Clinical Characteristics and Diagnosis of Ph-Positive Mixed Phenotype Acute Leukemia.

BACKGROUND: The goal was to improve the clinical cognition of Ph-positive mixed phenotype acute leukemia and avoid misdiagnosis or delayed diagnosis. METHODS: The clinical manifestations and laboratory results (bone marrow cell morphology, multiparameter flow cytometry, and cytogenetics) of a case of Ph-positive mixed phenotype acute leukemia were analyzed, and related literature was reviewed. RESULTS: Blood routine: WBC 386.35 x 109/L, HGB 117.00 g/L, PLT 31 x 109/L; 80% of the original cells can be seen by artificial classification. Morphological examination of bone marrow cells showed that the proliferation of nucleated cells was obviously active, and the original cells accounted for 76%. The size of the original cells was somewhat uniform, most of the cells had less mass, were stained light grayish blue, the cytoplasm particles were not obvious, the nuclei were mostly round or quasi-round, some of them showed distortion and nuclear notch, and the chromatin was coarse. Some of the cells were rich in mass, small azurin granules were seen, the nuclei were regular, most of them were round, the chromatin was fine, the myeloperoxidase and esterase staining were negative, the eosinophils accounted for 2.5%, and the basophils accounted for 0.5%. Flow cytometry immunotyping: Two groups of abnormal cells were seen in the bone marrow. 1. A group included 12.32% of nuclear cells and showed abnormal myeloid primitive cell phenotype. Main expression: CD117, CD34, CD38, HLA-DR, CD33, CD64, CD123, weak expression: CD13, CD19. 2. The other group included 45.61% of the nuclear cells and had a B-lymphoblastic phenotype. Main expression: CD34, CD38, HLA-DR, CD123, CD19, CD10, CD9, cCD79a, TDT, weak expression of CD13, CD22. Mixed phenotype acute leukemia (M/B) immunophenotype was considered. Chromosome: 46,XY,t(9; 22)(q34;q11.2) [20]. BCR-ABL (P210) fusion gene was positive. CONCLUSIONS: Mixed phenotype acute leukemia (MPAL) is a rare type of malignant hematologic disease. Its diagnosis is based on the comprehensive evaluation of bone marrow cell morphology, immunophenotype, molecular and cytogenetic features.

Differential diagnosis of thyroid nodules by DCE-MRI based on compressed sensing volumetric interpolated breath-hold examination: A feasibility study.

OBJECTIVES: To explore the potential and performance of quantitative and semi-quantitative parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on compressed sensing volumetric interpolated breath-hold (CS-VIBE) examination in the differential diagnosis of thyroid nodules. MATERIALS AND METHODS: A total of 208 patients with 259 thyroid nodules scheduled for surgery operation were prospectively recruited. All participants underwent routine and DCE-MRI. DCE-MRI quantitative parameters [Ktrans, Kep, Ve], semi-quantitative parameters [wash-in, wash-out, time to peak (TTP), arrival time (AT), peak enhancement intensity (PEI), and initial area under curve in 60 s (iAUC)] and time-intensity curve (TIC) types were analyzed. Differential diagnostic performances were assessed using area under the receiver operating characteristic curve (AUC) and compared with the Delong test. RESULTS: Ktrans, Kep, Ve, wash-in, wash-out, PEI and iAUC were statistically significantly different between malignant and benign nodules (P < 0.001). Among these parameters, ROC analysis revealed that Ktrans showed the highest diagnostic performance in the differentiation of benign and malignant nodules, followed by wash-in. ROC analysis also revealed that Ktrans achieved the best diagnostic performance for distinguishing papillary thyroid carcinoma (PTC) from non-PTC, follicular adenoma (FA) from non-FA, nodular goiter (NG) from non-NG, with AUC values of 0.854, 0.895 and 0.609, respectively. Type III curve is frequently observed in benign thyroid nodules, accounting for 77.4% (82/106). While malignant nodules are more common in type II, accounting for 57.5% (88/153). CONCLUSION: Thyroid examination using CS-VIBE based DCE-MRI is a feasible, non-invasive method to identify benign and malignant thyroid nodules and pathological types.

