Deep-reinforcement-learning-based water diversion strategy.

Water diversion is a common strategy to enhance water quality in eutrophic lakes by increasing available water resources and accelerating nutrient circulation. Its effectiveness depends on changes in the source water and lake conditions. However, the challenge of optimizing water diversion remains because it is difficult to simultaneously improve lake water quality and minimize the amount of diverted water. Here, we propose a new approach called dynamic water diversion optimization (DWDO), which combines a comprehensive water quality model with a deep reinforcement learning algorithm. We applied DWDO to a region of Lake Dianchi, the largest eutrophic freshwater lake in China and validated it. Our results demonstrate that DWDO significantly reduced total nitrogen and total phosphorus concentrations in the lake by 7% and 6%, respectively, compared to previous operations. Additionally, annual water diversion decreased by an impressive 75%. Through interpretable machine learning, we identified the impact of meteorological indicators and the water quality of both the source water and the lake on optimal water diversion. We found that a single input variable could either increase or decrease water diversion, depending on its specific value, while multiple factors collectively influenced real-time adjustment of water diversion. Moreover, using well-designed hyperparameters, DWDO proved robust under different uncertainties in model parameters. The training time of the model is theoretically shorter than traditional simulation-optimization algorithms, highlighting its potential to support more effective decision-making in water quality management.

Metformin combined with rapamycin ameliorates podocyte injury in idiopathic membranous nephropathy through the AMPK/mTOR signaling pathway.

Autophagy activation protects against podocyte injury in idiopathic membranous nephropathy (IMN). The AMPK/mTOR signaling pathway is a vital autophagy regulatory pathway. Metformin promotes autophagy, whereas rapamycin is an autophagy agonist. However, the therapeutic mechanisms of metformin and rapamycin in IMN remain unclear. Thus, we examined the mechanisms of action of metformin and rapamycin in IMN by regulating the AMPK/mTOR autophagy signaling pathway. Female Sprague-Dawley (SD) rats were treated with cationic bovine serum albumin (C-BSA) to establish an IMN model and were randomly divided into IMN model, metformin, rapamycin, and metformin + rapamycin groups. A control group was also established. Metformin and rapamycin were used as treatments. Renal histological changes, urinary protein excretion, the protein expression levels of key AMPK/mTOR signaling pathway proteins, renal tissue cell apoptosis, and autophagy-associated proteins (Beclin 1 and LC3) were examined. In addition, a C5b-9 sublysis model using the MPC-5 mouse podocyte cell line was established to verify the effect of metformin combined with rapamycin on podocytes. Metformin combined with rapamycin improved urinary protein excretion in IMN rats. Metformin combined with rapamycin attenuated the inflammatory response, renal fibrosis, and podocyte foot process fusion. In addition, it improved autophagy in podocytes as demonstrated by the enhanced expression of Beclin-1, p-AMPK/AMPK, LC3-II/I, and autophagosomes in podocytes and decreased p-mTOR/mTOR expression. In conclusion, metformin combined with rapamycin decreased proteinuria, improved renal fibrosis and podocyte autophagy via AMPK/mTOR pathway in IMN rats. The metformin and rapamycin decreased proteinuria and inproved renal fibrosis in IMN model rats.

Noninvasive detection of diabetes mellitus based on skin fluorescence and diffuse reflectance spectroscopy.

There is an urgent need for mass population screening tool for diabetes. Skin tissue contains a large number of endogenous fluorophores and physiological parameter markers related to diabetes. We built an excitation-emission spectrum measurement system with the excited light sources of 365, 395, 415, 430 and 455nm to extract skin characteristics. The modeling experiment was carried out to design and verify the accuracy of the recovery of tissue intrinsic discrete three-dimensional fluorescence spectrum. Blood oxygen modeling experiment results indicated the accuracy of physiological parameter extraction algorithm based on diffuse reflectance spectrum. A community population cohort study was carried out. The tissue reduced scattering coefficient and scattering power of the diabetes were significantly higher than normal control groups. The Gaussian multi-peak fitting was performed on each excitation-emission spectrum of the subject. A total of 63 fluorescence features containing information such as Gaussian spectral curve intensity, central wavelength position, and variance were obtained from each person. Logistic regression was used to construct the diabetes screening model. The results showed that the area under the receiver operating characteristic curve of the model for predicting diabetes was 0.816, indicating high diagnostic value. As a rapid and non-invasive detection method, it is expected to have high clinical value. This article is protected by copyright. All rights reserved.

