Uncertainty analysis and optimization for mild moxibustion.

During mild moxibustion treatment, uncertainties are involved in the operating parameters, such as the moxa-burning temperature, the moxa stick sizes, the stick-to-skin distance, and the skin moisture content. It results in fluctuations in skin surface temperature during mild moxibustion. Existing mild moxibustion treatments almost ignore the uncertainty of operating parameters. The uncertainties lead to excessive skin surface temperature causing intense pain, or over-low temperature reducing efficacy. Therefore, the interval model was employed to measure the uncertainty of the operation parameters in mild moxibustion, and the uncertainty optimization design was performed for the operation parameters. It aimed to provide the maximum thermal penetration of mild moxibustion to enhance efficacy while meeting the surface temperature requirements. The interval uncertainty optimization can fully consider the operating parameter uncertainties to ensure optimal thermal penetration and avoid patient discomfort caused by excessive skin surface temperature. To reduce the computational burden of the optimization solution, a high-precision surrogate model was established through a radial basis neural network (RBNN), and a nonlinear interval model for mild moxibustion treatment was formulated. By introducing the reliability-based possibility degree of interval (RPDI), the interval uncertainty optimization was transformed into a deterministic optimization problem, solved by the genetic algorithm. The results showed that this method could significantly improve the thermal penetration of mild moxibustion while meeting the skin surface temperature requirements, thereby enhancing efficacy.

Convenient tumor 3D spheroid arrays manufacturing via acoustic excited bubbles for in situ drug screening.

The quick and convenient fabrication of in vitro tumor spheroids models has been pursued for clinical drug discovery and personalized therapy. Here, uniform three-dimensional (3D) tumor spheroids are quickly constructed by acoustically excited bubble arrays in a microfluidic chip and performed drug response testing in situ. In detail, bubble oscillation excited by acoustic waves induces second radiation force, resulting in the cells rotating and aggregating into tumor spheroids, which obtain controllable sizes ranging from 30 to 300 µm. These spherical tumor models are located in microfluidic networks, where drug solutions with gradient concentrations are generated from 0 to 18 mg mL-1, so that the cell spheroids response to drugs can be monitored conveniently and efficiently. This one-step tumor spheroids manufacturing method significantly reduces the model construction time to less than 15 s and increases efficiency by eliminating additional transfer processes. These significant advantages of convenience and high-throughput manufacturing make the tumor models promising for use in tumor treatment and point-of-care diagnosis.

Calcium Determines Lactiplantibacillus plantarum Intraspecies Competitive Fitness.

The importance of individual nutrients for microbial strain robustness and coexistence in habitats containing different members of the same species is not well understood. To address this for Lactiplantibacillus plantarum in food fermentations, we performed comparative genomics and examined the nutritive requirements and competitive fitness for L. plantarum strains B1.1 and B1.3 isolated from a single sample of teff injera fermentation batter. Compared to B1.1 and other L. plantarum strains, B1.3 has a smaller genome, limited biosynthetic capacities, and large mobilome. Despite these differences, B1.3 was equally competitive with B1.1 in a suspension of teff flour. In commercially sourced, nutrient-replete MRS (cMRS) medium, strain B1.3 reached 3-fold-higher numbers than B1.1 within 2 days of passage. Because B1.3 growth and competitive fitness were poor in mMRS medium (here called mMRS), a modified MRS medium lacking beef extract, we used mMRS to identify nutrients needed for robust B1.3 growth. No improvement was observed when mMRS was supplemented with nucleotides, amino acids, vitamins, or monovalent metals. Remarkably, the addition of divalent metal salts increased the growth rate and cell yields of B1.3 in mMRS. Metal requirements were confirmed by inductively coupled plasma mass spectrometry, showing that total B1.3 intracellular metal concentrations were significantly (up to 2.7-fold) reduced compared to B1.1. Supplemental CaCl2 conferred the greatest effect, resulting in equal growth between B1.1 and B1.3 over five successive passages in mMRS. Moreover, calcium supplementation reversed a B1.3 strain-specific, stationary-phase, flocculation phenotype. These findings show how L. plantarum calcium requirements affect competitive fitness at the strain level. IMPORTANCE Ecological theory states that the struggle for existence is stronger between closely related species. Contrary to this assertion, fermented foods frequently sustain conspecific individuals, in spite of their high levels of phylogenetic relatedness. Therefore, we investigated two isolates of Lactiplantibacillus plantarum, B1.1 and B1.3, randomly selected from a single batch of teff injera batter. These strains spanned the known genomic and phenotypic range of the L. plantarum species, and in laboratory culture medium used for strain screening, B1.3 exhibited poor growth and was outcompeted by the more robust strain B1.1. Nonetheless, B1.1 and B1.3 were equally competitive in teff flour. This result shows how L. plantarum has adapted for coexistence in that environment. The capacity for the single macronutrient calcium to restore B1.3 competitive fitness in laboratory culture medium suggests that L. plantarum intraspecies diversity found in food systems is fine-tuned to nutrient requirements at the strain level.

