Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10-5). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.
Quality improvement is an international priority, and quality education and training are important parts of hospital quality management. The aim of this study was to understand the knowledge, attitudes and practices (KAP) and its influencing factors related to quality training in medical staff. A questionnaire survey was conducted by convenience sampling to assess the KAP of quality training in Taizhou Enze Medical Center. Principal component analysis was used to extract factors from the questionnaire. Descriptive statistics (frequency, median, mean), Kendall grade correlation analysis, and Mann-Whitney U tests were used to analyze the data. A total of 205 staff members participated in the questionnaire survey. For the 5 factors of the KAP scale, the highest score was factor F4, recognition and support for quality training (mean = 90.55, median = 100), followed by factor F3, perceived benefits (mean = 84.46, median = 85.65). Relatively lower scores were found for factor F2, quality knowledge learning and mastery (mean = 63.09, median = 63.89), and F5, quality management practices and sharing (mean = 82.07, median = 75.00). There was a correlation between the 5 factors. The scores of F2 (quality knowledge learning and mastery) for staff with senior professional titles were higher than those for staff with intermediate professional titles or below. The score of F3 (perceived benefits of quality training) in medical technicians and nurses was higher than in doctors and administrative personnel. Our findings showed that the respondents' attitude toward quality training was positive, but their knowledge mastery and practice behaviors should be further improved. Occupational category and professional title were the influencing factors of the quality training KAP. Therefore, hospital should conduct quality management training at a wider scope according to the competency requirements of different groups, and further optimize the improvement and innovation system.
Health Knowledge, Attitudes, Practice , Hospitals, General , Tertiary Care Centers , Humans , Cross-Sectional Studies , Male , Female , Adult , Surveys and Questionnaires , Quality Improvement , Middle Aged , Attitude of Health Personnel , Medical Staff, Hospital , China
Abnormal neuronal polarity leads to early deficits in Alzheimer's disease (AD) by affecting the function of axons. Precise and rapid evaluation of polarity changes is very important for the early prevention and diagnosis of AD. However, due to the limitations of existing detection methods, the mechanism related to how neuronal polarity changes in AD is unclear. Herein, we reported a ratiometric fluorescent probe characterized by neutral molecule to disclose the polarity changes in nerve cells and the brain of APP/PS1 mice. Cy7-K showed a sensitive and selective ratiometric fluorescence response to polarity. Remarkably, unlike conventional intramolecular charge transfer fluorescent probes, the fluorescence quantum yield of Cy7-K in highly polar solvents is higher than that in low polar solvents due to the transition of neutral quinones to aromatic zwitterions. Using the ratiometric fluorescence imaging, we found that beta-amyloid protein (Aß) inhibits the expression of histone deacetylase 6, thereby increasing the amount of acetylated Tau protein (AC-Tau) and ultimately enhancing cell polarity. There was a high correlation between polarity and AC-Tau. Furthermore, Cy7-K penetrated the blood-brain barrier to image the polarity of different brain regions and confirmed that APP/PS1 mice had higher polarity than Wild-type mice. The probe Cy7-K will be a promising tool for assessing the progression of AD development by monitoring polarity.
Structural variants (SVs) are infrequently observed in Duchenne muscular dystrophy (DMD), a condition mainly marked by deletions and point mutations in the DMD gene. SVs in DMD remain difficult to reliably detect due to the limited SV-detection capacity of conventionally used short-read sequencing technology. Herein, we present a family, a boy and his mother, with clinical signs of muscular dystrophy, elevated creatinine kinase levels, and intellectual disability. A muscle biopsy from the boy showed dystrophin deficiency. Routine molecular techniques failed to detect abnormalities in the DMD gene, however, dystrophin mRNA transcripts analysis revealed an absence of exons 59 to 79. Subsequent long-read whole-genome sequencing identified a rare complex structural variant, a 77 kb novel intragenic inversion, and a balanced translocation t(X;1)(p21.2;p13.3) rearrangement within the DMD gene, expanding the genetic spectrum of dystrophinopathy. Our findings suggested that SVs should be considered in cases where conventional molecular techniques fail to identify pathogenic variants.
