Effects of Propofol, Low and High Doses of Remimazolam on Hemodynamic and Inflammatory Response in Laparoscopic Surgery.

Background: This study explored the effects of different doses of remimazolam tosilate (RT) and propofol combined with remifentanil anesthesia on hemodynamic and inflammatory responses in patients undergoing laparoscopic surgery. Subjects and Methods: Ninety patients with a BMI of less than 35 kg/m², classified as ASA II-III and scheduled for laparoscopic surgery, were enrolled in this study. Patients were divided into three groups: low-dose RT group (A), high-dose RT group (B), and propofol group (C). The changes in hemodynamic indices such as SBP, DBP, HR, MAP, and inflammatory response indices such as IL-6, SAA, CRP, and PCT, along with extubation time and doses of sufentanil, remifentanil, urapidil, and phenylephrine, were compared among the three groups. Results: There were no statistically significant differences in extubation time, doses of sufentanil and remifentanil, or the usage rates and average doses of urapidil and phenylephrine between the three groups. The average dose of phenylephrine in group A was lower than in group B and group C, with a statistically significant difference. There were no statistically significant differences among the groups in SBP, DBP, HR, and MAP from T0 to T2, nor in IL-6, SAA, CRP, or PCT levels. Conclusion: Using RT for induction and maintenance of anesthesia in laparoscopic surgery ensures stable hemodynamic and inflammatory responses in patients. Low-dose RT may reduce the usage rate and dose of vasopressors such as phenylephrine during surgery.

Distinct phenotype and prognosis of immune-mediated necrotizing myopathy based on clinical-serological-pathological classification.

OBJECTIVE: The aim of the study was to investigate the characteristics and prognosis of patients with immune-mediated necrotizing myopathy (IMNM) based on clinical, serological and pathological classification. METHODS: A total of 138 patients with IMNM who met the 2018 European Neuromuscular Center criteria for IMNM including 62 anti-SRP, 32 anti-HMGCR-positive and 44 myositis specific antibody-negative were involved in the study. All patients were followed up and evaluated remission and relapse. Clustering analysis based on clinical, serological, and pathological parameters was used to define subgroups. RESULTS: Clustering analysis classified IMNM into three clusters. Cluster 1 patients (n = 35) had the highest CK levels, the shortest disease course, severe muscle weakness, and more inflammation infiltration in muscle biopsy. Cluster 2 patients (n = 79) had the lowest CK level and moderate inflammation infiltrate. Cluster 3 patients (n = 24) had the youngest age of onset, the longest disease course and the least frequency of inflammatory infiltration. Patients in cluster 3 had the longest time-to-remission (median survival time: 61[18.3, 103.7] vs 20.5[16.2, 24.9] and 27[19.6, 34.3] months) and shortest relapse-free time than those in cluster 1 and 2 (median remission time 95%CI: 34[19.9, 48.0] vs 73[49.0, 68.7] and 73[48.4, 97.6] months). Patients with age of onset >55 years, more regeneration of muscle fibers, more CD4+T infiltration, and MAC deposition had more favorable outcomes regarding time to achieving remission. CONCLUSIONS: Stratification combining clinical, serological, and pathological features could distinguish phenotypes and prognosis of IMNM. The pathological characteristics may impact the long-term prognosis of patients with IMNM.

Construction of a Risk Prediction Model for Intraoperative Hypothermia in Patients Undergoing Lower Extremity Joint Replacement.

PURPOSE: To investigate the influencing factors of intraoperative hypothermia (IOH) in patients undergoing total joint arthroplasty (TJA) of the lower extremities, establish a risk prediction model, and test the effect of application. DESIGN: A prospective, observational study was conducted. METHODS: Patients who underwent total knee arthroplasty and total hip arthroplasty from June 2020 to December 2021 were prospectively analyzed. According to the occurrence of IOH, patients were divided into the IOH group (temperature less than 36 °C) and non-IOH group (temperature ≥36 °C). We collected demographic, anesthesia, and surgical data for both groups to identify risk factors for IOH and develop a predictive model. The model's goodness of fit was assessed using the Hosmer-Lemeshow test, and its predictive efficacy was evaluated using the receiver operating characteristic curve. FINDINGS: A total of 258 patients were included in this study, with 79 patients in the IOH group and 179 patients in the non-IOH group. Logistic regression analysis showed that American Society of Anesthesiologists' grade, blood loss, and duration of surgery were independent risk factors for IOH in lower extremity TJA patients. Hosmer-Lemeshow test P = .803, area under receiver operating characteristic curve was 0.846, Youden index was 0.490, sensitivity was 65.4%, specificity was 83.6%. In the external validation cohort, the application accuracy of the model was 83.3%. CONCLUSIONS: The prediction model established in this study is suitable for the risk assessment of IOH in TJA patients with good prediction effect, which can provide a tool for clinical medical staff to identify high-risk populations preoperatively.

