The involvement of ROS-regulated programmed cell death in hepatocellular carcinoma.

Reactive oxidative species (ROS) is a crucial factor in the regulation of cellular biological activity and function, and aberrant levels of ROS can contribute to the development of a variety of diseases, particularly cancer. Numerous discoveries have affirmed that this process is strongly associated with "programmed cell death (PCD)," which refers to the suicide protection mechanism initiated by cells in response to external stimuli, such as apoptosis, autophagy, ferroptosis, etc. Research has demonstrated that ROS-induced PCD is crucial for the development of hepatocellular carcinoma (HCC). These activities serve a dual function in both facilitating and inhibiting cancer, suggesting the existence of a delicate balance within healthy cells that can be disrupted by the abnormal generation of reactive oxygen species (ROS), thereby influencing the eventual advancement or regression of a tumor. In this review, we summarize how ROS regulates PCD to influence the tumorigenesis and progression of HCC. Studying how ROS-induced PCD affects the progression of HCC at a molecular level can help develop better prevention and treatment methods and facilitate the design of more effective preventative and therapeutic strategies.

Metabolic flux analysis of hydrogen production network by Ethanoligenens harbinense B49: effect of product inhibition.

In order to further understand the effect of product inhibition on the metabolism of hydrogen production bacteria, and to seek an effective way to increase the hydrogen yield in fermentation, a simplified metabolic model of Ethanoligenens harbinense B49 was constructed to analyse the metabolic flux under acetate and ethanol inhibition separately and to analyse the flux changes of the nodes. Based on the changes in metabolic flux distribution, Glucose 6-phosphate (G6P), Pyruvate (PYR), and Acetyl-CoA (AcCoA) were identified as key nodes of hydrogen production in the metabolic network. Robustness analysis showed that G6P was flexible, while AcCoA and PYR were weakly rigid, indicating that acetate flux could be increased by adding inhibitors or using genetic manipulation. Furthermore, releasing inhibition of acetate could effectively increase hydrogen production. These findings suggested that the addition of acetate separation in ethanol-type fermentation process is expected to improve hydrogen production, which might be a promising way to full-scale produce biohydrogen in industrial applications. Further, for the first time, we report the effect of product inhibition on key nodes in the E. harbinense B49 hydrogen production metabolism network.

Short-term Changes in Epithelial and Optical Redistribution Induced by Different Orthokeratology Designs.

OBJECTIVES: This study aimed to investigate corneal epithelial and topographic changes caused by two commercial myopia orthokeratology (ortho-k) designs. METHODS: Twenty-six subjects fitted with vision shape treatment (VST) lenses and 30 subjects fitted with corneal reshaping therapy (CRT) lenses were reviewed 1 day, 1 week, and 1 month after lens initiation. A spectral-domain optical coherence tomography system was used to create epithelial maps that were in turn used to determine the average epithelial thickness of each zone and the diameter of treatment zone. By measuring the topographic tangential differential map, the treatment zone diameter and the power and width of the high convex zone (HCZ) were obtained. All epithelial thicknesses and topographic corneal variations recorded were analyzed. RESULTS: At the central zone, the epithelial thickness changes (△ET) decreased significantly after 1 day of ortho-k in two groups. At 2- to 9-mm peripheral zone, ortho-k increased △ET until 1 week in the VST group, whereas it kept increasing in the CRT group after 1 week. At 1 month, the central △ET is -9.51±2.38 mm in the VST group, which was comparable to -8.72±3.43 mm in the CRT group. The nasal HCZ power and the △ET of nasal and inferior nasal were significantly larger in the CRT group. A positive correlation was found between the HCZ power and △ET generated by VST-type lenses inferiorly and temporally. For the CRT group, a positive correlation was found between inferior HCZ power and △ET. CONCLUSIONS: At the early stage of ortho-k, epithelial thickness and topography change quickly and simultaneously. Epithelial changes were in line with corneal topography reshaping. Epithelial and optical remodelling were affected by different lens types.

