Enhancing infectious diseases early warning: A deep learning approach for influenza surveillance in China.

Objective: This study aimed to develop a universally applicable, feedback-informed Self-Excitation Attention Residual Network (SEAR) model. This model dynamically adapts to evolving disease trends and surveillance system changes, accommodating various scenarios. Thereby enhancing the effectiveness of early warning systems. Methods: Surveillance data on influenza-like illness (ILI) was collected from various regions including Northern China, Southern China, Beijing, and Yunnan. The reproduction number (Rt) was estimated to determine the threshold for issuing warnings. The Self-Excitation Attention Residual Network (SEAR) was devised employing deep learning algorithms and was trained, validated, and tested. The SEAR model's efficacy was assessed based on five metrics: accuracy rate, recall rate, F1 score, confusion matrix, and the receiver operating characteristic curve. Results: With an advance warning set at three days, the SEAR model outperformed five primary models - logistic regression, support vector machine, random forest, Extreme Gradient Boosting, and Long Short-Term Memory model - in all five evaluation metrics. Notably, the model's warning performance declined with an increase in the early warning value and the number of warning days, albeit maintaining a ROC value over 0.7 in all scenarios. Conclusion: The SEAR model demonstrated robust early warning performance for influenza in diverse Chinese regions with high accuracy and specificity. This novel model, augmenting traditional systems, supports widespread application for respiratory disease outbreak monitoring. Future evaluations could incorporate alternative indicators, with the model continuously updating through data feedback, thus enhancing its universal applicability. Ongoing optimization, using iterative feedback and expert judgment, heralds a transformative approach to surveillance-based early warning strategies.

Sulfated Polysaccharides with Anticoagulant Potential: A Review Focusing on Structure-Activity Relationship and Action Mechanism.

Thromboembolism is the culprit of cardiovascular diseases, leading to the highest global mortality rate. Anticoagulation emerges as the primary approach for managing thrombotic conditions. Notably, sulfated polysaccharides exhibit favorable anticoagulant efficacy with reduced side effects. This review focuses on the structure-anticoagulant activity relationship of sulfated polysaccharides and the underlying action mechanisms. It is concluded that chlorosulfonicacid-pyridine method serves as the preferred technique to synthesize sulfated polysaccharides. The anticoagulant activity of sulfated polysaccharides is linked to the substitution site of sulfate groups, degree of substitution, molecular weight, main side chain structure, and glycosidic bond conformation. Moreover, sulfated polysaccharides exert anticoagulant activity via various pathways, including the inhibition of blood coagulation factors, activation of antithrombin III and heparin cofactor II, antiplatelet aggregation, and promotion of the fibrinolytic system.

Interplay between mitochondrial dysfunction and lysosomal storage: challenges in genetic metabolic muscle diseases with a focus on infantile onset Pompe disease.

Background: Pompe disease (PD) is a rare, progressive autosomal recessive lysosomal storage disorder that directly impacts mitochondrial function, leading to structural abnormalities and potentially culminating in heart failure or cardiogenic shock. The clinical course and molecular mechanisms of the disease remain incompletely understood. Methods: We performed a retrospective analysis to examine the clinical manifestations, genetic traits, and the relationship between PD and mitochondrial function in a pediatric patient. This comprehensive evaluation included the use of ultrasound echocardiograms, computed tomography (CT) scans, electrocardiograms, mutagenesis analysis, and structural analysis to gain insights into the patient's condition and the underlying mechanisms of PD. For structural analysis and visualization, the structure of protein data bank ID 5KZX of human GAA was used, and VMD software was used for visualization and analysis. Results: The study revealed that a 5-month-old male infant was admitted due to fever, with physical examination finding abnormal cardiopulmonary function and hepatomegaly. Laboratory tests and echocardiography confirmed heart failure and hypertrophic cardiomyopathy. Despite a week of treatment, which normalized body temperature and reduced pulmonary inflammation, cardiac abnormalities did not show significant improvement. Further genetic testing identified a homozygous mutation c.2662G>T (p.E888) in the GAA gene, leading to a diagnosis of Infantile-Onset Pompe Disease (IOPD). Conclusions: Although enzyme replacement therapy can significantly improve the quality of life for patients with PD, enhancing mitochondrial function may represent a new therapeutic strategy for treating PD.

