Human umbilical cord mesenchymal stem cells promoted tumor cell growth associated with increased interleukin-18 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is experiencing a concerning rise in both incidence and mortality rates. Current therapeutic strategies are limited in their effectiveness, largely due to the complex causes of the disease and significant levels of drug resistance. Given the latest developments in human umbilical cord mesenchymal stem cells (hUC-MSCs) research, there is a debate over the continued use of stem cell transplantation for treating tumors. Consequently, this study seeks to explore the role of hUC-MSCs in the management of HCC. METHODS AND RESULTS: HUC-MSCs increased the number (10.75 ± 1.50) in the DEN/TCPOBOP-induced mice hepatoma model, compared with DMSO group (7.25 ± 1.71). Moreover, the liver index in hUC-MSCs group (0.21 ± 0.06) was greater than that in DMSO group (0.09 ± 0.01). Immunohistochemical (IHC) analysis revealed that while hUC-MSCs did not alter Foxp3 expression, they significantly stimulated Ki67 expression, indicative of increased tumor cellular proliferation. Additionally, immunofluorescence (IF) studies showed that hUC-MSCs increased CD8+ T cell counts without affecting macrophage numbers. Notably, granzyme B expression remained nearly undetectable. We observed that serum IL-18 levels were higher in the hUC-MSCs group (109.66 ± 0.38 pg/ml) compared to the DMSO group (91.14 ± 4.37 pg/ml). Conversely, IL-1ß levels decreased in the hUC-MSCs group (63.00 ± 0.53 pg/ml) relative to the DMSO group (97.38 ± 9.08 pg/ml). CONCLUSIONS: According to this study, hUC-MSCs promoted the growth of liver tumors. Therefore, we proposed that hUC-MSCs are not suitable for treating HCC, as they exhibit clinically prohibited abnormalities.

First report of plastic and non-plastic microparticles in stomach of slandertail lanternshark and shortspine spurdog from the edge of East China Sea.

This study investigates the presence of plastic and non-plastic microparticles in the gastrointestinal tracts of two deep-sea sharks, Etmopterus molleri (n = 118) and Squalus mitsukurii (n = 6), bycatch from the East China Sea continental shelf. We found a total of 117 microparticles, predominantly fibres (67.52 %), with blue (31.62 %) and black (23.94 %) being the most prevalent colours. E. molleri contained 70 microparticles (0.63 ± 0.93 items/shark), 61.42 % non-plastics like viscose and cotton, while plastics included polyethylene, polyethylene terephthalate, and acrylic. Despite S. mitsukurii's limited sample size, the results show that it takes in a lot of microparticles (47 microparticles, 7.83 ± 2.64 items/shark), 57.44 % non-plastics (viscose, cotton, and ethyl cellulose), and 42.56 % plastics. A positive correlation between microparticle presence and total length was observed for E. molleri. These results provide initial data on microparticle ingestion by these species, highlighting potential ecological risks and trophic transfer implications in deep-sea ecosystems.

Lysine acetyltransferase 14 mediates TGF-ß-induced fibrosis in ovarian endometrioma via co-operation with serum response factor.

