Phenotypic and functional characterizations of CD8+ T cell populations in malignant pleural effusion.

Malignant pleural effusions (MPE) are a common terminal pathway for many types of cancer, especially non-small cell lung cancer (NSCLC). However, the phenotype and differentiation status of MPE-infiltrating CD8+ T cells have not yet been systematically addressed. In this study, the surface molecules and cytokine secretion of T cells in MPE and peripheral blood (PB) were analyzed using flow cytometry. We found an increased frequency of CD8+ T cells in MPE compared to PB among lung cancer patients, of which the effector memory subset (Tem, CCR7- CD45RA-) and central memory subset (Tcm, CCR7+ CD45RA-) were upregulated. MPE-derived Tem and Tcm subsets expressed more PD1 or CD39, and there was a greater population of cells in these subsets that co-expressed them. In addition, Tem and Tcm cells from MPE had higher cytokine production than terminally differentiated effector memory cells (TemRA, CCR7- CD45RA+) and naïve cells (Tnaive, CCR7+CD45RA+). Our results demonstrate that the Tem and Tcm cells in MPE may have advantages in both tumor reactivity and immune functionality. Altogether, these findings help to characterize the phenotype of MPE-derived CD8+ T cells in terms of differentiation and tumor reactivity and reveal their potential as a target for immunotherapy.

Risk Factors and Impact on Outcomes of Lung Cancer Patients Concurrent with Deep Vein Thrombosis.

PURPOSE: Many investigations on prognostic factors in lung cancer have been conducted; however, little is known regarding the outcomes of lung cancer cases complicated by deep vein thrombosis (DVT). This study aimed to determine the risk factors and impact on outcomes of lung cancer patients concurrent with DVT. METHODS: Lung cancer patients who underwent lower-extremity venous ultrasound were enrolled in this study. The patients were divided into a DVT group and a non-DVT group. Demographic information, clinical characteristics, and survival were analyzed by t-test, Wilcoxon test, chi-squared test, and logistic regression analysis. RESULTS: Of the 160 enrolled lung cancer patients, DVT was detected in 30 patients. Among the DVT group, adenocarcinoma was the most common histological type (27/30, 90.00%). Lung cancer complicated with DVT was associated with advanced stage, more severe myocardial injury, and a hypercoagulable state (P < .05). Differences in driver genes between the two groups were not significant. Radiologically, lung cancer patients with DVT were more likely to present with pericardial effusion and pleural effusion than patients without DVT (P < .05). Following multivariable logistic regression analysis, advanced stage (OR 5.368, [95%CI 1.871-18.165], P = .021), NT-proBNP >300 pg/ml (OR 5.575, [95%CI 1.733-3.722], P = .018), D-dimer >5 mg/L (OR 8.449, [95%CI 4.323-18.536], P = .004), CRP >12 mg/L (OR 6.687, [95%CI 1.967-13.617], P = .010), and serum CEA >25 ng/ml (OR 4.755, [95%CI 1.358-3.123], P = .029) were independent risk factors for adenocarcinoma complicated with DVT. Finally, survival analysis revealed that the occurrence of DVT resulted in a poorer prognosis despite anticoagulant therapy (P < .05). CONCLUSION: DVT is a potential complication in patients with lung adenocarcinoma and could represent a prognostic marker for unfavorable outcome. It is essential to screen for DVT in high-risk adenocarcinoma patients.

A novel and effective approach to generate germline-like monoclonal antibodies by integration of phage and mammalian cell display platforms.

Phage display technology allows for rapid selection of antibodies from the large repertoire of human antibody fragments displayed on phages. However, antibody fragments should be converted to IgG for biological characterizations and affinity of antibodies obtained from phage display library is frequently not sufficient for efficient use in clinical settings. Here, we describe a new approach that combines phage and mammalian cell display, enabling simultaneous affinity screening of full-length IgG antibodies. Using this strategy, we successfully obtained a novel germline-like anti-TIM-3 monoclonal antibody named m101, which was revealed to be a potent anti-TIM-3 therapeutic monoclonal antibody via in vitro and in vivo experiments, indicating its effectiveness and power. Thus, this platform can help develop new monoclonal antibody therapeutics with high affinity and low immunogenicity.

