Novel fabrication of anti-VEGF drug ranibizumab loaded PLGA/PLA co-polymeric nanomicelles for long-acting intraocular delivery in the treatment of age-related macular degeneration therapy.

Age associated macular degeneration is the 3rd primary cause of blind fundus diseases globally. A reliable and long-lasting method of intraocular drug delivery is still needed. Herein, this study was aim to develop the novel fabrication of ranibizumab loaded co-polymeric nanomicelles (Rabz-CP-NMs) for AMD. The CMC of co-polymeric nanomicelles was determined to be low, at 6.2 µg/ml. The ring copolymerization method was employed to fabricate the NMs and characterize via FTIR, XRD, TEM, DLS and Zeta potential. Rabz-CP-NMs was spherical shape with 10-50 nm in size. Stable and prolonged drug release was achieved with the Rabz from CP-NMs at 48 h. D407 and ARPE19 ocular cell lines showed dose-dependent cell viability with Rabz-CP-NMs. The Rabz-CP-NMs also had less toxicity, higher uptake, lower cell death and prolonged VEGF-A inhibition, as shown by cytoviability assay. Thus, Rabz-CP-NMs were safe for ocular use, suggesting that could be used to improve intraocular AMD treatment.

Rapid Selection of Patients Suitable for Deep Inspiration Breath-Hold Using an Automatic Delineating System and RapidPlan Model in Patients With Left Breast Cancer Undergoing Adjuvant Radiation Therapy With IMRT.

PURPOSE: This study aimed to determine whether radiation therapy plans created using an automatic delineating system and a RapidPlan (RP) module could rapidly and accurately predict heart doses and benefit from deep inspiratory breath-hold (DIBH) in patients with left breast cancer. METHODS AND MATERIALS: One hundred thirty-six clinically approved free breathing (FB) plans for patients with left breast cancer were included, defined as manual delineation-manual plan (MD-MP). A total of 104 of 136 plans were selected for RP model training. A total of 32 of 136 patients were automatically delineated by software, after which the RP generated plans, defined as automatic delineation-RapidPlan (AD-RP). In addition, 40 patients who used DIBH were included to analyze differences in heart benefits from DIBH. RESULTS: Two RP models were established for post-breast-conserving surgery (BCS) and post-modified radical mastectomy. There were no significant differences in most of the dosimetric parameters between the MD-MP and AD-RP. The heart doses of the 2 plans were strongly correlated in patients after BCS (0.80 ≤ r ≤ 0.88, P < .05) and moderately correlated in patients after postmodified radical mastectomy (0.46 ≤ r ≤ 0.58, P <.05). The RP model predicted the mean heart dose (MHD) within ± 59.67 cGy and ± 63.32 cGy for patients who underwent the 2 surgeries described above. The heart benefits from DIBH were significantly greater in patients with FB-MHD ≥ 4 Gy than in those with FB-MHD < 4 Gy. CONCLUSIONS: The combined automatic delineation RP model allows for the rapid and accurate prediction of heart dose under FB in patients with left breast cancer. FB-MHD ≥ 4 Gy can be used as a dose threshold to select patients suitable for DIBH.

Educational attainment, income, and attention deficit hyperactivity disorder: A mediation analysis based on two-step Mendelian randomization.

Previous studies have reported the relationship between educational attainment and attention deficit hyperactivity disorder (ADHD). However, the mechanism of this relationship remains unknown. It is well known that educational attainment correlates with income. Therefore, based on summary data from a genome-wide association study we used two-step Mendelian randomization (MR) to explore the role of income between education and ADHD. The inverse variance weighted (IVW) method was used in our analysis. The IVW results suggested that educational attainment and income were protective factors against ADHD. Educational attainment affects ADHD through income [ADHD: Beta = -0.68, 95% confidence interval (CI) = -0.87, -0.49; female: Beta = -0.87, 95% CI = -1.28, -0.47; male: Beta = -1.01, 95% CI = -1.34, -0.68; childhood: Beta = -0.52, 95% CI = -0.74, -0.30; late-diagnosed: Beta = -0.78, 95% CI = -1.11, -0.47; persistent: Beta = -0.82, 95% CI = -1.33, -0.31]. Income also affected ADHD through educational attainment [female: Beta = -1.08, 95% CI = -1.35, -0.83; male: Beta = -1.16, 95% CI = -1.57, -0.77; persistent: Beta = -1.48, 95% CI = -2.09, -0.94]. In the final analysis, data with heterogeneity were analyzed using IVW random effects results. The mechanism is that income will mediate the relationship between educational attainment and ADHD.

