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1.
J Am Chem Soc ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39359104

ABSTRACT

G protein-coupled receptors (GPCRs) belong to the most diverse group of membrane receptors with a conserved structure of seven transmembrane (TM) α-helices connected by intracellular and extracellular loops. Intracellular loop 3 (ICL3) connects TM5 and TM6, the two helices shown to play significant roles in receptor activation. Herein, we investigate the activation and signaling of the ß1 adrenergic receptor (ß1AR) using mass spectrometry (MS) with a particular focus on the ICL3 loop. First, using native MS, we measure the extent of receptor coupling to an engineered Gαs subunit (mini Gs) and show preferential coupling to ß1AR with an intact ICL3 (ß1AR_ICL3) compared to the truncated ß1AR. Next, using hydrogen-deuterium exchange (HDX)-MS, we show how helix 5 of mini Gs reports on the extent of receptor activation in the presence of a range of agonists. Then, exploring a range of solution conditions and using comparative HDX, we note additional HDX protection when ICL3 is present, implying that mini Gs helix 5 presents a different binding conformation to the surface of ß1AR_ICL3, a conclusion supported by MD simulation. Considering when this conformatonal change occurs we used time-resolved HDX and employed two functional assays to measure GDP release and cAMP production, with and without ICL3. We found that ICL3 exerts its effect on Gs through enhanced cAMP production but does not affect GDP release. Together, our study uncovers potential roles of ICL3 in fine-tuning GPCR activation through subtle changes in the binding pose of helix 5, only after nucleotide release from Gs.

2.
Int J Med Sci ; 21(11): 2127-2138, 2024.
Article in English | MEDLINE | ID: mdl-39239555

ABSTRACT

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.


Subject(s)
Biomarkers , Coronary Artery Disease , Membrane Proteins , Mendelian Randomization Analysis , Proteomics , Humans , Coronary Artery Disease/blood , Coronary Artery Disease/genetics , Coronary Artery Disease/pathology , Mice , Animals , Membrane Proteins/genetics , Membrane Proteins/blood , Male , Female , Biomarkers/blood , Middle Aged , Cholesterol, LDL/blood , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Case-Control Studies , Atherosclerosis/blood , Atherosclerosis/genetics
3.
J Endourol ; 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39302046

ABSTRACT

Introduction To compare the clinical outcomes and complication rates of Convective Water Vapour Energy Ablation (Rezum®) and Prostatic Urethral Lift (Urolift®). To identify predictive factors for treatment failures in both treatments. Materials & Methods Prospective clinico-epidemiological data of patients who underwent Urolift® or Rezum® in a single institution for Benign Prostatic Hyperplasia (BPH) was collected. The choice of intervention depended on the preference of the patients after patient-centric discussions. Results From October 2019 to October 2022, 86 patients underwent Rezum® and 62 patients underwent Urolift®. Rezum® involved a longer indwelling catheter duration (12.38±5.548 versus 1.39±3.010 days, p<0.001) compared to Urolift®. Rezum® was associated with more complications compared to Urolift® (36 (41.9%) versus 10 (16.1%) cases, p<0.001). Rezum® had more cases of hematuria (17 (19.8%) versus 4 (6.5%) cases (p=0.022)) and urinary tract infections (27 (31.4%) versus 3 (4.8%) cases, p<0.001)), compared to Urolift®. There were no significant differences in Clavien-Dindo Grade 3-5 complications between the interventions. Urolift® was associated with higher re-operation rates (5 (8.1%) versus 0 (0%) cases, p=0.010) compared Rezum®. Rezum® had higher anti-cholinergic usage rates compared to Urolift® post-operation (22 (25.6%) versus 8 (12.9%) cases, p=0.024). Both interventions showed improvement in International Prostate Symptom Score (IPSS), Quality of Life score, and peak velocity flow over the 2 years with no significant difference between the two. Based on receiver operating characteristic curve, pre-operation IPSS ≥ 16 had 95.7% sensitivity and 38.4% specificity to predict the probability of treatment failures after the interventions. Conclusions There was no difference in clinical outcomes of patients who underwent Rezum® and Urolift®. However, patients who had undergone Rezum® faced more minor complications and more required anti-cholinergic medications. Lastly, physicians should note that patients with IPSS≥16 would unlikely benefit from either intervention.