A Risk Model for Prognosis and Treatment Response Prediction in Colon Adenocarcinoma Based on Genes Associated with the Characteristics of the Epithelial-Mesenchymal Transition.

The epithelial-mesenchymal transition (EMT) is an important process during metastasis in various tumors, including colorectal cancer (CRC). Thus, the study of its characteristics and related genes is of great significance for CRC treatment. In this study, 26 EMT-related gene sets were used to score each sample from The Cancer Genome Atlas program (TCGA) colon adenocarcinoma (COAD) database. Based on the 26 EMT enrichment scores for each sample, we performed unsupervised cluster analysis and classified the TCGA-COAD samples into three EMT clusters. Then, weighted gene co-expression network analysis (WGCNA) was used to investigate the gene modules that were significantly associated with these three EMT clusters. Two gene modules that were strongly positively correlated with the EMT cluster 2 (worst prognosis) were subjected to Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. Then, a prognosis-related risk model composed of three hub genes GPRC5B, LSAMP, and PDGFRA was established. The TCGA rectal adenocarcinoma (READ) dataset and a CRC dataset from the Gene Expression Omnibus (GEO) were used as the validation sets. A novel nomogram that incorporated the risk model and clinicopathological features was developed to predict the clinical outcomes of the COAD patients. The risk model served as an independent prognostic factor. It showed good predictive power for overall survival (OS), immunotherapy efficacy, and drug sensitivity in the COAD patients. Our study provides a comprehensive evaluation of the clinical relevance of this three-gene risk model for COAD patients and a deeper understanding of the role of EMT-related genes in COAD.

Boundary of ecosystem services: Guiding future development and application of the ecosystem service concepts.

Ecosystem Services (ESs) are either material or non-material benefits humans receive from ecosystems. Definitions, classifications, and typologies of ESs can vary to address different research and policy purposes. However, a boundary that distinguishes ESs from other ecosystem-related benefits (e.g., industrial products that consume raw materials, fossil fuels that used to be a part of ecosystems) is needed to avoid the risk of using ESs as an all-encompassing metaphor that captures any benefit. The boundary also maintains a common ground for communication and comparison of ESs across studies. To guide future development and application of the ES concepts, we suggest five criteria. ESs are (1) primary contributions of ecosystems, (2) flows assessed during a period or per time unit (not stock existing at a time point), (3) renewable (having the potential to be reproduced with a conceivable timeframe relevant to human use), (4) affected by biotic parts of ecosystems to occur. ESs include both biotic and some abiotic flows (e.g., water provisioning) but exclude abiotic flows (e.g., wind and solar energy) whose occurrence is unaffected by ecosystem functions, processes, or characteristics; and (5) inclusive to the benefits humans actually and potentially receive from ecosystems. These criteria link ESs with conservation of life-supporting and culturally important ecosystems, recognize use, option, and non-use values of ESs, and highlight ESs' sustainability.

Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer.

BACKGROUND: Cervical cancer remains one of the most prevalent cancers worldwide. Accumulating evidence suggests that specificity protein 1 (Sp1) plays a pivotal role in tumour progression. The underlying role and mechanism of Sp1 in tumour progression remain unclear. METHODS: The protein level of Sp1 in tumour tissues was determined by immunohistochemistry. The effect of Sp1 expression on the biological characteristics of cervical cancer cells was assessed by colony, wound healing, transwell formation, EdU, and TUNEL assays. Finally, the underlying mechanisms and effects of Sp1 on the mitochondrial network and metabolism of cervical cancer were analysed both in vitro and in vivo. RESULTS: Sp1 expression was upregulated in cervical cancer. Sp1 knockdown suppressed cell proliferation both in vitro and in vivo, while overexpression of Sp1 had the opposite effects. Mechanistically, Sp1 facilitated mitochondrial remodelling by regulating mitofusin 1/2 (Mfn1/2), OPA1 mitochondrial dynamin-like GTPase (Opa1), and dynamin 1-like (Drp1). Additionally, the Sp1-mediated reprogramming of glucose metabolism played a critical role in the progression of cervical cancer cells. CONCLUSIONS: Our study demonstrates that Sp1 plays a vital role in cervical tumorigenesis by regulating the mitochondrial network and reprogramming glucose metabolism. Targeting Sp1 could be an effective strategy for the treatment of cervical cancer.

