Reyanning mixture inhibits M1 macrophage polarization through the glycogen synthesis pathway to improve lipopolysaccharide-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Reyanning (RYN) mixture is a traditional Chinese medicine composed of Taraxacum, Polygonum cuspidatum, Scutellariae Barbatae and Patrinia villosa and is used for the treatment of acute respiratory system diseases with significant clinical efficacy. AIM OF THE STUDY: Acute lung injury (ALI) is a common clinical disease characterized by acute respiratory failure. This study was conducted to evaluate the therapeutic effects of RYN on ALI and to explore its mechanism of action. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the chemical components of RYN. 7.5 mg/kg LPS was administered to induce ALI in rats. RYN was administered by gavage at doses of 2 ml/kg, 4 ml/kg or 8 ml/kg every 8 h for a total of 6 doses. Observations included lung histomorphology, lung wet/dry (W/D) weight ratio, lung permeability index (LPI), HE staining, Wright-Giemsa staining. ELISA was performed to detect the levels of TNF-α, IL-6, IL-10, Arg-1,UDPG. Immunohistochemical staining detected IL-6, F4/80 expression. ROS, MDA, SOD, GSH/GSSG were detected in liver tissues. Multiple omics techniques were used to predict the potential mechanism of action of RYN, which was verified by in vivo closure experiments. Immunofluorescence staining detected the co-expression of CD86 and CD206, CD86 and P2Y14, CD86 and UGP2 in liver tissues. qRT-PCR detected the mRNA levels of UGP2, P2Y14 and STAT1, and immunoblotting detected the protein expression of UGP2, P2Y14, STAT1, p-STAT1. RESULTS: RYN was detected to contain 1366 metabolites, some of the metabolites with high levels have anti-inflammatory, antibacterial, antiviral and antioxidant properties. RYN (2, 4, and 8 ml/kg) exerted dose-dependent therapeutic effects on the ALI rats, by reducing inflammatory cell infiltration and oxidative stress damage, inhibiting CD86 expression, decreasing TNF-α and IL-6 levels, and increasing IL-10 and Arg-1 levels. Transcriptomics and proteomics showed that glucose metabolism provided the pathway for the anti-ALI properties of RYN and that RYN inhibited lung glycogen production and distribution. Immunofluorescence co-staining showed that RYN inhibited CD86 and UGP2 expressions. In vivo blocking experiments revealed that blocking glycogen synthesis reduced UDPG content, inhibited P2Y14 and CD86 expressions, decreased P2Y14 and STAT1 mRNA and protein expressions, reduced STAT1 protein phosphorylation expression, and had the same therapeutic effect as RYN. CONCLUSION: RYN inhibits M1 macrophage polarization to alleviate ALI. Blocking glycogen synthesis and inhibiting the UDPG/P2Y14/STAT1 signaling pathway may be its molecular mechanism.

Nontargeted Identification of Organic Components in Fine Particulate Matter Related to Lung Tumor Metastasis Based on an Adverse Outcome Pathway Strategy.

Emerging studies implicate fine particulate matter (PM2.5) and its organic components (OCs) as urgent hazard factors for lung cancer progression in nonsmokers. Establishing the adverse outcome pathway (AOP)-directed nontargeted identification method, this study aimed to explore whether PM2.5 exposure in coal-burning areas promoted lung tumor metastasis and how we identify its effective OCs to support traceability and control of regional PM2.5 pollution. First, we used a nude mouse model of lung cancer for PM2.5 exposure and found that the exposure significantly promoted the hematogenous metastases of A549-Luc cells in lung tissues and the adverse outcomes (AOs), with key events (KEs) including the changed expression of epithelial-mesenchymal transition (EMT) markers, such as suppression of E-cad and increased expression of Fib. Subsequently, using AOs and KEs as adverse outcome directors, we identified a total of 35 candidate chemicals based on the in vitro model and nontargeted analysis. Among them, tributyl phosphate (C12H27O4P), 2-bromotetradecane (C14H29Br), and methyl decanoate (C11H22O2) made greater contributions to the AOs. Finally, we clarified the interactions between these OCs and EMT-activating transcription factors (EMT-ATFs) as the molecular initiation event (MIE) to support the feasibility of the above identification strategy. The present study updates a new framework for identifying tumor metastasis-promoting OCs in PM2.5 and provides solid data for screening out chemicals that need priority control in polluted areas posing higher lung cancer risk.

