Indications and adverse events of teriparatide: based on FDA adverse event reporting system (FAERS).

Background: Teriparatide is approved for osteoporosis. Post-marketing surveillance is critical given its widespread use. Objective: To investigate adverse events (AEs) associated with teriparatide using the FAERS database, compare association strengths for key AEs, and explore potential applications to provide clinical reference. Methods: FAERS data from 2004 to 2023 were analyzed. Reports where teriparatide was the primary suspect drug were included. Adverse events were mapped to System Organ Classes and Preferred Terms. Disproportionality analysis using ROR, PRR, BCPNN and EBGM algorithms was conducted to detect safety signals. Results: Out of 107,123 reports with teriparatide as the primary suspect, key AEs identified included pain in extremity (PRR: 4.54), muscle spasms (PRR: 5.11), fractures (PRR range: 17.67-552.95), and increased calcium levels (PRR: 50.73). Teriparatide exhibited a stronger association with increased calcium levels (PRR: 50.73) compared to fractures (PRR range: 17.67-552.95). Notably, only 10.86% of AE reports were submitted by physicians and another 10% by other health professionals. Subset analyses showed a higher consistency of reported AEs from health professionals compared to the general dataset. Off-label uses were noted in conditions such as arthritis (0.57%) and cancer (0.12%). For osteoporosis, main AEs were pain (18.2%), fractures (12.4%), muscle spasms (7.7%), and nausea (6.5%), while glucocorticoid-induced osteoporosis AEs included fractures (24.1%), pain (13.2%), decreased bone density (9.8%), and nausea (5.1%). Conclusion: Our findings provide real-world safety data on teriparatide, revealing key AEs and their association strengths. The low proportion of reports by healthcare professionals suggests the need for cautious interpretation. Continuous vigilance and further research are imperative to guide teriparatide's clinical use.

The value of serum PCT/ALB and CRP/ALB ratios in evaluating the condition and prognosis of craniocerebral trauma.

INTRODUCTION: The aim of the study was to explore the value of serum procalcitonin to albumin (PCT/ALB) and C-reactive protein to albumin (CRP/ALB) ratios in evaluating the condition and prognosis of craniocerebral trauma (CT). MATERIAL AND METHODS: 158 patients with CT admitted to the emergency department of our hospital from January 2020 to June 2022 were selected as the study subjects. According to the Glasgow coma scale (GCS) score, 158 patients with CT were grouped in a mild group (GCS score 13-15 points, n = 68), a moderate group (GCS score 9-12 points, n = 61), and a severe group (GCS score 3-8 points, n = 29). Besides, according to the patient's Glasgow prognosis (GOS) score, 158 patients with CT were divided into a good prognosis group (GOS score 4-5 points, n = 110) and a poor prognosis group (GOS score 1-3 points, n = 48). Serum PCT/ALB and CRP/ALB levels of different groups were compared. The correlation between PCT/ALB and CRP/ALB ratios and the score of GCS and GOS was explored using Pearson correlation analysis. Prognosis-related influencing factors were found out through multivariate logistic regression. The value of serum PCT/ALB and CRP/ALB ratios in evaluating the condition and prognosis of CT was evaluated by the ROC curve. RESULTS: Patients in the moderate and severe groups had much higher ratios of PCT/ALB and CRP/ALB and sharply lower GCS scores than those in the mild group ( p < 0.001). Compared with the patients in the moderate group, those in the severe group had much higher PCT/ALB and CRP/ALB ratios and obviously lower GCS scores ( p < 0.001). Patients with poor prognosis had markedly higher PCT/ALB and CRP/ALB ratios and memorably lower GOS score than the patients with good prognosis ( p < 0.001). A negative correlation between PCT, CRP, PCT/ALB ratio, CRP/ALB ratio and GCS scores ( r = -0.821, -0.857, -0.750, -0.766, p < 0.001) and GOS scores ( r = -0.636, -0.628, -0.595, -0.628, p < 0.001) was revealed by Pearson correlation analysis. ALB was correlated positively with GCS score and GOS score ( r = 0.381, 0.413, p < 0.001). Multivariate logistic regression analysis exhibited that PCT/ALB ratio and CRP/ALB ratio were related to poor prognosis of CT patients ( p < 0.05). ROC curve analysis showed that the combined PCT/ALB ratio and CRP/ALB area under the curve (AUC) were 0.883 and 0.860, respectively, which were used to assess the severity and predict prognosis of patients with CT. CONCLUSIONS: PCT/ALB and CRP/ALB ratios were positively correlated with the severity and prognosis of patients with CT, and were risk factors for poor prognosis. Early determination of changes in PCT/ALB and CRP/ALB ratios had a certain clinical value for evaluating the condition and prognosis of CT patients.