Intermediate risk pulmonary embolism concomitant with or without lung cancer: a wide spectrum of features.

OBJECTIVES: We aimed to investigate the differences in clinical features between pulmonary embolism (PE) patients concomitant with lung cancer and without lung cancer (LC) and gain further understanding of the impact of lung cancer on pulmonary embolism. METHODS: This retrospective study sampled 114 patients diagnosed with pulmonary embolism from January 2017 to April 2021 in the First Affiliated Hospital of Soochow University. The patients were categorized into the LC group (n = 22) or non-LC group (n = 92). Myocardial injury, coagulation and blood cell parameters, along with imaging findings, were analyzed for the two groups. The primary outcome measure was the 90-day mortality. RESULTS: Of the 114 patients with pulmonary embolism in the present study, the 90 intermediate-risk patients were enrolled for further investigations. Compared to the non-LC group, patients in the LC group had milder myocardial injury, more severe coagulation function disorder, a higher incidence of central PE and a smaller change in diameter of the main pulmonary artery. We found that the occurrence of pericardial effusion created the risk of lung cancer in patients with pulmonary embolism, but there was no increase in the 90-day mortality for non-LC group versus LC group. CONCLUSION: Intermediate risk PE patients concomitant with lung cancer seem to be more likely to present specific clinical features, accordingly, clinicians must pay great attention to PE patients concomitant with lung cancer and implement effective treatments to simultaneously manage the two conditions.

Metformin Preserves VE-Cadherin in Choroid Plexus and Attenuates Hydrocephalus via VEGF/VEGFR2/p-Src in an Intraventricular Hemorrhage Rat Model.

Hydrocephalus induced by intraventricular hemorrhage (IVH) is associated with unfavorable prognosis. The increased permeability of choroid plexus and breakdown of the blood-brain barrier (BBB) was reported as a prominent mechanism of IVH-induced hydrocephalus, and vascular endothelial-cadherin (VE-cadherin) was demonstrated to be relevant. Metformin was reported to protect endothelial junction and preserve permeability widely; however, its role in hydrocephalus remains unclear. In this study, the decreased expression of VE-cadherin in the choroid plexus, accompanied with ventricle dilation, was investigated in an IVH rat model induced by intraventricular injection of autologous blood. Metformin treatment ameliorated hydrocephalus and upregulated VE-cadherin expression in choroid plexus meanwhile. We then observed that the internalization of VE-cadherin caused by the activation of vascular endothelial growth factor (VEGF) signaling after IVH was related to the occurrence of hydrocephalus, whereas it can be reversed by metformin treatment. Restraining VEGF signaling by antagonizing VEGFR2 or inhibiting Src phosphorylation increased the expression of VE-cadherin and decreased the severity of hydrocephalus after IVH. Our study demonstrated that the internalization of VE-cadherin via the activation of VEGF signaling may contribute to IVH-induced hydrocephalus, and metformin may be a potential protector via suppressing this pathway.

Rapid Elimination of Broadly Neutralizing Antibodies Correlates with Treatment Failure in the Acute Phase of Simian-Human Immunodeficiency Virus Infection.