MdWER interacts with MdERF109 and MdJAZ2 to mediate methyl jasmonate- and light-induced anthocyanin biosynthesis in apple fruit.

Anthocyanin generation in apples (Malus domestica) and the pigmentation that results from it may be caused by irradiation and through administration of methyl jasmonate (MeJA). However, their regulatory interrelationships associated with fruit coloration are not well defined. To determine whether MdERF109, a transcription factor (TF) involved in light-mediated coloration and anthocyanin biosynthesis, has synergistic effects with other proteins, we performed a yeast two-hybrid assessment and identified another TF, MdWER. MdWER was induced by MeJA treatment, and although overexpression of MdWER alone did not promote anthocyanin accumulation co-overexpression with MdERF109 resulted in significantly increase in anthocyanin biosynthesis. MdWER may form a protein complex with MdERF109 to promote anthocyanin accumulation by enhancing combinations between the proteins and their corresponding genes. In addition, MdWER, as a MeJA responsive protein, interacts with the anthocyanin repressor MdJAZ2. Transient co-expression in apple fruit and protein interaction assays allowed us to conclude that MdERF109 and MdJAZ2 interact with MdWER and take part in the production of anthocyanins upon MeJA treatment and irradiation. Our findings validate a role for the MdERF109-MdWER-MdJAZ2 module in anthocyanin biosynthesis and uncover a novel mechanism for how light and MeJA signals are coordinated anthocyanin biosynthesis in apple fruit.

A newly developed deep learning-based system for automatic detection and classification of small bowel lesions during double-balloon enteroscopy examination.

BACKGROUND: Double-balloon enteroscopy (DBE) is a standard method for diagnosing and treating small bowel disease. However, DBE may yield false-negative results due to oversight or inexperience. We aim to develop a computer-aided diagnostic (CAD) system for the automatic detection and classification of small bowel abnormalities in DBE. DESIGN AND METHODS: A total of 5201 images were collected from Renmin Hospital of Wuhan University to construct a detection model for localizing lesions during DBE, and 3021 images were collected to construct a classification model for classifying lesions into four classes, protruding lesion, diverticulum, erosion & ulcer and angioectasia. The performance of the two models was evaluated using 1318 normal images and 915 abnormal images and 65 videos from independent patients and then compared with that of 8 endoscopists. The standard answer was the expert consensus. RESULTS: For the image test set, the detection model achieved a sensitivity of 92% (843/915) and an area under the curve (AUC) of 0.947, and the classification model achieved an accuracy of 86%. For the video test set, the accuracy of the system was significantly better than that of the endoscopists (85% vs. 77 ± 6%, p < 0.01). For the video test set, the proposed system was superior to novices and comparable to experts. CONCLUSIONS: We established a real-time CAD system for detecting and classifying small bowel lesions in DBE with favourable performance. ENDOANGEL-DBE has the potential to help endoscopists, especially novices, in clinical practice and may reduce the miss rate of small bowel lesions.

Discovery of antitussive material basis and mechanisms in Citri Sarcodactylis Fructus by coupling UHPLC-Q/Orbitrap HRMS combined spectrum-effect relationship and metabolomics analyses.

