The impact of age and number of mutations on the size of clonal hematopoiesis.

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.

Robotic Versus Laparoscopic Pancreaticoduodenectomy for Pancreatic Cancer: Evaluation and Analysis of Surgical Efficacy.

BACKGROUND: Evidence is limited for the treatment of pancreatic cancer among minimally invasive pancreatoduodenectomy. METHODS: This retrospective analysis evaluated patients who underwent robotic pancreaticoduodenectomy (RPD) or laparoscopic pancreaticoduodenectomy (LPD) from April 2016 to April 2023. Their baseline and perioperative data, including operative time, R0 resection rates, and severe complications rates, were analyzed, and the follow-up data, such as disease-free survival (DFS) and overall survival (OS), were collected. RESULTS: A total of 253 cases of LPD and RPD were performed, and 101 cases with pancreatic cancer were included, of which 54 were LPD and 47 were RPD. The conversion rate (4.3% vs. 29.6%, p = 0.001) and blood loss (400 vs. 575 mL, p < 0.05) were lower in the RPD group. No significant difference was observed between the two groups in terms of operative time, vessel resection rates, and TNM-stage diagnosis; however, R0 resection rates (80.9% vs. 70.4%) and lymph node harvest (24.2 vs. 21.9) had a higher tendency in the RPD group, and postoperative length of stay was shorter in the RPD cohort (11 vs. 13 days). Moreover, improved 1- to 3-years DFS (75.7%, 61.7%, and 36.0% vs. 59.0%, 35.6%, and 21.9%) and OS (94.7%, 84.7%, and 50.8% vs. 84.1%, 63.6%, and 45.5%) was found in the RPD group in comparison with the LPD group. CONCLUSIONS: RPD had advantages in surgical safety and oncological outcomes compared with LPD, but was similar to the latter in perioperative outcomes. Long-term outcomes require further study.

Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21.

BACKGROUND: Single nuclear polymorphisms (SNPs) have been published to be correlated with multiple diseases. Transcription Factor 21 (TCF21) is a critical transcription factor involved in various types of cancers. However, the association of TCF21 genetic polymorphisms with gastric cancer (GC) susceptibility and prognosis remains unclear. METHODS: A case-control study comprising 890 patients diagnosed with GC and an equal number of cancer-free controls was conducted. After rigorous statistical analysis, molecular experiments were carried out to elucidate the functional significance of the SNPs in the context of GC. RESULTS: TCF21 rs2327430 (OR = 0.78, P = 0.026) provides protection against GC, while rs4896011 (OR = 1.39, P = 0.005) exhibit significant associations with GC risk. Furthermore, patients with the (TC + CC) genotype of rs2327430 demonstrate a relatively favorable prognosis (OR = 0.47, P = 0.012). Mechanistically, chromatin immunoprecipitation assay and luciferase reporter assay revealed that the C allele of rs2327430 disrupts the binding of Transcription Factor AP-2 Alpha (TFAP2A) to the promoter region of TCF21, resulting in increased expression of TCF21 and inhibition of malignant behaviors in GC cells. CONCLUSION: Our findings highlight the significant role of TCF21 SNPs in both the risk and prognosis of GC and provide valuable insights into the underlying molecular mechanisms. Specifically, the disruptive effect of rs2327430 on TCF21 expression and its ability to modulate malignant cell behaviors suggest that rs2327430 may serve as a potential predictive marker for GC risk and prognosis.

Structure-function interrelationships and associated neurotransmitter profiles in drug-naïve benign childhood epilepsy with central-temporal spikes patients.