Inhibition of LPA-LPAR1 and VEGF-VEGFR2 Signaling in IPF Treatment.

Due to the complex mechanism and limited treatments available for pulmonary fibrosis, the development of targeted drugs or inhibitors based on their molecular mechanisms remains an important strategy for prevention and treatment. In this paper, the downstream signaling pathways mediated by VEGFR and LPAR1 in pulmonary cells and the role of these pathways in pulmonary fibrosis, as well as the current status of drug research on the targets of LPAR1 and VEGFR2, are described. The mechanism by which these two pathways regulate vascular leakage and collagen deposition leading to the development of pulmonary fibrosis are analyzed, and the mutual promotion of the two pathways is discussed. Here we propose the development of drugs that simultaneously target LPAR1 and VEGFR2, and discuss the important considerations in targeting and safety.

Study on Optimal Extraction and Hypoglycemic Effect of Quercetin.

Quercetin was extracted from Portulaca oleracea L. through biphasic acid hydrolysis to investigate its potential as a suppressor of dipeptidyl peptidase IV (DPP-IV) and its hypoglycemic effect in type 2 diabetic mice. The extraction procedure was optimized utilizing the response surface method (RSM) in a single-factor experimental setting. An extraction efficiency of 0.675% was achieved using the following optimized parameters: 0.064 mol/L vitriol, 1 : 109.155 solid-liquid ratio, and 21.408 min ultrasonication. Overall, findings indicate the effectiveness of quercetin extraction. A mouse model for type 2 diabetes was established to receive oral treatment with various quercetin concentrations for 8 weeks. Fasting blood glucose (FBG) and the DPP-IV activity in the serum were significantly reduced. The weight and insulin levels of the mice in the quercetin group were raised compared to those in the model group (P < 0.01). Quercetin dose-dependently inhibited postprandial blood glucose excursions, as demonstrated by the oral glucose tolerance test. These results confirmed that quercetin has hypoglycemic effects and considerably improves insulin sensitivity via DPP-IV targeting.

Cellular and molecular mechanisms in vascular repair after traumatic brain injury: a narrative review.

Traumatic brain injury (TBI) disrupts normal brain function and is associated with high morbidity and fatality rates. TBI is characterized as mild, moderate or severe depending on its severity. The damage may be transient and limited to the dura matter, with only subtle changes in cerebral parenchyma, or life-threatening with obvious focal contusions, hematomas and edema. Blood vessels are often injured in TBI. Even in mild TBI, dysfunctional cerebral vascular repair may result in prolonged symptoms and poor outcomes. Various distinct types of cells participate in vascular repair after TBI. A better understanding of the cellular response and function in vascular repair can facilitate the development of new therapeutic strategies. In this review, we analyzed the mechanism of cerebrovascular impairment and the repercussions following various forms of TBI. We then discussed the role of distinct cell types in the repair of meningeal and parenchyma vasculature following TBI, including endothelial cells, endothelial progenitor cells, pericytes, glial cells (astrocytes and microglia), neurons, myeloid cells (macrophages and monocytes) and meningeal lymphatic endothelial cells. Finally, possible treatment techniques targeting these unique cell types for vascular repair after TBI are discussed.

Electrically insulating PBO/MXene film with superior thermal conductivity, mechanical properties, thermal stability, and flame retardancy.

Constructing flexible and robust thermally conductive but electrically insulating composite films for efficient and safe thermal management has always been a sought-after research topic. Herein, a nacre-inspired high-performance poly(p-phenylene-2,6-benzobisoxazole) (PBO)/MXene nanocomposite film was prepared by a sol-gel-film conversion method with a homogeneous gelation process. Because of the as-formed optimized brick and mortar structure, and the strong bridging and caging effects of the fine PBO nanofibre network on the MXene nanosheets, the resulting nanocomposite film is electrically insulating (2.5 × 109 Ω cm), and exhibits excellent mechanical properties (tensile strength of 416.7 MPa, Young's modulus of 9.1 GPa and toughness of 97.3 MJ m-3). More importantly, the synergistic orientation of PBO nanofibres and MXene nanosheets endows the film with an in-plane thermal conductivity of 42.2 W m-1 K-1. The film also exhibits excellent thermal stability and flame retardancy. This work broadens the ideas for preparing high-performance thermally conductive but electrically insulating composites.