Citri Sarcodactylis Fructus (CSF) is widely used as food raw material and traditional Chinese medicine. Fingerprints of different fractions of CSF were established for spectrum-effect relationship analysis, and the main compounds were identified by UHPLC Quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS). The antitussive effect was evaluated using a classical mouse model of cough induced by ammonia water. One-way ANOVA was used to determine differences in efficacy. The potential active compounds were screened by spectrum-effect relationship with grey relational degree analysis (GRA), Pearson bivariate correlation analysis (Pearson's), and partial least squares analysis (PLS) analyses. Differential metabolites associated with cough in serum were screened and identified using orthogonal partial least squares-discriminant analysis, HMDB database, and UHPLC-Q/Orbitrap HRMS. Metabolic pathway analysis was performed using MetaboAnalyst 5.0. Results indicate that 70 % ethanol elution fraction (70 % EF) is the major active fraction, and 8 components were identified to possess antitussive effects. Metabolomic analysis showed that 19 metabolites are potential biomarkers related to cough, and 70 % EF can remarkable restore 13 of them to normal levels (P < 0.05). These biomarkers are mainly involved in glycerophospholipid metabolism and sphingolipid metabolism. This study aims to reveal the main pharmacodynamic active sites and potential active ingredients of CSF's antitussive effect. In addition, metabolomics was used to preliminarily elucidate the in-vivo regulatory mechanism of the antitussive effect of the 70 % EF of CSF.

Total Synthesis of Tetracyclic Spirooxindole Alkaloids via a Double Oxidative Rearrangement/Cyclization Cascade.

Skeleton rearrangement could rapidly transfer simple molecules to complex structures and has significant potential in the total synthesis of natural products. We developed a one-pot reaction cascade of double oxidative rearrangement of furan and indole followed by a nucleophilic cyclization that was successfully applied for the formal synthesis of rhynchophylline/isorhynchophylline and the first total synthesis of (±)-7(R)-geissoschizol oxindole/(±)-7(S)-geissoschizol oxindole. In addition, the geissoschizol oxindoles were revised to their C3 epimers, and the mechanism for the reversed stereochemistry through the retro-Mannich/Mannich cascade was proposed and supported by density functional theory calculations.

Growth Factors-Loaded Temperature-Sensitive Hydrogel as Biomimetic Mucus Attenuated Murine Ulcerative Colitis via Repairing the Mucosal Barriers.

The pathogenesis of ulcerative colitis (UC) is associated with the shedding of the gut mucus. Herein, inspired by the biological functions of mucus, growth factors-loaded in situ hydrogel (PHE-EK) was designed for UC treatment by integrating dihydrocaffeic acid-modified poloxamer as a thermosensitive material with hyaluronic acid (colitis-specific adhesive), epigallocatechin-3-gallate (antibacterial agent), and bioactive factors (KPV tripeptide and epidermal growth factor). PHE-EK presented good thermosensitive properties, as a flowable liquid at room temperature and gelled within 10 s when exposed to body temperature. PHE-EK hydrogel presented good mechanical strength with a strain of 77.8%. Moreover, PHE-EK hydrogel displayed antibacterial activity against Escherichia coli. Importantly, in vitro and in vivo adhesive tests showed that the PHE-EK hydrogel could specifically adhere to the inflamed colon via electrostatic interaction. When PHE-EK as a biomimetic mucus was rectally administrated to colitis rats, it effectively hindered the body weight loss, reduced the disease activity index and improved the colonic shorting. Moreover, the expression of pro-inflammatory cytokines (e.g., IL-1ß, IL-6, and TNF-α) at the laminae propria or epitheliums of the colon for colitis rats was substantially inhibited by PHE-EK. Besides, the colonic epitheliums were well rearranged, and the tight junction proteins (Zonula-1 and Claudin-5) between them were greatly upregulated after PHE-EK treatment. Collectively, PHE-EK might be a promising therapy for UC.

Summary and future of medicine for hereditary angioedema.

Hereditary angioedema (HAE) is a rare autosomal genetic disease for which there are currently nine FDA-approved drugs. This review summarizes drug treatments for HAE based on four therapeutic pathways: inhibiting the contact system, inhibiting bradykinin binding to B2 receptors, supplying missing C1 inhibitors, and inhibiting plasminogen conversion. The review generalizes the clinical use, pharmacological effects and mechanisms of HAE drugs, and it also discusses possible development directions and targets to enhance understanding of HAE and help researchers.