Feasibility and reproducibility of semi-automated longitudinal strain analysis: a comparative study with conventional manual strain analysis.

BACKGROUND: Conventional approach to myocardial strain analysis relies on a software designed for the left ventricle (LV) which is complex and time-consuming and is not specific for right ventricular (RV) and left atrial (LA) assessment. This study compared this conventional manual approach to strain evaluation with a novel semi-automatic analysis of myocardial strain, which is also chamber-specific. METHODS: Two experienced observers used the AutoStrain software and manual QLab analysis to measure the LV, RV and LA strains in 152 healthy volunteers. Fifty cases were randomly selected for timing evaluation. RESULTS: No significant differences in LV global longitudinal strain (LVGLS) were observed between the two methods (-21.0% ± 2.5% vs. -20.8% ± 2.4%, p = 0.230). Conversely, RV longitudinal free wall strain (RVFWS) and LA longitudinal strain during the reservoir phase (LASr) measured by the semi-automatic software differed from the manual analysis (RVFWS: -26.4% ± 4.8% vs. -31.3% ± 5.8%, p < 0.001; LAS: 48.0% ± 10.0% vs. 37.6% ± 9.9%, p < 0.001). Bland-Altman analysis showed a mean error of 0.1%, 4.9%, and 10.5% for LVGLS, RVFWS, and LASr, respectively, with limits of agreement of -2.9,2.6%, -8.1,17.9%, and -12.3,33.3%, respectively. The semi-automatic method had a significantly shorter strain analysis time compared with the manual method. CONCLUSIONS: The novel semi-automatic strain analysis has the potential to improve efficiency in measurement of longitudinal myocardial strain. It shows good agreement with manual analysis for LV strain measurement.

Handheld photoacoustic imaging of indocyanine green clearance for real-time quantitative evaluation of liver reserve function.

Preoperative assessment of liver function reserve (LFR) is essential for determining the extent of liver resection and predicting the prognosis of patients with liver disease. In this paper, we present a real-time, handheld photoacoustic imaging (PAI) system-based noninvasive approach for rapid LFR assessment. A linear-array ultrasound transducer was sealed in a housing filled with water; its front end was covered with a plastic wrap. This PAI system was first implemented on phantoms to confirm that the photoacoustic (PA) intensity of indocyanine green (ICG) in blood reflects the concentration of ICG in blood. In vivo studies on normal rabbits and rabbits with liver fibrosis were carried out by recording the dynamic PA signal of ICG in their jugular veins. By analyzing the PA intensity-time curve, a clear difference was identified in the pharmacokinetic behavior of ICG between the two groups. In normal rabbits, the mean ICG clearance rate obtained by PAI at 15 min after administration (PAI-R15) was below 21.6%, whereas in rabbits with liver fibrosis, PAI-R15 exceeded 62.0% because of poor liver metabolism. The effectiveness of the proposed method was further validated by the conventional ICG clearance test and pathological examination. Our findings suggest that PAI is a rapid, noninvasive, and convenient method for LFR assessment and has immense potential for assisting clinicians in diagnosing and managing patients with liver disease.

Ginsenoside CK, rather than Rb1, possesses potential chemopreventive activities in human gastric cancer via regulating PI3K/AKT/NF-κB signal pathway.

