Machine learning based on biological context facilitates the identification of microvascular invasion in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a rare disease associated with a poor prognosis, primarily due to early recurrence and metastasis. An important feature of this condition is microvascular invasion (MVI). However, current predictive models based on imaging have limited efficacy in this regard. This study employed a random forest model to construct a predictive model for MVI identification and uncover its biological basis. Single-cell transcriptome sequencing, whole exome sequencing, and proteome sequencing were performed. The area under the curve of the prediction model in the validation set was 0.93. Further analysis indicated that MVI-associated tumor cells exhibited functional changes related to epithelial-mesenchymal transition and lipid metabolism due to alterations in the NF-kappa B and MAPK signaling pathways. Tumor cells were also differentially enriched for the IL-17 signaling pathway. There was less infiltration of SLC30A1+ CD8+ T cells expressing cytotoxic genes in MVI-associated ICC, whereas there was more infiltration of myeloid cells with attenuated expression of the MHC II pathway. Additionally, MVI-associated intercellular communication was closely related to the SPP1-CD44 and ANXA1-FPR1 pathways. These findings resulted in a brilliant predictive model and fresh insights into MVI.

Elevated blood pressure: a genetically determined risk factor for cerebral artery dissection.

BACKGROUND: We aim to investigate the potential causal link between blood pressure (BP) levels and cerebral artery dissection (CAD) risk employing a two-sample Mendelian randomization (TSMR) framework. METHODS: Utilizing large-scale genome-wide association studies (GWAS)-retrieved data, we employed various MR techniques, including inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode, to ascertain BP's causal impact on CAD. The MR-Egger intercept was calculated to assess pleiotropy presence, determining heterogeneity by Cochran's Q statistic. RESULTS: The findings highlighted a significant association between elevated systolic BP (SBP; IVW: OR=3.09, 95% CI: 1.11-8.61, p=0.031) and increased diastolic BP (DBP; IVW: OR=2.17, 95% CI: 1.14-6.21, p=0.023) with CAD risk. Sensitivity analyses reinforced the robustness and reliability of these results. CONCLUSIONS: The results from this TSMR study suggest a causal link between high SBP and DBP and the increased likelihood of CAD, which provide genetic evidence for a reduced risk of CAD under blood pressure control.

Illness uncertainty, resilience, and perceived social support among patients with moyamoya disease: a cross-sectional study.

Objective: The present study aims to investigate the levels of illness uncertainty in patients with moyamoya disease and to determine the association of socio-demographic characteristics, perceived social support and resilience with illness uncertainty in patients with moyamoya disease. Method: A cross-sectional survey using convenience sampling was conducted in two hospitals in China from August to December 2023. A socio-demographic characteristics questionnaire, the Chinese versions of Mishel's Unsurety in Disease Scale (MUIS), the Chinese version of Connor-Davidson Resilience Scale (CD-RISC), and the Chinese version of Multidimensional Scale of Perceived Social Support (MSPSS) were used to perform this research. The collected data were analyzed using SPSS 24.0 statistical software. The t-test, one-way analysis of variance (ANOVA), pearson correlation analysis and hierarchical regression analysis were used to identify associated factors. Result: A total of 263 patients with moyamoya disease were recruited in this survey. The score of illness uncertainty was at a moderate level of (100.03 ± 18.59). The present study identified a negative correlation between illness uncertainty with resilience perceived social support. Hierarchical regression analysis showed that gender, occupation, education level, resilience and perceived social support were the related factors of illness uncertainty. Conclusion: Patients with moyamoya disease experienced moderate disease uncertainty on average, which was related to gender, occupation, education level, resilience and perceived social support. Future research is needed to better explore the complex relationships between illness uncertainty, resilience, and perceived social support with different types of moyamoya disease using longitudinal research.

Lactiplantibacillus plantarum P9 for chronic diarrhea in young adults: a large double-blind, randomized, placebo-controlled trial.