Associations between exposure to various air pollutants and risk of metabolic syndrome: a systematic review and meta-analysis.

BACKGROUND: Metabolic Syndrome (MetS) is a widely observed metabolic disorder that is increasingly prevalent worldwide, leading to substantial societal consequences. Previous studies have conducted two separate meta-analyses to investigate the relationship between MetS and air pollutants. However, these studies yielded conflicting results, necessitating a thorough systematic review and meta-analysis to reassess the link between different air pollutants and the risk of developing MetS. METHODS: We conducted a comprehensive search of relevant literature in databases including PubMed, Embase, Cochrane Library, and Web of Science up to October 9, 2023. The search was specifically restricted to publications in the English language. Following the screening of studies investigating the correlation between air pollution and MetS, we utilized random-effects models to calculate pooled effect sizes along with their respective 95% confidence intervals (CIs). We would like to highlight that this study has been registered with PROSPERO, and it can be identified by the registration number CRD42023484421. RESULTS: The study included twenty-four eligible studies. The results revealed that an increase of 10 µg/m3 in annual concentrations of PM1, PM2.5, PM10, NO2, SO2, and O3 was associated with a 29% increase in metabolic syndrome (MetS) risk for PM1 (OR = 1.29 [CI 1.07-1.54]), an 8% increase for PM2.5 (OR = 1.08 [CI 1.06-1.10]), a 17% increase for PM10 (OR = 1.17 [CI 1.08-1.27]), a 24% increase for NO2 (OR = 1.24 [CI 1.01-1.51]), a 19% increase for SO2 (OR = 1.19 [CI 1.04-1.36]), and a 10% increase for O3 (OR = 1.10 [CI 1.07-1.13]). CONCLUSION: The findings of this study demonstrate a significant association between exposure to fine particulate matter (PM1, PM2.5, PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and the incidence of metabolic syndrome (MetS). Moreover, the results suggest that air pollution exposure could potentially contribute to the development of MetS in humans.

DNA Polymerase-Endonuclease Efficiently Synthesizes DNA to Prepare DNA Materials and Develop Novel Signal Amplification System.

DNA biosynthesis, a focus of fundamental and applied research, typically involves DNA polymerases by using templates, primers, and dNTPs. Some polymerases can polymerize dNTPs for DNA de novo synthesis, although this is generally to occur randomly. This novel synthesis method has garnered our attention and practical use. Herein, we observed that the addition of endonuclease significantly enhances the efficiency of the de novo synthesis reaction catalyzed by the DNA polymerase. We further investigated the reaction conditions that influence this efficiency. Building on the optimal reaction conditions, we developed a rapid and efficient strategy for preparing DNA hydrogel. Further, coupled with the CRISPR-Cas system, we developed a nucleic acid signal amplification system characterized by versatility, sensitivity, specificity, and no risk of aerosol contamination. We successfully detected viral nucleic acids in clinical samples. In summary, our study demonstrates the significant potential of DNA polymerase- and endonuclease-catalyzed DNA de novo synthesis in diverse applications.

Comparative analysis of the image quality and diagnostic performance of the zooming technique with diffusion-weighted imaging using different b-values for thyroid papillary carcinomas and benign nodules.