Ginsenoside Rb1, a main component of ginseng, is often transformed into ginsenoside CK by intestinal flora to exert various pharmacological activity. However, it remains unclear whether ginsenoside CK is responsible for the anti-gastric cancer effect of ginsenoside Rb1 in vivo. In this study, network pharmacology was applied to predict the key signal pathways of ginsenoside Rb1 and ginsenoside CK when treating gastric cancer. The anti-proliferative effects of ginsenoside Rb1 and ginsenoside CK and the underlying mechanism in gastric cancer cells were explored by MTT, Hoechst3328 staining, ELISA, RT-qPCR and Western blotting. The results showed that PI3K-AKT/NF-κB signal pathway was the common important pathway of ginsenoside Rb1 and CK in the treatment of gastric cancer. The results of MTT assay showed that ginsenoside Rb1 could hardly inhibit the proliferation of HGC-27 cells, whereas ginsenoside CK could inhibit the proliferation of HGC-27 cells. Hoechst3328 staining showed that cells in the ginsenoside CK group were densely stained bright blue and nuclear fragmented, indicating that apoptosis occurred. ELISA results showed that ginsenoside CK could effectively downregulate the levels of cyclin CyclinB1 and CyclinD1, but ginsenoside Rb1 had no significant effect. Also, the results of Western blot and RT-qPCR showed that ginsenoside CK inhibited the expressions of anti-apoptosis-related protein Bcl-2 and apoptosis-related pathway PI3K/AKT/NF-κB, and promoted the expression of pro-apoptosis proteins Bax and Caspase 3, whereas ginsenoside Rb1 exerted no effect. In short, ginsenoside Rb1 had no anti-gastric cancer cell activity in vitro, but ginsenoside CK could effectively inhibit cell proliferation and induce cell apoptosis in HGC-27 cells. The mechanism might relate to the inhibitory effect of ginsenoside CK on the PI3K/AKT/NF-κB pathway. These results suggest that ginsenoside CK might be the in vivo material basis for the anti-gastric cancer activity of ginsenosides.

Can aloin develop to medicines or healthcare products?

In folk medicine, Aloe, a genus of Aloaceae, is constantly developed into laxative drugs or products and skin remedies with tremendous popularity worldwide. However, almost all products of Aloe are in roughly processed form. Therefore, developing related products of the active ingredients derived from Aloe is of great medical value. Aloin is a quality standard compound based on the Chinese Pharmacopoeia (CHP). It has a wide range of pharmacological activities, including anti-tumor, anti-inflammatory, anti-osteoporotic, organ-protective, anti-viral, anti-microbial, anti-parasitic, and laxative potentials. Moreover, it regulates blood lipids and glucose and improves neuropathic pain effects, depicting potential to be transformed into promising medicines and healthcare products. In addition to the functional cosmetics and health products of Aloe, the availability, pharmacological activities, pharmacokinetics, formulation studies, and toxicity of aloin were summarized after investigating the literature from PubMed, Google, and other databases. Moreover, significant attention had been paid to the development of aloin-derived medicines and healthcare products. Thus, the present review clarified the possibility of aloin as medicines and healthcare products to develop and utilize Aloe resources.

Therapeutic potential of dietary flavonoid hyperoside against non-communicable diseases: targeting underlying properties of diseases.

Non-communicable diseases (NCDs) are a global epidemic with diverse pathogenesis. Among them, oxidative stress and inflammation are the most fundamental co-morbid features. Therefore, multi-targets and multi-pathways therapies with significant anti-oxidant and anti-inflammatory activities are potential effective measures for preventing and treating NCDs. The flavonol glycoside compound hyperoside (Hyp) is widely found in a variety of fruits, vegetables, beverages, and medicinal plants and has various health benefits, especially excellent anti-oxidant and anti-inflammatory properties targeting nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling pathways. In this review, we summarize the pathogenesis associated with oxidative stress and inflammation in NCDs and the biological activity and therapeutic potential of Hyp. Our findings reveal that the anti-oxidant and anti-inflammatory activities regulated by Hyp are associated with numerous biological mechanisms, including positive regulation of mitochondrial function, apoptosis, autophagy, and higher-level biological damage activities. Hyp is thought to be beneficial against organ injuries, cancer, depression, diabetes, and osteoporosis, and is a potent anti-NCDs agent. Additionally, the sources, bioavailability, pharmacy, and safety of Hyp have been established, highlighting the potential to develop Hyp into dietary supplements and nutraceuticals.

