Association between heart rate and mortality in patients with septic shock: an analysis revealed by time series data.

BACKGROUND: Heart rate is crucial for patients with septic shock, but there are few studies on the scope of heart rate. Therefore, we studied the relationship between different heart rates and mortality of critically ill patients with septic shock, and explored the optimal heart rate range, in order to provide new insights for clinical treatment of septic shock. METHODS: This retrospective study utilized time-series heart rate data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients with septic shock were identified as the Sepsis 3.0 criteria and received vasopressor therapy in the first 24 h since ICU admission. We calculated the time-weighted average heart rate (TWA-HR) based on the time-series data. The restricted cubic spline (RCS) analysis was employed to investigate the nonlinear relationship between heart rate and 28-day mortality, aiming to explore the optimal heart rate control target for septic patients and using this target as the exposure factor. The primary outcome was 28-day mortality, and the secondary outcome were ICU and in-hospital mortality. For the original cohort, we applied the log-rank test to infer the relationship between heart rate and mortality. To control for bias introduced by confounders, we utilized propensity score matching (PSM) to reduce imbalances between normal TWA-HR and high TWA-HR groups, and we established a series of models [the multivariable Cox model, matching weight (MW)-adjusted Cox model, multivariable logistic regression, MW-adjusted logistic regression, and doubly robust model] as sensitivity analyses and subgroup analyses to demonstrate the robustness of our findings. RESULTS: A total of 13492 patients were included in our study. The RCS analysis based on Cox and logistic regression showed increased risk of mortality (P < 0.001, non-linear P < 0.001) when TWA-HR > 85 beats per minute (bpm). The log-rank test revealed in terms of the 28-day mortality, the hazard ratio (HR) (95% confidence interval [CI]) was 1.92 (1.78-2.06, P < 0.001) for patients with high TWA-HR compared to normal TWA-HR group. Similarly, for the ICU mortality, the HR (95% CI) was 1.64 (1.52-1.78, P < 0.001), and for the in-hospital mortality, the HR (95% CI) was 1.61 (1.48-1.76, P < 0.001). Collectively, the sensitivity analysis consistently demonstrated higher 28-day mortality, ICU mortality, and in-hospital mortality in patients with TWA-HR > 85 bpm. CONCLUSION: Patients with septic shock whose heart rate was controlled no more than 85 bpm during ICU stay received survival benefit in terms of 28-day, ICU and in-hospital mortality. .

The triglyceride-glucose index dynamic trajectory reveals the association between the clinical subphenotype of insulin resistance and mortality in patients with sepsis.

BACKGROUND: The relationship between the dynamic changes in insulin resistance (IR) and the prognosis of septic patients remains unclear. This study aims to investigate the correlation between the clinical subphenotype of IR represented by the triglyceride-glucose (TyG) index trajectory and the mortality rate among patients with sepsis. METHODS: In this retrospective cohort study, we utilized data from septic patients within the Medical Information Mart for Intensive Care (MIMIC)-IV database version 2.0 to construct trajectories of the TyG index over 72 h. Subsequently, we computed the similarity among various TyG index trajectories with the dynamic time warping (DTW) algorithm and utilized the hierarchical clustering (HC) algorithm to demarcate distinct cluster and identified subphenotypes according to the trajectory trend. Subsequently, we assessed the mortality risk between different subphenotypes using analyses such as survival analysis and validated the robustness of the results through propensity score matching (PSM) and various models. RESULTS: A total of 2350 patients were included in the study. Two trajectory trends: TyG index decreasing (n = 926) and TyG index increasing (n = 1424) were identified, which indicated corresponding to the clinical subphenotype of increased and alleviative IR respectively. The 28-day and in-hospital mortality for the increased IR group was 28.51% and 25.49% respectively. In comparison, patients in the alleviative IR group with a 28-day mortality of 23.54% and an in-hospital mortality of 21.60%. These subphenotypes exhibited distinct prognosis, time dependent Cox model showed the increased IR group with a higher 28-day mortality [hazard ratio (HR): 1.07, 95% confidence interval (CI): 1.02-1.12, P = 0.01] and in-hospital mortality [HR: 1.05, 95% CI: 1.00-1.11, P = 0.045] compared to the alleviative IR group. Sensitivity analyses with various models further validated the robustness of our findings. CONCLUSION: Dynamic increase in the TyG index trajectory is associated with elevated mortality risk among patients with sepsis, which suggests that dynamic increased IR exacerbates the risk of poor outcomes in patients.