Objective: To compare image quality and diagnostic performance using different b-values for the zooming technique with diffusion-weighted imaging (ZOOMit-DWI) in thyroid nodules. Materials and methods: A total of 51 benign thyroid nodules and 50 thyroid papillary carcinomas were included. ZOOMit-DWI was performed with b-values of 0, 500, 1000, 1500 and 2000 s/mm2. The sharpness was evaluated as subjective index. The signal intensity ratio (SIR), signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) were measured as objective indices. Pairwise comparisons were performed among the different b-value groups using the Friedman test. A receiver operating characteristic curve of the ADC value was used to evaluate diagnostic performance. The DeLong test was used to compare diagnostic effectiveness among the different b-value groups. Results: In both the papillary carcinoma group (P = 0.670) and the benign nodule group (P = 0.185), the sharpness of nodules was similar between b-values of 1000 s/mm2and 1500 s/mm2. In the papillary carcinoma group, the SIRnodule was statistically higher in DWI images with a b-value of 1500 s/mm2than in DWI images with b-values of 500 s/mm2(P = 0.004), 1000 s/mm2(P = 0.002), and 2000 s/mm2(P = 0.003). When the b-values were 1500 s/mm2(P = 0.008) and 2000 s/mm2(P = 0.009), the SIRnodule significantly differed between the papillary carcinoma group and the benign nodule group. When b = 500 s/mm2, the ADC had an AUC of 0.888. When b = 1000 s/mm2, the ADC had an AUC of 0.881. When b = 1500 s/mm2, the ADC had an AUC of 0.896. When b = 2000 s/mm2, the ADC had an AUC of 0.871. The DeLong test showed comparable diagnostic effectiveness among the different b-value groups except for between b-values of 2000 s/mm2and 1500 s/mm2, with a b-value of 2000 s/mm2showing lower effectiveness. Conclusion: This study suggests that 1500 s/mm2may be a suitable b-value to differentiate benign and malignant thyroid nodules in ZOOMit-DWI images, which yielded better image quality.

Solvent Regulation Induced Cathode Aggregation-Induced Electrochemiluminescence of Tetraphenylethylene Nanoaggregates for Ultrasensitive Zearalenone Analysis.

Zearalenone (ZEN) is an extremely hazardous chemical widely existing in cereals, and its high-sensitivity detection possesses significant significance to human health. Here, the cathodic aggregation-induced electrochemiluminescence (AIECL) performance of tetraphenylethylene nanoaggregates (TPE NAs) was modulated by solvent regulation, based on which an electrochemiluminescence (ECL) aptasensor was constructed for sensitive detection of ZEN. The aggregation state and AIECL of TPE NAs were directly and simply controlled by adjusting the type of organic solvent and the fraction of water, which solved the current shortcomings of low strength and weak stability of the cathode ECL signal for TPE. Impressively, in a tetrahydrofuran-water mixed solution (volume ratio, 6:4), the relative ECL efficiency of TPE NAs reached 16.03%, which was 9.2 times that in pure water conditions, and the maximum ECL spectral wavelength was obviously red-shifted to 617 nm. In addition, "H"-shape DNA structure-mediated dual-catalyzed hairpin self-assembly (H-D-CHA) with higher efficiency by the synergistic effect between the two CHA reactions was utilized to construct a sensitive ECL aptasensor for ZEN analysis with a low detection limit of 0.362 fg/mL. In conclusion, solvent regulation was a simple and efficient method for improving the performance of AIECL materials, and the proposed ECL aptasensor had great potential for ZEN monitoring in food safety.

A "twelve-section ultrasonic screening and diagnosis method" and management system for screening and treating neonatal congenital heart disease at the grassroots level in Tang County, Hebei Province, China.