Prognostic and Immune Infiltration Signatures of GIMAP Family Genes in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system characterized by abundant immunocytes infiltration. The impact of guanosine triphosphatases (GTPases) of immunity-associated proteins (GIMAPs) on the tumor immune microenvironment (TIME) and prognosis of ccRCC is unclear. METHODS: The expression of GIMAPs in ccRCC was determined through multiple datasets (ONCOMINE, TCGA and UALCAN). The relationship between GIMAP family members was analyzed through Spearman correlation analysis. The interaction among the GIMAPs protein was analyzed using STRING. Prognostic values of GIMAPs were evaluated by Survival analysis, Lasso and Cox regression analysis; Prognostic risk model and nomogram were constructed. The correlation between GIMAPs and TIME was explored using TIMER, Cibersort and Pearson correlation analysis. Gene set enrichment analysis (GSEA) was performed to discuss their function and mechanism in ccRCC. RESULTS: GIMAPs were over-expressed in ccRCC and significantly related to overall survival (OS) of the patients. GIMAPs were positively correlated with each other, the risk model based on GIMAPs had good prognostic value in ccRCC. GIMAPs mainly expressed in TIME and were associated with abundant immunocytic infiltration in ccRCC, the risk model also had close correlation with TIME. Our results showed GIMAPs may affect the development of ccRCC by regulating the amount and antitumor activity of immunocytes in TIME. CONCLUSIONS: GIMAPs were over-expressed in ccRCC, and their expression levels were significantly related to the OS of patients and immunocytic infiltration in TIME. GIMAPs are potential therapeutic targets and prognostic biomarkers for ccRCC.

TBC1D15 deficiency protects against doxorubicin cardiotoxicity via inhibiting DNA-PKcs cytosolic retention and DNA damage.

Clinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity. Tamoxifen-induced cardiac-specific Tbc1d15 knockout (Tbc1d15CKO) or Tbc1d15 knockin (Tbc1d15CKI) male mice were challenged with a single dose of DOX prior to cardiac assessment 1 week or 4 weeks following DOX challenge. Adenoviruses encoding TBC1D15 or containing shRNA targeting Tbc1d15 were used for Tbc1d15 overexpression or knockdown in isolated primary mouse cardiomyocytes. Our results revealed that DOX evoked upregulation of TBC1D15 with compromised myocardial function and overt mortality, the effects of which were ameliorated and accentuated by Tbc1d15 deletion and Tbc1d15 overexpression, respectively. DOX overtly evoked apoptotic cell death, the effect of which was alleviated and exacerbated by Tbc1d15 knockout and overexpression, respectively. Meanwhile, DOX provoked mitochondrial membrane potential collapse, oxidative stress and DNA damage, the effects of which were mitigated and exacerbated by Tbc1d15 knockdown and overexpression, respectively. Further scrutiny revealed that TBC1D15 fostered cytosolic accumulation of the cardinal DDR element DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Liquid chromatography-tandem mass spectrometry and co-immunoprecipitation denoted an interaction between TBC1D15 and DNA-PKcs at the segment 594-624 of TBC1D15. Moreover, overexpression of TBC1D15 mutant (∆594-624, deletion of segment 594-624) failed to elicit accentuation of DOX-induced cytosolic retention of DNA-PKcs, DNA damage and cardiomyocyte apoptosis by TBC1D15 wild type. However, Tbc1d15 deletion ameliorated DOX-induced cardiomyocyte contractile anomalies, apoptosis, mitochondrial anomalies, DNA damage and cytosolic DNA-PKcs accumulation, which were canceled off by DNA-PKcs inhibition or ATM activation. Taken together, our findings denoted a pivotal role for TBC1D15 in DOX-induced DNA damage, mitochondrial injury, and apoptosis possibly through binding with DNA-PKcs and thus gate-keeping its cytosolic retention, a route to accentuation of cardiac contractile dysfunction in DOX-induced cardiotoxicity.

Sequence and directivity in cardiac muscle injury of COVID-19 patients: an observational study.