Metal-Organic Framework Featuring Cubic Caged Structures for One-Step Ethylene Purification from Ethylene/Ethane Mixtures.

Separation of C2H6/C2H4 mixtures is of significant importance in the chemical industry but remains a challenge due to the physicochemical similarities of C2H6 and C2H4. Herein, a metal-organic framework (MOF), [Zn4(µ4-O)(PCTF)3]n (Zn-PCTF) (PCTF2-= 5-trifluoromethyl-1H-pyrazole-4-carboxylic), is provided for the removal of C2H6 from C2H6/C2H4 mixtures. Zn-PCTF displays a three-dimensional framework featuring one-dimensional pore channels with periodic bottleneck segments. The well-balanced C2H6 adsorption capacity (79.0 cm3 g-1 at 298 K) and C2H6/C2H4 selectivity (1.8) for Zn-PCTF under ambient conditions boost Zn-PCTF with highly promising potentials for efficient purification of C2H4 from C2H6/C2H4 mixtures, which is verified by the dynamic column breakthrough experiments. The well-matched caged pores and suitable pore chemistry (particularly the presence of abundant Lewis base sites (N, O, and F) on the pore surfaces) for C2H6 account for the high-performance C2H6/C2H4 separation of Zn-PCTF unveiled by computational simulations.

Clinical and prognostic associations of anti-Jo-1 antibody levels in patients with antisynthetase syndrome.

OBJECTIVE: To investigate the association of serum anti-Jo-1 antibody levels with the disease activity and prognosis in anti-Jo-1-positive patients with antisynthetase syndrome (ASS). METHODS: This study included 115 anti-Jo-1-positive patients with ASS who were admitted to China-Japan Friendship Hospital between 2009 and 2019. Anti-Jo-1 antibody serum levels at initial admission and follow-up were determined by enzyme-linked immunosorbent assay (ELISA). Global and organ disease activity was assessed at baseline and follow-up according to the International Myositis Assessment and Clinical Studies guidelines. RESULTS: Among enrolled patients, 70 (60.9%) patients initially presented with interstitial lung disease (ILD), and 46 (40%) patients presented with with muscle weakness at initial admission. At baseline, patients with ILD had lower levels of anti-Jo-1 antibodies than those without ILD (p = 0.012). Baseline anti-Jo-1 antibody levels were higher in patients with muscle weakness, skin involvement, and arthritis (all p < 0.05) compared to those without these manifestations. Baseline anti-Jo-1 antibody levels were positively correlated with skin visual analogue scale (VAS) scores (r = 0.25, p = 0.006), but not with disease activity in other organs. However, changes in anti-Jo-1 antibody levels were significantly positively correlated with the changes in PGA (ß = 0.002, p = 0.001), muscle (ß = 0.003, p < 0.0001), and pulmonary (ß = 0.002, p = 0.013) VAS scores, but not with skin and joint VAS scores. Older age of onset (hazard ratio [HR] 1.069, 95% confidence interval [CI]:1.010-1.133, p = 0.022) and higher C-reactive protein (CRP) levels (HR 1.333, 95% CI: 1.035-1.717, p = 0.026) were risk factors for death. CONCLUSION: Anti-Jo-1 titers appear to correlate more with disease activity changes over time rather than with organ involvement at baseline, which provides better clinical guidance for assessing the disease course using anti-Jo-1 levels.

Advances in the mechanisms and applications of RNA silencing in crop protection.

RNA silencing (or RNA interference, RNAi) is a conserved mechanism for regulating gene expression in eukaryotes, which plays vital roles in plant development and response to biotic and abiotic stresses. The discovery of trans-kingdom RNAi and interspecies RNAi provides a theoretical basis for exploiting RNAi-based crop protection strategies. Here, we summarize the canonical RNAi mechanisms in plants and review representative studies associated with plant-pathogen interactions. Meanwhile, we also elaborate upon the principles of host-induced gene silencing, spray-induced gene silencing and microbe-induced gene silencing, and discuss their applications in crop protection, thereby providing help to establish novel RNAi-based crop protection strategies.