A comprehensive multiscale analysis was conducted to explore the effects of different ratios of these materials on its properties. The results show that KC played a crucial role in controlling solution viscosity and gel and sol temperatures. The dissolution time at high water temperatures primarily decreased with an increase in SA content. Higher KC and CS content increased tensile strength (TS) and elongation at break (ε), while also exhibiting better thermal stability. Water vapor transmission (WVT) and permeability (PV) initially decreased, then increased with the increase of SA and CS contents. Finally, an SA:KC:CS ratio of 1:3:2 showed optimal comprehensive properties, with a dissolution time of about 60.0 ± 3.8 s, TS of 23.80 ± 0.29 MPa, ε of 18.61 ± 0.34 %, WVT of 21.74 ± 0.62 g/m2·24h, and PV of 5.39 ± 0.17 meq/kg. Meanwhile, the SA:KC:CS edible food packaging only introduced minimal effects on food after dissolution, and the total bacterial count met regulatory standards.
Low concentrations of gelatin (0.02-0.20 wt%) were applied to regulate the surface and interface properties of CNC (0.50 wt%) by forming CNC/G complexes. As gelatin concentration increased from 0 to 0.20 wt%, the potential value of CNC/G gradually changed from -44.50 to -17.93 mV. Additionally, various gelatin concentrations led to micromorphology changes of CNC/G complexes, with the formation of particle interconnection at gelatin concentration of 0.10 wt%, followed by network structure and enhanced aggregation at gelatin concentration of 0.15 and 0.20 wt% respectively. The water contact angle (25.91°-80.23°) and interface adsorption capacity of CNC/G were improved due to hydrophobic group exposure of gelatin. When gelatin concentration exceeded 0.10 % at a fixed oil phase volume fraction (75 %), a high internal phase emulsion (HIPE) stabilized by CNC/G can be formed with a good storage stability. The rheological and microstructure results of HIPE confirmed that low gelatin concentration can assist CNC to form stable emulsion structure. Especially, the auxiliary stabilization mechanism of various gelatin concentration was different. CNC/G-0.10 % and CNC/G-0.15 % stabilized HIPE mainly depended on the enhanced interface adsorption and network structure, while CNC/G-0.20 % stabilized HIPE mainly relied on enhanced interface adsorption/accumulation due to weak electrostatic repulsion and aggregate granular morphology of CNC/G-0.20 %.
BACKGROUND: The aim of this study was to establish a simple and practical grading system for evaluating the status of the sphincter of Oddi (SO) during intraoperative choledochoscopy. This system helps identify relevant variables that influence the status of the SO and provides recommendations for preventing stone recurrence. METHODS: Ninety-three patients were selected retrospectively from a total of 316 patients diagnosed with choledocholithiasis between July 2020 and June 2023. All patients underwent common bile duct (CBD) exploration surgery and intraoperative choledochoscopy. The status of the SO was assessed during choledochoscopy. According to the severity of the condition, the patients were categorized into 4 groups. Data from each group, grades 1, 2, 3, 4, was analyzed statistically. RESULTS: The number of patients in grade 1 was significantly lower than that of the other 3 groups. Except for grade 1, patients in grade 4 exhibited significant differences compared with the other 2 groups in terms of the diameter of the CBD, size of stones, presence of pneumobilia, and history of endoscopic retrograde cholangiopancreatography (ERCP) (P<0.05). There were no significant differences between the groups in terms of sex, age, liver function, number of stones, history of gastrectomy, cholecystectomy, or CBD exploration. CONCLUSIONS: The grading system helps us classify different sphincter functions and better understand the formation of choledocholithiasis by subdividing the status of the SO. Endoscopic sphincterotomy (EST) treatment can easily result in the loss of SO function, which increases the risk of stone recurrence.