New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disorder in the elderly characterized by memory loss and cognitive dysfunction. The pathogenesis of AD is complex. One-targeted anti-AD drugs usually fail to delay AD progression. Traditional Chinese medicine records have documented the use of the roots of Panax ginseng (ginseng roots) and its prescriptions to treat dementia. Ginsenoside Rg1, the main ginsenoside component of ginseng roots, exhibits a certain therapeutic effect in the abovementioned diseases, suggesting its potential in the management of AD. Therefore, we combed the pathogenesis of AD and currently used anti-AD drugs, and reviewed the availability, pharmacokinetics, and pharmaceutic studies of ginsenoside Rg1. This review summarizes the therapeutic effects and mechanisms of ginsenoside Rg1 and its deglycosylated derivatives in AD in vivo and in vitro. The main mechanisms include improvement in Aß and Tau pathologies, regulation of synaptic function and intestinal microflora, and reduction of inflammation, oxidative stress, and apoptosis. The underlying mechanisms mainly involve the regulation of PKC, MAPK, PI3K/Akt, CDK5, GSK-3ß, BDNF/TrkB, PKA/CREB, FGF2/Akt, p21WAF1/CIP1, NF-κB, NLRP1, TLR3, and TLR4 signaling pathways. As the effects and underlying mechanisms of ginsenoside Rg1 on AD have not been systematically reviewed, we have provided a comprehensive review and shed light on the future directions in the utilization of ginsenoside Rg1 and ginseng roots as well as the development of anti-AD drugs.

Early detect left ventricular subclinical myocardial dysfunction in patients with systemic lupus erythematosus by a left ventricular pressure-strain loop.

OBJECTIVE: Noninvasive myocardial work (MW) is a new technology which is based on strain after considering the load influence on myocardial deformation. We aimed to investigate the feasibility of quantitatively assessing left ventricular myocardial work (LVMW) in patients with systemic lupus erythematosus (SLE) using a left ventricular pressure-strain loop (LVPSL). METHODS: 76 patients with SLE were included in the study (A), further divided into two subgroups according to the presence of lupus nephritis (LN). Global longitudinal strain (GLS), peak strain dispersion (PSD), global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained. RESULTS: 1: Patients with SLE demonstrated a significantly reduced GWE and GLS compared with control group, GWW and PSD were increased, above changes were more pronounced in patients with LN. There was no significant difference in GWI and GCW. 2: Receiver operating characteristic (ROC) analysis demonstrated that GWE was the most powerful tool for detecting myocardial insufficiency early in SLE patients, and the area under the curve (AUC) was 0.804, and was superior to GLS (AUC = 0.707). GWE remains the best indicator of subclinical myocardial injury in patients with LN. The AUC was 0.910, and the best cutoff point was 96.5% (sensitivity 83.3%, specificity 73.3%). CONCLUSIONS: LVPSL can be used to noninvasively assess changes in MW in patients with SLE. Noninvasive GWE is a more sensitive index than GLS to detect subclinical myocardial injury early in SLE patients. This is a potential valuable clinical tool to assist in the early-find myocardial damage.

Value of UGT2B7-161 Single Nucleotide Polymorphism in Predicting the Risk of Cardiotoxicity in HER-2 Positive Breast Cancer Patients Who Underwent Pertuzumab Combined with Trastuzumab Therapy by PSL.