BACKGROUND: Fibrogenesis within ovarian endometrioma (endometrioma), mainly induced by transforming growth factor-ß (TGF-ß), is characterized by myofibroblast over-activation and excessive extracellular matrix (ECM) deposition, contributing to endometrioma-associated symptoms such as infertility by impairing ovarian reserve and oocyte quality. However, the precise molecular mechanisms that underpin the endometrioma- associated fibrosis progression induced by TGF-ß remain poorly understood. METHODS: The expression level of lysine acetyltransferase 14 (KAT14) was validated in endometrium biopsies from patients with endometrioma and healthy controls, and the transcription level of KAT14 was further confirmed by analyzing a published single-cell transcriptome (scRNA-seq) dataset of endometriosis. We used overexpression, knockout, and knockdown approaches in immortalized human endometrial stromal cells (HESCs) or human primary ectopic endometrial stromal cells (EcESCs) to determine the role of KAT14 in TGF-ß-induced fibrosis. Furthermore, an adeno-associated virus (AAV) carrying KAT14-shRNA was used in an endometriosis mice model to assess the role of KAT14 in vivo. RESULTS: KAT14 was upregulated in ectopic lesions from endometrioma patients and predominantly expressed in activated fibroblasts. In vitro studies showed that KAT14 overexpression significantly promoted a TGF-ß-induced profibrotic response in endometrial stromal cells, while KAT14 silencing showed adverse effects that could be rescued by KAT14 re-enhancement. In vivo, Kat14 knockdown ameliorated fibrosis in the ectopic lesions of the endometriosis mouse model. Mechanistically, we showed that KAT14 directly interacted with serum response factor (SRF) to promote the expression of α-smooth muscle actin (α-SMA) by increasing histone H4 acetylation at promoter regions; this is necessary for TGF-ß-induced ECM production and myofibroblast differentiation. In addition, the knockdown or pharmacological inhibition of SRF significantly attenuated KAT14-mediating profibrotic effects under TGF-ß treatment. Notably, the KAT14/SRF complex was abundant in endometrioma samples and positively correlated with α-SMA expression, further supporting the key role of KAT14/SRF complex in the progression of endometrioma-associated fibrogenesis. CONCLUSION: Our results shed light on KAT14 as a key effector of TGF-ß-induced ECM production and myofibroblast differentiation in EcESCs by promoting histone H4 acetylation via co-operating with SRF, representing a potential therapeutic target for endometrioma-associated fibrosis.

Thyroid cancer trends in China and its comparative analysis with G20 countries: Projections for 2020-2040.

Background: Thyroid cancer, a leading type of endocrine cancer, accounts for 3-4% of all cancer diagnoses. This study aims to analyse and compare thyroid cancer patterns in China and the Group twenty (G20) countries, and predict these trend for the upcoming two decades. Methods: This observational longitudinal study utilised data from the Global Burden of Disease (GBD) study 2019. We used metrics including incidence, mortality, mortality-incidence ratio (MIR), age-standardised rate (ASR) and average annual percent change (AAPC) to examine thyroid cancer trends. Joinpoint regression analysis was used to identify periods manifesting notable changes. The association between sociodemographic index (SDI) and AAPC were investigated. The autoregressive integrated moving average (ARIMA) model was used to predict thyroid cancer trends from 2020 to 2040. Results: From 1990 to 2019, thyroid cancer incidence cases in China increased by 289.6%, with a higher AAPC of age-standardised incidence rate (ASIR) in men. Contrastingly, the G20 demonstrated a smaller increase, particularly among women over 50. Despite the overall age-standardised mortality rate (ASMR) was higher in the G20, the increase in mortality was less pronounced than in China. Age-standardised incidence rate increased across all age groups and genders, with a notable rise among men aged 15-49. ASMR decreased in specific age groups and genders, especially among women. Conversely, the ASMR significantly increased in group aged over 70. The MIR exhibited a declining trend, but this decrease was less noticeable in men and the group aged over 70. Joinpoint analysis pinpointed significant shifts in overall ASIR and ASMR, with the most pronounced increase in ASIR during 2003-2011 in China and 2003-2010 in the G20. Predictions suggested a continual ASIR uptrend, especially in the 50-69 age group, coupled with a predicted ASMR downturn among the elderly by 2040. Moreover, the proportion of thyroid cancer deaths attributable to high body mass index (BMI) escalated, with significant increase in Saudi Arabia and a rise to 7.4% in China in 2019. Conclusions: Thyroid cancer cases in incidence and mortality are escalating in both China and the G20. The increasing trend may be attributed to factors beyond overdiagnosis, including environmental and genetic factors. These findings emphasise the necessity for augmenting prevention, control, and treatment strategies. They also highlight the significance of international collaboration in addressing the global challenge posed by thyroid cancer.