Research hotspots and frontiers in post-stroke dysphagia: a bibliometric analysis study.

Background: Dysphagia is a common complication of stroke that can result in serious consequences. In recent years, more and more papers on post-stroke dysphagia have been published in various journals. However, there is still a lack of bibliometric analysis of post-stroke dysphagia. This study visually analyzes the global research situation of post-stroke dysphagia from 2013 to 2022, aiming to explore the current research status, frontier trends, and research hotspots in this field. Methods: Articles and reviews relevant to post-stroke dysphagia were obtained and retrieved from the Web of Science core collection database in the last 10 years (from 2013 to 2022). CiteSpace and Microsoft Excel 2019 were used for bibliographic analysis. Results: A total of 1,447 articles were included in the analysis. The number of publications showed an overall upward trend, from 72 in 2013 to 262 in 2022. The most influential authors, institutions, journals, and countries were Hamdy S, University of London, Dysphagia, and the People's Republic of China. An analysis of keywords and the literature indicated that current studies in the field of post-stroke dysphagia focused on dysphagia and aspiration, dysphagia classification, dysphagia rehabilitation, and daily living. Conclusion: This bibliometric analysis reveals the latest advancements and emerging trends in the field of post-stroke dysphagia, spanning the years 2013 to 2022. It highlights the paramount importance of conducting large-scale randomized controlled trials examining the efficacy of dysphagia screening protocols and non-invasive intervention techniques in improving the quality of life for these patients. Such research efforts hold significant academic implications for the development of evidence-based treatment strategies in this field.

Evaluation of Quantitative and Selective Sensory Fiber Dysfunction in Patients with Cirrhosis.

BACKGROUND: Chronic liver disease has been reported to be associated with peripheral neuropathy. However, which sensory fibers are affected remains unknown. The objective of this study was to examine the function of sensory nerve fibers in patients with cirrhosis using the current perception threshold (CPT) test, as well as the correlation between blood biochemical indicators related to cirrhosis and CPT values. METHODS: We recruited 44 patients with liver cirrhosis and 37 healthy controls of the same age and gender. The Neurometer® system for the CPT test was used to stimulate the median nerve on the right index finger, as well as the deep and superficial peroneal nerves on the right hallux, using three distinct parameters (2000 Hz, 250 Hz, and 5 Hz). Comparative analysis was performed on the CPT values of the sensory nerves. Additionally, the correlation between CPT values and biochemical blood indicators in the study participants was analyzed. RESULTS: Under 2000 Hz electrical stimulation, there was a significant difference between the cirrhosis and healthy control groups in the median nerve as well as the deep and superficial peroneal nerves (p < 0.05). In addition, the median nerve CPT value of the cirrhosis group was significantly higher than that of the control group at an electrical stimulation frequency of 250 Hz (p = 0.005). There was no correlation between CPT values and blood biochemical indicators. CONCLUSION: According to the results, the sensory peripheral neuropathy in liver cirrhosis is mainly manifested as Aß fiber neuropathy.

LRRC75A-AS1 drives the epithelial-mesenchymal transition in cervical cancer by binding IGF2BP1 and inhibiting SYVN1-mediated NLRP3 ubiquitination.