OBJECTIVES: To explore the interrelationships between structural and functional changes as well as the potential neurotransmitter profile alterations in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients. METHODS: Structural magnetic resonance imaging (sMRI) and resting-state functional MRI data from 20 drug-naïve BECTS patients and 33 healthy controls (HCs) were acquired. Parallel independent component analysis (P-ICA) was used to identify covarying components among gray matter volume (GMV) maps and fractional amplitude of low-frequency fluctuations (fALFF) maps. Furthermore, we explored the spatial correlations between GMV/fALFF changes derived from P-ICA and neurotransmitter maps in JuSpace toolbox. RESULTS: A significantly positive correlation (p < 0.001) was identified between one structural component (GMV_IC6) and one functional component (fALFF_IC4), which showed significant group differences between drug-naïve BECTS patients and HCs (GMV_IC6: p < 0.01; fALFF_IC4: p < 0.001). GMV_IC6 showed increased GMV in the frontal lobe, temporal lobe, thalamus, and precentral gyrus as well as fALFF_IC4 had enhanced fALFF in the cerebellum in drug-naïve BECTS patients compared to HCs. Moreover, significant correlations between GMV alterations in GMV_IC6 and the serotonin (5HT1a: p < 0.001; 5HT2a: p < 0.001), norepinephrine (NAT: p < 0.001) and glutamate systems (mGluR5: p < 0.001) as well as between fALFF alterations in fALFF_IC4 and the norepinephrine system (NAT: p < 0.001) were detected. CONCLUSION: The current findings suggest co-altered structural/functional components that reflect the correlation of language and motor networks as well as associated with the serotonergic, noradrenergic, and glutamatergic neurotransmitter systems. CLINICAL RELEVANCE STATEMENT: The relationship between anatomical brain structure and intrinsic neural activity was evaluated using a multimodal fusion analysis and neurotransmitters which might provide an important window into the multimodal neural and underlying molecular mechanisms of benign childhood epilepsy with central-temporal spikes. KEY POINTS: Structure-function relationships in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients were explored. The interrelated structure-function components were found and correlated with the serotonin, norepinephrine, and glutamate systems. Co-altered structural/functional components reflect the correlation of language and motor networks and correlate with the specific neurotransmitter systems.

Endovascular recanalization for pediatric hypertension secondary to total renal artery occlusion.

PURPOSE: To assess the feasibility and efficacy of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH) secondary to total renal artery occlusion (RAO). METHODS: From 2011 to 2021, 13 pediatric patients with RVH confirmed with 14 occluded renal artery lesions were reviewed. The mean age was11.2 years (range 4 to 16). Nine lesions involved main artery occlusion, while five lesions featured branch occlusion. Blood Pressure Ratio (BPR) was defined as the ratio of the actual BP value to the 95th percentile value adjusted for age, gender, and height. RESULTS: PTRA was performed on nine patients (9/13, 69%). Technical success was achieved in five patients (5/9, 56%), with stent placement in two children (2/9, 22%). During the 12-month follow-up, restenosis was identified in two stent-receiving patients at the 12-month follow-up visit (2/9, 22%). Mean systolic BPR decreased from 1.20 ± 0.07 to 0.96 ± 0.06 (p = 0.003), mean diastolic BPR decreased from 1.19 ± 0.07 to 0.95±0.08 (p = 0.005) and the number of required medications decreased from 3.8 ± 0.8 to 2.4 ± 0.9 (p = 0.052) following PTRA. Subsequent to PTRA, the mean GFR of the occluded kidney improved from 19.5 ± 12.3 mL/ min to 36.3 ± 10.8 mL/ min (p = 0.007) and the mean longitudinal dimension of the affected kidneys significantly increased from 8.2 ± 1.5 cm to 9.2 ± 1.7 cm (p = 0.006). CONCLUSIONS: Endovascular treatment is feasible for pediatric RAO, results in acceptable BP control and preserves renal function.

Synthesis and anti-proliferative effect of novel 4-Aryl-1, 3-Thiazole-TPP conjugates via mitochondrial uncoupling process.

With the advent of mitochondrial targeting moiety such as triphenlyphosphonium cation (TPP+), targeting mitochondria in cancer cells has become a promising strategy for combating tumors. Herein, a series of novel 4-aryl-1,3-thiazole derivatives linked to TPP+ moiety were designed and synthesized. The cytotoxicity against a panel of four cancer cell lines was evaluated by CCK-8 assay. Most of these compounds exhibited moderate to good inhibitory activity over HeLa, PC-3 and HCT-15 cells while MCF-7 cells were less sensitive to most compounds. Among them, compound 12a exhibited a significant anti-proliferative activity against HeLa cells, and prompted for further investigation. Specifically, 12a decreased mitochondrial membrane potential and enhanced levels of reactive oxygen species (ROS). The flow cytometry analysis revealed that compound 12a could induce apoptosis and cell cycle arrest at G0/G1 phase in HeLa cells. In addition, mitochondrial bioenergetics assay revealed that 12a displayed mild mitochondrial uncoupling effect. Taken together, these findings suggest the therapeutic potential of compound 12a as an antitumor agent targeting mitochondria.