In vivo selection in non-human primates identifies AAV capsids for on-target CSF delivery to spinal cord.

Systemic administration of adeno-associated virus (AAV) vectors for spinal cord gene therapy has challenges including toxicity at high doses and pre-existing immunity that reduces efficacy. Intrathecal (IT) delivery of AAV vectors into cerebral spinal fluid can avoid many issues, although distribution of the vector throughout the spinal cord is limited, and vector entry to the periphery sometimes initiates hepatotoxicity. Here we performed biopanning in non-human primates (NHPs) with an IT injected AAV9 peptide display library. We identified top candidates by sequencing inserts of AAV DNA isolated from whole tissue, nuclei, or nuclei from transgene-expressing cells. These barcoded candidates were pooled with AAV9 and compared for biodistribution and transgene expression in spinal cord and liver of IT injected NHPs. Most candidates displayed increased retention in spinal cord compared with AAV9. Greater spread from the lumbar to the thoracic and cervical regions was observed for several capsids. Furthermore, several capsids displayed decreased biodistribution to the liver compared with AAV9, providing a high on-target/low off-target biodistribution. Finally, we tested top candidates in human spinal cord organoids and found them to outperform AAV9 in efficiency of transgene expression in neurons and astrocytes. These capsids have potential to serve as leading-edge delivery vehicles for spinal cord-directed gene therapies.

The prognostic and immunological role of MCM3 in pan-cancer and validation of prognosis in a clinical lower-grade glioma cohort.

Background: Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers. Methods: We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG. Results: MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort. Conclusion: Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.

Professional characteristics, numbers, distribution and training of China's mental health workforce from 2000 to 2020: a scoping review.

Over the last 20 years, the numbers, types, distribution, and qualifications of mental health professionals in China have changed dramatically. However, there has been no systematic attempt to collect information about this transformation in the human resources available to provide mental health services-information that needs to be regularly updated to improve the country's coordination of these services. This scoping review compiles current details about China's mental health workforce and identifies critical gaps in available research and reporting. We reviewed all relevant studies and reports published between 1 January 2000 and 30 June 2021 in two English-language and four Chinese-language databases, the website of China's National Health Commission, and national and provincial health services yearbooks. In addition to summarising data from government yearbooks, we integrated relevant results from 82 peer-reviewed publications and two government reports. From 2000 to 2020, the number of psychiatrists in the country increased by 139%, and the number of psychiatric nurses increased by 340%. However, the much higher ratio of mental health professionals per 100,000 population and the better quality of training of mental health professionals in urban, eastern provinces compared to rural, western provinces has not changed. Progress has been made in standardising the training of psychiatrists, but there are no standardised training programs for psychiatric nurses, clinical psychologists, or psychiatric social workers. Future research needs to address several issues that limit the effectiveness of policies aimed at increasing the size, quality and equitable distribution of China's mental health workforce: 1) limited data available about the numbers and characteristics of professionals who provide mental health services, 2) absence of nationally standardised training programs for non-psychiatric medical professionals and non-medical personnel who provide essential monitoring and supportive care to persons with mental illnesses, and 3) failure to scientifically assess the outcomes of currently available training programs.

Differential responses of the electron transfer capacities of soil humic acid and fulvic acid to long-term wastewater irrigation.