Relationships between position of patellar ridge high point and morphology of resected surface for patellar resurfacing in total knee arthroplasty.

Background: Reproducing the native patellar ridge high point while maximizing osseous coverage is important for the success of patellar replacement, but it cannot always be achieved simultaneously. This study aimed to thoroughly investigate the relationships and their influencing factors between the positions of the high point of patellar ridge (HPPR) and the morphology of the patellar resected surface. Methods: Four hundred seventy-three patients (265 men, 208 women) aged 18 to 50 years with knee injuries before arthroscopy were retrospectively collected for this cross-sectional study. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to construct 3D computer models of the patella and patellar cartilage. The morphometric characteristics of the patellar cut after virtual resection and the HPPR position relative to the patellar cut centre were measured and analyzed. Results: The medial displacements of the HPPR were positively correlated with Wiberg's classification and index (all P<0.001). The mean values of HPPR's medial displacements were 0.15 of the medial width of patellar cut, and 93.2% of all patella ranged from 0 to 0.3. When the implant's apex were placed at 0.15 of the medial width of patellar cut medialized, the proportion of implant placement errors within 1 mm of the native high point was 12% more in female patella (P=0.01), and 7% more in all patella (P=0.03) than 3 mm medialized. Conclusions: Wiberg's system can roughly predicted the medial-lateral position of the HPPR. The HPPR was mainly medially located at the 0.15 of the medial patellar width approximately, and 15% medialized of the implant's apex can better reproduce the native patellar high point than 3 mm medialized. The current results provide basic data for patellar implant selection, preoperative planning, and implant design to reproduce the native patellar high point better while maximizing osseous coverage for patellar resurfacing.

Extraction of DNA from trace forensic samples with a modified lysis buffer and chitosan coated magnetic beads.

The trace amounts of human tissue cells or body fluids left at the crime scene are often mixed with inhibitors such as rust, pigments, and humic acid. The extraction of the DNA from the trace cells is crucial for the investigation of cases. Usually, specially designed magnetic nanoparticles were chosen by the case investigators to enrich and elute DNA, which was then used for polymerase chain reaction (PCR) and short tandem repeat (STR) analysis. The traditional approach often had the following problems, such as low DNA enrichment efficiency, possible DNA breakage, and complex operations. Here, the 1%(w/v) of chitosan (75% deacetylation degree) was used to modify the 50 nm magnetic nanoparticles to gain the Chitosan@Beads, which theoretically carried positively charged in the pH = 5 of lysis buffer so as to adsorb negatively charged DNA through electrostatic interactions. The XPS and FT-IR results demonstrated that chitosan was successfully attached to the surface of magnetic nanoparticles. A set of simulated samples, containing 20 mg/µL of humic acid, pigments, iron ions (Fe2+, Fe3+), and the coexistence of the above three substances, were prepared to simulate the case scene. Human bronchial epithelial cells were mixed with the 200 µL of the above simulated samples for DNA extraction. 400 µL of lysis buffer, 20 µL of proteinase K (10 mg/mL) and 20 µL of Chitosan@Beads solution (20 mg/mL) was used for cell disruption and DNA enrichment. The extraction sensitivity of Chitosan@Beads was confirmed to be 10 cells, superior to commercial reagent kits. The Chitosan@Beads@DNA can directly use for "In-situ PCR" with elution-free operations. The STR loci rate of DNA extracted by Chitosan@Beads was around 97.9%, higher than the commercial kit (66.7%). In short, we foresee here developed novel Chitosan@Beads and modified lysis buffer could provide a new model for the DNA extraction of forensic trace evidence.

Neuromorphic regenerative memory optoelectronic oscillator.