Innovative 3D printing and molding process for secondary-skin-collimator fabrication.

Purpose. Secondary skin collimation (SSC) is essential for shielding normal tissues near tumors during electron and orthovoltage radiation treatments. Traditional SSC fabrication methods, such as crafting in-house lead sheets, are labor-intensive and produce SSCs with low geometric accuracy. This study introduces a workflow that integrated 3D scanning and 3D printing technologies with an in-house mold process, enabling the production of patient-specific SSCs within six hours.Methods. An anthropomorphic head phantom was scanned with a handheld 3D scanner. The resulting scan data was imported into 3D modeling software for design. The completed model was exported to a 3D printer as a printable file. Subsequently, molten Cerrobend was poured into the mold and allowed to set, completing the SSC production. Geometric accuracy was assessed using CT images, and the shielding effectiveness was evaluated through film dosimetry.Results. The 3D printed mold achieved submillimeter accuracy (0.5 mm) and exhibited high conformity to the phantom surface. It successfully endured the weight and heat of the Cerrobend during pouring and curing. Dosimetric analysis conducted with radiochromic film demonstrated good agreement between the measured and expected attenuation values of the SSC slab, within ±3%.Conclusions. This study presents a proof of concept for novel mold room workflows that produce patient-specific SSCs within six hours, a significant improvement over the traditional SSC fabrication process, which takes 2-3 days. The submillimeter accuracy and versatility of 3D scanning and printing technologies afford greater design freedom and enhanced delivery accuracy for cases involving irregular geometries.

An automation of Monte Carlo workflow for dosimetry study of an Elekta LINAC delivery system in radiotherapy.

Purpose: This study aims to automate the Monte Carlo (MC) workflow utilized for radiotherapy dosimetry, focusing on an Elekta LINAC delivery system. It addresses the challenge of integrating MC simulations into routine clinical practice, making this accurate yet complex method more accessible and efficient for radiotherapy dosimetry. Methods and Materials: We developed a user-friendly software featuring a graphical user interface (GUI) that integrates EGSnrc for MC simulations. The software streamlines the process from retrieving Digital Imaging and Communications in Medicine (DICOM) data to executing dose calculations and comparing dose distributions. To validate our proposed tool, we compared its computed doses for IMRT and VMAT plans from the Pinnacle TPS for an Elekta Versa HD linear accelerator against MC simulation results. This comparison utilized our in-house software and GUI as the tool, covering various treatment sites and prescriptions. Results: The automated MC workflow demonstrated high accuracy in dose calculations and streamlined integration with clinical workflows. The comparison between the MC-simulated and TPS-calculated doses revealed excellent agreement, highlighting the reliability of MC for independent dose verification in complex treatment scenarios. Conclusions: The automated MC workflow developed represents a substantial improvement in the practicality and efficiency of MC simulations in radiotherapy. This advancement not only simplifies the dosimetry process but also ensures high accuracy, establishing it as a valuable tool for routine patient-specific quality assurance and the development of specialized treatment procedures.

Determination of the effective dose of remimazolam combined with sufentanil for inhibiting body movement during surgical abortion: An up-and-down sequential allocation trial.

BACKGROUND: Remimazolam, a recently developed anesthetic characterized by its rapid and ultra-short-acting properties, exhibits pharmacological attributes that make it potentially suitable for painless surgical abortion procedures. The objective of this study was to determine the effective dose of remimazolam when administered in combination with sufentanil, with the intention of inhibiting body movement during surgical abortion. Additionally, a secondary objective was to assess the recovery profile from general anesthesia. METHODS: The study enrolled a total of 25 healthy women aged 20 to 40, with a body mass index between 18 and 28 kg/m2, in their first trimester of pregnancy (up to 12 weeks), and American Society of Anesthesiologists status I and II. Anesthesia induction was initiated by administering sufentanil at a dose of 0.1 µg/kg. The modified Dixon up-and-down method was employed to determine the induction dose of remimazolam for each patient. RESULTS: The 50% and 95% effective dose of remimazolam for inhibitory effects of body movement was estimated using centered isotonic regression to be 0.145 mg/kg (95% CI: 0.115, 0.207), and 0.242 mg/kg (95% CI: 0.232, 0.620), respectively. Five out of 25 (20%) experienced hiccups, with 1 patient having persistent hiccups until the end of the surgery. The mean time to first eye-opening was 51.4 ±â€…20.5 seconds, and the time to obey verbal command was 54.5 ±â€…20.6 seconds. Upon arrival at the postanesthesia care unit, 95.7% of the patients achieved a Modified Aldrete score ≥ 9. CONCLUSIONS: The 50% and 95% effective dose of remimazolam for inhibiting body movement during surgical abortion when used in combination with 0.1 µg/kg of sufentanil were 0.145 mg/kg and 0.242 mg/kg, respectively.

