Effects of Hypertension on Alzheimer's Disease: Updates in Pathophysiological and Neuroimaging Findings.

Alzheimer's disease (AD) is recognized as the leading cause of dementia, imposing a significant economic toll on society. Despite the emergence of novel therapeutic approaches for AD, their efficacy and safety mandates further validation through rigorous clinical trials. In this context, hypertension (HTN) has garnered considerable attention as an amendable risk factor for AD. Research indicates that hypertension during midlife is associated with an elevated risk of AD in later years, influencing both the onset and progression of the disease. Nevertheless, the relationship between AD and hypertension in the later stages of life remains a subject of debate. Moreover, the consequences of blood pressure reduction on cognitive function, along with the optimal pharmacological interventions and therapeutic thresholds for hypertension, have emerged as pivotal areas of inquiry. This review synthesizes findings on epidemiology, neuroimaging, and biomarkers, and the effects of antihypertensive medications to elucidate the link between hypertension and cognitive performance. We particularly investigate how hypertension and AD are related by plasma sulfide dysregulation, offering possible indicators for future diagnosis and therapy.

Developing and validating a predictive model of delivering large-for-gestational-age infants among women with gestational diabetes mellitus.

BACKGROUND: The birth of large-for-gestational-age (LGA) infants is associated with many short-term adverse pregnancy outcomes. It has been observed that the proportion of LGA infants born to pregnant women with gestational diabetes mellitus (GDM) is significantly higher than that born to healthy pregnant women. However, traditional methods for the diagnosis of LGA have limitations. Therefore, this study aims to establish a predictive model that can effectively identify women with GDM who are at risk of delivering LGA infants. AIM: To develop and validate a nomogram prediction model of delivering LGA infants among pregnant women with GDM, and provide strategies for the effective prevention and timely intervention of LGA. METHODS: The multivariable prediction model was developed by carrying out the following steps. First, the variables that were associated with LGA risk in pregnant women with GDM were screened by univariate analyses, for which the P value was < 0.10. Subsequently, Least Absolute Shrinkage and Selection Operator regression was fit using ten cross-validations, and the optimal combination factors were selected by choosing lambda 1se as the criterion. The final predictors were determined by multiple backward stepwise logistic regression analysis, in which only the independent variables were associated with LGA risk, with a P value < 0.05. Finally, a risk prediction model was established and subsequently evaluated by using area under the receiver operating characteristic curve, calibration curve and decision curve analyses. RESULTS: After using a multistep screening method, we establish a predictive model. Several risk factors for delivering an LGA infant were identified (P < 0.01), including weight gain during pregnancy, parity, triglyceride-glucose index, free tetraiodothyronine level, abdominal circumference, alanine transaminase-aspartate aminotransferase ratio and weight at 24 gestational weeks. The nomogram's prediction ability was supported by the area under the curve (0.703, 0.709, and 0.699 for the training cohort, validation cohort, and test cohort, respectively). The calibration curves of the three cohorts displayed good agreement. The decision curve showed that the use of the 10%-60% threshold for identifying pregnant women with GDM who are at risk of delivering an LGA infant would result in a positive net benefit. CONCLUSION: Our nomogram incorporated easily accessible risk factors, facilitating individualized prediction of pregnant women with GDM who are likely to deliver an LGA infant.

Nanoporous Titanium Implant Surface Accelerates Osteogenesis via the Piezo1/Acetyl-CoA/ß-Catenin Pathway.

Osseointegration is the most important factor determining implant success. The surface modification of TiO2 nanotubes prepared by anodic oxidation has remarkable advantages in promoting bone formation. However, the mechanism behind this phenomenon is still unintelligible. Here we show that the nanomorphology exhibited open and clean nanotube structure and strong hydrophilicity, and the nanomorphology significantly facilitated the adhesion, proliferation, and osteogenesis differentiation of stem cells. Exploring the mechanism, we found that the nanomorphology can enhance mitochondrial oxidative phosphorylation (OxPhos) by activating Piezo1 and increasing intracellular Ca2+. The increase in OxPhos can significantly uplift the level of acetyl-CoA in the cytoplasm but not significantly raise the level of acetyl-CoA in the nucleus, which was beneficial for the acetylation and stability of ß-catenin and ultimately promoted osteogenesis. This study provides a new interpretation for the regulatory mechanism of stem cell osteogenesis by nanomorphology.