Cervical cancer severely affects women's health with increased incidence and poor survival for patients with metastasis. Our study aims to investigate the mechanism by which lncRNA LRRC75A-AS1 regulates the epithelial-mesenchymal transition (EMT) of cervical cancer through modulating m6A and ubiquitination modification. In this study, tumor tissues were collected from patients to analyze the expression of LRRC75A-AS1 and SYVN1. Migratory and invasive capacities of HeLa and CaSki cells were evaluated with wound healing and transwell assays. CCK-8 and EdU incorporation assays were employed to examine cell proliferation. The interaction between LRRC75A-AS1, IGF2BP1, SYVN1, and NLRP3 was evaluated through RNA immunoprecipitation, RNA pull-down, FISH, and Co-IP assays, respectively. MeRIP-qPCR was applied to analyze the m6A modification of SYVN1 mRNA. A subcutaneous tumor model of cervical cancer was established. We showed LRRC75A-AS1 was upregulated in tumor tissues, and LRRC75A-AS1 enhanced EMT through activating NLRP3/IL-1ß/Smad2/3 signaling in cervical cancer. Furthermore, LRRC75A-AS1 inhibited SYVN1-mediated NLRP3 ubiquitination by destabilizing SYVN1 mRNA. LRRC75A-AS1 competitively bound to IGF2BP1 protein and subsequently impaired the m6A modification of SYVN1 mRNA and its stability. Knockdown of LRRC75A-AS1 repressed EMT and tumor growth via inhibiting NLRP3/IL-1ß/Smad2/3 signaling in mice. In conclusion, LRRC75A-AS1 competitively binds to IGF2BP1 protein to destabilize SYVN1 mRNA, subsequently suppresses SYVN1-mediated NLRP3 ubiquitination degradation and activates IL-1ß/Smad2/3 signaling, thus promoting EMT in cervical cancer. Implications: LRRC75A-AS1 promotes cervical cancer progression, and this study suggests LRRC75A-AS1 as a new therapeutic target for cervical cancer.

Primordial Drivers of Diabetes Heart Disease: Comprehensive Insights into Insulin Resistance.

Insulin resistance has been regarded as a hallmark of diabetes heart disease (DHD). Numerous studies have shown that insulin resistance can affect blood circulation and myocardium, which indirectly cause cardiac hypertrophy and ventricular remodeling, participating in the pathogenesis of DHD. Meanwhile, hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with insulin resistance can directly impair the metabolism and function of the heart. Targeting insulin resistance is a potential therapeutic strategy for the prevention of DHD. Currently, the role of insulin resistance in the pathogenic development of DHD is still under active research, as the pathological roles involved are complex and not yet fully understood, and the related therapeutic approaches are not well developed. In this review, we describe insulin resistance and add recent advances in the major pathological and physiological changes and underlying mechanisms by which insulin resistance leads to myocardial remodeling and dysfunction in the diabetic heart, including exosomal dysfunction, ferroptosis, and epigenetic factors. In addition, we discuss potential therapeutic approaches to improve insulin resistance and accelerate the development of cardiovascular protection drugs.

Polymer carbon nitride nanosheet-based lamellar membranes inspired by "couple hardness with softness" for ultrafast molecular separation in organic solvents.

Membranes with ultrafast molecular separation ability in organic solvents can offer unprecedented opportunities for efficient and low-cost solvent recovery in industry. Herein, a graphene-like polymer carbon nitride nanosheet (PCNN) with a low-friction surface was applied as the main membrane building block to boost the ultrafast transport of the solvent. Meanwhile, inspired by the concept of "couple hardness with softness", soft and flexible graphene oxide (GO) was chosen to fix the random stack of the rigid PCNN and tailor the lamellar structure of the PCNN membrane. The optimal PCNN/GO lamellar membrane shows a remarkable methanol permeance of 435.5 L m-2 h-1 bar-1 (four times higher than that of the GO membrane) while maintaining a high rejection for reactive black (RB, 98.9% in ethanol). Molecular dynamics simulations were conducted to elucidate the ultrafast transport mechanism of the PCNN/GO membrane. This study reveals that PCNN is a promising building block for lamellar membranes and may open up new avenues for high-performance molecular separation membranes.

Chronic Inflammation in Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is an increasingly prevalent disease that affects approximately 10-12% of the global population. Therefore, it is considered a public health priority. Persistent and systemic low-grade chronic inflammation (CI) is an important part of the poor prognosis in CKD, especially for patients with advanced disease. For example, CI worsens anemia and promotes atherosclerosis. Therefore, CI deserves our attention. SUMMARY: The formation of CI in CKD involves many aspects. Among them, the decline in the glomerular filtration rate leads to the influence of substances or inflammatory cytokines that should be cleared in time. In addition, oxidative stress, the gut, and the gut microbiota are also influencing factors. KEY MESSAGES: In this review, we highlight the mechanisms involved in the development of CI in CKD.