Numerical Simulation of Temperature Distribution during Mild Moxibustion.

Mild moxibustion is a treatment approach belonging to moxa-hanging moxibustion. The burning end of the moxa stick is kept at a fixed distance from the moxibustion skin, aiming to make the patient feel warm without burning pain. The appropriate temperature distribution is critical for the mild moxibustion treatment. The purpose of this paper is to improve the efficacy of mild moxibustion on human tissues. By combining the radiative and conductive models with surface-to-surface heat transfer, biological heat transfer simulations are realized based on biological tissues in particular media. A finite element model of mild moxibustion was established to obtain the characteristics of skin tissue temperature distribution under various conditions. The model considers multiple factors, such as the moxa-burning temperature, the stick-to-skin distance, the moxa stick sizes, and the ambient temperature. The results show that the temperature distribution under various conditions is centered at the moxibustion point and the temperature decreases in the surrounding direction. The higher the moxa-burning temperature, the higher the skin surface temperature and the worse the stability in heating. The stick-to-skin distance is inversely proportional to the skin surface temperature. The moxa stick diameter is proportional to the skin surface temperature. The longer the moxibustion time, the higher the skin surface temperature. And the temperature change gradually flattened in the late stage of mild moxibustion. Finally, a set of moxibustion conditions with optimal temperature distribution was obtained by comparing the data of all groups.

Tobacco smoking was positively associated with metabolic syndrome among patients with psoriasis in Shanghai: A cross-sectional study.

INTRODUCTION: A number of studies have reported a high correlation between psoriasis and metabolic syndrome (MetS), and tobacco smoking is one independent risk factor accounting for the increased prevalence both for psoriasis and MetS. However, few studies have been conducted to assess the effects of tobacco smoking on co-morbidities of psoriasis and MetS. METHODS: We conducted a cross-sectional study with 1014 psoriasis patients recruited from January to May 2021. Patients were recruited with a cluster survey method in Yueyang Hospital (affiliated with Shanghai University of Traditional Chinese Medicine) and Shanghai Skin Diseases Hospital (affiliated with Tongji University). Data were collected by face-to-face questionnaire interviews which included basic information, personal life habits, medical history, and clinical examinations. SPSS 24.0 was used for data analysis and a p<0.05 was considered statistically significant. RESULTS: The 1014 psoriasis patients were predominantly males (65.58%), with an average age of 45.98 years (IQR: 34.00-57.00). Of these, 25.74% (261) of psoriasis had MetS and 31.85% (323) were tobacco smokers. Male psoriasis patients had higher tobacco smoking prevalence than female patients. With increasing age and BMI, the prevalence of tobacco smoking among psoriasis patients increased dramatically (p<0.01). Logistic regression indicated that psoriasis patients with tobacco smoking had 1.78 times (95% CI: 1.21-2.60) the probability to have MetS than those without tobacco smoking, even adjusting for potential confounding factors. Moreover, smoking psoriasis patients with MetS consumed more cigarettes per day, with longer smoking duration, but with an older age of smoking initiation. CONCLUSIONS: The prevalence of tobacco smoking and MetS among psoriasis patients was high in Shanghai, and tobacco smoking was positively associated with the MetS among psoriasis patients. Clinicians should recommend psoriasis patients to abstain from tobacco smoking and provide tobacco cessation assistance regularly.