Neuromorphic spiking information processing based on neuron-like excitable effect has achieved rapid development in recent years due to its advantages such as ultra-high operation speed, programming-free implementation and low power consumption. However, the current physical platforms lack building blocks like compilers, logic gates, and more importantly, data memory. These factors become the shackles to construct a full-physical layer neural network. In this paper, a neuromorphic regenerative memory scheme is proposed based on a time-delayed broadband nonlinear optoelectronic oscillator (OEO), which enables reshaping and regenerating on-off keying encoding sequences. Through biasing the dual-drive Mach-Zehnder electro-optic modulator in the OEO cavity near its minimum transmission point, the OEO can work in excitable regime, where localized states are maintained for robust nonlinear spiking response. Both simulation and experiment are carried out to demonstrate the proposed scheme, where the simulation results and the experimental results fit in with each other. The proposed OEO-based neuromorphic regenerative memory scheme exhibits long-term response ability for short-term excitation, which shows an enormous application potential for high-speed neuromorphic information buffering, optoelectronic interconnection and computing.

Instantaneous bandwidth expansion of photonic sampling analog-to-digital conversion for linear frequency modulation waveforms based on up-sampling and fractional Fourier transform signal processing.

An approach to expanding the instantaneous bandwidth of a photonic sampling analog-to-digital converter (ADC) for receiving linear frequency modulation waveforms (LFMWs) is proposed and experimentally demonstrated based on up-sampling and filtering in the fractional Fourier domain. Through twice zero interpolation, the equivalent sampling rate is quadrupled, which also quadruples the nominal instantaneous bandwidth of the photonic sampling ADC. In addition, with the assistance of bandpass filtering in the fraction Fourier domain, the image signals and the harmonic distortions generated in the interpolation process are filtered out. As a result, the effective instantaneous bandwidth of the photonic sampling ADC is doubled. In the experiment, the instantaneous bandwidth of a photonic sampling ADC with a sampling rate of 5 GSa/s for receiving LFMWs is increased from 2.5 GHz to 5 GHz by using the proposed method. Input LFMWs within the frequency range of 24-27 GHz and 30-33 GHz, i.e., with an instantaneous bandwidth of 3 GHz, are digitized without frequency-domain aliasing. Besides, the ability of the proposed method to enhance the ranging accuracy in a broadband radar system is demonstrated. This method reduces the hardware complexity of the photonic sampling ADC for receiving broadband LFMWs in radar systems.

Enhanced Photoluminescence Quantum Yield of Metal Halide Perovskite Microcrystals for Multiple Optoelectronic Applications.

Recently, metal 1halide perovskites have shown compelling optoelectronic properties for both light-emitting devices and scintillation of ionizing radiation. However, conventional lead-based metal halide perovskites are still suffering from poor material stability and relatively low X-ray light yield. This work reports cadmium-based all-inorganic metal halides and systematically investigates the influence of the metal ion incorporation on the optoelectronic properties. This work introduces the bi-metal ion incorporation strategy and successfully enhances the photoluminescence quantum yield (98.9%), improves thermal stability, and extends the photoluminescence spectra, which show great potential for white light emission. In addition, the photoluminescent decay is also modulated with single metal ion incorporation, the charge carrier lifetime is successfully reduced to less than 1 µs, and the high luminescent efficiency and X-ray light yield (41 000 photons MeV-1 ) are maintained. Then, these fast scintillators are demonstrated for high-speed light communication and sensitive X-ray detection and imaging.

Polyzwitterionic micelles with antimicrobial-conjugation for eradication of drug-resistant bacterial biofilms.

The presence of bacterial biofilms has presented a significant challenge to human health. This study presents the development of biofilm microenvironment-responsive polymeric micelles as a novel approach to address the challenges posed by bacterial biofilms. These micelles are composed of two key components: a zwitterionic component, inspired by protein isoelectric points, containing balanced quantities of primary amines and carboxylic groups that undergo a positive charge transformation in acidic microenvironments, and a hydrophobic triclosan conjugate capable of releasing triclosan in the presence of bacterial lipases. Through the synergistic combination of pH-responsiveness and lipase-responsiveness, we have significantly improved drug penetration into biofilms and enhanced its efficacy in killing bacteria. With their remarkable drug-loading capacity and the ability to specifically target and eliminate bacteria within biofilms, these zwitterionic polymeric micelles hold great promise as an effective alternative for treating biofilm-associated infections. Their unique properties enable efficient drug delivery and heightened effectiveness against biofilm-related infections.