A new perspective in the prevention and treatment of antitumor therapy-related cardiotoxicity: Intestinal microecology.

The continuous development of antitumor therapy has significantly reduced the mortality of patients with malignancies. However, the antitumor-related cardiotoxicity has become the leading cause of long-term mortality in patients with malignancies. Besides, the pathogenesis of antitumor-related cardiotoxicity is still unclear, and practical means of prevention and treatment are lacking in clinical practice. Therefore, the major challenge is how to combat the cardiotoxicity of antitumor therapy effectively. More and more studies have shown that antitumor therapy kills tumor cells while causing damage to sensitive tissues such as the intestinal mucosa, leading to the increased permeability of the intestine and the dysbiosis of intestinal microecology. In addition, the dysbiosis of intestinal microecology contributes to the development and progression of cardiovascular diseases through multiple pathways. Thus, the dysbiosis of intestinal microecology may be a potential mechanism and target for antitumor-related cardiotoxicity. We summarized the characteristics of intestinal microecology disorders induced by antitumor therapy and the association between intestinal microecological dysbiosis and CVD. And on this basis, we hypothesized the potential mechanisms of intestinal microecology mediating the occurrence of antitumor-related cardiotoxicity. Then we reviewed the previous studies targeting intestinal microecology against antitumor-associated cardiotoxicity, aiming to provide a reference for future studies on the occurrence and prevention of antitumor-related cardiotoxicity by intestinal microecology.

Nuclear magnetic resonance-based metabolomic study of rat serum after anterior cruciate ligament injury.

Anterior cruciate ligament (ACL) injury, a common sports injury, is associated with a high risk of subsequent osteoarthritis (OA), which can cause serious pain and disability. Understanding the detailed mechanism underlying the predisposition of knee with ACL injury to secondary OA at an early stage is key to preventing future degradation and progression to a clinically significant disease. A total of 56 male Sprague Dawley rats (age, 8 weeks; weight, 180-220 g) were randomly divided into three experimental groups: control, ACL transection (ACLT; where surgical procedure was performed with ACLT), and sham (where surgical procedure was performed without ACLT). The ACLT and sham groups were further divided into three subgroups based on when the rats were sacrificed: 4, 8, and 12 weeks after the surgical procedure. The control group and the aforementioned subgroups contained 8 rats each. We used nuclear magnetic resonance (NMR)-based metabolomic analysis to analyze rat serum samples for the metabolic characteristics and the underlying mechanisms. In total, 28 metabolites were identified in the NMR spectra of the rat sera. At 4 and 8 weeks postoperatively, the sham group demonstrated metabolic profiles different from those of the ACLT group. However, this difference was not observed 12 weeks postoperatively. In total, five metabolites (acetate, succinate, sn-glycero-3-phosphocholine, glucose, and phenylalanine) and five metabolic pathways (phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism; pyruvate metabolism; starch and sucrose metabolism; and histidine metabolism) demonstrated significant differences between the ACLT and sham groups. ACL injury was noted to considerably affect biochemical homeostasis and metabolism; however, these metabolic changes persisted briefly. Moreover, glucose was a characteristic metabolite, and several energy-related metabolic pathways were significantly disturbed. Therefore, an ACL injury may lead to considerable impairments in energy metabolism. Abnormal glucose levels facilitate chondrocyte function impairment and thereby lead to OA progression. Furthermore, lactate may aid in identifying metabolic changes specific to knee trauma not related to an ACL injury. Overall, the metabolic changes in rat serum after an ACL injury were closely related to disturbances in energy metabolism and amino acid metabolism. The current results may aid in understanding the pathogenesis of posttraumatic osteoarthritis.

Investigation into the Effectiveness of Combining Transcranial Direct Current Stimulation and Transcutaneous Electrical Nerve Stimulation as Treatment Options for Poststroke Shoulder Pain by Utilizing Functional Near-Infrared Spectroscopy.

