Non-invasive efficacy assessment of pulsed dye laser and photodynamic therapy for port-wine stain.

Port wine stain (PWS) is a congenital vascular malformation that commonly occurs on the face and neck. Currently, the main treatments for port wine stain are pulsed dye laser (PDL) and photodynamic therapy (PDT). However, the efficacy evaluation of PWS mostly relies on the subjective judgement of clinicians, and it is difficult to accurately respond to many small changes after treatment. Therefore, some non-invasive and efficient efficacy assessment methods are also needed. With the continuous development of technology, there are currently many visualisation instruments to evaluate PWS, including dermoscopy, VISIA-CR™ system, reflectance confocal microscopy (RCM), high-frequency ultrasound (HFUS), optical coherence tomography (OCT), Photoacoustic imaging (PAI), laser speckle imaging (LSI) and laser Doppler imaging (LDI). Among them, there are simple and low-cost technologies such as dermoscopy and the VISIA-CR™ system, but they may not be able to observe the deeper structures of PWS. At this time, combining techniques such as HFUS and OCT to increase penetration depth is crucial to evaluate PWS. In the future, the combination of these different technologies could help overcome the limitations of a single technology. This article provides a systematic overview of non-invasive methods for evaluating treatment efficacy in port wine stains and summarises their advantages and disadvantages.

Trends in the burden and determinants of HIV in the Asia-Pacific region (1990-2019): An age-period-cohort analysis of the 2019 Global Burden of Disease Study.

Although the burden of the human immunodeficiency virus (HIV) in the Asia-Pacific region is increasingly severe, comprehensive evidence of the burden of HIV is scarce. We aimed to report the burden of HIV in people aged 15-79 years from 1990 to 2019 using data from the Global Burden of Disease Study (GBD) 2019. We analyzed rates of age-standardized disability-adjusted life years (ASDR), age-standardized mortality (ASMR), and age-standardized incidence (ASIR) in our age-period-cohort analysis by sociodemographic index (SDI). According to HIV reports in 2019 from 29 countries in the Asia-Pacific region, the low SDI group in Papua New Guinea had the highest ASDR, ASMR, and ASIR. From 1990 to 2019, the ASDR, ASIR, and ASMR of persons with acquired immune deficiency syndrome (AIDS) increased in 21 (72%) of the 29 countries in the Asia-Pacific region. During the same period, the disability-adjusted life years (DALYs) of AIDS patients in the low SDI group in the region grew the fastest, particularly in Nepal. The incidence of HIV among individuals aged 20-30 years in the low-middle SDI group was higher than that of those in the other age groups. In 2019, unsafe sex was the main cause of HIV-related ASDR in the region's 29 countries, followed by drug use. The severity of the burden of HIV/AIDS in the Asia-Pacific region is increasing, especially among low SDI groups. Specific public health policies should be formulated based on the socioeconomic development level of each country to alleviate the burden of HIV/AIDS.

Significantly underestimated traffic-related ammonia emissions in Chinese megacities: Evidence from satellite observations during COVID-19 lockdowns.

Ammonia (NH3) plays an important role in the formation of atmospheric particulate matter, but the contribution of traffic-related emissions remains unclear, particularly in megacities with a large number of vehicles. Taking the opportunity of the stringent COVID-19 lockdowns implemented in Beijing and Shanghai in 2022, this study aims to estimate the traffic-related NH3 emissions in these two megacities based on satellite observations. Differences between urban and suburban areas during the lockdown and non-lockdown periods are compared. It was found that despite different dominating sources, the overall NH3 concentrations in urban and suburban areas were at a similar level, and the lockdown resulted in a more prominent decrease in urban areas, where traffic activities were most heavily affected. The traffic-related contribution to the total emission was estimated to be ∼30% in megacities, and ∼40% in urban areas, which are about 2-10 times higher than that in previous studies. The findings indicate that the traffic-related NH3 emissions have been significantly underestimated in previous studies and may play a more critical role in the formation of air pollution in megacities, especially in winter, when agricultural emissions are relatively low. This study highlights the importance of traffic-related NH3 emissions in Chinese megacities and the need to reassess the emissions and their impacts on air quality.