Deciphering the Underlying Mechanism of the Fourth Entity in Medium-Entropy NiCoFeMP toward Boosting Oxygen Evolution Electrocatalysis.

High-/medium-entropy materials have been explored as promising electrocatalysts for water splitting due to their unique physical and chemical properties. Unfortunately, state-of-the-art materials face the dilemma of explaining the enhancement mechanism, which is now limited to theoretical models or an unclear cocktail effect. Herein, a medium-entropy NiCoFeMnP with an advanced hierarchical particle-nanosheet-tumbleweed nanostructure has been synthesized via simple precursor preparation and subsequent phosphorization. Evaluated as the electrocatalyst for oxygen evolution reaction (OER), the medium-entropy NiCoFeMnP displays a lower overpotential of 272 mV at a current density of 10 mA cm-2, and more favorable kinetics than the binary NiFeP, ternary NiCoFeP, quaternary NiCoFeCuP and NiCoFeCrP counterparts, and other reported high-/medium-entropy electrocatalysts. Careful experimental analyses reveal that the incorporation of Mn can significantly regulate the electronic structure of Ni, Co, and Fe sites. More importantly, the Mn introduction and entropy stabilization effect in the reconstructed metal (oxy)hydroxide simultaneously promote the lattice oxygen mechanism, improving the activity. This work sheds new light on the design of high-/medium-entropy materials from an in-depth understanding of the underlying mechanism for improving energy conversion efficiency.

Development and validation of a nomogram-based model to predict combined esophageal injury post-esophagoscopy for esophageal foreign bodies.

OBJECTIVE: The aim of this study is to create and validate a nomogram model for predicting complications of esophageal injury post-esophagoscopy in patients with esophageal foreign bodies (EFB). METHODS: We examined 303 patients who underwent esophagoscopy from January 2019 to December 2022 at a leading hospital in Anhui, known for its expertise in otorhinolaryngology-head and neck surgery. The patients were split into a modeling group and a validation group in a 7:3 ratio. Logistic regression analysis was employed to determine the risk factors for esophageal injury after undergoing esophagoscopy in patients with EFB. Based on these factors, a nomogram risk prediction model was developed and assessed using a goodness of fit test. RESULTS: Logistic regression analysis revealed that the type of foreign body, failure of gastroscopic retrieval, duration of lodgment, lodgment site, and presence of combined cardiovascular and cerebrovascular diseases were significant (p < 0.05) independent risk factors for esophageal injury following esophagoscopy for EFB. The area under the ROC curve for the training set was 0.850, and the Hosmer-Lemeshow goodness of fit test resulted in a p value of 0.908. For the validation set, the area under the ROC curve was 0.848, and the Hosmer-Lemeshow test gave a p value of 0.665. The calibration curve showed a close alignment between the predicted and observed values. CONCLUSION: The type of foreign body, duration of lodgment, lodgment site, previous failure of gastroscopic retrieval, and history of combined cardiovascular and cerebrovascular diseases are significant risk factors for esophageal injury following EFB esophagoscopy. This model accurately quantifies the risk of esophageal injury after EFB esophagoscopy.

HIF-1α stabilization inhibits Japanese encephalitis virus propagation and neurotoxicity via autophagy pathways.

