The profound review of Fenton process: What's the next step?

Fenton and Fenton-like processes, which could produce highly reactive species to degrade organic contaminants, have been widely used in the field of wastewater treatment. Therein, the chemistry of Fenton process including the nature of active oxidants, the complicated reactions involved, and the behind reason for its strongly pH-dependent performance, is the basis for the application of Fenton and Fenton-like processes in wastewater treatment. Nevertheless, the conflicting views still exist about the mechanism of the Fenton process. For instance, reaching a unanimous consensus on the nature of active oxidants (hydroxyl radical or tetravalent iron) in this process remains challenging. This review comprehensively examined the mechanism of the Fenton process including the debate on the nature of active oxidants, reactions involved in the Fenton process, and the behind reason for the pH-dependent degradation of contaminants in the Fenton process. Then, we summarized several strategies that promote the Fe(II)/Fe(III) cycle, reduce the competitive consumption of active oxidants by side reactions, and replace the Fenton reagent, thus improving the performance of the Fenton process. Furthermore, advances for the future were proposed including the demand for the high-accuracy identification of active oxidants and taking advantages of the characteristic of target contaminants during the degradation of contaminants by the Fenton process.

"Hepatic hilum area priority, liver posterior first": An optimized strategy in laparoscopic resection for type III-IV hilar cholangiocarcinoma.

BACKGROUND: In recent years, pure laparoscopic radical surgery for Bismuth-Corlette type III and IV hilar cholangiocarcinoma (HCCA) has been preliminarily explored and applied, but the surgical strategy and safety are still worthy of further improvement and attention. AIM: To summarize and share the application experience of the emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types III and IV. METHODS: The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types III and IV who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed. RESULTS: Among the 6 patients, 4 were males and 2 were females. The average age was 62.2 ± 11.0 years, and the median body mass index was 20.7 (19.2-24.1) kg/m2. The preoperative median total bilirubin was 57.7 (16.0-155.7) µmol/L. One patient had Bismuth-Corlette type IIIa, 4 patients had Bismuth-Corlette type IIIb, and 1 patient had Bismuth-Corlette type IV. All patients successfully underwent pure laparoscopic radical resection following the strategy of "hepatic hilum area dissection priority, liver posterior separation first". The operation time was 358.3 ± 85.0 minutes, and the intraoperative blood loss volume was 195.0 ± 108.4 mL. None of the patients received blood transfusions during the perioperative period. The median length of stay was 8.3 (7.0-10.0) days. Mild bile leakage occurred in 2 patients, and all patients were discharged without serious surgery-related complications. CONCLUSION: The emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types III and IV. This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA, shortens the learning curve, and is worthy of further clinical application.

Sigmoid Volvulus in the Setting of Type 4 Hiatal Hernia: An Uncommon Presentation and Literature Review.

Hiatal hernias occur when intra-abdominal contents protrude into the diaphragmatic opening. Of the four classifications, Type 4 hiatal hernias are the most rare and severe. They develop from herniation of the gastroesophageal junction and abdominal viscera other than the stomach into the thoracic cavity. The resulting increase in intrathoracic pressure can cause a wide variety of symptoms on presentation and potentially lead to misdiagnosis. We present a rare case in which a 78-year-old woman presented with nonspecific symptoms and was diagnosed with incarcerated Type 4 hiatal hernia with sigmoid volvulus. We also report a literature review from 2015 to emphasize the importance of recognizing diverse symptomatic presentations in complex Type 4 hiatal hernias and the need for a comprehensive evaluation, as early detection and prompt intervention are essential in preventing life-threatening complications.

Evaluation of Anticancer Efficacy of D-α-Tocopheryl Polyethylene-Glycol Succinate and Soluplus® Mixed Micelles Loaded with Olaparib and Rapamycin Against Ovarian Cancer.