Risk factor evaluation of cuff pressure of >30 cmH2O to stop air leakage during mechanical ventilation: A prospective observational study.

AIM: The commonly recommended endotracheal tube cuff pressure is 20-30 cmH2O. However, some patients require a cuff pressure of >30 cmH2O to prevent air leakage. The study aims to determine the risk factors that contribute to the endotracheal tube cuff pressure of >30 cmH2O to prevent air leakage. DESIGN: A multi-centre prospective observational study. METHODS: Eligible patients undergoing mechanical ventilation in the intensive care unit of three hospitals between March 2020 and July 2022 were included. The endotracheal tube cuff pressure to prevent air leakage was determined using the minimal occlusive volume technique. The patient demographics and clinical information were collected. RESULTS: A total of 284 patients were included. Among these patients, 55 (19.37%) patients required a cuff pressure of >30 cmH2O to prevent air leakage. The multivariate logistic regression results revealed that the surgical operation (odds ratio [OR]: 8.485, 95% confidence interval [CI]: 1.066-67.525, p = 0.043) was inversely associated with the endotracheal tube cuff pressure of >30 cmH2O, while the oral intubation route (OR: 0.127, 95% CI: 0.022-0.750, p = 0.023) and cuff inner diameter minus tracheal area (OR: 0.949, 95% CI: 0.933-0.966, p < 0.001) were negatively associated with the endotracheal tube cuff pressure of >30 cmH2O. Therefore, a significant number of patients require an endotracheal tube cuff pressure of ＞30 cmH2O to prevent air leakage. Several factors, including the surgical operation, intubation route, and difference between the cuff inner diameter and tracheal area at the T3 vertebra, should be considered when determining the appropriate cuff pressure during mechanical ventilation.

Advances in circular RNA in the pathogenesis of epilepsy.

Recent studies evidenced the involvement of circular RNA (circRNA) in neuroinflammation, apoptosis, and synaptic remodeling suggesting an important role for circRNA in the occurrence and development of epilepsy. This review provides an overview of circRNAs considered to be playing regulatory roles in the process of epilepsy and to be involved in multiple biological epilepsy-related processes, such as hippocampal sclerosis, inflammatory response, cell apoptosis, synaptic remodeling, and cell proliferation and differentiation. This review covers the current research status of differential expression of circRNA-mediated seizures, m6A methylation, demethylation-mediated seizures in post transcriptional circRNA modification, as well as the mechanisms of m5C- and m7G-modified circRNA. In summary, this article reviews the research progress on the relationship between circRNA in non-coding RNA and epilepsy.

The adiponectin-derived peptide ALY688 protects against the development of metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is the severe form of non-alcoholic fatty liver disease which has a high potential to progress to cirrhosis and hepatocellular carcinoma, yet adequate effective therapies are lacking. Hypoadiponectinemia is causally involved in the pathogenesis of MASH. This study investigated the pharmacological effects of adiponectin replacement therapy with the adiponectin-derived peptide ALY688 (ALY688-SR) in a mouse model of MASH. Human induced pluripotent stem (iPS) cell-derived hepatocytes were used to test cytotoxicity and signaling of unmodified ALY688 in vitro. High-fat diet with low methionine and no added choline (CDAHF) was used to induce MASH and test the effects of ALY688-SR in vivo. Histological MASH activity score (NAS) and fibrosis score were determined to assess the effect of ALY688-SR. Transcriptional characterization of mice through RNA sequencing was performed to indicate potential molecular mechanisms involved. In cultured hepatocytes, ALY688 efficiently induced adiponectin-like signaling, including the AMP-activated protein kinase and p38 mitogen-activated protein kinase pathways, and did not elicit cytotoxicity. Administration of ALY688-SR in mice did not influence body weight but significantly ameliorated CDAHF-induced hepatic steatosis, inflammation, and fibrosis, therefore effectively preventing the development and progression of MASH. Mechanistically, ALY688-SR treatment markedly induced hepatic expression of genes involved in fatty acid oxidation, whereas it significantly suppressed the expression of pro-inflammatory and pro-fibrotic genes as demonstrated by transcriptomic analysis. ALY688-SR may represent an effective approach in MASH treatment. Its mode of action involves inhibition of hepatic steatosis, inflammation, and fibrosis, possibly via canonical adiponectin-mediated signaling.