Metal-Organic Frameworks Possessing Suitable Pores for Xe/Kr Separation.

Adsorption separation of the Xe/Kr mixture remains a tough issue since Xe and Kr have an inert nature and similar sizes. Here we present a chlorinated metal-organic framework (MOF) [JXNU-19(Cl)] and its nonchlorinated analogue (JXNU-19) for Xe/Kr separation. The two isostructural MOFs constructed from the heptanuclear cobalt-hydroxyl clusters bridged by organic ligands are three-dimensional structures. Detailed contrast of the Xe/Kr adsorption separation properties of the MOF shows that significantly enhanced Xe uptakes and Xe/Kr adsorption selectivity (17.1) are observed for JXNU-19 as compared to JXNU-19(Cl). The main binding sites for Xe in the MOF revealed by computational simulations are far away from the chlorine sites, suggesting that the introduction of the chlorine groups results in the unfavorable Xe adsorption for JXNU-19(Cl). The optimal pores, high surface area, and multiple strong Xe-framework interactions facilitate the effective Xe/Kr separation for JXNU-19.

An Expeditious Neutralization Assay for Porcine Reproductive and Respiratory Syndrome Virus Based on a Recombinant Virus Expressing Green Fluorescent Protein.

Due to the extensive genetic and antigenic variation in Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), as well as its rapid mutability and evolution, PRRS prevention and control can be challenging. An expeditious and sensitive neutralization assay for PRRSV is presented to monitor neutralizing antibodies (NAbs) in serum during vaccine research. Here, a PRRSV expressing eGFP was successfully rescued with reverse genetics based on the infectious clone HuN4-F112-eGFP which we constructed. The fluorescent protein expressions of the reporter viruses remained stable for at least five passages. Based on this reporter virus, the neutralization assay can be easily used to evaluate the level of NAbs by counting cells with green fluorescence. Compared with the classical CPE assay, the newly developed assay increases sensitivity by one- to four-fold at the early antibody response stage, thus saving 2 days of assay waiting time. By using this assay to unveil the dynamics of neutralizing antibodies against PRRSV, priming immunity through either a single virulent challenge or only vaccination could produce limited NAbs, but re-infection with PRRSV would induce a faster and stronger NAb response. Overall, the novel HuN4-F112-eGFP-based neutralization assay holds the potential to provide a highly efficient platform for evaluating the next generation of PRRS vaccines.

Exploring the potential mechanism and molecular targets of Taohong Siwu Decoction against deep vein thrombosis based on network pharmacology and analysis docking.

This study aims to investigate the mechanism of Taohong Siwu Decoction (THSWD) against deep vein thrombosis (DVT) using network pharmacology and molecular docking technology. We used the Traditional Chinese Medicine Systems Pharmacology database and reviewed literature to identify the main chemical components of THSWD. To find targets for DVT, we consulted GeneCards, Therapeutic Target Database, and PharmGKB databases. We used Cytoscape 3.8.2 software to construct herb-disease-gene-target networks. Additionally, we integrated drug targets and disease targets on the STRING platform to create a protein-protein interaction network. Then, we conducted Kyoto Encyclopedia of Genes and Genomes and gene ontology analysis. Finally, We employed the molecular docking method to validate our findings. We identified 56 potential targets associated with DVT and found 61 effective components. beta-sitosterol, quercetin, and kaempferol were the most prominent among these components. Our analysis of the protein-protein interaction network revealed that IL6, L1B, and AKT1 had the highest degree of association. Gene ontology analysis showed that THSWD treatment for DVT may involve response to inorganic substances, negative regulation of cell differentiation, plasma membrane protein complex, positive regulation of phosphorylation, and signaling receptor regulator activity. Kyoto Encyclopedia of Genes and Genomes analysis indicated that lipid and atherosclerosis, pathways in cancer, as well as the PI3K-Akt pathway are the main signal pathways involved. Molecular docking results demonstrated strong binding affinity between beta-sitosterol, quercetin, kaempferol, and AKT1 proteins as well as IL1B and IL6 proteins. The main targets for THSWD treatment of DVT may include AKT1, IL1B, and IL6. Beta-sitosterol, quercetin, and kaempferol may be the active ingredients responsible for producing this effect. These compounds may slow down the progression of DVT by regulating the inflammatory response through the PI3K/Akt pathway.