Early human immunodeficiency virus type 1 (HIV-1) treatment during the acute period of infection can significantly limit the seeding of viral reservoirs and modify the course of disease. However, while a number of HIV-1 broadly neutralizing antibodies (bnAbs) have demonstrated remarkable efficacy as prophylaxis in macaques chronically infected with simian-human immunodeficiency virus (SHIV), intriguingly, their inhibitory effects were largely attenuated in the acute period of SHIV infection. To investigate the mechanism for the disparate performance of bnAbs in different periods of SHIV infection, we used LSEVh-LS-F, a bispecific bnAb targeting the CD4 binding site and CD4-induced epitopes, as a representative bnAb and assessed its potential therapeutic benefit in controlling virus replication in acutely or chronically SHIV-infected macaques. We found that a single infusion of LSEVh-LS-F resulted in rapid decline of plasma viral loads to undetectable levels without emergence of viral resistance in the chronically infected macaques. In contrast, the inhibitory effect was robust but transient in the acutely infected macaques, despite the fact that all macaques had comparable plasma viral loads initially. Infusing multiple doses of LSEVh-LS-F did not extend its inhibitory duration. Furthermore, the pharmacokinetics of the infused LSEVh-LS-F in the acutely SHIV-infected macaques significantly differed from that in the uninfected or chronically infected macaques. Host SHIV-specific immune responses may play a role in the viremia-dependent pharmacokinetics. Our results highlight the correlation between the fast clearance of infused bnAbs and the treatment failure in the acute period of SHIV infection and may have important implications for the therapeutic use of bnAbs to treat acute HIV infections.IMPORTANCE Currently, there is no bnAb-based monotherapy that has been reported to clear the virus in the acute SHIV infection period. Since early HIV treatment is considered critical to restricting the establishment of viral reservoirs, investigation into the mechanism for treatment failure in acutely infected macaques would be important for the therapeutic use of bnAbs and eventually towards the functional cure of HIV/AIDS. Here we report the comparative study of the therapeutic efficacy of a bnAb in acutely and chronically SHIV-infected macaques. This study revealed the correlation between the fast clearance of infused bnAbs and treatment failure during the acute period of infection.

[Preparation and Photocatalytic Properties of Supported TiO2 Photocatalytic Material].

Titanium dioxide (TiO2) supported on spherical alumina substrate was prepared by using sol-gel method combined with dip-coating process. The surface morphology and structure of the synthesized samples were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD) pattern. The results show that the morphology of the supported TiO2 composite material was obviously different from that of the original support. It reveals a layer formed by anatase TiO2 nanoparticles of 10-20 nm was deposited on the alumina substrate. Energy dispersive X-ray spectroscopy (EDX) analyses on the spherical alumina substrate and the resulting TiO2 composite catalyst were performed to determine the TiO2 loading content in the samples. It indicates that the TiO2 loading content on alumina substrate could be effectively increased by increasing the times of dip-coating alumina support in TiO2 sol. When dip-coating times increased to 5, the TiO2 loading content increased from 3.8 Wt. % to 15.7 Wt. %. In addition, the photocatalytic performances of the supported TiO2 materials prepared by different dip-coating times have been investigated by degrading methylene blue. It was found that the surface morphology of the supported TiO2 material was not only improved, but also the photocatalytic activity could be promoted significantly by increasing the dip-coating times. When the alumina substrate was dip-coated in TiO2 sol from 1 to 4 times, the degradation rate of methylene blue increased from 40% to 83.1%. However, after dip-coating the alumina support in TiO2 sol for 5 times, the degradation of methylene blue was only up to 85.6%. This indicates that the photocatalytic activity increased slowly when the TiO2 content in the supported catalyst was up to some extent. It is attributed to the continuous dip-coating resulted in less opportunities and weak intensity of illumination for the TiO2 nano-particles that under lower layer. The photocatalytic activity was relatively stable after repeated use of the supported TiO2 material for 5 times.

Global trends and hotpots in standardised patients research in the last 30 years: A bibliometric analysis.

Background: The research trends regarding standardised patients(SPs) in the education of health professions students have not been systematically studied. Methods: All published literature on SPs from January 1994 to January 2024 in Web of Science was screened by two reviewers. Bibliometric analysis and knowledge mapping visualisation analysis were performed using Cite Space software. The country, institution, journal, keyword co-occurrence, and keyword emergence were visualised. Result: A total of 3259 records were analysed. The amount of relevant literature in the past 30 years showed an upward trend involving 109 disciplinary categories, with the United States dominating. The five central research teams were from the United States and Canada. Nursing education is increasingly using SPs, especially in advanced nursing practice. As for the hotspot and trend analysis, the results indicate that there is still continuous attention to the impact of applying standardised patients on improving the communication ability, competence and performance of medical students. Additionally, there is a growing interest in exploring the application of visual simulation or artificial intelligence in standardised patient-related research. Conclusions: Research on SPs' has received continued attention. To cater to the diverse requirements of education and clinical context, there is a need for further exploration of SPs utilisation. AI-relevant SPs might be a new alternative for various scenarios in the future.