TRPV4 mediates IL-1-induced Ca2+ signaling, ERK activation and MMP expression.

Ca2+ permeation through TRPV4 in fibroblasts is associated with pathological matrix degradation. In human gingival fibroblasts, IL-1ß binding to its signaling receptor (IL-1R1) induces activation of extracellular regulated kinase (ERK) and MMP1 expression, processes that require Ca2+ flux across the plasma membrane. It is not known how IL-1R1, which does not conduct Ca2+, generates Ca2+ signals in response to IL-1. We examined whether TRPV4 mediates the Ca2+ fluxes required for ERK signaling in IL-1 stimulated gingival fibroblasts. TRPV4 was immunostained in fibroblasts of human gingival connective tissue and in focal adhesions of cultured mouse gingival fibroblasts. Human gingival fibroblasts treated with IL-1ß showed no change of TRPV4 expression but there was increased MMP1 expression. In mouse, gingival fibroblasts expressing TRPV4, IL-1 strongly increased [Ca2+]i. Pre-incubation of cells with IL-1 Receptor Antagonist blocked Ca2+ entry induced by IL-1 or the TRPV4 agonist GSK101. Knockout of TRPV4 or expression of a non-Ca2+-conducting TRPV4 pore-mutant or pre-incubation with the TRPV4 inhibitor RN1734, blocked IL-1-induced Ca2+ transients and expression of the mouse interstitial collagenase, MMP13. Treatment of mouse gingival fibroblasts with GSK101 phenocopied Ca2+ and ERK responses induced by IL-1; these responses were absent in TRPV4-null cells or cells expressing a non-conducting TRPV4 pore-mutant. Immunostained IL-1R1 localized with TRPV4 in adhesions within cell extensions. While TRPV4 immunoprecipitates analyzed by mass spectrometry showed no association with IL-1R1, TRPV4 associated with Src-related proteins and Src co-immunoprecipitated with TRPV4. Src inhibition reduced IL-1-induced Ca2+ responses. The functional linkage of TRPV4 with IL-1R1 expands its repertoire of innate immune signaling processes by mediating IL-1-driven Ca2+ responses that drive matrix remodeling in fibroblasts. Thus, inhibiting TRPV4 activity may provide a new pharmacological approach for blunting matrix degradation in inflammatory diseases.

Dietary α-linolenic acid supplementation enhances resistance to Salmonella Typhimurium challenge in chickens by altering the intestinal mucosal barrier integrity and cecal microbes.

Salmonella is an important foodborne pathogen. Given the ban on the use of antibiotics during the egg-laying period in China, finding safe and effective alternatives to antibiotics to reduce Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infections in chickens is essential for the prevention and control of this pathogen and the protection of human health. Numerous studies have shown that unsaturated fatty acids have a positive effect on intestinal inflammation and resistance to infection by intestinal pathogens. Here we investigated the protective effect of α-linolenic acid (ALA) against S. Typhimurium infection in chickens and further explored its mechanism of action. We added different proportions of ALA to the feed and observed the effect of ALA on S. Typhimurium colonization using metagenomic sequencing technology and physiological index measurements. The role of gut flora on S. Typhimurium colonization was subsequently verified by fecal microbiota transplantation (FMT). We found that ALA protects chickens from S. Typhimurium infection by reducing intestinal inflammation through remodeling the gut microbiota, up-regulating the expression of ileocecal barrier-related genes, and maintaining the integrity of the intestinal epithelium. Our data suggest that supplementation of feed with ALA may be an effective strategy to alleviate S. Typhimurium infection in chickens.