Improving Differentiable Architecture Search via self-distillation.

Differentiable Architecture Search (DARTS) is a simple yet efficient Neural Architecture Search (NAS) method. During the search stage, DARTS trains a supernet by jointly optimizing architecture parameters and network parameters. During the evaluation stage, DARTS discretizes the supernet to derive the optimal architecture based on architecture parameters. However, recent research has shown that during the training process, the supernet tends to converge towards sharp minima rather than flat minima. This is evidenced by the higher sharpness of the loss landscape of the supernet, which ultimately leads to a performance gap between the supernet and the optimal architecture. In this paper, we propose Self-Distillation Differentiable Neural Architecture Search (SD-DARTS) to alleviate the discretization gap. We utilize self-distillation to distill knowledge from previous steps of the supernet to guide its training in the current step, effectively reducing the sharpness of the supernet's loss and bridging the performance gap between the supernet and the optimal architecture. Furthermore, we introduce the concept of voting teachers, where multiple previous supernets are selected as teachers, and their output probabilities are aggregated through voting to obtain the final teacher prediction. Experimental results on real datasets demonstrate the advantages of our novel self-distillation-based NAS method compared to state-of-the-art alternatives.

Transient absorption study on fluorescence quenching of InP/ZnS quantum dots by MXene.

Fluorescence quenching due to energy transfer from InP/ZnS quantum dots (QDs) to Ti3C2Tx MXene materials was investigated by the transient absorption spectroscopy. During the fluorescence quenching, the photo-induced absorption feature in the transient spectrum was blue-shifted due to the higher photon energy required for the upward transition. The lifetime of stimulated emission was gradually extended from 0.86 µs to 2.28 µs with increasing Ti3C2Tx MXene. The fluorescence quenching of QDs can be quantitatively characterized by analyzing the lifetime of the stimulated emission feature in the transient absorption spectrum, which was used as a Ti3C2Tx MXene detection with the sensitivity of 6.63 mL/mg. The results of this study provide the basis for the design of optical sensors.

Chinese Herbal Medicine for the Treatment of Adult Viral Myocarditis: An Overview of Systematic Reviews and Meta-Analyses of Randomized Controlled Trials.

PURPOSE: Viral myocarditis (VMC) is a life-threatening disease that can affect all ages and genders, with middle-aged adults being particularly susceptible. Numerous systematic reviews have been conducted to investigate the efficacy and safety of Chinese herbal medicine (CHM) in treating adult viral myocarditis (AVM). The objective of this study was to conduct a comprehensive overview of systematic reviews and meta-analyses of randomized controlled trials (RCTs) regarding the efficacy and safety of CHM for AVM. METHODS: A comprehensive systematic search was conducted across 8 electronic databases from their inception to June 23, 2022, augmented by manual searches of the gray literature. Systematic reviews were independently selected and data extracted in accordance with predetermined criteria by 2 reviewers. Included systematic reviews were assessed for methodologic and reporting quality using Assessing the Methodological Quality of Systematic Reviews 2 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The quality of evidence relating to outcome measures was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Recalculation of effect sizes and subsequent determination of 95% CIs were conducted with either a fixed-effects or random-effects model. FINDINGS: The current overview of systematic reviews included a total of 6 systematic reviews, which reported on 67 RCTs with a participant pool of 5611 individuals. The findings of our study indicate that the combination of CHM and Western medications had positive effects on the effective rate, cure rate, ECG recovery, atrial premature contraction/premature ventricular contraction, left ventricular ejection fraction, myocardial enzymes, and improvement of clinical symptoms for AVM. The adverse drug reactions in the combination therapy group were generally less than or lighter than that in the Western medication group (relative risk = 0.79; 95% CI, 0.44-1.40; P > 0.05, I2 = 0). IMPLICATIONS: Our research results provide evidence that combining CHM with Western medicine could offer potential benefits for patients with AVM. However, the number of studies included in our review is limited and the methodologic quality of these studies is modest. Therefore, there are potential uncertainties regarding the conclusion that CHM with Western medication may benefit patients with AVM. We call for more large-scale, high-quality studies with standardized designs to further verify and support our findings. This would promote a better understanding of the efficacy and safety profile of CHM and provide reliable reference evidence for clinical practice and policy making. Moreover, future research should explore optimal drug combinations, examine therapeutic doses and durations of CHM combination therapy, and evaluate its long-term efficacy and safety.