Japanese encephalitis (JE) is a widespread flavivirus that induces brain inflammation and affects the central nervous system (CNS). Deferoxamine, an iron chelator, has shown promising results in stabilizing HIF-1α, a protein that improves hypoxic conditions, offers protective effects against neurological, and neurodegenerative diseases. This study aimed to assess the impact of HIF-1α stabilization during JEV infection using SH-SY5Y neuroblastoma cell lines as a model. Our findings demonstrated that deferoxamine treatment increased HIF-1α protein levels, leading to a reduction in JEV propagation. Moreover, RT-PCR analysis revealed that deferoxamine ameliorated JEV-induced neuroinflammation and neurotoxicity. We proved that inducing HIF-1α is essential for having an impact of deferoxamine against JEV-mediated neurotoxicity. Thus, our findings offer a potential therapeutic approach to mitigate the detrimental effects of JEV infection on neuronal cells. Further investigations also demonstrated that deferoxamine could reverse JEV-induced autophagy inhibition by stabilizing HIF-1α, which plays a crucial role in mitigating neuronal cell damage and neuroinflammation. Based on our data, HIF-1α stabilization emerges as a vital factor against JEV infection in the neurons, highlighting deferoxamine as a promising and innovative target for developing anti-JEV agents.

Batch effects correction in scRNA-seq based on biological-noise decoupling autoencoder and central-cross loss.

Technical or biologically irrelevant differences caused by different experiments, times, or sequencing platforms can generate batch effects that mask the true biological information. Therefore, batch effects are typically removed when analyzing single-cell RNA sequencing (scRNA-seq) datasets for downstream tasks. Existing batch correction methods usually mitigate batch effects by reducing the data from different batches to a lower dimensional space before clustering, potentially leading to the loss of rare cell types. To address this problem, we introduce a novel single-cell data batch effect correction model using Biological-noise Decoupling Autoencoder (BDA) and Central-cross Loss termed BDACL. The model initially reconstructs raw data using an auto-encoder and conducts preliminary clustering. We then construct a similarity matrix and a hierarchical clustering tree to delineate relationships within and between different batches. Finally, we introduce a Central-cross Loss (CL). This loss leverages cross-entropy loss to prompt the model to better distinguish between different cluster labels. Additionally, it employs the Central Loss to encourage samples to form more compact clusters in the embedding space, thereby enhancing the consistency and interpretability of clustering results to mitigate differences between different batches. The primary innovation of this model lies in reconstructing data with an auto-encoder and gradually merging smaller clusters into larger ones using a hierarchical clustering tree. By using reallocated cluster labels as training labels and employing the Central-cross Loss, the model effectively eliminates batch effects in an unsupervised manner. Compared to current methods, BDACL can mitigate batch effects without losing rare cell types.

The effects of pulsed electromagnetic field therapy on muscle strength and pain in patients with end-stage knee osteoarthritis: a randomized controlled trial.

Background: Osteoarthritis (OA) of the knee is one of the most common chronic degenerative joint conditions affecting aging population. Aim: To investigate the effectiveness of a combination of home-based exercise and pulsed electromagnetic field (PEMF) therapy to improve muscle strength, physical function, and pain. Methods: Sixty patients were randomly assigned to either home-based exercise alone (control group; n = 30) or combined with PEMF therapy (treatment group; n = 30) twice a week for eight weeks. Knee extension, flexion muscle strength, gait speed (GS), 5 time sit-to-stand test (5STS), Visual Analogue Scale (VAS) pain and Knee Injury and Osteoarthritis Outcome Score (KOOS) were recorded at baseline and 4 and 8 weeks. Results: Significant improvements in symptomatic knee extension muscle strength (SKE, p = 0.001), flexion strength (SKF, p = 0.011), contralateral knee extension muscle strength (CKE, p = 0.002), and flexion strength (CKF, p = 0.009) were observed for the PEMF treatment group at 8 weeks. Significant reductions in VAS pain scores were observed in both the treatment (p < 0.001, partial η2 = 0.505) and control (p < 0.001, partial η2 = 0.268) groups. Significant differences were reported between groups in the 4 (p = 0.010, partial η2 = 0.111) and 8 (p = 0.046, partial η2 = 0.068) week assessment in VAS pain. A significant time difference was found in GS and 5STS between baseline and week 8 (GS: difference 0.051, p = 0.026; 5STS: difference 2.327, p < 0.001) in the treatment group. The significant group difference at week 8 was observed in SKE (p = 0.013) in female patients while pain in male patients (p = 0.026). Patients aged over 70 years have a significantly superior improvement in SKE, SKF, and CKF after 8 weeks of PEMF therapy. Conclusion: The combination of PEMF therapy and home-based exercise superiorly improved knee muscle strength and reduced pain in end-stage knee OA subjects and showed a promising tendency to improve performance-based physical function. PEMF therapy was shown to preferentially benefit knee muscle strength in female patients and patients aged over 70 years, whereas male patients were more responsive to PEMF therapy in the form of pain relief. Clinical trial registration: clinicalTrials.gov, NCT05550428.