Analysis of the Dysfunctional Lens Index as a Novel Criterion for Surgical Decision-Making in Age-Related Cataracts.

BACKGROUND: The dysfunctional lens index (DLI) provided by a ray-tracing aberrometry system is an objective index in cataract assessment. The purpose of this study is to evaluate correlations among Lens Opacities Classification System III (LOCS III) grades, Catquest 9SF scores, and the (DLI) and the DLI's role in surgical decision-making in age-related mixed cataract. METHODS: This trial was registered at NIH (clinicaltrial.gov) on January 5, 2021 (NCT04711395). In this prospective cross-sectional study, age-related mixed cataract patients were recruited. One high-volume and two low-volume surgeons made surgical decisions based on corrected distance visual acuity (CDVA), LOCS III graded photographs, and Catquest 9SF scores. Their decision-making agreement was evaluated with Cohen's kappa coefficient. Correlations among the parameters were analyzed. The optimal cut-off DLI was calculated using a receiver operating characteristic curve. RESULTS: Overall, 106 patients (106 eyes) were included. Very good agreement levels were noted among the high- and low-volume surgeons (Cohen's kappa coefficient, 0.848) (95% CI, 0.748-0.948). The DLI had the strongest correlation with Catquest 9SF scores (R2 = 0.566), followed by with posterior subcapsular (R2 = 0.418), nuclear opalescence (R2 = 0.388), and cortical (R2 = 0.333, all P < .0001) cataract LOCS III grades. Catquest 9SF scores were correlated with cortical (R2 = 0.249), nuclear opalescence (R2 = 0.278), and posterior subcapsular (R2 = 0.235, all P < .0001) cataract LOCS III grades. A cut-off DLI of 5.36 was identified as a surgical criterion (specificity, 86.9%; sensitivity, 93.3%). CONCLUSIONS: The DLI is valuable for objectively assessing patient complaints and lens opacity severity. LOCS III remains effective and economical in assessing early cortical cataracts with relatively clear central lenses. A cut-off DLI ≤5.36 could be a criterion for preoperative decision-making.

EIF4A3-induced circBRWD3 promotes tumorigenesis of breast cancer through miR-142-3p_miR-142-5p/RAC1/PAK1 signaling.

CircBRWD3 is a newly discovered circRNA, and its potential function has not been probed. Here, we aimed to molecularly dissect the role of circBRWD3 in the tumorigenesis and progression of breast cancer (BC). qRT-PCR analysis revealed that circBRWD3 expression was dramatically upregulated in BC tissues, a feature that was positively correlated with the poor prognosis of patients with BC. CircBRWD3 knockdown repressed cell proliferation and metastasis, while promoting cell apoptosis in vitro. Consistently, an in vivo circBRWD3 deficiency model exhibited suppressed tumor metastasis and oncogenesis. On the other hand, circBRWD3 overexpression promoted cancer cell activity and tumorigenesis. Further, mechanistic studies elucidated that circBRWD3 sponged both miR-142-3p and miR-142-5p to modulate RAC1 expression, which subsequently activated the RAC1/PAK1 signaling to facilitate the tumorigenesis and progression of BC. Moreover, we discovered that EIF4A3 facilitated circBRWD3 expression by targeting the upstream of BRWD3 pre-mRNA. In conclusion, our study reveals that circBRWD3 facilitates BC tumorigenesis by regulating the circBRWD3/miR-142-3p_miR-142-5p /RAC1/PAK1 axis. In addition, circBRWD3 expression is positively regulated by an RNA-binding protein, EIFA3. Our results provide valuable scientific data for early diagnosis and therapy for breast cancer patients.

PD-L1/p-STAT3 promotes the progression of NSCLC cells by regulating TAM polarization.