Diagnostic potential of TSH to HDL cholesterol ratio in vulnerable carotid plaque identification.

Objective: This study aimed to investigate the predictive value of the thyroid-stimulating hormone to high-density lipoprotein cholesterol ratio (THR) in identifying specific vulnerable carotid artery plaques. Methods: In this retrospective analysis, we included 76 patients with carotid plaques who met the criteria for admission to Zhejiang Hospital from July 2019 to June 2021. High-resolution magnetic resonance imaging (HRMRI) and the MRI-PlaqueView vascular plaque imaging diagnostic system were utilized to analyze carotid artery images for the identification of specific plaque components, including the lipid core (LC), fibrous cap (FC), and intraplaque hemorrhage (IPH), and recording of the area percentage of LC and IPH, as well as the thickness of FC. Patients were categorized into stable plaque and vulnerable plaque groups based on diagnostic criteria for vulnerable plaques derived from imaging. Plaques were categorized based on meeting one of the following consensus criteria for vulnerability: lipid core area over 40% of total plaque area, fibrous cap thickness less than 65 um, or the presence of intraplaque hemorrhage. Plaques meeting the above criteria were designated as the LC-associated vulnerable plaque group, the IPH-associated group, and the FC-associated group. Multivariate logistic regression was employed to analyze the factors influencing carotid vulnerable plaques and specific vulnerable plaque components. Receiver operating characteristic (ROC) curves were used to assess the predictive value of serological indices for vulnerable carotid plaques. Results: We found that THR (OR = 1.976; 95% CI = 1.094-3.570; p = 0.024) and TSH (OR = 1.939, 95% CI = 1.122-3.350, p = 0.018) contributed to the formation of vulnerable carotid plaques. THR exhibited an area under the curve (AUC) of 0.704 (95% CI = 0.588-0.803) (p = 0.003), and the AUC for TSH was 0.681 (95% CI = 0.564-0.783) (p = 0.008). THR was identified as an independent predictor of LC-associated vulnerable plaques (OR = 2.117, 95% CI = 1.064-4.212, p = 0.033), yielding an AUC of 0.815. THR also demonstrated diagnostic efficacy for LC-associated vulnerable plaques. Conclusion: This study substantiated that THR and TSH have predictive value for identifying vulnerable carotid plaques, with THR proving to be a more effective diagnostic indicator than TSH. THR also exhibited predictive value and specificity in the context of LC-associated vulnerable plaques. These findings suggest that THR may be a promising clinical indicator, outperforming TSH in detecting specific vulnerable carotid plaques.

Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field.

Acetaminophen (APAP), the most frequently used mild analgesic and antipyretic drug worldwide, is implicated in causing 46% of all acute liver failures in the USA and between 40% and 70% in Europe. The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine (NAC); however, its efficacy is limited in cases of advanced liver injury or when administered at a late stage. In the current study, we discovered that treatment with a moderate intensity static magnetic field (SMF) notably reduced the mortality rate in mice subjected to high-dose APAP from 40% to 0%, proving effective at both the initial liver injury stage and the subsequent recovery stage. During the early phase of liver injury, SMF markedly reduced APAP-induced oxidative stress, free radicals, and liver damage, resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione (GSH). During the later stage of liver recovery, application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation. Moreover, the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery, even 24 h post overdose, when the effectiveness of NAC alone substantially declines. Overall, this study provides a non-invasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose. Of note, this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP, and potentially other toxic overdoses.

Inhibition of NKCC1 Ameliorates Anxiety and Autistic Behaviors Induced by Maternal Immune Activation in Mice.

Autism spectrum disorder (ASD) is thought to result from susceptibility genotypes and environmental risk factors. The offspring of women who experience pregnancy infection have an increased risk for autism. Maternal immune activation (MIA) in pregnant animals produces offspring with autistic behaviors, making MIA a useful model for autism. However, how MIA causes autistic behaviors in offspring is not fully understood. Here, we show that NKCC1 is critical for mediating autistic behaviors in MIA offspring. We confirmed that MIA induced by poly(I:C) infection during pregnancy leads to autistic behaviors in offspring. We further demonstrated that MIA offspring showed significant microglia activation, excessive dendritic spines, and narrow postsynaptic density (PSD) in their prefrontal cortex (PFC). Then, we discovered that these abnormalities may be caused by overexpression of NKCC1 in MIA offspring's PFCs. Finally, we ameliorated the autistic behaviors using PFC microinjection of NKCC1 inhibitor bumetanide (BTN) in MIA offspring. Our findings may shed new light on the pathological mechanisms for autism caused by pregnancy infection.

