Microwave frequency switching delays in phase-locked period-one dynamics of semiconductor lasers.

Modern microwave switches require high switching speeds to rapidly route data over multiple radio channels while minimizing the routing delay. This Letter proposes a novel, to the best of our knowledge, microwave frequency switching system using phase-locked Period-one (P1) dynamics of semiconductor lasers. When a semiconductor laser is optically injected by microwave-modulated optical signals, which carry two-tone input microwaves at 29 and 37 GHz, with proper injection power controlled by dual-voltage control signals, P1 dynamics are excited in the semiconductor laser and subsequently phase-locked by one of the input microwave tones. We have observed positive and negative switching delays in the switching process. For instance, a positive delay is observed when the system requires additional optical power to transition from a phase-locked state at 29 GHz to an unlocked state. Conversely, a negative delay occurs when the unlocked P1 dynamics approach but do not reach a 37-GHz frequency and then rapidly lock to the tone, thereby surpassing the speed of the control signals. These dual delays are instrumental in enhancing the switching speed of our system, enabling it to surpass the voltage switching time of the control signals by a factor of 3.6. In addition, by leveraging these dual delays, the duration of the microwave tones can be further extended in the switching process.

CSGAN: Modality-Aware Trajectory Generation via Clustering-based Sequence GAN.

Human mobility data is useful for various applications in urban planning, transportation, and public health, but collecting and sharing real-world trajectories can be challenging due to privacy and data quality issues. To address these problems, recent research focuses on generating synthetic trajectories, mainly using generative adversarial networks (GANs) trained by real-world trajectories. In this paper, we hypothesize that by explicitly capturing the modality of transportation (e.g., walking, biking, driving), we can generate not only more diverse and representative trajectories for different modalities but also more realistic trajectories that preserve the geographical density, trajectory, and transition level properties by capturing both cross-modality and modality-specific patterns. Towards this end, we propose a Clustering-based Sequence Generative Adversarial Network (CSGAN) that simultaneously clusters the trajectories based on their modalities and learns the essential properties of real-world trajectories to generate realistic and representative synthetic trajectories. To measure the effectiveness of generated trajectories, in addition to typical density and trajectory level statistics, we define several new metrics for a comprehensive evaluation, including modality distribution and transition probabilities both globally and within each modality. Our extensive experiments with real-world datasets show the superiority of our model in various metrics over state-of-the-art models.

Differences in the prevalence of uveitis between Crohn's disease and ulcerative colitis: A systematic review and meta-analysis.

PURPOSE: Uveitis is one of the ocular manifestations of inflammatory bowel disease (IBD) that is often overlooked and has been considered a sign of severe IBD. As typical subtypes of IBD, differences exist in the prevalence of uveitis between Crohn's disease (CD) and ulcerative colitis (UC). Our study systematically assessed differences in the prevalence of uveitis between CD and UC. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. We performed a systematic review of published literature from PubMed and Embase on 30 March 2022. Two investigators independently selected studies, extracted data and evaluated methodological quality. Either a fixed- or a random-effects model was used to calculate the risk ratio (RR), odds ratio (OR) and 95% confidence interval (95% CI) depending on the heterogeneity of studies. Sensitivity analysis was used to examine the heterogeneity by removing article by article, while subgroup analysis was conducted in accordance with various regions. RESULTS: Our study included data from 14 studies encompassing 115 854 participants. The prevalence of uveitis in IBD was estimated to be 2.38% (95% CI 1.60%-3.17%). The prevalence of uveitis in CD (3.27%, 95% CI 2.15%-4.39%) was significantly higher than in UC (1.60%, 95% CI 0.93%-2.27%; RR 1.76, 95% CI 1.39-2.22, p < 0.05). In subgroup analysis, a higher incidence of CD combined with uveitis was also observed in IBD patients residing in Europe (RR 1.75, 95% CI 1.37-2.24). CONCLUSIONS: Data from 115 854 IBD patients showed that CD patients were more likely to suffer from uveitis than UC patients. Ocular manifestations in IBD, particularly CD, warrant greater attention.

Differentiate Clinical Characteristics Between Viral Pneumonia and Mycoplasma pneumoniae and Nomograms for Predicting Mycoplasma pneumoniae : A Retrospective Study in Primary Hospitals.