BACKGROUND: To explore a method for screening and diagnosing neonatal congenital heart disease (CHD) applicable to grassroots level, evaluate the prevalence of CHD, and establish a hierarchical management system for CHD screening and treatment at the grassroots level. METHODS: A total of 24,253 newborns born in Tang County between January 2016 and December 2020 were consecutively enrolled and screened by trained primary physicians via the "twelve-section ultrasonic screening and diagnosis method" (referred to as the "twelve-section method"). Specialized staff from the CHD Screening and Diagnosis Center of Hebei Children's Hospital regularly visited the local area for definite diagnosis of CHD in newborns who screened positive. Newborns with CHD were managed according to the hierarchical management system. RESULTS: The centre confirmed that, except for 2 newborns with patent ductus arteriosus missed in the diagnosis of ventricular septal defect combined with severe pulmonary hypertension, newborns with other isolated or concomitant simple CHDs were identified at the grassroots level. The sensitivity, specificity and diagnostic coincidence rate of the twelve-section method for screening complex CHD were 92%, 99.6% and 84%, respectively. A total of 301 children with CHD were identified. The overall CHD prevalence was 12.4‰. According to the hierarchical management system, 113 patients with simple CHD recovered spontaneously during local follow-up, 48 patients continued local follow-up, 106 patients were referred to the centre for surgery (including 17 patients with severe CHD and 89 patients with progressive CHD), 1 patient died without surgery, and 8 patients were lost to follow-up. Eighteen patients with complex CHD were directly referred to the centre for surgery, 3 patients died without surgery, and 4 patients were lost to follow-up. Most patients who received early intervention achieved satisfactory results. The mortality rate of CHD was approximately 28.86 per 100,000 children. CONCLUSIONS: The "twelve-section method" is suitable for screening neonatal CHD at the grassroots level. The establishment of a hierarchical management system for CHD screening and treatment is conducive to the scientific management of CHD, which has important clinical and social significance for early detection, early intervention, reduction in mortality and improvement of the prognosis of complex and severe CHDs.

Prediction of small intracranial aneurysm rupture status based on combined Clinical-Radiomics model.

Background: Accumulating small unruptured intracranial aneurysms are detected due to the improved quality and higher frequency of cranial imaging, but treatment remains controversial. While surgery or endovascular treatment is effective for small aneurysms with a high risk of rupture, such interventions are unnecessary for aneurysms with a low risk of rupture. Consequently, it is imperative to accurately identify small aneurysms with a low risk of rupture. The purpose of this study was to develop a clinically practical model to predict small aneurysm ruptures based on a radiomics signature and clinical risk factors. Methods: A total of 293 patients having an aneurysm with a diameter of less than 5 mm, including 199 patients (67.9 %) with a ruptured aneurysm and 94 patients (32.1 %) without a ruptured aneurysm, were included in this study. Digital subtraction angiography or surgical treatment was required in all cases. Data on the clinical risk factors and the features on computed tomography angiography images associated with the aneurysm rupture status were collected simultaneously. We developed a clinical-radiomics model to predict aneurysm rupture status using multivariate logistic regression analysis. The combined clinical-radiomics model was constructed by nomogram analysis. The diagnostic performance, clinical utility, and model calibration were evaluated by operating characteristic curve analysis, decision curve analysis, and calibration analysis. Results: A combined clinical-radiomics model (Area Under Curve [AUC], 0.85; 95 % confidence interval [CI], 0.757-0.947) showed effective performance in the operating characteristic curve analysis. In the validation cohort, the performance of the combined model was better than that of the radiomics model (AUC, 0.75; 95 % CI, 0.645-0.865; Delong's test p-value = 0.01) and the clinical model (AUC, 0.74; 95 % CI, 0.625-0.851; Delong's test p-value <0.01) alone. The results of the decision curve, nomogram, and calibration analyses demonstrated the clinical utility and good fitness of the combined model. Conclusion: Our study demonstrated the effectiveness of a clinical-radiomics model for predicting rupture status in small aneurysms.

Catalysts with Trimetallic Sites on Graphene-like C2N for Electrocatalytic Nitrogen Reduction Reaction: A Theoretical Investigation.