Preimplantation genetic testing for Cockayne syndrome with a novel ERCC6 variant in a Chinese family.

Background: Cockayne syndrome (CS) is a rare, multisystem, autosomal recessive disorder characterized by cachectic dwarfism, nervous system abnormalities, and premature aging. Mutations in the ERCC6 and ERCC8 genes are the predominant causes of Cockayne syndrome, with ERCC6 gene mutations present in approximately 75% of cases. Methods: Trio-based whole-exome sequencing (trio-WES) was employed to identify potential pathogenic variants associated with CS. Preimplantation genetic testing for monogenic disorders (PGT-M) was conducted to prevent the transmission of the pathogenic variant. Results: Two compound heterozygous mutations were identified in ERCC6-c.1297G>T (p. Glu433*) and c.1607T>G (p. Leu536Trp)-with c.1297G>T representing a novel mutation. Four blastocysts resulting from intracytoplasmic sperm injection were subjected to biopsy. Genetic analyses revealed that E1 harbored maternal mutations in diploid embryos, E2 and E3 carried both paternal and maternal mutations in non-diploid embryos, and E4 did not carry paternal or maternal mutations in diploid embryos. Following the transfer of the E4 embryos, a single successful pregnancy was achieved. Conclusion: The successful application of PGT-M in this family offers a potential approach for addressing other monogenic diseases. The findings of this study broaden the variant spectrum of ERCC6 and will contribute to the molecular diagnosis and genetic counseling of CS. This case highlights the feasibility and effectiveness of PGT-M in preventing CS and provides valuable insights for similarly affected families.

[Effect of acupuncture on AMPK/ULK1 signaling pathway of hippocampus in chronic stress-induced depression rats]. / é’ˆåˆºå¯¹æ ¢æ€§åº”æ¿€æŠ‘éƒå¤§é¼ æµ·é©¬AMPK/ULK1信号通路和自噬的影响.

OBJECTIVES: To observe the effect of manual acupuncture stimulation on changes of behavior and hippocampal signaling pathways of AMP-activated kinase (AMPK)/UNC-51-like kinase 1 (ULK1) in rats with chronic unpredictable mild stress (CUMS)-induced depression, so as to explore its molecular mechanism underlying improvement of depression. METHODS: Thirty-two male SD rats were randomly divided into normal control, model, acupuncture and medication (fluoxetine) groups, with 8 rats in each group. The depression model was established by using CUMS (fasting, water depredation, restraint, swimming in cold water, crowding, stroboscope stimulation, and tail clipping, each of which was used once a week) for 6 weeks. Manual acupuncture stimulation was applied to "Baihui"(GV20) and "Yintang"(EX-HN3) for 10 min, once daily, 6 times a week for 6 weeks before every-day modeling. Rats of the medication group received gavage of fluoxetine (10 mg/kg) once a day for 6 weeks before every-day modeling. The percentage of sucrose preference, and the percentages of open arm times and open arm time in the elevated plus maze experiments were detected. The expression levels of AMPK, phosphorylated (p)-AMPK, ULK1, p-ULK1, mammalian target of rapamycin (mTOR) and p-mTOR proteins in the hippocampus tissue were detected by Western blot, and the expression of autophagy effecting protein (Beclin-1) and the selective autophagy receptors (p62) mRNA in the hippocampal tissue was detected using real-time fluorescence quantitative PCR, respectively. RESULTS: Compared with the normal group, the percentage of sucrose preference, percentage of times of entering the open arm and percentage of open arm time, the expression levels of p-AMPK /AMPK ratio, p-ULK1 /ULK1 ratio of proteins, and Beclin-1 mRNA were significantly decreased (P<0.01, P<0.05), and the expression levels of p-mTOR /mTOR ratio and p62 mRNA were significantly increased (P<0.01, P<0.05) in the model group. In comparison with the model group, the percentage of sucrose preference, percentage of open arm times and open arm time, the expression levels of p-AMPK /AMPK ratio, p-ULK1/ULK1 ratio of proteins, and Beclin-1 mRNA were significantly increased in both acupuncture and medication groups (P<0.01, P<0.05), while the expression levels of p-mTOR /mTOR ratio of proteins, and p62 mRNA were markedly decreased only in the medication group (P<0.05). CONCLUSIONS: Acupuncture treatment can alleviate depression-like behavior in CUMS rats, which may be related to its functions in up-regulating AMPK/ULK1 signaling pathway to induce cellular autophagy in the hippocampus.