OBJECTIVE: To identify the difference in clinical characteristics between viral pneumonia and Mycoplasma pneumoniae , providing cues on their differential diagnosis for primary hospitals with the insufficient pathogen detection capacity. METHODS: We retrospectively reviewed the medical records of hospitalized children with acute respiratory tract infections, and pathogenic microbes test results were analyzed. Clinical characteristics, routine blood parameters and hospitalization duration and fee were compared between M. pneumoniae and viral pneumonia. We used in the multivariable logistic regression to predict the probability of children with M. pneumoniae and graphically represented by a dynamic nomogram. The discrimination and clinical utility of the model were confirmed by receiver operating characteristic and decision curve analysis curves. RESULT: A total of 375 children with community-acquired pneumonia were included. Mycoplasma infection accounted for the largest proportion (22.13%). The incidence of both hypothermia and vomiting was lower in M. pneumoniae compared to viral pneumonia (hypothermia: 10.50% vs. 0.00%; vomiting: 7.90% vs. 0.00%). The prevalence of hyperthermia was higher in M. pneumoniae (hyperthermia: 89.5% vs. 100%). Procalcitonin, peripheral blood white blood cell count and lymphocyte levels were higher in the viral pneumonia group, and eosinophil levels were conversely lower. As for the duration of illness, the mean length of stay was 5.20 ± 2.12 (viral pneumonia) and 6.27 ± 2.48 days ( M. pneumoniae ). Children with M. pneumoniae had higher overall hospital costs and required more medical treatment. The above were all statistically significant with a P < 0.05. The scoring system was established based on the above results. Receiver operating characteristic curves showed good model-discrimination ability with 0.844 of the area under the curve in the training set and 0.778 in the test set. Decision curve analysis curves demonstrated the discriminative superiority of this model. The web-based dynamic nomogram calculator is accessible at https://zhxylxy0160128.shinyapps.io/Nomogram/ . CONCLUSION: Nomograms have satisfactory discrimination, and clinical utility may benefit in predicting the probability of developing M. pneumoniae in children. Children with M. pneumoniae have a higher burden than those with viral pneumonia and may require more intensive in-hospital monitoring.

Effect of Myopia Severity on the Health-Related Quality of Life in Children and Their Parents.

PURPOSE: To investigate the effect of different myopia severity on the health-related quality of life (QOL) in both children and their parents. METHODS: Cross-sectional study from October to November, 2021. Age and sex-matched children with binocular emmetropia (-0.5D < spherical equivalence [SE] < 0.5D), low myopia (-5.0D < SE ≤ -0.5D), and high myopia (SE ≤ -5.0D), as well as their parents, were enrolled. All children underwent ocular examinations. The Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales, Version 4 (child-report, 23 items) and the PedsQL Family Impact Module, Version 2 (parent-report, 36 items) was used for QOL assessment of the children and their parents, respectively. RESULTS: Forty-one, 48 and 45 age- and sex-matched children with their accompanying parents were included in the emmetropia, low myopia and high myopia group, respectively. Parents in the three groups also did not differ in age, sex, or education level. The median total QOL scores were comparable for emmetropic and low myopic children (96.74 [IQR: 93.48-97.83] vs. 96.74 [IQR: 94.57-98.37]) but were significantly lower for high myopic children (88.04 [IQR: 82.61-92.39], both p < .001). A decreasing trend was observed in the median total QOL for parents in the emmetropia (96.53, IQR: 86.81-100), low myopia (82.30, IQR: 70.83-97.22), and high myopia group (70.83, IQR: 60.42-84.03) (p for trend <.001). The effect of per myopic diopter change on QOL was larger in parents than children (coefficient: 1.48 (95%CI: 1.19-1.78) vs. 2.58 [95%CI: 1.83-3.32]), and parents with higher educational level appeared to have more reduction in QOL (p = .008). CONCLUSIONS: More severe myopia resulted in a larger QOL decrease in both children and parents. Significantly reduced QOL were identified in children with high myopia and parents of children with any myopia.

Inhibition of toll-like receptor 4 activation by apigenin and chrysin via competition for sites and conformational changes.