Objective: The aim of this study is to explore the therapeutic effects of transcranial direct current stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) on post stroke shoulder pain (PSSP). Methods: We enrolled 13 individuals in this study who underwent three different treatments in a random sequence: active tDCS+active TENS, active tDCS+sham TENS, and sham tDCS+active TENS. Each treatment was administered once, with a 3-day washout period between interventions. A blinded rater assessed the visual analog scale (VAS) scores, fNIRS readings, and sensory and pain tolerance thresholds of the participants before and after the stimulation. Results: All three treatment methods can significantly alleviate PSSP (p<0.05). Compared with using tDCS alone, tDCS+TENS can significantly improve pain, with a statistically significant difference (p<0.05). In the 2KHz PTT task, the three treatment methods showed significant differences (p<0.05) in the mean oxygenated hemoglobin (HbO) levels in the false premotor cortex (PMC)/auxiliary motor area (SMA) before and after intervention. Conclusion: The combination of tDCS+TENS can increase the pain-relieving impact on PSSP when compared to using tDCS alone. TENS may contribute an additional effect on the inhibitory systems influenced by tDCS that help reduce pain. Clinical Registration Number: Registration website: https://www.chictr.org.cn. Registration date: 2022-02-25. Registration number: ChiCTR2200056970.

Circadian rhythm disturbances involved in ozone-induced glucose metabolism disorder in mouse liver.

Ozone (O3) is a key environmental factor for developing diabetes. Nevertheless, the underlying mechanisms remain unclear. This study aimed to investigate alterations of glycometabolism in mice after O3 exposure and the role of circadian rhythms in this process. C57BL/6 male mice were randomly assigned to O3 (0.5 ppm) or filtered air for four weeks (4 h/day). Then, hepatic tissues of mice were collected at 4 h intervals within 24 h after O3 exposure to test. The results showed that hepatic circadian rhythm genes oscillated abnormally, mainly at zeitgeber time (ZT)8 and ZT20 after O3 exposure. Furthermore, detection of glycometabolism (metabolites, enzymes, and genes) revealed that O3 caused change in the daily oscillations of glycometabolism. The serum glucose content decreased at ZT4 and ZT20, while hepatic glucose enhanced at ZT16 and ZT24(0). Both G6pc and Pck1, which are associated with hepatic gluconeogenesis, significantly increased at ZT20. O3 exposure disrupted glycometabolism by increasing gluconeogenesis and decreasing glycolysis in mice liver. Finally, correlation analysis showed that the association between Bmal1 and O3-induced disruption of glycometabolism was the strongest. The findings emphasized the interaction between adverse outcomes of circadian rhythms and glycometabolism following O3 exposure.

Novel treatment from a botanical formulation Si-Miao-Yong-an decoction inhibits vasa vasorum angiogenesis and stabilizes atherosclerosis plaques via the Wnt1/ß-catenin signalling pathway.

CONTEXT: Si-Miao-Yong-An (SMYA) has been widely used for the clinical treatment of atherosclerosis (AS). Yet, its complete mechanism of action is not fully understood. OBJECTIVE: To investigate the mechanism by which SMYA stabilizes AS plaques from the perspective of inhibiting vasa vasorum (VV) angiogenesis. MATERIALS AND METHODS: We used male ApoE-/- mice to establish an AS model. The mice were divided into model, SMYA (11.7 mg/kg/d), and simvastatin (SVTT) (2.6 mg/kg/d) groups. Mice were given SMYA or SVTT by daily gavage for 8 weeks. HE staining, immunofluorescence double-labelling staining, and immunohistochemical staining were used to observe the pathological changes in the plaques. Finally, the protein and mRNA expression levels of the Wnt1/ß-catenin signalling pathway were detected by Western blot and qRT-PCR, respectively. RESULTS: SMYA significantly attenuated cholesterol crystallization, and lipid accumulation in AS plaques, resulting in smaller plaque size (0.25 mm2 vs. 0.46 mm2), and lowering ratio of plaque to lumen area (20.04% vs. 38.33%) and VV density (50.64/mm2 vs. 98.02/mm2). Meanwhile, SMYA suppressed both the positive area percentage of Wnt1 (2.53 vs. 3.56), ß-catenin (3.33 vs. 5.65) and Cyclin D1 (2.10 vs. 3.27) proteins in the aortic root plaques, and mRNA expression of Wnt1 (1.38 vs. 2.09), ß-catenin (2.05 vs. 3.25) and Cyclin D1 (1.39 vs. 2.57). DISCUSSION AND CONCLUSIONS: SMYA has a protective effect against AS, which may be related to its anti-VV angiogenesis in plaques, suggesting that SMYA has the potential as a novel botanical formulation in the treatment of AS.