Objective: To explore the value of uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7)-161 single nucleotide polymorphism in predicting the occurrence of cardiotoxicity in Chinese human epidermal growth factor 2 (HER-2) positive breast cancer patients who underwent pertuzumab combined with trastuzumab Therapy. Methods: Fifty patients with HER-2 positive breast cancer who planned to receive trastuzumab and pertuzumab therapy for more than four cycles were enrolled in this study, and blood samples were collected. Thirty healthy volunteers of matching ages were selected as the control group. Myocardial parameters such as global work index, global effective work, and global wasted work were measured before treatment (M0) and at the end of four cycles of treatment month three (M3). Blood samples were collected from patients at the M0 stage, and polymorphisms of the UGT2B7-161 gene were detected to evaluate the predictive ability of different gene phenotypes on the myocardial drug toxicity injury. Results: There were 35 myocardial work decreased events among 50 patients. There were 24 (47.3%), 15 (40.8%), and 11 (11.8%) patients carrying UGT2B7-161 CC, CT, and TT genotypes, respectively. The occurrence of myocardial work decreased was decreased in UGT2B7-161 TT and CT genotypes (12.5%) compared with CC genotype (41.7%) with statistical significance (P < 0.001). Multivariate logistic regression model analysis exhibited that UGT2B7-161 genotypes, body mass index, and cardiac troponin I were independent factors influencing the risk of cardiotoxicity. Conclusion: UGT2B7-161 single nucleotide polymorphism is a potential predictive factor for cardiotoxicity in HER-2 positive breast cancer patients receiving trastuzumab and pertuzumab dual-targeted drug therapy.

Vasorelaxant Activities and its Underlying Mechanisms of Magnolia Volatile Oil on Rat Thoracic Aorta Based on Network Pharmacology.

Objective: Magnolia volatile oil (MVO) is a mixture mainly containing eudesmol and its isomers. This study was to investigate the vasorelaxant effects and the underlying mechanism of MVO in rat thoracic aortas. Method: The present study combined gas chromatography-mass spectrometry (GC-MS) and network pharmacology analysis with in vitro experiments to clarify the mechanisms of MVO against vessel contraction. A compound-target network, compound-target-disease network, protein-protein interaction network, compound-target-pathway network, gene ontology, and pathway enrichment for hypertension were applied to identify the potential active compounds, drug targets, and pathways. Additionally, the thoracic aortic rings with or without endothelium were prepared to explore the underlying mechanisms. The roles of the PI3K-Akt-NO pathways, neuroreceptors, K+ channels, and Ca2+ channels on the vasorelaxant effects of MVO were evaluated through the rat thoracic aortic rings. Results: A total of 29 compounds were found in MVO, which were identified by GC-MS, of which 21 compounds with a content of more than 0.1% were selected for further analysis. The network pharmacology research predicted that beta-caryophyllene, palmitic acid, and (+)-ß-selinene might act as the effective ingredients of MVO for the treatment of hypertension. Several hot targets, mainly involving TNF, CHRM1, ACE, IL10, PTGS2, REN, and F2, and pivotal pathways, such as the neuroactive ligand-receptor interaction, the calcium signaling pathway, and the PI3K-Akt signaling, were responsible for the vasorelaxant effect of MVO. As expected, MVO exerted a vasorelaxant effect on the aortic rings pre-contracted by KCl and phenylephrine in an endothelium-dependent and non-endothelium-dependent manner. Importantly, a pre-incubation with indomethacin (Indo), N-nitro-L-arginine methyl ester, methylene blue, wortmannin, and atropine sulfate as well as 4-aminopyridione diminished MVO-induced vasorelaxation, suggesting that the activation of the PI3K-Akt-NO pathway and KV channel were involved in the vasorelaxant effect of MVO, which was consistent with the results of the Kyoto Encyclopedia of Genes and the Genomes. Additionally, MVO could significantly inhibit Ca2+ influx resulting in the contraction of aortic rings, revealing that the inhibition of the calcium signaling pathway exactly participated in the vasorelaxant activity of MVO as predicted by network pharmacology. Conclusion: MVO might be a potent treatment of diseases with vascular dysfunction like hypertension. The underlying mechanisms were related to the PI3K-Akt-NO pathway, KV pathway, as well as Ca2+ channel, which were predicted by the network pharmacology and verified by the experiments in vitro. This study based on network pharmacology provided experimental support for the clinical application of MVO in the treatment of hypertension and afforded a novel research method to explore the activity and mechanism of traditional Chinese medicine.