Clinical application of multidisciplinary team- and evidence-based practice project in gynecological patients with perioperative hypothermia.

BACKGROUND: Perioperative hypothermia (PH) negatively affects the physical and mental health of patients to varying degrees. Currently, there is no effective multidisciplinary team (MDT) intervention for gynecological patients with PH. AIM: To apply the best evidence on the prevention and management of PH in gynecological patients, improve the quality of perioperative evidence-based care based on treatment by an MDT for gynecological patients and analyze the effect of MDT- and evidence-based practice (EBP) projects on the psychological status and cognitive function of gynecological patients with PH. METHODS: Under the guidance of knowledge translation and combined with the opinions of involved stakeholders and clinical experts, the best evidence for PH prevention and management in gynecological patients was selected and adjusted to suit the practice setting. Based on the evidence, the practice plan was developed, and the MDT intervention was carried out in the preoperative ward, the preoperative preparation room, the intraoperative operating room, the postanesthesia care unit, and the 24-hour postoperative gynecological ward through the EBP program. The incidence of hypothermia, the nurses' awareness, the implementation rate of examination indicators, and the thermal comfort level, psychological status and cognitive function of patients were compared before and after the implementation of the program. RESULTS: The incidence of PH in gynecological patients decreased from 43.33% to 13.33% after the implementation of the scheme. The implementation rate of examination indicators 6-10, 12, 14, 16-18, 21, and 22 reached 100%, and that of other indicators was above 90%, except for examination indicators 5 and 13, which was 66.67%; the indices were significantly improved compared with the baseline (before evidence application) (P < 0.05). The score of nurses' awareness of PH prevention and management in gynecological patients increased from 60.96 ± 9.70 to 88.08 ± 8.96, and the difference was statistically significant (P < 0.001). The total score of the perioperative thermal comfort level of patients undergoing gynecological surgery was 27.97 ± 2.04, which was significantly increased compared with the score of 21.27 ± 1.57 observed by researchers at baseline (P < 0.001). The perioperative Hamilton Depression Scale and Hamilton Anxiety Scale scores of patients undergoing gynecological surgery decreased from 15.03 ± 3.16 and 13.93 ± 2.64 to 4.30 ± 1.15 and 3.53 ± 0.78, respectively, with statistically significant differences (P < 0.001). The perioperative Montreal Cognitive Assessment Scale score of the gynecological surgery patients increased from 23.17 ± 1.68 to 26.93 ± 1.11, also with statistical significance (P < 0.001). CONCLUSION: MDT-based EBP for PH prevention and management in gynecological patients during the perioperative period can standardize nursing operations, improve nurses' awareness and behavioral compliance with gynecological hypothermia management, and reduce the occurrence of PH in gynecological patients while playing a positive role in reducing patients' negative emotions and enhancing their cognitive function.

Gut mycobiome as a potential non-invasive tool in early detection of lung adenocarcinoma: a cross-sectional study.

BACKGROUND: The gut mycobiome of patients with lung adenocarcinoma (LUAD) remains unexplored. This study aimed to characterize the gut mycobiome in patients with LUAD and evaluate the potential of gut fungi as non-invasive biomarkers for early diagnosis. METHODS: In total, 299 fecal samples from Beijing, Suzhou, and Hainan were collected prospectively. Using internal transcribed spacer 2 sequencing, we profiled the gut mycobiome. Five supervised machine learning algorithms were trained on fungal signatures to build an optimized prediction model for LUAD in a discovery cohort comprising 105 patients with LUAD and 61 healthy controls (HCs) from Beijing. Validation cohorts from Beijing, Suzhou, and Hainan comprising 44, 17, and 15 patients with LUAD and 26, 19, and 12 HCs, respectively, were used to evaluate efficacy. RESULTS: Fungal biodiversity and richness increased in patients with LUAD. At the phylum level, the abundance of Ascomycota decreased, while that of Basidiomycota increased in patients with LUAD. Candida and Saccharomyces were the dominant genera, with a reduction in Candida and an increase in Saccharomyces, Aspergillus, and Apiotrichum in patients with LUAD. Nineteen operational taxonomic unit markers were selected, and excellent performance in predicting LUAD was achieved (area under the curve (AUC) = 0.9350) using a random forest model with outcomes superior to those of four other algorithms. The AUCs of the Beijing, Suzhou, and Hainan validation cohorts were 0.9538, 0.9628, and 0.8833, respectively. CONCLUSIONS: For the first time, the gut fungal profiles of patients with LUAD were shown to represent potential non-invasive biomarkers for early-stage diagnosis.