PD-L1 is closely related to the immune escape process of tumour cells, and targeted PD-L1 clinical immunotherapy has been implemented. However, whether PD-L1 is involved in TAM/M2 polarization in the TME of NSCLC and its specific mechanism remain unclear. In order to clarify the specific role of PD-L1 in NSCLC and to seek new treatments for NSCLC, we designed a series of experimental studies. After constructing the co-culture system and conditioned medium system, the proliferation, apoptosis, metastasis, angiogenesis, EMT process and stemness of NSCLC were detected by MTT, flow cytometry, Transwell, endothelial cell tube formation and western blot assays. The results showed that αPD-L1 reversed TAM/M2 polarization by suppressing STAT3 phosphorylation in TAM/M2, therapy inhibiting NSCLC cell migration, angiogenesis, EMT process and stemness. However, αPD-L1 had no effect on the proliferation and apoptosis abilities of NSCLC cells. In vivo experiments showed that αPD-L1 inhibited lung metastasis of NSCLC and reversed TAM/M2 polarization in TME. The study investigates the mechanism by which PD-L1 regulates TAMs polarization in TME and promotes malignant progression of NSCLC, providing a new theoretical basis for PD-L1 targeted therapy of NSCLC.

PD­L1 mediates triple­negative breast cancer evolution via the regulation of TAM/M2 polarization.

Tumor­associated macrophages/M2­type (TAM/M2) play a key role in the metastasis and angiogenesis of cancer, and are considered to be critical targets for cancer treatment. However, it remains unclear whether α­programmed death­ligand 1 (αPD­L1; PD­L1 inhibitor) inhibits tumor progression via targeting TAMs. In the present study, it was demonstrated that αPD­L1 significantly inhibited IL­13­induced TAM/M2 polarization in vitro. Moreover, αPD­L1 inhibited the epithelial­mesenchymal transition (EMT) process and the stemness of triple­negative breast cancer (TNBC) cells, which were mediated via the reversal of TAM/M2 polarization. This therefore inhibited the migration and angiogenesis of TNBC cells. Furthermore, αPD­L1 prevented STAT3 phosphorylation and nuclear translocation, which resulted in the arrest of TAM/M2 polarization. In vivo experiments further demonstrated that αPD­L1 reduced the number of lung metastases without affecting tumor growth. Moreover, αPD­L1 reduced the expression levels of TAM/M2, EMT, stemness and vascular markers in tumor tissues. In summary, these data suggest that αPD­L1 plays a vital role in the anti­metastasis and anti­angiogenesis of TNBC in vitro and in vivo via the inhibition of TAM/M2 polarization. These findings may thus provide a novel therapeutic strategy for clinically refractory TNBC.

[Ginsenoside Rg3 Regulates Cisplatin Resistance in Gastric Cancer by Wnt/ß-catenin Signaling Pathway].