Clinical characteristics and literature review of chronic active Epstein-Barr virus-associated enteritis.

Chronic active Epstein-Barr virus (EBV) infection-associated enteritis (CAEAE) in nonimmunodeficient individuals is rare. To report a case of CAEAE, relevant articles were searched through databases. The clinical manifestations, endoscopic findings, strategies of treatment, prognoses, and follow-up results of CAEAE patients were analyzed. Including this report, seven citations in the literature provide descriptions of 27 cases of CAEAE. There were 21 males and six females, with a mean age of 40 years. The main clinical manifestations were fever (25/27), abdominal pain (14/27), diarrhea (16/27), hematochezia or bloody stools (13/27), and decreased hemoglobin and red blood cell counts in routine blood tests (14/27). Elevations in inflammatory markers, white blood cell (WBC) counts, and C-reactive protein (CRP) were common. Coagulation was often abnormal. Histopathology confirmed EBV-encoded small nuclear RNA (EBER) in the affected tissue via in situ hybridization. The average serum EBV DNA load was 6.3 × 10^5 copies/mL. All patients had varying degrees of intestinal ulcers endoscopically, and the ulcers and pathology were uncharacterized and misdiagnosed mostly as inflammatory bowel disease (IBD). The course of the disease was progressive and later complicated by intestinal bleeding, intestinal perforation, septic shock, and a high rate of emergency surgery. However, the conditions of the patients often did not improve after surgery, and some patients soon died due to reperforation or massive hematochezia. Hormone and antiviral treatment had no obvious effect. There was a significant difference in surgical and nonsurgical survival (p < 0.05). The proportion of patients who died within 6 months was as high as 63.6% (7/11). CAEAE belongs to a group of rare, difficult conditions, has an insidious clinical course, has a high case fatality rate, and may later develop into EBV-positive lymphoproliferative disorder (EBV-LPD), which in turn leads to carcinogenesis. Clinicians should raise awareness that in patients with multiple ulcers in the intestine of unknown etiology, attention should be paid to EBV serology, and histology to make the diagnosis as early as possible.

Exploiting tertiary lymphoid structures gene signature to evaluate tumor microenvironment infiltration and immunotherapy response in colorectal cancer.

Background: Tertiary lymphoid structures (TLS) is a particular component of tumor microenvironment (TME). However, its biological mechanisms in colorectal cancer (CRC) have not yet been understood. We desired to reveal the TLS gene signature in CRC and evaluate its role in prognosis and immunotherapy response. Methods: The data was sourced from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Based on TLS-related genes (TRGs), the TLS related subclusters were identified through unsupervised clustering. The TME between subclusters were evaluated by CIBERSORT and xCell. Subsequently, developing a risk model and conducting external validation. Integrating risk score and clinical characteristics to create a comprehensive nomogram. Further analyses were conducted to screen TLS-related hub genes and explore the relationship between hub genes, TME, and biological processes, using random forest analysis, enrichment and variation analysis, and competing endogenous RNA (ceRNA) network analysis. Multiple immunofluorescence (mIF) and immunohistochemistry (IHC) were employed to characterize the existence of TLS and the expression of hub gene. Results: Two subclusters that enriched or depleted in TLS were identified. The two subclusters had distinct prognoses, clinical characteristics, and tumor immune infiltration. We established a TLS-related prognostic risk model including 14 genes and validated its predictive power in two external datasets. The model's AUC values for 1-, 3-, and 5-year overall survival (OS) were 0.704, 0.737, and 0.746. The low-risk group had a superior survival rate, more abundant infiltration of immune cells, lower tumor immune dysfunction and exclusion (TIDE) score, and exhibited better immunotherapy efficacy. In addition, we selected the top important features within the model: VSIG4, SELL and PRRX1. Enrichment analysis showed that the hub genes significantly affected signaling pathways related to TLS and tumor progression. The ceRNA network: PRRX1-miRNA (hsa-miR-20a-5p, hsa-miR-485-5p) -lncRNA has been discovered. Finally, IHC and mIF results confirmed that the expression level of PRRX1 was markedly elevated in the TLS- CRC group. Conclusion: We conducted a study to thoroughly describe TLS gene signature in CRC. The TLS-related risk model was applicable for prognostic prediction and assessment of immunotherapy efficacy. The TLS-hub gene PRRX1, which had the potential to function as an immunomodulatory factor of TLS, could be a therapeutic target for CRC.