Efficacy and safety of anti-PD-1 monotherapy versus anti-PD-1 antibodies plus lenvatinib in patients with advanced hepatocellular carcinoma: a real-world experience.

Background: The efficacy of anti-programmed cell death (PD)-1 monotherapy in advanced hepatocellular carcinoma (aHCC) is limited, and combination therapy with lenvatinib and pembrolizumab has shown promising results. However, comparative studies between immune monotherapies and combination therapies are lacking. Objectives: To investigate the efficacy and safety of anti-PD-1 monotherapy (PD-1) and anti-PD-1 plus lenvatinib (PD-1 + L) in patients with aHCC to guide clinical treatment decisions. Design: A retrospective study was conducted on a cohort of patients with aHCC who received either PD-1 monotherapy or PD-1 + L combination therapy between January 2018 and January 2020. Methods: The study retrospectively reviewed the medical records of 94 eligible patients with aHCC, with 39 in the PD-1 group and 55 in the PD-1 + L group. The efficacy outcomes, including objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety, were assessed. Results: With a median follow-up of 30.1 months, the PD-1 + L group demonstrated a significantly higher ORR (32.7% versus 10.3%, p = 0.013), better DCR (80.0% versus 53.8%, p = 0.012), longer median PFS (10.6 versus 4.4 months, p < 0.001) and longer median OS (18.4 versus 8.5 months, p = 0.013) than PD-1 group. For the responders, the efficacy of the two groups was durable (DOR was 11.6 versus 3.5 months, p = 0.009). Subgroup analyses based on prior tyrosine kinase inhibitor (TKI) treatment and the presence or absence of macrovascular tumor thrombosis or extrahepatic metastases favored the PD-1 + L group. The combination therapy was a good predictor of PFS and OS in multivariate analysis. Grade 3/4 treatment-related adverse events were more common in PD-1 + L group, with higher incidences of hypertension and hand-foot skin reactions. Conclusions: PD-1 monotherapy and PD-1 plus lenvatinib combination therapy were well-tolerated in patients with aHCC. PD-1 + L showed significantly better survival benefits than PD-1 monotherapy.

Understanding the impact of PD-1 and lenvatinib combination therapy on advanced hepatocellular carcinoma Abstract: This plain language summary provides a description of our research on the combination therapy of PD-1 and lenvatinib for advanced Hepatocellular carcinoma (aHCC). We aimed to investigate the effectiveness and safety of this treatment approach and offer insights for clinical decisions. Why was this study done? HCC is a challenging condition to treat, especially in advanced stages. We explored whether the combination of two drugs, PD-1 and lenvatinib, can offer better outcomes for patients with aHCC than PD-1 monotherapy. What did the researchers do? We conducted a retrospective study on patients diagnosed with aHCC who received PD-1 alone or PD-1 combined with lenvatinib between January 2018 and January 2020. We analysed the medical records to assess the treatment's efficacy and safety. What did the researchers find? After a median follow-up of 30.1 months, we observed significant improvements in the combination therapy group, with higher response rates, better disease control, longer progression free survival, and more extended overall survival than those in the PD-1 monotherapy group. Responders in the combination group also experienced a longer duration of response. What do the findings mean? Our results address the lack of data for real-world clinical experiences regarding anti-PD-1 monotherapy for patients with aHCC compared to immunotherapy plus lenvatinib are lacking. The combination of PD-1 and lenvatinib was more effective and offered better survival benefits for patients with aHCC than PD-1 alone. These results could provide new hope for patients with this challenging condition. Limitations: The study was conducted at a single centre with relatively few patients. Additionally, most patients had hepatitis B-associated liver cancer, which may limit the generalisability of our findings to other populations. Conclusions: PD-1 plus lenvatinib is a promising treatment option for patients with aHCC. It is well-tolerated, and its effectiveness surpasses that of PD-1 therapy alone. Our findings could potentially guide clinicians in making treatment decisions for patients with aHCC.