The activation of toll-like receptor 4 (TLR4) signaling is crucial for initiating and coordinating the immune response against infections, and is proved as a vital target for inflammatory diseases. Herein, TLR4 with sufficient amount and functional activity was generated by heterologous expression and used to investigate the mechanism of apigenin (Api)/chrysin (Chr) inhibition of TLR4 activation. The results demonstrated that Api/Chr exhibited a strong fluorescence quenching effect through a static quenching and a high binding affinity (Ka > 105 L·mol-1) with TLR4, indicating the potential of Api/Chr as a TLR4 inhibitor. Additionally, the binding of Api/Chr induced a loose and unstable conformation of TLR4 with evidence like the decreased hydrophobicity of the tryptophan microenvironment, decreased α-helix content and increased free sulfhydryl content, resulting in reduced stability of the TLR4. The computer simulations revealed that Api/Chr occupied the myeloid differentiation factor 2 (MD-2) binding region, preventing MD-2 from binding to TLR4. Furthermore, the accuracy of the binding site between Api/Chr and TLR4 was confirmed through genetic mutations. Overall, the mechanism by which Api/Chr inhibited TLR4 activation was elucidated at the macroscopic and molecular levels, providing the worthful information concerning the future therapeutic application of Api/Chr as a natural TLR4 inhibitor.

First Report of Shoot Blight on Clausena lansium Caused By Fusarium proliferatum in China.

Wampee (Clausena lansium [Lour.] Skeels) is a tropical fruit. In July 2022, shoot rot symptom was observed in wampee (cv. JIXIN) in a field ((21°25'N, 110°10'E, about 100 ha ), Guangdong Province, China. The most obvious symptom of the disease was the rotting and withering of the tops. Disease incidence was approximately 90% (n = 500). Twenty diseased samples were randomly collected from the field and cut into 2 mm × 2 mm pieces next to the margins of diseased tissues. These pieces were then sterilized with 75% alcohol for 30 s and 2% sodium hypochlorite for 3 min and subsequently washed with sterile water three times. Tissue pieces were placed onto potato dextrose agar (PDA) and incubated at 25℃ for 3 days. Pure cultures were obtained by transferring hyphal tips to new PDA plates. Sixty isolates of Fusarium ssp. (60/80 = 75%) were obtained. Three representative single-spore isolates (CLFP-1, CLFP-2, and CLFP-3) were used for further study. Colonies were white to pink on PDA. Conidiogenous cells were monophialidic or polyphialidic. Macroconidia were slightly curved, tapering apically with 3 to 5 septa, and measured from 31.7 to 55.5 µm × 2.5 to 5.0 µm in size (n=50). The morphological features of these fungi were analogous to F. proliferatum (Leslie and Summerell 2006). For molecular identification, a colony PCR method (Lu et al. 2012) was used to amplify the internal transcribed spacer (ITS) and portions of elongation factor 1-α (EF1-α), RNA polymerase II largest subunit (RPB1), and RNA polymerase II second largest subunit (RPB2) genes using primers ITS1/ITS4, EF1-728F/EF1-986R, RPB1-R8/RPB1-F5, and RPB2-7CF/fRPB2-11aR, respectively (O'Donnell et al. 1998; 2010). The sequences were submitted to GenBank under accession numbers OP740961 to OP740963 (ITS), and OP800846 to OP800854 (RPB1, RPB2, EF1-α). The BLAST comparison of the sequences showed the three isolates were 100% similar to F. proliferatum (ITS: MT378328; TEF1: MH582344; RPB1: MN193921; RPB2: MN892349). The sequences of the three isolates were 100% identical (ITS, 537/537 bp; RPB1, 1606/1606 bp; RPB2, 770/770 bp and EF1-α, 683/683 bp) with those of F. proliferatum (accession nos. MT378328, MN193921, MH582196, and MH582344) through BLAST analysis. Analysis of the concatenated sequences revealed a 99.87 to 100% identity with the isolates of the F. proliferatum (F. fujikuroi species complex, Asian clade) by polyphasic identification using the FUSARIUM-ID database (Yilmaz et al. 2021). The sequences were also concatenated for phylogenetic analysis by the maximum likelihood method. The isolates clustered with F. proliferatum. Pathogenicity was tested through in vivo experiments. The inoculated and control plants (n = 5, 3 months old, cv. JIXIN) were sprayed with a spore suspension (1 × 105 per mL) of the three isolates and sterile distilled water, respectively, until run-off (Feng and Li. 2019). The test was performed three times. The plants were grown in pots in a greenhouse at 25℃ to 28℃, with relative humidity of approximately 80%. Symptoms were observed on the inoculated plants with disease incidence 100% after 2 weeks, while the control plants remained healthy. The pathogen re-isolated from all the inoculated plants was identical to the inoculated isolates in morphology and ITS sequences. No pathogen were isolated from the control plants. To the best of our knowledge, this study is the first to report F. proliferatum causing shoot blight symptom in wampee (cv. JIXIN). This disease has caused severe losses and will provide the foundation for management strategies.