Objective: To compare cardiac function indicators between mild and moderate to severe COVID-19 patients and to try to identify the sequence and directivity in cardiac muscle injury of COVID-19 patients. Methods: From December 2022 to January 2023, all patients with laboratory-confirmed SARS-CoV-2 infection in Shanghai General Hospital Jiading Branch were enrolled. The clinical classification was stratified into mild, moderate, or severe groups. We collected the clinical and laboratory information, transthoracic echocardiographic and speckle-tracking echocardiographic parameters of patients and compared the differences among different groups. Results: The values of echocardiographic parameters in mild group were lower than that in moderate or severe group (P < 0.05) except LVEF. The values of LVEF of mild and moderate group were higher than severe group (P < 0.05). There were no significant differences between moderate and severe group. Positive correlations were observed between left ventricular global longitudinal strain (LVGLS) and myoglobin (r = 0.72), E/e' and age (r = 0.79), E/e' and BNP (r = 0.67). The multivariate analysis shows that SpO2 (OR = 0.360, P = 0.02), LVGLS (OR = 3.196, P = 0.003) and E/e' (OR = 1.307, P = 0.036) were the independent risk factors for mild cases progressing to moderate or severe. According to the receiver operating characteristic (ROC) curves, when all the COVID-19 patients was taken as the sample size, the area under the curve (AUC) of the LVGLS was the highest (AUC = 0.861). The AUC of the LVGLS was higher than LVGCS (AUC = 0.565, P < 0.001). Conclusion: When mild COVID-19 progresses to moderate or severe, both systolic and diastolic functions of the heart are impaired. LVGLS was the independent risk factor for mild cases progressing to moderate or severe cases. Longitudinal changes may manifest earlier than circumferential changes as myocardial disease progresses in COVID-19.

Nursing care of patients with relapsed and refractory multiple myeloma treated with B-cell mature antigen-targeted universal chimeric antigen receptor T cells.

To investigate the efficacy of a nursing approach using B-cell maturation antigen (BCMA)-targeted universal chimeric antigen receptor T-cell (BCMA-UCART) immunotherapy in the treatment of 8 patients with relapsed refractory multiple myeloma (MM). In this study, 16 patients with relapsed and refractory MM who were treated with BCMA-targeted UCART in our department from May 2020 to November 2022 were selected, and were divided into a control group and an experimental group of 8 cases each according to the difference in the nursing methods, and the control group adopted the conventional universal nursing program. The experimental group used the nursing protocol that cooperated with the immunotherapy of this study, and the main points of nursing care included timely assessment of organ functional status, safe and accurate infusion of BCMA-UCART, identification and management of hyperthermia, hypotension, arrhythmia and central nervous system adverse reactions caused by cytokine release after BCMA-UCART infusion, as well as management of fluid imbalance, maintenance of stable blood pressure, and cooperation with physicians to effectively control of inflammatory factors. In addition, patients were provided with psychological and dietary support. The duration of hospitalization was compared between the two groups after the intervention. The discharge time of the experimental group was significantly shorter than that of the control group (P he.05), and the experimental group effectively controlled cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and acute graft-versus-host disease. The nursing program with BCMA-UCART immunotherapy is effective in intervening MM patients and promotes their early recovery and discharge from the hospital.

Gender and age disparities in small-to-medium arterial stiffness among the Chinese population.

BACKGROUND AND AIMS: Arterial pressure-volume index (API) is a non-invasive tool for assessing small-to-medium-sized arterial stiffness. This study aimed to investigate the potential age- and sex-related differences in the API and explore the practical implications of such differences. METHODS AND RESULTS: The study analysed 7620 subjects for whom API measurements were available. Linear regression and restrictive cubic spline models were used to investigate the associations between potential risk conditions and the API. Additionally, this study employed a backward stepwise regression method to identify the independent factors associated with a high API. Middle-aged to older women had higher API values and a higher prevalence of high API than men in the same age group. However, the opposite was observed among younger individuals, with women having lower API values than men. This study also identified a J-shaped relationship between API and age, where API values began to increase at a certain age and rapidly increased after that. In women, the API started to increase at 31 years of age and rapidly increased after 54 years of age. In men, the API started to increase at 38 years of age, followed by a rapid increase after 53 years of age. CONCLUSION: This study's observation of a significant age-sex interaction in small-to-medium-sized arterial stiffening offers a valuable explanation for cardiovascular disease risk and provides important parameters for using API measurements to evaluate such risk.