Electrocatalytic nitrogen reduction reaction (NRR) is a green and highly efficient way to replace the industrial Haber-Bosch process. Herein, clusters consisting of three transition metal atoms loaded on C2N as NRR electrocatalysts are investigated using density functional theory (DFT). Meanwhile, Ca was introduced as a promoter and the role of Ca in NRR was investigated. It was found that Ca anchored to the catalyst can act as an electron donor and effectively promote the activation of N2 on M3. In both M3@C2N and M3Ca@C2N (M = Fe, Co, Ni), the limiting potential (UL) is less negative than that of the Ru(0001) surface and has the ability to suppress the competitive hydrogen evolution reaction (HER). Among them, Fe3@C2N is suggested to be the most promising candidate for NRR with high thermal stability, strong N2 adsorption ability, low limiting potential, and good NRR selectivity. The concepts of trimetallic sites and alkaline earth metal promoters in this work provide theoretical guidance for the rational design of atomically active sites in electrocatalytic NRR.

Localized Phonon Transport Study of GaN/SiO2 Core/shell Nanowires under Thermal-Stress Coupling.

In order to comprehensively explore the intricate mechanisms of thermo-mechanical interactions, this study employs the molecular dynamics method to investigate the influence of heat flux density, shell thickness and length, as well as stress on the radial interface phonon transport in GaN/SiO2 core/shell nanowire. Additionally, the surface eigenmode decomposition method is employed to analyze the interface phonon dispersion curves. The investigation reveals that with increasing heat flux density, internal thermal stresses intensify, leading to a complex distribution of thermal stresses within the system. Under the influence of thermal stress, the nonlinear acoustic properties interact with phonon scattering, resulting in the pronounced localization of interface phonons. Compressive stress causes an upshift in low-frequency phonons, while tensile stress induces a downward shift in the high-frequency optical branches at the interface. The localized phonon vibrations at the SiO2/GaN interface under nonuniform stress are identified as the primary cause for the abundant presence of nondispersive phonon modes at the radial interface. By elucidating the subtle interplay between lattice vibrations and stress fields, this study offers a novel and profound understanding of thermo-mechanical coupling effects, thereby providing innovative theoretical foundations for the design and performance management of thermoelectric devices.

Crosstalk between T lymphocyte and extracellular matrix in tumor microenvironment.

The extracellular matrix (ECM) is a complex three-dimensional structure composed of proteins, glycans, and proteoglycans, constituting a critical component of the tumor microenvironment. Complex interactions among immune cells, extracellular matrix, and tumor cells promote tumor development and metastasis, consequently influencing therapeutic efficacy. Hence, elucidating these interaction mechanisms is pivotal for precision cancer therapy. T lymphocytes are an important component of the immune system, exerting direct anti-tumor effects by attacking tumor cells or releasing lymphokines to enhance immune effects. The ECM significantly influences T cells function and infiltration within the tumor microenvironment, thereby impacting the behavior and biological characteristics of tumor cells. T cells are involved in regulating the synthesis, degradation, and remodeling of the extracellular matrix through the secretion of cytokines and enzymes. As a result, it affects the proliferation and invasive ability of tumor cells as well as the efficacy of immunotherapy. This review discusses the mechanisms underlying T lymphocyte-ECM interactions in the tumor immune microenvironment and their potential application in immunotherapy. It provides novel insights for the development of innovative tumor therapeutic strategies and drug.

Case Report: Rapid and progressive left ventricular endocardial calcification in an infant with Williams syndrome.

Williams syndrome (WS) is characterized by a range of clinical features, including cardiovascular disease, distinctive facial traits, neurobehavioral disorders, and a condition known as transient infantile hypercalcemia. Among these, endocardial calcification represents a non-specific response to severe, etiologically diverse myocardial injuries. In this report, we document a unique case involving an infant with WS who exhibited rapidly progressive arterial stenosis and left ventricular endocardial calcification, associated with a novel heterozygous deletion. While arterial stenosis is the most frequently observed cardiovascular issue in WS, instances of endocardial calcification during infancy are exceedingly rare and have not previously been reported in the context of WS.

A novel method for precise implantation of tracheal Y-shaped stent.