Qualitative insights into the effectiveness of a targeted nursing research support program: Understanding and experiences of support recipients and providers.

AIM: The aims of this study were to examine the effectiveness of a targeted nursing research support program for clinical nurses. BACKGROUND: Nursing research capacity is increasingly essential to clinical nurses and currently relatively low. Therefore, effective and systematic nursing research training programs are urgently needed to improve the scientific research abilities of nurses. METHODS: Qualitative research was conducted to investigate the effectiveness of a targeted nursing research support program. The program was formulated by considering the research training requirements of nurses and standard nursing research procedures, through literature review and group deliberations. The program was implemented for 973 nurses using a "plan-action-observation-reflection" learning cycle. The research outcomes achieved by nurses were evaluated and thematic analysis conducted to assess the perspectives of nurses and teachers regarding the research support program. RESULTS: Nurses participating in the targeted nursing research support program collectively accomplished 195 research proposals and authored 332 original research articles. Nurses shared their rich experience as "understanding my needs and achieving my potential", including: (1) systematic procedures and coherence; (2) easy to learn, easy to use; (3) a sense of belonging and mutual support; (4) self-confidence growth; and (5) high expectations. Further, the experiences of teachers were summarized as "helping others is helping myself", including: (1) teaching is learning; (2) the happiness of being needed; and (3) the importance of scientific teaching. CONCLUSION: This study evaluated the experiences of nurses and educators involved in a targeted nursing research support program and assessed its preliminary effectiveness. The findings revealed that the program, grounded in scientific and systematic research principles, was beneficial to both nurses and teachers. Based on our findings, we recommend that nursing educators should prioritize comprehensive, practice-integrated research training programs and create supportive environments, to effectively enhance the research capacity of nurses.

Anticancer effects of high-dose extracellular citrate treatment in pancreatic cancer cells under different glucose concentrations.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive solid tumor. Recently, the uptake of extracellular citrate by the sodium-dependent citrate transporter (NaCT), encoded by SLC13A5, has been demonstrated to exert profound effects on cancer cell metabolism. However, research on the function of extracellular citrate in PDAC pathogenesis and the relationship between NaCT expression and the tumor metabolic microenvironment is limited. Therefore, we aimed to evaluate the expression of citrate transporters across a spectrum of glucose concentrations in pancreatic cancer and systematically explore the effects of sodium citrate treatment on pancreatic cancer cells at different glucose concentrations. We observed a positive correlation between glucose concentration and NaCT expression in PDAC cell lines. Extracellular sodium citrate significantly reduced cell viability partially due to reduction in intracellular Ca2+ levels and decreased the migration of human PDAC cells. Furthermore, we observed a decrease in the levels of the stem cell marker prominin I (CD133) following sodium citrate treatment. Notably, the combination treatment of gemcitabine and extracellular sodium citrate exhibited a synergistic anticancer effect in both two-dimensional (2D) and three-dimensional (3D) culture systems. Additionally, we confirmed that pH slightly increased upon administration of sodium citrate, indicating that this could potentially augment the efficacy of gemcitabine. Altogether, these findings suggest that exogenous sodium citrate treatment, particularly in combination with gemcitabine, may represent a novel therapeutic strategy for treating PDAC. This approach holds promise for disrupting PDAC cell metabolism and inhibiting tumor progression.

RG108 attenuates acute kidney injury by inhibiting P38 MAPK/FOS and JNK/JUN pathways.