Current treatments for chronic diarrhea have limited efficacy and several side effects. Probiotics have the potential to alleviate symptoms of diarrhea. This randomized, double-blind, placebo-controlled trial evaluates the effects of administering the probiotic Lactiplantibacillus plantarum P9 (P9) strain in young adults with chronic diarrhea (Clinical Trial Registration Number: ChiCTR2000038410). The intervention period lasts for 28 days, followed by a 14-day post-intervention period. Participants are randomized into the P9 (n = 93) and placebo (n = 96) groups, with 170 individuals completing the double-blind intervention phase (n = 85 per group). The primary endpoint is the diarrhea symptom severity score. Both intention-to-treat (n = 189) and per-protocol (n = 170) analyses reveal a modest yet statistically significant reduction in diarrhea severity compared to the placebo group (20.0%, P = 0.050; 21.4%, P = 0.048, respectively). In conclusion, the results of this study support the use of probiotics in managing chronic diarrhea in young adults. However, the lack of blood parameter assessment and the short intervention period represent limitations of this study.

Estimate the number of lives saved by a SARS-CoV-2 vaccination campaign in six states in the United States with a simple model.

Objectives: Vaccination and the emergence of the highly transmissible Omicron variant changed the fate of the COVID-19 pandemic. It is very challenging to estimate the number of lives saved by vaccination given the multiple doses of vaccination, the time-varying nature of transmissibility, the waning of immunity, and the presence of immune evasion. Methods: We established a S-SV-E-I-T-D-R model to simulate the number of lives saved by vaccination in six states in the United States (U.S.) from March 5, 2020, to March 23, 2023. The cumulative number of deaths were estimated under three vaccination scenarios based on two assumptions. Additionally, immune evasion by the Omicron and loss of protection afforded by vaccination or infection were considered. Results: The number of deaths averted by COVID-19 vaccinations (including three doses) ranged from 0.154-0.295% of the total population across six states. The number of deaths averted by the third dose ranged from 0.008-0.017% of the total population. Conclusions: Our estimate of death averted by COVID-19 vaccination in the U.S. was largely in line with an official estimate (at a level of 0.15-0.20% of the total population). We found that the additional contribution of the third dose was small but significant.

Factors Affecting Low Anterior Resection Syndrome following Anus-Preserving Surgery for Rectal Cancer and Assessing the Impact of Nursing Interventions in Rapid Rehabilitation Surgery.