Wastewater irrigation is used to supplement agricultural irrigation because of its benefits and freshwater resource scarcity. However, whether wastewater irrigation for many years affects the electron transfer capacity (ETC) of natural organic matter in soil remains unclear, and organic matter could influence the decomposition and mineralization of substances with redox characteristics in soil through electron transfer, ultimately affecting the soil environment. The composition of soil humic substances (HS) is highly complex, and the effects of soil humic acid (HA) and fulvic acid (FA) on ETC is poorly understood. In this study, we separately evaluated the responses of the electron-accepting capacity (EAC) and electron-donating capacity (EDC) of soil HA and FA in agricultural fields to various durations of wastewater irrigation. Results showed that the EAC of HA and FA increased significantly with increasing the duration of wastewater irrigation. When wastewater irrigation lasted for 56 years, the EAC of HA showed a higher increment (590 %) than that of FA (223 %). The EDC of soil HA and FA, conversely, decreased compared to the control, with the highest reduction of 35.6 % for HA and 65.9 % for FA. Specifically, the EDC of HA gradually decreased starting from 29 years of wastewater irrigation, whereas the decrease in the EDC of FA exhibited no clear pattern in relation to the duration of wastewater irrigation. Increased soil organic matter and total nitrogen content under long-term wastewater irrigation led to an increase in sucrase and phosphatase activities, along with an increase in EAC and a decrease in EDC of HS. This suggests that soil enzyme activities may ultimately lead to changes in ETC. The results of this research provide practical insights into the redox system in soil and its driving role in soil organic matter transformation and nutrient cycling under wastewater irrigation.

Measurement of permanganate index in environmental water via indirect phase-conversion strategy.

In this work, we proposed an indirect phase-conversion strategy to construct a new approach for accurately and efficiently determining the permanganate index in water samples via headspace GC measurement. After the reducible substances in water reacted with excess potassium permanganate, the remaining potassium permanganate underwent a reaction with sodium oxalate under acidic conditions. The carbon dioxide generated from the gas-evolving reaction was then analyzed by headspace GC. Our findings showed that this new approach boasts high precision (relative standard deviation ≤ 2.18%) and accuracy for permanganate index analysis, thus validating the effectiveness of this new method in analyzing permanganate index. The introduction of the indirect phase-conversion strategy in this study is expected to set a precedent for further advancements in methodologies designed to indirectly evaluate substances capable of undergoing gas-producing reactions.

Research Progress of Warburg Effect in Hepatocellular Carcinoma.

The Warburg effect, also called aerobic glycolysis, refers to tumor cells that metabolize glucose through glycolysis even in the presence of oxygen. This rapid breakdown of glucose fuels the fast development, growth, and migration of tumor cells. Lactate, the final product of aerobic glycolysis, contributes to an acidic environment within the tumor, promoting the formation of an immunosuppressive microenvironment and accelerating tumor progression by impeding anti-tumor immunity. Numerous studies have confirmed the critical role of aerobic glycolysis in the occurrence and development of hepatocellular carcinoma by influencing tumor cells proliferation, invasion, metastasis, apoptosis, immune escape, angiogenesis, and more. Clinical trials have shown that inhibitors of rate-limiting enzymes in the glycolysis pathway can enhance the effectiveness of sorafenib, a targeted drug for hepatocellular carcinoma, by reducing drug resistance. Additionally, active components of traditional Chinese medicine and specific compound prescriptions are gaining attention for their potential to target and regulate aerobic glycolysis in hepatocellular carcinoma. Therefore, inhibiting the aerobic glycolysis pathway holds promise as a therapeutic strategy for treating liver tumors. This manuscript aims to review the role, research directions, and clinical studies of aerobic glycolysis in hepatocellular carcinoma.

Preparation of (S)-epichlorohydrin using a novel halohydrin dehalogenase by selective conformation adjustment.

Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheCPS to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheCPS mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheCPS, the catalytic efficiency (kcat(S)-ECH/Km(S)-ECH) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM-1 s-1), while the catalytic efficiency (kcat(1,3-DCP)/Km(1,3-DCP)) of the forward reaction only reduced from 0.83 to 0.71 mM-1 s-1. With 40 mM 1,3-DCP as substrate, HheCPS E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.

Sediment DNA Records the Critical Transition of Bacterial Communities in the Arid Lake.