CRISPR/Cas9-induced LEAP2 and GHSR1a knockout mutant zebrafish displayed abnormal growth and impaired lipid metabolism.

Investigating the principles of fish fat deposition and conducting related research are current focal points in fish nutrition. This study explores the endocrine regulation of LEAP2 and GHSR1a in zebrafish by constructing mutantmodels andexamining the effects of the endocrine factors LEAP2 and its receptor GHSR1a on zebrafish growth, feeding, and liver fat deposition. Compared to the wild type (WT), the mutation of LEAP2 results in increased feeding and decreased swimming in zebrafish. The impact is more pronounced in adult female zebrafish, characterized by increased weight, length, width, and accumulation of lipid droplets in the liver.Incontrast, deficiency in GHSR1a significantly reduces the growth of male zebrafish and markedly decreases liver fat deposition.These research findings indicate the crucial roles of LEAP2 and GHSR1a in zebrafish feeding, growth, and intracellular fat metabolism. This study, for the first time, investigated the endocrine metabolic regulation functions of LEAP2 and GHSR1a in the model organism zebrafish, providing initial insights into their effects and potential mechanisms on zebrafish fat metabolism.

A preclinical animal study to evaluate the operability and safety of domestic one-way endobronchial valves.

Purpose: To evaluate the operability and safety of bronchoscopic domestic one-way endobronchial valves (EBV) on animals. Methods: Nine pigs were randomly assigned (2:1) to receive domestic one-way EBV (the experimental group, n = 6) and Zephyr® EBV (the control group, n = 3). Routine blood tests, arterial blood gases, and CT scans of the lungs were performed 1 day pre-procedure in addition to 1 week and 1 month post-procedure to assess changes in blood markers and lung volumes. At 1 month post-procedure, the animals were sacrificed, followed by removal of all valves via bronchoscopy. Pathological examinations of critical organs were subsequently performed. Results: A total of 15 valves were placed in the experimental group and 6 valves were placed in the control group, without serious complications. Routine blood tests and arterial blood gas examinations at 1 day pre-procedure, 1 week post-procedure, and 1 month post-procedure did not differ significantly in both groups. No EBV displacement was noted under bronchoscopy, and the valve was smoothly removable by bronchoscope at 1 month post-procedure. At 1 week post-procedure, varying degrees of target lung lobe volume reduction were observed on lung CT in both groups. Lung volume reduction was achieved at 1 month post-procedure in both groups, without significant statistical difference. Although 3 cases in the experimental group and 1 case in the control group developed varying degrees of pneumonia, the inflammatory response did not increase over time during the experimental period. Pathological examination revealed no significant abnormal changes in the critical organs for both groups. Conclusion: Our results demonstrate that domestic EBV is safe and reliable for endobronchial application in general-grade laboratory white pigs. The safety of domestic EBV is similar to that of Zephyr® EBV, with good ease of use and operability. This kind of domestic EBV can meet the safety evaluation requirements for animal testing.