A prospective study comparing the gasless endoscopic thyroidectomy trans-axillary approach to conventional open thyroidectomy: health and quality of life outcomes.

BACKGROUND: The relationship between different surgical treatments and quality of life remains uncertain for differentiated thyroid carcinoma (DTC). The aim of this study is to compare the gasless endoscopic thyroidectomy trans-axillary approach (ET) and traditional open thyroidectomy (OT) through a prospective cohort study focusing on the rate of the efficacy, and quality of life (QoL). METHODS: This prospective observational longitudinal cohort study enrolled 134 female patients diagnosed with DTC from December 01/2021 to December 31/2022. Multiple scales were applicated to evaluate the differences in quality of life, effectiveness, safety, etc. between the two groups during preoperative and postoperative follow-up periods, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, version 3.0 (QOL-C30), Symptom Checklist (SCL-90), Scar Cosmesis Assessment and Rating (SCAR-Q), voice impairment score (VIS), swallowing impairment score (SIS), and neck impairment score (NIS). RESULTS: Among them, 68 accepted ET and 66 patients underwent OT. To enhance comparability between the two groups, the patients enrolled in this study are female. Compared with the OT group, the ET group performed significantly better postoperative physical quality of life, including sound (p = 0.036), swallowing (p < 0.001), and neck function (p = 0.010). The ET group was also associated with significantly better cosmetic satisfaction (p < 0.001), and relatively faster recovery in psychological and emotional situation. CONCLUSIONS: Gasless endoscopic thyroidectomy through an axillary approach leads to good cosmetic and psychological effects, improves postoperative QoL, and could be recommended for rapid postoperative recovery and involvement in daily and social activities.

Comparisons of laparoscopic and robotic pancreaticoduodenectomy using barbed and conventional sutures for pancreaticojejunostomy: a propensity score matching study.

BACKGROUND: There are limited data on the effect of different sutures and surgical approaches on the quality of pancreaticojejunostomy in minimally invasive pancreaticoduodenectomy (MIPD). This study compares the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) between the use of barbed sutures (BSs) and conventional sutures (CSs). METHODS: A retrospective cohort study was conducted on 253 consecutive patients who had undergone MIPD from July 2016 to April 2023. Patients were excluded if conversion to open surgery or open anastomosis was necessary. 220 patients were enrolled and divided into BS (n = 148) and CS (n = 72) groups. After 1:1 propensity score matching (PSM), 67 cases remained in each group. Univariate and multivariate analyses identified factors associated with CR-POPF. Comparisons were also made between laparoscopic (LPD) and robotic (RPD) pancreaticoduodenectomy. RESULTS: After PSM, BSs were associated with significantly lower rates of CR-POPF (7.5 vs. 22.4%, P = 0.015) and severe complications (Clavien-Dindo ≥ III) (7.5vs. 19.4%, P = 0.043). No significant differences were found in operative time, length of postoperative hospital stay, or other major morbidities. Multivariate analyses revealed BMI ≥ 22 kg/m2 (OR = 5.048, 95% CI: 1.256-20.287, P = 0.023) and the use of BSs (OR = 0.196, 95% CI: 0.059-0.653, P = 0.008) as the independent predictors of CR-POPF. There were no significant differences in postoperative outcomes between the LPD and RPD groups, but RPD was associated with significantly shorter operative time (402.8 min vs. 429.4 min, P = 0.015). CONCLUSIONS: In conclusion, using BSs for PJ during MIPD is feasible and has the potential to reduce CR-POPF and severe complications.

In vivo detection of the epimer metabolites of sweroside via ultra-performance liquid chromatography time-of-flight mass spectrometry combined with DNPH derivatization.

The metabolites of sweroside were first investigated in vivo with ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) in combination with 2,4-dinitrophenylhydrazine derivatization. In addition, the mass detection sensitivity of the major metabolites, epinaucledal and naucledal, via UPLC-TOF-MS was significantly enhanced, and the epimer metabolites were distinctly discovered from plasma following gavage of sweroside in rats. The plasma concentration of epinaucledal and naucledal was quantified via UPLC-TOF-MS in negative mode using erythrocentaurin as the internal standard. The maximum mean plasma concentrations of naucledal and epinaucledal were 75.36 ± 20.10 and 43.52 ± 15.60 ng/ml within 2 h, respectively, following gavage of sweroside at 20 mg/kg. Moreover, the area under the concentration-time curve of naucledal was three times that of epinaucledal. The metabolic process of conversion of sweroside to epinaucledal and naucledal was deduced, and the pharmacological effects of epinaucledal and naucledal will clarify the clinical efficacy of sweroside.

