Prognostic implications of residual mild coarctation gradient after interventional repair.

There is limited data on the prognostic implications of residual mild coarctation (RMC) in patients with repaired native coarctation of the aorta (CoA). To explore the association of RMC with mid-term comorbidities in post-interventional patients, and the predictive value of the residual pressure gradient. The authors retrospectively analyzed 79 native CoA patients who received successful intervention at our hospital between October 2010 and June 2023. The outcomes of the study were late arterial hypertension (either raised blood pressure or commencement of hypotensive medications) only in normotensive patients at early follow-up and the composite mid-term comorbidities including new-onset aortic injury, re-stenosis, and re-intervention. At a median follow-up of 60 months, late hypertension and mid-term comorbidities occurred in 16 (28.1%) and nine (11.4%) patients, respectively. Multivariate Cox proportional hazard regression analysis identified invasive peak systolic CoA pressure gradient (PSPG) as the best independent predictor of both outcomes. The maximally selected rank statistics indicated 10 mm Hg as the best PSPG cut-off value for predicting late hypertension. Compared to patients with PSPG < 11 mm Hg, the cumulative event rates of both outcomes were higher in those with PSPG ≥ 11 mm Hg (log-rank test, p < .001 for both endpoints). PSPG ≥ 11 mm Hg was proved to be the independent predictor of late hypertension with a significantly increased risk. In patients with non-surgical CoA repair, the post-interventional RMC and PSPG ≥11 mm Hg are important predictors of clinical comorbidities at mid-term follow-up.

The altered functional status in vestibular migraine: A meta-analysis.

PURPOSE: Vestibular migraine (VM) is a disorder with prominent vestibular symptoms that are causally correlated with migraine and is the most prevalent neurological cause of episodic vertigo. Nevertheless, the functional underpinnings of VM remain largely unclear. This study aimed to reveal concordant alteration patterns of functional connectivity (FC) in VM patients. METHODS: We searched literature measuring resting-state FC abnormalities of VM patients in PubMed, Embase, Cochrane, and Scopus databases before May 2023. Furthermore, we applied the anisotropic effect size-signed differential mapping (AES-SDM) to conduct a whole-brain voxel-wise meta-analysis to identify the convergence of FC alterations in VM patients. RESULTS: Nine studies containing 251 VM patients and 257 healthy controls (HCs) were included. Relative to HCs, VM patients showed reduced activity in the left superior temporal gyrus and left midcingulate/paracingulate gyri, and increased activity in the precuneus, right superior parietal gyrus, and right middle frontal gyrus. Jackknife's analysis and subgroup analysis further supported the generalization and robustness of the main results. Furthermore, meta-regression analyses indicated that the Dizziness Handicap Inventory (DHI) ratings were positively correlated with the activity in the precuneus, while higher Headache Impact Test-6 and DHI scores were associated with lower activity within the left midcingulate/paracingulate gyri. CONCLUSIONS: The study indicates that VM is associated with specific functional deficits of VM patients in crucial regions involved in the vestibular and pain networks and provides further information on the pathophysiological mechanisms of VM.

Synthesis and biological evaluation of novel 1,2,3,4-tetrahydro-ß-carboline derivatives as potential antibacterial agents.

The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.

Process approach as a cognitive biomarker related to gray matter volume in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Process approach is valuable for memory assessment in Alzheimer's disease (AD) and mild cognitive impairment (MCI), yet its underlying mechanisms remain elusive. This study aims to synergize the process approach with brain structure analysis to explore both the discriminative capacity and potential mechanisms underlying the process approach. METHODS: 37 subjects of MCI, 35 subjects of AD and 38 subjects of healthy control (HC) were included. The process approach in Auditory Verbal Learning Test (AVLT), including discriminability (A'), response bias (B"D), semantic clustering (LBCsem) and serial clustering (LBCser) was performed. The gray matter volume (GMV) was analyzed by voxel-based morphometry. Receiver operating characteristic (ROC) analysis and partial correlations were conducted to explore the value of the process approach and investigate the relationship between the process approach, traditional indices of AVLT and GMV. RESULTS: ROC analysis showed the value of A', B"D and LBCser in differentiating MCI and AD. Combining AVLT-Immediately Recall (AVLT-IR) and LBCser showed a higher value in diagnosing MCI. Partial correlations revealed that in the MCI group, A' and B"D were mainly positively associated with GMV of the hippocampus and temporal lobe. CONCLUSION: This study indicated that the process approach is a promising cognitive biomarker to detect MCI and AD.