It is necessary to predict the critical transition of lake ecosystems due to their abrupt, non-linear effects on social-economic systems. Given the promising application of paleolimnological archives to tracking the historical changes of lake ecosystems, it is speculated that they can also record the lake's critical transition. We studied Lake Dali-Nor in the arid region of Inner Mongolia because of the profound shrinking the lake experienced between the 1300 s and the 1600 s. We reconstructed the succession of bacterial communities from a 140-cm-long sediment core at 4-cm intervals and detected the critical transition. Our results showed that the historical trajectory of bacterial communities from the 1200 s to the 2010s was divided into two alternative states: state1 from 1200 to 1300 s and state2 from 1400 to 2010s. Furthermore, in the late 1300 s, the appearance of a tipping point and critical slowing down implied the existence of a critical transition. By using a multi-decadal time series from the sedimentary core, with general Lotka-Volterra model simulations, local stability analysis found that bacterial communities were the most unstable as they approached the critical transition, suggesting that the collapse of stability triggers the community shift from an equilibrium state to another state. Furthermore, the most unstable community harbored the strongest antagonistic and mutualistic interactions, which may imply the detrimental role of interaction strength on community stability. Collectively, our study showed that sediment DNA can be used to detect the critical transition of lake ecosystems.

Dihydroartemisinin breaks the positive feedback loop of YAP1 and GLUT1-mediated aerobic glycolysis to boost the CD8+ effector T cells in hepatocellular carcinoma.

Aerobic glycolysis is a hallmark of hepatocellular carcinoma (HCC). Dihydroartemisinin (DHA) exhibits antitumor activity towards liver cancer. Our previous studies have shown that DHA inhibits the Warburg effect in HCC cells. However, the mechanism still needs to be clarified. Our study aimed to elucidate the interaction between YAP1 and GLUT1-mediated aerobic glycolysis in HCC cells and focused on the underlying mechanisms of DHA inhibiting aerobic glycolysis in HCC cells. In this study, we confirmed that inhibition of YAP1 expression lowers GLUT1-mediated aerobic glycolysis in HCC cells and enhances the activity of CD8+T cells in the tumor niche. Then, we found that DHA was bound to cellular YAP1 in HCC cells. YAP1 knockdown inhibited GLUT1-mediated aerobic glycolysis, whereas YAP1 overexpression promoted GLUT1-mediated aerobic glycolysis in HCC cells. Notably, liver-specific Yap1 knockout by AAV8-TBG-Cre suppressed HIF-1α and GLUT1 expression in tumors but not para-tumors in DEN/TCPOBOP-induced HCC mice. Even more crucial is that YAP1 forms a positive feedback loop with GLUT1-mediated aerobic glycolysis, which is associated with HIF-1α in HCC cells. Finally, DHA reduced GLUT1-aerobic glycolysis in HCC cells through YAP1 and prevented the binding of YAP1 and HIF-1α. Collectively, our study revealed the mechanism of DHA inhibiting glycolysis in HCC cells from a perspective of a positive feedback loop involving YAP1 and GLUT1 mediated-aerobic glycolysis and provided a feasible therapeutic strategy for targeting enhanced aerobic glycolysis in HCC.

ASSOCIATION OF MACULAR STRUCTURE WITH MICROPERIMETRY SENSITIVITY FOLLOWING VITRECTOMY FOR PROLIFERATE DIABETIC RETINOPATHY.