A prospective observational cohort study of the efficacy of tofacitinib plus iguratimod on rheumatoid arthritis with usual interstitial pneumonia.

Objectives: This study aims to assess the efficacy of tofacitinib (TOF) plus iguratimod (IGU) in rheumatoid arthritis (RA) with usual interstitial pneumonia (UIP) (RA-UIP). Methods: This was a prospective observational cohort, single-center study. Data from 78 RA-UIP patients treated with TOF plus IGU, IGU plus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), and csDMARDs were analyzed. Clinically relevant responses in RA activity assessment, pulmonary function tests (PFTs), and high-resolution computed tomography (HRCT) assessment at baseline and follow-up were compared between groups to evaluate the efficacy of TOF plus IGU. Results: A total of 78 patients were followed up for at least 6 months after treatment. There were significant changes in sedimentation rate (ESR), C reactive protein (CRP), and disease activity score (DAS) 28-CRP during the follow-up within each treatment group, but there was no statistically significant difference between the two groups. After 6 months of TOF plus IGU treatment, forced vital capacity (FVC)% (84.7 ± 14.7 vs. 90.7 ± 15.4) and HRCT fibrosis score (7.3 ± 3.4 vs. 7.0 ± 5.6) showed a significant improvement compared to the csDMARDs group (P = 0.031, P = 0.015). The TOF plus IGU-treated patients had a significantly higher regression and lower deterioration than the csDMARDs-treated patients (P = 0.026, P = 0.026) and had a significantly higher response (regression + stability), with overall response rates of 66.7% (16/24) vs. 35.7% (10/28) (P = 0.027), respectively. Conclusion: Our results indicate that TOF plus IGU can simultaneously relieve RA and RA-UIP and be better than the csDMARDs with a higher response rate in RA-UIP, which may be a potential choice for "dual treat-to-target".

Cucurbituril-Shaped Cd18(triazolate)12 Unit-Based Metal-Organic Framework Exhibiting an C2H2/CO2 Separation Ability.

Herein, a metal-organic framework (MOF), {[(Me2NH2)4][Cd(H2O)6][Cd18(TrZ)12(TPD)15(DMF)6]}n (denoted as JXNU-18, TrZ = triazolate), constructed from the unique cucurbituril-shaped Cd18(TrZ)12 secondary building units bridged by 2,5-thiophenedicarboxylic (TPD2-) ligands, is presented. The formation of the cucurbituril-shaped Cd18(TrZ)12 unit is unprecedented, demonstrating the geometric compatibility of the organic linkers and the coordination configurations of the cadmium atoms. Each Cd18(TrZ)12 unit is connected to eight neighboring Cd18(TrZ)12 units through 30 TPD2- linkers, affording the three-dimensional structure of JXNU-18. More interesting is that JXNU-18 displays an efficient C2H2/CO2 separation ability, as revealed by the gas adsorption experiments and dynamic gas breakthrough experiments, which afford insights into the potential applications of JXNU-18 in gas separation. The tubular pores composed of two Cd18(TrZ)12 units bridged by six 2,5-thiophenedicarboxylic linkers provide the suitable pore space for C2H2 trapping, as unveiled by computational simulations.

Serum Amyloid A 4 as a Common Marker of Persistent Inflammation in Patients with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

Background: Neovascular age-related macular degeneration (nAMD) and its subtype, polypoidal choroidal vasculopathy (PCV), are common choroidal vasculopathies. Although they share many common clinical manifestations and treatment strategies, a lack of comprehensive analysis of these conditions means that it is difficult for researchers to further explore the common pathomechanisms of nAMD and PCV. The aim of this study was to characterize aqueous humor (AH) proteome alterations and identify a novel biomarker related to both nAMD and PCV. Methods: Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) was adopted to analyze the AH proteomes of nAMD, PCV and controls. The target protein was validated using the enzyme-linked immunosorbent assay (ELISA) and subjected to receiver operating characteristic (ROC) curve analysis. Results: A total of 737 different proteins were identified in all the groups, of which 544 were quantifiable. The bioinformatics analysis suggested that immune response activation is the essential event in both nAMD and PCV. Serum amyloid A (SAA) 4 is closely associated with a number of chronic inflammatory diseases, and it was enriched as the hub protein. ROC analysis showed that SAA4 could distinguish both nAMD and PCV from the controls. Conclusion: This comprehensive study provides insights into, and furthers our understanding of, the pathological mechanism of nAMD and PCV. Additionally, the SAA4 level alteration may serve as a common biomarker of nAMD and PCV.