Selenium Vacancies and Synergistic Effect of Near- and Far-Field-Enabled Ultrasensitive Surface-Enhanced Raman-Scattering-Active Substrates for Malaria Detection.

Defect engineering with the active control of defect states brings remarkable enhancement on surface-enhanced Raman scattering (SERS) by magnifying semiconductor-molecule interaction. Such light-trapping architectures can increase the light path length, which promotes photon-analytes interactions and further improves the SERS sensitivity. However, by far the reported semiconductor SERS-active substrates based on these strategies are often nonuniform and commonly in the form of isolated laminates or random clusters, which limit their reliability and stability for practical applications. Herein, we develop self-grown single-crystalline "V-shape" SnSe2-x (SnSe1.5, SnSe1.75, SnSe2) nanoflake arrays (SnSe2-x NFAs) with controlled selenium vacancies over large-area (10 cm × 10 cm) for ultrahigh-sensitivity SERS. First-principles density functional theory (DFT) is used to calculate the band gap and the electronic density of states (DOS). Based on the Herzberg-Teller theory regarding the vibronic coupling, the results of theoretical calculation reveal that the downshift of band edge and high DOS of SnSe1.75 can effectively enhance the vibronic coupling within the SnSe1.75-R6G system, which in turn enhances the photoinduced charge transfer resonance and contributes to the SERS activity with a remarkable enhancement factor of 1.68 × 107. Furthermore, we propose and demonstrate ultrasensitive (10-15 M for R6G), uniform, and reliable SERS substrates by forming SnSe1.75 NFAs/Au heterostructures via a facile Au evaporation process. We attribute the superior performance of our SnSe1.75 NFAs/Au heterostructures to the following reasons: (1) selenium vacancies and (2) synergistic effect of the near and far fields. In addition, we successfully build a detection platform to achieve rapid (∼15 min for the whole process), antibody-free, in situ, and reliable early malaria detection (100% detection rate for 10 samples with 160 points) in whole blood, and molecular hemozoin (<100/mL) can be detected. Our approach not only provides an efficient technique to obtain large-area, uniform, and reliable SERS-active substrates but also offers a substantial impact on addressing practical issues in many application scenarios such as the detection of insect-borne infectious diseases.

Mechanism of Hepatitis B Virus cccDNA Formation.

Hepatitis B virus (HBV) remains a major medical problem affecting at least 257 million chronically infected patients who are at risk of developing serious, frequently fatal liver diseases. HBV is a small, partially double-stranded DNA virus that goes through an intricate replication cycle in its native cellular environment: human hepatocytes. A critical step in the viral life-cycle is the conversion of relaxed circular DNA (rcDNA) into covalently closed circular DNA (cccDNA), the latter being the major template for HBV gene transcription. For this conversion, HBV relies on multiple host factors, as enzymes capable of catalyzing the relevant reactions are not encoded in the viral genome. Combinations of genetic and biochemical approaches have produced findings that provide a more holistic picture of the complex mechanism of HBV cccDNA formation. Here, we review some of these studies that have helped to provide a comprehensive picture of rcDNA to cccDNA conversion. Mechanistic insights into this critical step for HBV persistence hold the key for devising new therapies that will lead not only to viral suppression but to a cure.

Molten salt synthesis and luminescence of Dy3+ -doped Y3 Al5 O12 phosphors.

Dy3+ -doped Y3 Al5 O12 phosphors were prepared at a relatively low temperature using molten salt synthesis. The phase of the prepared Dy3+ -doped Y3 Al5 O12 phosphors was confirmed using X-ray powder diffraction. Results indicated that Dy3+ doping did not change the Y3 Al5 O12 phase. Following excitation at 352 nm, emission spectra of the Dy3+ -doped Y3 Al5 O12 phosphors consisted of blue, yellow, and red emission bands. The influence of Dy3+ concentration and excitation wavelength on emission was investigated. The ratio of yellow light to blue light varied with change in Dy3+ doping concentration, due to changes in the structure around Dy3+ . Emission intensities also changed when the excitation wavelength was changed. This variation is luminescence generated a system for tunable white light for Dy3+ -doped Y3 Al5 O12 phosphors.