Background and objective: This study aimed to investigate the factors affecting the development of low anterior resection syndrome (LARS) following anus-preserving surgery for rectal cancer, and to assess the impact of a rapid rehabilitation surgical nursing intervention on patient outcomes. LARS is a significant issue for patients undergoing these surgeries, as it can severely impact quality of life. Understanding the risk factors for LARS is crucial to develop targeted interventions to improve post-operative recovery. Methods: The study retrospectively analyzed the clinical data of 78 rectal cancer patients who underwent anus-preserving radical resection. The occurrence of LARS was assessed using the LARS score scale. Univariate and multivariate logistic regression analyses were performed to identify factors that may affect the development of LARS, including distance of the anastomosis from the anal verge, preoperative chemoradiotherapy, and postoperative anastomotic leakage. Additionally, the study compared outcomes between two patient groups - a control group receiving routine surgical nursing care, and an experimental group receiving a rapid rehabilitation surgical nursing intervention. This intervention included preoperative patient education, optimized anesthesia and surgical techniques, and intensive postoperative rehabilitation. Key outcomes measured included time to first flatus, time to first defecation, duration of pain-free days, length of hospital stay, and total hospitalization costs. Results: The univariate regression analysis showed that the distance from the anastomosis to the anal verge (OR=4.364, P < .001, 95% CI 2.732-7.257), preoperative chemoradiotherapy (OR=9.135, P = .004, 95% CI 1.963-40.316), and postoperative anastomotic leakage (OR=2.636, P < .001, 95% CI 1.641-4.245) were significant risk factors for the development of LARS. The multivariate logistic regression analysis confirmed that a shorter distance between the anastomosis and anal margin, preoperative radiotherapy, and postoperative anastomotic leakage were independent predictors of LARS (all P < .05). Comparison of the two patient groups showed that the rapid rehabilitation surgical nursing intervention had a significant positive impact. Patients in the experimental group (group E) had a significantly shorter time to first exhaust (62.19±7.43 minutes vs. 96.18±10.62 minutes in group C, P < .001) and first defecation (85.26±8.41 minutes vs. 130.26±12.38 minutes in group C, P < .001). Group E also experienced a longer duration of 0 pain score days (3.57±0.72 days vs. 5.42±1.05 days in group C, P < .001), shorter hospital stays (10.15±2.05 days vs. 15.33±1.23 days in group C, P < .001), and lower total hospitalization costs (31.80±3.70 thousand Yuan vs. 42.80±5.60 thousand Yuan in group C, P < .001). Conclusion: This study identified the distance between the anastomosis and anal margin, preoperative radiotherapy, and postoperative anastomotic leakage as independent risk factors for the development of LARS in patients undergoing anus-preserving surgery for rectal cancer. These findings can inform preoperative risk assessment and guide surgical planning to mitigate the risk of LARS. Patients identified as high-risk may benefit from more intensive preoperative counseling and targeted nursing interventions to optimize postoperative bowel function. Notably, the rapid rehabilitation surgical nursing intervention demonstrated significant benefits in accelerating patient recovery, reducing complications, and lowering overall healthcare utilization. This comprehensive nursing approach, encompassing preoperative education, optimized perioperative management, and intensive postoperative rehabilitation, offers a promising model to improve standards of care for rectal cancer patients undergoing anus-preserving surgeries. Widespread adoption of such targeted nursing interventions has the potential to enhance patient outcomes, quality of life, and healthcare resource efficiency in this patient population.

MRI versus Dual-Energy CT in Local-Regional Staging of Gastric Cancer.

Background Preoperative local-regional tumor staging of gastric cancer (GC) is critical for appropriate treatment planning. The comparative accuracy of multiparametric MRI (mpMRI) versus dual-energy CT (DECT) for staging of GC is not known. Purpose To compare the diagnostic accuracy of personalized mpMRI with that of DECT for local-regional T and N staging in patients with GC receiving curative surgical intervention. Materials and Methods Patients with GC who underwent gastric mpMRI and DECT before gastrectomy with lymphadenectomy were eligible for this single-center prospective noninferiority study between November 2021 and September 2022. mpMRI comprised T2-weighted imaging, multiorientational zoomed diffusion-weighted imaging, and extradimensional volumetric interpolated breath-hold examination dynamic contrast-enhanced imaging. Dual-phase DECT images were reconstructed at 40 keV and standard 120 kVp-like images. Using gastrectomy specimens as the reference standard, the diagnostic accuracy of mpMRI and DECT for T and N staging was compared by six radiologists in a pairwise blinded manner. Interreader agreement was assessed using the weighted κ and Kendall W statistics. The McNemar test was used for head-to-head accuracy comparisons between DECT and mpMRI. Results This study included 202 participants (mean age, 62 years ± 11 [SD]; 145 male). The interreader agreement of the six readers for T and N staging of GC was excellent for both mpMRI (κ = 0.89 and 0.85, respectively) and DECT (κ = 0.86 and 0.84, respectively). Regardless of reader experience, higher accuracy was achieved with mpMRI than with DECT for both T (61%-77% vs 50%-64%; all P < .05) and N (54%-68% vs 51%-58%; P = .497-.005) staging, specifically T1 (83% vs 65%) and T4a (78% vs 68%) tumors and N1 (41% vs 24%) and N3 (64% vs 45%) nodules (all P < .05). Conclusion Personalized mpMRI was superior in T staging and noninferior or superior in N staging compared with DECT for patients with GC. Clinical trial registration no. NCT05508126 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Méndez and Martín-Garre in this issue.