Upregulation of the CD155-CD226 Axis Is Associated With Muscle Inflammation and Disease Severity in Idiopathic Inflammatory Myopathies.

BACKGROUND AND OBJECTIVES: The CD155-CD226/T-cell Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) pathway plays a critical role in regulating T-cell responses and is being targeted clinically. However, research on the role of this pathway in autoimmune diseases is limited. This study aimed to investigate the expression and tissue-specific roles of CD155-CD226/TIGIT pathway molecules in the inflamed muscles of patients with idiopathic inflammatory myopathies (IIMs). METHODS: Immunohistochemistry, Western blot analysis, and polychromatic immunofluorescence staining were performed to examine the expression of CD155, CD226, and TIGIT in skeletal muscle biopsies from 30 patients with dermatomyositis (DM), 10 patients with amyopathic DM (ADM), 20 patients with immune-mediated necrotizing myopathy (IMNM), 5 patients with dysferlinopathy, and 4 healthy controls. Flow cytometry analysis was used to analyze the functions of T cells with different phenotypes. RESULTS: Strong expression of CD155 was observed in patients with DM and IMNM, while its expression was largely negative in those with ADM and dysferlinopathy and healthy controls. The costimulatory receptor CD226 was highly expressed on muscle-infiltrating cells, while the coinhibitory receptor TIGIT was expressed at low levels. These infiltrating CD226+ cells were mainly activated effector T cells that localized adjacent to CD155-expressing myofibers, but were faintly detectable within the muscle fascicles lacking CD155. A strong positive correlation between CD155 and CD226 expression scores was also observed. Polychromatic immunofluorescence staining revealed that CD155+ muscle cells coexpressed major histocompatibility complex classes I and II, and tumor necrosis factor alpha expression was detected in CD226+ T cells at their close sites with the myofibers. Furthermore, the expression levels of CD155 and CD226 showed a positive correlation with creatine kinase, lactate dehydrogenase, and the muscle histopathology damage scores and an inverse correlation with the Manual Muscle Testing-8 scores. In addition, CD155 and CD226 expressions were significantly decreased in representative patients who achieved remission posttreatment. DISCUSSION: These findings demonstrate that the CD155-CD226 axis is highly activated in inflamed muscle tissues of patients with IIM and is associated with muscle disease severity. Our data uncover the immunopathogenic role of the axis in the pathology of IIMs.

Boosting the C2H2/CO2 Separation Performance of Metal-Organic Frameworks through Fluorine Substitution.

A pair of metal-organic frameworks (MOFs) of JXNU-15 (formulated as [Co6(µ3-OH)6(BTB)2(BPY)3]n, BTB3- = benzene-1,3,5-tribenzoate and BPY = 4,4'-bipyridine) and its fluorinated JXNU-15(F) ([Co6(µ3-OH)6(SFBTB)2(BPY)3]n) based on the fluorous 1,3,5-tri(3,5-bifluoro-4-carboxyphenyl)benzene (SFBTB3-) ligands were presented. The detailed comparisons of the acetylene/carbon dioxide (C2H2/CO2) separation abilities between the isostructural JXNU-15(F) and JXNU-15 were presented. In comparison with the parent JXNU-15, the higher C2H2 uptake, larger adsorption selectivity of the C2H2/CO2 (50/50) mixture, and enhanced C2H2/CO2 separation performance endow JXNU-15(F) with highly efficient C2H2/CO2 separation performance, which is demonstrated by singe-component gas adsorptions and dynamic gas mixture breakthrough experiments. The fluorine substituents exert the crucial effects on the enhanced C2H2/CO2 separation ability of JXNU-15(F) and play the dominant role in the C2H2-framework interactions, as uncovered by computational simulations. This work illustrates a powerful fluorine substitution strategy for boosting C2H2/CO2 separation ability for MOFs.

Risk of diabetic retinopathy and retinal neurodegeneration in individuals with type 2 diabetes: Beichen Eye Study.