Objective To investigate the inhibitory effect of ginsenoside Rg3 combined with cisplatin (DDP) on DDP-resistant cell line SGC-7901/DDP and their molecular mechanism.Methods SGC-7901/DDP cells were divided into four groups including a control group,a ginsenoside Rg3 (40 µg/ml) treatment group,a DDP (1.40 µg/ml) treatment group,and a drug combination treatment group.The proliferation ability of SGC-7901/DDP cells was detected by MTT,EdU,and colony formation assays.The apoptosis ability of SGC-7901/DDP cell was detected by flow cytometry and Hoechst 33342 staining.The protein levels of apoptosis-related markers were detected by Western blotting.The migration ability of SGC-7901/DDP cells was detected by wound healing and Transwell assays.The expression levels of proteins in epithelial-mesenchymal transformation (EMT) and Wnt/ß-catenin signaling pathway were determined by Western blotting and immunofluorescence staining.Results Compared with the ginsenoside Rg3 or the DDP treatment groups,the drug combination treatment group inhibited the proliferation (t=8.062,P=0.001;t=7.090,P=0.002),colony formation (t=8.062,P=0.001;t=6.144,P=0.004),and migration (t=7.424,P=0.002;t=4.317,P=0.013),and promoted the apoptosis (t=5.530,P=0.031;t=6.036,P=0.026) of SGC-7901/DDP cells.Compared with the ginsenoside Rg3 and the DDP treatment groups,the drug combination treatment group down-regulated the expression levels of EMT-associated proteins including vimentin (t=24.450,P<0.001;t=14.750,P<0.001),Snail (t=29.640,P<0.001;t=70.700,P<0.001),Slug (t=89.230,P<0.001;t=87.360,P<0.001),matrix metalloproteinase (MMP) 2 (t=84.540,P<0.001;t=67.120,P<0.001),and MMP9 (t=19.010,P<0.001;t=10.890,P<0.001),as well as those of Wnt/ß-catenin signaling pathway related proteins including Wnt (t=35.480,P<0.001;t=14.670,P<0.001),ß-catenin (t=155.800,P<0.001;t=118.100,P<0.001),C-myc (t=20.870,P<0.001;t=3.334,P=0.029),and cyclin D1 (t=5.007,P=0.008;t=8.347,P=0.001).Meanwhile,it up-regulated the expression of epithelial cells including E-cadherin (t=36.450,P<0.001;t=33.810,P<0.001) and ZO-1 (t=37.060,P<0.001;t=37.030,P<0.001).Conclusion Ginsenoside Rg3 enhanced the sensitivity of SGC-7901/DDP cells to DDP by inhibiting the activity of Wnt/ß-catenin signaling pathway.

Regulation of wheat bran feruloyl oligosaccharides in the intestinal antioxidative capacity of rats associated with the p38/JNK-Nrf2 signaling pathway and gut microbiota.

BACKGROUND: Feruloyl oligosaccharides (FOs), the ferulic acid ester of oligosaccharides, may possess the physiological functions of both ferulic acid and oligosaccharides, including antioxidative activity and gut microbiota modulation capacity. The present study aimed to investigate whether FOs could regulate the intestinal antioxidative capacity of rats by modulating the MAPKs/Nrf2 signaling pathway and gut microbiota. Thirty Wistar rats were randomly divided into five groups. Rats received a standard diet and were gavaged once daily with 0.85% normal saline, 100 mg kg-1 body weight vitamin C or FOs solution at doses of 20, 40 and 80 mg kg-1 body weight for 21 days. RESULTS: FOs strengthened the antioxidative capacity of the jejunum, as indicated by increased in contents of catalase, superoxide dismutase and glutathione peroxidase, as well as glutathione. Moreover, FOs administration upregulated the mRNA expression level of antioxidant-related genes (glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit and heme oxygenase-1) in the jejunum. Increases in phosphorylation levels of Nrf2, p38 and JNK were also observed. Administration with 40 mg kg-1 FOs altered the structure and composition of the cecal microbiota, which was indicated by the increased the relative abundances of Actinobacteria, Proteobacteria and Acidobacteriota, and the decreased the relative abundances of Firmicutes, Lachnospiraceae_NK4A136_group and Blautia. Furthermore, Spearman correlation analysis revealed that the altered cecal microbiota closely correlated with jejunal antioxidative capacity of rats. CONCLUSION: FOs could be used as an antioxidant for gut heath improvement through modulating the p38/JNK-Nrf2 signaling pathway and gut microbiota. © 2022 Society of Chemical Industry.

Macular Morphologic and Microvascular Analysis in Pseudophakic Children with Previous Pediatric Cataract Using Optical Coherence Tomography Angiography.