Protein design is central to nearly all protein engineering problems, as it can enable the creation of proteins with new biological functions, such as improving the catalytic efficiency of enzymes. One key facet of protein design, fixed-backbone protein sequence design, seeks to design new sequences that will conform to a prescribed protein backbone structure. Nonetheless, existing sequence design methods present limitations, such as low sequence diversity and shortcomings in experimental validation of the designed functional proteins. These inadequacies obstruct the goal of functional protein design. To improve these limitations, we initially developed the Graphormer-based Protein Design (GPD) model. This model utilizes the Transformer on a graph-based representation of three-dimensional protein structures and incorporates Gaussian noise and a sequence random masks to node features, thereby enhancing sequence recovery and diversity. The performance of the GPD model was significantly better than that of the state-of-the-art ProteinMPNN model on multiple independent tests, especially for sequence diversity. We employed GPD to design CalB hydrolase and generated nine artificially designed CalB proteins. The results show a 1.7-fold increase in catalytic activity compared to that of the wild-type CalB and strong substrate selectivity on p-nitrophenyl acetate with different carbon chain lengths (C2-C16). Thus, the GPD method could be used for the de novo design of industrial enzymes and protein drugs. The code was released at https://github.com/decodermu/GPD.
Protein Engineering , Proteins , Proteins/chemistry , Amino Acid Sequence , Protein Engineering/methods
The aggregation of superoxide dismutase 1 (SOD1) results in amyloid deposition and is involved in familial amyotrophic lateral sclerosis, a fatal motor neuron disease. There have been extensive studies of its aggregation mechanism. Noncanonical amino acid 5-cyano-tryptophan (5-CN-Trp), which has been incorporated into the amyloid segments of SOD1 as infrared probes to increase the structural sensitivity of IR spectroscopy, is found to accelerate the overall aggregation rate and potentially modulate the aggregation process. Despite these observations, the underlying mechanism remains elusive. Here, we optimized the force field parameters of 5-CN-Trp and then used molecular dynamics simulation along with the Markov state model on the SOD128-38 dimer to explore the kinetics of key intermediates in the presence and absence of 5-CN-Trp. Our findings indicate a significantly increased probability of protein aggregate formation in 5CN-Trp-modified ensembles compared to wildtype. Dimeric ß-sheets of different natures were observed exclusively in the 5CN-Trp-modified peptides, contrasting with wildtype simulations. Free-energy calculations and detailed analyses of the dimer structure revealed augmented interstrand interactions attributed to 5-CN-Trp, which contributed more to peptide affinity than any other residues. These results explored the key events critical for the early nucleation of amyloid-prone proteins and also shed light on the practice of using noncanonical derivatives to study the aggregation mechanism.
Molecular Dynamics Simulation , Protein Aggregates , Superoxide Dismutase-1 , Tryptophan , Tryptophan/chemistry , Tryptophan/metabolism , Superoxide Dismutase-1/chemistry , Superoxide Dismutase-1/metabolism , Humans , Protein Multimerization , Kinetics , Markov Chains
CpG islands near promoters are normally unmethylated despite being surrounded by densely methylated regions. Aberrant hypermethylation of these CpG islands has been associated with the development of various human diseases. Although local genetic elements have been speculated to play a role in protecting promoters from methylation, only a limited number of methylation barriers have been identified. In this study, we conducted an integrated computational and experimental investigation of colorectal cancer methylomes. Our study revealed 610 genes with disrupted methylation barriers. Genomic sequences of these barriers shared a common 41-bp sequence motif (MB-41) that displayed homology to the chicken HS4 methylation barrier. Using the CDKN2A (P16) tumor suppressor gene promoter, we validated the protective function of MB-41 and showed that loss of such protection led to aberrant hypermethylation. Our findings highlight a novel sequence signature of cis-acting methylation barriers in the human genome that safeguard promoters from silencing.