The protective effect of social support on all-cause and cardio-cerebrovascular mortality among middle-aged and older adults in the US.

The relationship between social support and mortality, especially cardio-cerebrovascular mortality, still has some limitations in the assessment of social support, sample selection bias, and short follow-up time. We used the data from 2005 to 2008 National Health and Nutrition Examination Survey to examine this relationship. The study analyzed a total of 6776 participants, divided into Group 1, Group 2, and Group 3 according to the social support score (0-1; 2-3; 4-5). Multivariable adjusted COX regression analyses of our study showed that Group 3 and Group 2 had a reduced risk of all-cause and cardio-cerebrovascular mortality (Group 3 vs 1, HR: 0.55, P < 0.001; HR: 0.4, P < 0.001; Group 2 vs 1, HR: 0.77, P = 0.017; HR: 0.58, P = 0.014) compared with Group 1. The same results were observed after excluding those who died in a relatively short time. Additionally, having more close friends, being married or living as married, and enough attending religious services were significantly related to a lower risk of mortality after adjustment. In brief, adequate social support is beneficial in reducing the risk of all-cause mortality and cardio-cerebrovascular mortality in middle-aged and older adults, especially in terms of attending religious services frequency, the number of close friends, and marital status.

Urinary-derived extracellular vesicle microRNAs as non-invasive diagnostic biomarkers for early-stage renal cell carcinoma.

BACKGROUND AND AIMS: The potential of urinary-derived extracellular vesicle (uEV) microRNAs (miRNAs) as noninvasive molecular biomarkers for identifying early-stage renal cell carcinoma (RCC) patients is rarely explored. The present study aims to explore the possibility of uEV miRNAs as novel molecular biomarkers for distinguishing early-stage RCC. MATERIALS AND METHODS: uEVs were extracted by ExoQuick-TC™ kit and miRNA concentrations were measured by RT-qPCR. ROC curves and bioinformatics analysis were employed to predict the diagnostic efficacy and regulatory mechanisms of dysregulated miRNAs. RESULTS: Through a multiphase case-control study on uEV miRNAs screening, training, and validation in RCC cells (ACHN, Caki-1) and control cells (HK-2) and in uEVs of 125 RCC patients and 128 age- and sex-matched controls, we successfully identified four uEVs miRNAs (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) were significantly and stably upregulated in RCC in vitro and in vivo. When adjusted with estimated glomerular filtration rate (eGFR), the AUC of the three-uEV miRNA panel (miR-135b-5p, miR-200c-3p, and miR-203a-3p) was 0.785 (95 % CI = 0.729-0.842, P < 0.0001) for discriminating RCC patients from controls. Notably, this panel exhibited similar performance in distinguishing early-stage (stage Ⅰ) RCC patients, with an AUC of 0.786 (95 %CI = 0.727-0.844, P < 0.0001). Bioinformatics analysis predicted that candidate miRNAs were involved in cancer progressing. CONCLUSION: Our study identified a four uEV miRNAs panel (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) may serve as an auxiliary noninvasive indication of early-stage RCC.

Clinical evaluation of ventilation mode on acute exacerbation of chronic obstructive pulmonary disease with respiratory failure.