Application of real time shear wave elastography to the differential diagnosis of secondary parathyroid hyperplasia and adenoma.

We aimed to explore the value of ultrasonic elastic imaging in the diagnosis of parathyroid hyperplasia and adenoma in patients with secondary hyperparathyroidism and provide more evidence for clinical treatment. Forty patients who were on dialysis and underwent parathyroid surgery were selected All patients underwent routine ultrasound, ultrasound elasticity examination and blood biochemical examination before surgery, including calcium, phosphorus, parathyroid hormone (PTH), etc. According to postoperative results, adenoma group and hyperplasia group were divided into 2 groups. Receiver operating characteristic curve was drawn to evaluate the diagnostic efficacy and combined diagnostic efficacy of each index. The PTH levels significantly differed between the adenoma and hyperplasia groups (P < .001). The volume and blood flow grades significantly differed between the adenoma and hyperplasia groups (P < .001) The minimum of the adenoma group was 14.62 ±â€…6.79 kPa, mean was 19.42 ±â€…6.29 kPa, and maximum was 24.25 ±â€…6.35 kPa which were significantly different from those in the hyperplasia group (P < .05). The combinations of more than 6 indicators in the diagnosis of parathyroid adenoma resulted in an area under the curve of 0.892 (P < .001), and the sensitivity and specificity were 78.9% and 97.4%, respectively. Shear wave elastography can be used as an effective tool to distinguish secondary parathyroid hyperplasia from adenoma. When combined with PTH, conventional ultrasound blood flow grading and volume measurement, it has higher diagnostic efficacy.

Transcriptomics reveals the molecular regulation of Chinese medicine formula on improving bone quality in broiler.

Skeletal disorder is of concern to the poultry industry as it affects animal welfare and production performance. Traditional Chinese medicine could improve bone quality and reduce the incidence of bone disease, but the molecular regulation of Chinese medicine formula (CMF) on improving bone quality in broilers is still unclear. This study was performed to research the effects of CMF on skeletal performance of Cobb broilers and reveal the molecular regulation. A total of 120 one-day-old Cobb broilers were randomly allocated into 4 equal groups of 30 chickens, with 5 replicates and 6 chickens in each replicate. The control (CON) group was fed a diet without CMF, while the CMF1, CMF2, and CMF3 groups were supplemented with different CMF at 6,000 mg/kg diet, respectively. The broilers were raised to 60 d of age, then bone tissues were collected for biomechanical properties, micro-CT detection and transcriptomic sequencing analysis. The results showed that CMF3 improved the biomechanical properties of broiler tibia, via increasing the elastic modulus (P < 0.05), yield strength (P > 0.05), maximum stress (P < 0.05) and fracture stress (P < 0.05) of the tibia. Micro-CT analysis indicated that CMF3 increased the bone mineral density (BMD), bone volume/total volume (BV/TV), bone surface density (BS/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and decreased the trabecular separation (Tb.Sp) of femur cancellous bone (P < 0.05). RNA-seq analysis revealed 2,177 differentially expressed genes (DEGs) (|log2FoldChange| ≥ 1, FDR < 0.05) between the CMF3 group and CON group. Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis showed 13 pathways mostly associated with bone growth and development and bone metabolism, and we identified 39 bone-related DEGs. This study suggests that CMF3 could improve bone strength and bone microstructure of broilers, and showed a positive effect on bone performance. Our research could provide a theoretical reference for the development of pollution-free feed additives to improve the skeletal performance of broilers, which could help promote healthy farming of chickens.

Association Between Systemic Immune Inflammation Level and Poor Prognosis Across Different Glucose Metabolism Status in Coronary Artery Disease Patients.