Boston Naming Test as a Screening Tool for Early Postoperative Cognitive Dysfunction in Elderly Patients After Major Noncardiac Surgery.

PURPOSE: The Boston naming test (BNT), as a simple, fast, and easily administered neuropsychological test, was demonstrated to be useful in detecting language function. In this study, BNT was investigated whether it could be a screening tool for early postoperative cognitive dysfunction (POCD). METHODS: This prospective observational cohort study included 132 major noncardiac surgery patients and 81 nonsurgical controls. All participants underwent a mini-mental state examination (MMSE) and BNT 1 day before and 7 days after surgery. Early POCD was assessed by reliable change index and control group results. RESULTS: Seven days after surgery, among 132 patients, POCD was detected in 30 (22.7%) patients (95% CI, 15.5%-30.0%) based on MMSE, and 45 (34.1%) patients (95% CI, 26.3%-41.9%) were found with postoperative language function decline based on BNT and MMSE. Agreement between the BNT spontaneous naming and MMSE total scoring was moderate (Kappa .523), and the sensitivity of BNT spontaneous naming for detecting early POCD was .767. Further analysis showed that areas under receiver operating characteristics curves (AUC) did not show statistically significant differences when BNT spontaneous naming (AUC .862) was compared with MMSE language functional subtests (AUC .889), or non-language functional subtests (AUC .933). CONCLUSION: This study indicates the feasibility of implementing the BNT spontaneous naming test to screen early POCD in elderly patients after major noncardiac surgery.

Optimizing spot intensity with lower bound constraints for IMPT: Exposing shortcomings and introducing an enhanced strategy.

BACKGROUND: Intensity Modulated Proton Therapy (IMPT) is a sophisticated radiation treatment allowing for precise dose distributions. However, conventional spot selection strategies in IMPT face challenges, particularly with minimum monitor unit (MU) constraints, affecting planning quality and efficiency. PURPOSE: This study introduces an innovative Two-Stage Mixed Integer Linear Programming (MILP) method to optimize spot intensity in IMPT with Lower Bound (LB) constraints. This method seeks to improve treatment planning efficiency and precision, overcoming limitations of existing strategies. METHODS: Our approach evaluates prevalent IMPT spot selection strategies, identifying their limitations, especially concerning MU constraints. We integrated LB constraints into a MILP framework, using a novel three-phase strategy for spot pool selection, to enhance performance over traditional heuristic methods and L1 + L∞ strategies. The method's efficacy was tested in eight study cases, using Dose-Volume Histograms (DVHs), spot selection efficiency, and computation time analysis for benchmarking against established methods. RESULTS: The proposed method showed superior performance in DVH quality, adhering to LB constraints while maintaining high-quality treatment plans. It outperformed existing techniques in spot selection, reducing unnecessary spots and balancing precision with efficiency. Cases studies confirmed the method's effectiveness in producing clinically feasible plans with enhanced dose distributions and reduced hotspots, especially in cases with elevated LB constraints. CONCLUSIONS: Our Two-Stage MILP strategy signifies a significant advancement in IMPT treatment planning. By incorporating LB constraints directly into the optimization process, it achieves superior plan quality and deliverability compared to current methods. This approach is particularly advantageous in clinical settings requiring minimum spot number and high MU LB constraints, offering the potential for improved patient outcomes through more precise and efficient radiation therapy plans.

NMR Studies of the Interactions between Sialyllactoses and the Polysialytransferase Domain for Polysialylation Inhibition.