4.
Liver Cancer ; 13(4): 438-450, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39114763

ABSTRACT

Introduction: For patients with large unresectable hepatocellular carcinoma (HCC), the effectiveness of conventional transarterial chemoembolization (cTACE) remains suboptimal. This study investigated the efficacy and safety of modified TACE using low-dose chemotherapy with blank microspheres (BMS-TACE) plus low-dose lenvatinib (LD-LEN) and microwave ablation (MWA) in patients with large unresectable HCC. Methods: In this prospective, single-arm, phase 2 study, patients with unresectable HCC exceeding the up-to-seven criteria, with maximum tumor diameter ≥7 cm, and without macrovascular invasion or extrahepatic metastases, received initial BMS-TACE (lipiodol, low-dose doxorubicin, and lobaplatin up to 30 mg each, and blank microspheres; subsequently modified and repeated in most patients) plus LD-LEN (4-8 mg/day) and MWA. The primary endpoint was downstaging rate (DSR); secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: From November 2019 to March 2022, 43 patients were enrolled. Median follow-up was 21.2 months. Median largest tumor diameter was 11.2 cm (interquartile range [IQR], 7-25). Following BMS-TACE and LD-LEN, downstaging occurred in 37 (86.0%) patients, 32 of whom received MWA, and 8 of whom had a complete response (CR) without MWA. ORR was 93.0% (CR in 32 [74.4%] and partial response in 8 [18.6%] patients). The 1-, 2-, and 3-year PFS rates were 57.5%, 25.9%, and 18.1%, respectively (median PFS, 14.7 months [95% CI: 8.1-19.5]). The 1-, 2-, and 3-year OS rates were 85.8%, 67.7%, and 61.6%, respectively (median OS, 36.4 months [95% CI: 26.8-not reached]). After BMS-TACE, a significant decline in CD11b+/CD33+/HLA-DR- myeloid-derived suppressor cells and early elevation in CXCR5+/CD8+ and CXCR5+/CD4+ T cells were observed (both p < 0.05). Conclusion: BMS-TACE plus LD-LEN and MWA resulted in promising efficacy and tolerable toxicity in patients with large unresectable HCC exceeding the up-to-seven criteria with a maximum tumor diameter ≥7 cm and without macrovascular invasion or extrahepatic metastases.

5.
World J Gastrointest Surg ; 16(7): 1986-2002, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39087130

ABSTRACT

A pancreatic pseudocyst is defined as an encapsulated fluid collection with a well-defined inflammatory wall with minimal or no necrosis. The diagnosis cannot be made prior to 4 wk after the onset of pancreatitis. The clinical presentation is often nonspecific, with abdominal pain being the most common symptom. If a diagnosis is suspected, contrast-enhanced computed tomography and/or magnetic resonance imaging are performed to confirm the diagnosis and assess the characteristics of the pseudocyst. Endoscopic ultrasound with cyst fluid analysis can be performed in cases of diagnostic uncertainty. Pseudocyst of the pancreas can lead to complications such as hemorrhage, infection, and rupture. The management of pancreatic pseudocysts depends on the presence of symptoms and the development of complications, such as biliary or gastric outlet obstruction. Management options include endoscopic or surgical drainage. The aim of this review was to summarize the current literature on pancreatic pseudocysts and discuss the evolution of the definitions, diagnosis, and management of this condition.