New Clerodane Diterpenoids from Tinospora Capillipes with Antibacterial and Anti-Inflammatory Properties.

Four new clerodane diterpenoids, namely tinocapills A-D (1-4), and one known analogue (5) were isolated from the roots of Tinospora capillipes in the present study. The structures of these new compounds, including their absolute configurations, were determined through a combination of detailed spectroscopic analysis and theoretical statistical approaches, including electronic circular dichroism (ECD) analyses and quantum mechanical (QM)-NMR methods. Additionally, the stereostructure of 5 was confirmed via X-ray diffraction analysis. Furthermore, all these isolates were evaluated for their antibacterial and anti-inflammatory activities. Compounds 1, 2 and 5 demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with MICs ranging from 4-64 µg/mL, and compounds 3 and 4 exhibited potential anti-inflammatory effects by suppressing LPS-induced TNF-α and NO releases in RAW264.7 cells.

Association between daily consumption of spicy food and bone mineral density in middle-aged and older adults: a cross-sectional study.

Background: Many studies have reported the effects of spicy food on human health, but no studies have been conducted on the impact of long-term spicy food consumption on bone mineral density (BMD). This study aimed to investigate the impact of daily consumption of spicy food on BMD in the population aged 50 years and older. Methods: This cross-sectional study was conducted from 2020 to 2022 in Jiangxi Province, China. This study investigated the differences in BMD between non-consumers and daily spicy food consumers in adults aged 50-85 years. A multiple linear regression model was used to investigate the association between spicy food consumption and BMD of the total lumbar spine (LS), femoral neck (FN), and total hip, as well as biochemical markers of bone metabolism (BMBM) levels. Results: The results showed that daily consumption of spicy food was negatively associated with total LS BMD (ß = -0.013, P = 0.015). Subgroup analyses showed this negative association was more pronounced among smokers and drinkers compared to non-smokers (ß: -0.006 vs. -0.042; P for interaction <0.05) and non-drinkers (ß: -0.004 vs. -0.037; P for interaction <0.05). In addition, according to the daily frequency of spicy food consumption, the daily spicy food consumers were categorized into one meal per day, two meals per day, and three meals per day groups. Further analysis revealed that the negative association between spicy food and total LS BMD was progressively stronger as the frequency of daily consumption of spicy food increased (P for trend <0.05). For BMBM, daily consumption of spicy food was positively associated with serum PINP levels and negatively associated with serum Ca and serum Mg levels. Conclusions: Our study suggested that daily consumption of spicy food was associated with lower LS BMD in middle-aged and older Chinese adults, and this association was more pronounced in the smoking and drinking populations. The adverse effects of spicy food on LS BMD become progressively stronger with increasing frequency of daily consumption of spicy food. In addition, daily consumption of spicy food was associated with higher PINP levels and lower serum Ca and Mg levels.

Synergistic effect of folate and MTHFR C677T on hippocampal subfields and perfusion in Alzheimer's disease.

BACKGROUND: Low folate intake and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have been suggested to increase the risk of Alzheimer's disease (AD). However, the synergistic effects and their impact on brain structure and perfusion remain unclear. METHODS: This study explored the effects of dietary and genetic deficiencies in folate metabolism on the volume of the hippocampal subregions, cerebral perfusion, and cognitive decline in 71 cognitively unimpaired (CU) individuals and 102 patients with mild cognitive impairment (MCI) due to AD or AD. All participants underwent magnetic resonance imaging, laboratory examinations, and neuropsychological assessments. The hippocampal subfields were segmented using Freesurfer, and arterial spin labeling was used to measure the cerebral blood flow. RESULTS: We found a significant group-by-MTHFR interaction effect on folate. Patients with AD and the 677 T allele showed hypoperfusion in the left precuneus compared to patients without this mutation, which mediated the relationship between low folate level and cognitive decline in patients carrying the 677 T allele. Moreover, a synergistic effect was observed for the combination of decreased folate concentrations and the presence of the MTHFR 677 T allele on the atrophy of specific hippocampal subregions in patients with AD. CONCLUSIONS: In addition to offering insights into the neuronal mechanism underlying gene-dependent folate-induced cognitive impairment in AD, these findings may have clinical significance for the allocation of auxiliary folate supplementation therapy in patients with AD with low folate levels and carrying the MTHFR 677 T allele and may eventually promote the selection of early individualized AD drug therapy.