Resveratrol protects against a high-fat diet-induced neuroinflammation by suppressing mitochondrial fission via targeting SIRT1/PGC-1α.

Various health issues have emerged due to consuming high-fat diets (HFD), particularly the detrimental impact they have on mitochondrial dynamics and subsequet cognition functions. Specially, mitochondrial fission can serve as an upstream signal in the regulation of cortical inflammation and neural pyroptosis. Our study was designed to verify the existence of neuroinflammation in the pathogenesis of HFD-induced cognitive dysfunction and demonstrated that resveratrol (RSV) attenuated neural deficits via regulation of cortical mitochondrial fission. A total of 50 male Sprague Dawley rats were randomly divided into five groups: control (Cont, 26 weeks on normal rodent diet); high-fat diet (HFD); dietary adjustments (HFD + ND); resveratrol intervention (HFD + R); joint intervention (HFD + ND + R) for 26 weeks. The spatial learning and memory function, spine density, NLRP3 inflammasome associated protein, mRNA and protein expression involved in mitochondrial dynamics and SIRT1/PGC-1α signaling pathway in brain were measured. Furthermore, reactive oxygen species (ROS) accumulation and resultant mitochondrial membrane potential (MMP) alteration in PC12 cells exposed to palmitic acid (PA) or Drp1 inhibitor (Mdivi-1) were detected to reflect mitochondrial function. The findings suggested that prolonged treatment of RSV improved cognitive deficits and neuronal damage induced by HFD, potentially attributed to activation of the SIRT1/PGC-1α axis. We further indicated that the activation of the NLRP3 inflammasome in PA (200 µM) treated PC12 cells could be inhibited by Mdivi-1. More importantly, Mdivi-1 (10 µM) reduced intracellular ROS levels and enhanced MMP by reversing Drp1-mediated aberrant mitochondrial fission. To summarize, those results clearly indicated that a HFD inhibited the SIRT1/PGC-1α pathway, which contributed to an imbalance in mitochondrial dynamics and the onset of NLRP3-mediated pyroptosis. This effect was mitigated by the RSV possibly through triggering the SIRT1/PGC-1α axis, prevented aberrant mitochondrial fission and thus inhibited the activation of the NLRP3 inflammatory pathway.

Investigating the involvement of potato (Solanum tuberosum L.) StPHR1 gene in the combined stress response to phosphorus deficiency and aluminum toxicity.

Phosphorus deficiency and aluminum toxicity in acidic soils are important factors that limit crop yield. To further explore this issue, we identified 18 members of the StPHR gene family in the potato genome in this study. Through bioinformatics analysis, we found that the StPHR1 gene, an important member of this family, exhibited high expression levels in potato roots, particularly under conditions of phosphorus deficiency and aluminum toxicity stress. This suggested that the StPHR1 gene may play a crucial regulatory role in potato's resistance to phosphorus deficiency and aluminum toxicity. To validate this hypothesis, we conducted a series of experiments on the StPHR1 gene, including subcellular localization, GUS staining for tissue expression, heterologous overexpression, yeast two-hybrid hybridization, and bimolecular fluorescence complementation (BiFC). The results demonstrated that the StPHR1 gene is highly conserved in plants and is localized in the nucleus of potato cells. The heterologous overexpression of the gene in Arabidopsis plants resulted in a growth phenotype that exhibited resistance to both aluminum toxicity and phosphorus deficiency. Moreover, the heterologous overexpressing plants showed reduced aluminum content in the root system compared to the control group. Furthermore, we also identified an interaction between StPHR1 and StALMT6. These results highlight the potential application of regulating the expression of the StPHR1 gene in potato production to enhance its adaptation to the dual stress of phosphorus deficiency and high aluminum toxicity in acidic soils.