Angiogenesis-related lncRNAs index: A predictor for CESC prognosis, immunotherapy efficacy, and chemosensitivity.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is a common gynecologic tumor and patients with advanced and recurrent disease usually have a poor clinical outcome. Angiogenesis is involved in the biological processes of tumors and can promote tumor growth and invasion. In this paper, we created a signature for predicting prognosis based on angiogenesis-related lncRNAs (ARLs). This provides a prospective direction for enhancing the efficacy of immunotherapy in CESC patients. We screened seven OS-related ARLs by univariate and multivariate regression analyses and Lasso analysis and developed a prognostic signature at the same time. Then, we performed an internal validation in the TCGA-CESC cohort to increase the precision of the study. In addition, we performed a series of analyses based on ARLs, including immune cell infiltration, immune function, immune checkpoint, tumor mutation load, and drug sensitivity analysis. Our created signature based on ARLs can effectively predict the prognosis of CESC patients. To strengthen the prediction accuracy of the signature, we built a nomogram by combining signature and clinical features.

Characteristics of Virology and Immune Inflammation of Epstein-Barr Virus Infection Related Non-Neoplastic Diseases in Children.

BACKGROUND: The goal was to study the difference of virological, immunologic, and inflammatory indicators between Epstein-Barr associated infectious mononucleosis (EBV-IM) and EBV associated hemophagocytic lymphohistiocytosis (EBV-HLH) and to explore the evaluation indicators for monitoring the therapeutic efficacy of EBV-HLH. METHODS: Twenty children with EBV-IM (IM group) and 10 children with EBV-HLH (HLH group) were selected. Virology indicators were detected; the absolute count of lymphocyte, and lymphocyte subsets were detected; the levels of immunoglobulin and ferritin were assayed. RESULTS: Compared to the IM group, the HLH group showed a decrease in EBV-specific VCA-IgM antibody levels (U = 29.0, p = 0.006) and an increase in EBV-specific NA-IgG antibody levels (U = 17.0, p = 0.001), while there was no significant difference in EB-DNA loads (t = 0.417, p = 0.680). The counts of lymphocytes, and various lymphocyte subsets in the HLH group were lower than those in the IM group. Inflammatory markers in the HLH group were significantly higher than those in IM group. Dynamic monitoring of virological, immunological, and inflammatory indicators in HLH patients during treatment showed that EBV DNA gradually decreased in patients with good prognosis. Inflammatory indicators significantly decreased and returned to normal, lymphocyte count significantly increased and returned to normal during treatment. However, patients with poor prognosis showed rebound increase in EBV DNA and inflammatory indicators in the later stage of treatment, while lymphocyte count further decreased with the recurrence of the disease. CONCLUSIONS: Exhausted and damaged immune function in host by persistent stimulation of EB viral antigen is one of the main pathogeneses of EB-HLH. Lymphocyte count and serum ferritin level are effective indicators to monitor the therapeutic efficacy during the treatment to HLH.

Clinical research progress of callisperes® of drug-loaded microsphere arterial chemoembolisation in the treatment of solid tumors.