6.
Phys Med Biol ; 69(18)2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39191289

ABSTRACT

Objective.The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is challenging due to nonspecific early symptoms, complex diagnostic processes, and small lesion sizes. This study aims to develop an automatic diagnosis method for CTEPH using non-contrasted computed tomography (NCCT) scans, enabling automated diagnosis without precise lesion annotation.Approach.A novel cascade network (CN) with multiple instance learning (CNMIL) framework was developed to improve the diagnosis of CTEPH. This method uses a CN architecture combining two Resnet-18 CNN networks to progressively distinguish between normal and CTEPH cases. Multiple instance learning (MIL) is employed to treat each 3D CT case as a 'bag' of image slices, using attention scoring to identify the most important slices. An attention module helps the model focus on diagnostically relevant regions within each slice. The dataset comprised NCCT scans from 300 subjects, including 117 males and 183 females, with an average age of 52.5 ± 20.9 years, consisting of 132 normal cases and 168 cases of lung diseases, including 88 cases of CTEPH. The CNMIL framework was evaluated using sensitivity, specificity, and the area under the curve (AUC) metrics, and compared with common 3D supervised classification networks and existing CTEPH automatic diagnosis networks.Main results. The CNMIL framework demonstrated high diagnostic performance, achieving an AUC of 0.807, accuracy of 0.833, sensitivity of 0.795, and specificity of 0.849 in distinguishing CTEPH cases. Ablation studies revealed that integrating MIL and the CN significantly enhanced performance, with the model achieving an AUC of 0.978 and perfect sensitivity (1.000) in normal classification. Comparisons with other 3D network architectures confirmed that the integrated model outperformed others, achieving the highest AUC of 0.8419.Significance. The CNMIL network requires no additional scans or annotations, relying solely on NCCT. This approach can improve timely and accurate CTEPH detection, resulting in better patient outcomes.


Subject(s)
Automation , Hypertension, Pulmonary , Pulmonary Embolism , Tomography, X-Ray Computed , Humans , Hypertension, Pulmonary/diagnostic imaging , Female , Middle Aged , Male , Chronic Disease , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/complications , Machine Learning , Image Processing, Computer-Assisted/methods , Adult , Neural Networks, Computer , Aged
7.
Anal Chem ; 96(33): 13379-13388, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39105793

ABSTRACT

Highly sensitive detection of low-frequency EGFR-L858R mutation is particularly important in guiding targeted therapy of nonsmall-cell lung carcinoma (NSCLC). To this end, a ligase chain reaction (LCR)-based electrochemical biosensor (e-LCR) with an inverted sandwich-type architecture was provided by combining a cooperation of lambda exonuclease-RecJf exonuclease (λ-RecJf exo). In this work, by designing a knife-like DNA substrate (an overhang ssDNA part referred to the "knife arm") and introducing the λ-RecJf exo, the unreacted DNA probes in the LCR were specially degraded while only the ligated products were preserved, after which the ligated knife-like DNA products were hybridized with capture probes on the gold electrode surface through the "knife arms", forming the inverted sandwich-type DNA structure and bringing the methylene blue-label close to the electrode surface to engender the electrical signal. Finally, the sensitivity of the e-LCR could be improved by 3 orders of magnitude with the help of the λ-RecJf exo, and due to the mutation recognizing in the ligation site of the employed ligase, this method could detect EGFR-L858R mutation down to 0.01%, along with a linear range of 1 fM-10 pM and a limit detection of 0.8 fM. Further, the developed method could distinguish between L858R positive and negative mutations in cultured cell samples, tumor tissue samples, and plasma samples, whose accuracy was verified by the droplet digital PCR, holding a huge potential in liquid biopsy for precisely guiding individualized-treatment of NSCLC patients with advantages of high sensitivity, low cost, and adaptability to point-of-care testing.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Electrochemical Techniques , ErbB Receptors , Exodeoxyribonucleases , Lung Neoplasms , Mutation , ErbB Receptors/genetics , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Exodeoxyribonucleases/chemistry , Exodeoxyribonucleases/metabolism , Exodeoxyribonucleases/genetics , Biosensing Techniques , Ligase Chain Reaction , Limit of Detection , Viral Proteins
8.
Research (Wash D C) ; 7: 0411, 2024.
Article in English | MEDLINE | ID: mdl-38974011