Uncoupling of the center-to-periphery arterial stiffness gradient and pulse pressure amplification in viral pneumonia infection.

OBJECTIVES: Arterial stiffness is a common manifestation of viral pneumonia infections, including COVID-19. Nevertheless, the relationship between the center-to-periphery arterial stiffness gradient and pulse pressure amplification (PPA) in infectious diseases remains unclear. This study aimed to investigate this relationship utilizing arterial pressure volume index (API) and arterial velocity pulse index (AVI) ratio. METHODS: API/AVI and PPA were measured in 219 participants with COVID-19 and 374 normal participants. Multiple linear regression was used to assess the association of API/AVI and PPA, and restricted cubic spline was used to investigate the non-linear relationship between API/AVI and PPA. Receiver operating characteristic curve (ROC) analysis was used to evaluate the effects of API/AVI in identifying COVID-19 infection and severe stage. RESULTS: There was a significant J-shaped relationship between API/AVI and PPA in COVID-19 group, while a M-shaped relationship was observed in normal group. API/AVI decreased rapidly as PPA decreased until API/AVI decreased slowly at PPA of 1.07, and then API/AVI decreased slowly again at PPA of 0.78. ROC results showed that API/AVI demonstrated excellent accuracy in identifying COVID-19 infection (AUC = 0.781) and a high specificity (84.88%) in identifying severe stage. CONCLUSIONS: There was a J-shaped association between the API/AVI and PPA in viral infected patients, while a M-shaped relationship in the normal participants. API/AVI is better for identifying infected and uninfected patients, with a high specificity in identifying those in severe stages of the disease. The attenuation or reversal of API/AVI may be associated with the loss of PPA coupling.

Fusobacterium nucleatum promotes colorectal cancer metastasis by excretion of miR-122-5p from cells via exosomes.

Fusobacterium nucleatum (Fn) infection and microRNAs (miRNAs) are closely associated with colorectal cancer (CRC) development, but the mechanism by which Fn regulates tumor-suppressive miRNAs via exosomes and facilitates CRC metastasis remains unclear. Here, we identified that Fn infection significantly increased exosomal miR-122-5p levels in the serum of CRC patients and CRC cell culture supernatants through two miRNA panels of high-throughput sequencing and RT-qPCR analysis. In Fn-infected patients, the serum exosomal levels of miR-122-5p were negatively associated with their expression levels of tissues. Downregulated miR-122-5p was demonstrated to enhance the migration, invasion, and metastasis abilities of CRC cells in vivo and in vitro. Secretion of miR-122-5p into exosomes is mediated by hnRNPA2B1. Mechanistically, Fn activated the TGF-ß1/Smads signaling pathway to promote EMT by regulation of the miR-122-5p/FUT8 axis. In conclusion, Fn infection may stimulate CRC cells to excrete exosome-wrapped miR-122-5p, and activate the FUT8/TGF-ß1/Smads axis to promote metastasis.

CircHIPK3 contributes to cisplatin resistance in gastric cancer by blocking autophagy-dependent ferroptosis.

Cisplatin is the first-line chemotherapy for gastric cancer (GC). However, its efficacy is dampened by the development of chemoresistance, which leads to poor prognosis in GC patients. Recently, evidence has revealed that circular RNAs (circRNAs) and dysregulation of autophagy-dependent ferroptosis play critical roles in cancer chemoresistance. Herein, for the first time we report that circHIPK3 has a vital role in GC cisplatin resistance. CircHIPK3 regulated cisplatin resistance by targeting autophagy and ferroptosis. In brief, knockdown circHIPK3 decreased GC cell cisplatin resistance by enhancing ferroptosis via the miR-508-3p/Bcl-2/beclin1/SLC7A11 axis. Taken together, our results demonstrate that ferroptosis is a promising strategy to ameliorate cisplatin resistance. Importantly, serum exosomal circHIPK3 could also be a noninvasive indicator to evaluate cisplatin resistance in GC.