BACKGROUND: At present, understanding of the most effective ventilation methods for treating chronic obstructive pulmonary disease (COPD) patients experiencing acute worsening symptoms and respiratory failure remains relatively limited. This report analyzed the efficiency and side effects of various ventilation techniques used for individuals experiencing an acute COPD exacerbation. AIM: To determine whether pressure-controlled ventilation (PCV) can lower peak airway pressures (PAPs) and reduce the incidence of barotrauma compared to volume-controlled ventilation (VCV), without compromising clinical outcomes and oxygenation parameters. METHODS: We have evaluated 600 patients who were hospitalized due to a severe COPD exacerbation, with 400 receiving mechanical ventilation for the respiratory failure. The participants were divided into two different groups, who were administered either VCV or PCV, along with appropriate management. We thereafter observed patients' attributes, clinical factors, and laboratory, radiographic, and arterial blood gas evaluations at the start and during their stay in the intensive care unit (ICU). We have also employed appropriate statistical methods for the data analysis. RESULTS: Both the VCV and PCV groups experienced significant enhancements in the respiratory rate, tidal volume, and arterial blood gas values during their time in the ICU. However, no significant distinctions were detected between the groups in terms of oxygenation indices (partial pressures of oxygen/raction of inspired oxygen ratio) and partial pressures of carbon dioxide improvements. There was no considerable disparity observed between the VCV and PCV groups in the hospital mortality (32% vs 28%, P = 0.53), the number of days of ICU stay [median interquartile range (IQR): 9 (6-14) d vs 8 (5-13) d, P = 0.41], or the duration of the mechanical ventilation [median (IQR): 6 (4-10) d vs 5 (3-9) d, P = 0.47]. The PCV group displayed lower PAPs compared to the VCV group (P < 0.05) from the beginning of mechanical ventilation until extubation or ICU departure. The occurrence of barotrauma was considerably lower in the PCV group in comparison to the VCV group (6% vs 16%, P = 0.03). CONCLUSION: Both VCV and PCV were found to be effective in treating patients with acute COPD exacerbation. However, PCV was associated with lower PAPs and a significant decrease in barotrauma, thus indicating that it might be a safer ventilation method for this group of patients. However, further large-scale study is necessary to confirm these findings and to identify the best ventilation approach for patients experiencing an acute COPD exacerbation.

Rescuing "hopeless" avulsed teeth using autologous platelet-rich fibrin following delayed reimplantation: Two case reports.

BACKGROUND: Tooth avulsion is one of the most severe types of dental trauma. Most avulsed teeth undergo long-term ankylosis and replacement resorption after delayed reimplantation and exhibit a poor prognosis. The aim of this work was to improve the success rate of avulsed teeth after delayed reimplantation using autologous platelet-rich fibrin (PRF). CASE SUMMARY: Case 1 was a 14-year-old boy who fell and knocked out his left upper central incisor 18 h prior to his arrival at the department. The diagnoses were avulsion of tooth 21, lateral luxation of tooth 11 and alveolar fracture of teeth 11 and 21. In case 2, a 17-year-old boy fell 2 h prior to his presentation to the hospital, and his left upper lateral incisor was completely knocked out of the alveolar socket. The diagnoses included avulsion of tooth 22, complicated crown fracture of tooth 11 and complicated crown-root fracture of tooth 21. The avulsed teeth were reimplanted along with autologous PRF granules and splinted using a semiflexible titanium preshaped labial arch. The root canals of the avulsed teeth were filled with calcium hydroxide paste, and root canal filling was performed 4 wk after reimplantation. The reimplanted teeth showed no symptoms of inflammatory root resorption or ankylosis at the 3-, 6-, and 12-mo follow-up examinations after reimplantation with autologous PRF. In addition to the avulsed teeth, the other injured teeth were treated using corresponding conventional treatment methods. CONCLUSION: These cases provide examples of the successful use of PRF to reduce pathological root resorption of the avulsed teeth, and the application of PRF may provide new healing opportunities for traditionally "hopeless" avulsed teeth.

Detecting vulnerable carotid plaque and its component characteristics: Progress in related imaging techniques.

Carotid atherosclerotic plaque rupture and thrombosis are independent risk factors for acute ischemic cerebrovascular disease. Timely identification of vulnerable plaque can help prevent stroke and provide evidence for clinical treatment. Advanced invasive and non-invasive imaging modalities such as computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy can be employed to image and classify carotid atherosclerotic plaques to provide clinically relevant predictors used for patient risk stratification. This study compares existing clinical imaging methods, and the advantages and limitations of different imaging techniques for identifying vulnerable carotid plaque are reviewed to effectively prevent and treat cerebrovascular diseases.

Increased serum piwi-interacting RNAs as a novel potential diagnostic tool for brucellosis.