INTRODUCTION: The macular morphologic and microvascular changes in children with pseudophakia after pediatric cataract surgery remain unknown. The aim of this study was to analyze macular morphologic and microvascular remodeling in children with pseudophakia after pediatric cataract surgery using optical coherence tomography angiography (OCTA). METHODS: Consecutive cases between December 1, 2018, and November 31, 2020 were recruited. Sixty-one participants (31 pseudophakic children and 30 healthy controls) met the inclusion criteria and were included for final analysis. OCTA was used to measure macular vascular density, the foveal avascular zone (FAZ), and macular thickness. The parameters were compared between pseudophakic and healthy eyes using binary logistic regression, with adjustment for the effect of refractive error, age, and axial length. RESULTS: Compared with normal eyes, a significantly reduced area of the FAZ (p = 0.042), increased superficial foveal vascular density (p = 0.033), and increased inner and outer foveal thickness (p = 0.034 and 0.029, respectively) were noted in pseudophakic eyes. The deep parafoveal vascular density was generally lower in eyes with cataracts (p ≤ 0.044). The inner foveal thickness was positively correlated with the superficial foveal vascular density (r = 0.889, p < 0.001) and negatively correlated with the area of the FAZ (r = -0.903, p < 0.001). The outer foveal thickness was positively correlated with the deep foveal vascular density (r = 0.399, p = 0.002). CONCLUSIONS: Morphological and microvascular remodeling in children with previous pediatric cataract indicates foveal underdevelopment. The underlying mechanism requires further investigation.

An advanced network pharmacology study to explore the novel molecular mechanism of Compound Kushen Injection for treating hepatocellular carcinoma by bioinformatics and experimental verification.

BACKGROUND: Compound Kushen Injection (CKI) is a Chinese patent drug that exerts curative effects in the clinical treatment of hepatocellular carcinoma (HCC). This study aimed to explore the targets and potential pharmacological mechanisms of CKI in the treatment of HCC. METHODS: In this study, network pharmacology was used in combination with molecular biology experiments to predict and verify the molecular mechanism of CKI in the treatment of HCC. The constituents of CKI were identified by UHPLC-MS/MS and literature search. The targets corresponding to these compounds and the targets related to HCC were collected based on public databases. To screen out the potential hub targets of CKI in the treatment of HCC, a compound-HCC target network was constructed. The underlying pharmacological mechanism was explored through the subsequent enrichment analysis. Interactive Gene Expression Profiling Analysis and Kaplan-Meier plotter were used to examine the expression and prognostic value of hub genes. Furthermore, the effects of CKI on HCC were verified through molecular docking simulations and cell experiments in vitro. RESULTS: Network analysis revealed that BCHE, SRD5A2, EPHX2, ADH1C, ADH1A and CDK1 were the key targets of CKI in the treatment of HCC. Among them, only CDK1 was highly expressed in HCC tissues, while the other 5 targets were lowly expressed. Furthermore, the six hub genes were all closely related to the prognosis of HCC patients in survival analysis. Molecular docking revealed that there was an efficient binding potential between the constituents of CKI and BCHE. Experiments in vitro proved that CKI inhibited the proliferation of HepG2 cells and up-regulated SRD5A2 and ADH1A, while down-regulated CDK1 and EPHX2. CONCLUSIONS: This study revealed and verified the targets of CKI on HCC based on network pharmacology and experiments and provided a scientific reference for further mechanism research.

Prognostic value of Mortalin correlates with roles in epithelial-mesenchymal transition and angiogenesis in lung adenocarcinoma.

Mortalin is involved in the malignant phenotype of many cancers. However, the specific molecular mechanisms involving Mortalin in lung adenocarcinoma remain unclear. In this study, we showed that both Mortalin mRNA and protein are overexpressed in lung adenocarcinoma. In addition, Mortalin overexpression was positively correlated with poor overall survival. In vitro experiments showed that Mortalin silencing inhibited the proliferation, colony formation and migration abilities of A549 and H1299 cells. Mortalin promotes EMT progression, angiogenesis and tumor progression by activating the Wnt/ß-catenin signaling pathway. In vivo experiments further confirmed that Mortalin promoted malignant progression of lung adenocarcinoma. Taken together, our data suggest that Mortalin represents an attractive prognostic marker and therapeutic target in lung adenocarcinoma patients.

Effect of age and cycloplegia on the morphology of the human crystalline lens: swept-source OCT study.