The tracheal Y-shaped stent is mainly used for the treatment of critical patients with airway stenosis or esophagotracheal fistula near carina. A novel method for precise implantation of Y-shaped tracheal stents was developed using double-lumen endotracheal intubation and flexible bronchoscopy. This approach aims to address the limitations associated with X-ray or rigid bronchoscopy guidance, such as operational difficulties and the risk of inaccurate stent placement leading to implantation failure or suffocation. With this new technique, 13 tracheal Y-shaped stents were successfully implanted. This method shows promise in reducing the complexity of stent implantation and facilitating timely treatment for patients in need. Additionally, it has the potential to update current operating standards and guidelines for this procedure.

Norfloxacin adsorption by urban green waste biochar: characterization, kinetics, and mechanisms.

Biochar, as a potential adsorbent, has been widely employed to remove pollutants from sewage. In this study, a lignin-based biochar (CB-800) was prepared by a simple high-temperature pyrolysis using urban green waste (Cinnamomum camphora leaves) as a feedstock to remove norfloxacin (NOR) from water. Batch adsorption test results indicated that CB-800 had a strong removal capacity for NOR at a wide range of pH values. The maximum adsorption achieved in the study was 50.90 ± 0.64 mg/g at 298 K. The pseudo-first and second-order kinetic models and the Dubinin-Radushkevich isotherm fitted the experimental data well, indicating that NOR adsorption by CB-800 was a complex process involving both physi-sorption and chemi-sorption. The physical properties of CB-800 were characterized by SEM and BET. The mesoporous structures were formed hierarchically on the surface of CB-800 (with an average pore size of 2.760 nm), and the spatial structure of NOR molecules was more easily adsorbed by mesoporous structures. Combined with Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis, it was showed that the main NOR adsorption mechanisms by CB-800 included ion exchange, π-electron coordination, hydrogen bonding, and electrostatic adsorption. Meanwhile, the reduction of C = O and pyridine nitrogen, and the presence of C-F2, also indicated the occurrence of substitution, addition, and redox. This study not only determined the reaction mechanism between biochar and NOR, but also provides guidance to waste managers for the removal of NOR from water by biochar. It is envisaged that the results will broaden the utilization of urban green waste.

Chemokines and Their Receptors: Predictors of Therapeutic Potential in Tumor Microenvironment on Esophageal Cancer.

Esophageal carcinoma (ESCA) is an aggressive solid tumor. The 5-year survival rate for patients with ESCA is estimated to be less than 20%, mainly due to tumor invasion and metastasis. Therefore, it is urgent to improve early diagnostic tools and effective treatments for ESCA patients. Tumor microenvironment (TME) enhances the ability of tumor cells to proliferate, migrate, and escape from the immune system, thus promoting the occurrence and development of tumor. TME contains chemokines. Chemokines consist of four major families, which are mainly composed of CC and CXC families. The main purpose of this review is to understand the CC and CXC chemokines and their receptors in ESCA, to improve the understanding of tumorigenesis of ESCA and determine new biomarkers for the diagnosis and prognosis of ESCA. We reviewed the literature on CC and CXC chemokines and their receptors in ESCA identified by PubMed database. This article introduces the general structures and functions of CC, CXC chemokines and their receptors in TME, as well as their roles in the progress of ESCA. Chemokines are involved in the development of ESCA, such as cancer cell invasion, metastasis, angiogenesis, and radioresistance, and are key determinants of disease progression, which have a great impact on patient prognosis and treatment response. In addition, a full understanding of their mechanism of action is essential to further verify that these chemokines and their receptors may serve as biomarkers or therapeutic targets of ESCA.

Exenatide reduces atrial fibrillation susceptibility by inhibiting hKv1.5 and hNav1.5 channels.