Near-Infrared-II Imaging Revealed Hypothermia Regulates Neuroinflammation Following Brain Injury by Increasing the Glymphatic Influx.

Advanced in vivo imaging techniques have facilitated the comprehensive visual exploration of animal biological processes, leading to groundbreaking discoveries such as the glymphatic system. However, current limitations of macroscopic imaging techniques impede the precise investigation of physiological parameters regulating this specialized lymphatic transport system. While NIR-II fluorescence imaging has demonstrated advantages in peripheral lymphatic imaging, there are few reports regarding its utilization in the glymphatic system. To address this, a noninvasive transcranial macroscopic NIR-II fluorescence imaging model is developed using a cyanine dye-protein coupled nanoprobe. NIR-II imaging with high temporal and spatial resolution reveals that hypothermia can increase the glymphatic influx by reducing the flow rate of cerebrospinal fluid. In addition, respiratory rate, respiratory amplitude, and heart rate all play a role in regulating the glymphatic influx. Thus, targeting the glymphatic influx may alter the trajectory of immune inflammation following brain injury, providing therapeutic prospects for treating brain injury with mild hypothermia.

Development of postoperative bronchopleural fistula after neoadjuvant immunochemotherapy in non-small cell lung cancer: case reports and review of the literature.

BACKGROUND: The advent of immune checkpoint inhibitors has dramatically changed the treatment paradigm for advanced non-small-cell lung cancer (NSCLC). Due to the complexity and diversity of stage III disease, the inclusion of immune checkpoint inhibitors (ICIs) in neoadjuvant treatment regimens is also required. However, immune-related adverse events (irAEs) limit the application of ICIs to a certain extent. Bronchopleural fistula (BPF) is a serious and fatal complication after pneumonectomy that is rarely reported, especially in patients who accept neoadjuvant immunotherapy or chemoimmunotherapy. CASE PRESENTATION: Herein, we reported four patients with postoperative BPF who received a neoadjuvant regimen of sintilimab plus chemotherapy. Postoperative BPF occurred in the late stage in three patients; one patient underwent bronchoscopic fistula repair, and the fistula was closed well after surgery, and the other two patients gradually recovered within 1-2 months after symptomatic treatment with antibiotics. One patient with BPF after left pneumonectomy died of respiratory failure due to pulmonary infection. We also reviewed the literature on the development of postoperative BPF in patients receiving immuno-neoadjuvant therapy to discuss the clinical process further, postoperative pathological changes, as well as risk factors of BPF patients. CONCLUSIONS: Central type lung cancer with stage III may be the risk factors of BPF in cases of neoadjuvant immunochemotherapy for lung cancers patients.

[Process Approach in Memory Assessment of Patients With Alzheimer's Disease and Mild Cognitive Impairment:A Review].

The process approach,a set of analytical methods used in neuropsychology,quantifies the word-list learning tests and conventional analytical methods and fully reflects the memory profile of the subject.Therefore,it is widely used in the memory assessment of patients with Alzheimer's disease(AD)and mild cognitive impairment(MCI).The common indices of process approach,such as learning slope,semantic clustering,serial position effects,discriminability,and response bias,are key components of memory assessment.This article reviews the application of common indices of process approach in memory assessment of AD and MCI patients and discusses the shortcomings and future research directions of process approach.

Efficacy and safety of Wuhu oral liquid in treating acute soft tissue injuries: a multicenter, randomized, double-blind, double-dummy, parallel-controlled trial.