The efficacy and safety of 0.01% atropine alone or combined with orthokeratology for children with myopia: A meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of 0.01% atropine alone and in combination with orthokeratology for myopia control using a meta-analysis. METHODS: PubMed, Cochrane Library, and EMBASE were searched. We included eligible randomized controlled trials (RCTs), non-RCTs, and retrospective cohort studies, published up to August 1, 2022. We calculated the weighted mean difference (WMD) and 95% confidence interval (CI) for all outcomes and plotted them in forest plots. RESULTS: Fourteen studies were included; 4 and 11 in the 0.01% atropine monotherapy and atropine-orthokeratology (AOK) groups, respectively. Compared with orthokeratology (OK) alone, 0.01% atropine alone had similar effects on slowing the axial elongation (WMD: -0.00 mm; 95% CI: -0.05-0.04, p<0.31), while AOK significantly lowered axial growth. Moreover, the baseline myopic degree and duration of treatment were influential for the change in axial elongation (WMD: -0.12 mm; 95% CI: -0.17--0.07, p = 0.00001 and WMD: -0.11 mm; 95% CI: -0.15--0.108, p<0.00001, respectively). Additionally, the AOK may reduce the change rate of the spherical equivalent refraction and the accommodation amplitude (WMD: -0.13 D; 95% CI: 0.07-0.19, p<0.001 and WMD: -1.08 mm; 95% CI: -1.73--0.43, p<0.0001, respectively), and cause a slight increase in the diameter of the pupil (WMD: 0.56 mm; 95% CI: 0.43-0.70, p = 0.007). No significant differences in the uncorrected distant visual acuity, best corrected visual acuity, intraocular pressure, tear film break-up time, lipid layer thickness, and corneal endothelial cell density were found between the OK and AOK groups. CONCLUSION: In slowing the axial elongation, 0.01% atropine alone and OK alone have similar effects, while AOK is more effective than OK alone in slowing down the axial elongation. Furthermore, the baseline degree of myopia and treatment duration may affect changes in axial elongation.

The Effect of W Content on the Microstructure, Mechanics and Electrical Performance of an FeCrCo Alloy.

In this paper, FeCrCoW alloys with different W contents (0.4, 2.1 and 3.4 at%) are designed and studied in order to overcome the existing shortcomings of resistance materials. These resistance materials have high resistivity and a low temperature coefficient of resistivity. It is observed that the addition of W has a remarkable effect on the phase structure of the alloy. In particular, when the W content is 3.4 at%, the single BCC phase of the alloy can be transformed into the BCC and FCC phase. Meanwhile, when analyzed by transmission electron microscopy, there are stacking faults and martensite in FeCrCoW alloy with W content of 3.4 at%. These features are related to excessive W content. In addition, the strength of the alloy can be improved, and the ultimate tensile strength and yield strength are both very high, which are considered as grain-boundary strengthening and solid solution strengthening, caused by the addition of W. The electrical resistivity of the FeCrCoW alloys decreases when the content of W is more than 2.1 at%. The maximum resistivity of the alloy is 170 ± 1.5 µΩ·cm. Moreover, the unique properties of the transition metal allow the alloy to have a low temperature coefficient of resistivity in the temperature range of 298~393 K. The temperature coefficient of resistivity values of the W0.4, W2.1 and W3.4 alloys are -0.0073, -0.0052 and -0.0051 ppm/K. Therefore, this work provides a vision for resistance alloys, which can achieve highly stable resistivity and high strengths in a certain temperature range.