Causal effect of COVID-19 on optic nerve and visual pathway disorders: genetic evidence of lung-brain axis.

Purpose: To investigate the potential causal association between COVID-19 exposure and optic nerve and visual pathway disorders through a two-sample bidirectional Mendelian randomization (MR) analysis, and to provide empirical support for the lung-brain axis. Methods: This MR analysis utilized publicly accessible summary-level data from genome-wide association studies on COVID-19 (n=158,783) and optic nerve and visual pathway diseases (n=412,181), primarily involving individuals of European descent. The random-effect inverse-variance weighted estimation was applied as the main analytical approach, complemented by MR-Egger, weighted median, and weighted mode methods. The heterogeneity and pleiotropy of the instrumental variables were assessed using Cochran's Q test, leave-one-out sensitivity analysis, MR-Egger intercept test, MR-PRESSO, and funnel plot evaluations. Results: In the forward analysis, the inverse-variance weighted method identified a significant causal effect of COVID-19 on optic nerve and visual pathway disorders (odds ratio = 1.697, 95% confidence interval: 1.086-2.652, p = 0.020). Directionally consistent results were also observed with MR-Egger regression, weighted median, and weighted mode approaches. Conversely, the reverse analysis revealed no causal effects of optic nerve and visual pathway disorders on COVID-19 susceptibility. Conclusion: Our findings suggest that COVID-19 exposure may increase the risk of developing optic nerve and visual pathway disorders, supporting the lung-brain axis hypothesis. These results underscore the importance of vigilant monitoring of the visual system in patients recovering from COVID-19 and suggest potential avenues for future therapeutic strategies.

Association of modified dementia risk score with cerebrospinal fluid biomarkers and cognition in adults without dementia.

Introduction: This study aimed to investigate the cognitive profile and prospective cognitive changes in non-demented adults with elevated Modified Dementia Risk Scores (MDRS), while also exploring the potential relationship between these associations and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology and neuroinflammation. Methods: Within the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database, 994 participants without dementia were assessed on MDRS, CSF biomarkers and cognition. We examined the associations of the MDRS with CSF biomarkers and cognitive scores using linear regressions. Causal mediation analyses were conducted to analyze the associations among MDRS, brain pathologies, and cognition. The Alzheimer's Disease Neuroimaging Initiative (ADNI) study was used to validate the mediation effects and to investigate the longitudinal association between MDRS and cognitive decline. Results: The results revealed that higher MDRS were linked to poorer cognitive performance (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and increases in CSF levels of phosphorylated tau (P-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), total tau (T-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), P-tau/Aß42 ratio (Model 1: PFDR = 0.023; Model 2: PFDR = 0.028), T-tau/Aß42 ratio (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and soluble triggering receptor expressed on myeloid cells 2 (sTrem2, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) in the CABLE study. The impact of MDRS on cognition was partially mediated by neuroinflammation and tau pathology. These mediation effects were replicated in the ADNI study. Baseline MDRS were significantly associated with future cognitive decline, as indicated by lower scores on the Mini-Mental State Examination (MMSE, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), ADNI composite memory score (ADNI-MEM, Model 1: PFDR = 0.005; Model 2: PFDR < 0.001), ADNI composite executive function score (ADNI-EF, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), and higher score on the Alzheimer's Disease Assessment Scale (ADAS13, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001). Discussion: The findings of this study revealed significant associations between MDRS and cognitive decline, suggesting a potential role of tau pathology and neuroinflammation in the link between MDRS and poorer cognitive performance in individuals without dementia. Consequently, the MDRS holds promise as a tool for targeted preventive interventions in individuals at high risk of cognitive impairment.

Spectral Characteristics of Unsaturated and Supersaturated Inorganic Aerosols: Insights into Deliquescence Kinetics.