Purpose: Ovarian cancer has the highest mortality rate and lowest survival rate among female reproductive system malignancies. There are treatment options of surgery and chemotherapy, but both are limited. In this study, we developed and evaluated micelles composed of D-α-tocopheryl polyethylene-glycol (PEG) 1000 succinate (TPGS) and Soluplus® (SOL) loaded with olaparib (OLA), a poly(ADP-ribose)polymerase (PARP) inhibitor, and rapamycin (RAPA), a mammalian target of rapamycin (mTOR) inhibitor in ovarian cancer. Methods: We prepared micelles containing different molar ratios of OLA and RAPA embedded in different weight ratios of TPGS and SOL (OLA/RAPA-TPGS/SOL) were prepared and physicochemical characterized. Furthermore, we performed in vitro cytotoxicity experiments of OLA, RAPA, and OLA/RAPA-TPGS/SOL. In vivo toxicity and antitumor efficacy assays were also performed to assess the efficacy of the mixed micellar system. Results: OLA/RAPA-TPGS/SOL containing a 4:1 TPGS:SOL weight ratio and a 2:3 OLA:RAPA molar ratio showed synergistic effects and were optimized. The drug encapsulation efficiency of this formulation was >65%, and the physicochemical properties were sustained for 180 days. Moreover, the formulation had a high cell uptake rate and significantly inhibited cell migration (**p < 0.01). In the in vivo toxicity test, no toxicity was observed, with the exception of the high dose group. Furthermore, OLA/RAPA-TPGS/SOL markedly inhibited tumor spheroid and tumor growth in vivo. Conclusion: Compared to the control, OLA/RAPA-TPGS/SOL showed significant tumor inhibition. These findings lay a foundation for the use of TPGS/SOL mixed micelles loaded with OLA and RAPA in the treatment of ovarian cancer.

Mitochondrial proteome analysis reveals that an augmented cytochrome c oxidase assembly and activity potentiates respiratory capacity in sarcoma.

Mitochondrial oxidative phosphorylation (OXPHOS) is an obligatory process in sarcoma. Despite that, the metabolic programming of sarcoma mitochondria is still unknown. To obtain a comprehensive metabolic insight of mitochondria, we developed a mouse fibrosarcoma model by injecting 3-methylcholanthrene and compared mitochondrial proteomes between sarcoma and its contralateral normal muscle using mass spectrometry. Our study identified ∼449 proteins listed in the SwissProt databases, and all the data sets are available via ProteomeXchange with the identifier PXD044903. In sarcoma, 49 mitochondrial proteins were found differentially expressed, including 36 proteins up-regulated and 13 proteins down-regulated, with the significance of p-value <0.05 and the log2[fold change] > 1 and < -1 as compared to normal muscle. Our data revealed that various anaplerotic reactions actively replenish the TCA cycle in sarcoma. The comparative expression profile and Western blotting analysis of OXPHOS subunits showed that complex-IV subunits, MT-CO3 and COX6A1, were significantly up-regulated in sarcoma vs. normal muscle. Further, biochemical and physiological assays confirmed enhanced complex-IV specific enzymatic and supercomplex activities with a concomitant increase of oxygen consumption rate in sarcoma mitochondria compared to normal muscle. Validation with human post-operative sarcoma tissues also confirms an increased MT-CO3 expression compared to normal tissue counterparts. Thus, our data comprehensively analyses the mitochondrial proteome and identifies augmented complex-IV assembly and activity in sarcoma.

Astragaloside IV attenuates ferroptosis and protects against iron overload-induced retinal injury.