ABSTRACT

Molecular materials possessing switchable magneto-optical properties are of great interest due to their potential applications in spintronics and molecular devices. However, switching their photoluminescence (PL) and single-molecule magnet (SMM) behavior via light-induced structural changes still constitutes a formidable challenge. Here, a series of cubane structures were synthesized via self-assembly of 9-anthracene carboxylic acid (HAC) and rare-earth ions. All complexes exhibited obvious photochromic phenomena and complete PL quenching upon Xe lamp irradiation, which were realized via the synergistic effect of photogenerated radicals and [4 + 4] photocycloaddition of the AC components. The quenched PL showed the largest fluorescence intensity change (99.72%) in electron-transfer photochromic materials. A reversible decoloration process was realized via mechanical grinding, which is unexpectedly in the electron-transfer photochromic materials. Importantly, an SMM behavior of the Dy analog was observed after room-temperature irradiation due to the photocycloaddition of AC ligands and the photogenerated stable radicals changed the electrostatic ligand field and magnetic coupling. Moreover, based on the remarkably photochromic and photoluminescent properties of these compounds, 2 demos were applied to support their application in information anti-counterfeiting and inkless printing. This work, for the first time utilizing the simultaneous modulation of photocycloaddition and photogenerated radicals in one system, realizes complete PL quenching and light-induced SMM behavior, providing a dynamical switch for the construction of multifunctional polymorphic materials with optical response and optical storage devices.

9.
Front Nutr ; 11: 1378969, 2024.
Article in English | MEDLINE | ID: mdl-38840695

ABSTRACT

Purpose: Specific nutrients found in food, such as minerals, antioxidants, and macronutrients, have a significant impact on immune function and human health. However, there is currently limited research exploring the relationship between specific nutrients, immune system function, and thyroid dysfunction commonly observed in autoimmune thyroid diseases, which manifest predominantly as hyperthyroidism or hypothyroidism. Therefore, the objective of this study was to investigate the connections between dietary traits and thyroid dysfunction, as well as the potential mediating role of immune cells, using Mendelian randomization (MR) analysis. Methods: The two-step MR analysis used single-nucleotide polymorphisms as instruments, with a threshold of p < 5e-08 for nutrients and thyroid dysfunction, and p < 5e-06 for immune cells. Data from different GWAS databases and UK Biobank were combined to analyze 8 antioxidants and 7 minerals, while the data for 4 macronutrients came from a cohort of 235,000 individuals of European. The outcome data (hypothyroidism, N = 3340; hyperthyroidism, N = 1840; free thyroxin [FT4], N = 49,269; thyroid-stimulating hormone [TSH], N = 54,288) were source from the ThyroidOmics consortium. Immune trait data, including 731 immune phenotypes, were collected from the GWAS catalog. Results: The results revealed that nutrient changes, such as lycopene, toenail and blood selenium, and α-tocopherol, impacted the immune system. Immune cells also affected thyroid function, with cDC cells promoting hypothyroidism and median fluorescence intensity (MFI) phenotypes correlating strongly with FT4 levels. Toenail and blood selenium reduce the relative cell counts (RCC) phenotypes of immune cells (CD62L- plasmacytoid DC %DC and transitional B cells %Lymphocyte), thereby diminishing its promoting effect on hypothyroidis. Furthermore, toenail and blood selenium mainly impacted phenotypes in three types of T cells (CD25 + ⁣ + CD8br, CD3 on CD45RA- CD4+, and CD45RA on Terminally Differentiated CD8br), reinforcing the negative regulation of FT4 levels. Conclusion: The role of immune cells as mediators in the relationship between nutrients and thyroid dysfunction highlights their potential as diagnostic or therapeutic markers. Toenail and blood selenium levels can indirectly impact hypothyroidism by influencing the RCC levels of two types of immune cells, and can indirectly affect FT4 levels by influencing three types of T cells.