The deliquescence phase transition of atmospheric aerosols is crucial for radiative forcing and atmospheric chemistry. However, the deliquescence kinetics of micrometer-sized aerosols, especially the formation and evolution of surface solution films, remain poorly understood. In this study, IR spectral characteristics were employed for the first time to quantify the solute concentration evolution in surface solution films. At a constant relative humidity (RH) of ∼65%, solution films on NaCl crystals exhibited a very low solute concentration (3.06 ± 0.18 mol/L), comparable to aqueous NaCl droplets above 90% RH. These films reached saturation at ∼74% RH, i.e., the deliquescence RH of NaCl, maintaining a nearly constant saturation level during deliquescence. In contrast, amorphous NaNO3 solids showed supersaturated solution films before deliquescence. Following deliquescence, the saturation level of solution phases increased due to faster solid dissolution rates than liquid water condensation. These findings address knowledge gaps in the complex nonequilibrium dissolution processes of crystalline or amorphous atmospheric aerosols.

APG-1252 combined with Cabozantinib inhibits hepatocellular carcinoma by suppressing MEK/ERK and CREB/Bcl-xl pathways.

BACKGROUND AND PURPOSE: Liver cancer is the fourth leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. APG-1252 is a small molecule inhibitor targeting Bcl-2 and Bcl-xl. However, its anti-tumor effects in HCC, alone or in combination with Cabozantinib, have not been extensively studied. EXPERIMENTAL: Approach: TCGA database analysis was used to analysis the gene expression levels of Bcl-2 and Bcl-xl in HCC tissues. Western blot was employed to detect the protein expression levels. And the inhibitory effects of APG-1252 and Cabozantinib on the proliferation of HCC cell lines was detected by CCK-8. The effect on the migration and invasion of HCC cells was verified by transwell assay. Huh7 xenograft model in nude mice was used to investigate the combination antitumor effect in vivo. KEY RESULTS: Our study demonstrated that APG-1252 monotherapy inhibited the proliferation and migration ability of HCC cells, and induced HCC cells apoptosis. The combination of APG-1252 and Cabozantinib showed significant synergistic antitumor effects. Furthermore, the in vivo experiment demonstrated that the combination therapy exerted a synergistic effect in delaying tumor growth, notably downregulating MEK/ERK phosphorylation levels. In terms of mechanism, Cabozantinib treatment caused an increase in the phosphorylation levels of CREB and Bcl-xl proteins, while the combination with APG-1252 mitigated this effect, thereby enhanced the antitumor effect of Cabozantinib. CONCLUSION AND IMPLICATIONS: Our findings suggest that APG-1252 in combination with Cabozantinib offers a more effective treatment strategy for HCC patients, warranting further clinical investigation.

The role of uncoupling protein 2 in experimental periodontitis-associated renal injury in rats.

OBJECTIVES: This study aims to explore changes in uncoupling protein 2 (UCP2) in experimental periodontitis-associated renal injury induced by ligation and investigate the effect of UCP2 on renal injury induced by periodontitis. METHODS: Twelve Wistar male rats were randomly divided into two groups: control and periodontitis groups. A periodontal model was built by ligating the maxillary first molars area with 0.2 mm orthodontic ligature wire. After 8 weeks, the intraoral condition of the rats was observed and periodontal clinical indices such as gingival bleeding index (BI), periodontal probing depth (PD), and tooth mobility (TM) were detected. The maxillary bone was scanned by Micro CT to observe the alveolar bone resorption. The tissue mineral density (TMD), bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular bone separation (Tb.Sp) were recorded, and the distance from the enamel bone boundary to the alveolar crest (CEJ-ABC) of the maxillary first molar was measured. The oxidative stress indexes such as malondialdehyde, glutathione (GSH), and superoxide dismutase (SOD) were detected using frozen rat kidney tissue. The gene expression of UCP2, nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) was observed by quantitative real-time polymerase chain reaction (qRT-PCR) test. The gingival tissue of the rats was used for immunohistochemical staining to observe the expression of the UCP2 protein. The fixed rat kidney tissue was used for hematoxylin-eosin (HE), periodic acid-schiff (PAS), MitoSOX Red, JC-1, and immunohistochemical staining to observe the renal histopathology, the level of reactive oxygen species (ROS), the level of mitochondrial membrane potential, and the expression of UCP2, Nrf2, and PGC-1α protein. Rat serum was collected to detect renal function indices, namely, blood urea nitrogen (BUN), creatinine (Cre), and albumin (Alb). RESULTS: Compared with the control group, the periodontitis group showed red, swollen, and soft gingival tissue, with gingival probing bleeding, periodontal PD increased, tooth loosening, alveolar bone resorption, decreased TMD, BMD, BV/TV, and Tb.Th indices, and increased Tb.Sp index, CEJ-ABC, and gingival UCP2 protein expression. Compared with the control group, the levels of MDA and ROS in the kidney tissue of periodontitis rats and the gene and protein expression of UCP2 increased, and the levels of MMP, GSH, and SOD and the gene and protein expression of Nrf2 and PGC-1α decreased. Renal functional indices, namely, BUN, Cre, and Alb, were not significantly different between the two groups. CONCLUSIONS: UCP2 may play a role in renal injury induced by periodontitis through oxidative stress.