PURPOSE: To evaluate the effect of age and cycloplegia on the morphology of the crystalline lens using a swept-source optical coherence tomography (SS-OCT) system. SETTING: Hospital. DESIGN: Prospective cross-sectional study. METHODS: The parameters including anterior chamber depth (ACD), the radii of curvature of the anterior and posterior surface of the crystalline lens (ALR and PLR), lens thickness (LT), lens equatorial diameter (LED), and lens vault (LV) were quantified by the SS-OCT before and after cycloplegia. The paired t test was used to compare the parameters before and after cycloplegia. A multivariate linear regression model was built to analyze the association between the parameters/cycloplegia-induced changes and age, while adjusting for the effect of axial length, refractive status, and sex. RESULTS: 76 individuals (age range, 18 to 86 years) were recruited. The ALR and ACD were negatively correlated with age (P ≤ .002), and the LT, LV, and LED were positively correlated with age (P ≤ .004). In participants younger than 60 years, the ALR and ACD significantly increased, whereas the LV and LT significantly decreased after cycloplegia (all P < .001). With aging, cycloplegia-induced differences of ALR (P = .001) and ACD (P = .014) significantly decreased, and of LT (P < .001), LT (P < .001), and LV (P = .001) significantly increased. CONCLUSIONS: The crystalline lens morphology measured by the SS-OCT revealed steepening anterior surface and increasing equatorial diameter with age. Cycloplegia caused a significant change of anterior surface morphology in participants younger than 60 years, and this effect diminished with age.

The Relationship Between Age and the Morphology of the Crystalline Lens, Ciliary Muscle, Trabecular Meshwork, and Schlemm's Canal: An in vivo Swept-Source Optical Coherence Tomography Study.

Purpose: To evaluate the effects of age on the morphologies of the crystalline lens, ciliary muscle (CM), Schlemm's canal (SC), and trabecular meshwork (TM) using swept-source optical coherence tomography (SS-OCT). Methods: Images of the crystalline lens and iridocorneal angle were obtained in healthy participants' eyes using SS-OCT. Morphological parameters of the crystalline lens, CM, and TM/SC were measured, and the relationship between these parameters and age was evaluated. Results: A total of 62 healthy participants were enrolled, with an age range of 7-79 years. With adjustments for the effects of axial length and sex, both the nasal and temporal SC cross-sectional areas (CSA) and the cross-sectional area of the CM (CMA), distance from the scleral spur to the inner apex of the ciliary muscle (IA-SS), and nasal SC volume were negatively correlated with age (P ≤ 0.041). Meanwhile, the lens thickness (LT) (P < 0.001) and lens vault (LV) (P < 0.001) were positively correlated with age, and the radius of the curvature of the anterior lens (ALR) was negatively correlated with age (P < 0.001). Conclusion: Increasing age was associated with a thicker crystalline lens, a steeper anterior lens curvature, an anteriorly located and smaller CM, and a narrower SC. Clinical Trial Registration: https://register.clinicaltrials.gov/prs/app/action/Select Protocol?sid=S000A3JZ&selectaction=Edit&uid=U00019K7&ts=4&cx=-c5xxp8, identifier [NCT04576884].

A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation.

BACKGROUND: Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated. METHODS: Here, to overcome the limitation of conventional network pharmacology methods with a weak combination with clinical information, this study proposes a network pharmacology approach of integrated bioinformatics that applies a weighted gene co-expression network analysis (WGCNA) to conventional network pharmacology, and then integrates molecular docking technology and biological experiments to verify the results of this network pharmacology analysis. RESULTS: The WGCNA analysis revealed 2 gene modules closely associated with classification, staging and survival status of PC. Further CytoHubba analysis revealed 10 hub genes (NCAPG, BUB1, CDK1, TPX2, DLGAP5, INAVA, MST1R, TMPRSS4, TMEM92 and SFN) associated with the development of PC, and survival analysis found 5 genes (TSPOAP1, ADGRG6, GPR87, FAM111B and MMP28) associated with the prognosis and survival of PC. By integrating these results into the conventional network pharmacology study of CKI treating PC, we found that the mechanism of CKI for PC treatment was related to cell cycle, JAK-STAT, ErbB, PI3K-Akt and mTOR signalling pathways. Finally, we found that CDK1, JAK1, EGFR, MAPK1 and MAPK3 served as core genes regulated by CKI in PC treatment, and were further verified by molecular docking, cell proliferation assay, RT-qPCR and western blot analysis. CONCLUSIONS: Overall, this study suggests that the optimized network pharmacology approach is suitable to explore the molecular mechanism of CKI in the treatment of PC, which provides a reference for further investigating biomarkers for diagnosis and prognosis of PC and even the clinical rational application of CKI.