10.
Int J Ophthalmol ; 17(6): 1138-1143, 2024.
Article in English | MEDLINE | ID: mdl-38895690

ABSTRACT

With the advancement of retinal imaging, hyperreflective foci (HRF) on optical coherence tomography (OCT) images have gained significant attention as potential biological biomarkers for retinal neuroinflammation. However, these biomarkers, represented by HRF, present pose challenges in terms of localization, quantification, and require substantial time and resources. In recent years, the progress and utilization of artificial intelligence (AI) have provided powerful tools for the analysis of biological markers. AI technology enables use machine learning (ML), deep learning (DL) and other technologies to precise characterization of changes in biological biomarkers during disease progression and facilitates quantitative assessments. Based on ophthalmic images, AI has significant implications for early screening, diagnostic grading, treatment efficacy evaluation, treatment recommendations, and prognosis development in common ophthalmic diseases. Moreover, it will help reduce the reliance of the healthcare system on human labor, which has the potential to simplify and expedite clinical trials, enhance the reliability and professionalism of disease management, and improve the prediction of adverse events. This article offers a comprehensive review of the application of AI in combination with HRF on OCT images in ophthalmic diseases including age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and other retinal diseases and presents prospects for their utilization.

11.
Healthcare (Basel) ; 12(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38891154

ABSTRACT

Patient activation, broadly defined as the ability of individuals to manage their health and navigate the healthcare system effectively, is crucial for achieving positive health outcomes. The Patient Activation Measure (PAM), a popularly used tool, was developed to assess this vital component of health care. This review is the first to systematically examine the validity of the PAM, as well as study its reliability, factor structure, and validity across various populations. Following the PRISMA and COSMIN guidelines, a search was conducted in MEDLINE, EMBASE, and Cochrane Library, from inception to 1 October 2023, using combinations of keywords related to patient activation and the PAM. The inclusion criteria were original quantitative or mixed methods studies focusing on PAM-13 or its translated versions and containing data on psychometric properties. Out of 3007 abstracts retrieved, 39 studies were included in the final review. The PAM has been extensively studied across diverse populations and geographical regions, including the United States, Europe, Asia, and Australia. Most studies looked at populations with chronic conditions. Only two studies applied the PAM to community-dwelling individuals and found support for its use. Studies predominantly showed a high internal consistency (Cronbach's alpha > 0.80) for the PAM. Most studies supported a unidimensional construct of patient activation, although cultural differences influenced the factor structure in some cases. Construct validity was established through correlations with health behaviors and outcomes. Despite its strengths, there is a need for further research, particularly in exploring content validity and differential item functioning. Expanding the PAM's application to more diverse demographic groups and community-dwelling individuals could enhance our understanding of patient activation and its impact on health outcomes.

12.
Dalton Trans ; 53(26): 10982-10990, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38874222

ABSTRACT

Two lanthanide complexes with formulae [DyIII(LN5)(pentafluoro-PhO)3] (1) and [DyIII(LN5)(2,6-difluoro-PhO)2](BPh4) (2) (LN5 = 2,14-dimethyl-3,6,10,13,19-pentaazabicyclo[13.3.1]nonadecal (19),2,13,15,17-pentaene) were structurally and magnetically characterized. DyIII ions lie in the cavity of a five coordinate nitrogen macrocycle, and in combination with the introduction of multi-fluorinated monodentate phenoxyl coligands a high axiality coordination symmetry is built. Using the pentafluorophenol co-ligand, complex 1 with a D2d coordination environment, is obtained and displays moderate single-molecule magnets (SMMs) behavior. When difluorophenol co-ligands were used, a higher local axisymmetric pentagonal bipyramidal coordination geometry was observed in complex 2, which displays apparent slow magnetic relaxation behavior with a hysteresis temperature of up to 5 K. Further magnetic studies of diluted samples combined with ab initio calculations indicate that the high axiality plays a crucial role in suppressing quantum tunneling of magnetization (QTM) and consequently results in good slow magnetic relaxation behavior. Different fluoro-substituted phenoxyl co-ligands have phenoloxy oxygen atoms with different electrostatic potentials as well as a different number of phenoloxy coligands along the magnetic axis, resulting in different ligand field strengths and coordination symmetries.