Swab Pressing vs Stromal Hydration to Prevent Incision Leakage and Transient Collapse of Anterior Chamber in Phacoemulsification: A Randomized Clinical Trial.

Importance: During phacoemulsification, incision leakage and the subsequent anterior chamber collapse often occur after the withdrawal of the handpiece, which cannot be prevented by current sealing techniques. A new technique called swab pressing is proposed here to apply pressure with a cotton swab to seal the incision immediately, but efficacy remains unknown. Objective: To determine if swab pressing is noninferior to stromal hydration, the current practice, in sealing incisions in phacoemulsification for age-related cataract. Design, Setting, and Participants: This noninferiority randomized controlled clinical trial was conducted between February 2022 and September 2022 at the Zhongshan Ophthalmic Center, Guangzhou, China. Patients aged 60 to 90 years with age-related cataract were enrolled. Interventions: Participants were randomly assigned (1:1) to receive swab pressing or stromal hydration. All surgeries were performed by a single experienced surgeon who was unmasked to the assignment. Main Outcomes and Measures: The proportion of closed clear corneal incisions evaluated using intraoperative optical coherence tomography. Results: A total of 126 eyes of 126 participants were randomized into the swab pressing group (63 [50%]) and stromal hydration group (63 [50%]). The mean (SD) age of participants was 69.2 (6.14) years and 70.1 (7.67) years in the pressing and stromal hydration groups, respectively. A total of 39 participants (61.9%) in the pressing group and 35 (55.6%) in the modified group were female. The proportion of closed incisions was 96.8% (61 of 63) in the swab pressing group and 93.7% (59 of 63) in the stromal hydration group. Noninferiority was met, as the lower 95% CI of -5.83 percentage points was greater than the prescribed noninferiority margin of -6.60 percentage points (difference, 3.17 percentage points; 95% CI, -5.83 to 12.18 percentage points). The rate of anterior chamber collapse (pressing: 0 of 63 vs stromal hydration: 35 of 63 [55.6%]; P < .001) was lower in the swab pressing group. There were no differences between the 2 groups in the proportion of closed incisions and central anterior chamber depth at postoperative hour 1 and day 1. Conclusions and Relevance: In this study, swab pressing was noninferior to stromal hydration in sealing clear corneal incisions in phacoemulsification for age-related cataract. While this trial involved only 1 surgeon who was not masked to the interventions, the results suggest that swab pressing is feasible and further investigations would be warranted to determine if it prevents the intraoperative transient collapse of anterior chamber or affects visual acuity outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT05242653.

Risk factors and prognostic nomogram for patients with second primary cancers after lung cancer using classical statistics and machine learning.