Colorectal Neoplasms , CpG Islands , DNA Methylation , Genome, Human , Promoter Regions, Genetic , Humans , Colorectal Neoplasms/genetics , Animals , Nucleotide Motifs , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p16/genetics , Cyclin-Dependent Kinase Inhibitor p16/metabolism
HSA (human serum albumin), a most abundant protein in blood serum, plays a key role in maintaining human health. Abnormal HSA level is correlated with many diseases, and thus has been used as an essential biomarker for therapeutic monitoring and biomedical diagnosis. Development of small-molecule fluorescent probes allowing the selective and sensitive recognition of HSA in in vitro and in vivo is of fundamental importance in basic biological research as well as medical diagnosis. Herein, we reported a series of new synthesized fluorescent dyes containing D-π-A constitution, which exhibited different optical properties in solution and solid state. Among them, dye M-H-SO3 with a hydrophilic sulfonate group at electron-acceptor part displayed selectivity for discrimination of HSA from BSA and other enzymes. Upon binding of dye M-H-SO3 with HSA, a significant fluorescence enhancement with a turn-on ratio about 96-fold was triggered. The detection limit was estimated to be â¼ 40 nM. Studies on the interaction mechanism revealed that dye M-H-SO3 could bind to site III of HSA with a 1:1 binding stoichiometry. Furthermore, dye M-H-SO3 has been applied to determine HSA in real urine samples with good recoveries, which provided a useful method for HSA analysis in biological fluids.
Fluorescent Dyes , Serum Albumin, Bovine , Serum Albumin, Human , Humans , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/metabolism , Serum Albumin, Human/chemistry , Serum Albumin, Human/metabolism , Molecular Structure , Cattle , Animals , Spectrometry, Fluorescence
BACKGROUND: The pathogenesis of memory impairment, a common complication of chronic neuropathic pain (CNP), has not been fully elucidated. Schwann cell (SC)-derived extracellular vesicles (EVs) contribute to remote organ injury. Here, we showed that SC-EVs may mediate pathological communication between SCs and hippocampal neurons in the context of CNP. METHODS: We used an adeno-associated virus harboring the SC-specific promoter Mpz and expressing the CD63-GFP gene to track SC-EVs transport. microRNA (miRNA) expression profiles of EVs and gain-of-function and loss-of-function regulatory experiments revealed that miR-142-5p was the main cargo of SC-EVs. Next, luciferase reporter gene and phenotyping experiments confirmed the direct targets of miR-142-5p. RESULTS: The contents and granule sizes of plasma EVs were significantly greater in rats with chronic sciatic nerve constriction injury (CCI)than in sham rats. Administration of the EV biogenesis inhibitor GW4869 ameliorated memory impairment in CCI rats and reversed CCI-associated dendritic spine damage. Notably, during CCI stress, SC-EVs could be transferred into the brain through the circulation and accumulate in the hippocampal CA1-CA3 regions. miR-142-5p was the main cargo wrapped in SC-EVs and mediated the development of CCI-associated memory impairment. Furthermore, α-actinin-4 (ACTN4), ELAV-like protein 4 (ELAVL4) and ubiquitin-specific peptidase 9 X-linked (USP9X) were demonstrated to be important downstream target genes for miR-142-5p-mediated regulation of dendritic spine damage in hippocampal neurons from CCI rats. CONCLUSION: Together, these findings suggest that SCs-EVs and/or their cargo miR-142-5p may be potential therapeutic targets for memory impairment associated with CNP.
Extracellular Vesicles , MicroRNAs , Neuralgia , Rats , Animals , MicroRNAs/metabolism , Neuralgia/metabolism , Neurons/metabolism , Schwann Cells/metabolism , Extracellular Vesicles/metabolism
BACKGROUND: Abusive supervision by the nurse manager significantly influences nurses' withholding voice about patient safety. The role of impression management motivation and speak up-related climate is crucial in understanding their connection. This study aimed to explore the relationship between abusive supervision, impression management motivation, speak up-related climate, and withholding voice about patient safety. METHODS: This cross-sectional study employed a convenience sampling method to recruit 419 clinical nurses from Taizhou Hospital, Zhejiang Province, China, between 1 November 2022 and 31 January 2023. The study adhered to the STROBE checklist. Abusive supervision and impression management motivation were assessed using the Chinese versions of the Abusive Supervision Scale and the Impression Management Motivation Scale, respectively. Withholding voice about patient safety and speak up-related climate were identified using the Chinese version of the Speaking Up about Patient Safety Questionnaire. RESULTS: Nurse leaders' abusive supervision (ß=0.40, p<0.01) and nurses' impression management motivation (ß=0.10, p<0.01) significantly and positively influenced nurses' withholding voice about patient safety. We introduced impression management motivation as a mediating variable, and the effect of abusive supervision on nurses' withholding voice decreased (ß from 0.40 to 0.38, p< 0.01). Nurses' speak up-related climate played a moderating role between abusive supervision and impression management motivation (ß= 0.24, p<0.05). CONCLUSIONS: Abusive supervision by nursing leaders can result in nurses withholding voice about patient safety out of self-protective impression management motives. This phenomenon inhibits nurses' subjective initiative and undermines their proactive involvement in improving patient safety, and hinders the cultivation of a culture encouraging full participation in patient safety, which should warrant significant attention.