It is known that sialyllactose (SL) in mammalians is a major source of sialic acid (Sia), which can further form cytidine monophosphate sialic acid (CMP-Sia), and the final product is polysialic acid (polySia) using polysialyltransferases (polySTs) on the neural cell adhesion molecule (NCAM). This process is called NCAM polysialylation. The overexpression of polysialylation is strongly related to cancer cell migration, invasion, and metastasis. In order to inhibit the overexpression of polysialylation, in this study, SL was selected as an inhibitor to test whether polysialylation could be inhibited. Our results suggest that the interactions between the polysialyltransferase domain (PSTD) in polyST and CMP-Siaand the PSTD and polySia could be inhibited when the 3'-sialyllactose (3'-SL) or 6'-sialyllactose (6'-SL) concentration is about 0.5 mM or 6'-SL and 3 mM, respectively. The results also show that SLs (particularly for 3'-SL) are the ideal inhibitors compared with another two inhibitors, low-molecular-weight heparin (LMWH) and cytidine monophosphate (CMP), because 3'-SL can not only be used to inhibit NCAM polysialylation, but is also one of the best supplements for infant formula and the gut health system.

Global Trends in Research of Programmed Cell Death in Osteoporosis: A Bibliometric and Visualized Analysis (2000-2023).

Osteoporosis (OP) is a systemic metabolic bone disease that is characterized by decreased bone mineral density and microstructural damage to bone tissue. Recent studies have demonstrated significant advances in the research of programmed cell death (PCD) in OP. However, there is no bibliometric analysis in this research field. This study searched the Web of Science Core Collection (WoSCC) database for literature related to OP and PCD from 2000 to 2023. This study used VOSviewers 1.6.20, the "bibliometrix" R package, and CiteSpace (6.2.R3) for bibliometric and visualization analysis. A total of 2905 articles from 80 countries were included, with China and the United States leading the way. The number of publications related to PCD in OP is increasing year by year. The main research institutions are Shanghai Jiao Tong University, Chinese Medical University, Southern Medical University, Zhejiang University, and Soochow University. Bone is the most popular journal in the field of PCD in OP, and the Journal of Bone and Mineral Research is the most co-cited journal. These publications come from 14,801 authors, with Liu Zong-Ping, Yang Lei, Manolagas Stavros C, Zhang Wei, and Zhao Hong-Yan having published the most papers. Ronald S. Weinstein was co-cited most often. Oxidative stress and autophagy are the current research hot spots for PCD in OP. This bibliometric study provides the first comprehensive summary of trends and developments in PCD research in OP. This information identifies the most recent research frontiers and hot directions, which will provide a definitive reference for scholars studying PCD in OP.

The case of young people who use e-cigarettes infrequently: Who is this population? What becomes of them?

BACKGROUND: Emerging data indicate that many adolescents and young adults ("youth") engage in infrequent, or occasional, e-cigarette use. However, little is known about this population as they are often subsumed into the broader "any past-30-day use" category used to define youth "current use." This study aimed to focus on infrequent e-cigarette use by youth, examining its correlates and transitional outcomes. METHODS: Participants were from a prospective cohort study of youth (aged 15-24 at baseline). Among youth who had used e-cigarettes, we classified "infrequent use" as using e-cigarettes ≤5 days in the last 30 days (n=273) and "frequent use" as using e-cigarettes ≥6 days in the last 30 days (n=278). Descriptive statistics, Markov modeling, and logistic regression were utilized. RESULTS: By the 12-month follow-up, 76.8% of those using infrequently at baseline remained in the "infrequent use" category, 6.3% reported no recent use, and 16.8% had escalated to the "frequent use" category. Among the youth using infrequently at baseline, those who did (vs. did not) escalate to frequent use by follow-up had higher baseline nicotine dependence and were more likely to have family members who used tobacco. CONCLUSIONS: Infrequent e-cigarette use is extremely common, and often fairly stable, among young people. Prevention efforts must certainly attempt to reduce escalation and attend to both individual and interpersonal factors (e.g., nicotine dependence, family use). Yet prevention efforts must additionally attend to the case of continued infrequent use, given the high prevalence of people in this category and their regular exposure to e-cigarette harms.

The Bifunctional Effects of Lactoferrin (LFcinB11) in Inhibiting Neural Cell Adhesive Molecule (NCAM) Polysialylation and the Release of Neutrophil Extracellular Traps (NETs).

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.

[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

Nicotine information disclosed online by e-cigarette brands popular with young people.