Gas6/Axl signaling promotes hematoma resolution and motivates protective microglial responses after intracerebral hemorrhage in mice.

BACKGROUND: Intracerebral hemorrhage (ICH) stands out as the most fatal subtype of stroke, currently devoid of effective therapy. Recent research underscores the significance of Axl and its ligand growth arrest-specific 6 (Gas6) in normal brain function and a spectrum of neurological disorders, including ICH. This study is designed to delve into the role of Gas6/Axl signaling in facilitating hematoma clearance and neuroinflammation resolution following ICH. METHODS: Adult male C57BL/6 mice were randomly assigned to sham and ICH groups. ICH was induced by intrastriatal injection of autologous arterial blood. Recombinant mouse Gas6 (rmGas6) was administered intracerebroventricularly 30 min after ICH. Virus-induced knockdown of Axl or R428 (a selective inhibitor of Axl) treatment was administrated before ICH induction to investigate the protective mechanisms. Molecular changes were assessed using western blot, enzyme-linked immunosorbent assay and immunohistochemistry. Coronal brain slices, brain water content and neurobehavioral tests were employed to evaluate histological and neurofunctional outcomes, respectively. Primary glia cultures and erythrophagocytosis assays were applied for mechanistic studies. RESULTS: The expression of Axl increased at 12 h after ICH, peaking on day 3. Gas6 expression did not remarkably changed until day 3 post-ICH. Early administration of rmGas6 following ICH significantly reduced hematoma volume, mitigated brain edema, and restored neurological function. Both Axl-knockdown and Axl inhibitor treatment abolished the neuroprotection of exogenous Gas6 in ICH. In vitro studies demonstrated that microglia exhibited higher capacity for phagocytosing eryptotic erythrocytes compared to normal erythrocytes, a process reversed by blocking the externalized phosphatidylserine on eryptotic erythrocytes. The erythrophagocytosis by microglia was Axl-mediated and Gas6-dependent. Augmentation of Gas6/Axl signaling attenuated neuroinflammation and drove microglia towards pro-resolving phenotype. CONCLUSIONS: This study demonstrated the beneficial effects of recombinant Gas6 on hematoma resolution, alleviation of neuroinflammation, and neurofunctional recovery in an animal model of ICH. These effects were primarily mediated by the phagocytotic role of Axl expressed on microglia.

Imbalance of Circulating Monocyte Subsets in Subjects with Newly Emerged and Recurrent Hospital-Acquired Pneumonia.

OBJECTIVE: Hospital-acquired pneumonia (HAP) is one of the most common diseases in the intensive care unit, where the development of disease is closely related with the host immune response. Monocytes play an important role in both innate and adaptive immune system. We aimed to investigate the changes of circulating monocyte subsets in subjects with HAP to explore its value in monitoring HAP. METHODS: In total, 60 HAP patients and 18 healthy individuals were enrolled in this study. Human monocyte subsets are classified into 3 groups: nonclassical (NC), intermediate (ITM), and classical (CL). Also, programmed death ligand 1 (PD-L1) expression on circulating monocyte subsets was measured by flow cytometry. RESULTS: Data showed that the ratio of NC, ITM, and CL among monocytes was comparable between HAP patients and healthy controls (P > .05). There was a remarkable imbalance of NC and CL in newly emerged HAP compared to healthy controls (P < .05), subsequently reaching normalization in recurrent HAP (P > .05). Furthermore, although PD-L1 was seemly constitutively expressed by NC, ITM, and CL groups regardless of disease status, it was noted that PD-L1 was dominantly expressed in the CL group (P < .05). CONCLUSION: Given distinct PD-L1 expression, a shift of CL/NC in newly emerged HAP would constitute an inhibitory anti-pathogen immune response. Normalization of circulating monocyte subsets on recurrence of HAP might be the consequence of immune memory of bacterial infection.