Previous studies have revealed an increased risk of secondary primary cancers (SPC) after lung cancer. The prognostic prediction models for SPC patients after lung cancer are particularly needed to guide screening. Therefore, we study retrospectively analyzed the Surveillance, Epidemiology, and End Results (SEER) database using classical statistics and machine learning to explore the risk factors and construct a novel overall survival (OS) prediction nomogram for patients with SPC after lung cancer. Data of patients with SPC after lung cancer, covering 2000 to 2016, were gathered from the SEER database. The incidence of SPC after lung cancer was calculated by Standardized incidence ratios (SIRs). Cox proportional hazards regression, machine learning (ML), Kaplan-Meier (KM) methods, and log-rank tests were conducted to identify the important prognostic factors for predicting OS. These significant prognostic factors were used for the development of an OS prediction nomogram. Totally, 10,487 SPC samples were randomly divided into training and validation cohorts (model construction and internal validation) from the SEER database. In the random forest (RF) and extreme gradient boosting (XGBoost) feature importance ranking models, age was the most important variable which was also reflected in the nomogram. And, the models that combined machine learning with cox proportional hazards had a better predictive performance than the model that only used cox proportional hazards (AUC = 0.762 in RF, AUC = 0.737 in XGBoost, AUC = 0.722 in COX). Calibration curves and decision curve analysis (DCA) curves also revealed that our nomogram has excellent clinical utility. The web-based dynamic nomogram calculator was accessible on https://httseer.shinyapps.io/DynNomapp/ . The prognosis characteristics of SPC following lung cancer were systematically reviewed. The dynamic nomogram we constructed can provide survival predictions to assist clinicians in making individualized decisions.

Predicting the risk of clinically significant intraocular lens tilt and decentration in vitrectomized eyes.

PURPOSE: To identify predictors and develop a prognostic nomogram for clinically significant intraocular lens (IOL) tilt and decentration in vitrectomized eyes. SETTING: Zhongshan ophthalmic center, Guangzhou, China. DESIGN: Prospective observational study. METHODS: Patients with previous pars plana vitrectomy who underwent phacoemulsification with IOL implantation were enrolled in this study. The tilt and decentration of the lens and IOL were assessed by a swept-source anterior segment optical coherence tomography (CASIA2). Multiple logistic regression analysis and prognostic nomogram models were used to explore factors associated with clinically significant IOL tilt and decentration (defined as tilt ≥7 degrees and decentration ≥0.4 mm). RESULTS: 375 patients (375 eyes) with a mean age of 56.1 ± 9.81 years were included. Lens tilt (odds ratio [OR] = 1.44), lens decentration (OR = 1.74), lens diameter (OR = 0.49), and hydrophilic IOL (OR = 2.36) were associated with IOL tilt over 7 degrees (all P &lt; .05). Lens tilt (OR = 1.24), lens decentration (OR = 2.30), and incomplete capsulorhexis-IOL overlap (OR = 2.44) increased the risk of IOL decentration over 0.4 mm (all P &lt; .05). Preoperative lens tilt together with lens decentration was identified as the strongest predictor of incident clinically significant IOL tilt (area under the curve [AUC] = 0.82, 95% CI, 0.76-0.88) and decentration (AUC: 0.84, 95% CI, 0.78-0.89), and the nomogram was constructed accordingly. CONCLUSIONS: The tilt and decentration of the crystalline lens, hydrophilic IOL, and incomplete capsulorhexis-IOL overlap were risk factors for clinically significant IOL misalignment. Clinicians could use a prognostic nomogram model based on the preoperative lens position to make a strategy for higher-risk patients.

Comparison of axial length measurements in silicone oil-filled eyes using SS-OCT and partial coherence interferometry.

PURPOSE: To compare axial length (AL) measurements in silicone oil (SO)-filled eyes using swept-source optical coherence tomography (SS-OCT) (the IOLMaster 700 and OA2000) and partial coherence interferometry (the IOLMaster 500). SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Cross-sectional study. METHODS: We enrolled phakic patients who underwent SO removal surgery. The AL measurements by the IOLMaster 500, IOLMaster 700, and OA2000, both before and after SO removal, were compared. Multiple regression analysis was performed to identify risk factors for the differences between preoperative and postoperative AL measurements. RESULTS: 68 patients (68 eyes) with a mean age of 46.43 ± 13.24 years were included. No statistically significant difference was observed in the preoperative AL measurements between the IOLMaster 500 and IOLMaster 700 (25.48 ± 2.51 mm vs 25.49 ± 2.46 mm; P = .63), whereas the OA2000 yielded shorter AL (25.34 ± 2.36 mm) (both P < .001). After SO removal, the AL measurements showed no statistically significant differences among the 3 devices. In reference to the postoperative AL, the IOLMaster 500 and IOLMaster 700 tended to overestimate the AL in SO-filled eyes (both P < .001), and this measurement error increased with longer AL (ß = 0.08 and 0.05, respectively; both P < .001). No statistically significant difference was observed between preoperative and postoperative AL measurements by the OA2000 ( P = .18). CONCLUSIONS: The OA2000 is the preferred biometer for AL measurement in SO-filled eyes, whereas the IOLMaster 500 and IOLMaster 700 overestimate the AL especially for long eyes, which needs adjustment in clinical use.