PURPOSE: To evaluate macular sensitivity using microperimetry in patients with proliferate diabetic retinopathy following vitrectomy and to investigate the relationship between the sensitivity and foveal microstructures with optical coherence tomography/angiography. METHODS: Eighty-four eyes of 84 patients with proliferative diabetic retinopathy, who were indicated for vitrectomy, had no intraocular surgery history 3 months preoperatively, and were able to ensure fundus examination after the vitrectomy, were included. A logMAR best-corrected visual acuity, macular sensitivity of microperimetry, macular retinal thickness, and macular vessel perfusion using optical coherence tomography/angiography were examined at 1 week, 1 month, and 3 months postoperatively. RESULTS: The logMAR best-corrected visual acuity and mean macular sensitivity of patients with proliferative diabetic retinopathy improved postoperatively (P < 0.05). There was a significant correlation between best-corrected visual acuity and mean sensitivity (P < 0.05). Postoperative mean macular sensitivity was significantly correlated with outer retinal thickness in the 0 to 6 mm macular area (P < 0.05) and also significantly correlated with deep capillary plexus perfusion (P < 0.05). Fixation stability and mean macular sensitivity did not show any correlation with glycated hemoglobin, triglyceride, serum total cholesterol, carbamide, and creatinine and duration of diabetes mellitus (P > 0.05). CONCLUSION: Postoperative mean macular sensitivity was significantly correlated with outer retinal thickness and deep capillary plexus perfusion for patients with proliferative diabetic retinopathy. The authors found that the visual performance of patients can be evaluated by the outer retinal thickness and deep capillary plexus perfusion, so optical coherence tomography/angiography examination can be an important prognostic factor for visual performance in patients.Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn; Registration No.: ChiCTR2100043399).

Deep learning unlocks label-free viability assessment of cancer spheroids in microfluidics.

Despite recent advances in cancer treatment, refining therapeutic agents remains a critical task for oncologists. Precise evaluation of drug effectiveness necessitates the use of 3D cell culture instead of traditional 2D monolayers. Microfluidic platforms have enabled high-throughput drug screening with 3D models, but current viability assays for 3D cancer spheroids have limitations in reliability and cytotoxicity. This study introduces a deep learning model for non-destructive, label-free viability estimation based on phase-contrast images, providing a cost-effective, high-throughput solution for continuous spheroid monitoring in microfluidics. Microfluidic technology facilitated the creation of a high-throughput cancer spheroid platform with approximately 12 000 spheroids per chip for drug screening. Validation involved tests with eight conventional chemotherapeutic drugs, revealing a strong correlation between viability assessed via LIVE/DEAD staining and phase-contrast morphology. Extending the model's application to novel compounds and cell lines not in the training dataset yielded promising results, implying the potential for a universal viability estimation model. Experiments with an alternative microscopy setup supported the model's transferability across different laboratories. Using this method, we also tracked the dynamic changes in spheroid viability during the course of drug administration. In summary, this research integrates a robust platform with high-throughput microfluidic cancer spheroid assays and deep learning-based viability estimation, with broad applicability to various cell lines, compounds, and research settings.

Clinical value of the Patient Global Assessment with Ankylosing Spondylitis: A cross-sectional study.

To analyze the factors associated with the overall patient condition and explore the clinical value of the Patient Global Assessment (PGA) index for assessing the disease state in patients with Ankylosing Spondylitis (AS). This cross-sectional study used a standardized questionnaire to record the basic information of patients with AS. The collected data included the Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP), ASDAS-erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), PGA, and other clinical indicators. Statistical analysis was performed using SPSS 25.0 software, and the scale was assessed for retest reliability and structural validity. The Kruskal-Wallis H test and Spearman or Pearson correlation analysis were used to analyze the factors influencing PGA scores. The receiver operator characteristic (ROC) curve was used to identify the cutoff value of the PGA for predicting disease activity in AS. The patient age, disease duration, family history, and history of ocular inflammation significantly differed between PGA groups (P < .05). The median PGA was significantly lower in patients with disease remission than in those with disease activity (P < .01). The various clinical indexes significantly differed between PGA groups (P < .01). The PGA was significantly correlated with various clinical indicators (P < .01). The area under the ROC curve (AUC) for disease activity based on the ASDAS-CRP was 0.743 (P < .01) with a PGA cutoff value of 1.38; the AUC for disease activity based on the BASDAI was 0.715 (P < .01) with a PGA cutoff value of 1.63. The PGA was significantly correlated with patient-reported outcomes, disease activity, function, and psychological status, and may indicate the level of inflammation in patients with AS. A PGA of around 1.5 indicates disease activity.

Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial.

BACKGROUND: We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. METHODS: A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. RESULTS: BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). CONCLUSIONS: We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. TRIAL REGISTRATION: The trail has been registered at Chinese Clinical Trail Registry( https://www.chictr.org.cn ) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.

Icephobic Durability of Molecular Brush-Structured PDMS Soft Coatings.

The accumulation of ice can pose numerous inconveniences and potential hazards, profoundly affecting both human productivity and daily life. To combat the challenges posed by icing, extensive research efforts have been dedicated to the development of low-ice adhesion surfaces. In this study, we harness the power of molecular dynamics simulations to delve into the intricate dynamics of polymer chains and their role in determining the modulus of the material. We present a novel strategy to prepare ultralow-modulus poly(dimethylsiloxane) (PDMS) elastomers with a molecular brush configuration as icephobic materials. The process involves grafting monohydride-terminated PDMS (H-PDMS) as side chains onto backbone chain PDMS with pendant vinyl functional groups to yield a molecular brush structure. The segments of this polymer structure effectively restrict interchain entanglement, thereby rendering a lower modulus compared to traditional linear structures at an equivalent cross-linking density. The developed soft coating exhibits a remarkably ultralow ice adhesion strength of 13.1 ± 1.1 kPa. Even after enduring 50 cycles of icing and deicing, the ice adhesion strength of this coating steadfastly stayed below 16 kPa, showing no notable increase. Importantly, the molecular brush coating applied to glass demonstrated an impressive light transmittance of 92.1% within the visible light spectrum, surpassing the transmittance of bare glass, which was measured at 91.3%. This icephobic coating with exceptional light transmittance offers a wide range of applications and holds significant potential as a practical icephobic material.

Contralateral acupuncture for migraine without aura: a randomized trial protocol with multimodal MRI.

Introduction: Migraine is a common clinical disorder, ranks as the second most disabling disease worldwide, and often manifests with unilateral onset. Contralateral acupuncture (CAT), as a classical acupuncture method, has been proven to be effective in the treatment of migraine without aura (MWoA). However, its neural mechanisms have not been investigated using multimodal magnetic resonance imaging (MRI). Methods and analysis: In this multimodal neuroimaging randomized trial, a total of 96 female MWoA participants and 30 female healthy controls (HCs) will be recruited. The 96 female MWoA participants will be randomized into three groups: Group A (CAT group), Group B [ipsilateral acupuncture (IAT) group], and Group C (sham CAT group) in a 1:1:1 allocation ratio. Each group will receive 30 min of treatment every other day, three times a week, for 8 weeks, followed by an 8-week follow-up period. The primary outcome is the intensity of the migraine attack. Data will be collected at baseline (week 0), at the end of the 8-week treatment period (weeks 1-8), and during the 8-week follow-up (weeks 9-16). Adverse events will be recorded. Multimodal MRI scans will be conducted at baseline and after 8-week treatment. Discussion: This study hypothesized that CAT may treat MWoA by restoring pathological alterations in brain neural activity, particularly by restoring cross-integrated functional connectivity with periaqueductal gray (PAG) as the core pathological brain region. The findings will provide scientific evidence for CAT in the treatment of MWoA. Ethics and dissemination: The Medical Ethics Committee of the Second Affiliated Hospital of Yunnan University of Chinese Medicine has given study approval (approval no. 2022-006). This trial has been registered with the Chinese Clinical Trials Registry (registration no. ChiCTR2300069456). Peer-reviewed papers will be used to publicize the trial's findings. Clinical trial registration: https://clinicaltrials.gov/, identifier ChiCTR2300069456.