-related single nucleotide polymorphisms with abnormal semen quality in men].

OBJECTIVE: To explore the potential impact of lipid metabolism-related single nucleotide polymorphisms (SNP) on semen quality in men. METHODS: We selected 284 semen samples from Xingtai Infertility Hospital and Hebei Human Sperm Bank collected between February and October 2023, 33 from oligozoospermia (OS), 97 from asthenozoospermia (AS) and 54 from oligoasthenozoospermia (OAS) patients and the other 100 from normal men. We performed computer-assisted semen analysis (CASA) of the samples, extracted blood DNA and, using the MassARRAY System, genotyped the target genes, determined the genotypes of 13 SNPs and compared their distribution, their correlation with BMI and semen quality in different groups. RESULTS: The mutant homozygous (TT) genotype of the FADS2 rs2727270 gene seemed to be a risk factor for AS (OR = 4.420, P= 0.047), while the APOA2 rs5082-A allele and MC4R rs17782313 heterozygous (TC) genotype important protective factors for OS (OR = 0.422 and 0.389; P= 0.045 and 0.043, respectively). A significantly higher sperm concentration was found associated with the MC4R rs17782313 heterozygous (TC) genotype than with the homozygous (CC) genotype. Stratification analysis showed that the protective effect of the TC genotype was decreased with increased BMI and remained with the interaction of the rs5082 and rs17782313 genotypes. CONCLUSION: FADS2 rs2727270, APOA2 rs5082 and MC4R rs17782313 were significantly correlated with the risk of abnormal semen parameters.

Effective knockdown-replace gene therapy in a novel mouse model of DNM1 developmental and epileptic encephalopathy.

Effective gene therapy for gain-of-function or dominant-negative disease mutations may require eliminating expression of the mutant copy together with wild-type replacement. We evaluated such a knockdown-replace strategy in a mouse model of DNM1 disease, a debilitating and intractable neurodevelopmental epilepsy. To challenge the approach robustly, we expressed a patient-based variant in GABAergic neurons-which resulted in growth delay and lethal seizures evident by postnatal week three-and delivered to newborn pups an AAV9-based vector encoding a ubiquitously expressed, Dnm1-specific interfering RNA (RNAi) bivalently in tail-to-tail configuration with a neuron-specific, RNAi-resistant, codon-optimized Dnm1 cDNA. Pups receiving RNAi or cDNA alone fared no better than untreated pups, whereas the vast majority of mutants receiving modest doses survived with almost full growth recovery. Synaptic recordings of cortical neurons derived from treated pups revealed that significant alterations in transmission from inhibitory to excitatory neurons were rectified by bivalent vector application. To examine the mutant transcriptome and impact of treatment, we used RNA sequencing and functional annotation clustering. Mutants displayed abnormal expression of more than 1,000 genes in highly significant and relevant functional clusters, clusters that were abrogated by treatment. Together these results suggest knockdown-replace as a potentially effective strategy for treating DNM1 and related genetic neurodevelopmental disease.

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The "Guidelines for parenteral nutrition in preterm infants: the American Society for parenteral and enteral nutrition" were developed by the American Society for Parenteral and Enteral Nutrition and published in the Journal of Parenteral and Enteral Nutrition in September 2023. The guidelines provide recommendations on 12 key clinical questions regarding parenteral nutrition (PN) for preterm infants. In comparison to similar guidelines, this set offers more detailed perspectives on PN for preterm infants. It presents evidence-based recommendations for the commencement time, nutrient dosage, and composition of PN, considering primary outcomes such as growth and development, as well as secondary outcomes like sepsis, retinopathy of prematurity, parenteral nutrition-related liver disease, and jaundice. This article aims to interpret the guidelines to provide a reference for colleagues in the field.