Objective: Our aim was to evaluate associations of different risk factors with odds of diabetic retinopathy (DR) diagnosis and retinal neurodegeneration represented by macular ganglion cell-inner plexiform layer (mGCIPL). Methods: This cross-sectional study analyzed data from individuals aged over 50 years examined between June 2020 and February 2022 in the community-based Beichen Eye Study on ocular diseases. Baseline characteristics included demographic data, cardiometabolic risk factors, laboratory findings, and medications at enrollment. Retinal thickness in both eyes of all participants was measured automatically via optical coherence tomography. Risk factors associated with DR status were investigated using multivariable logistic regression. Multivariable linear regression analysis was performed to explore associations of potential risk factors with mGCIPL thickness. Results: Among the 5037 included participants with a mean (standard deviation, SD) age of 62.6 (6.7) years (3258 women [64.6%]), 4018 (79.8%) were control individuals, 835 (16.6%) were diabetic individuals with no DR, and 184 (3.7%) were diabetic individuals with DR. The risk factors significantly associated with DR status were family history of diabetes (odds ratio [OR], 4.09 [95% CI, 2.44-6.85]), fasting plasma glucose (OR, 5.88 [95% CI, 4.66-7.43]), and statins (OR, 2.13 [95% CI, 1.03-4.43]) relative to the control individuals. Compared with the no DR, diabetes duration (OR, 1.17 [95% CI, 1.13-1.22]), hypertension (OR, 1.60 [95% CI, 1.26-2.45]), and glycated hemoglobin A1C (HbA1c) (OR, 1.27 [95% CI, 1.00-1.59]) were significantly correlated with DR status. Furthermore, age (adjusted ß = -0.19 [95% CI, -0.25 to -0.13] µm; P < 0.001), cardiovascular events (adjusted ß = -0.95 [95% CI, -1.78 to -0.12] µm; P = 0.03), and axial length (adjusted ß = -0.82 [95% CI, -1.29 to -0.35] µm; P = 0.001) were associated with mGCIPL thinning in diabetic individuals with no DR. Conclusion: Multiple risk factors were associated with higher odds of DR development and lower mGCIPL thickness in our study. Risk factors affecting DR status varied among the different study populations. Age, cardiovascular events, and axial length were identified as potential risk factors for consideration in relation to retinal neurodegeneration in diabetic patients.

Treatment of stellate ganglion block in diseases: Its role and application prospect.

The stellate ganglion (SG), as a type of sympathetic ganglion, consists of the sixth and seventh cervical vertebrae and the first thoracic sympathetic ganglia. SG block (SGB) is a minimally invasive injection that aims to inject low-concentration local anesthetics to induce a broad sympathetic blocking effect near the SG. There have been no changes and progress in the clinical application of SGB since the 1830s due to several potential risks, including hematoma from blood vessel injury, hoarseness from recurrent laryngeal nerve injury, and cardiopulmonary arrest. The feasibility and safety of SGB have greatly improved since the appearance of ultrasound-guided SGB. In recent years, SGB has been widely applied in the field of non-anesthesiology sedation, with significant therapeutic effects on pain, immunological diseases, somnipathy, psychological disorders, arrhythmias, and endocrine diseases. The present study reviews the present application of SGB in clinical practice.

Hyphopodium-Specific Signaling Is Required for Plant Infection by Verticillium dahliae.

For successful colonization, fungal pathogens have evolved specialized infection structures to overcome the barriers present in host plants. The morphology of infection structures and pathogenic mechanisms are diverse according to host specificity. Verticillium dahliae, a soil-borne phytopathogenic fungus, generates hyphopodium with a penetration peg on cotton roots while developing appressoria, that are typically associated with leaf infection on lettuce and fiber flax roots. In this study, we isolated the pathogenic fungus, V. dahliae (VdaSm), from Verticillium wilt eggplants and generated a GFP-labeled isolate to explore the colonization process of VdaSm on eggplants. We found that the formation of hyphopodium with penetration peg is crucial for the initial colonization of VdaSm on eggplant roots, indicating that the colonization processes on eggplant and cotton share a similar feature. Furthermore, we demonstrated that the VdNoxB/VdPls1-dependent Ca2+ elevation activating VdCrz1 signaling is a common genetic pathway to regulate infection-related development in V. dahliae. Our results indicated that VdNoxB/VdPls1-dependent pathway may be a desirable target to develop effective fungicides, to protect crops from V. dahliae infection by interrupting the formation of specialized infection structures.