13.
World J Gastrointest Oncol ; 16(5): 1995-2005, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38764807

ABSTRACT

BACKGROUND: Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer. AIM: To investigate causal associations between blood metabolites and colon cancer. METHODS: The study utilized a two-sample Mendelian randomization (MR) analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer. The primary method of analysis used was the inverse variance weighted model. To further validate the results several sensitivity analyses were performed, including Cochran's Q test, MR-Egger intercept test, and MR robust adjusted profile score. These additional analyses were conducted to ensure the reliability and robustness of the findings. RESULTS: After rigorous selection for genetic variation, 486 blood metabolites were included in the MR analysis. We found Mannose [odds ratio (OR) = 2.09 (1.10-3.97), P = 0.024], N-acetylglycine [OR = 3.14 (1.78-5.53), P = 7.54 × 10-8], X-11593-O-methylascorbate [OR = 1.68 (1.04-2.72), P = 0.034], 1-arachidonoylglycerophosphocholine [OR = 4.23 (2.51-7.12), P = 6.35 × 10-8] and 1-arachidonoylglycerophosphoethanolamine 4 [OR = 3.99 (1.17-13.54), P = 0.027] were positively causally associated with colorectal cancer, and we also found a negative causal relationship between Tyrosine [OR = 0.08 (0.01-0.63), P = 0.014], Urate [OR = 0.25 (0.10-0.62), P = 0.003], N-acetylglycine [0.73 (0.54-0.98), P = 0.033], X-12092 [OR = 0.89 (0.81-0.99), P = 0.028], Succinylcarnitine [OR = 0.48 (0.27-0.84), P = 0.09] with colorectal cancer. A series of sensitivity analyses were performed to confirm the rigidity of the results. CONCLUSION: This study showed a causal relationship between 10 blood metabolites and colorectal cancer, of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors. The other five blood metabolites are protective factors.

15.
World J Methodol ; 14(1): 90590, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38577204

ABSTRACT

Randomized controlled trials (RCTs) have long been recognized as the gold standard for establishing causal relationships in clinical research. Despite that, various limitations of RCTs prevent its widespread implementation, ranging from the ethicality of withholding potentially-lifesaving treatment from a group to relatively poor external validity due to stringent inclusion criteria, amongst others. However, with the introduction of propensity score matching (PSM) as a retrospective statistical tool, new frontiers in establishing causation in clinical research were opened up. PSM predicts treatment effects using observational data from existing sources such as registries or electronic health records, to create a matched sample of participants who received or did not receive the intervention based on their propensity scores, which takes into account characteristics such as age, gender and comorbidities. Given its retrospective nature and its use of observational data from existing sources, PSM circumvents the aforementioned ethical issues faced by RCTs. Majority of RCTs exclude elderly, pregnant women and young children; thus, evidence of therapy efficacy is rarely proven by robust clinical research for this population. On the other hand, by matching study patient characteristics to that of the population of interest, including the elderly, pregnant women and young children, PSM allows for generalization of results to the wider population and hence greatly increases the external validity. Instead of replacing RCTs with PSM, the synergistic integration of PSM into RCTs stands to provide better research outcomes with both methods complementing each other. For example, in an RCT investigating the impact of mannitol on outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial, the baseline characteristics of comorbidities and current medications between treatment and control arms were significantly different despite the randomization protocol. Therefore, PSM was incorporated in its analysis to create samples from the treatment and control arms that were matched in terms of these baseline characteristics, thus providing a fairer comparison for the impact of mannitol. This literature review reports the applications, advantages, and considerations of using PSM with RCTs, illustrating its utility in refining randomization, improving external validity, and accounting for non-compliance to protocol. Future research should consider integrating the use of PSM in RCTs to better generalize outcomes to target populations for clinical practice and thereby benefit a wider range of patients, while maintaining the robustness of randomization offered by RCTs.