Clinical research progress on acupuncture for the treatment of otogenic vertigo.

Otogenic vertigo is a common disorder that affects the vestibular system, which often results in considerable discomfort and impaired daily functioning. Traditional Chinese medicine (TCM), including acupuncture and moxibustion, has been historically utilized to manage the symptoms of vertigo. However, the effectiveness and methodology of these treatments have rarely been investigated in the medical literature. This study reviews the existing literature on the point selection, method, and therapeutic effect of acupuncture and moxibustion to provide a reference for the TCM treatment of otogenic vertigo. A literature search was performed using the PubMed search engine. The terms used included otogenic vertigo, acupuncture treatment, and acupuncture point selection. A total of 34 relevant articles were retrieved from PubMed. These suggest that the clinical treatment of otogenic vertigo should consider the functions of zang-fu organs and meridians and select different acupuncture treatment methods according to syndrome differentiation based on the difference between deficiency and excess. Acupuncture and moxibustion therapy should be based on acupoint selection, considering the syndrome differentiation, supplemented with experience. The treatment of otogenic vertigo with acupuncture and moxibustion refers to the selection of appropriate acupuncture methods under the guidance of TCM theory and following the principles of syndrome, disease, and meridian differentiation. Common acupuncture methods include body acupuncture, auricular acupuncture, scalp acupuncture, acupoint injection, electroacupuncture, and moxibustion. There are many acupuncture and moxibustion acupoints selected for the treatment of otogenic vertigo. Individualized treatment according to the patient's specific condition is effective and safe, which can help to improve the patient's vertigo symptoms and cerebral blood perfusion.

Chronic Alcohol Exposure Alters the Levels and Assembly of the Actin Cytoskeleton and Microtubules in the Adult Mouse Hippocampus.

BACKGROUND: Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus. METHODS: Mice were provided ad libitum access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis. RESULTS: Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice. CONCLUSIONS: Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.

Revealing critical mechanisms in determining sorghum resistance to drought and salt using mRNA, small RNA and degradome sequencing.