Synthesis, Thermal Stability and Antifungal Evaluation of Two New Pyrrole Esters.

To develop new chemicals that are stable at high temperatures with biological activity, a pyrrole intermediate was firstly synthesized using glucosamine hydrochloride as raw materials through cyclization and oxidation. Further, two novel pyrrole ester derivatives were prepared via Steglich esterification from pyrrole intermediate with vanillin and ethyl maltol, respectively. Nuclear magnetic resonance (1 H-NMR, 13 C NMR), infrared spectroscopy (IR) and high resolution mass spectrometry (HRMS) were used to confirm the target compounds. Thermal behavior of the compounds was investigated by thermogravimetry (TG), differential scanning calorimeter (DSC) and the pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) methods. The plausible pyrolytic mechanism was proposed. Additionally, their biological activities against the pathogens Fusarium graminearum, Fusarium oxysporum, Fusarium moniliforme, Phytophthora nicotianae, and Rhizoctonia solani were assessed. These target compounds showed outstanding antifungal activities and the highest inhibitor rates of 62.50 % and 68.75 % against R. solani with EC50 values of 0.0296 and 0.0200 mg mL-1 , respectively. SDHI protein sequence was molecularly docked to identify the binding mechanisms in the active pocket and examine the interactions between both the molecules and the SDHI protein.

The Flame Retardant and Mechanical Properties of the Epoxy Modified by an Efficient DOPO-Based Flame Retardant.

Currently, the mechanical performance reduction caused by excessive phosphorus content in the halogen-free flame-retardant EP has been an obstacle to its extensive application. This study presents the effective synthesis of a novel flame-retardant BDD with great efficiency, achieving an optimum phosphorus level of merely 0.25 wt %. The structure of BDD was verified by FTIR, 1H NMR, 31P NMR and XPS spectra. To investigate the flame-retardant properties of BDD, several EPs with various phosphorus levels were synthesized. The addition of phosphorus to the EP significantly increases its LOI value from 25.8% to 33.4% at a phosphorus level of 0.25 wt%. Additionally, the resin achieves a V-0 grade in the UL 94 test. The P-HRR and THR of the modified resin measured by the cone calorimeter are also significantly reduced. At the same time, the addition of a modest quantity of BDD has a minimal impact on the mechanical properties of epoxy resin. This study shows that the removal of hydroxyl groups significantly enhances the fire resistance of phosphate-based flame retardants, thereby providing a novel approach to synthesizing efficient flame retardants.

Core network traffic prediction based on vertical federated learning and split learning.

Wireless traffic prediction is vital for intelligent cellular network operations, such as load-aware resource management and predictive control. Traditional centralized training addresses this but poses issues like excessive data transmission, disregarding delays, and user privacy. Traditional federated learning methods can meet the requirement of jointly training models while protecting the privacy of all parties' data. However, challenges arise when the local data features among participating parties exhibit inconsistency, making the training process difficult to sustain. Our study introduces an innovative framework for wireless traffic prediction based on split learning (SL) and vertical federated learning. Multiple edge clients collaboratively train high-quality prediction models by utilizing diverse traffic data while maintaining the confidentiality of raw data locally. Each participant individually trains dimension-specific prediction models with their respective data, and the outcomes are aggregated through collaboration. A partially global model is formed and shared among clients to address statistical heterogeneity in distributed machine learning. Extensive experiments on real-world datasets demonstrate our method's superiority over current approaches, showcasing its potential for network traffic prediction and accurate forecasting.

Efficacy of Whole-Brain Radiotherapy Plus Simultaneous Integrated Boost (SIB-WBRT) for Lung Cancer Brain Metastases.