Acute kidney injury (AKI) is an important clinical syndrome characterised by a sudden decline in renal function, often accompanied by renal inflammation and tubular epithelial cell damage. It has been reported that inhibiting DNA methylation significantly suppress the progression of AKI. In the current study, we investigate the effect of the DNA methyltransferase (DNMT) inhibitor RG108 in cisplatin- and hypoxia-reoxygenation-induced AKI. The expression of kidney injury molecules and inflammatory factors was examined by immunofluorescence, Western blotting and Real-time PCR. The results demonstrated that RG108 treatment significantly reduced kidney inflammation and injury. Furthermore, RNA-seq analysis was performed to reveal the regulatory mechanism of RG108 in AKI. The expression of the FOS and JUN genes, which are downstream of the MAPK pathway, were significant increased in AKI. Meanwhile, the expression of FOS and JUN were both inhibited by RG108, which is similar to what we found treatment with a specific JNK inhibitor and a specific p38 MAPK inhibitor, and thus attenuated renal inflammation and injury. In conclusion, we suggest that RG108 inhibits P38 MAPK/FOS and JNK/JUN pathways and attenuates renal injury and inflammatory responses. In these results, RG108 may become a novel MAPK pathway inhibitor and a clinical candidate for the treatment of AKI.

Exosomal miRNAs Differentiate Chronic Total Occlusion from Acute Myocardial Infarction.

Although coronary artery occlusion can have a negative effect on the myocardium, chronic total occlusion (CTO) exhibits different clinical features from those of acute myocardial infarction (AMI). In this study, we identify the differential associations of exosomal miRNAs with CTO and AMI. Exosomes were isolated from the plasma obtained from coronary arteries of patients undergoing percutaneous coronary intervention to treat CTO (n = 29) and AMI (n = 24), followed by small RNA sequencing, target gene predictions, and functional enrichment analyses. Promising miRNA markers were validated using real-time PCR in 35 CTO, 35 AMI, and 10 normal subjects. A total of 205 miRNAs were detected in all subjects, and 20 and 12 miRNAs were upregulated and downregulated in CTO compared to AMI patients, respectively (|fold change| > 4, FDR q < 0.05). The target genes of miRNAs that were higher in CTO patients were associated with "regulation of cell cycle phase transition", "cell growth", and "apoptosis". The target genes of miRNAs that were lower in CTO patients were enriched in terms such as "muscle cell differentiation", "response to oxygen levels", and "artery morphogenesis". On qRT-PCR analysis, the expression levels of miR-9-5p and miR-127-3p were significantly different between CTO and AMI patients. The miRNA expression levels accurately distinguished CTO from AMI patients with 79% specificity and 97% sensitivity. The miRNA contents of plasma exosomes were significantly different between CTO and AMI patients. The miRNAs may play important roles in CTO and AMI.

Label-Free Quantitative Proteomics Analysis of COVID-19 Vaccines by Nano LC-HRMS.

A nanoliter liquid chromatography-high resolution mass spectrometry-based method was developed for quantitative proteomics analysis of COVID-19 vaccines. It can be used for simultaneous qualitative and quantitative analysis of target proteins and host cell proteins (HCPs) in vaccine samples. This approach can directly provide protein information at the molecular level. Based on this, the proteomes of 15 batches of COVID-19 inactivated vaccine samples from two companies and 12 batches of COVID-19 recombinant protein vaccine samples from one company were successfully analyzed, which provided a significant amount of valuable information. Samples produced in different batches or by different companies can be systematically contrasted in this way, offering powerful supplements for existing quality standards. This strategy paves the way for profiling proteomics in complex samples and provides a novel perspective on the quality evaluation of bio-macromolecular drugs.

Incidence and risk factor analysis of neovascular glaucoma following vitrectomy in patients with proliferative diabetic retinopathy.