Background: Piwi-interacting RNAs (piRNAs) have emerged as potential novel indicators for various diseases; however, their diagnostic value for brucellosis remains unclear. This study aimed to evaluate the diagnostic potential of altered serum piRNAs in patients with brucellosis. Methods: Illumina sequencing via synthesis (SBS) technology was used to screen the serum piRNA profile in brucellosis patients, and markedly dysregulated piRNAs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) assay in two sets from a cohort of 73 brucellosis patients and 65 controls. Results: Illumina SBS technology results showed that seven piRNAs were markedly elevated in brucellosis patients compared to normal controls. The seven upregulated piRNAs were further validated individually by qRT-PCR, of which three piRNAs (piR-000753, piR-001312, and piR-016742) were confirmed to be significantly and steadily increased in the patients (> 2-fold, P < 0.01). The area under the receiver operating characteristic (ROC) curve (AUCs) for the three piRNAs ranged from 0.698 to 0.783. The AUC for the three piRNAs combination was 0.772, with a specificity of 86% and a positive predictive value of 90%, respectively. Conclusions: The three-piRNA panel identified in this study has potential as a novel blood-based auxiliary tool for brucellosis detection.

Occurrence of Intracranial Hemorrhage and Associated Risk Factors in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is thought to be a rare but probably underestimated presentation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We conducted a systematic review and meta-analysis with the aim of comprehensively revealing the occurrence of ICH in patients with CADASIL. METHODS: English-language studies published up to September 30, 2021 were searched for in the MEDLINE (PubMed), Web of Science, and Cochrane Library databases. The design, patient characteristics, occurrence rate of ICH, and associated risk factors were retrieved for each identified relevant study. RESULTS: We enrolled 13 studies in the final meta-analysis, which included 1,310 patients with CADASIL. The probability of ICH occurrence in patients with CADASIL was 10.1% (95% confidence interval [CI]=5.6%-18.0%, I²=85.1%). When stratified by geographic region, the occurrence rate of ICH was much higher in Asians (17.7%; 95% CI=11.0%-28.5%, I²=76.3%) than in Europeans (2.0%; 95% CI=0.4%-10.8%, I²=82.8%). A higher burden of cerebral microbleeds (CMBs) and a history of hypertension were the most commonly recorded risk factors for ICH, which were available for three and two of the included studies, respectively. CONCLUSIONS: Our study suggests that ICH is an important clinical manifestation of CADASIL, especially in Asians. A higher burden of CMBs and the existence of hypertension were found to be associated with a higher probability of ICH occurrence in patients with CADASIL.

miRNAs from Plasma Extracellular Vesicles Are Signatory Noninvasive Prognostic Biomarkers against Atherosclerosis in LDLr-/-Mice.

Circular microRNAs (miRNAs) have become central in pathophysiological conditions of atherosclerosis (AS). However, the biomarkers for diagnosis and therapeutics against AS are still unclear. The atherosclerosis models in low-density lipoprotein receptor deficiency (LDLr-/-) mice were established with a high-fat diet (HFD). The extraction kit isolated extracellular vesicles from plasma. Total RNAs were extracted from LDLr-/- mice in plasma extracellular vesicles. Significantly varying miRNAs were detected by employing Illumina HiSeq 2000 deep sequencing technology. Target gene predictions of miRNAs were employed by related software that include RNAhybrid, TargetScan, miRanda, and PITA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) further analyzed the intersection points of predicted results. The results showed that the HFD group gradually formed atherosclerotic plaques in thoracic aorta compared with the control group. Out of 17, 8 upregulated and 9 downregulated miRNAs with a significant difference were found in the plasma extracellular vesicles that were further cross-examined by sequencing and bioinformatics analysis. Focal adhesion and Ras signaling pathway were found to be the most closely related pathways through GO and KEGG pathway analyses. The 8 most differentially expressed up- and downregulated miRNAs were further ascertained by TaqMan-based qRT-PCR. TaqMan-based qRT-PCR and in situ hybridization further validated the most differentially expressed miRNAs (miR-378d, miR-181b-5p, miR-146a-5p, miR-421-3p, miR-350-3p, and miR-184-3p) that were consistent with deep sequencing analysis suggesting a promising potential of utility to serve as diagnostic biomarkers against AS. The study gives a comprehensive profile of circular miRNAs in atherosclerosis and may pave the way for identifying biomarkers and novel targets for atherosclerosis.