Exenatide, a promising cardioprotective agent, protects against cardiac structural remodeling and diastolic dysfunction. Combined blockade of sodium and potassium channels is valuable for managing atrial fibrillation (AF). Here, we explored whether exenatide displayed anti-AF effects by inhibiting human Kv1.5 and Nav1.5 channels. We used the whole-cell patch-clamp technique to investigate the effects of exenatide on hKv1.5 and hNav1.5 channels expressed in human embryonic kidney 293 cells and studied the effects of exenatide on action potential (AP) and other cardiac ionic currents in rat atrial myocytes. Additionally, an electrical mapping system was used to explore the effects of exenatide on electrical properties and AF activity in isolated rat hearts. Finally, a rat AF model, established using acetylcholine and calcium chloride, was employed to evaluate the anti-AF potential of exenatide in rats. Exenatide reversibly suppressed IKv1.5 with IC50 of 3.08 µM, preferentially blocked the hKv1.5 channel in its closed state, and positively shifted the voltage-dependent activation curve. Exenatide also reversibly inhibited INav1.5 with IC50 of 3.30 µM, negatively shifted the voltage-dependent inactivation curve, and slowed its recovery from inactivation with significant use-dependency at 5 and 10 Hz. Furthermore, exenatide prolonged AP duration and suppressed the sustained K+ current (Iss) and transient outward K+ current (Ito), but without inhibition of L-type Ca2+ current (ICa,L) in rat atrial myocytes. Exenatide prevented AF incidence and duration in rat hearts and rats. These findings demonstrate that exenatide inhibits IKv1.5 and INav1.5in vitro and reduces AF susceptibility in isolated rat hearts and rats.

[Computer-aided prediction and molecular mechanism investigation of active components in compound Kushen injection inhibiting p21-activated kinase 1].

Targeting p21-activated kinase 1 (PAK1) is a novel strategy for pancreatic cancer treatment. Compound Kushen injection contains many anti-pancreatic cancer components, but the specific targets are unknown. In this study, 14α-hydroxymatrine, an active component of Kushen injection, was found to possess high binding free energy with the allosteric site of PAK1 by molecular docking based virtual screening. Molecular dynamics simulations suggested that 14α-hydroxymatrine caused the α1 and α2 helices of the allosteric site of PAK1 to extend outward to form a deep allosteric regulatory pocket. Meanwhile, 14α-hydroxymatrine induced the ß-folding region at the adenosine triphosphate (ATP)-binding pocket of PAK1 to close inward, resulting in the ATP-binding pocket in a "semi-closed" state which caused the inactivation of PAK1. After removal of 14α-hydroxymatrine, PAK1 showed a tendency to change from the inactive conformation to the active conformation. We supposed that 14α-hydroxymatrine of compound Kushen injection might be a reversible allosteric inhibitor of PAK1. This study used modern technologies and methods to study the active components of traditional Chinese medicine, which laid a foundation for the development and utilization of natural products and the search for new treatments for pancreatic cancer.

Chimeric Porcine Parvovirus VP2 Virus-like Particles with Epitopes of South African Serotype 2 Foot-and-Mouth Disease Virus Elicits Specific Humoral and Cellular Responses in Mice.

Southern Africa Territories 2 (SAT2) foot-and-mouth disease (FMD) has crossed long-standing regional boundaries in recent years and entered the Middle East. However, the existing vaccines offer poor cross-protection against the circulating strains in the field. Therefore, there is an urgent need for an alternative design approach for vaccines in anticipation of a pandemic of SAT2 Foot-and-mouth disease virus (FMDV). The porcine parvovirus (PPV) VP2 protein can embed exogenous epitopes into the four loops on its surface, assemble into virus-like particles (VLPs), and induce antibodies and cytokines to PPV and the exogenous epitope. In this study, chimeric porcine parvovirus VP2 VLPs (chimeric PPV-SAT2-VLPs) expressing the T-and/or B-cell epitopes of the structural protein VP1 of FMDV SAT2 were produced using the recombinant pFastBac™ Dual vector of baculoviruses in Sf9 and HF cells We used the Bac-to-Bac system to construct the recombinant baculoviruses. The VP2-VLP--SAT2 chimeras displayed chimeric T-cell epitope (amino acids 21-40 of VP1) and/or the B-cell epitope (amino acids 135-174) of SAT FMDV VP1 by substitution of the corresponding regions at the N terminus (amino acids 2-23) and/or loop 2 and/or loop 4 of the PPV VP2 protein, respectively. In mice, the chimeric PPV-SAT2-VLPs induced specific antibodies against PPV and the VP1 protein of SAT2 FMDV. The VP2-VLP-SAT2 chimeras induced specific antibodies to PPV and the VP1 protein specific epitopes of FMDV SAT2. In this study, as a proof-of-concept, successfully generated chimeric PPV-VP2 VLPs expressing epitopes of the structural protein VP1 of FMDV SAT2 that has a potential to prevent FMDV SAT2 and PPV infection in pigs.