INTRODUCTION: E-cigarette use is most prevalent among adolescents and young adults - and there are often misperceptions about product risk. The purpose of this study was to determine what nicotine information is provided on e-cigarette brand websites. METHODS: Based on national and local surveys, we identified 44 e-cigarette brands commonly used in the US by adolescents and young adults. For each of these brands, their associated websites were analyzed for disclosed nicotine information. Specifically, for each brand's website, we coded whether there was information on nicotine concentration (recorded if a numerical value was provided such as '5% nicotine'), nicotine form (free-base, nicotine salts, or not stated), and nicotine type (tobacco-derived, synthetically derived, or not stated). Coding allowed for both lay (e.g. 'nic salts') as well as scientific (e.g. 'isomers') terms. RESULTS: Of the 44 brands examined, all provided basic information on nicotine concentration (e.g. '5% nicotine'). However, 23% of brands did not disclose information on nicotine form (i.e. nicotine salt vs free-base), and 66% of brands did not disclose information on nicotine type (i.e. synthetic vs tobacco-derived). CONCLUSIONS: Overall, these results suggest that the e-cigarette industry is not fully informing its consumers about the nicotine in their products. Given that nicotine form and type have implications for e-cigarette addiction potential, these findings highlight a public health concern. There is a need for more comprehensive national regulations for mandating product constituents and emissions disclosures.

Impact of proton PBS machine operating parameters on the effectiveness of layer rescanning for interplay effect mitigation in lung SBRT treatment.

BACKGROUND: Rescanning is a common technique used in proton pencil beam scanning to mitigate the interplay effect. Advances in machine operating parameters across different generations of particle therapy systems have led to improvements in beam delivery time (BDT). However, the potential impact of these improvements on the effectiveness of rescanning remains an underexplored area in the existing research. METHODS: We systematically investigated the impact of proton machine operating parameters on the effectiveness of layer rescanning in mitigating interplay effect during lung SBRT treatment, using the CIRS phantom. Focused on the Hitachi synchrotron particle therapy system, we explored machine operating parameters from our institution's current (2015) and upcoming systems (2025A and 2025B). Accumulated dynamic 4D dose were reconstructed to assess the interplay effect and layer rescanning effectiveness. RESULTS: Achieving target coverage and dose homogeneity within 2% deviation required 6, 6, and 20 times layer rescanning for the 2015, 2025A, and 2025B machine parameters, respectively. Beyond this point, further increasing the number of layer rescanning did not further improve the dose distribution. BDTs without rescanning were 50.4, 24.4, and 11.4 s for 2015, 2025A, and 2025B, respectively. However, after incorporating proper number of layer rescanning (six for 2015 and 2025A, 20 for 2025B), BDTs increased to 67.0, 39.6, and 42.3 s for 2015, 2025A, and 2025B machine parameters. Our data also demonstrated the potential problem of false negative and false positive if the randomness of the respiratory phase at which the beam is initiated is not considered in the evaluation of interplay effect. CONCLUSION: The effectiveness of layer rescanning for mitigating interplay effect is affected by machine operating parameters. Therefore, past clinical experiences may not be applicable to modern machines.

Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: A multicenter, double-blind, placebo-controlled, randomized trial.

BACKGROUND: Yiqi Peiyuan (YQPY) prescription, a composite prescription of traditional Chinese medicine, has been used to prevent or delay the continued deterioration of renal function after acute kidney injury (AKI) in some institutions and has shown considerable efficacy. OBJECTIVE: This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a prospective, double-blind, multicenter, randomized, and placebo-controlled clinical trial. A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule. Participants, caregivers and investigators assessing the outcomes were blinded to group assignment. Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days. Patients in the placebo group received a placebo in the same dose as the YQPY granules. MAIN OUTCOME MEASURES: The primary outcome was the change in the estimated glomerular filtration rate (eGFR) between baseline and after 4 and 24 weeks of treatment. The secondary outcomes were the change of serum creatinine (Scr) level between baseline and after treatment, and the incidence of endpoint events, defined as eGFR increasing by more than 25% above baseline, eGFR >75 mL/min per 1.73 m2 or the composite endpoint, which was defined as the sum of patients meeting either of the above criteria. RESULTS: Data from a total of 114 patients (59 in the YQPY group and 55 in the control group) were analyzed. The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups. In further subgroup analysis (22 in the YQPY group and 31 in the control group), the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2 in the YQPY group and 5.78 mL/min per 1.73 m2 in the placebo group, and the mean difference between groups was 21.61 mL/min per 1.73 m2 (P < 0.001). Thirteen (59.1%) patients in the YQPY group and 5 (16.1%) in the placebo group reached the composite endpoints (P = 0.002). During the intervention, 2 and 4 severe adverse events were reported in the YQPY and placebo groups, respectively. CONCLUSION: The YQPY granules can effectively improve the renal function of patients 4 weeks after the onset of AKI, indicating that it has good efficacy for improving short-term renal outcomes in patients with AKI. The YQPY granules may be a promising therapy for adults with AKI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100051723. Please cite this article as: Wu JJ, Zhang TY, Qi YH, Zhu MY, Fang Y, Qi CJ, Cao LO, Lu JF, Lu BH, Tang LM, Shen JX, Mou S. Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: a multicenter, double-blind, placebo-controlled, randomized trial. J Integr Med. 2024; 22(3): 279-285.