16.
Zhongguo Gu Shang ; 37(3): 311-5, 2024 Mar 25.
Article in Chinese | MEDLINE | ID: mdl-38515421

ABSTRACT

OBJECTIVE: To explore clinical effect of precast curvature internal fixation with Kirschner needle in treating forearm fracture in children. METHODS: From October 2019 to December 2022,32 children with forearm fractures were treated with precast curvature internal fixation with Kirkler's needles,including 25 males and 7 females,aged from 3 to 15 years old with an average of (8.0±0.5) years old,18 patients on the left side and 14 on the right side,24 patients with double fractures of radial and ulna,3 patients with Monteggia fractures,and 4 patients with Galeazzi fractures,and 1 patient with radial neck fracture of crooked cap. Operation time,intraoperative blood loss,C-arm fluoroscopy,fracture healing time and complications were recorded,and disabilities of arm,shoulder and hand (DASH) scale and Grace-Eversman forearm double fracture evaluation system were used to evaluate clinical efficacy of precast curvature internal fixation with Kirschner's needle for forearm fracture in children. RESULTS: All 32 patients were followed up for 2 to 12 months with an average of (7.16±2.51) months. Intraoperative blood loss was (20.68±5.50) ml,C-arm fluoroscopy was(5.80±2.50),and operation time was (24.34±5.10) min,fracture healing time was (8.82±1.62) weeks. Two patients occurred complications,including postoperative rupture of extensor pollicis longus tendon in 1 patient and obvious displacement of fracture caused by rotation of prefabricated curvature Kirschler needle on bone marrow cavity in 1 patient. DASH scores ranged from 0 to 16 scores with an average of (8.32±1.50) scores. According to Grace-Eversman double fracture evaluation system,28 patients got excellent result,2 good and 2 fair. CONCLUSION: The treatment of forearm fracture with Kirschner's needle prefabricated curvature internal fixation has advantages of less trauma,less bleeding,good reduction,stable fixation,fast fracture healing and good functional recovery.


Subject(s)
Forearm , Radius Fractures , Male , Child , Female , Humans , Child, Preschool , Adolescent , Blood Loss, Surgical , Fracture Fixation, Internal , Radius Fractures/surgery , Treatment Outcome , Retrospective Studies , Bone Wires
17.
Dalton Trans ; 53(13): 6120-6127, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38482711

ABSTRACT

A new hydrazone Schiff base ligand was condensed from 2-hydroxy-3-methoxybenzaldehyde and pyrimidine-4-carbohydrazide {H2L = (E)-N'-(2-hydroxy-3-methoxybenzylidene)pyrimidine-4-carbohydrazide}, which was used to assemble two new Dy2 complexes Dy2L2(DMF)2(NO3)2 (1) and Dy2L2(DMF)2(AcO)2 (2). Notably, the coordinated anions have a subtle effect on the coordination configurations of the Dy3+ ions and the magnetic properties of the two Dy2 complexes. The Dy3+ ions in 1 and 2 have the same N2O5 coordination environment but show the triangular dodecahedron and the biaugmented trigonal prism coordination configurations, respectively. Magnetic measurements revealed that both 1 and 2 have intramolecular ferromagnetic interactions between the Dy3+ ions and show single-molecule magnet behaviors at 0 Oe, with Ueff/k values of 58.2 K for 1 and 59.9 K for 2. These magnetic properties may be explained by theoretical calculations.