Combined effect of cortical superficial siderosis and cerebral microbleed on short-term and long-term outcomes after intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Cortical superficial siderosis (cSS) and cerebral microbleed (CMB) have distinct effects on intracerebral haemorrhage (ICH). We aim to investigate the combined effect of cSS and CMB on outcomes after ICH. METHODS: Based on a single-centre stroke registry database, patients with spontaneous ICH who had CT scan within 48 hours after ictus and MRI subsequently were identified. Eligible patients were divided into four groups (cSS-CMB-, cSS-CMB+, cSS+CMB-, cSS+CMB+) according to cSS and CMB on susceptibility-weighted image of MRI. Primary outcomes were haematoma volume on admission and unfavourable outcome defined as modified Rankin Scale scores ≥3 at 3 months. Secondary outcomes were all-cause death, recurrence of stroke and ICH during follow-up (median follow-up 2.0 years, IQR 1.0-3.0 years). RESULTS: A total of 673 patients were identified from 1044 patients with spontaneous ICH. 131 (19.5%) had cSS and 468 (69.5%) had CMB. Patients with cSS+CMB+ had the highest rate of poor outcome at 3 months, as well as all-cause death, recurrent stroke and ICH during follow-up. In cSS- patients, CMB was associated with smaller haematoma (ß -0.13; 95% CI -0.22 to -0.03; p=0.009), but it still increased risks of recurrent ICH (OR 4.6; 95% CI 1.3 to 15.6; p=0.015) and stroke (OR 2.0; 95% CI 1.0 to 4.0; p=0.049). These effects of CMB became unremarkable in the context of cSS+. CONCLUSIONS: Patients with different combinations of cSS and CMB have distinct patterns of short-term and long-term outcomes. Although CMB is related to restrained haematoma, it does not improve long-term outcomes. TRIAL REGISTRATION NUMBER: NCT04803292.

Cortical superficial siderosis, hematoma volume, and outcomes after intracerebral hemorrhage: a mediation analysis.

Background: Previous studies have shown that cortical superficial siderosis (cSS) can increase hematoma volume and predict poor outcomes following primary intracerebral hemorrhage (ICH). Objective: We aimed to determine whether a large hematoma volume was the essential factor contributing to worse outcomes of cSS. Methods: Patients with spontaneous ICH underwent a CT scan within 48 h after ictus. Evaluation of cSS was performed using magnetic resonance imaging (MRI) within 7 days. The 90-day outcome was assessed using the modified Rankin Scale (mRS). In addition, we investigated the correlation between cSS, hematoma volume, and 90-day outcomes using multivariate regression and mediation analyses. Results: Among the 673 patients with ICH [mean (SD) age, 61 (13) years; 237 female subjects (35.2%); median (IQR) hematoma volume, 9.0 (3.0-17.6) ml], 131 (19.5%) had cSS. There was an association between cSS and larger hematoma volume (ß = 4.449, 95% CI 1.890-7.009, p < 0.001) independent of hematoma location and was also related to worse 90-day mRS (ß = 0.333, 95% CI 0.008-0.659, p = 0.045) in multivariable regression. In addition, mediation analyses revealed that hematoma volume was an essential factor mediating the effect of cSS on unfavorable 90-day outcomes (proportion mediated:66.04%, p = 0.01). Conclusion: Large hematoma volume was the major charge of directing cSS to worse outcomes in patients with mild to moderate ICH, and cSS was related to a larger hematoma in both lobar and non-lobar areas. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04803292, identifier: NCT04803292.

What Is the Efficacy of Short Length of Biliopancreatic Limb in One-Anastomosis Gastric Bypass? A Systematic Review and Meta-analysis of Short-Term Results.

OBJECTIVE: To systematically review the efficacy of short length of biliopancreatic limb (BPL) in laparoscopic one anastomosis gastric bypass (OAGB). METHODS: By thoroughly investigating in PubMed, Embase, and the Cochrane Library, each research containing the comparison between short BPL and 200-cm BPL was included, inception in July 2021. The research followed the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) recommendations. RESULT: A total of 1288 patients were included for meta-analysis. Results showed that in the short term, compared with 200-cm BPL, percentage excess weight loss (%EWL) did not show significant reduction (p = 0.91), neither did the incidence of vitamin D deficiency (p = 0.87) nor hypoalbuminemia (p = 0.06), while percentage total weight loss (%TWL) was significantly higher in the 200-cm BPL group (p = 0.0005). At 1, 2, and 8 years postoperatively, patients with short BPL still obtained significantly reduced body mass index (BMI). CONCLUSION: Short BPL shows significant effect of weight loss; however, it seems no significantly lower rates of adverse events in the short term are found. More research with randomized controlled design is encouraged to further address the incidence of adverse events in the long term.