Screening of anti-cancer compounds from Vaccariae Semen by lung cancer A549 cell fishing and UHPLC-LTQ Orbitrap MS.

Vaccariae Semen, derived from the dried ripe seed of Vaccaria segetalis (Neck.) Garcke, has various therapeutic characteristics in traditional Chinese medicine (TCM), containing promoting blood circulation and unblocking meridians. It exhibits significant anti-cancer activity and is therapeutically utilized to treat and reduce chemotherapy adverse effects in cancer patients, notably those with lung cancer. However, the active ingredients responsible for its anti-lung cancer efficacy remain unknown. In this study, we used A549 cell fishing in conjunction with UHPLC-LTQ Orbitrap MS to screen for anti-lung cancer active components in Vaccariae Semen. The cell counting Kit-8 (CCK-8) assay revealed that the n-butanol extract substantially reduced A549 cell growth. Through the cell fishing assay, we found 14 A549 cell-binding compounds in the n-butanol extract, all of which were identified as triterpenoid saponins. The total saponins of Vaccariae Semen were subsequently purified using macroporous adsorption resin (MAR), and they showed a significant inhibitory effect on the proliferation of A549 lung cancer cells, as well as alterations in cell morphology, apoptosis, and fragmentation. In conclusion, saponins were discovered as the key active components responsible for the anti-lung cancer activity of Vaccariae Semen.

From the updated landscape of the emerging biologics for IBDs treatment to the new delivery systems.

Inflammatory bowel diseases (IBDs) treatments have shifted from small-molecular therapeutics to the oncoming biologics. The first-line biologics against the moderate-to-severe IBDs are mainly involved in antibodies against integrins, cytokines and cell adhesion molecules. Besides, other biologics including growth factors, antioxidative enzyme, anti-inflammatory peptides, nucleic acids, stem cells and probiotics have also been explored at preclinical or clinical studies. Biologics with variety of origins have their unique potentials in attenuating immune inflammation or gut mucosa healing. Great advances in use of biologics for IBDs treatments have been archived in recent years. But delivering issues for biologic have also been confronted due to their liable nature. In this review, we will focus on biologics for IBDs treatments in the recent publications; summarize the current landscapes of biologics and their promise to control disease progress. Alternatively, the confronted challenges for delivering biologics will also be analyzed. To combat these drawbacks, some new delivering strategies are provided: firstly, designing the functional materials with high affinity toward biologics; secondly, the delivering vehicle systems to encapsulate the liable biologics; thirdly, the topical adhering delivery systems as enema. To our knowledge, this review is the first study to summarize the updated usage of the oncoming biologics for IBDs, their confronted challenges in term of delivery and the potential combating strategies.

Relative contributions of arterial stiffness to cardiovascular disease risk score in Chinese women in framingham and China-PAR model.

Background: Arterial stiffness played an important role in the development of cardiovascular disease (CVD) events. The aim of this study was to verify the relative importance of arterial stiffness for different CVD risk scores in a large sample of Chinese women. Methods: We measured arterial velocity pulse index (AVI) and CVD risk scores in 2220 female participants (mean age 57 years). Framingham Risk Score (FRS), and the prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) were used to estimate CVD risk, respectively. The relationships between AVI and risk scores were investigated by linear regressions and restricted cubic spline (RCS) analysis. To determine the relative importance of AVI in predicting CVD risk scores, random forest analysis was used. Results: There was a significant positive correlation between AVI and FRS, China-PAR in all subgroup groups stratified by age, blood pressure and BMI. AVI showed higher importance in predicting CVD risk scores in FRS model, compared with these traditional risk factors. In China-PAR model, although AVI was not as predictive as SBP, it had better predictive power than many known risk factors such as lipids. Furthermore, AVI had significant J-shaped associations both with FRS and China-PAR scores. Conclusions: AVI was significantly associated with CVD risk score. In FRS and China-PAR model, AVI showed relatively high importance in predicting CVD risk scores. These findings may support the use of arterial stiffness measurements in CVD risk assessment.