Potential therapeutic targets and molecular details of anthocyan-treated inflammatory bowel disease: a systematic bioinformatics analysis of network pharmacology.

Anthocyans, containing anthocyanins and anthocyanidins, play a crucial role in preventing and treating inflammatory bowel disease (IBD). Most anthocyanins and their basic elements, namely anthocyanidins have been recognized for the effective treatment of IBD, but the key biomarkers of anthocyan-treated IBD remain unclear. In this study, a bioinformatics analysis based on network pharmacology was performed to demonstrate the core-targets, biological functions, and signaling pathways of most common anthocyanidins that existed in anthocyans to reveal their potential or major mechanisms. The network pharmacology of the multi-target drug molecular design with specific signal nodes was selected, which was used to analyse core targets and complete the bioinformatics analysis of core targets. The network assays indicated 44 common targeted genes, 5 of which were core targets of both six most common anthocyanidins and IBD. These 44 common targets related to major signaling mechanisms of the six most common anthocyanidins in IBD may involve following processes: promotion of intracellular metabolism and proliferation, inhibition of cell necrosis, anti-inflammation and regulation of intestinal epithelial survival mainly via pathways such as, the EGFR tyrosine kinase inhibitor resistance pathway, platelet activation, microRNAs in cancer, arachidonic acid metabolism and the cGMP-PKG signaling pathway. Thus, our findings may provide other molecular details about anthocyans in the treatment of IBD and contribute towards the use of anthocyanidins, which will be meaningful shedding light on the action mechanisms of anthocyanidins in treating IBD.

Accuracy of Intraocular Lens Calculation Formulas in Patients Undergoing Combined Phakic Intraocular Lens Removal and Cataract Surgery.

PURPOSE: To investigate the prediction accuracy of intraocular lens (IOL) calculation formulas, and the impact of anterior chamber depth (ACD) and lens thickness (LT) measurement errors on IOL power calculation in patients undergoing combined phakic IOL (PIOL) removal and cataract surgery. DESIGN: Retrospective, consecutive case series study. METHODS: Thirty-six PIOL implanted eyes (12 anterior chamber PIOLs and 24 posterior chamber PIOLs [PC-PIOL]) undergoing cataract surgery were included. The prediction accuracy of new formulas (Barrett universal II, Emmetropia verifying optical, Kane, and Ladas super formula) and traditional formulas (Haigis, Hoffer Q, Holladay 1 and SRK/T) with or without Wang-Koch (WK) axial length (AL) adjustment was evaluated. The influence of ACD and LT measurement errors of IOLMaster 700 on refractive outcomes was also investigated. RESULTS: The Kane and traditional formulas with WK AL adjustment had no significant systematic prediction error and displayed a smaller median absolute error, whereas the other formulas showed significant hyperopia shift (P < .05) and relatively lower prediction accuracy. The accuracy rate of IOLMaster 700 in measuring the ACD and LT was 100% in eyes with anterior chamber PIOL implantation, and 37.50% in the PC-PIOL subgroup. No significant difference was observed in refractive outcomes of formulas using correct and wrong parameters in the PC-PIOL subgroup (P > .05). CONCLUSIONS: The Kane and traditional formulas with WK AL adjustment exhibited relatively higher prediction accuracy in patients who underwent combined PIOL removal and cataract surgery. The IOLMaster 700 displayed low accuracy in ACD and LT measurements for PC-PIOL implanted eyes, but showed negligible impact on IOL prediction accuracy.

Chemical composition and pharmacological mechanism of ephedra-glycyrrhiza drug pair against coronavirus disease 2019 (COVID-19).