Engineered Chimeric Peptides with IGF-1 and Titanium-Binding Functions to Enhance Osteogenic Differentiation In Vitro under T2DM Condition.

Due to the complexity of the biomolecules and titanium (Ti) combination, it is a challenge to modify the implant surface with biological cytokines. The study proposed a new method for immobilizing cytokines on implant surface to solve the problem of low osseointegration under type 2 diabetes mellitus (T2DM) condition. This new modified protein that connected Ti-binding artificial aptamer minTBP-1 with Insulin-like growth factor I (IGF-I), had a special strong affinity with Ti and a therapeutic effect on diabetic bone loss. According to the copies of minTBP-1, three proteins were prepared, namely minTBP-1-IGF-1, 2minTBP-1-IGF-1 and 3minTBP-1-IGF-1. Compared with the other modified proteins, 3minTBP-1-IGF-1 adsorbed most on the Ti surface. Additionally, this biointerface demonstrated the most uniform state and the strongest hydrophilicity. In vitro results showed that the 3minTBP-1-IGF-1 significantly increased the adhesion, proliferation, and mineralization activity of osteoblasts under T2DM conditions when compared with the control group and the other modified IGF-1s groups. Real-time PCR assay results confirmed that 3minTBP-1-IGF-1 could effectively promote the expression of osteogenic genes, that is, ALP, BMP-2, OCN, OPG, and Runx2. All these data indicated that the 3minTBP-1-IGF-1 had the most efficacious effect in promoting osteoblasts osteogenesis in diabetic conditions, and may be a promising option for further clinical use.

Altered serum human cytomegalovirus microRNA levels are common and closely associated with the inflammatory status in patients with fever.

Background: Fever has a complicated etiology, and diagnosing its causative factor is clinically challenging. Human cytomegalovirus (HCMV) infection causes various diseases. However, the clinical relevance, prevalence, and significance of HCMV microRNAs (miRNA) in association with fever remain unclear. In the present study, we analyzed the HCMV miRNA expression pattern in the serum of patients with fever and evaluate its clinical associations with occult HCMV infection status in immune disorders. Methods: We included serum samples from 138 patients with fever and 151 age-gender-matched controls in this study. First, the serum levels of 24 HCMV miRNAs were determined using a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay in the training set. The markedly altered miRNAs were verified in the validation and testing sets. The serum HCMV IgG/IgM and DNA titers in the testing cohort were also assessed using enzyme-linked immunosorbent assay (ELISA) and RT-qPCR, respectively. Results: The majority of HCMV miRNAs were markedly upregulated in the serum of fever patients. We selected the five most significantly altered HCMV miRNAs: hcmv-miR-US4-3p, hcmv-miR-US29-3p, hcmv-miR-US5-2-3p, hcmv-miR-UL112-3p, and hcmv-miR-US33-3p for validation. These miRNAs were also significantly elevated in the serum of fever patients in the validation and testing sets compared with the controls. Logistic regression analysis revealed that the five miRNAs were novel potential risk factors for fever. Notably, the serum levels of four of the five confirmed HCMV miRNAs were significantly associated with blood C-reaction protein concentrations. Moreover, the five HCMV miRNA levels were closely correlated with the HCMV DNA titers in the testing cohort. Conclusion: HCMV infection and activation are common in fever patients and could be novel risk factors for fever. These differentially expressed HCMV miRNAs could enable HCMV activation status monitoring in immune disorders.

Hepatic Artery Infusion Pump Combined With Systemic Chemotherapy for Patients With Liver Metastases From Breast Carcinoma.