Retinal injury may be exacerbated by iron overload. Astragaloside IV (AS-IV) has potential applications in the food and healthcare industry to promote eye health. We sought to determine the mechanisms responsible for the protective effects of AS-IV on photoreceptor and retinal pigment epithelium cell death induced by iron overload. We conducted in vitro and in vivo experiments involving AS-IV pretreatment. We tested AS-IV for its ability to protect iron-overload mice from retinal injury. In particular, we analyzed the effects of AS-IV on iron overload-induced ferroptosis in 661W and ARPE-19 cells. AS-IV not only attenuated iron deposition and retinal injury in iron-overload mice but also effectively reduced iron overload-induced ferroptotic cell death in 661W and ARPE-19 cells. AS-IV effectively prevented ferroptosis by inhibiting iron accumulation and lipid peroxidation. In addition, inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) eliminated the protective effect of AS-IV against ferroptosis. The results suggest that ferroptosis might be a significant cause of retinal cell death associated with iron overload. AS-IV provides protection from iron overload-induced ferroptosis, partly by activating the Nrf2 signaling pathway.

Fetal bradycardia and acidosis during maternal parenteral iron: Case reports and literature review.

Iron deficiency anemia is an important problem among pregnant women, and intravenous (IV) iron infusions have been increasingly used. Whether fetal monitoring is required during infusion has been debated, with a recent guideline by Hematologists recommending against such. We report two cases of fetal bradycardia after iron isomaltoside (IIM), in women with otherwise good maternal and fetal health. Both developed dyspnea with desaturation minutes from infusion, followed by persistent fetal bradycardia. Both underwent category 1 CS, with cord arterial pH of 7.08 and 6.94 respectively. Upon literature review, only three case reports on fetal bradycardia in IV iron were identified. For older IV iron formulations, a case was reported after IV dextran test dose, while two cases after ferric gluconate were reported. For the new formulation IIM, only one case was reported so far, but in a woman with Crohn's disease and intrauterine growth restriction. IV iron in pregnancy carries risk of anaphylactic or hypersensitivity reactions, even with the newest formulations and in women with good maternal and fetal health. While rarely reported so far, fetal bradycardia is a possible consequence, commonly preceded by respiratory symptoms. Fetal monitoring should therefore be considered during infusion.

A novel multivariable Mendelian randomization framework to disentangle highly correlated exposures with application to metabolomics.

Mendelian randomization (MR) utilizes genome-wide association study (GWAS) summary data to infer causal relationships between exposures and outcomes, offering a valuable tool for identifying disease risk factors. Multivariable MR (MVMR) estimates the direct effects of multiple exposures on an outcome. This study tackles the issue of highly correlated exposures commonly observed in metabolomic data, a situation where existing MVMR methods often face reduced statistical power due to multicollinearity. We propose a robust extension of the MVMR framework that leverages constrained maximum likelihood (cML) and employs a Bayesian approach for identifying independent clusters of exposure signals. Applying our method to the UK Biobank metabolomic data for the largest Alzheimer disease (AD) cohort through a two-sample MR approach, we identified two independent signal clusters for AD: glutamine and lipids, with posterior inclusion probabilities (PIPs) of 95.0% and 81.5%, respectively. Our findings corroborate the hypothesized roles of glutamate and lipids in AD, providing quantitative support for their potential involvement.

Preparation, characterization, and mechanism of DPP-IV inhibitory peptides derived from Bactrian camel milk.

In this study, double enzyme hydrolysis significantly enhanced the DPP-IV inhibition rate compared to single enzyme. The α + K enzymes exhibited the highest inhibition rate. Ultrasonic pretreatment for 30 min improved the hydrolysis efficiency and DPP-IV inhibition rate, potentially due to the structural changes in hydrolysates, such as the increased surface hydrophobicity, and reduced particle size, α-helix and ß-turn. Six peptides were screened and verified in vitro. QPY, WPEYL, and YPPQVM displayed competitive inhibition, while LPAAP and IPAPSFPRL displayed mixed competitive/non-competitive inhibition. The interactions between these six peptides and DPP-IV primarily occurred through hydrogen bonds, electrostatic and hydrophobic interactions. Network pharmacological analysis indicated that LPAAP might inhibit DPP-IV activity trough interactions with diabetes-related targets such as CASP3, HSP90AA1, MMP9, and MMP9. These results uncover the potential mechanism of regulating blood glucose by camel milk hydrolysates, establishing camel milk peptide as a source of DPP-IV inhibitory peptide.