CPT1A mediates the succinylation of SP5 which activates transcription of PDPK1 to promote the viability and glycolysis of prostate cancer cells.

Succinylation modification involves in the progression of human cancers. The present study aimed to investigate the role of CPT1A, which is a succinyltransferase in the progression of prostate cancer (PCa). CCK-8 was used to detect the cell viability. Seahorse was performed to evaluate the cell glycolysis. Luciferase assay was used to detect the transcriptional regulation. ChIP was performed to assess the binding between transcriptional factors with the promoters. Co-IP was used to assess the binding between proteins. We found that CPT1A was highly expressed in PCa tissues and cell lines. Silencing of CPT1A inhibited the viability and glycolysis of PCa cells. Mechanistically, CPT1A promoted the succinylation of SP5, which strengthened the binding between SP5 and the promoter of PDPK1. SP5 activated PDPK1 transcription and PDPK1 activated the AKT/mTOR signal pathway. These findings might provide novel targets for the diagnosis or therapy of prostate cancer.

An Enzyme-responsive Porphyrin Metal-organic Framework Nanosystem for Targeted and Enhanced Synergistic Cancer Photo-chemo Therapy.

BACKGROUND: The clinical efficiency of photodynamic therapy (PDT) in combination with chemotherapy has proven to be a promising strategy for tumor treatment, yet is restricted by the high glutathione (GSH) concentration at the tumor site and nonspecific drug targeting. OBJECTIVE: The goal of the current research was to create a biocompatible GSH-depleting and tumor- targeting nanoparticle (denoted as DOX/CA@PCN-224@HA) for the combined photodynamic and chemo photo-chemo) therapy. METHODS: The nanoparticles were characterized by transmission electron microscopy (TEM). A UV-vis spectrophotometer was used to measure the drug loading efficiency (DE) and encapsulation efficiency (EE). The GSH-depleting ability was measured using Ellman's test. Confocal laser scan microscopy (CLSM) was used to assess the cellular uptake. MTT was adopted to evaluate the cytotoxicity of DOX/CA@PCN-224@HA against 4T1 cells. RESULTS: The altered PCN-224 showed excellent monodispersing with a dimension of approximately 193 nm ± 2 nm in length and 79 nm ± 3 nm in width. The larger and spindle grid-like structure of PCN-224 obtains better dual-drug loading ability (DOX: 20.58% ± 2.60%, CA: 21.81% ± 1.98%) compared with other spherical PCN-224 nanoparticles. The ultimate cumulative drug release rates with hyaluronidase (HAase) were 74% ± 1% (DOX) and 45% ± 2% (CA) after 72 h. DOX/CA@PCN-224@HA showed GSH-consuming capability, which could improve the PDT effect. The drug-loaded nanoparticles could accurately target 4T1 cells through biological evaluations. Moreover, the released DOX and CA display cooperative effects on 4T1 cells in vitro. DOX/CA@PCN-224@HA nanoparticles showed inhibition against 4T1 cells with an IC50 value of 2.71 µg mL-1. CONCLUSION: This nanosystem displays great potential for tumor-targeted enhanced (photo-chemo) therapy.

Optimal insertion site for ultrasound-guided radial artery catheterization utilizing the dynamic needle tip positioning technique: A prospective randomized controlled study.