BACKGROUND: Plant growth and development are severely threatened by drought and salt stresses. Compared with structural genes, transcription factors (TFs) play more pivotal roles in plant growth and stress adaptation. However, the underlying mechanisms of sorghum adapting to drought and salt are insufficient, and systematic analysis of TFs in response to the above stresses is lacking. RESULTS: In this study, TFs were identified in sorghum and model plants (Arabidopsis thaliana and rice), and gene number and conserved domain were compared between sorghum and model plants. According to syntenic analysis, the expansion of sorghum and rice TFs may be due to whole-genome duplications. Between sorghum and model plants TFs, specific conserved domains were identified and they may be related to functional diversification of TFs. Forty-five key genes in sorghum, including four TFs, were likely responsible for drought adaption based on differently expression analysis. MiR5072 and its target gene (Sobic.001G449600) may refer to the determination of sorghum drought resistance according to small RNA and degradome analysis. Six genes were associated with drought adaptation of sorghum based on weighted gene co-expression network analysis (WGCNA). Similarly, the core genes in response to salt were also characterized using the above methods. Finally, 15 candidate genes, particularly two TFs (Sobic.004G300300, HD-ZIP; Sobic.003G244100, bZIP), involved in combined drought and salt resistance of sorghum were identified. CONCLUSIONS: In summary, the findings in this study help clarify the molecular mechanisms of sorghum responding to drought and salt. We identified candidate genes and provide important genetic resource for potential development of drought-tolerant and salt-tolerant sorghum plants.

Value of circulating tumor cell assisting low-dose computed tomography in screening pulmonary nodules based on existing liquid biopsy techniques: a systematic review with meta-analysis and trial sequential analysis.

OBJECTIVE: This study aims to assess the diagnostic utility of circulating tumor cells (CTCs) in conjunction with low-dose computed tomography (LDCT) for differentiating between benign and malignant pulmonary nodules and to substantiate the foundation for their integration into clinical practice. METHODS: A systematic literature review was performed independently by two researchers utilizing databases including PubMed, Web of Science, The Cochrane Library, Embase, and Medline, to collate studies up to September 15, 2023, that investigated the application of CTCs in diagnosing pulmonary nodules. A meta-analysis was executed employing Stata 15.0 and Revman 5.4 to calculate the pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curve (AUC). Additionally, trial sequential analysis was conducted using dedicated TSA software. RESULTS: The selection criteria identified 16 studies, encompassing a total of 3409 patients. The meta-analysis revealed that CTCs achieved a pooled sensitivity of 0.84 (95% CI 0.80 to 0.87), specificity of 0.80 (95% CI 0.73 to 0.86), PLR of 4.23 (95% CI 3.12 to 5.72), NLR of 0.20 (95% CI 0.16 to 0.25), DOR of 20.92 (95% CI 13.52 to 32.36), and AUC of 0.89 (95% CI 0.86 to 0.93). CONCLUSIONS: Circulating tumor cells demonstrate substantial diagnostic accuracy in distinguishing benign from malignant pulmonary nodules. The incorporation of CTCs into the diagnostic protocol can significantly augment the diagnostic efficacy of LDCT in screening for malignant lung diseases.

Multiparametric Brain Hemodynamics Imaging Using a Combined Ultrafast Ultrasound and Photoacoustic System.

Studying brain-wide hemodynamic responses to different stimuli at high spatiotemporal resolutions can help gain new insights into the mechanisms of neuro- diseases and -disorders. Nonetheless, this task is challenging, primarily due to the complexity of neurovascular coupling, which encompasses interdependent hemodynamic parameters including cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral oxygen saturation (SO2). The current brain imaging technologies exhibit inherent limitations in resolution, sensitivity, and imaging depth, restricting their capacity to comprehensively capture the intricacies of cerebral functions. To address this, a multimodal functional ultrasound and photoacoustic (fUSPA) imaging platform is reported, which integrates ultrafast ultrasound and multispectral photoacoustic imaging methods in a compact head-mountable device, to quantitatively map individual dynamics of CBV, CBF, and SO2 as well as contrast agent enhanced brain imaging at high spatiotemporal resolutions. Following systematic characterization, the fUSPA system is applied to study brain-wide cerebrovascular reactivity (CVR) at single-vessel resolution via relative changes in CBV, CBF, and SO2 in response to hypercapnia stimulation. These results show that cortical veins and arteries exhibit differences in CVR in the stimulated state and consistent anti-correlation in CBV oscillations during the resting state, demonstrating the multiparametric fUSPA system's unique capabilities in investigating complex mechanisms of brain functions.