Physicochemical properties, biological chemistry and mechanisms of action of caries-arresting diammine-silver(I) fluoride and silver(I)-fluoride solutions for clinical use: a critical review.

This paper serves as a Part II follow-up of our research investigations performed on the molecular structures of silver(I)-fluoride (SF) and diammine-silver(I) fluoride (SDF) complexes in solution-based commercial products for clinical application, their precise chemical compositions, and their nature in aqueous solution, the latter including rapid fluoride-exchange processes at the silver(I) ion centre monitored by 19F NMR analysis (Part I). Part I of this series also explores the mechanisms of action (MoA) of these complexes, and is therefore largely focused on their chemical reactions with constituents of human saliva, which has access to their sites of application. Such reactions were found to slowly promote the generation of potentially physiologically-active Ag/AgCl nanoparticles from primarily-generated discoloured silver(I) chloride (AgCl) precipitates, a process involving salivary electron-donors such as thiocyanate and L-cysteine. Since this research has shed new light on potential MoAs for these products, in this accompanying report (Part II), we have performed a critical review of scientific literature in order to rationalize our results in relation to current views on these mechanisms for SF and SDF products employed for the successful clinical arrest of dental caries. Following an Introduction to the subject matter ( Section 1), this paper comprises a generalized overview of silver coordination chemistry ( Section 2), which is followed by a section focused on the aqueous solution status and equilibria involved in SF chemistry ( Section 3), the latter including results acquired from an original simulation of the electronic absorption spectra of coloured SF complexes in aqueous solution (Section 3.1). Section 4 then investigates detailed rationales for the biologically-relevant ligand-exchange and redox chemistries, disposition and fates of SF, SDF and silver(I)-nitrate when employed for the treatment of dental caries, with emphasis placed on their therapeutic MoAs. This Section is supported by the provision of valuable information centralized on (1) relevant biomolecular chemistry involved in solution- and solid-state matrices ( Section 4.1); (2) SF and perhaps silver(I)-nitrate as more cost-effective alternatives to SDF therapies ( Section 4.2); and (3) the potential therapeutic benefits and effects offered by silver-based nanoparticles and their associated MoAs ( Section 4.3). Recommendations for future investigations in this area are proposed.

The relationship between dexmedetomidine administration and prognosis in patients with sepsis-induced coagulopathy: a retrospective cohort study.

Background: This study aimed to investigate whether dexmedetomidine provides survival benefit in critically ill patients with sepsis-induced coagulopathy (SIC). Methods: Patients with sepsis-induced coagulopathy admitted to the ICU were identified from the Medical Information Marketplace for Intensive Care (MIMIC)-IV database. They were divided into two groups: patients who started dexmedetomidine within 48 h of ICU admission and lasted for more than 4 h and patients who did not receive dexmedetomidine as a control group. The primary outcome was 28-day hospital mortality, the secondary outcome was in-hospital mortality, and the extended outcomes included duration of mechanical ventilation and vasopressor use, ICU stay, and hospital stay. Propensity score matching (PSM) analysis was used to match patients who received dexmedetomidine with those who did not, and multivariable Cox models and logistics models were used to account for baseline differences and unmeasured confounders. An external validation was performed with the Critical care database comprising patients with infection at Zigong Fourth People's Hospital. Results: After PSM, 592 patients who received dexmedetomidine were matched with 592 patients who did not receive dexmedetomidine. In the primary and secondary endpoints, dexmedetomidine was associated with a lower risk of 28-day hospital mortality (19.3% vs. 14.2%, hazard ratio (HR) 0.71; P = 0.020) and in-hospital mortality (22.3% vs. 16.4%, odds ratio (OR) 0.68; P = 0.017) in patients with SIC. Regarding the extended outcome, dexmedetomidine was also associated with a longer length of hospital stay (median 12.54 days vs. 14.87 days, P = 0.002) and longer ICU stay (median 5.10 days vs. 6.22 days, P = 0.009). In addition, the duration of mechanical ventilation was significantly increased in the dexmedetomidine group (median 41.62 h vs. 48.00 h, p = 0.022), while the duration of vasopressor use was not significantly different (median 36.67 h vs. 39.25 h, p = 0.194). Within 48 h of ICU stay, receiving a dose of dexmedetomidine greater than 0.474 µg/kg/h and continuous dexmedetomidine administration for 24-48 h may be associated with 28-day hospitalization outcomes in patients with SIC. External cohort validation also found that the use of dexmedetomidine after admission to the ICU can reduce 28-day mortality in patients with SIC. Conclusion: Dexmedetomidine administration is associated with reduced 28-day hospital mortality and in-hospital mortality in critically ill patients with SIC, and these findings deserve further verification in randomized controlled trials.