Projection from the Anterior Cingulate Cortex to the Lateral Part of Mediodorsal Thalamus Modulates Vicarious Freezing Behavior.

Emotional contagion, a primary form of empathy, is present in rodents. Among emotional contagion behaviors, social transmission of fear is the most studied. Here, we modified a paradigm used in previous studies to more robustly assess the social transmission of fear in rats that experienced foot-shock. We used resting-state functional magnetic resonance imaging to show that foot-shock experience enhances the regional connectivity of the anterior cingulate cortex (ACC). We found that lesioning the ACC specifically attenuated the vicarious freezing behavior of foot-shock-experienced observer rats. Furthermore, ablation of projections from the ACC to the mediodorsal thalamus (MDL) bilaterally delayed the vicarious freezing responses, and activation of these projections decreased the vicarious freezing responses. Overall, our results demonstrate that, in rats, the ACC modulates vicarious freezing behavior via a projection to the MDL and provide clues to understanding the mechanisms underlying empathic behavior in humans.

Dexamethasone combined with berberine is an effective therapy for bleomycin-induced pulmonary fibrosis in rats.

Pulmonary fibrosis (PF) is a heterogeneous pathological process in lung tissues with a considerable mortality rate. Currently, combination therapy represents an effective approach to treat PF. Dexamethasone (Dxs) and berberine (BBR) are widely applied to inhibit the progression of PF. Dxs plus penehyclidine hydrochloride or alfacalcidol have been reported more effective in therapy compared with any single drug treatment. However, whether Dxs plus BBR induces an increased antifibrotic effect remains unknown. The current study aimed to evaluate the therapeutic effect of BBR plus Dxs in bleomycin (BLM)-induced PF. A PF model in rats was established and rats were divided into control, BLM, BBR, Dxs and BBR plus Dxs groups (n=9/group). On days 3, 7 and 14, blood samples were collected from the eyes of the rats (n=6/group). CXC chemokine ligand 14 (CXCL14), collagen I, collagen III, matrix metalloproteinase (MMP)2 and MMP9 serum levels were measured by ELISA. On day 14, all rats were sacrificed. Hematoxylin and eosin analysis, Masson staining and hydroxyproline (Hyp) assessment were performed to observe histopathological changes and collagen deposition. mRNA and protein levels of CXCL14, CXC chemokine receptor 4 (CXCR4), collagen I/III, α-smooth muscle actin (α-SMA), MMP2/9 and phosphorylated-Smad 2/3 in lung tissue were further evaluated. Similar effects in preventing lung damage were observed histopathologically for Dxs and BBR compared with the BLM group. These treatments further reduced levels of Hyp, CXCL14, CXCR4, collagen I/III, MMP2/9, α-SMA and p-Smad 2/3. The combination of Dxs and BBR exhibited increased effectiveness compared with the single treatments. Results further suggested that antifibrotic mechanisms were involved in inhibiting CXCL14 and MMP2/MMP9 expression, and preventing the activation of Smad2/3 and hedgehog signaling pathways. The combined use of Dxs and BBR may represent a potential therapeutic approach for PF.

The Evolution and Biocatalysis of FAD2 Indicate Its Correlation to the Content of Seed Oil in Plants.

Unsaturated fatty acids are the main components of vegetable oils. Fatty acid desaturase 2 (FAD2) catalyzes oleic acid (OA) into linoleic acid (LA) transformations, which are essential to the profile of FAs in seeds. To further understand the roles of FAD2s in the synthesis of oil, the evolution and biocatalysis of FAD2s were comprehensively analyzed. The evolution history of the FAD2 gene family showed that most of the FAD2 genes formed monophyletic clades except in eudicots. The FAD2 genes in some eudicots diverged into constitutive and seed-specific expression clades. Notably, the biocatalysis of seed-specific or -abundant expression FAD2s in soybean, perilla, rice, and spruce revealed that their catalytic activity was strongly correlated with the total oil content of their seeds in nature. Additionally, it was found that I and Y in site 143 of GmaFAD2-1 were strictly conserved in the seed-specific and constitutive expression clades of Fabaceae, respectively. Furthermore, the site-directed mutation demonstrated that I and Y are vital to improving and reducing the activity of GmaFAD2s. Therefore, the results indicate that the activity of FAD2s in seeds might be a reference to the total oil content of seeds, and site 143 might have been specifically evolved to be required for the activity of FAD2s in some expression-diverged eudicots, especially in legumes.