The Utility of the Fifth Edition of the BI-RADS Ultrasound Lexicon in Category 4 Breast Lesions: A Prospective Multicenter Study in China.

RATIONALE AND OBJECTIVES: The objective of this study was to evaluate the utility of the fifth edition of the Breast Imaging-Reporting and Data System (BI-RADS) in clinical breast radiology by using prospective multicenter real-time analyses of ultrasound (US) images. MATERIALS AND METHODS: We prospectively studied 2049 female patients (age range, 19-86 years; mean age 46.88 years) with BI-RADS category 4 breast masses in 32 tertiary hospitals. All the patients underwent B-mode, color Doppler US, and US elastography examination. US features of the mass and associated features were described and categorized according to the fifth edition of the BI-RADS US lexicon. The pathological results were used as the reference standard. The positive predictive values (PPVs) of subcategories 4a-4c were calculated. RESULTS: A total of 2094 masses were obtained, including 1124 benign masses (54.9%) and 925 malignant masses (45.1%). For BI-RADS US features of mass shape, orientation, margin, posterior features, calcifications, architectural distortion, edema, skin changes, vascularity, and elasticity assessment were significantly different for benign and malignant masses (p< 0.05). Typical signs of malignancy were irregular shape (PPV, 57.2%), spiculated margin (PPV, 83.7%), nonparallel orientation (PPV, 63.9%), and combined pattern of posterior features (PPV, 60.6%). For the changed or newly added US features, the PPVs for intraductal calcifications were 80%, 56.4% for internal vascularity, and 80% for a hard pattern on elastography. The associated features such as architectural distortion (PPV, 89.3%), edema (PPV, 69.2%), and skin changes (PPV, 76.2%) displayed high predictive value for malignancy. The rate of malignant was 7.4% (72/975) in category 4a, 61.4% (283/461) in category 4b, and 93.0% (570/613) in category 4c. The PPV for category 4b was higher than the likelihood ranges specified in BI-RADS and the PPVs for categories 4a and 4c were within the acceptable performance ranges specified in the fifth edition of BI-RADS in our study. CONCLUSION: Not only the US features of the breast mass, but also associated features, including vascularity and elasticity assessment, have become an indispensable part of the fifth edition of BI-RADS US lexicon to distinguish benign and malignant breast lesions. The subdivision of category 4 lesions into categories 4a, 4b, and 4c for US findings is helpful for further assessment of the likelihood of malignancy of breast lesions.

Nuciferine, an active ingredient derived from lotus leaf, lights up the way for the potential treatment of obesity and obesity-related diseases.

Obesity, is an increasingly global public health problem associated complications. However, the proven anti-obesity agents are inefficient with adverse side effects; hence attention is being paid to novel drugs from natural resources to manage obesity and obesity-related diseases. Nuciferine (NF) is a high-quality aporphine alkaloid present in lotus leaf. Unlike the chemical drugs, NF elicits anti-obesity, anti-dyslipidemia, anti-hyperglycemic, anti-hypouricemic, anti-inflammatory, and anti-tumor effects, and affinity to neural receptors, and protection against obesity-related diseases. The underlying mechanism of NF includes the regulation of targeted molecules and pathways related to metabolism, inflammation, and cancer and modulation of Ca2+ flux, gut microbiota, and ferroptosis. Besides, the clinical application, availability, pharmacokinetics, pharmaceutics, and security of NF have been established, highlighting the potential of developing NF as an anti-obesity agent. Therefore, this review provides a comprehensive summarization, which sheds light on future research in NF.

Panax ginseng and its ginsenosides: potential candidates for the prevention and treatment of chemotherapy-induced side effects.

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural non-toxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun N-terminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

Review of Natural Resources With Vasodilation: Traditional Medicinal Plants, Natural Products, and Their Mechanism and Clinical Efficacy.