Development of Serum Lactate Level-Based Nomograms for Predicting Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients.

Purpose: To establish nomograms integrating serum lactate levels and traditional risk factors for predicting diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients. Patients and methods: A total of 570 T2DM patients and 100 healthy subjects were enrolled. T2DM patients were categorized into normal and high lactate groups. Univariate and multivariate logistic regression analyses were employed to identify independent predictors for DKD. Then, nomograms for predicting DKD were established, and the model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA). Results: T2DM patients exhibited higher lactate levels compared to those in healthy subjects. Glucose, platelet, uric acid, creatinine, and hypertension were independent factors for DKD in T2DM patients with normal lactate levels, while diabetes duration, creatinine, total cholesterol, and hypertension were indicators in high lactate levels group (P<0.05). The AUC values were 0.834 (95% CI, 0.776 to 0.891) and 0.741 (95% CI, 0.688 to 0.795) for nomograms in both normal lactate and high lactate groups, respectively. The calibration curve demonstrated excellent agreement of fit. Furthermore, the DCA revealed that the threshold probability and highest Net Yield were 17-99% and 0.36, and 24-99% and 0.24 for the models in normal lactate and high lactate groups, respectively. Conclusion: The serum lactate level-based nomogram models, combined with traditional risk factors, offer an effective tool for predicting DKD probability in T2DM patients. This approach holds promise for early risk assessment and tailored intervention strategies.

Predicting COVID-19 Re-Positive Cases in Malnourished Older Adults: A Clinical Model Development and Validation.

Purpose: Building and validating a clinical prediction model for novel coronavirus (COVID-19) re-positive cases in malnourished older adults. Patients and Methods: Malnourished older adults from January to May 2023 were retrospectively collected from the Department of Geriatrics of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. They were divided into a "non-re-positive" group and a "re-positive" group based on the number of COVID-19 infections, and into a training set and a validation set at a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify predictive factors for COVID-19 re-positivity in malnourished older adults, and a nomogram was constructed. Independent influencing factors were screened by multivariate logistic regression. The model's goodness-of-fit, discrimination, calibration, and clinical impact were assessed by Hosmer-Lemeshow test, area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CIC), respectively. Results: We included 347 cases, 243 in the training set, and 104 in the validation set. We screened 10 variables as factors influencing the outcome. By multivariate logistic regression analysis, preliminary identified protective factors, risk factors, and independent influencing factors that affect the re-positive outcome. We constructed a clinical prediction model for COVID-19 re-positivity in malnourished older adults. The Hosmer-Lemeshow test yielded χ2 =5.916, P =0.657; the AUC was 0.881; when the threshold probability was >8%, using this model to predict whether malnourished older adults were re-positive for COVID-19 was more beneficial than implementing intervention programs for all patients; when the threshold was >80%, the positive estimated value was closer to the actual number of cases. Conclusion: This model can help identify the risk of COVID-19 re-positivity in malnourished older adults early, facilitate early clinical decision-making and intervention, and have important implications for improving patient outcomes. We also expect more large-scale, multicenter studies to further validate, refine, and update this model.