Background: Blood glucose levels significantly affect the clinical prognosis of patients with coronary artery disease (CAD), and systemic immune inflammation is a common risk factor for both CAD and diabetes. However, the relationship between immune inflammation levels and poor prognosis in patients with CAD with different glucose metabolic statuses remains unclear. Methods: Between January 2007 and December 2020, we recruited 84,645 patients with CAD. The systemic immune inflammation index (SII) was used to comprehensively reflect the immune and inflammatory levels of patients and was calculated using the following formula: neutrophils × platelets/lymphocytes. The patients were classified into nine groups according to their glucose metabolism status (diabetes mellitus [DM], pre-diabetes mellitus [pre-DM], and normal glucose regulation [NGR]). Cox regression models and competing risk Fine and Gray models were used to investigate the association between SII and clinical outcomes. Results: During the follow-up period, 12,578 patients died, including 5857 cardiovascular-related and 1251 cancer-related deaths. The risk of all-cause and cause-specific mortality increased with increasing SII tertiles in CAD patients with NGR, pre-DM, and DM. When considering glucose metabolism status, the multivariate cox regression revealed that CAD patients with DM and SII-H levels had the highest risk of all-cause mortality (1.69 [1.56-1.83]), cardiovascular mortality (2.29 [2.02-2.59]), and cancer mortality (1.29 [1.01-1.66]). Moreover, incorporating the SII into traditional risk factor models significantly improved the C-index for predicting all-cause and cardiovascular mortality. Conclusion: Systemic immune inflammation levels on admission were correlated with a higher risk of all-cause and cause-specific mortality in patients with CAD, particularly in those with DM.

Exploring the potential mechanisms of Yi-Yi-Fu-Zi-Bai-Jiang-San therapy on the immune-inflamed phenotype of colorectal cancer via combined network pharmacology and bioinformatics analyses.

BACKGROUND: The development and progression of colorectal cancer (CRC) is closely associated with its complex tumor microenvironment (TME). Assessment of the modified pattern of immune cell infiltration (ICI) will help increase knowledge regarding the characteristics of TME infiltration. Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) has been shown to have positive effects on the regulation of the immune microenvironment of CRC. However, its pharmacological targets and molecular mechanisms remain to be elucidated. METHODS: Network pharmacological analysis was used to identify the target of YYFZBJS in the TME of CRC. Patients with the immune-inflamed phenotype (IIP) were identified using CRC samples from The Cancer Genome Atlas (TCGA) database. Consensus genes were identified by intersecting YYFZBJS targets, CRC disease targets and differentially expressed genes in the CRC microenvironment. Then, least absolute shrinkage and selection operator (LASSO) Cox analyses were used to identify a prognostic signature from the consensus genes. Cytoscape software was further used to build a unique herb-compound-target network diagram of the important components of YYFZBJS and prognostic gene targets. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed using the prognostic gene sets to explore the molecular mechanism of the prognostic genes in drug therapy for CRC IIP patients. Finally, single-cell analysis was performed to validate the expression of the prognostic genes in the TME of CRC using the TISCH2 database. RESULTS: A total of 284 IIP patients were identified from 480 patients with CRC. A total of 35 consensus genes were identified as targets of YYFZBJS in the TME of CRC patients. An eleven-gene prognostic signature, including PIK3CG, C5AR1, PRF1, CAV1, HPGDS, PTGS2, SERPINE1, IDO1, TGFB1, CXCR2 and MMP9, was identified from the consensus genes, with areas under the receiver operating characteristic (ROC) curve (AUCs) values of 0.84 and 0.793 for the training and test cohorts, respectively. In the herb-compound-target network, twenty-four compounds were shown to interact with the 11 prognostic genes, which were significantly enriched in the IL-17 signaling, arachidonic acid metabolism and metabolic pathways. Single-cell analysis of the prognostic genes confirmed that their abnormal expression was associated with the TME of CRC. CONCLUSION: This study organically integrated network pharmacology and bioinformatics analyses to identify prognostic genes in CRC IIP patients from the targets of YYFZBJS. Although this data mining work was limited to the study of mechanisms related to prognosis based on the immune microenvironment, the methodology provides new perspectives in the search for novel therapeutic targets of traditional Chinese medicines (TCMs) and accurate diagnostic indicators of cancers targeted by TCMs.