Background: When liver metastasis in patients with breast cancer is diagnosed, treatment is generally palliative and usually consists of systemic therapies only. This study aimed to evaluate the efficacy and safety of hepatic arterial infusion (HAI) combined with systemic chemotherapy in patients with breast carcinoma liver metastases (BCLM). Methods: From January 2012 to December 2019, HAI catheter systems were implanted under the guide of digital subtract angiography (DSA) in 19 patients with BCLM. All patients received systemic chemotherapy and HAI gemcitabine plus floxuridine (FUDR). Methods: The overall response rate (ORR) of intrahepatic lesions was 73.7%, including 2 patients (10.5%) with complete remission (CR) and 12 patients (63.2%) with partial remission (PR). Additionally, we found that young patients (age < 55 years) had a higher ORR than the older (100% vs 44.4%, P = .011). The median overall survival (mOS) was 13.1 months. Kaplan-Meier survival curves demonstrated that the mOS was not significantly different between patients with < 9 intrahepatic lesions and those with ≥ 9 lesions (13.7 months vs 10.9 months, P = .225). The mOS was 14.3 and 10.6 months for patients without extrahepatic metastases and with extrahepatic metastases, respectively (P = .016). None of the patients had grade 4 toxicity. The grade 3 toxicities included leucopenia, neutropenia and diarrhea. Conclusions: HAI gemcitabine plus FUDR combined with systemic chemotherapy is effective in achieving a high local response and prolonging mOS for patients with BCLM and is associated with a relatively low rate of toxicity.

Evaluation of diagnostic and predictive values of the serum VEGF-A level and systemic immune-inflammation index in small cell lung cancer.

Purpose: To evaluate diagnostic and predictive values of the serum vascular endothelial growth factor-A (VEGF-A) level and systemic immune-inflammation index (SII) in small cell lung cancer (SCLC) patients. Methods: From January 2018 to April 2020, we prospectively enrolled 59 untreated SCLC patients in the study group and 50 non-neoplastic patients in the control group. Blood samples were collected at baseline, after the first two cycles of chemotherapy and at progression in the study group and at entry in the control group. Serum VEGF-A was measured by chemiluminescence, SII was calculated based on complete blood count results, and the relationship between the VEGF-A/SII and clinicopathological characteristics, chemotherapeutic efficacy and progression-free survival (PFS) of SCLC patients was analyzed. Results: Baseline serum VEGF-A was significantly higher in SCLC patients than in non-neoplastic patients (P<0.001), while baseline SII was not (P=0.114). There was no correlation between baseline VEGF-A and SII in SCLC patients (P=0.123); however, there was a significant correlation between baseline VEGF-A and disease stage and central nervous system (CNS) metastasis (P=0.021 and P=0.012, respectively), as well as between baseline SII and disease stage and liver metastasis (P=0.026 and P=0.018, respectively). Serum VEGF-A was significantly lower than the pretreatment level after 2 cycles of treatment (P=0.049) but was not different at progression (P=0.247). Baseline VEGF-A was correlated with the treatment response of first-line chemotherapy (P=0.001), while baseline SII was not (P=0.392). Kaplan-Meier survival analysis suggested that the PFS of first-line chemotherapy was significantly longer in the low-VEGF-A group at baseline than the high-VEGF-A group (11.37 vs. 6.17 months, P<0.001). There was a trend toward longer PFS of first-line chemotherapy in the low-SII group at baseline than the high-SII group, but the difference was not significant (12.10 vs. 9.10 months, P>0.050). Univariate and multivariate Cox regression analyses suggested that baseline VEGF-A (HR: 3.443, 95% CI: 1.330-8.908, P=0.011) was an independent prognostic factor for PFS in SCLC patients. Conclusions: Baseline serum VEGF-A and SII are associated with important clinicopathological characteristics of SCLC patients. VEGF-A, but not SII, has the ability of diagnosis and predicting first-line chemotherapeutic efficacy and prognosis in SCLC patients.

Study of aerodynamic focusing lens stacks (ALS) for long focal length aerosol-assisted focused chemical vapor deposition (AAFCVD).

Mask-free direct printing can alleviate the high cost and high consumption involved in photo-lithography for chip processing. Most of their technical routes are based on the traditional short focal length nozzles, which is suffered from higher probability of nozzle retardation or clogging as well as the higher mechanical burdens. While aerosol-assisted chemical vapor deposition (AACVD) has better deposition adaptability but usually lack of focused printing. In this study, a system that combines of long focal length ALS with AACVD, so called AAFCVD printing system has been developed. The single-point printing capability and aerosol precursor adaptability were verified, and the relationship between the single spot printing performance and the chemical reaction mechanisms were studied. Furthermore, a unique carbon injection effect brought by ALS was discovered. Finally, the linear graphics printing performances of the system were evaluated. This system is expected to become a new generation of high-performance mask-free printing system for chip manufacturing.