The incidence and mortality of cancer is ever-increasing, which poses a significant challengesto human health and a substantial economic burden to patients. At present, chemotherapy is still a primary treatment for various cancers. However, chemotherapy kills tumors but also induces the related side effects, whichadversely impacting patient quality of life and exacerbating suffering. Therefore, there is an urgent need for new and effective treatments that can control tumor growth while reducing the side effects for patients. Arterial chemoembolization has been attracted much attentionwhich attributed to the advantage of ability to embolize tumor vessels to block blood and nutrition supplies. Thus, to achieve local tumor control, it has become an effective means of local tumor control and has been widely used in clinical practice. Despite its efficacy, conventional arterial chemoembolization techniques, limited by embolization materials, have been associated with incomplete embolization and suboptimal drug delivery outcomes. Gradually, researchers have shifted their attention to a new type of embolic material called CalliSperes® drug-eluting embolic bead (DEB). DEB can not only load high doses of drugs, but also has strong sustained drug release ability and good biocompatibility. The integration of DEBs with traditional arterial chemoembolization (DEB-TACE) promises targeted vascular embolization, mitigated tumor ischemia and hypoxia, and direct intravascular chemotherapy delivery. It can prevent cancer cell differentiation and accelerate their death, meanwhile, directly injecting chemotherapy drugs into the target blood vessels reduced the blood concentration of the whole body, thus reduced the toxic and side effects of chemotherapy. Furthermore, DEB-TACE's sustained drug release capability elevates local drug concentrations at the tumor site, amplifying its antitumor efficacy. Therefore, DEB-TACE has become a hot spot in clinical research worldwide. This review introduces the pathogenesis of solid tumors, the background of research and biological characteristics of DEB, and the action mechanism of DEB-TACE, as well as its clinical research in various solid tumors and future prospects. This review aims to provide new ideas for the treatment of DEB-TACE in various solid tumors.

Effect of anterior segment structure on vault and position after implantable collamer lens implantation.

PURPOSE: To evaluate the effect of anterior-segment structure on vault and position after implantable collamer lens (ICL) implantation using ultrasound biomicroscopy. METHODS: The retrospective case-control study included insufficient vault eyes (<250 µm), ideal vault eyes (250-750 µm), and excessive vault eyes (>750 µm). The preoperative biometric parameters of the anterior-segment structure and basic data between the three groups were analyzed using one-way analysis of variance. RESULTS: There were significant differences ( P < 0.05) between the three groups in maximum ciliary body thickness (CBT max ), iris-zonule distance (IZD), and trabecular-ciliary angle (TCA). The vault gradually decreased as CBT max decreased and TCA increased. In the pairwise comparison, the CBT max comparison between the insufficient vault (<250 µm) group and the excessive vault (>750 µm) group was statistically significant ( P = 0.024, 95% CI: -0.17-0.017 µm); the TCA comparison between the insufficient vault (<250 µm) group and the excessive vault (>750 µm) group was statistically significant ( P = 0.005, 95% CI: 1.78°-12.15°); The IZD comparison between the insufficient vault (<250 µm) group and the excessive vault (>750 µm) group was statistically significant ( P = 0.037, 95% CI: 0.0027-0.1119 µm). The analysis of 284 ICL haptics locations showed that there were 16.67%, 32.69%, and 70.83% haptics located in the ciliary sulcus in three groups, respectively. CONCLUSION: The vault and ICL haptics position are related to anterior-segment structure. A thinner and posteriorly positioned ciliary body would increase the risk of low vault and fewer ICL haptics located in the ciliary sulcus after ICL implantation. This provides guidance for the selection of the ICL size and placement position before surgery.

Mechanochromic Polymer Film with High Sensitivity toward Tensile Strain by the Post-Curing Ring-Closure Induced Pre-Stretching.

Mechanochromic materials has received broad research interests recently, owing to its ability to monitor the in-situ stress/strain in polymer materials in a straight forward way. However, one major setback that hinder the practical application of these materials is their low sensitivity toward tensile strain. Here we show a new strategy for pre-stretching of the mechanochromic agent in a polymer film on the molecular scale, which can effectively enhance the mechanochromic sensitivity of a polymer film toward tensile strain. In-situ fluorescent measurement during tensile test showed an early activation of the mechanochromic agent at tensile strain as low as 50%. The pre-stretching effect is realized by firstly inducing ring-opening of the mechanochromic agent by molecular functionalization, and then compelling the ring-closure process in the cured film by elevated temperature. This post-curing ring-closure process will result in pre-stretched mechanochromic agent in a crosslinked network. The mechanism for mechanochromic activation of polymer films with different composition was elaborated by visco-elastic measurements, and the effect of pre-stretching was further confirmed by polymer films with other compositions. Combined with the simplicity of the method developed, we believe this work will offer an alternative strategy to enhance the sensitivity of different mechanochromic agents toward tensile strain. This article is protected by copyright. All rights reserved.