Physical Activity, Obesity, and Hypertension among Adults in a Rapidly Urbanised City.

BACKGROUND: Few studies have explored the relationship between the level of physical activity and the occurrence or prevalence of obesity and hypertension among people residing in urbanised areas. METHOD: A cross-sectional study involving a sample of 1,001 adults was conducted. Descriptive statistics were used to describe sociodemographic variables, physical activity levels, body mass index (BMI), and prevalence of hypertension. Logistic regression models were adopted to investigate the relationship between these factors. RESULTS: A total of 939 respondents who provided valid responses were included. Among them, 56.5% of the participants reported engaging in high levels of physical activity. However, 40.4% of the respondents were classified as overweight or obese, and 31.9% had diagnosed hypertension. After adjusting for sociodemographic factors, logistic regression analysis revealed that physical activity levels were negatively correlated with the prevalence of BMI (OR = 0.564, 95% CI: 0.352-0.905; OR = 0.583, 95% CI: 0.375-0.907) and hypertension (OR = 0.556, 95% CI: 0.348-0.888). CONCLUSIONS: Our study confirms recent evidence regarding the amount of physical activity that is associated with lower prevalence of obesity and hypertension in Pingshan District. Furthermore, different physical activities of various intensity levels had different effects on hypertension. Residents should be encouraged to engage in physical activities and maintain a healthy weight to improve their quality of life.

Investigation on the Efficiency of Tonic Chinese Herbal Injections for Treating Dilated Cardiomyopathy Based on Bayesian Network Meta-Analysis.

INTRODUCTION: This network meta-analysis investigated the efficacy of six tonic Chinese herbal injections (Huangqi injection, Shenfu injection, Shengmai injection, Shenmai injection, Shenqi Fuzheng injection, and Yiqifumai injection) compared to Western medicine for the treatment of the deteriorating state associated with dilated cardiomyopathy. METHODS: PubMed, the Cochrane Library, Embase, the Chinese Biological Medicine Database, China National Knowledge Infrastructure, the Wanfang Database, and the Chinese Scientific Journal Database were searched from their inception to October 15, 2020, to retrieve randomized controlled trials (RCTs). Study selection and data extraction conformed to a priori criteria. The risk of bias of the included RCTs was determined, and GRADE was used to evaluate outcomes. The network meta-analysis was calculated using WinBUGS 1.4.3 and Stata 13.0 software. The clinical effective rate, left ventricular ejection fraction, 6-minute walk test, left ventricular end-diastolic dimension, heart rate, and cardiac output were deemed outcomes. All outcomes were summarized as odds ratios or mean differences with their 95% credible intervals. The ranking probability of the interventions across various outcomes was also presented. RESULTS: Forty RCTs and 2970 patients were enrolled. Integration of the outcome results revealed that a combination of Shenfu injection and Western medicine ranked ahead of the other injections in most outcomes, especially in the clinical effective rate (OR = 0.21, 95% CI: 0.12-0.34), left ventricular ejection fraction (MD = 7.43, 95% CI: 2.41-12.38), and 6-minute walk test (MD = 50.39, 95% CI: 25.78-76.33). Shenmai injection plus Western medicine ranked ahead of the other injections in left ventricular end-diastolic dimension (69.5%) and cardiac output (60.9%). The cluster analysis suggested that Shenfu injection plus Western medicine was the most effective intervention for dilated cardiomyopathy. CONCLUSIONS: Shenfu injection plus Western medicine may be a preferable treatment in dilated cardiomyopathy. Clinicians should also consider the specific patient's various conditions when making diagnostic decisions. Due to an insufficient network meta-analysis, more high-quality RCTs need to be implemented to support our conclusions.