Convergent estimates of marine nitrogen fixation.

Uncertainty in the global patterns of marine nitrogen fixation limits our understanding of the response of the ocean's nitrogen and carbon cycles to environmental change. The geographical distribution of and ecological controls on nitrogen fixation are difficult to constrain with limited in situ measurements. Here we present convergent estimates of nitrogen fixation from an inverse biogeochemical and a prognostic ocean model. Our results demonstrate strong spatial variability in the nitrogen-to-phosphorus ratio of exported organic matter that greatly increases the global nitrogen-fixation rate (because phytoplankton manage with less phosphorus when it is in short supply). We find that the input of newly fixed nitrogen from microbial fixation and external inputs (atmospheric deposition and river fluxes) accounts for up to 50 per cent of carbon export in subtropical gyres. We also find that nitrogen fixation and denitrification are spatially decoupled but that nevertheless nitrogen sources and sinks appear to be balanced over the past few decades. Moreover, we propose a role for top-down zooplankton grazing control in shaping the global patterns of nitrogen fixation. Our findings suggest that biological carbon export in the ocean is higher than expected and that stabilizing nitrogen-cycle feedbacks are weaker than previously thought.

CSCD: a database for cancer-specific circular RNAs.

Circular RNA (circRNA) is a large group of RNA family extensively existed in cells and tissues. High-throughput sequencing provides a way to view circRNAs across different samples, especially in various diseases. However, there is still no comprehensive database for exploring the cancer-specific circRNAs. We collected 228 total RNA or polyA(-) RNA-seq samples from both cancer and normal cell lines, and identified 272 152 cancer-specific circRNAs. A total of 950 962 circRNAs were identified in normal samples only, and 170 909 circRNAs were identified in both tumor and normal samples, which could be further used as non-tumor background. We constructed a cancer-specific circRNA database (CSCD, http://gb.whu.edu.cn/CSCD). To understand the functional effects of circRNAs, we predicted the microRNA response element sites and RNA binding protein sites for each circRNA. We further predicted potential open reading frames to highlight translatable circRNAs. To understand the association between the linear splicing and the back-splicing, we also predicted the splicing events in linear transcripts of each circRNA. As the first comprehensive cancer-specific circRNA database, we believe CSCD could significantly contribute to the research for the function and regulation of cancer-associated circRNAs.

Extract of Fructus Cannabis Ameliorates Learning and Memory Impairment Induced by D-Galactose in an Aging Rats Model.

Hempseed (Cannabis sativa L.) has been used as a health food and folk medicine in China for centuries. In the present study, we sought to define the underlying mechanism by which the extract of Fructus Cannabis (EFC) protects against memory impairment induced by D-galactose in rats. To accelerate aging and induce memory impairment in rats, D-galactose (400 mg/kg) was injected intraperitoneally once daily for 14 weeks. EFC (200 and 400 mg/kg) was simultaneously administered intragastrically once daily in an attempt to slow the aging process. We found that EFC significantly increased the activity of superoxide dismutase, while lowering levels of malondialdehyde in the hippocampus. Moreover, EFC dramatically elevated the organ indices of some organs, including the heart, the liver, the thymus, and the spleen. In addition, EFC improved the behavioral performance of rats treated with D-galactose in the Morris water maze. Furthermore, EFC inhibited the activation of astrocytes and remarkably attenuated phosphorylated tau and suppressed the expression of presenilin 1 in the brain of D-galactose-treated rats. These findings suggested that EFC exhibits beneficial effects on the cognition of aging rats probably by enhancing antioxidant capacity and anti-neuroinflammation, improving immune function, and modulating tau phosphorylation and presenilin expression.

Nosocomial and Community-Acquired Spontaneous Bacterial Peritonitis in patients with liver cirrhosis in China: Comparative Microbiology and Therapeutic Implications.