For decades, chronic diseases including cardiovascular and cerebrovascular diseases (CCVDs) have plagued the world. Meanwhile, we have noticed a close association between CCVDs and vascular lesions, such as hypertension. More focus has been placed on TMPs and natural products with vasodilation and hypotension. TMPs with vasodilatory and hypotensive activities are mainly from Compositae, Lamiaceae, and Orchidaceae (such as V. amygdalina Del., T. procuinbens L., M. glomerata Spreng., K. galanga L., etc.) whereas natural products eliciting vasorelaxant potentials were primarily from flavonoids, phenolic acids and alkaloids (such as apigenin, puerarin, curcumin, sinomenine, etc.). Furthermore, the data analysis showed that the vasodilatory function of TMPs was mainly concerned with the activation of eNOS, while the natural products were primarily correlated with the blockage of calcium channel. Thus, TMPs will be used as alternative drugs and nutritional supplements, while natural products will be considered as potential therapies for CCVDs in the future. This study provides comprehensive and valuable references for the prevention and treatment of hypertension and CCVDs and sheds light on the further studies in this regard. However, since most studies are in vitro and preclinical, there is a need for more in-depth researches and clinical trials to understand the potential of these substances.

Risk-predicted dual nomograms consisting of clinical and ultrasound factors for downgrading BI-RADS category 4a breast lesions - A multiple centre study.

Purpose: To develop and to validate a risk-predicted nomogram for downgrading Breast Imaging Reporting and Data System (BI-RADS) category 4a breast lesions. Patients and Methods: We enrolled 680 patients with breast lesions that were diagnosed as BI-RADS category 4a by conventional ultrasound from December 2018 to June 2019. All 4a lesions were randomly divided into development and validation groups at the ratio of 3:1. In the development group consisting of 499 cases, the multiple clinical and ultrasound predicted factors were extracted, and dual-predicted nomograms were constructed by multivariable logistic regression analysis, named clinical nomogram and ultrasound nomogram, respectively. Patients were twice classified as either "high risk" or "low risk" in the two nomograms. The performance of these dual nomograms was assessed by an independent validation group of 181 cases. Receiver Operating Characteristic (ROC) curve and diagnostic value were calculated to evaluate the applicability of the new model. Results: After multiple logistic regression analysis, the clinical nomogram included 2 predictors: age and the first-degree family members with breast cancer. The area under the curve (AUC) value for the clinical nomogram was 0.661 and 0.712 for the development and validation groups, respectively. The ultrasound nomogram included 3 independent predictors (margins, calcification and strain ratio), and the AUC value in this nomogram was 0.782 and 0.747 in the development and validation groups, respectively. In the development group of 499 patients, approximately 50.90% (254/499) of patients were twice classified "low risk", with a malignancy rate of 1.18%. In the validation group of 181 patients, approximately 47.51% (86/181) of patients had been twice classified as "low risk", with a malignancy rate of 1.16%. Conclusions: A dual-predicted nomogram incorporating clinical factors and imaging characteristics is an applicable model for downgrading the low-risk lesions in BI-RADS category 4a and shows good stability and accuracy, which is useful for decreasing the rate of invasive examinations and surgery.

Emerging Significance of Ginsenosides as Potentially Reversal Agents of Chemoresistance in Cancer Therapy.

Chemoresistance has become a prevalent phenomenon in cancer therapy, which alleviates the effect of chemotherapy and makes it difficult to break the bottleneck of the survival rate of tumor patients. Current approaches for reversing chemoresistance are poorly effective and may cause numerous new problems. Therefore, it is urgent to develop novel and efficient drugs derived from natural non-toxic compounds for the reversal of chemoresistance. Researches in vivo and in vitro suggest that ginsenosides are undoubtedly low-toxic and effective options for the reversal of chemoresistance. The underlying mechanism of reversal of chemoresistance is correlated with inhibition of drug transporters, induction of apoptosis, and modulation of the tumor microenvironment(TME), as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (NRF2)/AKT, lncRNA cancer susceptibility candidate 2(CASC2)/ protein tyrosine phosphatase gene (PTEN), AKT/ sirtuin1(SIRT1), epidermal growth factor receptor (EGFR)/ phosphatidylinositol 3-kinase (PI3K)/AKT, PI3K/AKT/ mammalian target of rapamycin(mTOR) and nuclear factor-κB (NF-κB). Since the effects and the mechanisms of ginsenosides on chemoresistance reversal have not yet been reviewed, this review summarized comprehensively experimental data in vivo and in vitro to elucidate the functional roles of ginsenosides in chemoresistance reversal and shed light on the future research of ginsenosides.