Phospholipids of inhaled liposomes determine the in vivo fate and therapeutic effects of salvianolic acid B on idiopathic pulmonary fibrosis.

Since phospholipids have an important effect on the size, surface potential and hardness of liposomes that decide their in vivo fate after inhalation, this research has systematically evaluated the effect of phospholipids on pulmonary drug delivery by liposomes. In this study, liposomes composed of neutral saturated/unsaturated phospholipids, anionic and cationic phospholipids were constructed to investigate how surface potential and the degree of saturation of fatty acid chains determined their mucus and epithelium permeability both in vitro and in vivo. Our results clearly indicated that liposomes composed of saturated neutral and anionic phospholipids possessed high stability and permeability, compared to that of liposomes composed of unsaturated phospholipids and cationic phospholipids. Furthermore, both in vivo imaging of fluorescence-labeled liposomes and biodistribution of salvianolic acid B (SAB) that encapsulated in liposomes were performed to estimate the effect of phospholipids on the lung exposure and retention of inhaled liposomes. Finally, inhaled SAB-loaded liposomes exhibited enhanced therapeutic effects in a bleomycin-induced idiopathic pulmonary fibrosis mice model via inhibition of inflammation and regulation on coagulation-fibrinolytic system. Such findings will be beneficial to the development of inhalable lipid-based nanodrug delivery systems for the treatment of respiratory diseases where inhalation is the preferred route of administration.

Large-volume RT-LAMP enables extraction-free amplification of HIV RNA from fingerstick plasma.

BACKGROUND: Point-of-care (POC) nucleic acid amplification tests (NAAT) can significantly expand testing coverage, which is critical for infectious disease diagnostics and monitoring. The development of various isothermal amplification techniques greatly simplifies NAATs, but the cumbersome nucleic acid extraction step remains a bottleneck for the POC. Alternatively, extraction-free amplification, where crude samples are directly added into the assay, substantially simplifies the workflow. However, sample dilution is often needed in extraction-free amplification to reduce assay inhibition from sample matrices. Since NAATs are typically run at small volumes around 20 µL, the input sample quantity is therefore limited, resulting in an inevitable sensitivity loss. RESULTS: Here we explore the potential to perform isothermal amplification in larger reaction volumes to accommodate larger sample quantities, thereby improving sensitivity in extraction-free amplification. We demonstrated the approach by developing large-volume reverse transcription loop-mediated isothermal amplification (RT-LAMP) for HIV RNA detection from fingerstick plasma. We found that LAMP at reaction volumes up to 1 mL maintained the same performance. We then identified plasma dilution conditions needed to maintain the limit of detection in RT-LAMP. Subsequently, using inactivated HIV virus, we showed the successful detection of 24 HIV RNA copies in a 500 µL RT-LAMP reaction in the presence of 20 µL plasma (fingerstick volumes), translating to a viral load of 1200 copies per mL. To reduce the increased reagent cost with expanded reaction volumes, we further identified lower-cost reagents with maintained assay performance. Moreover, we showed that large-volume LAMP, compared to 20 µL reactions, could tolerate higher concentrations of various inhibitors in the sample, such as albumin and GuSCN. SIGNIFICANCE AND NOVELTY: NAATs are conventionally conducted at small reaction volumes. Here we demonstrated that LAMP can be run at large reaction volumes (over 100 µL) with maintained assay performance, allowing sample inhibition to be mitigated while accommodating larger sample quantities. The same strategy of expanding reaction volumes could be applied to other isothermal amplification methods and various POC applications, to streamline test workflows and/or improve assay sensitivity.