[Development Scenarios and Environmental Benefits Analysis of Future Power Generation Industry Under Two Modes in China].

In order to study the impact of the "carbon peak and neutrality" mode on future power generation and the environment in China, a Verhulst gray model was established to predict the development of the power generation industry from 2021 to 2060 under the non-"carbon peak and neutrality" mode. In addition, based on the "China 2030 Energy and Power Development Planning Research and 2060 Outlook Report," the development of the power generation industry from 2021 to 2060 under the "carbon peak and neutrality" mode was obtained, and the development scenarios of the future power generation industry in China under two models were compared and studied. The emission factors and emission reduction factors of CO2, SO2, NOx, PM, PM10, and PM2.5 were constructed through the conservation of elements and the generating performance standard, and then four environmental benefits A1-A4 were defined. The results showed that the installed capacity of thermal power will reach the carbon peak in 2026 under the "carbon peak and neutrality" mode. To achieve the carbon neutralization, the installed capacity of thermal power will be reduced by an average of 28 million kilowatts per year after 2026, and the installed capacity of renewable energy generated is required to increase by 154 million kilowatts per year after 2020. Compared with that in the non-"carbon peak and neutrality" mode, the installed capacity of thermal power generation will be greatly reduced, and the installed capacity of renewable energy power generation will be greatly increased under the "carbon peak and neutrality" mode, resulting in huge A1 and A2 environmental benefits. In the next four decades, the cumulative emission reductions in CO2, SO2, NOx, PM, PM10, and PM2.5 thermal power generation A1 are predicted to be 6.64×1010 tons, 1.54×107 tons, 1.55×107 tons, 3.18×106 tons, 1.71×106tons, and 2.23×105 tons, respectively. The cumulative emission reductions of renewable energy power generation A2 will be 5.77×1010 tons, 1.64×107 tons, 1.42×107 tons, 2.86×106 tons, 1.54×106 tons, and 2×105 t tons, respectively. Under the "carbon peak and neutrality" mode, compared with those from coal-fired power generation, the environmental benefits A3 and A4 produced by the relative cleanliness of renewable energy and nuclear power indicated that the cumulative emission reductions (A3+A4) in clean energy power generation of CO2, SO2, NOx, PM, PM10, and PM2.5 in the next four decades will be 3.014×1011 tons, 7.292×107 tons, 7.119×107 tons, 1.454×107 tons, 7.827×106tons, and 1.018×106 tons, respectively.

Elevated CD38 expression characterizes impaired CD8+ T cell immune response in metastatic pleural effusions.

Highly coordinated signaling following TCR stimulation triggers activation and subsequent differentiation of T cells. CD38 is a major mammalian nicotinamide adenine dinucleotide (NAD)+ glycohydrolase expressed on T cells, and appears to be an important modulator of T cell response in tumor models. However, the functional involvement of CD38 in T cells remains largely unknown. Therefore, we characterize the presence and function of CD38 in lymphocytes from metastatic pleural effusions (MPE). Of note, a significant accumulation of CD38+CD8+ T cells was observed in MPE compared with matched peripheral blood mononuclear cells (PBMC). Moreover, PD-1 expression was significantly increased within the CD38+CD8+ T cell fraction compared to CD38- counterparts. We further showed decreased amounts of IFNγ and TNFα production together with reduced mitochondrial membrane potential in CD38+CD8+ T cells. Indeed, the impaired capacity of secreting IFNγ and TNFα by CD38+CD8+ T cells was likely due to damaged mitochondrial function. Taken together, we have identified a subset of CD38+CD8+ T cells in MPE, which possessed exhausted phenotype accompanied by altered mitochondrial metabolism.