Prediction of spherical equivalent refraction and axial length in children based on machine learning.

Purpose: Recently, the proportion of patients with high myopia has shown a continuous growing trend, more toward the younger age groups. This study aimed to predict the changes in spherical equivalent refraction (SER) and axial length (AL) in children using machine learning methods. Methods: This study is a retrospective study. The cooperative ophthalmology hospital of this study collected data on 179 sets of childhood myopia examinations. The data collected included AL and SER from grades 1 to 6. This study used the six machine learning models to predict AL and SER based on the data. Six evaluation indicators were used to evaluate the prediction results of the models. Results: For predicting SER in grade 6, grade 5, grade 4, grade 3, and grade 2, the best results were obtained through the multilayer perceptron (MLP) algorithm, MLP algorithm, orthogonal matching pursuit (OMP) algorithm, OMP algorithm, and OMP algorithm, respectively. The R2 of the five models were 0.8997, 0.7839, 0.7177, 0.5118, and 0.1758, respectively. For predicting AL in grade 6, grade 5, grade 4, grade 3, and grade 2, the best results were obtained through the Extra Tree (ET) algorithm, MLP algorithm, kernel ridge (KR) algorithm, KR algorithm, and MLP algorithm, respectively. The R2 of the five models were 0.7546, 0.5456, 0.8755, 0.9072, and 0.8534, respectively. Conclusion: Therefore, in predicting SER, the OMP model performed better than the other models in most experiments. In predicting AL, the KR and MLP models were better than the other models in most experiments.

Posterior corneal elevation changes during 12 month of overnight orthokeratology.

Aims: the aim of this study to investigate the elevation changes in posterior corneal surface after 12 months of orthokeratology (ortho-k) treatment. Methods: In this retrospective chart review, medical records of 37 Chinese children who wore ortho-k lenses over 12 months were reviewed. The data of only right eye were analyzed. Variables including the flat and steep keratometry of anterior and posterior corneal principal meridians, central corneal thickness (CCT), posterior thinnest elevation of cornea (PTE), posterior central elevation of cornea (PCE) and posterior mean elevation of cornea (PME) were measured by Pentacam. Variables including anterior chamber depth (ACD), lens thickness (CLT) and ocular axis length (AL) were measured by optical biometry. All variables differences between baseline and 12 months after ortho-k treatment were assessed by statistical analyses. Results: The average age of all subjects was 10.70 ± 1.75 years (range 8-15 years old). The baseline spherical equivalent (SE) was -3.26 ± 1.52 D (-0.50D to -5.00D). Both flat and steep keratometry of anterior corneal surface and CCT were significantly decreased after 12 month follow up during ortho-k treatment (both P < 0.000). Both flat and steep keratometry of posterior corneal surface were not significantly different after 12 month follow up compared with that of baseline (P = 0.426, 0.134 respectively). PCE, PTE and PME were not significantly changed over 12 months of ortho-k treatment (P = 0.051, 0.952 and 0.197 respectively). The ACD was significantly decreased in 12 month follow up during ortho-k treatment (P = 0.001). The CLT and the AL were significantly increased during this period (both P < 0.000). Conclusion: Although the anterior corneal surface was significantly changed by ortho-k lens, the posterior corneal surface did not show any changes during 12 months follow up. Simultaneously, The ACD, CLT and AL were significantly changed during this period.

Integrative applications of network pharmacology and molecular docking: An herbal formula ameliorates H9c2 cells injury through pyroptosis.