To investigate the incidence and risk factors for neovascular glaucoma (NVG) after vitrectomy in patients with proliferative diabetic retinopathy (PDR). Patients were categorized into two subgroups based on their treatment regimen: one group received vitrectomy only (Group 1), while the other received combined phacovitrectomy (Group 2). A comparative analysis was conducted to evaluate the distinguishing characteristics of the two groups. Kaplan-Meier survival analysis was used to determine the incidence of NVG following surgery. Furthermore, multivariate analysis using the Cox proportional hazards model was conducted to identify the risk factors associated with the development of NVG after surgery. A total of 484 eyes of 484 patients were included in the study. When comparing Group 1 with Group 2, a significant difference was observed in the occurrence of NVG. In Group 1, there were 10 cases of NVG (3.9%), whereas 29 cases of NVG occurred in Group 2 (12.71%). Male sex, high preoperative intraocular pressure (IOP), and combined phacovitrectomy were found to be associated with the occurrence of NVG following phacovitrectomy. Higher creatinine levels had a protective effect in preventing the development of NVG. Male sex, high preoperative IOP, and combined phacovitrectomy were associated with a high incidence of NVG. Explore strategies to prevent NVG is important when performing combined phacovitrectomy in patients with PDR.

Phototriggered Self-Catalyzed Phosphorylation of 3,4-Dihydroquinoxalin-2(1H)-ones with Diarylphosphine Oxides in EtOH.

A highly effective external photocatalyst- and additive-free method for the phosphorylation of 3,4-dihydroquinoxalin-2(1H)-ones to produce phosphorylated dihydroquinoxalin-2(1H)-ones has been reported. A wide variety of phosphorylated products were formed in good to excellent yields. Preliminary mechanistic studies reveal that the phosphorylation process involves an EnT process, a SET process, a HAT process, and a deprotonation process.

Association between salt sensitivity of blood pressure and dietary habits in survey population: A case-control study.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular diseases (CVDs) and links dietary salt with blood pressure. However, the study on the relationship between SSBP and dietary habits is rare. This study investigated the relationship between diet and SSBP in different blood pressure statues. METHODS: 1459 subjects were assigned into four groups based on a case (hypertension)-control (normotension) study of SSBP and hypertension: 561 Salt-sensitive hypertension (SSH) and 235 non-salt-sensitive hypertension (NSSH) and 424 salt-sensitive normotension (SSN) and 239 non-salt-sensitive normotension (NSSN). Foods information of weekly or daily intakes were recalled. SSBP was tested with the modified salt stress test and was diagnosed with the Sullivan criteria. RESULTS: Compared with the NSSH and SSN groups, SSH group have lower intake of fresh fruits (both P < 0.05). Furthermore, NSSN group have the lowest intake of red meat, and bacon (P < 0.05). SSH group have the lowest intake of fresh vegetables (P < 0.05). SSN group have the highest intake of eggs, dairy products, white meat (all P < 0.05). In hypertensive patients, staple food (OR = 0.37, 95%CI: 0.10-0.64) was associated with decreased risk of salt sensitivity. In normotensive subjects, white meat (OR = 0.28, 95%CI: 0.14-0.43) was associated with reduced risk of salt sensitivity, bacon (OR = 5.39, 95%CI: 2.11-8.67) and dairy products (OR = 4.22, 95%CI: 1.82-6.56) and red meat (OR = 2.95, 95%CI: 1.15-4.84) were associated with elevated risk of salt sensitivity. CONCLUSIONS: Dietary habits play an important role in SSBP and the role varies with blood pressure especially among population.

Association of procalcitonin with voriconazole concentrations: a retrospective cohort study.

Inflammation is a potential risk factor of voriconazole (VCZ) overdose, procalcitonin (PCT) is reported to act as a diagnostic marker for bacterial infections. However, the association of PCT with VCZ trough serum concentrations (VCZ-Cmin) is not fully clear. Our study aims to investigate the associations between PCT and VCZ-Cmin. In this retrospective cohort study, we collected the clinical data of 147 patients who received VCZ and monitored the VCZ concentration of them in our hospital from August 2017 to August 2021. All patients underwent routine clinical examinations on the day or the day before VCZ administration. General information and clinical symptoms of these patients were recorded. Multivariate liner analysis showed that PCT was significantly associated with VCZ-Cmin (p < 0.001). Overall, it was shown that VCZ-Cmin was significantly increased by 0.32 µg/mL for each fold increment in PCT in crude model. In the minor adjusted model (Model 1, adjustment for sex, age, albumin, direct bi1irubin, WBC) and fully adjusted model (Model 2, adjustment for sex, age, albumin, direct bilirubin, WBC, AST and ALT), VCZ-Cmin was significantly increased by 0.23 µg/mL and 0.21 µg/mL, respectively, for each fold increment in PCT. In conclusion, this research reveals the correlation between PCT and VCZ-Cmin, indicating that PCT has the potential to serve as a valuable biomarker for drug monitoring in the treatment of VCZ.