Traditional Chinese medicine (TCM) had demonstrated effectiveness in the prevention and control of COVID-19. Statistics showed that Ephedra and Glycyrrhiza were frequently used in the treatment of COVID-19. We hypothesized that the Ephedra-Glycyrrhiza drug pair is a potential choice for the treatment of COVID-19. Here, 112 active compounds were identified from Ephedra-Glycyrrhiza via network pharmacology approach. Ephedra-Glycyrrhiza pair enrichment analysis demonstrated that these compounds might participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signaling pathways, which had a high correlation with respiratory, nervous, blood circulation and digestive system-related diseases. Pathway analysis between Ephedra-Glycyrrhiza and COVID-19 showed that the key targets were TNF-α, IL2, FOS, ALB, and PTGS2. They might control PI3K-Akt signaling pathway to exert immune regulation, organ protection and antiviral effects. Molecular docking results showed that the active compounds from the Ephedra-Glycyrrhiza pair bound well to COVID-19 related targets, including the main protease (Mpro, also called 3CLpro), the spike protein (S protein), and the angiotensin-converting enzyme 2 (ACE2). The Molecular dynamics simulation was analyzed for the stability and flexibility of the complex. In conclusion, our study elucidated the potential pharmacological mechanism of Ephedra-Glycyrrhiza in the treatment of COVID-19 through multiple targets and pathways.

Chemical composition and pharmacological mechanism of shenfu decoction in the treatment of novel coronavirus pneumonia (COVID-19).

PURPOSE: Shenfu decoction has outstanding curative effects in the treatment of COVID-19. This study aimed to explore the material basis and molecular mechanism of Shenfu Decoction through network pharmacology and molecular mechanisms, to provide a research basis for clinical medication and clues for subsequent research. METHODS: The active components and targets of Shenfu decoction were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the COVID-19-associated genes were collected using the Gene Cards platform. The target protein-protein interaction network map was constructed by mapping two genes, and the 'drug-active ingredient-target' network was constructed using Cytoscape software. The Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the mapping targets were analyzed. RESULT: Based on Traditional Chinese medicine, Shenfu Decoction can take effect in the lung, spleen, kidney and heart. Considering oral bioavailability (OB) ≥ 30% and drug-like (DL) ≥ 0.18 as the standard, 43 active compounds were screened and 114 Shenfu decoction action targets were collected. The key targets were CASP3, MAPK8, PTGS2, IL1B, PPARG, ICAM1, IFNG, RELA, NOS2, NOS3, HMOX1, CASP8, STAT1, and TGFB1. According to the standard of p < .05, GO function was enriched in 108 biological processes, 16 cell processes and 27 molecular processes. Sixty-three signaling pathways were enriched by KEGG, which can be divided into four types: viral infection pathways, signal pathways, biological process pathways and different disease pathways. The comparison of negative and positive prescriptions further reflects the positive effect of Shenfu decoction against COVID-19. Finally, the effective ingredients with the high degree were molecular docked with Mpro, Rdrp and Spro proteins to further confirm the intervention effect of Shenfu Decoction on COVID-19. CONCLUSION: Shenfu decoction played an important role in regulating the anti-virus process, regulating immunity, inhibiting inflammation and regulating apoptosis through the interrelated regulation mechanism of multi-components and multi-targets, to treat patients with severe COVID-19.

A Review on the Relationship between SGLT2 Inhibitors and Cancer.

Risk of increasing breast and bladder cancer remains a safety issue of SGLT2 (sodium glucose cotransporter type 2) inhibitors, a novel class of antidiabetic agent. We reviewed related papers published before January 29, 2014, through Pubmed search. Dapagliflozin and canagliflozin are the first two approved SGLT2 inhibitors for diabetes therapy. Although preclinical animal toxicology did not suggest a cancer risk of dapagliflozin and overall tumor did not increase, excess numbers of female breast cancer and male bladder cancer were noted in preclinical trials (without statistical significance). This concern of cancer risk hindered its approval by the US FDA in January, 2012. New clinical data suggested that the imbalance of bladder and breast cancer might be due to early diagnosis rather than a real increase of cancer incidence. No increased risk of overall bladder or breast cancer was noted for canagliflozin. Therefore, the imbalance observed with dapagliflozin treatment should not be considered as a class effect of SGLT2 inhibitors and the relationship with cancer for each specific SGLT2 inhibitor should be examined individually. Relationship between SGLT2 inhibition and cancer formation is still inconclusive and studies with larger sample size, longer exposure duration, and different ethnicities are warranted.