Neurocognitive performance of patients undergoing intravenous versus oral opioid agonist treatment: a prospective multicenter study on three-month treatment effects.

Introduction: The first-line treatment for opioid dependence is opioid agonist treatment (OAT) with oral opioids. However, in some cases, treatment with intravenous diacetylmorphine (IV-DAM) is indicated. Research on neurocognitive impairments and treatment effects of OAT - particularly with IV-DAM - on neurocognitive functioning, is scarce. The current study is the first to investigate the neurocognitive performance of individuals on OAT with IV-DAM. Using a prospective study design with two timepoints of measurement, the first aim was to assess the nature and extent of neurocognitive functioning in individuals with opioid dependence by comparing participants' neurocognitive performance with normative data of the general population on admission to treatment (baseline) and after an initial three-month period of OAT (study end). The second aim was to examine whether and to what extent neurocognitive performance would improve after three months on OAT. The third aim was to investigate whether, and if so, to what extent the treatment method (IV-DAM vs. oral opioids) would lead to higher neurocognitive improvements at study end. Methods: Forty-seven opioid-dependent individuals (baseline; 33 individuals at study end) participated in this study (mean age: 34.3 years; 27.7% female). Participants underwent neuropsychological testing with a battery of 12 tests covering different neurocognitive domains, including attention, memory, and executive functions. Results: Compared to normative data, opioid-dependent individuals showed impairments in almost every test both at baseline and at study end. At baseline, neurocognitive performance did not differ between individuals receiving IV-DAM or oral opioids for OAT. Compared to baseline, the neurocognitive performance did neither improve nor deteriorate after three months of treatment with neither IV-DAM nor oral opioids. However, a trend towards improvement was found for the memory domain. Discussion: Given that neurocognitive impairments should be considered in treatment planning and therapeutic interventions. Since a reduced cognitive performance may affect both the treatment outcome and the therapeutic relationship unfavorably, specific neurocognitive training at the beginning of treatment should be considered.

A versatile sample-delivery system for X-ray photoelectron spectroscopy of in-flight aerosols and free nanoparticles at MAX IV Laboratory.

Aerosol science is of utmost importance for both climate and public health research, and in recent years X-ray techniques have proven effective tools for aerosol-particle characterization. To date, such methods have often involved the study of particles collected onto a substrate, but a high photon flux may cause radiation damage to such deposited particles and volatile components can potentially react with the surrounding environment after sampling. These and many other factors make studies on collected aerosol particles challenging. Therefore, a new aerosol sample-delivery system dedicated to X-ray photoelectron spectroscopy studies of aerosol particles and gas molecules in-flight has been developed at the MAX IV Laboratory. The aerosol particles are brought from atmospheric pressure to vacuum in a continuous flow, ensuring that the sample is constantly renewed, thus avoiding radiation damage, and allowing measurements on the true unsupported aerosol. At the same time, available gas molecules can be used for energy calibration and to study gas-particle partitioning. The design features of the aerosol sample-delivery system and important information on the operation procedures are described in detail here. Furthermore, to demonstrate the experimental range of the aerosol sample-delivery system, results from aerosol particles of different shape, size and composition are presented, including inorganic atmospheric aerosols, secondary organic aerosols and engineered nanoparticles.