Continuous EEG (cEEG) is indicated for the workup of paroxysmal events. We aimed to assess whether primary admission diagnoses predict the yield of cEEG when ordered for evaluating paroxysmal events. We identified patients in the ICU who underwent at least 6 hours of cEEG monitoring to evaluate paroxysmal events. Primary admission diagnoses were categorized into neurological or non-neurological conditions. cEEG results were dichotomized into presence or absence of epileptiform discharges. We identified 159 recordings that were obtained for the evaluation of paroxysmal events. Most patients (n = 100, 63%) were admitted with primary admission diagnoses of neurological disorders, such as ischemic stroke, or intracranial hemorrhage. We found that patients with primary neurological conditions were more likely to have brain surgeries, abnormal brain imaging, and focal neurological deficits on examination compared to those with primary non-neurological conditions. However, there was no significant difference in the prevalence of epileptiform discharges in cEEG among patients with primary diagnoses of neurological or non-neurological disorders. These results suggest that cEEG is often necessary to evaluate paroxysmal events, even among patients without primary neurological disorders.
Disordered proteins are conformationally flexible proteins that are biologically important and have been implicated in devastating diseases such as Alzheimer's disease and cancer. Unlike stably folded structured proteins, disordered proteins sample a range of different conformations that needs to be accounted for. Here, we treat disordered proteins as polymer chains, and compute a dimensionless quantity called instantaneous shape ratio (Rs), as Rs = Ree2/Rg2, where Ree is end-to-end distance and Rg is radius of gyration. Extended protein conformations tend to have high Ree compared with Rg, and thus have high Rs values, whereas compact conformations have smaller Rs values. We use a scatter plot of Rs (representing shape) against Rg (representing size) as a simple map of conformational landscapes. We first examine the conformational landscape of simple polymer models such as Random Walk, Self-Avoiding Walk, and Gaussian Walk (GW), and we notice that all protein/polymer maps lie within the boundaries of the GW map. We thus use the GW map as a reference and, to assess conformational diversity, we compute the fraction of the GW conformations (fC) covered by each protein/polymer. Disordered proteins all have high fC scores, consistent with their disordered nature. Each disordered protein accesses a different region of the reference map, revealing differences in their conformational ensembles. We additionally examine the conformational maps of the nonviral gene delivery vector polyethyleneimine at various protonation states, and find that they resemble disordered proteins, with coverage of the reference map decreasing with increasing protonation state, indicating decreasing conformational diversity. We propose that our method of combining Rs and Rg in a scatter plot generates a simple, meaningful map of the conformational landscape of a disordered protein, which in turn can be used to assess conformational diversity of disordered proteins.
Photocatalytic selective oxidation plays an important role in developing green chemistry. However, it is challenging to design an efficient photocatalyst for controlling the selectivity of photocatalytic oxidation reaction and exploring its detailed mechanism. Here, we synthesized three conjugated microporous polymers (CMPs) with D-A structures, named M-SATE-CMPs (MZn, Cu and Co), with different d-band centers based on different metal centers, resulting in the discrepancy in adsorption and activation capacities for the reactants, which produces the selectivity of ß-keto esters being catalyzed into α-hydroperoxide ß-keto esters (ROOH) or to α-hydroxyl ß-keto esters (ROH). Density functional theory (DFT) calculations also demonstrate that the adsorption and activation capacities of the metal active centers in M-SATE-CMPs (MZn, Cu and Co) for ROOH are the key factors to influence the photocatalytic selective oxidation of ß-keto ester. This study provides a promising strategy for designing a metallaphotoredox catalyst whose photocatalytic selectivity depends on the d-band center of metal site in the catalyst.