Objective: To investigate the outcomes of SIB-WBRT in patients with brain metastases and analyze the impact of some factors on prognosis. Materials and Methods: This single-arm retrospective study analyzed patients with brain metastases who were treated with SIB-WBRT at Peking Union Medical College Hospital from September 2015 to December 2021. The primary endpoint was intracranial progression free survival (iPFS). Secondary endpoints included overall survival (OS), intracranial new foci, and tumor control. The Kaplan-Meier method was then used to depict and estimate iPFS, OS, intracranial neoplasia, and tumor control. Finally, the Cox model was used to analyze the association between some relevant factors and outcomes. Results: A total of 107 patients were included and the median iPFS in these patients treated with SIB-WBRT was 13.4 (95% CI: 4.2-22.6) months, with 68.0% (95% CI: 57.4%-78.6%) and 50.8% (95% CI: 38.3%-63.3%) iPFS at 6- and 12-months. The median local control was 37.6 (95% CI: 28.3-46.8) months, with local control rates of 84.3% (95% CI: 80.6%-88.0%) and 73.3% (95% CI: 68.2%-78.4%) at 6- and 12-months. The median time to appearance of new intracranial foci was 17.4 (95% CI: 14.1-20.8) months, and the 6- and 12-month control rates were 74.5% (95% CI: 64.5%-84.5%) and 61.5% (95% CI: 49.0%-74.0%). The number of brain metastases in patients before treatment was significantly associated with iPFS (HR=0.4, 95% CI: 0.2-0.973, P=0.043). Conclusions: The iPFS, local control, and intracranial new foci of patients with brain metastases after treatment with SIB-WBRT were acceptable. In addition, the number of brain metastases in patients before treatment may be associated with iPFS.

Dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology.

Background: Alzheimer's disease (AD) is an age-related neurodegenerative disorder with no effective interventions for curing or modifying its progression. However, emerging research suggests that vitamin A in the diet may play a role in both the prevention and treatment of AD, although the exact mechanisms are not fully understood. Objectives: This study aims to investigate the dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology shedding light on its potential as a dietary intervention for AD prevention and treatment. Methods: The APP/PS1-AD mouse model was employed and divided into three dietary groups: vitamin A-deficient (VAD), normal vitamin A (VAN), and vitamin A-supplemented (VAS) for a 12-week study. Neurobehavioral functions were assessed using the Morris Water Maze Test (MWM). Enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of Diamine Oxidase (DAO), D-lactate, IL-6, IL-1ß, and TNF-a cytokines. Serum vitamin A levels were analyzed via LC-MS/MS analysis. Immunohistochemical analysis and morphometry were performed to evaluate the deposition of Aß in brain tissue. The gut microbiota of APP/PS1 mice was analyzed using 16S rRNA sequencing analysis. Additionally, transcriptomic analysis was conducted on intestinal tissue from APP/PS1 mice. Results: No significant changes in food intake and body weight were observed among the groups. However, the VAD and VAS groups showed reduced food intake compared to the VAN group at various time points. In terms of cognitive function, the VAN group performed better in the Morris Water Maze Test, indicating superior learning and memory abilities. The VAD and VAS groups exhibited impaired performance, with the VAS group performing relatively better than the VAD group. Serum vitamin A concentrations differed significantly among the groups, with the VAS group having the highest concentration. Aß levels were significantly higher in the VAD group compared to both the VAN and VAS groups. Microbial analysis revealed that the VAS and VAN groups had higher microbial diversity than the VAD group, with specific taxa characterizing each group. The VAN group was characterized by taxa such as Actinohacteriota and Desulfovibrionaceae, while the VAD group was characterized by Parabacteroides and Tannerellaceae. The VAS group showed similarities with both VAN and VAD groups, with taxa like Desulfobacterota and Desulfovibrionaceae being present. The VAD vs. VAS, VAD vs. VAN, and VAS vs. VAN comparisons identified 571, 313, and 243 differentially expressed genes, respectively, which associated with cellular and metabolic processes, and pathway analysis revealed enrichment in pathways related to chemical carcinogenesis, drug metabolism, glutathione metabolism, and immune-related processes. The VAD group exhibited higher levels of D-lactate, diamine oxidase, and inflammatory cytokines (TNF-a, IL-1ß, IL-6) compared to the VAN and VAS groups. Conclusion: Dietary vitamin A supplementation modulates the gut microbiota, intestinal permeability, inflammatory factors, and Aß protein formation, offering insights into the pathogenesis of AD and potential therapeutic avenues for further exploration. This research highlights the intricate interplay between diet, gut microbiota, and neurodegenerative processes, emphasizing the importance of dietary interventions in managing AD-related pathologies.