Survival Outcomes of Primary versus Interval Cytoreductive Surgery for FIGO IV Ovarian Cancer (SOFI-4): a Nationwide Population-based Target Trial Emulation.

BACKGROUND: The effect of primary cytoreductive surgery versus interval cytoreductive surgery on FIGO IV ovarian cancer outcomes remains uncertain, and may vary depending on the stage and the extraperitoneal metastasis location. Emulating target trials through causal assessment combined with propensity score adjustment has become a leading method for evaluating interventions using observational data. OBJECTIVE: To assess the effect of primary versus interval cytoreductive surgery on progression-free and overall survival in patients with FIGO IV ovarian cancer using target trial emulation. STUDY DESIGN: Utilizing the comprehensive French national health insurance database, we emulated a target trial to explore primary versus interval cytoreductive surgery causal impacts on FIGO IV ovarian cancer prognosis (Surgery for Ovarian cancer FIGO 4: SOFI-4). The clone method with inverse probability of censoring weighting was used to adjust for informative censoring and balance baseline characteristics between the groups. Subgroup analyses were conducted based on FIGO stages and extraperitoneal metastasis locations. The study included patients under 75 years of age, in good health condition, diagnosed with FIGO IV ovarian cancer between January 1, 2014, and December 31, 2022. The primary and secondary outcomes were respectively five-year progression-free survival and seven-year overall survival. RESULTS: Among the 2,772 patients included in the study, 948 (34.2%) were classified as FIGO IVA and 1,824 (65.8%) as FIGO IVB at inclusion. Primary cytoreductive surgery was performed on 1,182 patients (42.6%), while interval cytoreductive surgery was conducted on 1,590 patients (57.4%). The median progression survival for primary cytoreductive surgery was 19.7 months (interquartile range [IQR]: 19.3-20.1), compared to 15.7 months (IQR: 15.7-16.1) for those who underwent interval cytoreductive surgery. The median overall survival was 63.1 months [IQR: 61.7-65.4] for primary cytoreductive surgery, in comparison to 55.6 months [IQR: 53.8-56.3] for interval cytoreductive surgery. The findings of our study indicate that primary cytoreductive surgery is associated with a 5.0-month increase in five-year progression-free survival (95% Confidence Intervals [CI]: 3.8-6.2) and a 3.9-month increase in seven-year overall survival (95% CI: 1.9-6.2). These survival benefits of primary over interval cytoreductive surgery were observed in both the FIGO IVA and IVB subgroups. Primary cytoreductive surgery demonstrated improved progression-free survival and overall survival in patients with pleural, supra-diaphragmatic, or extra-abdominal lymph node metastasis. CONCLUSIONS: SOFI-4 advocates for the benefits of primary cytoreductive surgery over interval cytoreductive surgery for patients with FIGO IV ovarian cancer, suggesting extraperitoneal metastases like supra-diaphragmatic or extra-abdominal lymph nodes should not automatically preclude primary cytoreductive surgery consideration in suitable patients.

Phase IV Drug Trials With a Canadian Site: A Comparison of Industry-Funded and Non-Industry-Funded Trials.