Spontaneous bacterial peritonitis (SBP) is a common complication of liver cirrhosis. This study was performed to compare the microbiological characteristics of nosocomial and community-acquired episodes of bacterial peritonitis in China. Five hundred and seventy-five strains were isolated from the ascitic fluid of cirrhotic patients from the Beijing 302 Hospital from January 2014 to December 2014. The patients in the community-acquired SBP (n = 264) and the nosocomial SBP (n = 311) groups exhibited significant differences in clinical symptoms (P < 0.01) [corrected]. In both groups, most of the bacteria were Escherichia coli, Klebsiella pneumoniae, coagulase-negative staphylococcus and Enterococcus. There were more frequent gram-positive cocci (G+ C) in the nosocomial group (n = 170). Compared with the community-acquired group, the proportion of Enterococcus was significantly increased in the nosocomial group (9.0% vs. 16.6%, P < 0.05). The resistance rate of the main pathogenic bacteria to the recommended first-line drug in the guideline was very high. Community-acquired and nosocomial SBP groups exhibited differences in clinical symptoms and antibiotic susceptibility tests. Optimal treatments should be provided for these patients. We recommend that cefoperazone/sulbactam or piperacillin/tazobactam should be used for the empirical treatment of SBP.

Intratumoral and Intertumoral Genomic Heterogeneity of Multifocal Localized Prostate Cancer Impacts Molecular Classifications and Genomic Prognosticators.

BACKGROUND: Next-generation sequencing is revealing genomic heterogeneity in localized prostate cancer (CaP). Incomplete sampling of CaP multiclonality has limited the implications for molecular subtyping, stratification, and systemic treatment. OBJECTIVE: To determine the impact of genomic and transcriptomic diversity within and among intraprostatic CaP foci on CaP molecular taxonomy, predictors of progression, and actionable therapeutic targets. DESIGN, SETTING, AND PARTICIPANTS: Four consecutive patients with clinically localized National Comprehensive Cancer Network intermediate- or high-risk CaP who did not receive neoadjuvant therapy underwent radical prostatectomy at Roswell Park Cancer Institute in June-July 2014. Presurgical information on CaP content and a customized tissue procurement procedure were used to isolate nonmicroscopic and noncontiguous CaP foci in radical prostatectomy specimens. Three cores were obtained from the index lesion and one core from smaller lesions. RNA and DNA were extracted simultaneously from 26 cores with ≥90% CaP content and analyzed using whole-exome sequencing, single-nucleotide polymorphism arrays, and RNA sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Somatic mutations, copy number alternations, gene expression, gene fusions, and phylogeny were defined. The impact of genomic alterations on CaP molecular classification, gene sets measured in Oncotype DX, Prolaris, and Decipher assays, and androgen receptor activity among CaP cores was determined. RESULTS AND LIMITATIONS: There was considerable variability in genomic alterations among CaP cores, and between RNA- and DNA-based platforms. Heterogeneity was found in molecular grouping of individual CaP foci and the activity of gene sets underlying the assays for risk stratification and androgen receptor activity, and was validated in independent genomic data sets. Determination of the implications for clinical decision-making requires follow-up studies. CONCLUSIONS: Genomic make-up varies widely among CaP foci, so care should be taken when making treatment decisions based on a single biopsy or index lesions. PATIENT SUMMARY: We examined the molecular composition of individual cancers in a patient's prostate. We found a lot of genetic diversity among these cancers, and concluded that information from a single cancer biopsy is not sufficient to guide treatment decisions.

Application ofH NMR-based metabolomics for discrimination of different parts and development of a new processing workflow for

(CD) is one of the two authoritative source plants of Cistanches Herba, a well-known medicinal plant. Herein,H NMR spectroscopy was employed to characterize the chemical profile and to distinguish the different parts, as well as to propose a new processing workflow for CD. Signal assignment was achieved by multiple one and two dimensional NMR spectroscopic techniques in combination with available databases and authentic compounds. The upper parts of the plant were distinguished from the lower parts by combiningH NMR spectroscopic dataset with multivariate statistical analysis. A new processing method that hyphenated steaming with freeze-drying, was demonstrated to be superior to either steaming coupled with oven-drying or direct freeze-dryingholisticH NMR-based metabolomic characterization. Phenylethanoid glycosides, mainly echinacoside and acteoside, were screened out and confirmed as the chemical markers responsible for exhibiting the superiority of the new processing workflow, whereas serial primary metabolites, especially carbohydrates and tricarboxylic acid cycle metabolites, were found as the primary molecules governing the discrimination between the upper and lower parts of the plant. Collectively,H NMR spectroscopy was demonstrated as a versatile analytical tool to characterize the chemical profile and to guide the in-depth exploitation of CD by providing comprehensive qualitative and quantitative information.

Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer.

Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent.

[Clinical Efficacy of Supplementary Treatment of Gukang Capsules to the Elder Patients with Fracture of Distal Radius].

OBJECTIVE: To study the clinical efficacy of supplementary treatment of tukang Capsules to the elder patients with fracture of the distal radius. METHODS: A total of 108 elder patients with fracture of the distal radius diagnosed by X-ray,who visited orthopedics department of Pu' ai Hospital in January 2012 - December 2013, were randomly divided into observation group and control group. Cases in both groups received the operation of internal fixation by T-type plate. Cases in control group received oral Calcium Carbonate Tablets, and cases in observation group received Gukang Capsules besides Calcium Carbonate Tablets. Treatment duration was four weeks. The painful and swelling degree of wrist joints, levels of type I propeptide carboxy-terminal procollagen (P I CP) and bone glaprotein(BGP) in serum were compared. Hospitalization and fracture healing time, as well as recovery condition of wrist joints in the sixth month after operation were compared. RESULTS: The VAS of both groups was not significantly different before operation and in the 28th day after operation(P >0. 05), but the VAS in observation group was significantly lower than that in control group in the 3rd,5th, 7th, 14th and 21th day after operation(P <0. 01). The swelling scale of both groups was not significantly different before operation and in the 28th day after operation(P >0. 05), but the swelling scale in observation group was significantly lower than that in control group in the 3rd, 5th, 7th, 14th and 21th day after operation(P <0. 01). The levels of P I CP and BGP in serum of both groups were not significantly different before operation(P >0. 05), but the levels of P I CP and BGP in serum of observation groups were significantly higher than that in control group one and two months after operation (P <0. 01). Hospitalization and fracture healing time in observation group was significantly shortened compared with control group (P <0. 05). The effective ratio in observation group was 79. 63%, significantly higher than that in control group (P <0. 05). CONCLUSION: Gukang Capsules supplementary to internal fixation by T-type plate has favorable efficacy to fracture of the distal radius, which can reduce pain and swelling, increase levels of P I CP and BGP in serum, as well as promote the heal of fracture and recovery of wrist joints function.

Attenuation of cartilage pathogenesis in post-traumatic osteoarthritis (PTOA) in mice by blocking the stromal derived factor 1 receptor (CXCR4) with the specific inhibitor, AMD3100.

SDF-1 was found to infiltrate cartilage, decrease proteoglycan content, and increase MMP-13 activity after joint trauma. In this study, we tested the hypothesis that interference of the SDF-1/CXCR4 signaling pathway via AMD3100 can attenuate pathogenesis in a mouse model of PTOA. We also tested the predictive and confirmatory power of fluorescence molecular tomography (FMT) for cartilage assessment. AMD3100 was continuously delivered via mini-osmotic pumps. The extent of cartilage damage after AMD3100 or PBS treatment was assessed by histological analysis 2 months after PTOA was induced by surgical destabilization of the medial meniscus (DMM). Biochemical markers of PTOA were assessed via immunohistochemistry and in vivo fluorescence molecular tomography (FMT). Regression analysis was used to validate the predictive power of FMT measurements. Safranin-O staining revealed significant PTOA damage in the DMM/PBS mice, while the DMM/AMD3100 treated mice showed a significantly reduced response with minimal pathology. Immunohistochemistry showed that AMD3100 treatment markedly reduced typical PTOA marker expression in chondrocytes. FMT measurements showed decreased cathepsins and MMP activity in knee joints after treatment. The results demonstrate that AMD3100 treatment attenuates PTOA. AMD3100 may provide a viable and expedient option for PTOA therapy given the drug's FDA approval and well-known safety profile.