BACKGROUND: The dynamic needle tip positioning technique represents an advanced version of the short-axis out-of-plane ultrasound-guided approach employed for radial artery catheterization. The study aimed to explore the most effective insertion site capable of expeditiously and accurately executing the procedure in a clinical setting. METHODS: A prospective randomized controlled study encompassed 246 elective surgery patients necessitating invasive arterial monitoring. Participants were randomly assigned to three distinct groups: Site 1 (targeting the radial styloid process), Site 2 (midway between Sites 1 and 3), and Site 3 (distal one-third of the forearm). The dynamic needle tip positioning technique was implemented across all groups. Crucial parameters, such as first-attempt success rate, time to success, overall success rate, total catheterization time, number of attempts, and complications, were meticulously documented and compared. RESULTS: The Site 2 cohort presented a significantly heightened first-attempt success rate compared to Site 1 (97.5% vs 80%, p = 0.003) and Site 3 (97.5% vs 81.25%, p = 0.006). Moreover, Site 2 displayed a reduced time to success in contrast to Site 1 (31.5 vs 38, p = 0.003) and Site 3 (31.5 vs 40, p = 0.006). Total catheterization time was significantly shorter in Site 2 compared to Site 1 (32 vs 42.5, p < 0.001) and Site 3 (32 vs 43.5, p < 0.001). Site 2 necessitated fewer attempts than Site 1 (p = 0.02) and Site 3 (p = 0.03). Male gender and puncture at Site 2 were associated with expedited time to success. Adverse events manifested more frequently in the Site 3 group compared to the Site 1 group (15% vs 3.75%, p = 0.03) and the Site 2 group (15% vs 2.5%, p = 0.01). CONCLUSIONS: The optimal insertion site for ultrasound-guided radial artery catheterization utilizing the dynamic needle tip positioning technique in adult patients is situated midway between the radial styloid process and the distal one-third of the forearm.

GLORI for absolute quantification of transcriptome-wide m6A at single-base resolution.

N6-methyladenosine (m6A) is the most abundant posttranscriptional chemical modification in mRNA, involved in regulating various physiological and pathological processes throughout mRNA metabolism. Recently, we developed GLORI, a sequencing method that enables the production of a globally absolute-quantitative m6A map at single-base resolution. Our technique utilizes the glyoxal- and nitrite-based chemical reaction, which selectively deaminates unmethylated adenosines while leaving m6A intact. The RNA library can then be prepared using a modified library construction protocol from enhanced UV crosslinking and immunoprecipitation (eCLIP) or commercial kits. Here we provide a detailed protocol for proper RNA sample handling and provide further guidelines for the use of a tailored bioinformatics pipeline (GLORI-tools) for subsequent data analysis. Compared with current methods, this new method is both exceptionally sensitive and robust, capable of identifying ~80,000 m6A sites with 50 Gb sequencing data in mammalian cells. It also provides a quantitative readout for m6A sites at single-base resolution. We hope the technique will provide a precise and unbiased tool for investigating m6A biology across various fields. Basic expertise in molecular biology and knowledge of bioinformatics are required for the protocol. The entire procedure can be completed within a week, with the library construction process taking ~4 d.

Demographic and Behavioral Differences Between Adolescents and Young Adults Who Use E-Cigarettes at Low and High Frequency.

BACKGROUND: Among adolescents and young adults (AYAs), "current use" of electronic cigarettes (e-cigarettes) is commonly defined as any use in the past 30 days. However, few studies have examined differences among those within this broad category. This study examined characteristics of AYAs who used e-cigarettes at a low frequency (within the last 3 months but <6 days out of the past 30 days) and those who used e-cigarettes at a high frequency (6+ days out of the past 30 days). METHODS: We conducted cross-sectional analyses among 551 Ohio AYAs (15- to 24-year-olds) who reported using an e-cigarette to vape nicotine in the past 3 months. We used descriptive statistics and logistic regression to characterize those using e-cigarettes at a low frequency and a high frequency. RESULTS: Among our sample of AYAs who reported past 3-month e-cigarette use, about half (50.8%) reported using an e-cigarette 6 or more days out of the past 30 days (ie, high frequency). In the multivariable analysis, reported nicotine dependence (Odds Ratio [OR]: 7.0, 95% CI: 4.8, 10.3) and current other tobacco product use (OR: 1.8, 95% CI: 1.1, 2.9) were associated with high-frequency e-cigarette use. CONCLUSION: Our results suggest that frequency of use is an important characteristic in understanding AYA e-cigarette use. Any use in the past 30 days may not be sensitive enough to understand dependence and tobacco-use behaviors. Further characterizing "current" e-cigarette use by frequency of use may provide meaningful information for public health professionals to better target intervention and cessation efforts to AYAs.