Recent regulatory reforms have favored expedited drug marketing and increased reliance on Phase IV clinical trials for safety and efficacy assurance. This study, utilizing ClinicalTrials.gov, assesses the characteristics of Phase IV trials, with at least one site in Canada, examining those funded by industry sponsors and those lacking industry funding. Additionally, it compares the publication status of industry-funded and non-industry-funded trials through a manual review of the medical literature. Between 2000 and 2022, 864 Phase IV trials were completed, with 480 (55.6%) receiving industry funding and 384 (44.4%) funded solely by non-industry sources. Industry-funded clinical trials were larger (mean 204 enrollees versus 70), more likely to be international (57.7% versus 9.6%) and reported results more promptly (1.21 years after completion versus 1.85 years), yet both types shared similar designs, outcomes, and completion times. Publication rates were 81.8% for industry-funded and 65.8% for non-industry-funded trials. The ClinicalTrials. gov registry displayed 48 inaccuracies in publication associations, raising concerns about its accuracy. Our findings underscore the existing institutional limitations in ensuring comprehensive reporting and publication of Phase IV trial results funded by both industry and non-industry sources.

Effect of different sedatives on the prognosis of patients with mechanical ventilation: a retrospective cohort study based on MIMIC-IV database.

Aim: To compare the effects of midazolam, propofol, and dexmedetomidine monotherapy and combination therapy on the prognosis of intensive care unit (ICU) patients receiving continuous mechanical ventilation (MV). Methods: 11,491 participants from the Medical Information Mart for Intensive Care (MIMIC)-IV database 2008-2019 was included in this retrospective cohort study. The primary outcome was defined as incidence of ventilator-associated pneumonia (VAP), in-hospital mortality, and duration of MV. Univariate and multivariate logistic regression analyses were utilized to evaluate the association between sedation and the incidence of VAP. Univariate and multivariate Cox analyses were performed to investigate the correlation between sedative therapy and in-hospital mortality. Additionally, univariate and multivariate linear analyses were conducted to explore the relationship between sedation and duration of MV. Results: Compared to patients not receiving these medications, propofol alone, dexmedetomidine alone, combination of midazolam and dexmedetomidine, combination of propofol and dexmedetomidine, combination of midazolam, propofol and dexmedetomidine were all association with an increased risk of VAP; dexmedetomidine alone, combination of midazolam and dexmedetomidine, combination of propofol and dexmedetomidine, combination of midazolam, propofol and dexmedetomidine may be protective factor for in-hospital mortality, while propofol alone was risk factor. There was a positive correlation between all types of tranquilizers and the duration of MV. Taking dexmedetomidine alone as the reference, all other drug groups were found to be associated with an increased risk of in-hospital mortality. The administration of propofol alone, in combination with midazolam and dexmedetomidine, in combination with propofol and dexmedetomidine, in combination with midazolam, propofol and dexmedetomidine were associated with an increased risk of VAP compared to the use of dexmedetomidine alone. Conclusion: Dexmedetomidine alone may present as a favorable prognostic option for ICU patients with mechanical ventilation MV.

Effectiveness of the proximal medial branch in DIEP flaps for breast reconstruction using Hartrampf zone IV.

BACKGROUND: When performing breast reconstruction using a deep inferior epigastric artery (DIEA) perforator (DIEP) flap, including Hartrampf zone IV, the bipedicled DIEP flap has been argued to be necessary to ensure stable perfusion. However, a proximal medial branch (PMB), which is the most proximal perforator of DIEA, may make it possible to obtain adequate perfusion in a unilateral DIEP flap. This study aimed to clarify the detailed anatomical characteristics of PMB and its potential clinical applications in breast reconstruction. METHODS: This retrospective study was conducted on breast reconstruction using the DIEP flap between May 2020 and July 2023. Data on PMB anatomy were collected from preoperative contrast-enhanced computed tomography angiography, and contralateral perfusion of the flap was estimated using intraoperative indocyanine green angiography. RESULTS: PMB was present in approximately 85% of the cases, arising near the lateral border of the rectus abdominis, branching caudomedially in more than half of the cases, and perforating 2.3 cm laterally and 8.8 cm caudally, on average, from the umbilicus. The average perfusion area of zones II and IV significantly expanded to 96.5% and 74.2%, respectively, when PMB was included in the DIEP flap, and 9 of 22 cases showed contrast extending to the entire zone IV. CONCLUSIONS: The use of the DIEP flap with PMB is a good option for substantial-volume breast reconstruction. When utilizing PMB, it is important to consider its specific anatomy, location of the main perforator, and pedicle length.