Can Combined Screening of Ultrasound and Elastography Improve Breast Cancer Identification Compared with MRI in Women with Dense Breasts-a Multicenter Prospective Study.

Objectives: To assess the performance of elastography (ES) and ultrasound (US) in predicting the malignancy of breast lesions and to compare their combined diagnostic value with that of magnetic resonance imaging (MRI). Materials and Methods: The study prospectively enrolled 242 female patients with dense breasts treated in 35 heath care facilities in China between November 2018 and October 2019. Based on conventional US and elastography, radiologists classified the degree of suspicion of breast lesions according to the US Breast Imaging Reporting and Data System (BI-RADS) criteria. The diagnostic value was compared between US BI-RADS and MRI BI-RADS, with pathological results used as the reference standard. Results: The results demonstrated that irregular tumor shape, a nonparallel growth orientation, indistinct margins, angular contours, microcalcifications, color Doppler flow and ES score on US imaging were significantly related to breast cancer in dense breasts (P=0.001; P=0.001; P=0.008; P<0.001; P=0.019; P=0.008; P=0.002, respectively). The sensitivity, specificity, PPV, NPV, accuracy and AUC of US BI-RADS category were 94.7%, 90.7%, 95.8%, 88.0%, 93.4% and 0.93 (95%CI, 0.88-0.97), respectively, while those of MRI BI-RADS category were 98.2%, 57.5%, 84.3%, 83.3%, 86.0% and 0.78 (95%CI, 0.71-0.85), respectively. MRI BI-RADS showed a significantly higher sensitivity than US BI-RADS (98.2% vs 94.7%, P=0.043), whereas US BI-RADS showed significantly higher specificity (90.7% vs 57.5%, P<0.001). US BI-RADS showed better diagnostic efficiency in differentiating nodules in dense breasts than MRI BI-RADS (AUC 0.93 vs 0.78, P<0.001). Conclusion: By combining the use of ES and conventional US, US BI-RADS had better diagnostic efficiency in differentiating nodules in dense breasts than MRI. For the diagnosis of malignant tumors in patients with dense breasts, MRI and US BI-RADS can be used as supplemental diagnostic tools to detect lesions, with US BI-RADS considered the preferred adjunctive resource.

Rapid and Sensitive Detection of Salmonella in Chickens Using Loop-Mediated Isothermal Amplification Combined with a Lateral Flow Dipstick.

Salmonellosis is a highly contagious bacterial disease that threatens both human and poultry health. Tests that can detect Salmonella in the field are urgently required to facilitate disease control and for epidemiological investigations. Here, we combined loop-mediated isothermal amplification (LAMP) with a chromatographic lateral flow dipstick (LFD) to rapidly and accurately detect Salmonella. LAMP primers were designed to target the Salmonella invA gene. LAMP conditions were optimized by adjusting the ratio of inner to outer primers, MgSO4 concentration, dNTP mix concentration, amplification temperature, and amplification time. We evaluated the specificity of our novel LAMP-LFD method using six Salmonella species and six related non-Salmonella strains. All six of the Salmonella strains, but none of the non-Salmonella strains, were amplified. LAMP-LFD was sensitive enough to detect concentrations of Salmonella enterica subsp. enterica serovar Pullorum genomic DNA as low as 89 fg/µl, which is 1,000 times more sensitive than conventional PCR. When artificially contaminated feed samples were analyzed, LAMP-LFD was also more sensitive than PCR. Finally, LAMP-LFD gave no false positives across 350 chicken anal swabs. Therefore, our novel LAMP-LFD assay was highly sensitive, specific, convenient, and fast, making it a valuable tool for the early diagnosis and monitoring of Salmonella infection in chickens.