TMEM100 acts as a TAK1 receptor that prevents pathological cardiac hypertrophy progression.

Pathological cardiac hypertrophy is the primary cause of heart failure, yet its underlying mechanisms remain incompletely understood. Transmembrane protein 100 (TMEM100) plays a role in various disorders, such as nervous system disease, pain and tumorigenesis, but its function in pathological cardiac hypertrophy is still unknown. In this study, we observed that TMEM100 is upregulated in cardiac hypertrophy. Functional investigations have shown that adeno-associated virus 9 (AAV9) mediated-TMEM100 overexpression mice attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis, and impaired heart structure and function. We subsequently demonstrated that adenoviral TMEM100 (AdTMEM100) mitigates phenylephrine (PE)-induced cardiomyocyte hypertrophy and downregulates the expression of cardiac hypertrophic markers in vitro, whereas TMEM100 knockdown exacerbates cardiomyocyte hypertrophy. The RNA sequences of the AdTMEM100 group and control group revealed that TMEM100 was involved in oxidative stress and the MAPK signaling pathway after PE stimulation. Mechanistically, we revealed that the transmembrane domain of TMEM100 (amino acids 53-75 and 85-107) directly interacts with the C-terminal region of TAK1 (amino acids 1-300) and inhibits the phosphorylation of TAK1 and its downstream molecules JNK and p38. TAK1-binding-defective TMEM100 failed to inhibit the activation of the TAK1-JNK/p38 pathway. Finally, the application of a TAK1 inhibitor (iTAK1) revealed that TAK1 is necessary for TMEM100-mediated cardiac hypertrophy. In summary, TMEM100 protects against pathological cardiac hypertrophy through the TAK1-JNK/p38 pathway and may serve as a promising target for the treatment of cardiac hypertrophy.

Comparative Study of Cu Ion Adsorption by Nano-Hydroxyapatite Powder Synthesized from Chemical Reagents and Clam Shell-Derived Calcium Sources.

The increasing contamination of water sources by heavy metals necessitates the development of efficient and sustainable adsorption materials. This study evaluates the potential of nano-hydroxyapatite (HA) powders synthesized from chemical reagents (Chem-HA) and clam shells (Bio-HA) as adsorbents for Cu ions in aqueous solutions. Both powders were synthesized using microwave irradiation at 700 W for 5 min, resulting in nano-sized rod-like particles confirmed as HA by X-ray diffraction (XRD). Bio-HA exhibited higher crystallinity (67.5%) compared to Chem-HA (34.9%), which contributed to Bio-HA's superior adsorption performance. The maximum adsorption capacities were 436.8 mg/g for Bio-HA and 426.7 mg/g for Chem-HA, as determined by the Langmuir isotherm model. Kinetic studies showed that the Cu ion adsorption followed the pseudo-second-order model, with Bio-HA achieving equilibrium faster and displaying a higher rate constant (6.39 × 10⁻4 g/mg·min) than Chem-HA (5.16 × 10⁻4 g/mg·min). Thermodynamic analysis indicated that the adsorption process was spontaneous and endothermic, with Bio-HA requiring less energy (ΔH° = 39.00 kJ/mol) compared to Chem-HA (ΔH° = 43.77 kJ/mol). Additionally, the activation energy for Bio-HA was lower (41.62 kJ/mol) than that for Chem-HA (46.39 kJ/mol), suggesting better energy efficiency. The formation of a new Cu2(OH)PO4 phase after adsorption, as evidenced by XRD, confirmed that the Cu ions replaced the Ca ions in the HA lattice. These findings demonstrate that Bio-HA, derived from natural sources, offers environmental benefits as a recyclable material, enhancing heavy metal removal efficiency while contributing to sustainability by utilizing waste materials and reducing an environmental impact.