A bibliometric analysis of interstitial cells of Cajal research.

Objective: The significance of interstitial cells of Cajal (ICC) in the gastrointestinal tract has garnered increasing attention. In recent years, approximately 80 articles on ICC have been published annually in various journals. However, no bibliometric study has specifically focused on the literature related to ICC. Therefore, we conducted a comprehensive bibliometric analysis of ICC to reveal dynamic scientific developments, assisting researchers in exploring hotspots and emerging trends while gaining a global perspective. Methods: We conducted a literature search in the Web of Science Core Collection (WoSCC) from January 1, 2013, to December 31, 2023, to identify relevant literature on ICC. We employed bibliometric software, namely VOSviewer and CiteSpace, to analyze various aspects including annual publication output, collaborations, research hotspots, current status, and development trends in this domain. Results: A total of 891 English papers were published in 359 journals by 928 institutions from 57 countries/regions. According to the keyword analysis of the literature, researchers mainly focused on "c-Kit," "expression," "smooth muscle," and "nitric oxide" related to ICC over the past 11 years. However, with "SIP syncytium," "ANO1," "enteric neurons," "gastrointestinal stromal tumors (GIST)," and "functional dyspepsia (FD)," there has been a growing interest in the relationship between ANO1, SIP syncytium, and ICC, as well as the role of ICC in the treatment of GIST and FD. Conclusion: Bibliometric analysis has revealed the current status of ICC research. The association between ANO1, SIP syncytium, enteric neurons and ICC, as well as the role of ICC in the treatment of GIST versus FD has become the focus of current research. However, further research and collaboration on a global scale are still needed. Our analysis is particularly valuable to researchers in gastroenterology, oncology, and cell biology, providing insights that can guide future research directions.

The Effect of Rifapentine and Rifampicin on Serum Voriconazole Levels Persist for 5 Days and 7 Days or More After Discontinuation in Tuberculosis Patients with Chronic Pulmonary Aspergillosis.

Purpose: Voriconazole, a first-line therapeutic agent for chronic pulmonary aspergillosis, is metabolized by the cytochrome 450 enzymes, specifically CYP2C19 and CYP3A4. Rifampicin and rifapentine act as inducers of the cytochrome P450 enzyme. The current study explored the potential drug interactions arising from the co-administration of voriconazole with either rifampicin or rifapentine, as well as the duration of this effect on serum voriconazole levels after discontinuation of rifampicin or rifapentine. Patients and Methods: A retrospective study was conducted in tuberculosis patients with chronic pulmonary aspergillosis. These patients underwent a combination therapy involving voriconazole and rifampicin or rifapentine, or they were treated with voriconazole after discontinuation of rifampicin or rifapentine. The serum concentrations of voriconazole at steady-state were monitored. Data on demographic characteristics and the serum voriconazole levels were used for statistical analyses. Results: A total of 124 serum voriconazole concentrations from 109 patients were included in the study. The average serum concentration of voriconazole fell below the effective therapeutic range in patients treated with both voriconazole and rifampicin or rifapentine. Notably the co-administration of rifapentine led to a substantial (>70%) decrease in serum voriconazole levels in two patients. Moreover, this interfering effect persisted for at least 7 days following rifampicin discontinuation, while it endured for 5 days or more after discontinuation of rifapentine. Conclusion: Concomitant use of voriconazole and rifampicin or rifapentine should be avoided, and it is not recommended to initiate voriconazole therapy within 5 or 7 days after discontinuation of rifapentine or rifampicin. Therapeutic drug monitoring not only provides a basis for the adjustment of clinical dose, but also serves as a valuable tool for identifying drug interactions.

Analysis of risk factors for lateral lymph node metastasis in T1 stage papillary thyroid carcinoma: a retrospective cohort study.