Locally unlocks prodrugs by radiopharmaceutical in tumor for cancer therapy.

Chemotherapy is the first-line treatment for cancer, but its systemic toxicity can be severe. Tumor-selective prodrug activation offers promising opportunities to reduce systemic toxicity. Here, we present a strategy for activating prodrugs using radiopharmaceuticals. This strategy enables the targeted release of chemotherapeutic agents due to the high tumor-targeting capability of radiopharmaceuticals. [18F]FDG (2-[18F]-fluoro-2-deoxy-D-glucose), one of the most widely used radiopharmaceuticals in clinics, can trigger Pt(IV) complex for controlled release of axial ligands in tumors, it might be mediated by hydrated electrons generated by water radiolysis resulting from the decay of radionuclide 18F. Its application offers the controlled release of fluorogenic probes and prodrugs in living cells and tumor-bearing mice. Of note, an OxaliPt(IV) linker is designed to construct an [18F]FDG-activated antibody-drug conjugate (Pt-ADC). Sequential injection of Pt-ADC and [18F]FDG efficiently releases the toxin in the tumor and remarkably suppresses the tumor growth. Radiotherapy is booming as a perturbing tool for prodrug activation, and we find that [18F]FDG is capable of deprotecting various radiotherapy-removable protecting groups (RPGs). Our results suggest that tumor-selective radiopharmaceutical may function as a trigger, for developing innovative prodrug activation strategies with enhanced tumor selectivity.

A sensitive fluorescence assay of serum dipeptidyl peptidase IV activity to predict the suitability of its inhibitors in patients with type 2 diabetes mellitus.

DPP-IV inhibitors, which are close to the natural hypoglycemic pathway of human physiology and have few side effects, have been extensively employed in the management of type 2 diabetes mellitus (T2DM). However, there are currently no specific blood indicators that can indicate or predict a patient's suitability for DPP-IV inhibitors. In this study, based on the self-developed high-specificity fluorescent substrate glycyl-prolyl-N-butyl-4-amino-1, 8-naphthimide (GP-BAN), a detection method of human serum DPP-IV activity was established and optimized. The method demonstrates a favorable lower limit of detection (LOD) at 0.32 ng/mL and a satisfactory lower limit of quantification (LOQ) of 1.12 ng/mL, and can be used for the detection of DPP-IV activity in trace serum (2 µL). In addition, Vitalliptin and Sitagliptin showed similar IC50 values when human recombinant DPP-IV and human serum were used as enzyme sources, and the intra-day and inter-day precision obtained by the microplate analyzer were less than 15 %. These results indicate that the microplate reader based detection technique has good accuracy, repeatability and reproducibility. A total of 700 volunteers were recruited, and 646 serum samples were tested for DPP-IV activity. The results showed that serum DPP-IV activity was higher in patients with T2DM than in controls (P < 0.01). However, the statistical data of family history of diabetes, gender and age of diabetic patients showed no statistical significance, and there was no contrast difference. The DPP-IV activity of serum in T2DM patients ranged from 2.4 µmol/min/L to 78.6 µmol/min/L, with a huge difference of up to 32-fold. These results suggest that it is necessary to test DPP-IV activity in patients with T2DM when taking DPP-IV inhibitors to determine the applicability of DPP-IV inhibitors in T2DM patients. These results suggest that it is necessary to detect the activity of DPP-IV in blood before taking DPP-IV inhibitors in patients with T2DM to judge the applicability of DPP-IV inhibitors in patients with T2DM.