18.
J Ultrasound ; 27(2): 225-239, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38457087

ABSTRACT

PURPOSE: The aim of this systematic review is to evaluate the usefulness of sural nerve ultrasonography in diagnosing diabetes mellitus (DM) and diabetic polyneuropathy (DPN), the latter of which is a common long-term complication for diabetic patients that frequently involves the sural nerve. METHODOLOGY: A meta-analysis of the cross-sectional areas (CSAs) of sural nerves in healthy individuals and patients with diabetes mellitus based on a total of 32 ultrasonographic-based studies from 2015 to 2023 was performed. Sub-analyses were performed for factors such as geographical location and measurement site. RESULTS: The meta-analysis showed that the mean CSA of the sural nerve was significantly larger in DM patients with DPN only compared to healthy individuals across all regions and when pooled together. An age-dependent increase in the CSA of healthy sural nerves is apparent when comparing the paediatric population with adults. CONCLUSION: Sural nerve ultrasonography can distinguish diabetic adults with DPN from healthy adults based on cross-sectional area measurement. Future studies are needed to clarify the relationships between other parameters, such as body metrics and age, with sural nerve CSAs. Cut-offs for DPN likely need to be specific for different geographical regions.


Subject(s)
Diabetic Neuropathies , Sural Nerve , Ultrasonography , Sural Nerve/diagnostic imaging , Humans , Diabetic Neuropathies/diagnostic imaging , Ultrasonography/methods
19.
Chin Clin Oncol ; 13(1): 9, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38372059

ABSTRACT

BACKGROUND AND OBJECTIVE: Liver resection (LR) is a commonly performed surgical procedure for the management of hepatocellular carcinoma and other liver conditions. Despite its benefits in providing patients a potential cure, it is also associated with significant postoperative complications and prolonged recovery periods. In recent years, pre-operative rehabilitation (prehabilitation) has emerged as an up-and-coming strategy to optimize patients' physical, psychological and functional status before LR, leading to improved surgical and patient postoperative outcomes. Hence, our review aims to explore and synthesize the existing literature on prehabilitation in LR to provide an overview of the current evidence to help guide physicians in managing their patients. METHODS: A comprehensive literature search was conducted in multiple electronic databases from inception to July 2023. The search strategy was tailored to capture studies investigating the role of prehabilitation in LR, and the factors that contribute to beneficial outcomes in the postoperative period. KEY CONTENT AND FINDINGS: Prehabilitation programs encompass a multifaceted approach to enhance surgical outcomes and patient well-being. This considers the specific needs of the varying patient populations, such as the elderly, or the cancer ridden. Improving physical fitness, nutritional supplementation and psychological support are the common tenets of prehabilitation. In physical prehabilitation, patients are engaged in intensive physical exercise often by means of a cycle ergometer. Addressing nutritional deficiencies through supplements and dietary interventions is also vital. Psychosocial assessments, advance care planning, music therapy, and progressive relaxation exercises are shown to enhance patient resilience and well-being. In addition, innovative approaches such as optimizing fluid balance, avoiding epidural analgesia, perioperative steroid administration, phosphate correction and branched-chain amino acid supplementation are being explored. CONCLUSIONS: Prehabilitation is important in optimizing patients before LR and is key in improving postoperative outcomes. Several prehabilitation strategies exist, but no formal consensus exists on patient selection and an ideal program.


Subject(s)
Preoperative Care , Preoperative Exercise , Humans , Aged , Preoperative Care/methods , Postoperative Complications/prevention & control , Postoperative Complications/rehabilitation , Hepatectomy , Liver
20.
Adv Sci (Weinh) ; 11(10): e2308220, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38233211

ABSTRACT

Single-molecule toroics are molecular magnets with vortex distribution of magnetic moments. The coupling between magnetic and electric properties such as the magnetodielectric effect will provide potential applications for them. Herein, the observation of significant magnetodielectric effect in a triangular Dy3 crystal with toroidal magnetic moment and multiple magnetic relaxations is reported. The analysis of magnetic and electric properties implies that the magnetodielectric effect is closely related to the strong spin-lattice coupling, magnetic interactions of Dy3+ ions, as well as molecular packing models.

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