Background: QiShen YiQi pills (QSYQ) is a Traditional Chinese Medicine (TCM) formula, which has a significant effect on the treatment of patients with myocardial infarction (MI) in clinical practice. However, the molecular mechanism of QSYQ regulation pyroptosis after MI is still not fully known. Hence, this study was designed to reveal the mechanism of the active ingredient in QSYQ. Methods: Integrated approach of network pharmacology and molecular docking, were conducted to screen active components and corresponding common target genes of QSYQ in intervening pyroptosis after MI. Subsequently, STRING and Cytoscape were applied to construct a PPI network, and obtain candidate active compounds. Molecular docking was performed to verify the binding ability of candidate components to pyroptosis proteins and oxygen-glucose deprivation (OGD) induced cardiomyocytes injuries were applied to explore the protective effect and mechanism of the candidate drug. Results: Two drug-likeness compounds were preliminarily selected, and the binding capacity between Ginsenoside Rh2 (Rh2) and key target High Mobility Group Box 1 (HMGB1)was validated in the form of hydrogen bonding. 2 µM Rh2 prevented OGD-induced H9c2 death and reduced IL-18 and IL-1ß levels, possibly by decreasing the activation of the NLRP3 inflammasome, inhibiting the expression of p12-caspase1, and attenuating the level of pyroptosis executive protein GSDMD-N. Conclusions: We propose that Rh2 of QSYQ can protect myocardial cells partially by ameliorating pyroptosis, which seems to have a new insight regarding the therapeutic potential for MI.

LRRC75A-AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression via enhancing SIX1 expression.

We aimed to investigate potential roles of LRRC75A-AS1 delivered by M2 macrophage exosomes in inducing cervical cancer progression. We demonstrated LRRC75A-AS1 was highly expressed in exosomes from M2 macrophages which could be absorbed by Hela cells. M2 macrophage-derived exosomes promoted Hela cell proliferation, migration, invasion, and EMT process by delivering LRRC75A-AS1. LRRC75A-AS1 directly targeted and suppressed miR-429 in Hela cells. The regulation of cell functions by exosomes from LRRC75A-AS1-overexpressing M2 macrophages was abrogated by miR-429 mimics. miR-429 directly targeted and repressed SIX1 expression. SIX1 overexpression alleviated the modulation of cellular functions and STAT3/MMP-9 signaling by miR-429 mimics. Also, miR-429 overexpression or SIX1 silence repressed tumor formation and metastasis in nude mice, which was mitigated by exosomes from LRRC75A-AS1-overexpressing M2 macrophages. In conclusion, LRRC75A-AS1 delivered by M2 macrophage exosomes repressed miR-429 to elevate SIX1 expression and promote cervical cancer progression through activating the STAT3/MMP-9 axis.

An Automatic Image Processing Method Based on Artificial Intelligence for Locating the Key Boundary Points in the Central Serous Chorioretinopathy Lesion Area.

Accurately and rapidly measuring the diameter of central serous chorioretinopathy (CSCR) lesion area is the key to judge the severity of CSCR and evaluate the efficacy of the corresponding treatments. Currently, the manual measurement scheme based on a single or a small number of optical coherence tomography (OCT) B-scan images encounters the dilemma of incredibility. Although manually measuring the diameters of all OCT B-scan images of a single patient can alleviate the previous issue, the situation of inefficiency will thus arise. Additionally, manual operation is subject to subjective factors of ophthalmologists, resulting in unrepeatable measurement results. Therefore, an automatic image processing method (i.e., a joint framework) based on artificial intelligence (AI) is innovatively proposed for locating the key boundary points of CSCR lesion area to assist the diameter measurement. Firstly, the initial location module (ILM) benefiting from multitask learning is properly adjusted and tentatively achieves the preliminary location of key boundary points. Secondly, the location task is formulated as a Markov decision process, aiming at further improving the location accuracy by utilizing the single agent reinforcement learning module (SARLM). Finally, the joint framework based on the ILM and SARLM is skillfully established, in which ILM provides an initial starting point for SARLM to narrow the active region of agent, and SARLM makes up for the defect of low generalization of ILM by virtue of the independent exploration ability of agent. Experiments reveal the AI-based method which joins the multitask learning, and single agent reinforcement learning paradigms enable agents to work in local region, alleviating the time-consuming problem of SARLM, performing location task in a global scope, and improving the location accuracy of ILM, thus reflecting its effectiveness and clinical application value in the task of rapidly and accurately measuring the diameter of CSCR lesions.