Background: Wuhu Oral Liquid (WHOL) is a modified preparation derived from the famous Wuhu Powder, which has a long history of use in treating traumatic injuries. This preparation has anti-inflammatory and analgesic properties and accelerates recovery following acute soft tissue injuries. Aims: To evaluate the efficacy and safety of WHOL in treating acute soft tissue injury associated with qi stagnation and blood stasis syndrome and to provide a basis for applying for the protection of varieties of Chinese medicine for WHOL. Methods: This study was a randomized, controlled, double-blind, multicenter clinical trial in which Fufang Shang Tong Capsule (FFSTC) was selected as the control drug. A total of 480 subjects with acute soft tissue injury associated with qi stagnation and blood stasis syndrome were randomly divided into a test and control group in a 3:1 ratio. The duration of drug treatment was 10 days. The primary outcome was Visual Analogue Scale (VAS) score for pain (including pain at rest and pain on activity). Secondary outcomes included the disappearance time of the pain at rest and on activity; the curative effect of TCM syndrome and improvement in the individual symptoms of TCM (swelling, ecchymosis, and dysfunction); and changes in C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Safety was assessed using vital signs, laboratory examinations, electrocardiograms, and physical examinations. Results: Patient compliance was satisfactory in both groups (all between 80% and 120%). After 4 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain at rest (-1.88 ± 1.13 vs. -1.60 ± 0.93, p < 0.05) and on activity (-2.16 ± 1.18 vs. -1.80 ± 1.07, p < 0.05). After 7 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain on activity (-3.87 ± 1.60 vs. -3.35 ± 1.30, p < 0.01) and improving swelling (cure rate: 60.4% vs. 46.2%, p < 0.05; obvious effective rate: 60.7% vs. 47.0%, p < 0.05). After 10 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the levels of CRP (-0.13 ± 2.85 vs. 0.25 ± 2.09, p < 0.05) and improving the TCM syndrome (cure rate: 44.1% vs. 30.8%, p < 0.05) and swelling (cure rate: 75.6% vs. 67.5%, p < 0.01; obvious effective rate: 75.6% vs. 68.4%, p < 0.05; effective rate: 77.0% vs. 71.8%, p < 0.05). The disappearance time of pain at rest was 8 days in both groups and 9 days on activity in both groups. In addition, there was no statistical difference between the incidence of adverse events (4.5% vs. 2.6%, p > 0.05) and adverse reactions (0.3% vs. 0%, p > 0.05) between the WHOL group and the FFSTC group. No serious adverse events occurred in either group, and no subjects were withdrawn because of adverse events. Conclusion: WHOL relieves the symptoms caused by acute soft tissue injury associated with qi stagnation and blood stasis syndrome more rapidly than FFSTC, and it is effective and safe in the treatment of acute soft tissue injury. Future studies still need a larger sample size to verify its efficacy and safety. Clinical Trial Registration: https:// www.chictr.org.cn/showproj.html?proj=149531, Identifier ChiCTR2200056411.

Apnea Testing Practice to Increase Baseline PaCO2 and Frequency of Blood Gas Analyses.

OBJECTIVE: To study the influence of the initial partial pressure of carbon dioxide (PaCO2) and frequency of blood gas analyses on the positivity rate and safety of apnea testing (AT). DESIGN: A prospective multicenter cohort study. SETTING: Seven teaching hospitals. PARTICIPANTS: A total of 55 patients who underwent AT. INTERVENTIONS: Patients were divided into 2 groups according to their initial PaCO2-the experimental group (≥40 mmHg, 27 patients) and the control group (<40 mmHg, 28 patients). Blood gas analysis was performed at 3, 5, and 8 minutes, and vital signs were taken. AT results and complications were compared between the groups. RESULTS: The initial PaCO2 of the experimental group was 42.8 ± 2.2 mmHg v 36.4 ± 2.9 mmHg in the controls. The AT positivity rate was 100%. The experimental group needed less time to reach the target PaCO2 than the control group (4.07 ± 1.27 minutes v 5.68 ± 2.06 minutes; p = 0.001). Twenty-six patients (96.3%) in the experimental group reached the target PaCO2 in 5 minutes v 17 in the control group (60.7%) (p = 0.001). Seven patients (12.7%) were unable to complete 8-minute disconnection due to hypotension. The experimental group had a slightly lower incidence of hypotension than the control group, but there was no statistical difference (7.4% v 17.9%, p = 0.245). CONCLUSION: Increasing the baseline PaCO2 and doing more blood gas analyses can significantly shorten the time needed for AT and improve the AT positivity rate.

Parthenolide induces ROS-dependent cell death in human gastric cancer cell.