PURPOSE: Marital status has been reported to influence the survival outcomes of various cancers, but its impact on patients with mantle cell lymphoma (MCL) remains unclear. This study aimed to assess the influence of marital status at diagnosis on overall survival (OS) and cancer-specific survival (CSS) in patients with MCL. METHODS: The study utilized data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-18 databases, including 6437 eligible individuals diagnosed with MCL from 2000 to 2018. A 1:1 propensity matching method (PSM) minimized confounding factor. Univariate and multivariate analyses determined hazard ratios (HR). Stratified hazard models were developed for married and unmarried statuses across time intervals. RESULTS: Married patients exhibited better 5-year OS and CSS rates compared to unmarried patients (54.2% vs. 39.7%, log-rank p < 0.001; 62.6% vs. 49.3%, log-rank p < 0.001). Multivariate analysis indicated that being unmarried was an independent risk factor for OS (adjusted HR 1.420, 95% CI 1.329-1.517) and CSS (adjusted HR 1.388, 95% CI 1.286-1.498). After PSM, being unmarried remained an independent risk factor for both OS and CSS. Among unmarried patients, widowed individuals exhibited the poorest survival outcomes compared to patients with other marital statuses, with 5-year OS and CSS rates of 28.5% and 41.0%, respectively. Furthermore, in the 10-year OS and CSS hazard model for widowed individuals had a significantly higher risk of mortality, with the probability of overall and cancer-specific mortality increased by 1.7-fold and 1.6-fold, respectively. CONCLUSION: Marital status at diagnosis is an independent prognostic factor for MCL patients, with widowed individuals showing worse OS and CSS than those who are married, single, or divorced/separated. Adequate psychological and social support for widowed patients is crucial for improving outcomes in this patient population.
Lymphoma, Mantle-Cell , Adult , Humans , Lymphoma, Mantle-Cell/diagnosis , Marital Status , Risk Factors , Proportional Hazards Models , Survival Rate , SEER Program , Prognosis
PURPOSE: To systematically review the impact of propranolol combined with oxytocin on the process and outcomes of labor. METHODS: A comprehensive literature search was performed across multiple databases, including China National Knowledge Infrastructure (CNKI), VIP, Wanfang, China Biomedical Literature Database, PubMed, Embase, and the Cochrane Library. All publicly published randomized controlled trials (RCTs) of propranolol combined with oxytocin compared to the use of oxytocin alone in labor were collected. After screening the literature and extracting data, the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 recommended bias risk assessment tool was used to assess the quality of the included studies. A meta-analysis was conducted using RevMan 5.3 software, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the quality of evidence for outcome measures. RESULTS: Meta-analysis results showed that the group receiving propranolol combined with oxytocin was more capable of reducing the cesarean section rate (eight studies, 815 women, RR = 0.67, 95% CI (0.53, 0.86), P = 0.001) and shortening the duration of the latent phase (two studies, 206 women, MD = - 1.20, 95% CI (- 1.97, - 0.43), P = 0.002) and the duration of the active phase on day 1 (two studies, 296 women, MD = - 0.69, 95% CI (- 0.83, - 0.54), P < 0.00001), compared to the oxytocin monotherapy group. No significant difference was found between the two groups in terms of the 5-min Apgar score (five studies, 609 women, MD = - 0.05, 95% CI (- 0.14, 0.04), P = 0.32) and the rate of admissions to the Neonatal Intensive Care Unit (NICU) (three studies, 359 women, RR = 0.82, 95% CI (0.38, 1.79), P = 0.62). CONCLUSION: The combined use of propranolol and oxytocin can significantly reduce the cesarean section rate, shorten the duration of the latent phase and the duration of the active phase on day 1, and is safe. However, due to the limitations, the conclusions of this article still need to be verified by large-sample, multicenter, rigorously designed high-quality clinical RCTs. TRIAL REGISTRATION: Registration number is INPLASY202390107.