Underlying microangiopathy and functional outcome of simultaneous multiple intracerebral hemorrhage.

Objective: To identify the predominant type of cerebral small vessel disease (SVD) and outcomes in patients with simultaneous multiple intracerebral hemorrhages (SMICH). Methods: Consecutive patients with intracerebral hemorrhage (ICH) from a single-center prospective cohort were retrospectively reviewed. Presumed etiology was classified according to the SMASH-U criteria. Demographics, clinical and laboratory variables, and neuroimaging data were compared between patients with primary SMICH and those with single ICH. Functional outcomes were assessed using the modified Rankin scale 90 days after ICH. Results: Of the 598 enrolled patients, 37 (6.2%) met the criteria for SMICH. Risk factors for SMICH included a high burden of deep cerebral microbleeds (CMBs) (odds ratio [OR] 1.06, 95% confidence interval [CI], 1.00-1.12; p = 0.040), white matter hyperintensity scores (OR 1.27, 95% CI 1.04-1.57; p = 0.021), history of ICH (OR 3.38, 95% CI 1.31-8.05; p = 0.008), and low serum magnesium levels (OR 0.01, 95% CI 0.00-0.25; p = 0.007). Based on the SMASH-U classification, 15(40.5%) SMICH were classified as hypertension, whereas 17 (45.9%) as undetermined-etiology. To further explore the potential microangiopathy underlying undetermined-SMICH, these patients with undetermined-etiology were compared to those with cerebral amyloid angiopathy-ICH, and were associated with a higher burden of deep CMBs but less severe centrum semiovale enlarged perivascular spaces. Likewise, compared with hypertension-ICH patients, those with undetermined SMICH were consistently associated with a higher deep CMB counts. Moreover, multivariate analysis revealed that SMICH was independently associated with poor outcomes (OR 2.23, 95%CI 1.03-4.76; p = 0.038). Conclusion: Our results suggest that most patients with primary SMICH harbor hypertensive-SVD as principal angiopathy. Patients with SMICH are at a high risk of poor outcomes. (ClinicalTrials.gov Identifier: NCT04803292).

Berberine inhibits osteogenic differentiation of aortic valve interstitial cells by interfering Smad1/5/8 and NF-κB pathways.

AIMS: Calcified aortic valve disease (CAVD) is a cardiovascular disease with increasing morbidity and mortality. The pathogenetic cellular mechanism is the phenotypic transition of aortic valve interstitial cells (VICs). Here, we explored the effect of berberine (BBR) on the phenotypic transition of VICs and elucidated the underlying molecular mechanisms, providing a theoretical basis in finding novel clinical treatments for CAVD. METHODS AND RESULTS: Calcific aortic valves and normal controls were collected for western blot and the results demonstrated that osteogenic and inflammatory markers were significantly up-regulated in calcific aortic valves. BBR inhibited inflammation and osteogenic differentiation of VICs under osteogenic conditions, as well as alkaline phosphatase activity and calcified nodule formation. Mechanistically, BBR could inhibit the activation of Smad1/5/8 and NF-κB pathways under OM conditions. LDN193189 and BAY11-7082, the inhibitor of Smad1/5/8 and NF-κB respectively, were added for further verification. Similarly, the osteogenic and fibrotic markers of VICs induced by osteogenic induction medium were decreased by LDN193189 and BAY11-7082. Western blot was used to examine upstream receptors of Smad1/5/8, the results showed that BBR inhibited the activation of Smad1/5/8 by downregulating ALK2 and ALK3. CONCLUSION: BBR decreased the inflammatory factors and suppressed the osteogenic differentiation of VICs, which might be associated with the inhibition of Smad1/5/8 and NF-κB signaling pathways.

Risk Factors for Radiological Progression Within Admissive One Week in the Hospitalized COVID-19 Omicron Variant-Infected Patients.