BACKGROUND: Parthenolide (PN), a key active ingredient of feverfew, has been used to treat gastrointestinal disorders. However, the mechanism of the cytotoxic effect exerted by PN on tumor cells has not been elucidated. OBJECTIVES: To study the cytotoxic effect of PN on human gastric cancer cells, the specific death mode, and gene expression changes induced by PN. MATERIAL AND METHODS: In this study, MGC-803 cells were used to study PN-induced cytotoxicity as a gastric cancer cell line. Assays of cell proliferation, cell cycle distribution, apoptosis, and reactive oxygen species (ROS) were performed using a Cell Counting Kit-8 (CCK-8) assay and a flow cytometer. MGC-803 cells treated with and without PN were separately subjected to high-throughput RNA sequencing. Western blotting was used to investigate the expression of some important proteins. RESULTS: Parthenolide exposure elicited cell proliferation inhibition in a doseand time-dependent manner. Parthenolide induced cell cycle arrest at the G1 and S stages. Parthenolide-induced caspase-dependent apoptosis and necroptosis were caused by the activation of RIP, RIP3 and MLKL. MGC-803 cells showed a response to ROS and oxidative stress after PN treatment. Moreover, ROS and cytotoxicity induced by PN were significantly attenuated by a ROS scavenger catalase. CONCLUSIONS: Parthenolide-induced gastric cancer cell death is a complex ROS-dependent process different from ordinary apoptosis and necrosis, suggesting that PN is a potential treatment option for gastric cancer.

Correlation between the non-use of cooking oil fume extractors and bone mineral density in population aged 45 years and older in China: a cross-sectional study.

Introduction: The correlation between the non-use of cooking oil fumes (COFs) extractors and bone mineral density (BMD) have not been clarified. Consequently, this study attempted to explore the impact of non-use COFs extractors on BMD in population aged 45 years and older based on a cross-sectional study. Methods: This study was a cross-sectional study within the framework of an ongoing prospective population-based cohort study in China. The multivariate linear regression models were used to evaluate the correlation between the non-use of fume extractors in family cooking and total lumbar spine (LS), femoral neck (FN), total hip BMD and levels of bone metabolism markers. Results: A total of 3433 participants were included in the final analyses, of which 2607 (75.93%) participants used fume extractors. The results of models indicated that there were significant correlations of the non-use of fume extractors on total LS BMD (ß = -0.024, 95% CI, -0.036, -0.012, p < 0.001), PINP (ß = 4.363, 95% CI, 2.371, 6.356, p < 0.001) and ALP (ß = 4.555, 95% CI, 2.593, 6.517, p < 0.001) levels. Conclusions: This study verified that the use of fume extractors is an efficacious measure to prevent LS bone loss. For the sake of public bone health, people should install a fume extractor in the kitchen and use it routinely when cooking.

Effect of TMAO on the incidence and prognosis of cerebral infarction: a systematic review and meta-analysis.

Objective: This study aimed to evaluate the effect of trimethylamine oxide (TMAO) on the incidence and prognosis of cerebral infarction. Methods: We searched PubMed, Embase, and Cochrane databases for all clinical studies on the association of TMAO with cerebral infarction incidence and prognosis from inception to April 2023. A systematic review and meta-analysis were conducted using the meta-analysis of observational studies in epidemiology (MOOSE) declaration list. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the study. This study protocol was registered on the PROSPERO database with the ID: CRD42023459661. The extracted data included the OR value of the effect of TMAO on the incidence and prognosis of cerebral infarction, the HR value between TMAO and underlying diseases, the RR value, 95% confidence intervals, and the AUC value of TMAO in the prediction model of cerebral infarction. Results: Fifteen studies including 40,061 patients were included. All the patients were from China or Germany. The TMAO level was significantly correlated with the Modified Rankin Score (mRS) 3 months after the onset of cerebral infarction (OR, 1.581; 95% CI, 1.259-1.987; p < 0.01). The TMAO level was significantly correlated with the rate of first-time incidence and recurrence of cerebral infarction (OR, 1.208; 95% CI, 1.085-1.344; p < 0.01 and HR, 1.167; 95% CI, 1.076-1.265; p < 0.01, respectively). The TMAO level was also highly correlated with disease severity at onset (National Institutes of Health Stroke Scale, NIHSS >5) (OR, 5.194; 95% CI, 1.206-22.363; p < 0.05), but had no significant correlation with mortality after cerebral infarction (p > 0.05). Correlation analysis of TMAO with underlying diseases in the population indicated that TMAO had a significant correlation with histories of hypertension, diabetes mellitus, coronary artery disease, and cerebral infarction (p < 0.05), but not with hyperlipidemia (p > 0.05). Six risk prediction models of TMAO for cerebral infarction reported in four studies were systematically evaluated; five of them had good predictive value (AUC ≥ 0.7). Conclusion: TMAO is an independent risk factor affecting the onset, prognosis, and severity of cerebral infarction.