Cesarean Section , Drug Therapy, Combination , Oxytocin , Propranolol , Randomized Controlled Trials as Topic , Humans , Propranolol/administration & dosage , Oxytocin/administration & dosage , Pregnancy , Female , Labor, Obstetric/drug effects , Oxytocics/administration & dosage , Oxytocics/therapeutic use
Accurate assessment of ecosystem service (ES) supply, demand, and flow is essential for identifying and enhancing the ES supply-demand relationship and promoting regional sustainable development. Based on the InVEST model, supply-demand ratio, coupling coordination analysis, breakpoint and field strength model, and GIS spatial analysis method, we evaluated the supply and demand of water yield, food supply, carbon storage, and soil conservation service in the Loess Plateau in 2000 and 2020 and analyzed the supply-demand relationship before and after considering the interregional ecosystem service flow (ESF). The results showed that (1) from 2000 to 2020, the supply and demand of the four types of ESs in the Loess Plateau increased. Before considering ESF, the surplus degree in water yield, food supply, and soil conservation increased, and carbon storage decreased. In most counties, the coupling coordination between the supply and demand of the soil conservation is mostly extreme incoordination and moderate incoordination, and other types of ESs are mostly reluctant coordination and moderate incoordination. The degree of incoordination in water yield and soil conservation have eased, while food supply and carbon storage have strengthened. For the comprehensive supply-demand relationship of ES, the degree of surplus and coordination increased, with most counties were in a state of surplus and coordination. (2) Water yield and soil conservation services flow primarily to the western and northwestern portions of the Loess Plateau, with a decrease in the number of flow paths but an increase in the total flow rate for the former and a decrease in flow paths and total flow rate for the latter. The food supply and carbon storage flow in all directions and the total flow rate increases, with a significant increase in the number of flow paths for carbon storage. (3) After considering ESF, the supply-demand relationship of each type of ES and the comprehensive ES supply-demand relationship are changed, in which the degree of surplus and coordination of deficit counties are significantly improved, and some counties even become surplus or improve the level of coordination. After considering ESF, the supply-demand ratio changes even more relative to the degree of coupling coordination. This study is of great significance for identifying the cross-regional transfer pattern of ES, understanding in-depth the dynamic supply-demand relationship of ES, and mitigating the mismatch between supply and demand of ES. It provides a scientific and objective theoretical basis for promoting regional sustainable development.
Conservation of Natural Resources , Ecosystem , Soil
RATIONALE AND OBJECTIVES: We aimed to evaluate clinical characteristics and quantitative CT imaging features for the prediction of liver metastases (LMs) in patients with pancreatic neuroendocrine tumors (PNETs). METHODS: Patients diagnosed with pathologically confirmed PNETs were included, 133 patients were in the training group, 22 patients in the prospective internal validation group, and 28 patients in the external validation group. Clinical information and quantitative features were collected. The independent variables for predicting LMs were confirmed through the implementation of univariate and multivariate logistic analyses. The diagnostic performance was evaluated by conducting receiver operating characteristic curves for predicting LMs in the training and validation groups. RESULTS: PNETs with LMs demonstrated significantly larger diameter and lower arterial/portal tumor-parenchymal enhancement ratio, arterial/portal absolute enhancement value (AAE/PAE value) (p < 0.05). After multivariate analyses, A high level of tumor marker (odds ratio (OR): 5.32; 95% CI, 1.54-18.35), maximum diameter larger than 24.6 mm (OR: 7.46; 95% CI, 1.70-32.72), and AAE value ≤ 51 HU (OR: 4.99; 95% CI, 0.93-26.95) were independent positive predictors of LMs in patients with PNETs, with area under curve (AUC) of 0.852 (95%CI, 0.781-0.907). The AUCs for prospective internal and external validation groups were 0.883 (95% CI, 0.686-0.977) and 0.789 (95% CI, 0.602-0.916), respectively. CONCLUSION: Tumor marker, maximum diameter and absolute enhancement value in arterial phase were independent predictors with good predictive performance for the prediction of LMs in patients with PNETs. Combining clinical and quantitative features may facilitate the attainment of good predictive precision in predicting LMs.