Background: The occurrence of cervical lymph node metastasis in T1 stage papillary thyroid carcinoma (PTC) is frequently observed. Notably, lateral lymph node metastasis (LLNM) emerges as a critical risk factor adversely affecting prognostic outcomes in PTC. The primary aim of this investigation was to delineate the risk factors associated with LLNM in the initial stages of PTC. Methods: This retrospective analysis encompassed 3,332 patients diagnosed with T1 stage PTC without evident LLNM at the time of diagnosis. These individuals underwent primary surgical intervention at West China Hospital, Sichuan University between June 2017 and February 2023. The cohort was divided into two groups: patients manifesting LLNM and those without metastasis at the time of surgery. Additionally, T1 stage PTC patients were subdivided into T1a and T1b categories. Factors influencing LLNM were scrutinized through both univariate and multivariate analyses. Results: The incidence of LLNM was observed in 6.2% of the cohort (206 out of 3,332 patients). Univariate analysis revealed significant correlations between LLNM and male gender (P<0.001), tumor localization in the upper lobe (P<0.001), maximal volume of the primary tumor (P<0.001), largest tumor diameter (P<0.001), multifocality (P<0.001), and bilaterality (P<0.001), with the exception of age (P=0.788) and duration of active surveillance (AS) (P=0.978). Multivariate logistic regression analysis identified male gender (P<0.001), upper lobe tumor location (P<0.001), maximal primary tumor volume (P<0.001), and multifocality (P<0.001) as independent predictors of LLNM. However, age categories (≤55, >55 years), maximum tumor diameter, bilaterality, and surveillance duration did not exhibit a significant impact. Comparative analyses between T1a and T1b subgroups showed congruent univariate results but revealed differences in multivariate outcomes. In the T1a subgroup, gender, tumor location, and multifocality (all P<0.05) were associated with elevated LLNM risk. Conversely, in the T1b subgroup, tumor location, dimensions, and multifocality (all P<0.05) were significant predictors of LLNM risk, whereas gender (P=0.097) exerted a marginal influence. Conclusions: The investigation highlights several key risk factors for LLNM in T1 stage PTC patients, including gender, upper lobe tumor location, larger tumor size, and multifocality. Conversely, prolonged AS and younger age did not significantly elevate LLNM risk, suggesting the viability of AS as a strategic option in selected cases.

BCI Improves Alcohol-Induced Cognitive and Emotional Impairments by Restoring pERK-BDNF.

Binge drinking causes a range of problems especially damage to the nervous system, and the specific neural mechanism of brain loss and behavioral abnormalities caused by which is still unclear. Extracellular regulated protein kinases (ERK) maintain neuronal survival, growth, and regulation of synaptic plasticity by phosphorylating specific transcription factors to regulate expression of brain-derived neurotrophic factor (BDNF). Dual-specific phosphatase 1 (DUSP1) and DUSP6 dephosphorylate tyrosine and serine/threonine residues in ERK1/2 to inactivate them. To investigate the molecular mechanism by which alcohol affects memory and emotion, a chronic intermittent alcohol exposure (CIAE) model was established. The results demonstrated that mice in the CIAE group developed short-term recognition memory impairment and anxiety-like behavior; meanwhile, the expression of DUSP1 and DUSP66 in the mPFC was increased, while the levels of p-ERK and BDNF were decreased. Micro-injection of DUSP1/6 inhibitor BCI into the medial prefrontal cortex (mPFC) restored the dendritic morphology by reversing the activity of ERK-BDNF and ultimately improved cognitive and emotional impairment caused by CIAE. These findings indicate that CIAE inhibits ERK-BDNF by increasing DUSP1/6 in the mPFC that may be associated with cognitive and emotional deficits. Consequently, DUSP1 and DUSP6 appear to be potential targets for the treatment of alcoholic brain disorders.

Hollow CoVOx/Ag nanoprism with tailored electronic structure for high efficiency oxygen evolution reaction.

Developing high-active and inexpensive electrocatalysts for oxygen evolution reaction (OER) is very important in the field of water splitting. The catalytic performance of electrocatalysts can be significantly improved by optimizing the electronic structure and designing suitable nanostructure. In this work, we represent the synthesis of hollow CoVOx/Ag-5 for OER. Due to the interaction of CoVOx and Ag nanoparticles, the electronic structure is optimized to improve the intrinsic catalytic activity. Additionally, the extrinsic catalytic activity of CoVOx/Ag is enhanced by the abundant active sites from the hollow structure. As a result, the CoVOx/Ag-5 demonstrates significantly enhanced OER catalytic activity with a low overpotential of 247 mV at 10 mA cm-2. In addition, it also exhibits excellent durability, without obvious attenuation in performance after continuous operation for 60 h. Furthermore, the catalyst can enable full water splitting with appropriate 100 % Faraday efficiency, demonstrating its practical application.