Purpose: Recently, the SARS-CoV-2 Omicron variant was identified as responsible for a novel wave of COVID-19 worldwide. We perform a retrospective study to identify potential risk factors contributing to radiological progression in the COVID-19 patients due to the Omicron variant infection. These findings would provide guiding information for making clinical decisions that could improve the Omicron infection prognosis and reduce disease-related death. Methods: This is a retrospective cohort study from a single center in China. According to the radiological change within admissive one week, enrolled cases were divided into two groups: the progressive (1w-PD) and the stable or improved disease (1w-non-PD). Separate analyses were performed on patients stratified into subgroups using the Mann-Whitney U-test, the Fisher exact test, or the Chi-squared test and a multivariable logistic regression analysis. Results: Both the 1w-non-PD and 1w-PD cohorts displayed comparable asymptomatic infection, have similar underlying disease, impairment in respiratory function, coagulation dysfunction, tissue injury, SARS-CoV-2 viral load, and disease severity. However, the 1w-PD cohort was more inclined to cluster in populations presented with age between 41 and 65, higher CURB-65 scores, undetectable SARS-CoV-2 IgG, and lung affection. Based on the multiple logistic regression analysis, complicated bilateral and ground-glass opacities (GGOs) like pneumonia at admission were independent risk factors to radiological progression within admissive one week. Conclusion: This study provided preliminary data regarding disease progression in Omicron-infected patients that indicated the development of pneumonia in the context of Omicron infection was worthy of potential risk factors.

An antigen-strengthened dye-modified fully-human-nanobody-based immunoprobe for second near infrared bioimaging of metastatic tumors.

Conventional immunoprobes have absorption capabilities across the visible to near infrared (NIR-I, 650-900 nm) region. Recently, second near infrared (NIR-II, 1000-1700 nm) window have gained much attention due to their deeper penetration depth and improved visualization. Here, we describe the design and synthesis of a fully human nanobody-based fluorescent immunoprobe (ICGM-n501) for NIR-II bioimaging with strengthened fluorescent emission by antigen for the first time. By site-directed conjugation of an FDA-approved dye analogue, indocyanine green decorated with maleimide (ICGM), into a tumor-specific n501, ICGM-n501 provides real-time monitoring of abdominal transportation pathway of antibody-based bioagents with high resolution (0.21 mm), presents better accuracy and lower dosage (0.21 µmol kg-1) in bioimaging of peritoneal metastatic tumors than bioluminescence agent D-luciferin. In this work, ICGM-n501 demonstrates its potential in clinical surgery guidance, provide an expanded category of available NIR-II fluorophores and a template for next-generation immunoassay bioagents.

Is Bariatric Surgery Effective for Chinese Patients with Type 2 Diabetes Mellitus and Body Mass Index < 35 kg/m2? A Systematic Review and Meta-analysis.

BACKGROUND: Bariatric surgery has been applied for weight loss and comorbidity control in China since 2000. Recent studies have shown positive results for bariatric surgery in patients with a body mass index (BMI) of less than 35 kg/m2. However, the effect of surgery on Chinese patients with type II diabetes mellitus (T2DM) has not yet been systematically investigated. METHODS: A comprehensive literature search was performed in the Cochrane Library, Embase, PubMed, and Web of Science from January 2014 to March 2020. All studies examined bariatric surgery outcomes on Chinese patients at 12-, 36-, and 60-month follow-up. The research followed the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) recommendations. RESULTS: Eleven studies containing 611 patients were included in this meta-analysis. Clinical indices at 12-, 36-, and 60-month follow-up were analyzed. Significant decreases were identified in body weight, BMI, waist circumference (WC), blood pressure (BP), fasting plasma glucose (FPG), glycosylated hemoglobin A1c (hemoglobin A1c, or HbA1c), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) postoperatively. An increasing trend in the T2DM remission rate was discovered. The remission group was observed to have significantly lower HbA1c and C-peptide level, a shorter duration of T2DM, and a higher BMI than the nonremission group at 12 months. CONCLUSIONS: Bariatric surgery successfully provided significant BMI control as well as a reduction and normalization of glucose- and lipid-related metabolism at 12, 36, and 60 months postoperatively in Chinese patients with T2DM with a preoperative BMI of less than 35 kg/m2. An increasing trend in the T2DM remission rate suggested promising future applications in this population.